| Inflammatory Pseudotumor of the Liver Tsen-Long Yang, Hong-Chuen Chang Journal of Cancer Research and Practice 2019 6(2):96-99 Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, characterized by chronic infiltration of inflammatory cells and areas of necrosis mimicking a malignant tumor. Few cases have been reported, and the precise etiology is still unknown. Patients usually present with abdominal pain, fever, and jaundice. Herein, we report the case of a 78-year-old male with a history of diabetes mellitus who had abdominal fullness and body weight loss for 4 months. A computed tomography scan showed a 15-cm liver tumor in segment 2 and 3 and suspected hepatocellular carcinoma. Left hepatectomy was performed, and the pathology showed IPT. After surgery, the symptom of abdominal fullness subsided. |
Παρασκευή 31 Μαΐου 2019
| Pembrolizumab-induced uveitis in a patient with metastatic urothelial carcinoma Lo-Ho Chen, Jhe-Cyuan Guo Journal of Cancer Research and Practice 2019 6(2):92-95 Immune checkpoint blockade, especially targeting the programmed cell death protein-1/programmed death-ligand 1 axis, has changed the paradigm of anticancer therapy in several cancer types. For urothelial carcinoma (UC), pembrolizumab is an immune checkpoint inhibitor approved by the US Food and Drug Administration for locally advanced or metastatic disease. The new anticancer modalities are complicated with immune-related adverse events (irAEs) which are significantly different from conventional treatment such as chemotherapy or targeted therapy. Herein, we present an 85-year-old man with metastatic UC who developed a rare kind of irAE, uveitis, under pembrolizumab therapy, who fortunately partially recovered with local and systemic steroids. |
| Detection of anaplastic lymphoma kinase gene rearrangement in a patient with right colon cancer Chun-Hui Lee, Chung-Ta Lee, Yi-Lin Chen, Bo-Wen Lin, Peng-Chang Lin, Meng-Ru Shen, Yu-Min Yeh Journal of Cancer Research and Practice 2019 6(2):89-91 Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity worldwide. Recent genome-scale molecular analyses have uncovered several potential therapeutic targets for this disease, including BRAF mutation, ERBB2 amplification, and neurotropic tropomyosin receptor kinase fusion gene. Gene rearrangements involving anaplastic lymphoma kinase (ALK) gene have been identified as oncogenic drivers in lung adenocarcinomas, and to be highly sensitive to selective kinase inhibitors. To the best of our knowledge, CRC harboring the ALK fusion gene has rarely been reported. Herein, we report a patient with right colon cancer harboring an ALK gene rearrangement and review the clinicopathologic features as well as potential therapeutic targeting of ALK-rearranged CRC in the literature. |
| A Patient with refractory metastatic germ cell tumor successful salvaged after treatment with paclitaxel, ifosfamide, and high-dose 5-Fluorouracil infusional therapy Keng-Man Chiang, Ann-Lii Cheng Journal of Cancer Research and Practice 2019 6(2):85-88 We report a case of a 24-year-old male with a metastatic extragonadal germ cell tumor (GCT) which was refractory to conventional chemotherapy and progressed after high-dose chemotherapy. The addition of a 24-h infusion of high-dose 5-fluorouracil (5-FU) with leucovorin regimen to a salvage regimen of paclitaxel and ifosfamide provided a durable clinical response. We also discuss the potential of repurposing 5-FU for the treatment of a refractory GCT. |
| Modulation of oxidative stress by doxorubicin loaded chitosan nanoparticles Ankita Leekha, Vijay Kumar, Imran Moin, Bahadur Singh Gurjar, Anita Kamra Verma Journal of Cancer Research and Practice 2019 6(2):76-84 Purpose of the Research: Chitosan nanoparticles (CHNP) are being used to modulate the generation of reactive oxygen species (ROS), as unwarranted generation of ROS can damage proteins, lipid membranes, and DNA of host cells. CHNP possess exceptional abilities to modulate antioxidants and suppress oxidative stress damage caused by the CHNP themselves in normal cells. Methods and Results: CHNP were prepared by ionic gelation in the size range of ~115 nm, with a polydispersity index of 0.365. Doxorubicin (DOX) was encapsulated in CHNP with entrapment efficiency ~48%. The modulation of free radicals and antioxidative enzymes by DOX-loaded CHNP (DLCHNP) was evaluated. The glutathione s-transferase and glutathione levels induced by DLCHNP were lower in Ehrlich ascites carcinoma cells(EACs) cells (6.60 ± 0.02 nM/min/mg protein and 0.92 ± 0.05 nM/min/mg protein, respectively) compared to void CHNP and DOX per se decreased levels of nitric oxide and superoxide dismutase (0.03 ± 0.001 nMoles and 28.84 ± 0.016 Unit/mg protein), elevated levels of GSSG (11.69 ± 0.004 nM/min/mg protein), marginally reduced levels of GSH reductase (1.87 ± 0.002 Unit/mg protein), reduced levels of GPx (31.35 ± 0.022 Unit/mg protein) and significantly enhanced levels of LPO (1.56 ± 0.01 nMoles/mg protein) indicated cellular damage. As observed in DNA fragmentation assay, void nanoparticles did not show any DNA damage whereas DLCHNP caused significant damage. Enhanced gene expressions of Cyt. C and p21 on EACs cells was observed in DLCHNP-treated cells compared to DOX per se. Conclusion: CHNP were not efficient in generating remarkable oxidative stress, but when coupled with a drug (i.e., DLCHNP) severe damage was caused to the cancer cells compared to the free drug. This indicated the potential of our encapsulated nanoparticles in drug delivery. |
| Antiproliferative effect of oxidative stress induced by tellurite in breast carcinoma cells Ayesha Noreen, Abdul Rehman, Saira Aftab, Abdul Rauf Shakoori Journal of Cancer Research and Practice 2019 6(2):68-75 Background: Recent studies have revealed that tellurium (Te) compounds have pharmacological and/or antioxidant properties against tumors as they have antitumor and chemoprotective properties. The toxic nature of tellurium compounds and their beneficial effects as antitumor agents have led to an increasing number of studies on their toxicological and pharmacological modes of action. Materials and Methods: The breast cancer cell line, MDA-MB-231, was cultured in the absence or presence of tellurite for biochemical and morphological analysis to measure the extent of cell death. The roles of antioxidant compounds 3-methyladenine, N-acetylcysteine, and 1,2-bis (2-aminophenoxy) ethane-N, N, N′, N′-tetra acetic acid (acetoxymethyl ester) in supporting proliferation in the presence of tellurite were investigated. Results: There was significant oxidative stress in the tellurite-exposed cells, which curtailed cell Adenosine triphosphate (ATP) levels. Tellurite-induced cytotoxicity substantially increased lactate dehydrogenase leakage, lipid peroxidation, and DNA damage, as analyzed by micronuclei and comet formation. Conclusions: Tellurite-induced damage led to cell cycle arrest, resulting in cell death by activating apoptotic machinery by increasing p21 gene expression in tellurite-treated cells. |
| High-intensity focused ultrasound for localized prostate Cancer , Shu-Wei Tsai, Teh-Sheng Hsieh Journal of Cancer Research and Practice 2019 6(2):64-67 Purpose: The purpose of this study is to report our results regarding the use of transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. Materials and Methods: From January 2012 to January 2017, 57 patients with localized prostate cancer (cT1c-T2cN0M0) were treated with an Ablatherm™ HIFU device. Of these patients, we excluded those with <12 months of follow-up. In total, 33 patients with localized prostate cancer were enrolled in this study. We assessed the efficacy according to posttreatment prostate-specific antigen (PSA) levels and complications. PSA levels were monitored immediately after HIFU therapy as well as every 3 months thereafter. Biochemical failure was defined as an increase in PSA of 2 ng/mL or more above the PSA nadir. Result: The mean age of all patients was 69.12 ± 8.21 (range: 49–80) years,and the average pretreatment PSA level was 15.19 ± 12.89 (range: 4.44–62.91) ng/mL. The Gleason score ranged from 6 (3 + 3) to 9 (4 + 5) and the mean prostate volume was 38.72 ± 17.90 (range: 21–77) mL. The mean follow-up duration was 36.4 ± 10.8 (range: 13–60) months.Ten patients were classified as low risk, 10 patients were classified as intermittent risk, and 13 patients were classified as high risk according to the National Comprehensive Cancer Network guidelines regarding the risk of recurrence. The PSA levels of all patients decreased significantly after HIFU therapy, and an undetectable PSA (0.04 ng/mL) level was observed in four patients (12.12%). The posttreatment mean PSA nadir was 0.609 ± 0.91 (range: 3.21–0.04) ng/mL, and the mean follow-up duration was 3.1 ± 1.9 (range: 1–8) months. The survival rate was 100%. The PSA biochemical failure rate was 27.3% (9/33). Posttreatment complications included urge incontinence (3/33), total urinary incontinence (0/33), bladder neck contracture (5/33), and urethral stricture (1/33). Conclusion: HIFU therapy appeared to be an effective minimally invasive therapy with acceptable complication rate in selected localized prostate cancer patients. |
Prevention and management catheter-associated urinary tract infection in intensive care unit
Mehdi Rahimi, Khosro Farhadi, Hossein Babaei, Firouz Soleymani
Journal of Nursing and Midwifery Sciences 2019 6(2):98-103
Context: Urinary tract infection (UTI) is the most common hospital-acquired infection. Around 80% of UTIs are associated with urinary catheters. Aims: The aim of this study was to review and to describe epidemiology and approaches for the prevention and management of catheter-associated urinary tract infection (CAUTI) in intensive care unit (ICU) patients. Settings and Design: A narrative review of studies was undertaken. Materials and Methods: A review of PubMed, Google Scholar, Medline, and CINAHL databases were conducted to identify peer-reviewed, English language, and studies published between 1999 and 2018. Related papers were reviewed with using standard keywords. The research was conducted on epidemiology and management of CAUTI in the ICU. Of the 186 English publications, 36 were duplicates. Statistical Analysis Used: Quality assessments, data extractions, and analysis were completed on all included studies. Results: The prevalence of UTI in the ICU is directly related to the widespread use of urethral catheter (32.2%). Guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections for CAUTI. Conclusions: Further studies are needed due to the importance and high prevalence of these infections. We recommend the opportunity to increase any strategy able to reduce the incidence of infections related to urinary catheterization and its consequences in ICUs.
