Medicine and Pharmacology

Abstract: Background: There is no generally accepted, routine screening for bladder cancer (BC), which is among the ten most common malignancies in men and the most expensive cancer to treat. We examined possibility of using the urinary metabolite concentration 1-Hydroxypyrene (1-OHP) for screening high-risk male individuals for BC. Methods: This was a clinical controlled study. Numerical data were arithmetic mean with standard deviation or median with interquartile range, while categorical data were shown as percentages. Two independent samples were compared by Student t-test or Mann-Whitney U test, depending on the data distribution. Normality was evaluated by Shapiro-Wilk test and box plots. The analysis was performed in the statistical software IBM SPSS ver. 31. Results: This study comprised 117 urinary BC male patients and 110 healthy male controls. The mean urinary values of 1-OHP at first measurement – in patients 205.0 pg/ml (IQR = 116.5-456.5) and in controls 136.5 pg/ml (IQR =76-374.5) with statistically higher values in urinary BC male patients than in controls (p = 0.020). At second measurement – in patients 183.0 pg/ml (IQR = 141.8-407.3) and 137.0 pg/ml (IQR = 73-353.0) with statistically higher values in urinary BC male patients than in controls (p=0.013). Conclusion: 1- OHP values were higher in the BC patients group, but it is not sufficient for urinary screening of high-risk males for BC. We suggest High Performance Liquid Chromatography (HPLC) and Induced Coupled Plasma (ICP) concentration values of urinary biomarkers from other chemical carcinogens incriminated as causes of BC, from Group 1 carcinogens according to the International Agency for Research Cancer (IARC). We reasonably assume that by having urinary biomarker values of chemical carcinogens for BC in men, it would be possible to create an algorithm that could identify men at high risk for developing BC.

Abstract: Background/Objectives: Superficially serrated adenoma is a recently recognized subtype of colorectal serrated lesions. Case Reports: We report a case of a rectal superficially serrated adenoma in a 57-year-old Japanese woman with ulcerative colitis and a history of follicular lymphoma. Endoscopically, the lesion presented as a superficial sessile lesion without a nodule component and was completely removed by cold snare polypectomy. Histopathological examination revealed a characteristic combination of superficially serrated epithelium and vertically oriented adenoma-like glands. Immunohistochemistry confirmed serrated differentiation of the superficial epithelial component. Molecular analyses identified a KRAS Q61H mutation and a novel PTPRK::RSPO3 fusion that retained the entire RSPO3 coding region. Conclusions: To our knowledge, this represents the first reported case of RSPO3 fusion in a superficially serrated adenoma associated with ulcerative colitis in Japan. Although some aspects of the molecular pathogenesis of superficially serrated adenoma have been increasingly investigated, its clinicopathological features, particularly in the setting of ulcerative colitis, remain poorly characterized. Additional clinicopathological and molecular studies are required to determine whether superficially serrated adenomas arising in patients with ulcerative colitis represent incidental sporadic lesions or a distinct subset associated with the inflammatory bowel disease setting.

Abstract: Background: Bone marrow-derived CD133⁺ cells have been tested as autologous products in acute and chronic ischaemic heart disease, but their mechanism and clinical value remain uncertain. Objective: To map the clinical, mechanistic, manufacturing, and regulatory evidence for bone marrow-derived immunoselected CD133+ products and identify gaps relevant to potency assessment. Methods: PubMed and Europe PMC were searched from inception through August 2026, supplemented by backward citation searching and official regulatory sources. Records were organised in a single-reviewer PRISMA-ScR workflow and charted by evidence domain, cell source, design, delivery/manufacturing context, endpoints, and limitations. Results: The searches yielded 482 database records and 18 additional sources. After the removal of 289 duplicates, 211 unique records were screened, and 57 sources were included: 35 clinical reports, six direct preclinical/mechanistic studies, six manufacturing/quality studies, five contextual mechanistic studies, and five guidance/regulatory documents. Clinical studies support feasibility and limited-population safety but show no consistent improvement in global ventricular function or clinical outcomes. Direct adult bone marrow CD133+ mechanistic evidence remains sparse, while RECARDIO provides an associative product-to-perfusion bridge. Conclusions: A mechanism-linked potency strategy should prioritise source-specific endothelial rescue under hypoxia–reoxygenation, supported by migration, network formation, and a restricted directional secretome panel. Prospective product-to-perfusion validation is required before CD133+ therapy can be considered clinically established.

