Mechanistic insight of cyclin-dependent kinase 5 in modulating lung cancer growth G. M. Shazzad Hossain Prince, Tsung-Ying Yang, Ho Lin, Mei-Chih Chen Chinese Journal of Physiology 2019 62(6):231-240 Lung harbors the growth of primary and secondary tumors. Even though numerous factors regulate the complex signal transduction and cytoskeletal remodeling toward the progression of lung cancer, cyclin-dependent kinase 5 (Cdk5), a previously known kinase in the central nervous system, has raised much attention in the recent years. Patients with aberrant Cdk5 expression also lead to poor survival. Cdk5 has already been employed in various cellular processes which shape the fate of cancer. In lung cancer, Cdk5 mainly regulates tumor suppressor genes, carcinogenesis, cytoskeletal remodeling, and immune checkpoints. Inhibiting Cdk5 by using drugs, siRNA or CRISP-Cas9 system has rendered crucial therapeutic advantage in the combat against lung cancer. Thus, the relation of Cdk5 to lung cancer needs to be addressed in detail. In this review, we will discuss various cellular events modulated by Cdk5 and we will go further into their underlying mechanism in lung cancer.

Identification of the force–velocity curve on dynamic resistance exercise for rats Hugo A. P. Santana, Hamilton Miotto, Keemilyn K. S. Silva, Rodolfo A Dellagrana, Jeeser A Almeida Chinese Journal of Physiology 2019 62(6):241-244 The aim of this study was to identify force–velocity and power–velocity curves in climbing activity protocols, used as dynamic resistance exercise in rats. Eighteen 45-day-old male Wistar rats (weight = 211.9 ± 5.2 g) were evaluated. After familiarization to the climbing procedure, the animals performed an incremental climbing test (load relative to 75% of the body mass at first stage, followed by 30 g increments with and 120 s recovery between climbs) to determine the maximum carrying capacity (MCC). After this, the animals climbed with different loads (without load, 10%, 20%, 30%, 40%, 50%, 75%, 90%, and 100% of MCC) with 120 s recovery between climbs. Time for each climb was recorded to calculate the mechanical power. The peak power was reached at 30% of MCC. For the force–velocity curve, an inversely proportional relation was observed between force and velocity, as expected, greater forces were expressed in lower velocities. Therefore, our results suggest that training at 30% of MCC should be encouraged aiming the target for greater power output and 90%–100% of MCC should be the load aiming for strength training in climbing activities for rats.

Sex differences and the modulating effects of gonad intactness on behavioral conformity in a mouse model Chianfang G Cherng, Lung Yu Chinese Journal of Physiology 2019 62(6):245-255 Although gender differences in conformity are noticed in human studies, cultural norms and psychosocial factors inevitably affect such differences. Biological factors, especially the gonadal hormones and the brain regions involved, contributing to the sex differences in behavioral conformity remained scarcely explored. To prevent psychosocial and cultural norm confounds, intact and gonadectomized male and female mice were used to assess the modulating effects of gonadal hormones on behavioral conformity and such conformity-related brain regions using an approach of choice paradigm. Intact and gonadectomized mice' choices for the nonrewarded runway were assessed when these experimental mice were alone versus with a group, consisting of three same-sex noncagemates choosing the respective experimental mice' nonrewarded runway, in a double-J-shaped maze test. Although male and female mice exhibited comparable rewarded runway choices at the conclusion of the operant training procedures and in the test individually, male mice demonstrated greater conformity index as compared to female mice when group tested. Gonadectomy, done at their 4 or 9 weeks of age, decreased males' conformity index but did not affect females' when both sexes were group tested. Such gonadectomy did not affect the conditioning or conformity index when tested individually in either sex. Female mice had higher serum corticosterone (CORT) levels when group tested as compared to the female mice tested individually and male mice. Finally, the number of FOS-staining cells in high conformity-displaying mice was found less than it in the low conformity-performing mice in the nucleus accumbens. Taken together, we conclude that testis-derived hormones, at least, play a role in enhancing behavioral conformity in male mice. CORT and nucleus accumbal neuronal activity deserve further investigation for their involvement in behavioral conformity.

Changes in the microvasculature and hemostatic system in rats after insonation Yuliya Bondarchuk, Marina Nosova, Igor Shakhmatov Chinese Journal of Physiology 2019 62(6):256-260 Ultrasound, one of the most physically impactful factors of the modern human living environment, can cause hemodynamic changes in the microvasculature and the hemostatic system. Such shifts can be considered as possible predictors of cardiovascular diseases and their complications. This study aimed to examine the effect of 7-day in-air insonation on the microvasculature and hemostatic system of rats. The study included 28 male Wistar rats. A group of study animals was insonated over 7 days at a frequency of 25 kHz. The emitters were installed in a vertical position at a distance of 10 cm from both the sidewalls of a coarse wire cage. The sound pressure was 89.0 dB and power flux density was 7.73 ± 0.03 W/cm2. The microvasculature values of the study rats obtained by laser Doppler flowmetry were compared to those of control animals. To evaluate the hemostatic system, an integral research method, thromboelastography, was used. In the study rats, in response to 7-day insonation, statistically significant decreases in the active and passive factors of blood circulation modulation were observed compared to the control animals: microcirculation, flux, amplitude of endothelial and vasomotor vibrations, and amplitude of respiratory and pulse waves. According to the thromboelastography data, prolonged coagulation time at the initial stage and inhibited fibrinolytic activity were recorded. Thus, the study animals showed signs of a stress reaction based on changes in their microcirculatory parameters confirmed by increased serum concentrations of adrenocorticotropic hormone and cortisol and analysis of behavioral reactions in the open-field test.

Sex Differences in antiaging response to short- and long-term high-intensity interval exercise in rat cardiac muscle: Telomerase activity, total antioxidant/oxidant status Marziyeh Saghebjoo, Saber Sadeghi-Tabas, Iman Saffari, Azin Ghane, Ivan Dimauro Chinese Journal of Physiology 2019 62(6):261-266 Cardiovascular disease prevails with age which varies according to sex. Telomere length plays an important role in aging. Despite the great benefits of high-intensity interval training (HIIT), the acute responses to HIIT with different intervals have not been elucidated in different sexes. This study was conducted to investigate the sex-dependent responses of telomerase enzyme activity, total oxidant status (TOS), total antioxidant capacity (TAC), and the ratio of TAC/TOS to short- and long-term high-intensity interval exercise (HIIE) in cardiac muscle of male and female rats. Forty adult Wistar rats were randomly allocated to six groups: male and female HIIE with short-term intervals (MHIIESh and FHIIESh, respectively), male and female HIIE with long-term intervals (MHIIEL and FHIIEL, respectively), and controls groups. Telomerase activity, TAC, and TOS levels were examined immediately after exercise in the cardiac muscle. The level of telomerase enzyme activity, TOS level, and the ratio of TAC/TOS did not change after HIIE with short-term interval and HIIE with long-term interval (HIIEL) in male and female rats (P = 0.52, 0.69, and 0.08, respectively). There was a statistically significant decrease in the TAC level in the MHIIESh group (P = 0.04). Furthermore, a significant decrease was observed in the HIIEL in both male and female rats (P = 0.03 and 0.04, respectively). Acute exposure to HIIE with short- and long-term intervals would not result in a significant change in some indicators of biological aging. However, due to gender-specific biological differences, further studies will provide evidence regarding the roles of HIIE at different times of intervals, which contribute to aging prevention.