people suffering from special phobias
Alireza Sangani, Paria Jangi, Nahid Ramak, Aniseh Ahmadi
Journal of Nursing and Midwifery Sciences 2019 6(2):84-90
Context: The basis of anxiety disorders in cognitive and emotional fields can be effective in coping strategies to anxiety. Aims: This research aimed to investigate the mediating role of emotional distress tolerance in relationship between self-discrepancy with anxiety in people suffering from special phobias. Settings and Design: The present study was a correlational research with structural equation modeling. Materials and Methods: The statistical population of this study was all individuals suffering from specific phobia disorders in the 5th Azar Hospital in Gorgan City. The sample size selection, which was made by Loehlin method (2004), was 220 persons suffering from anxiety disorder referring to Psychiatric Clinics of 5 Azar Hospital in Gorgan City and was investigated by purposeful sampling. Data gathering tools included Distress Tolerance Scale, self-discrepancy questionnaire, and Spielberger State-Trait Anxiety Inventory. Statistical Analysis Used: The collected data were analyzed using structural regression equations using SPSS 18 and Amos 23 software. Results: The findings showed that the research model is fit and overall, 42% of the anxiety could be explained through emotional stress tolerance and self-discrepancy, and emotional distress tolerance has a mediating role in relationship self-discrepancy with anxiety. Conclusions: The results of this research emphasized the necessity of self-discrepancy as well as the role of mediator of emotional distress tolerance in anxiety in people suffering from special phobias, which can provide applied templates for improving the psychological state of anxious individuals with therapists and counselors.
Alireza Sangani, Paria Jangi, Nahid Ramak, Aniseh Ahmadi
Journal of Nursing and Midwifery Sciences 2019 6(2):84-90
Context: The basis of anxiety disorders in cognitive and emotional fields can be effective in coping strategies to anxiety. Aims: This research aimed to investigate the mediating role of emotional distress tolerance in relationship between self-discrepancy with anxiety in people suffering from special phobias. Settings and Design: The present study was a correlational research with structural equation modeling. Materials and Methods: The statistical population of this study was all individuals suffering from specific phobia disorders in the 5th Azar Hospital in Gorgan City. The sample size selection, which was made by Loehlin method (2004), was 220 persons suffering from anxiety disorder referring to Psychiatric Clinics of 5 Azar Hospital in Gorgan City and was investigated by purposeful sampling. Data gathering tools included Distress Tolerance Scale, self-discrepancy questionnaire, and Spielberger State-Trait Anxiety Inventory. Statistical Analysis Used: The collected data were analyzed using structural regression equations using SPSS 18 and Amos 23 software. Results: The findings showed that the research model is fit and overall, 42% of the anxiety could be explained through emotional stress tolerance and self-discrepancy, and emotional distress tolerance has a mediating role in relationship self-discrepancy with anxiety. Conclusions: The results of this research emphasized the necessity of self-discrepancy as well as the role of mediator of emotional distress tolerance in anxiety in people suffering from special phobias, which can provide applied templates for improving the psychological state of anxious individuals with therapists and counselors.
singing on the happiness of older people
Maryam Entezari, Manijeh Zakizadeh, Jamshid Yazdani, Zohreh Taraghi
Journal of Nursing and Midwifery Sciences 2019 6(2):78-83
Context: Happiness is important for all age groups; however, it is more highlighted in elders. Aims: The aim of the current study was to determine the effect of group singing on the happiness of older people. Setting and Design: In this quasi-experimental study, sixty participants selected among elderly referred to two Day Care Centers of Mazandaran. Materials and Methods: Samples were assigned to two groups of intervention (n = 30)and control (n = 30). The intervention group was assigned into three groups of 10. Each group selected a song from the list of songs and performed it for 10 min. This process was repeated one more time. The intervention was performed two times a week, for 3 weeks. In the control group, no intervention was performed and the elderly received the usual care. The happiness score of both groups, before and 1 month after the end of the intervention, was measured using the Oxford Happiness Inventory. Statistical Analysis Used: Data were analyzed using independent t-test, Chi-square test, and ANCOVA. Results: Before intervention, the mean scores of happiness in the intervention and control groups were 4.38 ± 0.48 and 4. 53 ± 0.26, respectively (P = 0.138). One month after intervention, the mean scores of happiness in the intervention and control groups were 4.77 ± 0.37 and 4.35 ± 0.18, respectively (P = 0.004). Conclusion: The results of this study showed that group singing was effective on the happiness of the elderly. More studies in day-care centers and other settings, especially nursing homes, are recommended. Implementation of such measures is recommended in the day-care centers.
Maryam Entezari, Manijeh Zakizadeh, Jamshid Yazdani, Zohreh Taraghi
Journal of Nursing and Midwifery Sciences 2019 6(2):78-83
Context: Happiness is important for all age groups; however, it is more highlighted in elders. Aims: The aim of the current study was to determine the effect of group singing on the happiness of older people. Setting and Design: In this quasi-experimental study, sixty participants selected among elderly referred to two Day Care Centers of Mazandaran. Materials and Methods: Samples were assigned to two groups of intervention (n = 30)and control (n = 30). The intervention group was assigned into three groups of 10. Each group selected a song from the list of songs and performed it for 10 min. This process was repeated one more time. The intervention was performed two times a week, for 3 weeks. In the control group, no intervention was performed and the elderly received the usual care. The happiness score of both groups, before and 1 month after the end of the intervention, was measured using the Oxford Happiness Inventory. Statistical Analysis Used: Data were analyzed using independent t-test, Chi-square test, and ANCOVA. Results: Before intervention, the mean scores of happiness in the intervention and control groups were 4.38 ± 0.48 and 4. 53 ± 0.26, respectively (P = 0.138). One month after intervention, the mean scores of happiness in the intervention and control groups were 4.77 ± 0.37 and 4.35 ± 0.18, respectively (P = 0.004). Conclusion: The results of this study showed that group singing was effective on the happiness of the elderly. More studies in day-care centers and other settings, especially nursing homes, are recommended. Implementation of such measures is recommended in the day-care centers.
| Modeling of cardiac function of patients with acute myocardial infarction based on Type-D personality: Mediating role of negative emotions Marzieh Mohammadi Pashaki, Yarali Dousti, Bahram Mirzaian Journal of Nursing and Midwifery Sciences 2019 6(2):63-71 Context: Cardiac function of patients with acute myocardial infarction (MI) plays a central role in their prognosis. Aims: The purpose of this study was to model the cardiac function of these patients based on Type-D personality and the mediating role of negative emotions (anger, depression, and anxiety) in this relationship. Setting and Design: This correlational study was performed using the structural equation modeling method, and specifically the regression equations (combination of path analysis and second-order factor analysis). Material and Methods: The study population was the patients with acute ST-segment elevation MI (STEMI) who were hospitalized at Mazandaran Cardiovascular Hospital and underwent under primary percutaneous coronary intervention treatment in 2017 and 2018. Using Mueller's formula modeling formula (1996) based on a sample size-to-free parameter ratio, the sample size was calculated to 220 patients were chosen by the purposive method. Data were collected using Denollet'sType-DScale-14, the Spielberger's state-trait anxiety inventory, short-form of the beck depression inventory-13, and Spielberger's state-trait anger expression inventory-2. Statistical Analysis Used: Data analysis was performed using SPSS-18 and AMOS 23. Results: Type-D personality can directly predict of the cardiac function of patients with acute STEMI. This variable also predicts the the cardiac function of these patients via the mediation of negative emotions (anger, depression, and anxiety). Conclusion: Type-D personality affects the incidence and prognosis of myocardial infarction via negative emotions. It is, therefore, recommended to screen the susceptible populations for this personality type. |
patients with spinal muscular atrophy
,
Ali-Asghar Jesmi, Leila Jouybari, Akram Sanagoo
Journal of Nursing and Midwifery Sciences 2019 6(2):57-62
Context: Spinal muscular atrophy (SMA) is a neuromuscular disease which, in addition to physical disability, causes psychological and social problems for patients and their families. If physiological and mental disorders continue to persist for a long time, it leads to serious deterioration in the patient's physical condition, influences the treatment process, and prevents the outcome of the therapies. Aims: The aim of this study was to explore the lived experiences of patients with SMA. Setting and Design: In this qualitative study, a total of six participants (five patients and one patients' wife) were selected by purposive sampling method. Material and Methods: Data were collected by semi-structured interview. Eleven interviews were conducted and analyzed by Colaizzi's descriptive phenomenological approach. Statistical Analysis Used: Data were analyzed by One Note soft ware version 14.0 with Colaizzi's descriptive phenomenological approach. Results: Two main themes – “tragic life” and “vague future” – emerged from data analysis. They had four categories including “physical and psychological problems,” “limitations and lost opportunities,” “concerns,” and “uncertain future.” Conclusions: These patients experienced a lot of physical and psychological impairments in their life. They have many concerns and lost some opportunities. Therefore, policymakers and authorities should support these patients for participating as an effective members in the society, consequently their feeling improve by getting independent.