Abstract: Background/Objectives: Systemic inflammatory indices may differ prognostically between resectable and palliative pancreatic cancer. We compared associations of the aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR) with overall survival after pan-creatic resection or palliative bypass. Methods: This single-center retrospective cohort included 240 patients treated during 2013–2023 (99 resections; 141 palliative bypasses). Indices derived from preoperative blood counts were natural-log transformed, standardized to 1 SD, and entered separately into operative-group-stratified Cox models. Group-specific associations and interactions were estimated. Reconstructed AJCC eighth-edition stage was incorporated only in the resection stratum. Interaction p values were Holm-adjusted. AISI was designated primary and SIRI key secondary. Results: Overall, 215 deaths occurred. Median overall survival was 17.9 months after resection and 5.4 months after palliative bypass. AISI was associated with mortality following bypass (adjusted hazard ratio [HR] per 1-SD increase in ln(AISI), 1.54; 95% confidence interval [CI], 1.28–1.86) but not following resection (HR, 0.97; 95% CI, 0.75–1.25; interaction p = 0.003; Holm-adjusted p = 0.010). SIRI showed corresponding HRs of 1.60 (95% CI, 1.30–1.96) and 0.93 (95% CI, 0.72–1.20), respectively (interaction p = 0.001; Holm-adjusted p = 0.004). MLR also demonstrated heterogeneity, whereas NLR and SII did not. The AISI and SIRI findings remained robust in sensitivity analyses. Conclusions: AISI and SIRI demonstrated operative-context-dependent associations, principally after palliative bypass. Because comparable staging was unavailable in this group, residual confounding by disease extent remains possible. Prospective multicenter validation is required before clinical implementation.

Abstract: Background: A narrow waist is one of the central objectives of aesthetic body contour-ing, and it is closely tied to the waist-to-hip ratio that observers associate with a feminine silhouette. Conventional soft-tissue techniques such as liposuction and liposculpture are constrained by patient-specific anatomy, including the pattern of adipose tissue distribution and the transverse dimensions of the bony rib cage. Minimally invasive rib re-modeling was developed to overcome these constraints and to produce a more pronounced waist-narrowing effect without rib removal. The factors that determine the magnitude of the result and patient satisfaction have not been characterized in sufficient detail. Methods: A combined retrospective–prospective single-center study was conducted on 60 female patients aged 22 to 55 years (mean age, 35.5 years) who underwent minimally invasive rib remodeling using the Kudzaev technique between 2017 and 2025. The variables assessed included anthropometric measurements, body mass index (BMI), sub-cutaneous and visceral adipose distribution, body shape, endocrine status, and psycho-logical readiness to adhere to the postoperative regimen. Outcomes were evaluated at three months on the basis of the change in waist circumference, standardized photo-graphic documentation, and patient satisfaction (5-point scale) and the BODY-Q Satis-faction with body scale. Results: The mean reduction in waist circumference was 7.82 ± 2.14 cm. Both the re-duction and patient satisfaction decreased with increasing BMI (Pearson r = −0.30 and −0.42, respectively): patients with a BMI ≤ 25 kg/m² (n = 59) achieved a mean reduction of 7.86 ± 2.12 cm and a satisfaction score of 4.25 ± 0.96, whereas the single patient with a BMI > 25 kg/m² obtained a smaller reduction (5 cm) and the lowest satisfaction score. The BODY-Q Satisfaction with body scale corroborated these results (Rasch-transformed score, 82.6 ± 18.3) and correlated strongly with the 5-point rating (Pearson r = 0.90). Elevated BMI and a pronounced visceral fat component were associated with a less favorable aesthetic outcome. Endocrine disease, in particular hyperparathyroidism, was associated with delayed rib consolidation and lower satisfaction. Poor postoperative compliance, especially inconsistent corset wear, was linked to unsatisfactory results. Conclusions: The effectiveness of minimally invasive rib remodeling depends substantially on patient selection. The most favorable outcomes were obtained in patients with a normal BMI, minimal adipose tissue, and a high level of compliance. Elevated BMI, excess visceral fat, endocrine disorders, and low motivation are risk factors for an unfavorable outcome. These findings support rigorous preoperative selection that accounts for both somatic and behavioral characteristics.

