Venetoclax, a potent B-cell lymphoma-2 (BCL-2) inhibitor, has demonstrated clinical efficacy in chronic lymphocytic leukemia (CLL). VENICE II is an open-label, single-arm, phase 3b study (NCT02980731) evaluating the impact of venetoclax monotherapy (400 mg once daily) for ≤2 years on health-related quality of life (HRQoL) of patients with relapsed/refractory CLL. The primary endpoint was mean change in the global health status (GHS)/quality of life (QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to Week 48.
View Article and Find Full Text PDFThe formation of Tröger's Base (TB) configuration is a useful approach to synthesize polymers of intrinsic microporosity (PIM). Herein, the V-shaped TB scaffold is incorporated to prepare electrochromic (EC) polyamide with electroactive triphenylamine (TPA) moiety. The presence of intrinsic microporosity derived from inefficient packing of TB scaffolds can facilitate the counterions diffusion between electroactive species and electrolytes.
View Article and Find Full Text PDFThe COVID-19 pandemic has impacted health systems and health programs across the world. For tuberculosis (TB), it is predicted to set back progress by at least twelve years. Public private mix (PPM)has made a vital contribution to reach End TB targets with a ten-fold rise in TB notifications from private providers between 2012 and 2019.
View Article and Find Full Text PDFThe COVID-19 pandemic has caused widespread disruptions to tuberculosis (TB) care and service delivery in 2020, setting back progress in the fight against TB by several years. As newer COVID-19 variants continue to devastate many low and middle-income countries in 2021, the extent of this setback is likely to increase. Despite these challenges, the TB community can draw on the comprehensive approaches used to manage COVID-19 to help restore progress and mitigate the impact of COVID-19 on TB.
View Article and Find Full Text PDFAcquired hemophilia A is a potentially severe bleeding disorder caused by antibodies against the patient's own factor VIII. Acquired hemophilia A is rare. It is most commonly diagnosed in older individuals; about one-half of cases of acquired hemophilia are associated with underlying conditions, including autoimmune disease, cancer, and pregnancy.
View Article and Find Full Text PDFRes Pract Thromb Haemost
August 2021
Adenoviral-vector based vaccines for coronavirus disease 2019 (COVID-19) have been linked with a thrombotic syndrome, vaccine-induced thrombotic thrombocytopenia (VITT). A key clinical question is whether VITT can be reliably ruled out by the absence of thrombocytopenia. We report on three patients who presented to our institute with this syndrome.
View Article and Find Full Text PDFThe proteomic analysis of the human brain tissue over the last decade has greatly enhanced our understanding of the brain. However, brain related disorders continue to be a major contributor of deaths around the world, necessitating the need for even greater understanding of their pathobiology. Traditional antibody-based techniques like western blotting or immunohistochemistry suffer from being low-throughput besides being labor-intensive and qualitative or semi-quantitative.
View Article and Find Full Text PDFBackground: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD).
Methods And Findings: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening).
J Clin Tuberc Other Mycobact Dis
December 2021
Purpose: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models.
Experimental Design: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38).
Physiological and biochemical changes occur in pregnancy to nurture the developing fetus. Pregnancy-related experience is unique to every woman. Pregnancy symptoms and complications can range from mild to severe.
View Article and Find Full Text PDFIntroduction: Endometriosis is one of the common, gynaecological disorders associated with chronic pelvic pain and subfertility affecting ~10% of reproductive age women. The clinical presentation, etiopathogenesis of endometriosis subtypes and associated risk factors are largely unknown. Genome-Wide Association (GWA) Studies (GWAS) provide strong evidence for the role of genetic risk factors contributing to endometriosis.
View Article and Find Full Text PDFBackground: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. In preparation for an upcoming guideline, the ITP Emergency Management Guideline Panel, including clinical experts in hematology, emergency medicine, research methodology, and patient representatives, identified the need for a standardized definition of a critical ITP bleed. The goal of the definition was to distinguish critical bleeds from bleeds that may not require urgent treatment, typically in the context of severe thrombocytopenia.
View Article and Find Full Text PDFUnlabelled: We assessed the association between work status beyond state pension age (SPA) and the long-term trajectories of cognitive and mental health for men and women separately, and the extent to which this relationship is conditioned by their occupational status and whether the choice to retire or continue working is voluntary or involuntary. Data are pensioners (aged between SPA and SPA + 9) from the English Longitudinal Study of Ageing waves 4 (2008/09) through 9 (2018/19). The analytic sample includes 959 men and 1217 women when considering cognitive outcomes and 1131 men and 1434 women when evaluating depression.
View Article and Find Full Text PDFBackground: Few studies have assessed psychological pathways that connect the association between non-psychotropic chronic disease and cognition. We assessed the extent to which the association between the two was mediated by depressive symptoms in older adults.
Methods: Data came from waves 10-13 (2010-2016) of the Health and Retirement Study in the United States (7,651 men and 10,248 women).
Background: Automated radiologic analysis using computer-aided detection software (CAD) could facilitate chest X-ray (CXR) use in tuberculosis diagnosis. There is little to no evidence on the accuracy of commercially available deep learning-based CAD in different populations, including patients with smear-negative tuberculosis and people living with human immunodeficiency virus (HIV, PLWH).
Methods: We collected CXRs and individual patient data (IPD) from studies evaluating CAD in patients self-referring for tuberculosis symptoms with culture or nucleic acid amplification testing as the reference.
Antimicrob Agents Chemother
September 2021
The optimal polymyxin B dosage needed to achieve an efficacy target of 50 to 100 mg · h/liter when treating multidrug-resistant bacterial infections in adult cystic fibrosis (CF) patients is unclear. The pharmacokinetics of intravenous polymyxin B were evaluated to better inform dosing. This was a prospective, observational pharmacokinetic (PK) study of nine CF adults receiving intravenous polymyxin B as part of usual clinical care.
View Article and Find Full Text PDFIntroduction: Myofascial pain syndrome (MPS) affects most patients with chronic shoulder pain. Dry needling (DN) is a common treatment for MPS, but its temporal pattern and sensory effects remain unknown.
Objectives: We evaluated in a randomized, sham-controlled study the pattern of analgesic efficacy and local sensory changes of a single session of DN for MPS in patients with chronic shoulder pain.
Aim: High-dose valproic acid (VPA) improves the survival and neurologic outcomes after asphyxial cardiac arrest (CA) in rats. We characterized the pharmacokinetics, pharmacodynamics, and safety of high-dose VPA in a swine CA model to advance clinical translation.
Methods: After 8 min of untreated ventricular fibrillation CA, 20 male Yorkshire swine were resuscitated until return of spontaneous circulation (ROSC).