,
Ali-Asghar Jesmi, Leila Jouybari, Akram Sanagoo
Journal of Nursing and Midwifery Sciences 2019 6(2):57-62
Context: Spinal muscular atrophy (SMA) is a neuromuscular disease which, in addition to physical disability, causes psychological and social problems for patients and their families. If physiological and mental disorders continue to persist for a long time, it leads to serious deterioration in the patient's physical condition, influences the treatment process, and prevents the outcome of the therapies. Aims: The aim of this study was to explore the lived experiences of patients with SMA. Setting and Design: In this qualitative study, a total of six participants (five patients and one patients' wife) were selected by purposive sampling method. Material and Methods: Data were collected by semi-structured interview. Eleven interviews were conducted and analyzed by Colaizzi's descriptive phenomenological approach. Statistical Analysis Used: Data were analyzed by One Note soft ware version 14.0 with Colaizzi's descriptive phenomenological approach. Results: Two main themes – “tragic life” and “vague future” – emerged from data analysis. They had four categories including “physical and psychological problems,” “limitations and lost opportunities,” “concerns,” and “uncertain future.” Conclusions: These patients experienced a lot of physical and psychological impairments in their life. They have many concerns and lost some opportunities. Therefore, policymakers and authorities should support these patients for participating as an effective members in the society, consequently their feeling improve by getting independent.
Effect of cognitive behavior therapy integrated with mindfulness on perceived pain and pain self-efficacy in patients with breast cancer
Mohammad-Rasul Mozafari-Motlagh, Hamid Nejat, Hasan Tozandehjani, Ali-Akbar Samari
Journal of Nursing and Midwifery Sciences 2019 6(2):51-56
Context: Cancer pain in a complicated situation for patients with breast cancer. Researchers suggested to use complementary and alternative method in order to reduction pain and side effects in these patients. Aims: This study was aimed to investigate the effectiveness of mindfulness integrated with cognitive behavioral therapy (MiCBT) on perceived pain and pain self-efficacy in patients with breast cancer. Settings and Design: In this clinical trial study, a semi-experimental method was used. Patients with breast cancer were recurred from cancer clinic of a hospital of Mashhad University of Medical Sciences. Material and Methods: Twenty-four patients with breast cancer selected through purposive sampling method and randomly assigned with permutation blocks in two groups of intervention (n = 12) and control (n = 12). The groups were assessed by demographic questionnaire, Perceived Pain Scale, and Pain Self-efficacy Scale before, immediate, and 1 month after the intervention. Participants in the interventional group received MiCBT for 8 weeks. Statistical Analysis Used: Data were analyzed using descriptive methods and multivariate analysis of covariance. Results: The results showed that the interventional group had a significant decrease in perceived pain (P > 0.05). The pain self-efficacy of patients significantly increased in comparison to the control group in posttest and follow-up stage (P < 0.05). Conclusion: According to the results, it can be concluded that using integrated therapy with mindfulness has been effective in reducing pain and enhancing pain self-efficacy in breast cancer patients. Therefore, it can be an adequate complementary therapy for patients with breast cancer.
Mohammad-Rasul Mozafari-Motlagh, Hamid Nejat, Hasan Tozandehjani, Ali-Akbar Samari
Journal of Nursing and Midwifery Sciences 2019 6(2):51-56
Context: Cancer pain in a complicated situation for patients with breast cancer. Researchers suggested to use complementary and alternative method in order to reduction pain and side effects in these patients. Aims: This study was aimed to investigate the effectiveness of mindfulness integrated with cognitive behavioral therapy (MiCBT) on perceived pain and pain self-efficacy in patients with breast cancer. Settings and Design: In this clinical trial study, a semi-experimental method was used. Patients with breast cancer were recurred from cancer clinic of a hospital of Mashhad University of Medical Sciences. Material and Methods: Twenty-four patients with breast cancer selected through purposive sampling method and randomly assigned with permutation blocks in two groups of intervention (n = 12) and control (n = 12). The groups were assessed by demographic questionnaire, Perceived Pain Scale, and Pain Self-efficacy Scale before, immediate, and 1 month after the intervention. Participants in the interventional group received MiCBT for 8 weeks. Statistical Analysis Used: Data were analyzed using descriptive methods and multivariate analysis of covariance. Results: The results showed that the interventional group had a significant decrease in perceived pain (P > 0.05). The pain self-efficacy of patients significantly increased in comparison to the control group in posttest and follow-up stage (P < 0.05). Conclusion: According to the results, it can be concluded that using integrated therapy with mindfulness has been effective in reducing pain and enhancing pain self-efficacy in breast cancer patients. Therefore, it can be an adequate complementary therapy for patients with breast cancer.
Warning System Designed to Predict Severe Sepsis and Septic Shock
Objective: To assess clinician perceptions of a machine learning–based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). Design: Prospective observational study. Setting: Tertiary teaching hospital in Philadelphia, PA. Patients: Non-ICU admissions November–December 2016. Interventions: During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert’s helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. Measurements and Main Results: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient’s risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. Conclusions: In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning–based sepsis alerts. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Ginestra, Dr. Schweickert, Ms. Meadows, Mr. Lynch, and Ms. Pavan helped with data collection; Dr. Ginestra helped with analysis and interpretation of the data, and drafting of the article; and all authors helped with conception and design, and critical revision of the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http;/journals.lww.com/ccmjournal). Dr. Umscheid’s contribution to this project was supported, in part, by the National Center for Research Resources (grant no: UL1RR024134), which is now at the National Center for Advancing Translational Sciences (grant no: UL1TR000003). Presented as a poster at the 2017 Society of Hospital Medicine Annual Meeting, Las Vegas, NV. Dr. Schweickert has received funding from the American College of Physicians and Arjo. Dr. Umscheid’s institution has received funding from the National Institutes of Health, Food and Drug Administration, and Agency for Healthcare Research and Quality Evidence-based Practice Center contracts, and he has received funding from the Patient-Centered Outcomes Research Institute Advisory Panel and Northwell Health (grand rounds honoraria). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Craig A. Umscheid, MD, MS, Office of Clinical Excellence, University of Chicago Medicine, American School Building, 850 E. 58th Street, Suite 123, Office 128, MC 1135, Chicago, IL 60637. E-mail: craigumscheid@medicine.bsd.uchicago.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Objective: To assess clinician perceptions of a machine learning–based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). Design: Prospective observational study. Setting: Tertiary teaching hospital in Philadelphia, PA. Patients: Non-ICU admissions November–December 2016. Interventions: During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert’s helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. Measurements and Main Results: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient’s risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. Conclusions: In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning–based sepsis alerts. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Ginestra, Dr. Schweickert, Ms. Meadows, Mr. Lynch, and Ms. Pavan helped with data collection; Dr. Ginestra helped with analysis and interpretation of the data, and drafting of the article; and all authors helped with conception and design, and critical revision of the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http;/journals.lww.com/ccmjournal). Dr. Umscheid’s contribution to this project was supported, in part, by the National Center for Research Resources (grant no: UL1RR024134), which is now at the National Center for Advancing Translational Sciences (grant no: UL1TR000003). Presented as a poster at the 2017 Society of Hospital Medicine Annual Meeting, Las Vegas, NV. Dr. Schweickert has received funding from the American College of Physicians and Arjo. Dr. Umscheid’s institution has received funding from the National Institutes of Health, Food and Drug Administration, and Agency for Healthcare Research and Quality Evidence-based Practice Center contracts, and he has received funding from the Patient-Centered Outcomes Research Institute Advisory Panel and Northwell Health (grand rounds honoraria). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Craig A. Umscheid, MD, MS, Office of Clinical Excellence, University of Chicago Medicine, American School Building, 850 E. 58th Street, Suite 123, Office 128, MC 1135, Chicago, IL 60637. E-mail: craigumscheid@medicine.bsd.uchicago.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
| Neurologic Complications of Infective Endocarditis: A Joint Model for a Septic Thromboembolism and Inflammatory Small Vessel Disease Objectives: Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model. Design: Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls. Setting: Research laboratory of a university hospital. Subjects: Male Wistar rats. Interventions: Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions. Measurements and Main Results: In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02). Conclusions: This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the Société Française NeuroVasculaire. Dr. Cantier received support for article research from Société Française de Neurologie Vasculaire. Dr. Olivot received funding from consulting for Servier, Medtronic, and Astra Zeneca, and he received speaker fees from Bristol Myers Squibb and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: marie.cantier@aphp.fr; mikael.mazighi@aphp.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass
Objectives: Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass–related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression. Design: In vitro studies with human peripheral blood mononuclear cells. Setting: Cardiosurgical ICU, University Research Laboratory. Patients: Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018). Interventions: Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15+ cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested. Measurements and Main Results: After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8+-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence. Conclusions: Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass. Drs. Hübner and Tomasi contributed equally to this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by institutional grants of the LMU Munich. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Simone Kreth, MD, PhD, Department of Anesthesiology, University Hospital, LMU Munich, Marchioninistr 15, 81377 Munich, Germany. E-mail: simone.kreth@med.uni-muenchen.de Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Objectives: Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass–related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression. Design: In vitro studies with human peripheral blood mononuclear cells. Setting: Cardiosurgical ICU, University Research Laboratory. Patients: Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018). Interventions: Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15+ cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested. Measurements and Main Results: After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8+-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence. Conclusions: Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass. Drs. Hübner and Tomasi contributed equally to this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by institutional grants of the LMU Munich. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Simone Kreth, MD, PhD, Department of Anesthesiology, University Hospital, LMU Munich, Marchioninistr 15, 81377 Munich, Germany. E-mail: simone.kreth@med.uni-muenchen.de Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Tumour Spheroids-on-a-Chip
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M Ibrahim Khot, Mark A Levenstein, Nikil Kapur, David G Jayne
Journal of Cancer Research and Practice 2019 6(2):55-63
Introduction: Three-dimensional (3D) cell cultures are identified as more accurate and representative models of human cancers than conventional two-dimensional monolayer cell cultures. However, currently established 3D culturing techniques are technically challenging, time- and resource-consuming, and performed using traditional laboratory tissue culturing equipment. In recent years, microfluidics has been introduced into biomedical research, allowing cells and tissues to be cultured in microfabricated devices. The current challenge is to adapt existing 3D cell culturing techniques to microfluidic devices, allowing for the fabrication of low-cost, rapid evaluation devices to facilitate biomedical research and clinical application. The aim of this review was to evaluate microfluidics and 3D cell culture research with particular relevance to oncological research. Methods: Journal articles were acquired from different scientific databases and were identified using specific keywords. Three-Dimensional Cell Culturing Microfluidic Concepts: Various 3D cell culturing microfluidic devices have been designed, based on existing 3D cell culturing methods. This includes non-cell adherent-based devices, matrix-embedding, hanging drop, and droplet-based culturing methods. These platforms facilitate the culturing, treatment, and analysis of 3D spheroids, while simultaneously scaling down traditional experimental requirements. Limitations and Future Perspectives: Beyond superficial analysis, a major drawback in the current scope of 3D cell culturing microfluidic devices is the inability to extract spheroids for examining histology. Polydimethylsiloxane is the preferred material to fabricate devices but may need revision for commercializing microfluidic platforms in the future. Integrating 3D bioprinting and organoid cultures could potentially improve the quality of 3D models in microfluidic devices. Conclusion: 3D spheroids are an effective representation of in vivo cancers and microfluidics has streamlined the culture, treatment, and analysis of 3D models. Considerable improvements have been made in combining the two entities, but further work is required to manufacture 3D cell culturing microfluidic devices on a commercial scale.
,
M Ibrahim Khot, Mark A Levenstein, Nikil Kapur, David G Jayne
Journal of Cancer Research and Practice 2019 6(2):55-63
Introduction: Three-dimensional (3D) cell cultures are identified as more accurate and representative models of human cancers than conventional two-dimensional monolayer cell cultures. However, currently established 3D culturing techniques are technically challenging, time- and resource-consuming, and performed using traditional laboratory tissue culturing equipment. In recent years, microfluidics has been introduced into biomedical research, allowing cells and tissues to be cultured in microfabricated devices. The current challenge is to adapt existing 3D cell culturing techniques to microfluidic devices, allowing for the fabrication of low-cost, rapid evaluation devices to facilitate biomedical research and clinical application. The aim of this review was to evaluate microfluidics and 3D cell culture research with particular relevance to oncological research. Methods: Journal articles were acquired from different scientific databases and were identified using specific keywords. Three-Dimensional Cell Culturing Microfluidic Concepts: Various 3D cell culturing microfluidic devices have been designed, based on existing 3D cell culturing methods. This includes non-cell adherent-based devices, matrix-embedding, hanging drop, and droplet-based culturing methods. These platforms facilitate the culturing, treatment, and analysis of 3D spheroids, while simultaneously scaling down traditional experimental requirements. Limitations and Future Perspectives: Beyond superficial analysis, a major drawback in the current scope of 3D cell culturing microfluidic devices is the inability to extract spheroids for examining histology. Polydimethylsiloxane is the preferred material to fabricate devices but may need revision for commercializing microfluidic platforms in the future. Integrating 3D bioprinting and organoid cultures could potentially improve the quality of 3D models in microfluidic devices. Conclusion: 3D spheroids are an effective representation of in vivo cancers and microfluidics has streamlined the culture, treatment, and analysis of 3D models. Considerable improvements have been made in combining the two entities, but further work is required to manufacture 3D cell culturing microfluidic devices on a commercial scale.
Cancer Research and Practice
| A Review on the Recent Advancement in "Tumour Spheroids-on-a-Chip" M Ibrahim Khot, Mark A Levenstein, Nikil Kapur, David G Jayne Journal of Cancer Research and Practice 2019 6(2):55-63 Introduction: Three-dimensional (3D) cell cultures are identified as more accurate and representative models of human cancers than conventional two-dimensional monolayer cell cultures. However, currently established 3D culturing techniques are technically challenging, time- and resource-consuming, and performed using traditional laboratory tissue culturing equipment. In recent years, microfluidics has been introduced into biomedical research, allowing cells and tissues to be cultured in microfabricated devices. The current challenge is to adapt existing 3D cell culturing techniques to microfluidic devices, allowing for the fabrication of low-cost, rapid evaluation devices to facilitate biomedical research and clinical application. The aim of this review was to evaluate microfluidics and 3D cell culture research with particular relevance to oncological research. Methods: Journal articles were acquired from different scientific databases and were identified using specific keywords. Three-Dimensional Cell Culturing Microfluidic Concepts: Various 3D cell culturing microfluidic devices have been designed, based on existing 3D cell culturing methods. This includes non-cell adherent-based devices, matrix-embedding, hanging drop, and droplet-based culturing methods. These platforms facilitate the culturing, treatment, and analysis of 3D spheroids, while simultaneously scaling down traditional experimental requirements. Limitations and Future Perspectives: Beyond superficial analysis, a major drawback in the current scope of 3D cell culturing microfluidic devices is the inability to extract spheroids for examining histology. Polydimethylsiloxane is the preferred material to fabricate devices but may need revision for commercializing microfluidic platforms in the future. Integrating 3D bioprinting and organoid cultures could potentially improve the quality of 3D models in microfluidic devices. Conclusion: 3D spheroids are an effective representation of in vivo cancers and microfluidics has streamlined the culture, treatment, and analysis of 3D models. Considerable improvements have been made in combining the two entities, but further work is required to manufacture 3D cell culturing microfluidic devices on a commercial scale. |
| High-intensity focused ultrasound for localized prostate Cancer in Cathay General Hospital Shu-Wei Tsai, Teh-Sheng Hsieh Journal of Cancer Research and Practice 2019 6(2):64-67 Purpose: The purpose of this study is to report our results regarding the use of transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. Materials and Methods: From January 2012 to January 2017, 57 patients with localized prostate cancer (cT1c-T2cN0M0) were treated with an Ablatherm™ HIFU device. Of these patients, we excluded those with <12 months of follow-up. In total, 33 patients with localized prostate cancer were enrolled in this study. We assessed the efficacy according to posttreatment prostate-specific antigen (PSA) levels and complications. PSA levels were monitored immediately after HIFU therapy as well as every 3 months thereafter. Biochemical failure was defined as an increase in PSA of 2 ng/mL or more above the PSA nadir. Result: The mean age of all patients was 69.12 ± 8.21 (range: 49–80) years,and the average pretreatment PSA level was 15.19 ± 12.89 (range: 4.44–62.91) ng/mL. The Gleason score ranged from 6 (3 + 3) to 9 (4 + 5) and the mean prostate volume was 38.72 ± 17.90 (range: 21–77) mL. The mean follow-up duration was 36.4 ± 10.8 (range: 13–60) months.Ten patients were classified as low risk, 10 patients were classified as intermittent risk, and 13 patients were classified as high risk according to the National Comprehensive Cancer Network guidelines regarding the risk of recurrence. The PSA levels of all patients decreased significantly after HIFU therapy, and an undetectable PSA (0.04 ng/mL) level was observed in four patients (12.12%). The posttreatment mean PSA nadir was 0.609 ± 0.91 (range: 3.21–0.04) ng/mL, and the mean follow-up duration was 3.1 ± 1.9 (range: 1–8) months. The survival rate was 100%. The PSA biochemical failure rate was 27.3% (9/33). Posttreatment complications included urge incontinence (3/33), total urinary incontinence (0/33), bladder neck contracture (5/33), and urethral stricture (1/33). Conclusion: HIFU therapy appeared to be an effective minimally invasive therapy with acceptable complication rate in selected localized prostate cancer patients. |
