Specific Plasma MicroRNA Signatures Underlying the Clinical Outcomes of Hepatitis E Virus Infection.

The pathogenic mechanisms determining the diverse clinical outcomes of HEV infection (e.g., self-limiting versus chronic or symptomatic versus asymptomatic) are not yet understood.

A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand.

A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016−31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%.

Effect of LHRH analogs on lower urinary tract symptoms associated with advanced prostate cancer in real clinical practice: ANALUTS study.

Aims: To estimate the prevalence of lower urinary tract symptoms (LUTS) in patients with prostate cancer scheduled to receive LHRH analogs, and to assess the effectiveness of LHRH analogs on LUTS in patients presenting moderate/severe symptoms.

Methods: Prospective, noninterventional, multicenter study conducted at 28 centers in Spain and Portugal. LUTS were evaluated using the International Prostate Symptom Score (IPSS) at baseline, 24 and 48 weeks after initiation of treatment.

Corrigendum to 'Chronic hepatitis D associated with worse patient-reported outcomes than chronic hepatitis B' [JHEP Reports 3 (2021)].

[This corrects the article DOI: 10.1016/j.jhepr.

Clinical Benefit and Expedited Approval of Cancer Drugs in the United States, European Union, Switzerland, Japan, Canada, and Australia.

Purpose: Regulatory agencies have sought to speed up the review of new cancer medicines and reduce delays in approval between countries. We examined trends in regulatory review times and association with clinical benefit for new cancer medicines in six jurisdictions: United States (Food and Drug Administration [FDA]), European Union (European Medicines Agency [EMA]), Switzerland (Swissmedic), Japan (Pharmaceuticals and Medical Devices Agency [PMDA]), Canada (Health Canada), and Australia (Therapeutic Goods Administration).

Methods: We studied all new cancer drugs approved in the six aforementioned jurisdictions from 2007 to 2020.

Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities.

Background: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine.

Methods: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF.

Validation of an electronic frailty index with electronic health records: eFRAGICAP index.

Objective: To create an electronic frailty index (eFRAGICAP) using electronic health records (EHR) in Catalunya (Spain) and assess its predictive validity with a two-year follow-up of the outcomes: homecare need, institutionalization and mortality in the elderly. Additionally, to assess its concurrent validity compared to other standardized measures: the Clinical Frailty Scale (CFS) and the Risk Instrument for Screening in the Community (RISC).

Methods: The eFRAGICAP was based on the electronic frailty index (eFI) developed in United Kingdom, and includes 36 deficits identified through clinical diagnoses, prescriptions, physical examinations, and questionnaires registered in the EHR of primary health care centres (PHC).

Neural plasticity of the uterus: New targets for endometrial cancer?

Endometrial carcinoma is the most common gynecological malignancy in Western countries and is expected to increase in the following years because of the high index of obesity in the population. Recently, neural signaling has been recognized as part of the tumor microenvironment, playing an active role in tumor progression and invasion of different solid tumor types. The uterus stands out for the physiological plasticity of its peripheral nerves due to cyclic remodeling brought on by estrogen and progesterone hormones throughout the reproductive cycle.

Spontaneous changes in brain striatal dopamine synthesis and storage dynamics ex vivo reveal end-product feedback-inhibition of tyrosine hydroxylase.

Synaptic events are important to define treatment strategies for brain disorders. In the present paper, freshly obtained rat brain striatal minces were incubated under different times and conditions to determine dopamine biosynthesis, storage, and tyrosine hydroxylase phosphorylation. Remarkably, we found that endogenous dopamine spontaneously accumulated during tissue incubation at 37 °C ex vivo while dopamine synthesis simultaneously decreased.

Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy.

Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.

Methods: Participants were at least 18 years old and had FSHD1/FSHD2.

Autologous stem-cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: a multicenter GELTAMO/FIL study.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare lymphoid malignancies that mostly have poor prognoses with currently available treatments. Upfront consolidation with autologous stem cell transplantation (ASCT) is frequently carried out, but its efficacy has never been investigated in randomized trials. We designed a multicenter, international, retrospective study with the main objective of comparing progression-free survival and overall survival of patients with PTCL who underwent ASCT in complete remission (CR) after first-line chemotherapy with a control group who did not undergo ASCT.

Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation.

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent).

Pooled testing of sputum with Xpert MTB/RIF and Xpert Ultra during tuberculosis active case finding campaigns in Lao People's Democratic Republic.

Introduction: Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive.

