Exploring SERPINA3 as a neuroinflammatory modulator in Alzheimer's disease with sex and regional brain variations.

SERPINA3, a serine protease inhibitor, is strongly associated with neuroinflammation, a typical condition of AD. Its expression is linked to microglial and astrocytic markers, suggesting it plays a significant role in modulating neuroinflammatory responses. In this study, we examined the SERPINA3 expression levels, along with CHI3L1, in various brain regions of AD patients and non-demented healthy controls (NDHC).

Retrospective-Prospective Observational Study of Italian Patients Treated in Melanoma Adjuvant Cohort MAP-MADAM (Maximing ADjuvAnt MAP): Interim Analysis.

: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. : The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective-prospective observational study that included patients who received at least one dose of D + T through the MAP.

Osteoporosis in Systemic Mastocytosis: A Scoping Review.

: Mastocytosis (MS) is a rare disease that can involve various organs, including the bone. Given the incidence of the disease in the global population, MS poses a challenge for physicians, and early therapeutic intervention in the initial stages could significantly impact the quality of life of affected patients. : The aim of this scoping review was to provide an overview of secondary osteoporosis in systemic mastocytosis (SM), focusing on the heterogeneity of its manifestations, the benefits of early diagnosis, and appropriate pharmacological treatment.

Self-selected speed provides more accurate human gait kinematics and spatiotemporal parameters than overground simulated speed on a treadmill: a cross-sectional study.

Background: Walking speed, a key element of gait analysis, is essential for evaluating the biomechanics of the musculoskeletal system and is typically assessed on flat surfaces, such as walkways or treadmills. While many authors have compared the differences and similarities between treadmill and overground walking, no studies have yet investigated the differences between treadmill gait analysis at self-selected speed (SS) and overground simulated speed (OS). The hypothesis is that accurate kinematic measurements depend on selecting the correct gait speed; however, a mismatch between the perceived comfortable treadmill speed and actual overground speed may affect the accuracy of treadmill gait analyses.

Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.

Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.

Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).

Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238.

Purpose: In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.

Patients And Methods: Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent.

Appendicular Skeletal Muscle Mass in Older Adults Can Be Estimated With a Simple Equation Using a Few Zero-Cost Variables.

Background And Purpose: Assessing appendicular skeletal muscle (ASM) mass is crucial for the diagnosis of numerous pathologies related to the decline of muscle mass in old age, such as sarcopenia, malnutrition, or cachexia. The dual-energy X-ray absorptiometer (DEXA) radiological technique, which is the gold standard for its assessment, is particularly costly and not routinely used in clinical practice. The aim of this study was to derive computationally simple equations capable of estimating the DEXA-measured ASM at zero cost in older adult populations.

Effects of high-flow nasal therapy on swallowing function: a scoping review.

Background: High-flow nasal therapy is widely used in patients with respiratory failure in different clinical settings, but the effect of high-flow nasal therapy on respiratory-swallow coordination is unknown. Understanding this relationship is crucial, considering the necessity for patients to maintain adequate nutrition during daytime high-flow nasal therapy. This scoping review aims to synthesise available data on the effects of high-flow nasal therapy flow rates on swallowing function and the possible risk of aspiration during treatment, focusing on knowledge and evidence gaps.

Efficacy of rehabilitation treatments in improving functioning in patients with fibromyalgia: A systematic review and meta-analysis of randomized controlled trials.

Background: Fibromyalgia is a debilitating condition marked by persistent pain and reduced functionality. Various therapeutic methods have been suggested to alleviate symptoms in individuals with fibromyalgia, yet the impact of diverse rehabilitation strategies remains unclear.

Objective: This systematic review and meta-analysis aimed at assessing the efficacy of rehabilitation interventions in improving functioning in fibromyalgia patients.

Extracorporeal ShockWave Treatment vs. mesotherapy in the treatment of myofascial syndromes: a clinical trial.

Numerous scientific papers have compared different treatment options in the management of myofascial pain syndrome. This study evaluated the efficacy of Extracorporeal ShockWave Treatment (ESWT) and mesotherapy in patients with Myofascial Pain Syndrome (MPS) in terms of improvement in pain, functional capacity, and quality of life. A case-control study was conducted on 54 patients, who were randomized into 2 groups: group A, consisting of 27 patients, who were treated with 5 sessions of focal ESWT on a weekly basis; and group B, consisting of 27 patients, who underwent 5 sessions of mesotherapy with Thiocolchicoside fl 4 mg/2 mL and Mepivacaine fl 10 mg/1 mL on a weekly basis.

Skeletal muscle of young females under resistance exercise exhibits a unique innate immune cell infiltration profile compared to males and elderly individuals.

Muscle damage resulting from physical activities such as exercise triggers an immune response crucial for tissue repair and recovery. This study investigates the immune cell profiles in muscle biopsies of individuals engaged in resistance exercise (RE) and explores the impact of age and sex on the immune response following exercise-induced muscle damage. Microarray datasets from muscle biopsies of young and old subjects were analyzed, focusing on the gene expression patterns associated with immune cell activation.

Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors.

Introduction: About 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR).

Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial.

Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.

Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study.

JCO Pembrolizumab adjuvant therapy was shown to significantly improve recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB or IIC melanoma in earlier analyses of the randomized, double-blind, phase III KEYNOTE-716 study (ClinicalTrials.gov identifier: NCT03553836). We report results of the protocol-specified final analysis of DMFS for KEYNOTE-716.

Plain language summary of the CheckMate 76K study results: nivolumab given after stage 2B/2C melanoma is removed by surgery.

What Is This Summary About?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells.

Melanoma and sex hormones: Pathogenesis, progressive disease and response to treatments.

Cutaneous melanoma represents the fifth tumor in terms of incidence in young adults, with a major involvement of males than females. Despite the significant changes in available effective treatments for cutaneous melanoma, there is still a proportion of patients that do not benefit long-term disease control with immune checkpoint inhibitors and/or inhibitors, and eventually develop progressive disease. In addition to the emerging biomarkers under investigation to understand resistance to treatments, recent studies resumed the role of sex hormones (estrogens, progesterone and androgens) in melanoma patients.

Damage for gain: The useful damage of the Pitcher's paradox.

Introduction: Sport-specific adaptations of the glenohumeral joint may arise in adolescent overhead athletes who begin high-performance sports early in life. Research mainly addresses overuse injuries, leaving gaps in prevention, with adults studied more than youths.

Objective: This study aims to investigate sport-adaptations of the glenohumeral joint in asymptomatic adolescent volleyball players to identify potential shoulder injury risk factors.

Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

Background: Congenital disorders of glycosylation (CDG) are genetic diseases caused by impaired synthesis of glycan moieties linked to glycoconjugates. Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent CDG, is characterized by prominent neurological involvement. Gait disturbance is a major cause of functional disability in patients with PMM2-CDG.

Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial.

Background: The primary analysis of the phase III NIBIT-M2 study showed a 41% 4-year overall survival (OS) of melanoma patients with asymptomatic brain metastases treated with ipilimumab plus nivolumab.

Methods: Here, we report the 7-year efficacy outcomes and the Health-Related Quality of Life (HRQoL) analyses of the NIBIT-M2 study.

Results: As of May 1, 2023, at a median follow-up of 67 months (mo), the median OS was 8.