| Antiproliferative effect of oxidative stress induced by tellurite in breast carcinoma cells Ayesha Noreen, Abdul Rehman, Saira Aftab, Abdul Rauf Shakoori Journal of Cancer Research and Practice 2019 6(2):68-75 Background: Recent studies have revealed that tellurium (Te) compounds have pharmacological and/or antioxidant properties against tumors as they have antitumor and chemoprotective properties. The toxic nature of tellurium compounds and their beneficial effects as antitumor agents have led to an increasing number of studies on their toxicological and pharmacological modes of action. Materials and Methods: The breast cancer cell line, MDA-MB-231, was cultured in the absence or presence of tellurite for biochemical and morphological analysis to measure the extent of cell death. The roles of antioxidant compounds 3-methyladenine, N-acetylcysteine, and 1,2-bis (2-aminophenoxy) ethane-N, N, N′, N′-tetra acetic acid (acetoxymethyl ester) in supporting proliferation in the presence of tellurite were investigated. Results: There was significant oxidative stress in the tellurite-exposed cells, which curtailed cell Adenosine triphosphate (ATP) levels. Tellurite-induced cytotoxicity substantially increased lactate dehydrogenase leakage, lipid peroxidation, and DNA damage, as analyzed by micronuclei and comet formation. Conclusions: Tellurite-induced damage led to cell cycle arrest, resulting in cell death by activating apoptotic machinery by increasing p21 gene expression in tellurite-treated cells. |
| Modulation of oxidative stress by doxorubicin loaded chitosan nanoparticles Ankita Leekha, Vijay Kumar, Imran Moin, Bahadur Singh Gurjar, Anita Kamra Verma Journal of Cancer Research and Practice 2019 6(2):76-84 Purpose of the Research: Chitosan nanoparticles (CHNP) are being used to modulate the generation of reactive oxygen species (ROS), as unwarranted generation of ROS can damage proteins, lipid membranes, and DNA of host cells. CHNP possess exceptional abilities to modulate antioxidants and suppress oxidative stress damage caused by the CHNP themselves in normal cells. Methods and Results: CHNP were prepared by ionic gelation in the size range of ~115 nm, with a polydispersity index of 0.365. Doxorubicin (DOX) was encapsulated in CHNP with entrapment efficiency ~48%. The modulation of free radicals and antioxidative enzymes by DOX-loaded CHNP (DLCHNP) was evaluated. The glutathione s-transferase and glutathione levels induced by DLCHNP were lower in Ehrlich ascites carcinoma cells(EACs) cells (6.60 ± 0.02 nM/min/mg protein and 0.92 ± 0.05 nM/min/mg protein, respectively) compared to void CHNP and DOX per se decreased levels of nitric oxide and superoxide dismutase (0.03 ± 0.001 nMoles and 28.84 ± 0.016 Unit/mg protein), elevated levels of GSSG (11.69 ± 0.004 nM/min/mg protein), marginally reduced levels of GSH reductase (1.87 ± 0.002 Unit/mg protein), reduced levels of GPx (31.35 ± 0.022 Unit/mg protein) and significantly enhanced levels of LPO (1.56 ± 0.01 nMoles/mg protein) indicated cellular damage. As observed in DNA fragmentation assay, void nanoparticles did not show any DNA damage whereas DLCHNP caused significant damage. Enhanced gene expressions of Cyt. C and p21 on EACs cells was observed in DLCHNP-treated cells compared to DOX per se. Conclusion: CHNP were not efficient in generating remarkable oxidative stress, but when coupled with a drug (i.e., DLCHNP) severe damage was caused to the cancer cells compared to the free drug. This indicated the potential of our encapsulated nanoparticles in drug delivery. |
| A Patient with refractory metastatic germ cell tumor successful salvaged after treatment with paclitaxel, ifosfamide, and high-dose 5-Fluorouracil infusional therapy Keng-Man Chiang, Ann-Lii Cheng Journal of Cancer Research and Practice 2019 6(2):85-88 We report a case of a 24-year-old male with a metastatic extragonadal germ cell tumor (GCT) which was refractory to conventional chemotherapy and progressed after high-dose chemotherapy. The addition of a 24-h infusion of high-dose 5-fluorouracil (5-FU) with leucovorin regimen to a salvage regimen of paclitaxel and ifosfamide provided a durable clinical response. We also discuss the potential of repurposing 5-FU for the treatment of a refractory GCT. |
| Detection of anaplastic lymphoma kinase gene rearrangement in a patient with right colon cancer Chun-Hui Lee, Chung-Ta Lee, Yi-Lin Chen, Bo-Wen Lin, Peng-Chang Lin, Meng-Ru Shen, Yu-Min Yeh Journal of Cancer Research and Practice 2019 6(2):89-91 Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity worldwide. Recent genome-scale molecular analyses have uncovered several potential therapeutic targets for this disease, including BRAF mutation, ERBB2 amplification, and neurotropic tropomyosin receptor kinase fusion gene. Gene rearrangements involving anaplastic lymphoma kinase (ALK) gene have been identified as oncogenic drivers in lung adenocarcinomas, and to be highly sensitive to selective kinase inhibitors. To the best of our knowledge, CRC harboring the ALK fusion gene has rarely been reported. Herein, we report a patient with right colon cancer harboring an ALK gene rearrangement and review the clinicopathologic features as well as potential therapeutic targeting of ALK-rearranged CRC in the literature. |
| Pembrolizumab-induced uveitis in a patient with metastatic urothelial carcinoma Lo-Ho Chen, Jhe-Cyuan Guo Journal of Cancer Research and Practice 2019 6(2):92-95 Immune checkpoint blockade, especially targeting the programmed cell death protein-1/programmed death-ligand 1 axis, has changed the paradigm of anticancer therapy in several cancer types. For urothelial carcinoma (UC), pembrolizumab is an immune checkpoint inhibitor approved by the US Food and Drug Administration for locally advanced or metastatic disease. The new anticancer modalities are complicated with immune-related adverse events (irAEs) which are significantly different from conventional treatment such as chemotherapy or targeted therapy. Herein, we present an 85-year-old man with metastatic UC who developed a rare kind of irAE, uveitis, under pembrolizumab therapy, who fortunately partially recovered with local and systemic steroids. |
| Inflammatory Pseudotumor of the Liver Tsen-Long Yang, Hong-Chuen Chang Journal of Cancer Research and Practice 2019 6(2):96-99 Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, characterized by chronic infiltration of inflammatory cells and areas of necrosis mimicking a malignant tumor. Few cases have been reported, and the precise etiology is still unknown. Patients usually present with abdominal pain, fever, and jaundice. Herein, we report the case of a 78-year-old male with a history of diabetes mellitus who had abdominal fullness and body weight loss for 4 months. A computed tomography scan showed a 15-cm liver tumor in segment 2 and 3 and suspected hepatocellular carcinoma. Left hepatectomy was performed, and the pathology showed IPT. After surgery, the symptom of abdominal fullness subsided. |
| Cervical cancer with breast metastasis Ching-Ting Wei, Cheuk-Kwan Sun, Jen-Wei Tsai, Chi-Feng Fu Journal of Cancer Research and Practice 2019 6(2):100-102 Breast metastasis from extramammary solid malignancies is rare, and cervical cancer is an especially uncommon origin. It is clinically challenging to differentiate a primary breast cancer from a metastatic lesion if the patient presents with inflammatory breast skin, axillary lymphadenopathy, and ipsilateral upper-limb lymphedema. Herein, we described the first case of cervical squamous cell carcinoma with breast metastasis presenting as an inflammatory breast lesion in Taiwan. A 41-year-old woman visited our outpatient clinic with edema of bilateral lower legs as well as a reddish left breast and indurated skin. After systemic workup, she was diagnosed as having cervical cancer with peritoneal carcinomatosis and breast and multiple lymph node metastases for which she received palliative chemotherapy. However, bone metastasis developed, and she died 9 months after the diagnosis. We also reviewed relevant literature on breast metastases from an extramammary origin. |
| Pulmonary pleomorphic carcinoma harboring epidermal growth factor receptor mutation: Response to afatinib Abeer Hussien Anter, Majid Al-Jahel, Rasha Mohamed AbdelLatif, Mohamed Fouad AbdELmohsen, Ahmed Shata Journal of Cancer Research and Practice 2019 6(2):103-106 Pulmonary pleomorphic carcinoma (PPC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy. We report a case of a 56-year-old female, diagnosed with PPC of the lung at clinical Stage IV in July 2017. She underwent first-line chemotherapy. The disease progressed after 6 cycles of chemotherapy, and we shift to afatinib due to presence of epidermal growth factor receptor (EGFR) mutation in exon 19. We then started second-line treatment in the form of molecular targeted therapy (afatinib), to which she had a partial response. Hence, we recommend the evaluation of driver gene alterations such as EGFR in the treatment of advanced PPC. |
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
Nursing and Midwifery Sciences