Abstract: Did Franklin D. Roosevelt really have polio? For most of the twentieth century, the answer seemed settled. Roosevelt’s 1921 paralytic illness was diagnosed as poliomyelitis by leading specialists of the era and permanently disabled his legs. Decades later, however, a widely cited Bayesian analysis argued that Guillain–Barré syndrome (GBS) was more likely. This article revisits that medical mystery using Roosevelt’s surviving clinical records, contemporary epidemiology, and modern neurological knowledge. Several features do support GBS, including his age, ascending weakness, facial involvement, and sensory complaints. But other findings point more strongly toward polio: fever during the evolution of paralysis, preserved objective sensation, highly uneven muscle weakness, focal atrophy and fasciculations, and a lifelong pattern of selective leg paralysis. The influential 2003 statistical argument also counted partly overlapping clinical features separately and did not calculate a single joint probability incorporating the entire case. Although no retrospective diagnosis can be certain, the available evidence supports paralytic poliomyelitis more convincingly than GBS. The controversy illustrates both the appeal—and the limitations—of using modern diagnostic tools to rewrite medical history.

Abstract: Neurodegenerative diseases are a growing global health burden associated with aging and characterized by progressive neuronal dysfunction, metabolic failure, mitochondrial impairment, oxidative stress, and chronic neuroinflammation. Among the metabolic pathways implicated in these disorders, coenzyme A (CoA)-linked biology has emerged as a potentially important but still underexplored contributor to neuronal resilience and vulnerability. Pantethine, a disulfide derivative of pantetheine and a CoA-related metabolic precursor, has attracted attention because of its reported effects on cellular metabolism, redox balance, and inflammatory signaling. However, its relevance across neurodegenerative diseases remains unevenly defined, with direct support strongest in pantothenate kinase-associated neurodegeneration (PKAN) and more limited evidence in common disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This narrative review critically examines the mechanistic and translational evidence linking pantethine to neurodegeneration. PKAN represents the most logical disease context for pantethine investigation because impaired CoA biosynthesis is proximal to disease pathogenesis, although pantethine remains investigational and its clinical efficacy has not been established. By contrast, proposed applications in AD and PD remain highly theoretical and hypothesis-generating. Nevertheless, research on pantethine and related CoA-restoring strategies may identify new intervention targets across neurodegenerative diseases and other disorders characterized by impaired cellular bioenergetics, including selected neuropsychiatric disorders. These possibilities require biomarker-informed, disease-specific studies that establish active-species exposure, target engagement, and clinically meaningful effects.

Abstract: Background: Early systemic antibiotics are central to open-fracture care, and administration within 60 minutes is widely used as a quality benchmark. Whether 60 minutes represents a biological threshold for deep infection remains uncertain. Methods: We conducted a PRISMA 2020- and MOOSE-informed systematic review of acute open long-bone fractures in adults. The protocol and amendment history were retrospectively archived on OSF (doi:10.17605/OSF.IO/7J8QN). Injury-to-antibiotic, first-medical-contact, first-hospital-arrival, and receiving-trauma-centre intervals were analysed separately. Exact 60-, 120-, and 180-minute thresholds were prespecified. Deep infection or fracture-related infection assessed at 90 days or longer was prioritised, and adjusted estimates were preferred. Results: Twenty-four records were screened, 18 full reports were assessed, and 16 reports were retained in the evidence map; 13 provided explicitly adult-only data. No threshold-by-clock stratum contained two compatible adjusted estimates. At 60 minutes, adjusted estimates were centred near the null, including an adjusted odds ratio of 1.02 (95% CI 0.39–2.68). One 120-minute study reported an adjusted hazard ratio of 2.40. An exploratory 180-minute synthesis yielded an odds ratio of 1.15 (95% CI 0.58–2.31; I² = 0%) but combined adjusted and crude evidence. A delay beyond 12 hours was associated with fracture-related infection in one adjusted study (adjusted odds ratio 4.92, 95% CI 1.63–16.90). Certainty was very low for all threshold questions. Conclusions: Available evidence does not establish a universal 60-minute biological cutoff. This uncertainty should not be interpreted as evidence that delay is safe; antibiotics should be administered as soon as feasible.