Contrasting actions of ginsenosides Rb1 and Rg1 on glucose tolerance in rats Rungchai Chaunchaiyakul, Naruemon Leelayuwat, Jin-Fu Wu, Chih-Yang Huang, Chia-Hua Kuo Chinese Journal of Physiology 2019 62(6):267-272 Ginsenoside profile of Panax ginseng is changing with season and cultivated soil. Yet, dose-response relationship of main ginsenosides on metabolic measures has not been documented in vivo. Here, we examined glucose and insulin responses after an oral glucose challenge (0.5 g/kg body weight) at various doses (0.01, 0.1, 1, and 10 mg/kg of body weight) under acute and chronic Rb1 and Rg1 supplemented conditions. The results show that Rb1 (0.01 and 0.1 mg/kg body weight) increased, whereas Rg1 (0.01 mg/kg body weight) decreased postprandial glucose levels compared with the Vehicle group (P < 0.05). This contrasting effect reduced as dose increased. Both Rb1 and Rg1 decreased the mitochondrial enzyme citrate synthase activity (P < 0.05) together with decreases in glycogen content in red gastrocnemius muscle and body temperature at low doses (P < 0.05), compared with the Vehicle group. These differences also diminished as dosage increases. For reliable ginseng research, dose standardization on Rg1 and Rb1 is essential based on their opposing action and peculiar dose-response relationship. Both major ginsenosides may influence dynamics of mitochondria turnover and alter muscle metabolism.

The impact of high-intensity laser therapy on oxidative stress, lysosomal enzymes, and protease inhibitor in athletes Łukasz Sielski, Paweł Sutkowy, Pawlak-Osińska Katarzyna, Alina Woźniak, Agnieszka Skopkowska, Bartosz Woźniak, Jolanta Czuczejko Chinese Journal of Physiology 2019 62(6):273-278 The aim of the study was to assess the effect of one session of high-intensity laser therapy (HILT) on the levels of selected oxidative stress parameters, lysosomal hydrolases, and anti-inflammatory serine protease inhibitor in the peripheral blood of amateur athletes with torn or pulled tendons of the ankle or the knee joint. The group of injured athletes comprised 16 males and females aged 16.3 ± 1.3 years, while the control group of 14 healthy, noninjured amateur athletes of both sexes (controls; age 17.4 ± 4.6 years). Material for the study was peripheral blood taken at three study time points: Immediately before, 30 min after, and 24 h after HILT intervention. In plasma and erythrocytes, thiobarbituric acid reactive substances (TBARSpl and TBARSer, respectively) were determined. In erythrocytes, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. In serum, the activity of acid phosphatase (AcP), arylsulfatase (ASA), cathepsin D (CTS D), and α1-antitrypsin (AAT) were determined. Among oxidative stress parameters, only the CAT activity significantly decreased 24 h after HILT compared to measurement 30 min after the treatment in the injured individuals (P < 0.01), while the GPx activity in that group was meaningfully higher 30 min after HILT compared to controls (P < 0.05). Thirty min after the intervention, the activities of AcP and ASA were lower in the injured participants compared to the uninjured ones (P < 0.01 and P < 0.05, respectively). The CTS D activity was lower 30 min and 24 h after HILT in both groups (P < 0.001) and did not differ significantly between them (P > 0.05). Moreover, the study showed statistically significant linear relationships between the TBARSer concentration and the SOD activity before HILT in the healthy participants (r = -0.6, P = 0.021) and 24 h after HILT in the injured ones (r = 0.6, P = 0.025). In the noninjured athletes before HILT, the CTS D activity linearly correlated with the AAT activity (r = -0.70, P = 0.005), and 30 min after the treatment, with the AcP activity (r = 0.5, P = 0.041). 24 h after the HILT intervention, the CTS D and AcP activities were also correlated in the injured athletes (r = 0.8, P = 0.002). The study suggests that one HILT intervention does not significantly influence the redox equilibrium but stabilizes lysosomal membranes.

Blood dopamine level enhanced by caffeine in men after treadmill running Jeong-Beom Lee, Hye-Jin Lee, Seung-Jea Lee, Tae-Wook Kim Chinese Journal of Physiology 2019 62(6):279-284 The aim of this study was to investigate the plasma dopamine and serum serotonin levels in humans with and without caffeine (CAFF) ingestion during treadmill running exercise. Thirty male volunteers participated in the randomized experiment involving two groups: CON (n = 15, 200 mL of tap water) versus CAFF (n = 15, 3 mg/kg CAFF and 200 mL tap water). After treadmill running, the dopamine level was significantly increased in the CAFF group (P < 0.01) and was significantly higher than in the CON group (P < 0.01). Serotonin was significantly increased in both groups after treadmill running (P < 0.05). However, serotonin levels showed no significant statistical difference between the groups. Prolactin and cortisol were significantly increased in both groups after treadmill running (P < 0.01). However, there was no significant statistical difference between groups. β-endorphin level was significantly increased in the CAFF group at after treadmill running (P < 0.01) and was significantly higher than in CON after treadmill running (P < 0.01). In conclusion, 3 mg/kg CAFF ingestion before treadmill running stimulated dopamine release without inhibiting serotonin, which may reduce central fatigue.

Corrigendum: Action of citral on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in juvenile mice Chinese Journal of Physiology 2019 62(6):285-285

Author Index for Volume 62 Chinese Journal of Physiology 2019 62(6):0-0

Developing Your Career as a Nurse Educator: Try These Strategies No abstract available

Mentoring Clinical Teachers Using Mobile Telepresence Technology No abstract available

TeamSTEPPS Training for Nursing Students Using Pop Culture Media No abstract available

Fostering Prioritization Using a Blended Group and Individual Simulation Approach No abstract available

Getting to the Heart of the Matter: Drawing Cardiovascular Anatomy to Facilitate Learning No abstract available

Teaching Quality Improvement in Prelicensure Education No abstract available

DNP Program Faculty and Graduates' Knowledge and Use of QI and Safety Processes Background Across doctor of nursing practice (DNP) programs, wide variation exists for DNP project expectations and curricular integration of Quality and Safety Education for Nurses competencies. Purpose This study examined DNP project characteristics and compared knowledge, skills, and attitudes about quality improvement (QI) processes between DNP program faculty and graduates. Methods This descriptive study used a national convenience sample of DNP program faculty and graduates from multiple settings (N = 147) who completed an electronic survey of a modified version of the Quality Improvement Knowledge, Skills, and Attitudes Survey. Results Most DNP projects were QI/practice improvement (85.5%) and required interprofessional collaboration (65%) and implementation of a practice change (55.8%) with evaluation (65.5%). DNP program faculty (n = 73) and graduates (n = 30) had no significant differences in QI knowledge or skills; faculty reported less confidence in their knowledge (P = .002) and skills (P = .007) than graduates. Conclusions Faculty development efforts to improve QI knowledge and skills for DNP program faculty are needed.

