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

alexandrossfakianakis shared this article with you from Inoreader Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV via Clinical Infectious Diseases Advance Access 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. View on Web

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Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial

alexandrossfakianakis shared this article with you from Inoreader Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial via Clinical Infectious Diseases Advance Access Abstract Background This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation. Methods PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in th e number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18. Results Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib. Conclusions Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. View on Web

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Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091)

alexandrossfakianakis shared this article with you from Inoreader Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091) via Clinical Infectious Diseases Advance Access Abstract Background Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Methods Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization. Results Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemothe rapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5–10.8%) in Arm B versus 6.6% (95%CI, 3.6–9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p < 0.001). Conclusions The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. View on Web

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Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study

alexandrossfakianakis shared this article with you from Inoreader Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study via International Journal of Epidemiology - Advance Access 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. View on Web

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Impact of a prognostic model for overall survival on the decision‐making process in a head and neck cancer multidisciplinary consultation meeting

alexandrossfakianakis shared this article with you from Inoreader Impact of a prognostic model for overall survival on the decision‐making process in a head and neck cancer multidisciplinary consultation meeting via Head & Neck Abstract Background Multidisciplinary decision-making in head and neck cancer care is complex and requires a tradeoff between prolonging survival and optimizing quality of life. To support prognostication and decision-making in head and neck cancer care, an individualized prognostic model for overall survival (OncologIQ) is available. Methods By quantitative and qualitative research we have studied user value of OncologIQ and its impact on the decision-making process in a multidisciplinary consultation meeting. Results Healthcare professionals experienced added value upon using prognostic estimates of survival from OncologIQ in half (47.5%) of the measurements. Significant impact on the decision making process was seen when OncologIQ was used for older patients, patients having a WHO performance score ≥ 2, or high tumor stage. Conclusions The prognostic model OncologIQ enables patient-centered decision-making in a multidisciplinary consultation meeting and was mostly valued in complex patients. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader Long-term wellbeing and neurocognitive functioning of diffuse low-grade glioma patients and their caregivers: a longitudinal study spanning two decades via Neuro-Oncology Advance Access 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Facial nerve palsy: Narrative review on the importance of the eye and its assessment via Head & Neck 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. View on Web

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STATIN USE MAY BE ASSOCIATED WITH A LOWER RISK OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS

alexandrossfakianakis shared this article with you from Inoreader STATIN USE MAY BE ASSOCIATED WITH A LOWER RISK OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS via Clinical Infectious Diseases Advance Access 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. View on Web

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Genetic predisposition & evolutionary traces of pediatric cancer risk: A prospective 5-year population-based genome sequencing study of children with CNS tumors

alexandrossfakianakis shared this article with you from Inoreader Genetic predisposition & evolutionary traces of pediatric cancer risk: A prospective 5-year population-based genome sequencing study of children with CNS tumors via Neuro-Oncology Advance Access Abstract Background The etiology of central nervous system (CNS) tumors in children is largely unknown and population-based studies of genetic predisposition are lacking. Methods In this prospective, population-based study, we performed germline whole-genome sequencing in 128 children with CNS tumors, supplemented by a systematic pedigree analysis covering 3,543 close relatives. Results Thirteen children (10%) harbored pathogenic variants in known cancer genes. These children were more likely to have medulloblastoma (OR 5.9, CI 1.6-21.2) and develop metasynchronous CNS tumors (p=0.01). Similar carrier frequencies were seen among children with low-grade glioma (12.8%) and high-grade tumors (12.2%). Next, considering the high mortality of childhood CNS tumors throughout most of human evolution, we explored known pediatric-onset cancer genes, showing that they are more evolutionarily constrained than genes associated with risk of adult-onset malignancies (p=5e-4) and all other genes (p=5e-17). Based on this observation, we expanded our analysis to 2 986 genes exhibiting high evolutionary constraint in 141 456 humans. This analysis identified eight directly causative loss-of-functions variants, and showed a dose-response association between degree of constraint and likelihood of pathogenicity - raising the question of the role of other highly constrained gene alterations detected. Conclusions ∽10% of pediatric CNS tumors can be attributed to rare variants in known cancer genes. Genes associated with high risk of childhood cancer show evolutionary evidence of constraint. View on Web

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Neuropsychological, behavioral, and quality‐of‐life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series

alexandrossfakianakis shared this article with you from Inoreader Neuropsychological, behavioral, and quality‐of‐life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series via Pediatric Blood & Cancer Abstract Background/objectives Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT. Design/methods Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol. Results Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ = 92.1, SD 9.0; n = 8) and 2 years post-HCT (mean FSIQ = 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = −.54) and fine motor speed and dexterity (Cohen's d = −.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44). Conclusion Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed. View on Web

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