Abstract: Background and Objectives: Bile duct injury remains a major safety concern during laparoscopic cholecystectomy, and reliable interpretation of hepatocystic anatomy is fundamental to safe dissection. Artificial intelligence (AI)-based computer vision may support anatomical recognition, critical-view-of-safety (CVS) assessment, and intraoperative decision support. This narrative review synthesized the current evidence, clinical applications, readiness for implementation, and future requirements of anatomy-aware AI during laparoscopic cholecystectomy. Materials and Methods: Five bibliographic databases were searched through 15 August 2026, supplemented by citation tracking and targeted searches. Studies were classified according to clinical task, dataset, reference standard, validation design, performance metrics, real-time capability, human-factor assessment, and clinical-readiness stage. The evidence base comprised 105 verified references: 50 primary AI reports and 55 contextual or methodological sources; 39 direct model-development or evaluation reports were characterized in detail. Results: Investigated applications included landmark detection, semantic segmentation, CVS assessment, safe- and hazard-zone mapping, multimodal analysis incorporating indocyanine green fluorescence, automated documentation, education, and real-time perceptual prompting. Among the 39 direct reports, 24 remained at the offline proof-of-concept or internal-validation stage, eight achieved temporal, external, or multicenter validation, six demonstrated prospective operating-room feasibility, and one reached post-deployment surveillance. The latter evaluated a surgical-process outcome rather than patient morbidity. Generalizability was constrained by dataset overlap, heterogeneous reference standards and metrics, domain shift, and underrepresentation of difficult cholecystectomy. No included study demonstrated reduced bile duct injury or other patient-level benefit. Conclusions: Anatomy-aware AI has progressed from technical feasibility to early clinical translation, with the strongest near-term rationale in documentation, video triage, education, coaching, and quality assurance. Surgeon-facing deployment should remain adjunctive, staged, and risk proportionate, requiring multicenter and temporal validation, explicit uncertainty and abstention mechanisms, human-factor evaluation, comparative-effectiveness studies, and continuous post-deployment surveillance before routine clinical adoption.

Abstract:

Background/Objectives: Therapeutic cancer vaccines can generate measurable immunity without tumor regression. Adjuvants initiate innate activation, but antitumor efficacy also requires antigen presentation, lymphoid priming, effector differentiation, tumor trafficking, cancer-cell recognition and killing, and persistence. We compared the magnitude, duration, and downstream breadth of clinically used adjuvant responses with live vaccination. Methods: We reanalyzed transcriptomic data from six randomized human vaccine studies and one controlled mouse experiment; one human study sequenced six sorted leukocyte populations. Twenty-three prespecified gene sets spanning innate ignition, antigen presentation, adaptive differentiation, trafficking, and effector programs were scored by participant-paired, baseline-adjusted comparisons with matched controls. One trial sampled placebo, adjuvanted, unadjuvanted, and live attenuated vaccines daily. Results: AS01B, AS01E, AS03, and MF59 increased type I interferon by 9.6, 8.6, 7.5, and 3.2 percentile points at 24 hours; AS04 and aluminum salt remained at control levels. Yellow fever 17D sustained interferon through day 7; MF59 resolved by day 3 and AS01/AS03 by day 7. Antigen-presenting-cell activation and MHC class I machinery rose with interferon. Apart from a small day-7 germinal-center/plasmablast signal in two AS03 trials, no reproducible sustained downstream program was detected in blood; acute cytotoxic and natural-killer-cell decreases mainly reflected blood-cell composition. Conclusions: Adjuvants produce robust ignition, but these blood datasets do not establish the later cellular functions required for tumor-cell killing. Duration is one candidate determinant of this transition. Cancer-vaccine trials should measure ignition together with compartment-appropriate priming, trafficking, cytotoxic function, and persistence across repeated doses.