Asthma Medications: A Think-Pair-Share-Square Activity for Nursing Students No abstract available

Using Virtual Site Visits in the Clinical Evaluation of Nurse Practitioner Students: Student and Faculty Perspectives Background The use of telehealth technology to conduct virtual site visits is an innovative strategy for evaluating the performance of nurse practitioner (NP) students in remote settings. Although there is an abundance of studies on telehealth for the remote monitoring and assessment of patients, there are limited data on its use for evaluating NP students during clinical learning experiences. Purpose The purpose of this project was to understand the perspectives of NP students and faculty on the feasibility of using virtual site visits to evaluate the students' performance during clinical experiences. Methods Online surveys were used to collect student and faculty perspectives on the use of virtual technology during clinical site observations. Results Overall, students and faculty reported positive experiences with the virtual site visits. Conclusion Virtual site visits are feasible in most clinical settings.

Innovative Model to Recognize Previous Military Training of BSN Students Background Many of our military transitioning to civilian life are expertly trained medics, corpsmen, and health care specialists. Problem The medical training of these veterans does not follow traditional degree granting academic protocols. These individuals seeking formal academic credentials to work in the nonmilitary sector are often forced to start their health education over from the beginning. Approach An innovative model was developed for waiving the requirements for specific nursing courses for veteran-students. Using a skills self-assessment tool and a validation process, veteran-students are able to demonstrate their knowledge, training, and experience. Outcomes As part of the program, 32 veteran-students have validated out of 65 courses for 115 credit hours. All students have successfully progressed through the BSN program. Conclusion This skills validation model represents a model that can be implemented for students entering a nursing program with a variety of health care backgrounds.

Renal damage in primary aldosteronism: a systematic review and meta-analysis Objectives: In experimental animal models, exogenous aldosterone excess has been linked to the progression of renal disease. However, the evidence of an increased risk of renal damage in patients affected by primary aldosteronism remains controversial. We aimed at evaluating the association between primary aldosteronism and renal damage through a meta-analysis. Methods: We performed a quantitative review of studies evaluating parameters of renal function in patients affected by primary aldosteronism compared with hypertensive patients without primary aldosteronism and in patients affected by primary aldosteronism before and after treatment. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1960 up to April 2019. Results: Forty-six studies including 6056 patients with primary aldosteronism and 9733 patients affected by arterial hypertension without primary aldosteronism were included. After 8.5 years from hypertension diagnosis, patients with primary aldosteronism had an increased estimated glomerular filtration rate (eGFR) compared with hypertensive patients without primary aldosteronism [by 3.37 ml/min IQR (0.82–5.93)] and a more severe albuminuria [standard mean difference 0.55 (0.19–0.91)], resulting into an association with microalbuminuria [odds ratio (OR) 2.09 (1.40; 3.12)] and proteinuria [OR 2.68 (1.89;3.79)]. Following primary aldosteronism treatment, after a median follow-up of 12 months, a reduction in eGFR was observed [by −10.69 ml/min (−13.23; −8.16)], consistent in both medically and surgically treated patients. Similarly, a reduction in albumin excretion and an increase in serum creatinine were observed after treatment. Conclusion: Patients affected by primary aldosteronism, compared with patients affected by arterial hypertension without primary aldosteronism, display a more pronounced target organ damage, which can be mitigated by the specific treatment.

Prognostic value of office blood pressure measurement in patients with atrial fibrillation on anticoagulation therapy: systematic review and meta-analysis Objective: In patients with atrial fibrillation (AF), the clinical relevance of office blood pressure (OBP) measurement in terms of predicting morbidity and mortality is questionable, mainly because such measurements in these patients are variable and uncertain. This study reviewed the evidence on the prognostic value of OBP in AF. Methods: A systematic PubMed/Embase search was performed for prospective trials in AF patients on oral anticoagulants, reporting OBP measurements or hypertension diagnosis and outcome. A meta-analysis of the predictive ability of OBP values or hypertension diagnosis for stroke/systemic embolism, major haemorrhage and all-cause mortality was performed. Results: The meta-analysis included nine studies (n = 65 637; 126 926 person-years). There was considerable heterogeneity in the OBP methodology, which was not standardized in most studies. Five studies reported baseline OBP or hypertension diagnosis, two average OBP control during follow-up, and two both baseline and follow-up OBP control. Meta-analysis of six studies (n = 61 055; 105 373 person-years) showed elevated vs. low OBP or hypertension vs. normotension to predict stroke and/or systemic embolism [hazard ratio (HR) 1.29; 95% confidence intervals (CI) 1.12, 1.47]. Meta-analysis of three studies (n = 29 233, 51 528 person-years) showed a worse follow-up OBP control to predict higher stroke/systemic embolism risk (HR 1.79, 95% CI 1.38, 2.32). OBP and hypertension diagnosis did not appear to predict major haemorrhagic events (HR 1.10; 95% CI 0.97, 1.25) or all-cause mortality (HR 0.96; 95% CI 0.89, 1.05). Conclusion: In AF patients, OBP and hypertension diagnosis predict stroke or systemic embolism, and follow-up OBP control appears to have even stronger predictive ability.

Lancet Commission on Hypertension group position statement on the global improvement of accuracy standards for devices that measure blood pressure The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organisation for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

Unraveling new factors associated with hypertension: the Mendelian randomization approach No abstract available

Hypertensive crisis management in the emergency room: time to change? No abstract available

Renin–angiotensin system blockers exposure in utero: a life-long risk for the offspring health No abstract available

The impact of glycated hemoglobin on risk of hypertension: a Mendelian randomization study using UK Biobank Background: Observational studies suggest higher glycated hemoglobin (HbA1c) associated with higher hypertension risk although these associations could be confounded. We examined the relation using a Mendelian randomization design in a large Biobank, the UK Biobank. Methods: We identified 38 single nucleotide polymorphisms (SNPs) strongly and independently related to HbA1c from a large genome wide association study (n = 123 665) and applied them to the UK Biobank (n = 376 644). We used inverse variance weighting (IVW) to assess the relation of HbA1c with risk of hypertension (defined using the American College of Cardiology/American Heart Association 2017 guidelines), and SBP and DBP. Sensitivity analyses included Mendelian randomization-Egger, weighted median, Mendelian randomization pleiotropy residual sum and outlier and exclusion of pleiotropic SNPs. Results: HbA1c was not clearly associated with hypertension risk using IVW (odds ratio 1.11, 95% confidence interval 0.76–1.62) in the main analysis. However, Mendelian randomization pleiotropy residual sum and outlier suggested potential horizontal pleiotropy. After excluding potentially invalid SNPs, HbA1c was associated with hypertension risk (IVW odds ratio 1.22 per %, 95% confidence interval 1.01–1.46), with consistent estimates from sensitivity analyses. HbA1c was positively associated with SBP in some, but not all analyses, albeit with directionally consistent estimates. The relation with DBP was unclear. Conclusion: Our study suggests HbA1c may increase hypertension risk and could be one underlying mechanistic pathway between HbA1c and coronary artery disease risk.

