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Κυριακή 31 Ιουλίου 2022

Intra‐articular non‐steroidal anti‐inflammatory drugs may promote cartilage degeneration

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Incidence, risk factors, outcomes, and clinical management of BK viremia in the modern era of kidney transplantation

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ABSTRACT

Background

: BK viremia is endemic among kidney transplant recipients (KTR). Incidence, risk factors, outcomes, and clinical management of detectable versus high BK viremia have not been considered previously in KTR in the modern era.

Methods

: This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥103 copies/mL constituted high viremia.

Results

: Among 1,193 KTR, the cumulative probability of developing detectable and high BK viremia within two years post-transplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), non-depleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 mL/min/1.72 m2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, anti-proliferative dose reductions were the most common initial management.

Conclusion

: BK viremia remains a common early complication in a modern cohort of KTR. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation.

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No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas

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AbstractThe relationship between the middle ear acoustic reflex (AR) and inner hair cell (IHC) loss is currently unknown. Given that IHC are believed to convey nearly all acoustic information to the central auditory nervous system, it has been assumed that loss of IHC would significantly impact the AR. To evaluate this relationship, we assessed the presence and amplitude of the AR in chinchillas before and after treatment with carboplatin, an anticancer drug that reliably and selectively destroys IHC in this species. Baseline measures of hearing sensitivity, including auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE), were assessed and then re-evaluated following carboplatin treatment. Post-carboplatin ABR thresholds and DPOAE were found to b...
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Genomic Annotation and Molecular Evolution of Monkeypox Virus Outbreak in 2022

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ABSTRACT

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several non-endemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 non-synonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that ten proteins in the monkeypox virus are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, 4 and 3 nucleotide substitutions are observed in OPG105 and OPG210 , respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

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Abstract
Background
Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks.
Methods
Among 609 post-menopausal women (1,234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors.
Results
Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.
Conclusions
HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.
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Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study

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Abstract
Background
Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers.
Methods
In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3–6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child� �s sex, gestational age, age at follow-up, and other maternal factors.
Results
Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, β (95% CI): −1.31 mmHg (−2.57, −0.06); DBP: −0.79 mmHg (−1.74, 0.15)] and body fat percentage [SBP: −1.46 mmHg (−2.73, −0.19); DBP: −0.80 mmHg (−1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (−1.29, 1.83)]; DBP: −0.14 mmHg (−1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk.
Conclusions
At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.
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Eano-Euracan-Sno Guidelines on Circumscribed Astrocytic GLIOMAS, Glioneuronal and Neuronaltumors

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Abstract
In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, molecular workup is important for differential diagnosis, in particular DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasingly of prognostic and predictive importance. MRI finding are non specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas .Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies.
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Long-term wellbeing and neurocognitive functioning of diffuse low-grade glioma patients and their caregivers: a longitudinal study spanning two decades

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Abstract
Background
While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumour progression which may impact on patients' long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M=7 and T2 M=13 years after diagnosis).
Methods
Participants completed HRQOL (SF-36; EORTC-BN20), fatigue (Checklist Individual Strength (CIS)), and depression (Center for Epidemiological Studies-Depression (CES-D)) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Change over time (T1-T2-T3) on group and participant level were assessed. Where available, histology of the initial tumour was revised and immunohistochemical staining for IDH1 R 132H mutant protein was performed.
Results
Thirty patients and nineteen caregivers participated. Of N=11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M=26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers' HRQOL was similar to controls, but reported high rates of fatigue (63.2%). Over time, patients' mental health improved (p<.05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients.
Conclusions
While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, d epressive symptoms and fatigue are persistent.
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Πέμπτη 28 Ιουλίου 2022

Facial nerve palsy: Narrative review on the importance of the eye and its assessment

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Abstract

New solutions are emerging that address specific facial regions in facial nerve palsy (FNP). However the most dreaded consequence of FNP is paralytic lagophthalmos threatening the eye. A way to prioritize these regions is thus required. A review of the literature is conduced to capture the current concepts in evaluating FNP. Overall, patients are assessed from three perspectives: from the clinician's perspective using validated clinician-based grading instruments, from patient's perspective based on FNP-specific patient-reported outcome measures, and from the perspective of the layperson. The existing tools however provide limited information regarding the relative importance of different regions of the face. The eye appears to be an area of great concern for the patient where most surgical therapies are directed at. Addressing ocular problems in FNP carry a high priority but this is not clearly reflected by the standard systems.
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STATIN USE MAY BE ASSOCIATED WITH A LOWER RISK OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS

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Abstract
Background
Statins are competitive inhibitors of HMG-CoA reductase that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented.
Methods
This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of two weeks duration prior to IA), adjusting for other known IA risk factors.
Results
We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (IQR: 305 to 346). 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (p = 0.002, SHR 0.30, CI 95% 0.14-0.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs. 123 (27%) in the statin group (p = 0.038).
Conclusions
The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.
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