Abstract: Osteoporosis is a major skeletal disorder. Increasing evidence suggests that gut microbiota-derived mechanisms may contribute to bone remodeling. The biological rationale for a gut–bone axis is well supported, but the clinical relevance of microbiome-targeted interventions remains uncertain. In this narrative review, we focus on prebiotics, probiotics, synbiotics, and postbiotics. We searched in the literature the progress from mechanistic observations to measurable skeletal outcomes in humans. We searched PubMed, Scopus, and Web of Science for literature published mainly between 2021 and 2026. We included also earlier studies when they were important for the mechanistic framework. The evidence was evaluated according to intervention type and outcome. We focused on bone turnover markers, bone mineral density, and the duration of exposure required for these outcomes to become clinically meaningful. Recent randomized trials and meta-analyses were also compared in a semi-quantitative synthesis to show where findings are consistent and where they remain conflicting.

Abstract: Background: Anemia is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with impaired functional capacity, poorer quality of life, increased hospitalization, and mortality. However, data from sub-Saharan Africa, particularly Ethiopia, remain limited. Objective: To determine the prevalence of anemia and identify factors associated with anemia among patients with HFrEF attending the cardiac clinic of Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. Methods: We conducted a hospital-based cross-sectional study among adults with established HFrEF (left ventricular ejection fraction ≤40%) attending the TASH cardiac clinic between June 1 and October 30, 2020. Demographic, clinical, and laboratory data were collected through patient interviews and medical record review. Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12). Anemia was defined according to World Health Organization criteria. Multivariable logistic regression was performed to identify factors independently associated with anemia. Results: A total of 138 patients were included, of whom 27 (19.6%) had anemia. Compared with patients without anemia, those with anemia had lower KCCQ-12 scores (33.7 vs 40.5, p=0.003), higher serum creatinine levels (1.6 vs 0.9 mg/dL, p=0.024), lower mean corpuscular volume (83.1 vs 88.9 fL, p=0.008), and more previous hospitalizations (44.4% vs 12.6%, p<0.001). In multivariable analysis, male sex (adjusted odds ratio [AOR] 5.34, 95% CI 1.33–21.50; p=0.018), higher serum creatinine (AOR 3.76, 95% CI 1.11–12.72; p=0.033), and lower KCCQ-12 score (AOR 0.91 per-point increase, 95% CI 0.84–0.98; p=0.008) were independently associated with anemia. Conclusions: Anemia affected approximately one in five patients with HFrEF in this Ethiopian cohort. Male sex, impaired renal function, and poorer health-related quality of life were independently associated with anemia. Routine assessment of hemoglobin status should be incorporated into the comprehensive management of patients with HFrEF.

Abstract: Dengue remains the most important arboviral disease in the Americas and a growing global public health threat. The region experienced the largest dengue epidemic in recorded history during 2023–2024, with more than 13 million reported cases in 2024 alone, reflecting the combined effects of rapid urbanization, climate variability, population mobility, persistent social inequities, and weakened vector-control programs. This review summarizes and expands on the principal discussions of the First Dengue Summit of the Dengue Initiative of the Americas, held in Cartagena, Colombia, in September 2025. Major themes included the changing epidemiology of dengue; implementation and development of new-generation vaccines, including TAK-003 and Butantan-DV; advances in digital surveillance, outbreak forecasting, and clinical management; and integrated vector-control strategies. Particular attention is given to Wolbachia-mediated population replacement, supported by evidence from a cluster-randomized trial in Indonesia and large-scale quasi-experimental evaluations in Colombia and Brazil, which show substantial and sustained reductions in dengue incidence and hospitalization. In the Aburrá Valley, Colombia, city-wide deployment in Bello, Medellín, and Itagüí was associated with reductions exceeding 90% in notified dengue incidence where Wolbachia became established. The review also examines mathematical modeling, artificial intelligence, climate-informed surveillance, and integrated public health approaches. Persistent challenges include financial sustainability, healthcare inequities, climate change, insecticide resistance, and heterogeneous surveillance and health-system capacity. Coordinated, multisectoral, and sustainable strategies that integrate vaccination, vector control, surveillance, community participation, and healthcare strengthening are essential for reducing the dengue burden and improving regional resilience.