Apparent therapy-resistant hypertension as risk factor for the development of type 2 diabetes mellitus Objective: To evaluate whether the relationship between hypertension and type 2 diabetes mellitus (T2DM) is different for patients with uncontrolled hypertension, controlled hypertension or patients with apparent therapy-resistant hypertension (aTRH), compared with patients without hypertension. Methods: Using Cox proportional hazard models we evaluated the risk of new-onset T2DM in 8756 patients, at high risk for vascular disease. Hypertensive patients were subdivided according to blood pressure (BP) and use of BP-lowering drugs. BP ≥ 140/90 mmHg was defined as uncontrolled BP. aTRH was defined as uncontrolled BP despite being treated with at least three BP-lowering drugs including a diuretic, or the use at least four BP-lowering drugs irrespective of BP levels. Further analysis evaluated the risk of new-onset T2DM for patients with uncontrolled hypertension and for patients with aTRH, compared with patients with controlled hypertension and without hypertension, respectively. Results: Forty-five percent had controlled hypertension, 20% had uncontrolled hypertension, 5.7% had aTRH, and 29% were nonhypertensive. During a follow-up of 7.0 (interquartile range: 0–14) years there were 705 new cases of T2DM. Patients with hypertension had a 1.48 (95% confidence interval 1.22–1.80) times higher risk of new-onset T2DM than nonhypertensive patients. There was no significant difference in risk among different hypertension groups. Conclusion: Patients at high risk for cardiovascular disease with hypertension have a 1.48 times higher risk of new-onset T2DM than nonhypertensive counterparts. The risk did not differ between patients with controlled hypertension, uncontrolled hypertension, or aTRH.

Hypertensive emergencies and urgencies: a single-centre experience in Northern Italy 2008–2015 Background: An increasing attention is given to emergency departments (EDs) admissions for an acute and severe rise in blood pressure (BP). Data on epidemiology and treatment of hypertensive emergencies and urgencies admitted to ED are still limited. The aim of our study was to evaluate the prevalence, clinical presentation and treatment of patients admitted for hypertensive emergencies or hypertensive urgencies. Methods: Medical records of consecutive patients aged at least 18 years, admitted to the ED of the Spedali Civili in Brescia in 2008 and in 2015 and presenting with SBP at least 180 mmHg and/or DBP at least 120 mmHg were prospectively collected and analysed. Results: The prevalence of patients admitted with acute BP rise was 2.0% (n = 1551, age 70 ± 14 years) in 2008 and 1.75% (n = 1214, age 69.7 ± 15 years) in 2015. According to the clinical presentation and the presence of acute organ damage, patients were defined hypertensive emergencies (20.4 and 15.4%, respectively, in 2008 and 2015) or as hypertensive urgencies (79.6 and 84.5%, respectively, in 2008 and 2015). SBP and DBP values were higher in patients with emergencies than in those with urgencies (BP 193 ± 15/102 ± 15 vs. 189 ± 13/96 ± 13 mmHg in 2008 and 192 ± 17/98 ± 15 vs. 189 ± 12/94 ± 15 mmHg in 2015, P < 0.001 for both). Among hypertensive emergencies, the different forms of organ damage were 25% acute coronary syndromes and 1% aortic dissection in both periods, 34 and 38% acute heart failure, 40 and 37% stroke. Conclusion: Admission to the ED for hypertensive emergencies and hypertensive urgencies is still high. Diagnosis and treatment are still not appropriate and require the rapid application of recently published guidelines.

The role of cannabis in treating anxiety: an update Purpose of review Cannabis use for medical purposes has become increasingly common, including as treatment for mental health disorders such as anxiety. Unfortunately, the evidence examining its use in mental health has been slow to evolve, but is emerging. Given the widespread use of cannabis, it is important for both clinicians and those who suffer with anxiety to understand the effects of cannabis on symptoms of anxiety. In this review, we present recent, available evidence from animal models, clinical trials, and survey studies and evaluate the contribution of these studies to the current understanding of the role of cannabis in treating anxiety. Recent findings In reviewing recent evidence, we observed significant inconsistencies across findings from preclinical studies. Large-scale surveys suggest that cannabis may be effective in reducing anxiety, however, these results stand in contrast to equivocal findings from clinical trials. Summary The literature evaluating the efficacy of cannabis in anxiety disorders is in its infancy. The survey data is generally positive. Although, while some animal studies posit cannabis constituents to have anxiolytic effects, others suggest the opposite or null results. Few new clinical trials have been conducted recently, and the extant trials have significant flaws in methodology. Although anecdotal evidence from survey studies, and a small signal found in animal studies and single-dose clinical trials provide early support that cannabis may be effective for alleviating anxiety, ultimately, the current evidence is equivocal. More high-quality clinical trials must be published before sound conclusions regarding the efficacy of cannabis for treating anxiety can be drawn.

Does cannabis use increase anxiety disorders? A literature review Purpose of review Cannabis is widely used worldwide and cannabis use disorders are highly comorbid with anxiety disorders. In this review, we consider the recent literature on the effects of cannabis on the incidence, course, and treatment outcomes of anxiety disorders. Recent findings Although cannabis use is mostly found to be associated with increased incidence of anxiety disorders, these findings are generally not sustained in adjusted analyses controlling for multiple confounders. There are some equivocal data suggesting higher risk for anxiety disorders among heavy cannabis users. The scarce data available indicates no clear effect of cannabis use on the course and treatment outcomes of anxiety disorders. Summary Further research is needed focusing on trajectories of cannabis-induced acute anxiety, effects of cannabis use on treatment outcomes in anxiety disorders, and common genetic factors. Future epidemiological studies should utilize more precise measures of cannabis use and address several confounding factors which may affect the association between cannabis use and anxiety disorders.

Problems with defining cannabis dependence Purpose of review Cannabis enjoys a unique social status, widely perceived as a relatively harmless drug, with several benefits reported by the people who use it. Several jurisdictions have opened up access to cannabis to their populations for medicinal and/or recreational reasons. Given this changing regulatory environment, this article is intended to prompt debate about what is known about cannabis dependence and what has still to be revealed. Recent findings Evidence suggests that 1 in 10 cannabis users are at risk of developing dependence. However, investigation of the way risk is estimated and the diagnosis of cannabis use disorder is constructed highlight some methodological problems, which call into question the incidence and prevalence of this diagnosis. Summary There is scope to improve the way cannabis dependence is defined and counted in at-risk populations. Improving our understanding of this risk could lead to identifying who might be at risk of developing dependence prior to exposure to the drug.

Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans Purpose of review This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use. Recent findings There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD. Summary The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.

Editorial: Arrangement for personality disorder in the 11th Revision of the International Classification of Diseases No abstract available

Recent neuro-imaging findings with respect to conduct disorder, callous-unemotional traits and psychopathy Purpose of review To review recent neuro-imaging findings with respect to conduct disorder and callous-unemotional traits in childhood and comparable psychopathy in adult-hood that deepen the literature in important ways. Recent findings Recent structural findings particularly bring clarity to the literature. First, they reinforce previous work indicating that severity of psychopathy is positively associated with extent of cavum septum pellucidum. This suggests psychopathy is associated with early neurodevelopmental disruption within limbic structures. Second, they clarify the direction of the association between conduct disorder and particularly callous-unemotional traits and white matter tract abnormalities even if it remains less transparent exactly which tracts are disrupted. However, conclusions based on recent functional imaging studies are more equivocal with inconsistencies in direction of emotional (albeit with notably more work confirming the previous reports of hypo-responsiveness in limbic regions) and reward responsiveness. Summary The recent data are, for the most part, consistent with a view that callous-unemotional traits/psychopathy represents an early appearing neuro-developmental disorder particularly associated with compromised emotional (limbic) functioning. However, some patients presenting with severe antisocial behavior may also show hyper-threat sensitivity, perhaps reflecting trauma exposure, and require different clinical interventions.