| Effect of cognitive behavior therapy integrated with mindfulness on perceived pain and pain self-efficacy in patients with breast cancer Mohammad-Rasul Mozafari-Motlagh, Hamid Nejat, Hasan Tozandehjani, Ali-Akbar Samari Journal of Nursing and Midwifery Sciences 2019 6(2):51-56 Context: Cancer pain in a complicated situation for patients with breast cancer. Researchers suggested to use complementary and alternative method in order to reduction pain and side effects in these patients. Aims: This study was aimed to investigate the effectiveness of mindfulness integrated with cognitive behavioral therapy (MiCBT) on perceived pain and pain self-efficacy in patients with breast cancer. Settings and Design: In this clinical trial study, a semi-experimental method was used. Patients with breast cancer were recurred from cancer clinic of a hospital of Mashhad University of Medical Sciences. Material and Methods: Twenty-four patients with breast cancer selected through purposive sampling method and randomly assigned with permutation blocks in two groups of intervention (n = 12) and control (n = 12). The groups were assessed by demographic questionnaire, Perceived Pain Scale, and Pain Self-efficacy Scale before, immediate, and 1 month after the intervention. Participants in the interventional group received MiCBT for 8 weeks. Statistical Analysis Used: Data were analyzed using descriptive methods and multivariate analysis of covariance. Results: The results showed that the interventional group had a significant decrease in perceived pain (P > 0.05). The pain self-efficacy of patients significantly increased in comparison to the control group in posttest and follow-up stage (P < 0.05). Conclusion: According to the results, it can be concluded that using integrated therapy with mindfulness has been effective in reducing pain and enhancing pain self-efficacy in breast cancer patients. Therefore, it can be an adequate complementary therapy for patients with breast cancer. |
| The lived experiences of patients with spinal muscular atrophy: A phenomenological study Ali-Asghar Jesmi, Leila Jouybari, Akram Sanagoo Journal of Nursing and Midwifery Sciences 2019 6(2):57-62 Context: Spinal muscular atrophy (SMA) is a neuromuscular disease which, in addition to physical disability, causes psychological and social problems for patients and their families. If physiological and mental disorders continue to persist for a long time, it leads to serious deterioration in the patient's physical condition, influences the treatment process, and prevents the outcome of the therapies. Aims: The aim of this study was to explore the lived experiences of patients with SMA. Setting and Design: In this qualitative study, a total of six participants (five patients and one patients' wife) were selected by purposive sampling method. Material and Methods: Data were collected by semi-structured interview. Eleven interviews were conducted and analyzed by Colaizzi's descriptive phenomenological approach. Statistical Analysis Used: Data were analyzed by One Note soft ware version 14.0 with Colaizzi's descriptive phenomenological approach. Results: Two main themes – “tragic life” and “vague future” – emerged from data analysis. They had four categories including “physical and psychological problems,” “limitations and lost opportunities,” “concerns,” and “uncertain future.” Conclusions: These patients experienced a lot of physical and psychological impairments in their life. They have many concerns and lost some opportunities. Therefore, policymakers and authorities should support these patients for participating as an effective members in the society, consequently their feeling improve by getting independent. |
| Modeling of cardiac function of patients with acute myocardial infarction based on Type-D personality: Mediating role of negative emotions Marzieh Mohammadi Pashaki, Yarali Dousti, Bahram Mirzaian Journal of Nursing and Midwifery Sciences 2019 6(2):63-71 Context: Cardiac function of patients with acute myocardial infarction (MI) plays a central role in their prognosis. Aims: The purpose of this study was to model the cardiac function of these patients based on Type-D personality and the mediating role of negative emotions (anger, depression, and anxiety) in this relationship. Setting and Design: This correlational study was performed using the structural equation modeling method, and specifically the regression equations (combination of path analysis and second-order factor analysis). Material and Methods: The study population was the patients with acute ST-segment elevation MI (STEMI) who were hospitalized at Mazandaran Cardiovascular Hospital and underwent under primary percutaneous coronary intervention treatment in 2017 and 2018. Using Mueller's formula modeling formula (1996) based on a sample size-to-free parameter ratio, the sample size was calculated to 220 patients were chosen by the purposive method. Data were collected using Denollet'sType-DScale-14, the Spielberger's state-trait anxiety inventory, short-form of the beck depression inventory-13, and Spielberger's state-trait anger expression inventory-2. Statistical Analysis Used: Data analysis was performed using SPSS-18 and AMOS 23. Results: Type-D personality can directly predict of the cardiac function of patients with acute STEMI. This variable also predicts the the cardiac function of these patients via the mediation of negative emotions (anger, depression, and anxiety). Conclusion: Type-D personality affects the incidence and prognosis of myocardial infarction via negative emotions. It is, therefore, recommended to screen the susceptible populations for this personality type. |
| The effect of teaching on team-based learning and group discussion on learning and academic motivation of operating room students in the technology of gastrointestinal surgery lesson Zahra Aliakbarzadeh Arani, Mahsa Haji Mohammad Hoseini, Leila Ghanbari Afra, Maede Mohammadzade Journal of Nursing and Midwifery Sciences 2019 6(2):72-77 Context: Using of varied teaching methods may be effective in motivating to learn better. Aims: The present study aimed to compare the effect of teaching based on team-based learning (TBL) and group discussion methods on academic motivation and learning of operating room students in the technology of gastrointestinal surgery lesson in Qom University of Medical Sciences. Settings and Design: This semi-experimental study was conducted among two groups of continuous and discontinuous undergraduate course students of operating room in Qom University of Medical Sciences in 2016–2017. The sampling method was the census. A combination of the TBL method and lecture was conducted randomly among group of continuous undergraduate course students (21 persons) and group discussion among discontinuous undergraduate course students (14 persons). Material and Methods: Hartler's motivation questionnaire completed by the students at the first and last semesters. The test was also carried out immediately after the end of the term and four months after that. Statistical Analysis Used: Data were analyzed using frequency, percent, and independent and paired t-test in SPSS 13 software. Results: Comparison of educational motivation score in both groups before and after the intervention was not significant (P > 0.05). Academic motivation, after the intervention, was significant in both groups (P > 0.05). Comparison of scores did not differ between the two groups immediately after training and 4 months later (P > 0.05). Conclusions: Considering the lack of significant difference between TBL and group discussion in learning and increasing the level of academic motivation of students due to the use of these two methods, it is suggested that TBL and the group discussion replace with the common teaching methods, including lectures. |
| The effect of group singing on the happiness of older people Maryam Entezari, Manijeh Zakizadeh, Jamshid Yazdani, Zohreh Taraghi Journal of Nursing and Midwifery Sciences 2019 6(2):78-83 Context: Happiness is important for all age groups; however, it is more highlighted in elders. Aims: The aim of the current study was to determine the effect of group singing on the happiness of older people. Setting and Design: In this quasi-experimental study, sixty participants selected among elderly referred to two Day Care Centers of Mazandaran. Materials and Methods: Samples were assigned to two groups of intervention (n = 30)and control (n = 30). The intervention group was assigned into three groups of 10. Each group selected a song from the list of songs and performed it for 10 min. This process was repeated one more time. The intervention was performed two times a week, for 3 weeks. In the control group, no intervention was performed and the elderly received the usual care. The happiness score of both groups, before and 1 month after the end of the intervention, was measured using the Oxford Happiness Inventory. Statistical Analysis Used: Data were analyzed using independent t-test, Chi-square test, and ANCOVA. Results: Before intervention, the mean scores of happiness in the intervention and control groups were 4.38 ± 0.48 and 4. 53 ± 0.26, respectively (P = 0.138). One month after intervention, the mean scores of happiness in the intervention and control groups were 4.77 ± 0.37 and 4.35 ± 0.18, respectively (P = 0.004). Conclusion: The results of this study showed that group singing was effective on the happiness of the elderly. More studies in day-care centers and other settings, especially nursing homes, are recommended. Implementation of such measures is recommended in the day-care centers. |
| The mediating role of emotional distress tolerance in relationship between self-discrepancy with anxiety in people suffering from special phobias Alireza Sangani, Paria Jangi, Nahid Ramak, Aniseh Ahmadi Journal of Nursing and Midwifery Sciences 2019 6(2):84-90 Context: The basis of anxiety disorders in cognitive and emotional fields can be effective in coping strategies to anxiety. Aims: This research aimed to investigate the mediating role of emotional distress tolerance in relationship between self-discrepancy with anxiety in people suffering from special phobias. Settings and Design: The present study was a correlational research with structural equation modeling. Materials and Methods: The statistical population of this study was all individuals suffering from specific phobia disorders in the 5th Azar Hospital in Gorgan City. The sample size selection, which was made by Loehlin method (2004), was 220 persons suffering from anxiety disorder referring to Psychiatric Clinics of 5 Azar Hospital in Gorgan City and was investigated by purposeful sampling. Data gathering tools included Distress Tolerance Scale, self-discrepancy questionnaire, and Spielberger State-Trait Anxiety Inventory. Statistical Analysis Used: The collected data were analyzed using structural regression equations using SPSS 18 and Amos 23 software. Results: The findings showed that the research model is fit and overall, 42% of the anxiety could be explained through emotional stress tolerance and self-discrepancy, and emotional distress tolerance has a mediating role in relationship self-discrepancy with anxiety. Conclusions: The results of this research emphasized the necessity of self-discrepancy as well as the role of mediator of emotional distress tolerance in anxiety in people suffering from special phobias, which can provide applied templates for improving the psychological state of anxious individuals with therapists and counselors. |
