Hospitalised older adults with community-acquired pneumonia and sepsis have dysregulated neutrophil function but preserved glycolysis.

Objective: Community-acquired pneumonia (CAP) is a leading cause of hospitalisation in older adults and is associated with a high likelihood of adverse outcomes. Given the ageing population and lack of therapeutic advances in CAP, new strategies to manage the burden of this disease are needed. Neutrophil dysfunction has been widely demonstrated in CAP and is associated with poor outcomes.

SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers.

Purpose: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs).

Methods: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m, cisplatin 25 mg/m, and nab-paclitaxel 100 mg/m intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m and cisplatin 25 mg/m intravenously once per day on days 1 and 8 of a 21-day cycle).

Results: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC.

Vitamin D deficiency and duration of COVID-19 symptoms in UK healthcare workers.

Objectives: Vitamin D has a role in the innate immunity against pathogens and is also involved in mechanisms for reducing inflammation. VD deficiency (VDD) may increase COVID-19 infection susceptibility, however research is limited on the association between VDD and COVID-19 symptom prevalence and duration. The study aimed to determine whether VDD is a risk factor for the presence and extended duration of COVID-19 symptoms.

Role of gene expression in colorectal cancer: a comprehensive molecular profiling study.

Background: In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages.

DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.

Purpose: The outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.

Patients And Methods: Patients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.

Metagenomics in the Diagnosis of Pneumonia: Protocol for a Systematic Review.

Background: Causative pathogens are currently identified in only a minority of pneumonia cases, which affects antimicrobial stewardship. Metagenomic next-generation sequencing (mNGS) has potential to enhance pathogen detection due to its sensitivity and broad applicability. However, while studies have shown improved sensitivity compared with conventional microbiological methods for pneumonia diagnosis, it remains unclear whether this can translate into clinical benefit.

Total Ankle Arthroplasty Templating: Preoperative Computer Templating Correlates Highly with Intraoperative Component Selection.

Proper alignment and sizing are critical to the performance of a successful total ankle arthroplasty. While it is common practice in preoperative planning prior to total knee and total hip arthroplasty, preoperative computer templating has not been well established in the setting of total ankle arthroplasty. A retrospective review of all total ankle arthroplasties performed during a 10-year period by a single fellowship-trained orthopaedic surgeon was conducted.

Peptide clustering enhances large-scale analyses and reveals proteolytic signatures in mass spectrometry data.

Recent advances in mass spectrometry-based peptidomics have catalyzed the identification and quantification of thousands of endogenous peptides across diverse biological systems. However, the vast peptidomic landscape generated by proteolytic processing poses several challenges for downstream analyses and limits the comparability of clinical samples. Here, we present an algorithm that aggregates peptides into peptide clusters, reducing the dimensionality of peptidomics data, improving the definition of protease cut sites, enhancing inter-sample comparability, and enabling the implementation of large-scale data analysis methods akin to those employed in other omics fields.

High-throughput functional analysis provides novel insight into type VII secretion in .

Successful colonization by the opportunistic pathogen depends on its ability to interact with other microorganisms. strains harbour a T7b subtype of type VII secretion system (T7SSb), a protein secretion system found in a wide variety of Bacillota, which functions in bacterial antagonism and virulence. Assessment of T7SSb activity in has been hampered by low secretion activity under laboratory conditions and the lack of a sensitive assay to measure secretion.

Management of Locally Advanced Rectal Cancer: ASCO Guideline.

. .PURPOSETo provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed.

Age Influence on Total Ankle Arthroplasty Outcomes: A Systematic Review.

Total ankle arthroplasty has gained popularity as advancing technology has resulted in higher survivorship and lower complication rates. In the past, total ankle replacement candidates have been reserved for patients greater than 50 years old with low physical demands and minimal deformity. However, with newer designs, surgeons have begun to expand their patient inclusion criteria.

Dorsal Cheilectomy.

Dorsal cheilectomy refers to a surgical resection of the dorsal osteophyte from the first metatarsal head. It is most often performed in patients with hallux rigidus, who have little to no midrange pain of the first metatarsophalangeal joint. The procedure is simple, quick, and maintains range of motion.

Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors.

Functional copy-number alterations (fCNAs) are DNA copy-number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene-expression data from 31 pancreatic (pNETs) and 33 small-bowel neuroendocrine tumors (sbNETs).

Demographic Comparisons of Self-Reported Fall Risk Factors Among Older Adults Attending Outpatient Rehabilitation.

Purpose: Identify the prevalence and prevalence differences of fall risk factors by sex, clinic rurality, and race/ethnicity among older adults (≥65 years old) receiving outpatient rehabilitation.

Patients And Methods: Our secondary analysis used Electronic Health Record data of 108,751 older adults attending outpatient rehabilitation (2018-2022) within a large health system across 7 states and completed the Stay Independent Questionnaire. The mean age was 73.

11β hydroxysteroid dehydrogenase type 1 transgenic mesenchymal stem cells attenuate inflammation in models of sepsis.

Background: Human bone marrow mesenchymal stem cell (MSC) administration reduces inflammation in pre-clinical models of sepsis and sepsis-related lung injury, however clinical efficacy in patients has not yet been demonstrated. We previously showed that Alveolar Macrophage (AM) 11β-hydroxysteroid dehydrogenase type-1 (HSD-1) autocrine signalling is impaired in critically ill sepsis patients, which promotes inflammatory injury. Administration of transgenic MSCs (tMSCs) which overexpress HSD-1 may enhance the anti-inflammatory effects of local glucocorticoids and be more effective at reducing inflammation in sepsis than cellular therapy alone.

A novel cell model of the proteinase/antiproteinase balance observed in alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting from mutations in the alpha-1 antitrypsin (AAT) protein, a major systemic antiproteinase, resulting in reduced/no release of AAT, disrupting the proteinase/antiproteinase balance. A sustained imbalance can cause structural changes to the lung parenchyma, leading to emphysema. Predicting and assessing human responses to potential therapeutic candidates from preclinical animal studies have been challenging.

Towards personalised anti-microbial and immune approaches to infections in acute care. Can real-time genomic-informed diagnosis of pathogens, and immune-focused therapies improve outcomes for patients? An observational, experimental study protocol.

Introduction: Infection causes a vast burden of disease, with significant mortality, morbidity and costs to health-care systems. However, identifying the pathogen causative infection can be challenging, resulting in high use of broad-spectrum antibiotics, much of which may be inappropriate. Novel metagenomic methods have potential to rapidly identify pathogens, however their clinical utility for many infections is currently unclear.

Predictive Factors of Postoperative Pain in Patients With Tibiotalocalcaneal Arthrodesis With an Intramedullary Nail: A Retrospective Review.

Tibiotalocalcaneal arthrodesis has been shown in literature to have good results in regards to low complication rates and deformity correction. While previous studies have investigated functional outcomes and complication rates, no large-scale studies have looked at pain outcomes. The present study performed a retrospective review of 154 extremities to analyze how a patient's comorbidities and characteristics influence pain outcomes following a tibiotalocalcaneal arthrodesis.

Primary Arthrodesis versus Open Reduction and Internal Fixation for Lisfranc Joint Fracture-Dislocations in Adults: A Systematic Review.

Background: The Lisfranc joint is an intricate podiatric medical structure that when injured can prove difficult to treat. No consensus has been established on optimal surgical management for this injury. It is widely debated whether open reduction and internal fixation or primary arthrodesis provides better outcomes for patients.