What's old is new again: updated findings on personality disorders and substance use disorders Purpose of review Personality disorders, mental disorders marked by long-term deviations from societal expectations that cause distress, and substance use and related disorders (SUDs), mental disorders marked by engaging with substances or behaviors that activate the brain's reward system to the point that normal activities are neglected, are common debilitating conditions. Personality disorders and SUDs are highly comorbid, potentially resistant to treatment, and their presence increases all-cause mortality, particularly when found together. Recent findings The present review highlights the most notable findings on prevalence, comorbidity, biological and behavioral pathways between the disorders, impact on incarcerated people and treatment for the disorders. Summary Personality disorders and SUDs are relatively common, highly comorbid, and increase the risk of all-cause mortality: particularly in those who have both conditions. Possible shared pathways between personality disorders and SUDs include emotional dysregulation, shared genes, and certain neurotransmitters. Personality disorders and SUDs are common in people who have been incarcerated, and this morbidity and comorbidity has been found throughout the world. Finally, comorbidity between personality disorders and SUDs greatly complicates treatment, with emerging treatment modalities such as mentalization-based treatment, schema modes, and attentional training showing potential, but lacking strong evidence of efficacy.

Recovery in borderline personality disorder: time for optimism and focussed treatment strategies Purpose of review Borderline personality disorder (BPD) is prevalent, debilitating and clinically challenging. The evolving field of intervention and outcomes in BPD research is considered with a focus on recent research. Recent findings A pattern of clinical and functional improvement is to be expected in patients experiencing BPD. Specialized psychotherapies are shown to be beneficial, but generalist, low-intensity interventions in nonspecialized centres are also showing efficacy. Long-term naturalistic studies show that remission of the disorder is common and promising outcomes are not only possible, but likely. Training in vocational functioning, improving personal competence and promoting resilience needs to be further developed. Summary BPD diagnosis does not need to overwhelm clinicians, nor does it require therapeutic pessimism. Targeted interventions, including meaningful psychoeducation, are helpful in promoting optimism and enhancing recovery-oriented treatments.

Personality functioning in anxiety disorders Purpose of review The alternative model for personality disorders in DSM-5 and the upcoming ICD-11 stimulated an increased interest in the concept of personality functioning for the diagnosis of personality disorders. Furthermore, the impact of personality functioning on other mental disorders has become the focus of recent research efforts. The purpose of this review is to provide a comprehensive and critical study of the empirical literature on the relationship between personality functioning and anxiety disorders. Recent findings Recent studies predominantly show a positive association of anxiety symptoms and disorders with an impairment in personality functioning. However, no evidence was found for different levels of personality functioning according to the type of anxiety disorder. Anxiety disorders can occur at all levels of personality organization. Summary Anxiety disorders are associated with significant impairment in personality functioning. As the underlying personality structure is known to play a crucial role for treatment outcome, the evaluation of personality functioning should be a central part of a comprehensive diagnostic process and treatment planning in patients with anxiety disorders.

Editorial: Body composition measurements in older adults No abstract available

Vitamin D for the older patient: from hype to hope? Purpose of review The review critically appraises the most recent and important meta-analyses that have assessed the effect of vitamin D supplementation on bone health in the older population. Recent findings Vitamin D status is generally lower in study participants with bone wasting. However, studies on the effects of vitamin D supplementation on bone health, summarized in different meta-analyses, have provided conflicting results, likely because of the heterogeneity between studies. Interventional studies performed using more physiological doses of vitamin D (i.e. avoiding very large, nonphysiological doses) or in study participants with low vitamin D status have provided more beneficial effects on bone health. Summary Meta-analyses assessing the impact of vitamin D in the treatment of osteoporosis are heterogeneous in their conception or their results and sometimes have included inappropriate studies to answer the useful research question for the clinician, making the interpretation and the clinical use of these conflicting meta-analyses quite difficult.

Effects of Citrulline alone or combined with exercise on muscle mass, muscle strength, and physical performance among older adults: a systematic review Purpose of review To Establish the potential of Citrulline supplementation (CIT) combined or not with exercise on muscle function and physical performance via a systematic review of randomized controlled trials (RCTs) in human aged 50 years and older. Recent findings Based on Preferred Reporting Items for Systematic Reviews and Meta-analysis guideline, 103 references have been identified. Among this number, only six RCTs (250 participants) matched the inclusion criteria and were included in the present systematic review. Among the included studies, five of six reported beneficial effects of CIT on muscle mass. Then, four of six studies reported CIT effects on muscle strength but also that CIT when combined to exercise results in further improvements in upper muscle strength. Finally, three of six studies reported beneficial CIT effect on physical performance and suggested that CIT with exercise displayed greater improvements in walking speed than exercise alone. Summary CIT supplementation seems to be able to improve muscular and physical factors in frail elderly people (malnourished, hypertensive, obese, dynapenic-obese) compared to placebo. More importantly, CIT combined to exercise is more efficient than exercise or CIT alone. However, because of the small number (six) and heterogeneity (dose, duration, population) of the studies realized in older adults, further studies are needed to confirm its promising potential.

Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Purpose of review We would like to inform clinicians that the systematic administration of oral and intravenous L-arginine is therapeutically beneficial and clinically useful for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), when they maintain plasma arginine concentration at least 168 μmol/l. Recent findings MELAS is associated with endothelial dysfunction by decreased plasma L-arginine, nitric oxide (NO), and cyclic guanosine monophosphate. Endothelial dysfunction is also evident using flow-mediated vasodilation measurement by high-resolution Doppler echocardiography in the forearm artery in patients with MELAS. L-arginine is known to be an important precursor of NO to normalize the endothelial function in MELAS. In our clinical trial followed by 7 years follow-up study, the systematic administration of L-arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. Maintaining plasma arginine concentration at least 168 μmol/l may prevent the ictuses through the putative pathophysiologic mechanism and optimal normalization of endothelial dysfunction. Summary Neither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. Therapeutic regimen of L-arginine on MELAS may be beneficial and clinically useful for patient care with MELAS.

Formate and its role in amino acid metabolism Purpose of review The aim of this report is to examine critical relationships between amino acid and formate metabolism with particular reference to the production of formate, and to review novel functions of formate. Recent findings In addition to well established mechanisms in one-carbon metabolism, formate may play an important role in early pregnancy by preventing the onset of neural tube defects in sensitive strains of mice, including mice with deficiencies in MTHFD1L, the glycine cleavage system and the mitochondrial folate transporter. Markedly elevated, circulating levels of formate are found in late pregnancy, including in cord blood, as well as elevated levels of amino acid precursors. These are consistent with specific roles for formate in late pregnancy. Serine metabolism may reduce NADP+ to NADPH and permit the use of NADPH in reductive reactions. Novel, noncanonical functions of formate include high rates of formate production from serine in cells and in cancers. Summary Novel, noncanonical functions of formate continue to be discovered. Integrating their functions with well established elements of one-carbon metabolism remains an important future objective.