| Relationship between Self-efficacy and Perceived Burden among Schizophrenic Patients' Caregivers Azar Ramzani, Mehran Zarghami, Jamshid Yazdani Charati, Maedeh Bagheri, Hamideh Azimi Lolaty Journal of Nursing and Midwifery Sciences 2019 6(2):91-97 Context: Caregiver burden is high in schizophrenia. Self-efficacy is an emotional and behavioral response to such stressors. Aims: The aim of the study is to determine the relationship between self-efficacy and the perceived' burden among schizophrenic patients' caregivers. Setting and Design: A total of 384 schizophrenic patients' caregivers referring to a psychiatry Clinic in Sari, Iran, were selected via convenient sampling, for this descriptive correlational study. Materials and Methods: The caregivers filled the demographic questionnaire (the patient and the caregivers), the Zarit burden interview, and the general self-efficacy scale. Statistical Analysis Used: Using SPPS 20 software, the demographics of the caregivers were compared using Chi-square tests for categorical data and t- tests for continuous data. Pearson's correlation and regression method were applied after normality testing (P > 0.05). Results: Among 40.5%, 38.7%, and 7.7% of the caregivers, the burden was mild-to-average, average-to-severe, and highly severe, respectively. The mean of caregivers' self-efficacy and burden was 28.79 ± 5.60 and 40.11 ± 13.60, respectively. Furthermore, the burden had significant relationship with the patient's disease duration and income, caregiver's educational level, job, economic status, and relationship with the patient (P < 0.05). Besides, the caregivers' self-efficacy had meaningful relationship with the patient's gender, income potential, housing status, and with the caregiver's age, gender, educational level, job, housing status, economic status, and relationship with the patient (P < 0.05). The relationship between caregivers' burden and self-efficacy was significantly negative (r = −0.445, P = 0.001). Conclusion: When the self-efficacy increases, the caregiver's burden decreases. The importance of economic status of the caregivers and the patient requires special attention. |
| Prevention and management catheter-associated urinary tract infection in intensive care unit Mehdi Rahimi, Khosro Farhadi, Hossein Babaei, Firouz Soleymani Journal of Nursing and Midwifery Sciences 2019 6(2):98-103 Context: Urinary tract infection (UTI) is the most common hospital-acquired infection. Around 80% of UTIs are associated with urinary catheters. Aims: The aim of this study was to review and to describe epidemiology and approaches for the prevention and management of catheter-associated urinary tract infection (CAUTI) in intensive care unit (ICU) patients. Settings and Design: A narrative review of studies was undertaken. Materials and Methods: A review of PubMed, Google Scholar, Medline, and CINAHL databases were conducted to identify peer-reviewed, English language, and studies published between 1999 and 2018. Related papers were reviewed with using standard keywords. The research was conducted on epidemiology and management of CAUTI in the ICU. Of the 186 English publications, 36 were duplicates. Statistical Analysis Used: Quality assessments, data extractions, and analysis were completed on all included studies. Results: The prevalence of UTI in the ICU is directly related to the widespread use of urethral catheter (32.2%). Guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections for CAUTI. Conclusions: Further studies are needed due to the importance and high prevalence of these infections. We recommend the opportunity to increase any strategy able to reduce the incidence of infections related to urinary catheterization and its consequences in ICUs. |
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
Critical Care Medicine
| Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass Objectives: Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass–related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression. Design: In vitro studies with human peripheral blood mononuclear cells. Setting: Cardiosurgical ICU, University Research Laboratory. Patients: Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018). Interventions: Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15+ cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested. Measurements and Main Results: After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8+-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence. Conclusions: Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass. Drs. Hübner and Tomasi contributed equally to this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by institutional grants of the LMU Munich. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Simone Kreth, MD, PhD, Department of Anesthesiology, University Hospital, LMU Munich, Marchioninistr 15, 81377 Munich, Germany. E-mail: simone.kreth@med.uni-muenchen.de Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| Factors Associated With Quality of Death in Korean ICUs As Perceived by Medical Staff: A Multicenter Cross-Sectional Survey Objectives: Facilitating a high quality of death is an important aspect of comfort care for patients in ICUs. The quality of death in ICUs has been rarely reported in Asian countries. Although Korea is currently in the early stage after the implementation of the "well-dying" law, this seems to have a considerable effect on practice. In this study, we aimed to understand the status of quality of death in Korean ICUs as perceived by medical staff, and to elucidate factors affecting patient quality of death. Design: A multicenter cross-sectional survey study. Setting: Medical ICUs of two tertiary-care teaching hospitals and two secondary-care hospitals. Patients: Deceased patients from June 2016 to May 2017. Interventions: Relevant medical staff were asked to complete a translated Quality of Dying and Death questionnaire within 48 hours after a patient's death. A higher Quality of Dying and Death score (ranged from 0 to 100) corresponded to a better quality of death. Measurements and Main Results: Total 416 completed questionnaires were obtained from 177 medical staff (66 doctors and 111 nurses) of 255 patients. All 20 items of the Quality of Dying and Death received low scores. Quality of death perceived by nurses was better than that perceived by doctors (33.1 ± 18.4 vs 29.7 ± 15.3; p = 0.042). Performing cardiopulmonary resuscitation and using inotropes within 24 hours before death were associated with poorer quality of death, whereas using analgesics was associated with better quality of death. Conclusions: The quality of death of patients in Korean ICUs was considerably poorer than reported in other countries. Provision of appropriate comfort care, avoidance of unnecessary life-sustaining care, and permission for more frequent visits from patients' families may correspond to better quality of death in Korean medical ICUs. It is also expected that the new legislation would positively affect the quality of death in Korean ICUs. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Dr. J. Y. Cho received funding from Seoul National University Bundang Hospital research grant. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Yeon Joo Lee, MD, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea. E-mail: yjlee1117@snubh.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| Neurologic Complications of Infective Endocarditis: A Joint Model for a Septic Thromboembolism and Inflammatory Small Vessel Disease Objectives: Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model. Design: Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls. Setting: Research laboratory of a university hospital. Subjects: Male Wistar rats. Interventions: Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions. Measurements and Main Results: In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02). Conclusions: This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by the Société Française NeuroVasculaire. Dr. Cantier received support for article research from Société Française de Neurologie Vasculaire. Dr. Olivot received funding from consulting for Servier, Medtronic, and Astra Zeneca, and he received speaker fees from Bristol Myers Squibb and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: marie.cantier@aphp.fr; mikael.mazighi@aphp.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| Pro: Should Patients With Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation Have Ventilatory Support Reduced to the Lowest Tolerable Settings? No abstract available |
| Why the Adjunctive Corticosteroid Treatment in Critically Ill Patients With Septic Shock (ADRENAL) Trial Did Not Show a Difference in Mortality? No abstract available |
| Impact on Patient Outcomes of Pharmacist Participation in Multidisciplinary Critical Care Teams: A Systematic Review and Meta-Analysis Objectives: The objective of this systematic review and meta-analysis was to assess the effects of including critical care pharmacists in multidisciplinary ICU teams on clinical outcomes including mortality, ICU length of stay, and adverse drug events. Data Sources: PubMed, EMBASE, and references from previous relevant systematic studies. Study Selection: We included randomized controlled trials and nonrandomized studies that reported clinical outcomes such as mortality, ICU length of stay, and adverse drug events in groups with and without critical care pharmacist interventions. Data Extraction: We extracted study details, patient characteristics, and clinical outcomes. Data Synthesis: From the 4,725 articles identified as potentially eligible, 14 were included in the analysis. Intervention of critical care pharmacists as part of the multidisciplinary ICU team care was significantly associated with the reduced likelihood of mortality (odds ratio, 0.78; 95% CI, 0.73–0.83; p < 0.00001) compared with no intervention. The mean difference in ICU length of stay was –1.33 days (95% CI, –1.75 to –0.90 d; p < 0.00001) for mixed ICUs. The reduction of adverse drug event prevalence was also significantly associated with multidisciplinary team care involving pharmacist intervention (odds ratio for preventable and nonpreventable adverse drug events, 0.26; 95% CI, 0.15–0.44; p < 0.00001 and odds ratio, 0.47; 95% CI, 0.28–0.77; p = 0.003, respectively). Conclusions: Including critical care pharmacists in the multidisciplinary ICU team improved patient outcomes including mortality, ICU length of stay in mixed ICUs, and preventable/nonpreventable adverse drug events. Drs. Lee and Ryu contributed equally to this work as co-first authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by the Korean Hospital Pharmaceutical Education & Research Center (No. KSHPERC-18-01). The authors have disclosed that they have no potential conflicts of interest. For information regarding this article, E-mail: eykimjcb777@cau.ac.kr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| Adjusting for Disease Severity Across ICUs in Multicenter Studies Objectives: To compare methods to adjust for confounding by disease severity during multicenter intervention studies in