Neurofilament heavy chain in secondary progressive multiple sclerosis.

Background: Biomarkers are needed to track progression in MS trials. Neurofilament heavy chain (NfH) has been underutilized due to assay limitations.

Objective: To investigate the added value of cerebrospinal fluid (CSF) NfH in secondary progressive multiple sclerosis (SPMS) using contemporary immunoassays.

Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study.

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19).

Minimal clinically important difference (MCID), patient-acceptable symptom state (PASS), and substantial clinical benefit (SCB) following surgical knee ligament reconstruction: a systematic review.

Introduction: The minimal clinically important difference (MCID), patient-acceptable symptom state (PASS), and substantial clinical benefit (SCB) are designed to prioritise clinically significant outcomes that demonstrate true clinical benefit rather than relying solely on statistical significance. These instruments aid clinicians in understanding the patient's perspective, allowing healthcare professionals to set treatment goals that align with patients' desires and expectations. This systematic review analysed tools to estimate the clinical relevance of the most commonly used PROMs to assess patients following surgical knee ligament reconstruction.

Understanding Staff Needs for Improving End-Of-Life Care in Critical Care Units: A Qualitative Focus Group Analysis and Service Evaluation.

Critical care is a place of frequent death, up to a quarter of those admitted die during admission. Caring for dying people provides many challenges, practically, professionally and personally. The aim of this study was to better understand the perspectives of staff caring for dying people in critical care and identify their priorities for improvement.

Importance of integrin transmembrane helical interactions for antagonistic versus agonistic ligand behavior: Consequences for medical applications.

Integrins are well-characterized receptors involved in cell adhesion and signaling. With six approved drugs, they are recognized as valuable therapeutic targets. Here, we explore potential activation mechanisms that may clarify the agonist versus antagonist behavior of integrin ligands.

Peri-Intubation Cardiac Arrest in a Patient With Hypertensive Cardiac Tamponade.

Cardiac tamponade is widely known to be associated with life-threatening hypotension and rarely with hypertension. We present the case of a 53-year-old woman with hypertension and echocardiographic features of tamponade who had a cardiac arrest on intubation. The paradoxical hypertension is thought to be due to tachycardia and increased peripheral vascular resistance resulting from the compensatory sympathetic surge following impaired cardiac filling caused by the effusion.

A novel oncolytic Vaccinia virus armed with IL-12 augments antitumor immune responses leading to durable regression in murine models of lung cancer.

Oncolytic vaccinia viruses (VVs) are potent stimulators of the immune system and induce immune-mediated tumor clearance and long-term surveillance against tumor recurrence. As such they are ideal treatment modalities for solid tumors including lung cancer. Here, we investigated the use of VVL-m12, a next-generation, genetically modified, interleukin-12 (IL-12)-armed VV, as a new therapeutic strategy to treat murine models of lung cancer and as a mechanism of increasing lung cancer sensitivity to antibody against programmed cell death protein 1 (α-PD1) therapy.

Update on the treatment navigation for functional cure of chronic hepatitis B: expert consensus 2.0.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements.

"If that would have lessened my symptoms, that would have been great...": a qualitative study about the acceptability of tecovirimat as treatment for mpox.

Background: Tecovirimat, an antiviral treatment for smallpox, was approved as a treatment for mpox by the European Medicines Agency in January 2022. Approval was granted under "exceptional circumstances" based on effectiveness found in pre-clinical challenge studies in animals and safety studies in humans showing minimal side effects. As clinical efficacy studies are still ongoing, there is currently limited information with regard to the acceptability of tecovirimat to treat mpox.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Tumour growth rate and invasive interval cancer characteristics in a UK breast cancer screening population.

Objectives: To estimate tumour volume doubling time (TVDT) of interval cancers (ICs).

Methods: Two radiologists retrospectively reviewed prior screening and diagnostic mammograms and measured mean diameter on "visible" ICs. Univariate analyses of clinicopathological variables (ER, HER2, grade, age at diagnosis, and breast density) were undertaken, and those with p < 0.

Prognostic impact of albuminuria in early-stage chronic kidney disease on cardiovascular outcomes: a cohort study.

Background: The impact of early-stage chronic kidney disease (CKD) on cardiovascular outcomes, particularly when albuminuria is present, remains unclear. This study examined the associations between early CKD (stages 1 and 2) with and without albuminuria and the incidence of major adverse cardiovascular events (MACEs), heart failure (HF) and all-cause mortality.