Arginine supplementation and cardiometabolic risk Purpose of review Because arginine is the substrate for nitric oxide synthesis, which is pivotal to vascular homeostasis and linked to the insulin response, it has long been posited that supplemental arginine could benefit cardiometabolic health. Recent findings Recent data have supported the view that supplemental arginine could alleviate the initiation and development of endothelial dysfunction and also shown that it may reduce the risk of type 2 diabetes. One important finding is that these effects may indeed vary as a function of the amount of arginine, its form and notably the metabolic status of the population. Some studies have shown that low doses of slow-release arginine are better used for nitric oxide synthesis and beneficial in individuals with abnormal arginine metabolism/bioavailability. Pathophysiological data in rodents have emphasized the importance of arginase activation during the development of cardiometabolic risk, which lends credence to a potential benefit for arginine supplements. Likewise, epidemiological evidence suggests that alterations to arginine bioavailability are important regarding the cardiometabolic risk. However, other metabolic mechanisms linked to the multiple pathways of arginine metabolism may also play a role. Summary Further studies are needed to confirm and analyze how and when supplemental arginine is beneficial to cardiometabolic health.

Effect of branched-chain amino acid supplementation, dietary intake and circulating levels in cardiometabolic diseases: an updated review Purpose of review Branched-chain amino acids (BCAAs) are essential amino acids derived from diet. BCAA supplementation has been recommended in elderly and athletes, but recent studies suggest an association between high dietary BCAAs and blood levels of BCAAs with greater risk of cardiometabolic diseases (CMD). This review aims to integrate current epidemiological evidence analyzing the association between BCAAs and related-CMD risk factors. Recent findings Most epidemiological studies consistently show that dietary BCAAs are associated with higher risk of type-2 diabetes (T2D) whereas there is limited evidence related with other cardiovascular risk factors. Evidence also exists showing an association between higher circulating BCAA levels and risk of T2D and cardiovascular disease, and also probably with metabolic syndrome and overweight/obesity. Several clinical trials suggest beneficial cardiometabolic effect of BCAAs supplementation, although with a small sample size and short follow-up. Studies show a weak correlation between dietary BCAAs and circulating BCAA levels. Protein quality sources and whole dietary pattern are key aspects to improve our understanding of the effect of BCAAs as well as factors associated with higher protein needs, such as age or frailty. Summary Dietary and circulating BCAAs exhibit possible detrimental cardiometabolic effects, but BCAA supplementation may have some positive influence on target groups with nutritional deficiencies.

Protein intake and outcome in critically ill patients Purpose of review The objective of this review is to describe the impact of protein intake on the outcomes of critically ill patients in the literature published in the preceding 2 years. Recent findings Observational studies showed inconsistent results regarding the association of higher protein intake and outcomes of critically ill patients. Randomized controlled trials that directly compared higher versus lower protein intake in ICU patients are scarce, varied considerably in their designs and primary outcomes, and generally had relatively small differences in the amount of delivered protein between the study arms. Systematic reviews of existing studies showed no difference in mortality with higher protein intake. In addition, there is uncertainty regarding high protein provision in the early phase of critical illness. Summary The optimal amount of protein intake in critically ill patients remains largely unclear and is considered a high priority for research. Ongoing clinical trials are likely to provide additional evidence on several important questions including the dose, timing, type of protein and the interaction with caloric intake and exercise.

Tackling the question of micronutrients intake as one of the main levers in terms of Inuit food security Purpose of review The Inuit population living in North Canada is facing a drastic change in lifestyle, which has brought about a dramatic nutrition transition characterized by a decrease in the traditional foods consumption and an increasing reliance on processed, store-bought foods. This rapid dietary shift leads to a significant public health concern, as wild-harvested country foods are rich in many micronutrients including vitamins, trace elements and minerals while the most frequently eaten Western foods mainly provide energy, fat, carbohydrates and sodium. This review addresses the emerging strategies to tackle food insecurity in this population. Recent findings Recent studies indicate that diets with a higher fraction of traditional foods (and a lower fraction of ultra-processed foods) exhibit a better Healthy Eating Index. This provides a basis to develop new dietary policies anchored in contemporary food realities. Summary In Northern remote communities, improving food security requires holistic approaches. A mixed strategy that targets the revitalization of traditional foods systems and local food production initiatives seems the most promising strategy, to meet the dietary needs in terms of micronutrients, with respect to the cultural identity of local populations.

Editorial: Surgical advancements and innovations in cataract surgery for the complex patient No abstract available

Management of cataract in the setting of uveitis: a review of the current literature Purpose of review This review aims to cover the preoperative planning, intraoperative considerations, and postoperative management that aids in successful outcomes of patients with cataract and uveitis. Disease-specific management and pediatric management will also be addressed. Recent findings Dexamethasone implants appear to be a safe and effective addition to standard steroid treatment in decreasing the incidence of postoperative cystoid macular edema (CME). Intravitreal steroids and topical difluprednate have shown utility in CME treatment. Summary Cataract surgery in eyes with uveitis is generally safe and effective if inflammation is well controlled; however, complication rates are still higher than in eyes without uveitis. Future investigations should delineate outcomes for eyes with different etiologies of uveitis, and further research is needed to adequately control inflammation and avoid postoperative complications.

How much astigmatism to treat in cataract surgery Purpose of review Astigmatism correction in cataract surgery is a common surgical challenge. Although there are numerous approaches to its treatment during cataract surgery, there remains a lack of consensus on what level of postoperative astigmatism to target. We examine the literature to determine the effect of astigmatism on visual function and provide a recommendation on how much to treat in cataract surgery. Recent findings Distance visual acuity decreases as myopic, hyperopic, or mixed astigmatism increases. Near visual acuity decreases with hyperopic astigmatism but improves with myopic astigmatism. The effect of astigmatism is generally independent of axis; however, against-the-rule (ATR) astigmatism with mild myopia may benefit reading. A progressive ATR shift occurs with age whether or not an individual undergoes cataract surgery. In the presence of higher order aberrations, correction of astigmatism below 0.5 D shows minimal practical benefit. Presbyopia-correcting intraocular lenses (IOLs) are sensitive to astigmatism but achieve distance visual acuities similar to monofocal IOLs and reach their full near and/or intermediate potential when residual astigmatism 0.5 D or less. Summary In cataract surgery, we recommend correction to 0.5 D or less of postoperative residual astigmatism to achieve optimum visual function and patient satisfaction following cataract surgery.

Cataract surgery and intraocular pressure in glaucoma Purpose of review To review the current literature on the relationship between cataract extraction and intraocular pressure (IOP). Recent findings Cataract extraction can be an effective IOP lowering treatment for open and closed angle glaucoma as well as ocular hypertension. In comparative trials studying novel micro-invasive glaucoma surgeries in open angle glaucoma, the control group undergoing cataract extraction alone routinely achieved significant reductions in IOP and medication use postoperatively. Data from the Effectiveness in Angle Closure Glaucoma of Lens Extraction (EAGLE) trials have demonstrated that lens extraction is more effective at lowering IOP than peripheral iridotomy in patients with angle closure and should be considered as first line therapy. Additionally, patients in the ocular hypertension treatment study who underwent cataract extraction over the course of follow-up demonstrated significant IOP lowering sustained over 3 years. Summary Cataract extraction is an effective method to lower IOP in patients with glaucoma. Pressure lowering is more significant in eyes with narrow angles and those with higher baseline IOP levels. In eyes with angle closure, phacoemulsification alone can lower IOP, but when combined with GSL it may be even more effective. Recent large multicenter randomized trials have further elucidated the benefit of standalone cataract extraction to treat mild to moderate primary open angle glaucoma. Prospective and longitudinal studies that systematically investigate the variables that may influence degree and duration of IOP lowering post cataract extraction are lacking.