Abstract: Severe traumatic brain injury is a leading cause of death and disability worldwide. The optimal role of invasive intracranial pressure and cerebral perfusion pressure monitoring compared with non‑invasive clinical and imaging‑based management remains uncertain, particularly in low‑resource settings. The objective of this study was to design and evaluate new diagnostic and treatment algorithms for adult patients with severe TBI. A quasi‑experimental study was carried out between January 2010 and December 2024. Patients were assigned to two groups: Group I received continuous invasive ICP and CPP monitoring together with clinical and CT monitoring; Group II received only clinical and CT monitoring. The primary outcome was functional status at one-year post‑discharge according to the Glasgow Outcome Scale (GOS). A total of 250 patients were included: 145 (58%) in Group I and 105 (42%) in Group II. In Group I, the most frequent outcome was GOS V (good recovery), whereas in Group II, GOS I (death) predominated. Satisfactory recovery was achieved in 104/145 patients (71.72%) in Group I vs. 65/105 (61.90%) in Group II. Mortality was 39/145 (26.9%) in Group I vs. 44/105 (41.9%) in Group II (difference 15.0 percentage points; p ≤ 0.05). Continuous invasive ICP and CPP monitoring, was associated with significantly lower mortality and higher rates of satisfactory recovery compared with clinical and imaging‑based management alone. These findings support the use of invasive neuromonitoring where resources permit, while the non‑invasive algorithm may serve as an alternative in low‑resource settings.

Abstract: Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist tirzepatide are increasingly prescribed for type 2 diabetes and obesity, but post-marketing comparisons usually rest on unadjusted report counts, which reflect prescribing volume as much as risk. We estimated exposure-adjusted adverse drug reaction (ADR) reporting rates for six GLP-1-based therapies. Methods: This retrospective observational pharmacovigilance study covered February 2021 to January 2026. Suspected ADRs reported UK-wide to the Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card Scheme were divided by English National Health Service (NHS) general practice (GP) and hospital prescribing volumes, combined at medicine and time-period level; hospital quantities were converted to items using GP quantity-per-item ratios. Rates per million items were pooled in a generalised linear mixed model; temporal trends used Poisson regression with a log-exposure offset. Sensitivity analyses used GP-only and hospital-only denominators and re-fitted the temporal models on reports. Results: We analysed 140,462 UK Yellow Card ADRs against 17,005,924 English NHS prescribed items. The denominator omits private prescribing, which supplies most UK weight-management use, so these rates are differentially inflated, most for tirzepatide and semaglutide. Rates per million items varied more than 200-fold: tirzepatide 27,511.52 (95% confidence interval [CI] 27,339.39–27,684.73), semaglutide 5,905.83 (5,847.98–5,964.25), liraglutide 1,326.64 (1,268.16–1,387.82), exenatide 443.36, dulaglutide 256.42 and lixisenatide 129.68; heterogeneity was extreme (I² = 99.995%) and the ordering was unchanged under both sensitivity denominators. Rates rose for semaglutide (incidence rate ratio [IRR] 1.675, 1.657–1.693) and tirzepatide (IRR 1.139, 1.118–1.160) and fell for dulaglutide (IRR 0.810, 0.774–0.848); report-based models reproduced these trends. Conclusions: Exposure-adjusted reporting rates differ markedly across GLP-1-based therapies, the newest agents reporting most. These are reporting rates under an incomplete NHS denominator, not incidence estimates; differential exposure capture and reporting behaviour prevent interpretation as comparative medicine risk.