Methods: We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR.

Differences in the Area of Proximal and Distal Entry Tears at CT Angiography Predict Long-term Clinical Outcomes in Aortic Dissection.

Purpose: To identify entry tear variables that are related to adverse clinical events by using CT angiography (CTA) performed during the subacute phase of aortic dissection.

Materials And Methods: In this prospective study conducted from January 2000 to December 2013, participants with an aortic dissection with a patent false lumen and no comorbidities underwent CTA during the subacute phase. Participants were followed up for a survival analysis to assess the time to an adverse aortic event (AAE).

Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma.

Background: Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines.

Methods: We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy.

A Randomized Phase II Study of Anti-CSF1 Monoclonal Antibody Lacnotuzumab (MCS110) Combined with Gemcitabine and Carboplatin in Advanced Triple-Negative Breast Cancer.

Purpose: This phase II study determined the efficacy of lacnotuzumab added to gemcitabine plus carboplatin (gem-carbo) in patients with advanced triple-negative breast cancer (TNBC).

Patients And Methods: Female patients with advanced TNBC, with high levels of tumor-associated macrophages not amenable to curative treatment by surgery or radiotherapy were enrolled. Lacnotuzumab was dosed at 10 mg/kg every 3 weeks, ± a dose on cycle 1, day 8.

Single Anastomosis Duodeno-ileal Bypass As a Revisional Procedure Following Sleeve Gastrectomy: Review of the Literature.

Laparoscopic sleeve gastrectomies (LSGs) can experience weight-loss failure and conversion to another bariatric procedure. An analysis of the bariatric literature concerning the single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as revisional surgery after LSG in terms of safety and efficacy identified 607 studies. Fifty-nine studies were analyzed for full content review and 9 primary studies (398 patients) were included.

Associations With Definitive Outcomes and Clinical Benefit of Cancer Drugs at the Time of Marketing Approval and in the Postmarketing Period.

Background: Most anticancer drugs are approved by regulatory agencies based on surrogate measures. This article explores the variables associated with overall survival (OS), quality of life (QoL), and substantial clinical benefit among anticancer drugs at the time of approval and in the postmarketing period.

Methods: Anticancer drugs approved by the FDA between January 2006 and December 2015 and with postmarketing follow-up until April 2019 were identified.

The impact of radiological assessment schedules on progression-free survival in metastatic breast cancer: A systemic review and meta-analysis.

Background: The impact of interval of restaging on the observed magnitude of benefit of progression-free survival (PFS) is undefined.

Materials And Methods: Phase 3 randomized controlled trials (RCTs) investigating anti-neoplastic drugs for metastatic breast cancer which reported the restaging interval and hazard ratio (HR) for PFS were included. Data on study design and study population were collected.

21st century excitatory amino acid research: A Q & A with Jeff Watkins and Dick Evans.

In 1981 Jeff Watkins and Dick Evans wrote what was to become a seminal review on excitatory amino acids (EAAs) and their receptors (Watkins and Evans, 1981). Bringing together various lines of evidence dating back over several decades on: the distribution in the nervous system of putative amino acid neurotransmitters; enzymes involved in their production and metabolism; the uptake and release of amino acids; binding of EAAs to membranes; the pharmacological action of endogenous excitatory amino acids and their synthetic analogues, and notably the actions of antagonists for the excitations caused by both nerve stimulation and exogenous agonists, often using pharmacological tools developed by Jeff and his colleagues, they provided a compelling account for EAAs, especially l-glutamate, as a bona fide neurotransmitter in the nervous system. The rest, as they say, is history, but far from being consigned to history, EAA research is in rude health well into the 21st Century as this series of Special Issues of Neuropharmacology exemplifies.

Fragility of randomized trials supporting cancer drug approvals stratified by approval pathway and review designations.

Background: It has been suggested that the results from fragile trials are less likely to translate into benefit in routine clinical practice.

Methods: We searched the Food and Drug Administration (FDA) archives to identify drug approvals for solid organ malignancies between 2010 and 2019. We calculated the Fragility Index (FI) supporting each approval, using methods to account for time-to-event.

Editorial: Thalamic Subregions Are Differentially Associated With Obsessive-Compulsive Symptoms in Children.

Weeland et al. discuss the relationship between subregional thalamic volumes and obsessive-compulsive symptoms (OCS) in children from the general population. The thalamus is the last relay node of the so-called corticostriatal-thalamocortical (CSTC) circuits before information reenters the cortex.