Methods: A cohort of 456 015 participants from the UK Biobank was categorised by CKD stage using serum creatinine to calculate estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (≥3 mg/mmol) to define albuminuria.

Replicating Dynamic Immune Responses at Single-Cell Resolution within a Microfluidic Human Skin Equivalent.

To enable in vitro investigation of human skin immunology, this study develops a microfluidic human skin equivalent (HSE) that supports the delivery of circulating immune cells via a vascular microchannel embedded within the dermis of a full-thickness construct. Within this platform, activation of keratinocyte inflammation promotes monocyte migration out of the vascular channel and into the dermal and epidermal compartments. Single-cell transcriptomic analysis reveals dynamic and cell-specific patterns of gene expression that are characteristic of acute activation and resolution of an inflammatory immune response, and the gene signatures of the monocyte-derived cells closely matches the differentiation trajectory of the monocytes into mature dermal macrophages.

A new model of experimental diabetic cardiomyopathy using combination of multiple doses of anomer-equilibrated streptozotocin and high fat diet: sex matters.

Diabetes mellitus (DM) leads to a more rapid development of DM cardiomyopathy (dbCM) and progression to heart failure in women than men. Combination of high-fat diet (HFD) and freshly-injected streptozotocin (STZ) has been widely used for DM induction, however emerging data shows that anomer-equilibrated STZ produces an early onset and robust DM model. We designed a novel protocol utilising a combination of multiple doses of anomer-equilibrated STZ injections and HFD to develop a stable murine DM model featuring dbCM analogous to humans.

Delirium prevention in hospices: Opportunities and limitations - A focused ethnography.

Background: Delirium is common and distressing for hospice in-patients. Hospital-based research shows delirium may be prevented by targeting its risk factors. Many preventative strategies address patients' fundamental care needs.

Anatomic and Functional Outcomes of Scleral Buckling Surgery for Advanced Retinopathy of Prematurity: A Systematic Review and Proportional Meta-Analysis.

A significant percentage of patients with retinopathy of prematurity (ROP) who progressed to stages 4 and 5 of ROP will require surgical intervention. Scleral buckling surgery is widely employed for the restoration of retinal detachment in advanced cases of ROP. This systematic review and meta-analysis aim to review the anatomical and visual outcomes following scleral buckling surgery in ROP of stages 4 and 5.

Improving Communication and Teamwork Between Resident Doctor Teams Using a Group Messaging Application: A Quality Improvement Project.

Background Communication and teamwork are essential in medicine. Established standards emphasise the importance of collaboration and access to support. Some departments divide doctors into teams; however, inter-team communication is not always efficient.

Assessing Human Ribosomal DNA Variation and Its Association With Phenotypic Outcomes.

Although genome-scale analyses have provided insights into the connection between genetic variability and complex human phenotypes, much trait variation is still not fully understood. Genetic variation within repetitive elements, such as the multi-copy, multi-locus ribosomal DNA (rDNA), has emerged as a potential contributor to trait variation. Whereas rDNA was long believed to be largely uniform within a species, recent studies have revealed substantial variability in the locus, both within and across individuals.

Combination therapy versus monotherapy: retrospective analysis of antibiotic treatment of enterococcal endocarditis.

Background: Guidelines suggest treating fully penicillin-susceptible Enterococcus faecalis strains causing infective endocarditis with amoxicillin combined with gentamicin or ceftriaxone, but clinical evidence to support this practice is limited and monotherapy cohorts were excluded from studies. We describe antibiotic treatment, complications, and outcomes in patients with Enterococcus faecalis infective endocarditis, specifically comparing monotherapy versus combination therapy.

Methods: Retrospective analysis of prospectively collected cohort of patients with definite or possible infective endocarditis from 2 English centres between 2006 and 2021.

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

Rigour of Development of European Society of Cardiology, American College of Cardiology and American Heart Association guidelines over a 12-year period (2013-2024): a systematic review of guidelines.

Introduction: The ESC and ACC/AHA regularly publish guidelines for the management of cardiovascular disease. By definition, a guideline should follow strict methodological criteria, and have a transparent, traceable and reproducible development process. We aimed to assess the overall strength of the recommendations and rigour of methodological development in ESC and ACC/AHA guidelines.