Cataract surgery in corneal transplantation Purpose of review Corneal diseases are often associated with lens opacity. The present article reviews the recent advances in the management of cataract and corneal transplant. Recent findings Thanks to the development of lamellar transplant techniques and the evolution of cataract surgery, we now have several strategies to address corneal diseases and cataract including ‘lamellar triple procedure’. Numerous precautions have been identified to have a successful surgery with good visual recovery. Summary Corneal diseases associated with cataract can be successfully managed using separate or combined surgical procedures, as appropriate. In most cases the intraocular lens power can be calculated with a predictable outcome.

Hand hygiene and instrument sanitization in ophthalmology clinics Purpose of review This article reviews the various challenges in infection control in eye clinics and successful measures taken to prevent nosocomial infections. Recent findings The Center for Disease Control recommends hand-washing when hands are visibly soiled, and after direct contact with patients, and inanimate objects such as medical equipment. Published studies have identified poor hygiene in clinical settings as a major cause of nosocomial outbreaks, particularly in cases of epidemic keratoconjunctivitis (EKC). Some studies of EKC outbreaks are able to support direct observation of hygiene lapses with molecular analysis that can match viral strains on particular instruments to those found in infected patients. Although most studies are about adenoviral infection and tonometer use, researchers have found viral and bacterial loads on other common surfaces, indicating a need for further research. Summary Proper hygiene in eye clinics requires special attention because of the potential to examine many patients at a time and because multiple instruments are often used during a single exam. Studies reinforce the link between hygiene and outbreak prevention, and more research can be done to determine the specific links between certain instruments and nosocomial infections.

Methods for achieving adequate pupil size in cataract surgery Purpose of review Cataract surgery is the most common surgical procedure performed worldwide. Small pupils have been an eternal challenge for cataract surgeons; insufficient pupil dilation is associated with increased complication rates, including capsule rupture, vitreous loss, iris trauma or postoperative inflammation. The aim of the current review is to present the methods for pupil dilation and the risk factors for a small pupil in a cataract patient. Recent findings Risk factors for intraoperative small pupil include diabetes, intraoperative floppy iris syndrome, pseudoexfoliation syndrome, receiving glaucoma medications, having undergone previous ocular surgery and iris sphincter sclerosis from aging. There is a wide range of options to manage the small pupil, including pharmacological treatment, mechanical stretching, dilation with iris hooks or pupil expanders. We recommend a stepwise approach for intraoperative pupil dilation, from pharmacological mydriasis to pupil expanders. Summary The current article discusses risk factors for a small pupil and the methods for pupil dilation in a cataract patient. Every cataract surgeon needs to be ready to cope with a small pupil, both manifesting preoperatively and intraoperatively.

Iris reconstruction suturing techniques Purpose of review When patients have large iris defects, they may experience debilitating glare, halos, and unfavorable cosmetic appearance. Surgical iris reconstruction can alleviate these symptoms. This article will review current suturing techniques for iris reconstruction, as well as the benefits and drawbacks to various suturing methods. Alternative reconstructive methods are also discussed. Recent findings One of the earliest iris suturing methods described was the McCannel technique. This technique allows direct suturing of the iris using three incisions. The Siepser slipknot is another method used in closed chamber iris suturing techniques. This knot, and its recent modifications, utilizes a sliding knot, which is created outside the eye and slid into place atop the iris defect. The cerclage iris suture, in which small bites are taken around the pupillary circumference, is especially useful when treating a mydriatic pupil. Recently, a number of surgeons have adapted these techniques and developed novel suturing strategies to address complex ocular conditions. Summary The various iris suturing methods, as well as alternative techniques including cautery, corneal tattooing, and iris prosthetics, each have unique benefits, providing surgeons with a wide array of tools for iris reconstruction.

Scleral fixation of intraocular lenses Purpose of review To review current, effective and more popular techniques for scleral fixation of intraocular lens (IOLs) and IOL–capsular bag complex. Recent findings Scleral fixation of IOLs became popular, originally with sutured scleral fixated IOLs and later the Scharioth technique of intrascleral haptic fixation. This was further developed as the Glued IOL technique which enjoys widespread adoption all over the world. Recently the Yamane technique has also become popular and is being widely adopted as well. Summary Scleral fixated IOLs have evolved in the last 2 decades with technical modifications, extended indications and improvised instrumentation. Though sutured and sutureless techniques have been growing equally, the sutureless scleral fixation techniques have attracted special interest. Reduced suture-related complications, technical ease and high-quality functional outcomes may be possible reasons. Sutureless capsular bag fixation also has distinct advantages.

Papillary thyroid microcarcinoma: optimal management versus overtreatment Purpose of review The treatment of small, low-risk papillary thyroid carcinoma has undergone a paradigm shift, with many tumors now initially treated with active surveillance rather than upfront surgery. Further studies on patients enrolled in active surveillance have refined our knowledge of the clinical behavior of papillary thyroid microcarcinomas. Recent findings This article summarizes the major conclusions of landmark trials that launched active surveillance as a viable treatment option for selected patients. We discuss patient factors such as age and tumor size, the assessment of candidates for active surveillance, barriers to acceptance of active surveillance, quality of life issues, and economic considerations. Summary Active Surveillance is a viable first-line treatment option for select papillary microcarcinomas.

Circulating biomarkers for the detection of tumor recurrence in the postsurgical follow-up of differentiated thyroid carcinoma Purpose of review To discuss advances and challenges in thyroglobulin and Tg-antibody (TgAb) measurement and their impact on clinical management of differentiated thyroid carcinoma (DTC). Recent findings Basal high-sensitive Tg (hsTg) measurement avoids the need for stimulation and greatly simplifies DTC patients’ management. In addition, patients with undetectable hsTg after thyroid ablation are at a very low risk of recurrence and can be safely managed by periodic hsTg measurement alone. When TgAb is present, its trend over time serves as primary (surrogate) tumor marker. However, an undetectable hsTg measurement appears to indicate a complete remission of DTC even in the presence of TgAb. Finally, reliable reference values are not yet available for low-risk DTC who are treated with less than total thyroid ablation, and caution is needed before well-designed studies addressing these issues have been published. Summary The use of hsTg assays has changed paradigms for DTC monitoring even in the presence of TgAb, and greatly reduced patients’ discomfort and overall case-management costs. Reliable Tg interpretation criteria are urgently needed for patients treated with less than total thyroid ablation.

Novel therapeutic options for radioiodine-refractory thyroid cancer: redifferentiation and beyond Purpose of review Radioiodine-refractory thyroid cancers represent the main cause of thyroid cancer-related death. At present, targeted therapies with multikinase inhibitors represent a unique therapeutic tool, though they have limited benefit on patient survival and severe drug-associated adverse events. This review summarizes current treatment strategies for radioiodine-refractory thyroid cancer and focuses on novel approaches to redifferentiate thyroid cancer cells to restore responsiveness to radioiodine administration. Recent findings We summarize and discuss recent clinical trial findings and early data from real-life experiences with multikinase-inhibiting drugs. Possible alternative strategies to traditional redifferentiation are also discussed. Summary The current review focuses primarily on the major advancements in the knowledge of the pathophysiology of iodine transport and metabolism and the genetic and epigenetic alterations occurring in thyroid neoplasia as described using preclinical models. Results of clinical studies employing new compounds to induce thyroid cancer cell redifferentiation by acting against specific molecular targets are also discussed. Finally, we describe the current scenario emerging from such findings as well as future perspectives.