Abstract: Background Prehospital invasive ventilation is used across a range of critically ill adult patients, yet reported practices, monitoring approaches, and clinical outcomes vary considerably be-tween systems. Existing literature has focused largely on airway management, and the overall landscape of evidence regarding invasive ventilation strategies in the prehospital setting remains unclear. This scoping review aimed to map the extent and nature of the literature on prehospital invasive ventilation in adults, describe the clinical contexts in which it is applied, and identify knowledge gaps. Methods This scoping review was conducted according to Joanna Briggs Institute methodology and PRISMA-ScR guidelines. MEDLINE (via PubMed), Embase, and the Cochrane Library were searched from inception to the date of search. Studies were eligible if they included adult patients (≥18 years) receiving invasive ventilation in a prehospital setting. Random-ized and non-randomized controlled trials and observational studies were included. Two reviewers independently screened studies, charted data, and summarized findings de-scriptively. Results A total of 3,461 records were identified, of which 25 studies met inclusion criteria. Nine studies evaluated out-of-hospital cardiac arrest, ten focused on trauma, one examined sep-tic shock, and five included mixed populations. Across clinical contexts, deviations from recommended ventilation targets—particularly hyperventilation and inconsistent appli-cation of lung-protective tidal volumes—were common. Mechanical ventilation generally improved physiological parameters compared with manual ventilation, but consistent benefits in survival or neurological outcomes were not demonstrated. Capnogra-phy-guided ventilation and real-time feedback systems improved adherence to ventilation targets. Evidence was predominantly observational and heterogeneous in design and re-porting. Conclusion Prehospital invasive ventilation in adults is characterized by substantial variability in practice and limited high-quality comparative evidence. Ventilation quality and monitor-ing may be more important than ventilation modality alone. Prospective controlled studies and standardized reporting of prehospital ventilation practices are needed to create evi-dence-based recommendations.

Abstract: Purpose. To develop a proband-level five-tier outcome classification for trio genome sequencing (GS) in neurodevelopmental disorders (NDD), and, in a small subgroup, to explore what is associated with a full versus partial phenotype match to a candidate gene’s disease spectrum. Methods. A rule-based five-tier framework integrating ACMG/AMP classification, ClinGen gene-disease validity, phenotype concordance, and orthogonal validation was applied to 40 probands with unresolved NDD (36 after exclusions); two reviewers assigned tiers by consensus. Phenotype matching used clinician-documented Human Phenotype Ontology terms, characterised against documentation-derived metrics. Results. Of 36 probands, 7 (19.4%; 95% CI 8.2–36.0%) received a confirmed diagnosis (Tier 1) and 5 (13.9%) a high-priority, unvalidated candidate (Tier 3); none were Tier 2 (Provisional). The remainder had a low-priority candidate (22, 61.1%) or no candidate (2, 5.6%). Among 12 probands with strong disease-association evidence, a full phenotype match was associated with richer documentation than a partial match, not a higher similarity score (p = 0.005); this preliminary finding warrants replication. All confirmed diagnoses involved variant types detectable by exome sequencing (ES), not genome-specific findings like deep intronic variants. Conclusion. The five-tier framework resolves the diagnostic intermediate collapsed by binary solved/unsolved reporting. Comprehensive, disease-specific phenotyping is the practical lever for framework performance.

Abstract: Background: Glutamatergic overactivity mediated by metabotropic glutamate receptor 5 (mGluR5) is implicated in levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). Mavoglurant (AFQ056), a selective mGluR5 antagonist, has shown inconsistent efficacy across clinical trials. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in PD patients with LID. Methods: Randomized controlled trials (RCTs) comparing mavoglurant with placebo in patients with PD and LID were systematically identified. Outcomes were pooled using random-effects models. Primary outcome was dyskinesia severity measured by the modified Abnormal Involuntary Movement Scale (mAIMS). Secondary outcomes included daily OFF-time, ON-time without troublesome dyskinesia, Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS), Unified Parkinson’s Disease Rating Scale (UPDRS) Parts III and IV, and safety outcomes. PROSPERO (CRD420261446524). Results: Four publications reporting six RCTs involving 485 participants were included. Mavoglurant significantly improved mAIMS scores compared with placebo (MD −2.43, 95% CI −3.79 to −1.07; p < 0.001). No significant benefits were observed for daily OFF-time (MD −0.27 h/day, 95% CI −0.79 to 0.24), ON-time without troublesome dyskinesia, total ON-time, LFADLDS, UPDRS Part III, or total UPDRS-IV (MD −0.33, 95% CI −0.70 to 0.04). Improvement was observed for UPDRS-IV Item 32 (duration of dyskinesia) (MD −0.35, 95% CI −0.66 to −0.04). Conclusion: Mavoglurant provides modest improvement in dyskinesia severity as measured by the mAIMS but does not consistently improve motor fluctuations, motor function, or overall dyskinesia-related disability. Its limited efficacy and increased adverse-event risk suggest restricted clinical utility for LID management in PD.