ICU, when different disease severity measures are collected across centers. Design: In silico simulation study using national registry data. Setting: Twenty mixed ICUs in The Netherlands. Subjects: Fifty-five–thousand six-hundred fifty-five ICU admissions between January 1, 2011, and January 1, 2016. Interventions: None. Measurements and Main Results: To mimic an intervention study with confounding, a fictitious treatment variable was simulated whose effect on the outcome was confounded by Acute Physiology and Chronic Health Evaluation IV predicted mortality (a common measure for disease severity). Diverse, realistic scenarios were investigated where the availability of disease severity measures (i.e., Acute Physiology and Chronic Health Evaluation IV, Acute Physiology and Chronic Health Evaluation II, and Simplified Acute Physiology Score II scores) varied across centers. For each scenario, eight different methods to adjust for confounding were used to obtain an estimate of the (fictitious) treatment effect. These were compared in terms of relative (%) and absolute (odds ratio) bias to a reference scenario where the treatment effect was estimated following correction for the Acute Physiology and Chronic Health Evaluation IV scores from all centers. Complete neglect of differences in disease severity measures across centers resulted in bias ranging from 10.2% to 173.6% across scenarios, and no commonly used methodology—such as two-stage modeling or score standardization—was able to effectively eliminate bias. In scenarios where some of the included centers had (only) Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology Score II available (and not Acute Physiology and Chronic Health Evaluation IV), either restriction of the analysis to Acute Physiology and Chronic Health Evaluation IV centers alone or multiple imputation of Acute Physiology and Chronic Health Evaluation IV scores resulted in the least amount of relative bias (0.0% and 5.1% for Acute Physiology and Chronic Health Evaluation II, respectively, and 0.0% and 4.6% for Simplified Acute Physiology Score II, respectively). In scenarios where some centers used Acute Physiology and Chronic Health Evaluation II, regression calibration yielded low relative bias too (relative bias, 12.4%); this was not true if these same centers only had Simplified Acute Physiology Score II available (relative bias, 54.8%). Conclusions: When different disease severity measures are available across centers, the performance of various methods to control for confounding by disease severity may show important differences. When planning multicenter studies, researchers should make contingency plans to limit the use of or properly incorporate different disease measures across centers in the statistical analysis. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Dr. Brakenhoff and Dr. Plantinga contributed equally. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Dr. de Keizer institution received funding from National Intensive Care Evaluation foundation, during the conduct of the study (grants and advisory board member). Dr. Groenwold was supported financially by the Netherlands Organisation for Scientific Research (project 917.16.430). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: N.L.Plantinga@umcutrecht.nl Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| Recommendation of New Medical Alarms Based on Audibility, Identifiability, and Detectability in a Randomized, Simulation-Based Study Objectives: Accurate and timely identification of existing audible medical alarms is not adequate in clinical settings. New alarms that are easily heard, quickly identifiable, and discernable from one another are indicated. The "auditory icons" (brief sounds that serve as metaphors for the events they represent) have been proposed as a replacement to the current international standard. The objective was to identify the best performing icons based on audibility and performance in a simulated clinical environment. Design: Three sets of icon alarms were designed using empirical methods. Subjects participated in a series of clinical simulation experiments that examined the audibility, identification accuracy, and response time of each of these icon alarms. A statistical model that combined the outcomes was used to rank the alarms in overall efficacy. We constructed the "best" and "worst" performing sets based on this ranking and prospectively validated these sets in a subsequent experiment with a new subject sample. Setting: Experiments were conducted in simulated ICU settings at the University of Miami. Subjects: Medical trainees were recruited from a convenience sample of nursing students and anesthesia residents at the institution. Interventions: In Experiment 1 (formative testing), subjects were exposed to one of the three sets of alarms; identical setting and instruments were used throughout. In Experiment 2 (summative testing), subjects were exposed to one of the two sets of alarms, assembled from the best and worst performing alarms from Experiment 1. Measurements and Main Results: For each alarm, we determined the minimum sound level to reach audibility threshold in the presence of background clinical noise, identification accuracy (percentage), and response time (seconds). We enrolled 123 medical trainees and professionals for participation (78 with < 6 yr of training). We identified the best performing icon alarms for each category, which matched or exceeded the other candidate alarms in identification accuracy and response time. Conclusions: We propose a set of eight auditory icon alarms that were selected through formative testing and validated through summative testing for adoption by relevant regulatory bodies and medical device manufacturers. This work was performed at the University of Miami. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http;/journals.lww.com/ccmjournal). Supported, in part, by grant from Association for the Advancement of Medical Instrumentation. Drs. Bennett's, Dudaryk's, Edworthy's, and McNeer's institution received funding from Association for the Advancement of Medical Instrumentation. Dr. Crenshaw disclosed that she does not have any potential conflicts of interest. For information regarding this article, E-mail: mcneer@miami.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| A 360° Rotational Positioning Protocol of Organ Donors May Increase Lungs Available for Transplantation Objectives: To evaluate the improvement in lung donation and immediate lung function after the implementation of a 360° rotational positioning protocol within an organ procurement organization in the Midwest. Design: Retrospective observational study. Setting: The Midwest Transplant Network from 2005 to 2017. Rotational positioning of donors began in 2008. Subjects: Potential deceased lung donors. Interventions: A 360° rotational protocol. Presence of immediate lung function in recipients, change in PaO2:FIO2 ratio during donor management, initial and final PaO2:FIO2 ratio, and proportion of lungs donated were measured. Outcomes were compared between rotated and nonrotated donors. Measurements and Main Results: A total of 693 donors were analyzed. The proportion of lung donations increased by 10%. The difference between initial PaO2:FIO2 ratio and final PaO2:FIO2 ratio was significantly different between rotated and nonrotated donors (36 ± 116 vs 104 ± 148; p < 0.001). Lungs transplanted from rotated donors had better immediate function than those from nonrotated donors (99.5% vs 68%; p < 0.001). Conclusions: There was a statistically significant increase in lung donations after implementing rotational positioning of deceased donors. Rotational positioning significantly increased the average difference in PaO2:FIO2 ratios. There was also superior lung function in the rotated group. The authors recommend that organ procurement organizations consider adopting a rotational positioning protocol for donors to increase the lungs available for transplantation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). University of Missouri Kansas City and Midwest Transplant Network are sponsoring institutions. Dr. Whitt received funding from Midwest Transplant Network. Dr. Wilkins disclosed that he is the administrative Medical Director for, and is also a member of, Midwest Transplant Network. The remaining authors have disclosed that they do not have any potential conflicts of interest For information regarding this article, E-mail: mendezmar@umkc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
| Clinician Perception of a Machine Learning–Based Early Warning System Designed to Predict Severe Sepsis and Septic Shock Objective: To assess clinician perceptions of a machine learning–based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). Design: Prospective observational study. Setting: Tertiary teaching hospital in Philadelphia, PA. Patients: Non-ICU admissions November–December 2016. Interventions: During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert's helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. Measurements and Main Results: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient's risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. Conclusions: In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning–based sepsis alerts. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Ginestra, Dr. Schweickert, Ms. Meadows, Mr. Lynch, and Ms. Pavan helped with data collection; Dr. Ginestra helped with analysis and interpretation of the data, and drafting of the article; and all authors helped with conception and design, and critical revision of the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http;/journals.lww.com/ccmjournal). Dr. Umscheid's contribution to this project was supported, in part, by the National Center for Research Resources (grant no: UL1RR024134), which is now at the National Center for Advancing Translational Sciences (grant no: UL1TR000003). Presented as a poster at the 2017 Society of Hospital Medicine Annual Meeting, Las Vegas, NV. Dr. Schweickert has received funding from the American College of Physicians and Arjo. Dr. Umscheid's institution has received funding from the National Institutes of Health, Food and Drug Administration, and Agency for Healthcare Research and Quality Evidence-based Practice Center contracts, and he has received funding from the Patient-Centered Outcomes Research Institute Advisory Panel and Northwell Health (grand rounds honoraria). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Craig A. Umscheid, MD, MS, Office of Clinical Excellence, University of Chicago Medicine, American School Building, 850 E. 58th Street, Suite 123, Office 128, MC 1135, Chicago, IL 60637. E-mail: craigumscheid@medicine.bsd.uchicago.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
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