Malignant pheochromocytoma and paraganglioma: management options Purpose of review Although the majority of pheochromocytoma and paraganglioma are benign, 15–17% develop metastatic disease, being present at the initial diagnosis in about 11–31% of cases. The natural course of metastasized disease is highly heterogeneous, with an overall 5-year survival rate varying between 40% and 85%. For individual patients, overall survival, progression-free survival, and clinical outcome are difficult to predict. Management of metastasized pheochromocytoma and paraganglioma is challenging. Currently available therapeutic options are surgical debulking, treatment with radiopharmaceuticals (131I-MIBG, 90Y and 177Lu-DOTATATE), chemotherapy and targeted therapy. Recent findings The pathogenesis of pheochromocytoma and paraganglioma (PPGL) is largely driven by genomic alterations in PPGL susceptibility genes related to three different clusters: altered pseudo-hypoxic signaling (cluster-1), altered MAP-kinase signaling (cluster-2) and altered Wnt signaling (cluster-3). Novel targeted therapies (tyrosine kinase inhibitors) and potential future therapeutic options, guided by improved knowledge about the oncogenic cluster 1–3 signaling pathways, will be discussed. Summary Treatment of metastasized pheochromocytoma and paraganglioma remains challenging. Profiling of gene expression and methylation can serve as a powerful tool for characterizing disease clusters and for guiding targeted therapy to improve selectivity and efficacy. Current knowledge of signatures involved in molecular signaling, metabolism, and resistance mechanisms of PPGLs suggests that therapeutic regimens can be optimized to each molecular subtype.

Adrenal tumours: open surgery versus minimally invasive surgery Purpose of review The aim of this article is to focus on state-of-the-art minimally invasive adrenalectomy (MIA) and the most recent role of open adrenalectomy for adrenal tumours, respect to MIA and open adrenalectomy for adrenocortical cancer (ACC). Recent findings The laparoscopic (both transperitoneal and retroperitoneal) approach is the first-choice treatment in cases of small-to-medium benign adrenal tumours. This approach is feasible and well tolerated even for larger lesions without radiological signs of malignancy. Robotic adrenalectomy has recently increased in popularity, although the results appear to be fully comparable with those of laparoscopy. Open approach is the keystone of ACC surgery, especially when neighbour tissues, organs, or vessels are involved. Recent evidence suggests caution in treating localized ACC with laparoscopy, because of the higher rate of local or peritoneal recurrence, and shorter recurrence-free survival rates with respect to open adrenalectomy. Summary MIA has progressively replaced the traditional open approach and plays a complementary role in the treatment of adrenal tumour. It is the first option for benign lesions, whereas open adrenalectomy is a cornerstone treatment for ACC. The overlap of indications for laparoscopic adrenalectomy and open adrenalectomy is today confined to the treatment of organ-confined adrenal cancer, in which the role of laparoscopic surgery is far from being clearly defined.

Editorial: Individualizing treatment of nonsmall cell lung cancer No abstract available

Novel molecular targets for the treatment of lung cancer Purpose of review The mutational landscape in lung adenocarcinoma (LADC) is broadly recognized, particularly regarding the presence of the epidermal growth factor receptor (EGFR) mutation in non-smokers. However, even in the EGFR canonical-mutant LADC, other accompanying alterations surface which may have a major impact in prognosis and open possibilities to explore new therapeutic approaches. Recent findings Complex genomic rearrangements, including chromothripsis and chromoplexy, are the origin of most-known fusion oncogenes, including echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, Cluster of Differentiation 74-c-ros oncogene 1, and kinesin-1 heavy chain- rearranged during transfection. Quite often LADCs driven by fusion oncogenes are accompanied by SET domain containing 2 (SETD2) mutations. SETD2 mutations have been described in renal cancer and have been related to cisplatin resistance in LADCs. Suppression of the SETD2 function inhibits the signal transducer and transcription activator function and the interferon-signaling pathway, which could partially explain the lack of effectiveness of immunotherapy in LADCs driven by fusion oncogenes. Summary Targeted next-generation sequencing of DNA in the tumor tissue or in the circulating plasma of LADC is becoming indispensable for the accurate classification of LADCs that can receive appropriate targeted therapy. It is unquestionable that additional techniques, like RNA sequencing or the nCounter technology, can accomplish accurate assessment of an ample array of fusion oncogenes involved in LADCs.

Angiogenesis inhibition in non-small cell lung cancer: a critical appraisal, basic concepts and updates from American Society for Clinical Oncology 2019 Purpose of review Recently, the combination of antiangiogenic agents, chemotherapy and immunotherapy has shown synergistic anticancer effects in non-small cell lung cancer (NSCLC). The future for this approach appears bright in lung cancer treatment; however, many challenges remain to be overcome regarding its true potential, optimal sequence and timing of therapy, and safety profile. In this review, we will discuss the current status and future direction of antiangiogenic therapy for the treatment of NSCLC, and highlight emerging strategies, such as tumor vessel normalization (TVN). Recent findings Bevacizumab was the first antiangiogenic agent approved for the treatment of advanced NSCLC. Recently, the combination of chemotherapy/antiangiogenic therapy with immunotherapy showed high efficacy in first-line settings. A subgroup of patients with liver metastasis and driver mutation-addicted tumors benefited most, suggesting that the metastatic location, as well as the genetic background of the tumor, are key determinants for therapy responses. Summary The efficacy of antiangiogenic therapies in unselected patients is rather limited. The tumor microenvironment has appeared to be more complex and heterogeneous than previously assumed. Only a contextual rather than a cell-specific approach might provide valuable insights towards the clinical validation of combinational therapies.

Local treatment of stage IIIA-N2 nonsmall cell lung cancer: surgery and/or radiotherapy Purpose of review Controversy exists regarding the optimal treatment of patients with stage IIIA-N2 nonsmall cell lung cancer because of its heterogeneity. Patients are at risk for both local and distant disease relapse after primary local treatment. However, there may be a window of opportunity for surgery, if mediastinal downstaging has been obtained after induction therapy. This manuscript reviews the outcome of patients treated by neo-adjuvant chemotherapy (NA-C) followed by surgery, compared with patients treated with either definitive sequential or concurrent chemoradiotherapy (cCRT), illustrated by a single-centre retrospective case series. Recent findings Of 53 eligible patients, 19 received NA-C and underwent surgical resection, whilst 20 and 14 received concurrent or sequential definitive CRT, respectively. A significant difference in progression-free survival favouring NA-C followed by surgery over both CRT modalities was found. However, this translated only in an overall survival benefit in comparison with sequential definitive CRT. A trend for better outcome was observed in selected surgical patients with single-level mediastinal involvement and complete resection. Summary Our case series results are consistent with the present standard of care of CRT, which restricts surgical resection to carefully selected patients. Immunotherapy will likely change the treatment paradigm.