Abstract: Objective: Ovarian, fallopian tube, and primary peritoneal cancers are the deadliest gynecological malignancies, largely due to delayed diagnosis, tumor heterogeneity, and lack of effective methods for early detection. Increasing evidence suggests that most high-grade serous ovarian carcinomas originate from the fallopian tube epithelium. Consequently, recent studies have focused on fallopian tube cytology and its correlation with histological findings. We aimed to evaluate the exploratory diagnostic performance of ex vivo fallopian tube cytology and the CytoSaLPs score for detecting adnexal malignancies in women undergoing salpingectomy. Methods: We conducted a prospective observational study including 304 women undergoing salpingectomy or salpingo-oophorectomy for benign or malignant gynecological indications between 2020 and 2023. Ex vivo cytological brushing of the fimbrial end was performed before fixation. The primary endpoint was diagnostic accuracy compared with histology. Secondary endpoints included evaluation of the CytoSaLPs score using receiver operating characteristic analysis. Results: 491 speciments were obtained. Cytological findings were correlated with histology, demonstrating the diagnostic value of tubal cytology. For fallopian tubes, cytology showed a sensitivity of 94.4%, specificity of 71.0%. and accuracy of 72.7%. Ovarian cytology showed lower sensitivity (72.9%) and specificity (70.7%). For the adnexa as a single entity, sensitivity was 76.5% and specificity 70.7%. ROC analysis demonstrated strong performance of the CytoSaLPs Score for fallopian tubes (AUC 82.9%), moderate performance for ovaries (AUC 63.4%), and fair performance for adnexa overall (AUC 69.9%). Conclusion: This exploratory proof-of-concept study suggests that ex vivo fallopian tube cytology combined with the CytoSaLPs score may represent a promising adjunctive approach for future early detection strategies. External validation is required before clinical implementation.

Abstract: Background/Objectives: Subacromial impingement syndrome (SAIS) is the most prevalent musculoskeletal disorder of the shoulder, accounting for 44% to 65% of clin-ical presentations. This condition involves mechanical stress on the soft tissues within the subacromial space. This review aims to synthesize evidence on acromial, glenoid, and ligamentous variations to provide a framework for individualized surgical and rehabilitative strategies. Methods: A rigorous literature search was performed across PubMed, Embase, and Scopus. Eligibility was strictly limited to original re-search—including cross-sectional and retrospective designs—that evaluated demo-graphic and anatomic predictors such as age, sex, and hand dominance in relation to shoulder morphology. Results: Acromial morphology is classified using the Bigliani system into Type I (flat), Type II (curved), and Type III (hooked). Os acromiale, present in 7–15% of the population, causes dynamic narrowing of the subacromial space. Gle-noid dimensions exhibit significant sexual dimorphism and ethnic variability, while hand dominance typically increases retroversion on the dominant side. In gleno-humeral osteoarthritis, humeral head osteophytes ≥13 mm are strong predictors of ec-centric B2 glenoid morphology. Biomechanically, SAIS patients demonstrate excessive superior humeral translation (1.5–5 mm) and disrupted scapulothoracic kinematics, often exacerbated by slouched posture. Finally, recognizing congenital variants like the Buford complex is vital to avoid unnecessary surgical repairs. Conclusions: Shoulder pathology is multifactorial, arising from a convergence of static anatomical deviations and dynamic kinematic failures. The profound morphometric diversity between sexes and ethnicities necessitates patient-specific, individualized approaches to shoulder arthroplasty and rehabilitation.