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176 papers

The development and evolution of the Irish Hip Fracture Database: a quality care initiative 2013-2024.

Brent L et al. · Jun 25, 2026

Clinical audits are central to quality improvement in healthcare, yet practical real-world descriptions of how they are implemented, governed and sustained are limited. This paper describes the establishment, evolution and impact of the Irish Hip Fracture Database (IHFD) within the Irish healthcare system as an exemplar. Introduction Clinical audits compare clinical practice against defined standards to identify areas for improvement and showcase excellence. International literature provides limited insight into how they are governed and sustained. Using the IHFD, a mature national audit, this paper reviews its development, evolution and sustained momentum from 2013 to 2024. Methods Longitudinal data were captured via the Hospital Inpatient Enquiry (HIPE) system, encompassing all eligible Irish acute hospitals. Included cases were patients aged ≥ 60 years with hip fractures, as defined by IHFD. Three organisational surveys (2016, 2020, 2024) were undertaken to assess hospital resources, care pathways, governance structures and audit supports. Results In total, 41,304 cases were included in the analysis. National coverage exceeded 90% from 2017. Demographic characteristics remain consistent. Improvements in data quality, adherence to Irish Hip Fracture Standards were observed, including geriatrician assessment (11% in 2013 to 86% in 2024) and bone health assessment (65% in 2013 to 90% in 2024). Service reconfigurations and resourcing to support hip fracture care occurred over this period. Engagement with the audit remained robust despite major challenges including COVID-19, a national cyberattack and ongoing health system reform. Conclusion Sustained success of a national hip fracture clinical audit requires strong leadership, effective governance, clear clinical standards, accessible data and timely reporting. Continued relevance requires agility and alignment with evolving system needs.

Medicine

Appraisal of sexual functioning before and after cancer: insights from adolescent and young adult (AYA) cancer survivors and matched healthy controls.

Acquati C et al. · Jun 25, 2026

Purpose Adolescence and young adulthood (AYA) are developmental phases in which individuals establish their identity. A cancer diagnosis during this stage disrupts sexual health, but research remains limited, particularly outside of reproductive-organ cancers. This study examined perceived changes in sexual functioning from pre- to post-diagnosis among survivors and compared their current sexual functioning and satisfaction with matched controls. Methods Dutch-speaking AYA cancer survivors (N = 174; age = 32.7 years; 85.6% female) recruited via convenience sampling and N = 348 matched controls completed self-reported measures of sexual functioning [MOS-SF] and satisfaction [GMSEX]. Paired sample t-tests assessed perceived changes in sexual functioning. Repeated measures ANOVAs tested the effects of sociodemographic and cancer-related factors on these variations. Independent sample t-tests compared current sexual functioning and satisfaction between survivors and controls. Results Survivors reported significant declines in multiple domains of sexual functioning, including interest, arousal, orgasm function, pleasure, and lubrication (women). Greater dysfunction was observed among females, individuals diagnosed in their 30s, those in early survivorship, and those who remained with the same partner. Survivors who had engaged in partnered sexual activity reported less dysfunction than those who had not. Compared with controls, survivors reported significantly greater dysfunction and lower sexual satisfaction, while retrospectively rating their pre-diagnosis sexual functioning as more positive. Conclusions AYA cancer survivors reported declines in sexual functioning over time, worse outcomes than controls, and more favorable recollections of their pre-diagnosis sexual health, a pattern consistent with response shift. Findings emphasize the need for comprehensive survivorship care that includes routine, proactive sexual health discussions, and tailored interventions responsive to survivors' evolving needs.

Medicine

Role of the nonhelical tailpiece of myosin-II in regulating filament architecture and function.

Wang K et al. · Jun 25, 2026

Mammalian nonmuscle myosin-II isoforms (NM-IIA, NM-IIB, and NM-IIC) each contain a nonhelical tailpiece (NHT) at their C terminus. Stop-codon mutations in the NHT of NM-IIA are linked to diseases such as macrothrombocytopenia. However, the role of the NHT in NM-II filament assembly and function remains poorly understood. Here, we show that NM-II isoforms lacking the NHT, including disease-associated NM-IIA truncations, form enlarged bipolar filaments with reduced bare zones. NHT length emerges as a key determinant of filament size. Moreover, NM-IIA NHT truncations generate stress fibers composed of enlarged bipolar filaments that exhibit reduced FRAP recovery and an increased tendency to aggregate, resulting in impaired cell migration. We further provide in vivo evidence that NM-IIA assembles into bipolar filaments in the absence of RLC phosphorylation, a property enhanced by NHT deletion. Together, these findings establish the NHT as a critical regulator of NM-II filament architecture, dynamics, and function and provide mechanistic insight into NM-IIA NHT-associated diseases.

Medicine

Surgical strategies and long-term survival for third ventricle chordoid gliomas: a systematic review and clinical algorithm.

Alomari O et al. · Jun 25, 2026

Chordoid gliomas are rare World Health Organization Grade II neoplasms of the third ventricle. While Gross Total Resection (GTR) has traditionally been the primary surgical objective, the intimate adherence to the hypothalamus and optic apparatus of these tumors creates a therapeutic dilemma for balancing oncological control against the risk of severe neurological and endocrine morbidity. This study aims to guide optimal management by bridging the evidence gap with the largest systematic review to date, analyzing clinical characteristics, surgical outcomes, and survival data. A systematic review was conducted according to PRISMA 2020 guidelines, searching Web of Science, PubMed, Scopus, and Embase for studies from database inception to November 2025. Data included patient demographics, clinical presentation, radiological phenotypes, surgical techniques, molecular profiles, and follow-up outcomes. Kaplan-Meier survival estimates and log-rank tests were used to assess survival outcomes by extent of resection. All analyses were performed using R-software (version 4.3.1). The cohort (N = 198; mean age 41.8 years; female-to-male ratio 2:1) predominantly presented with headache (51.3%), visual disturbances (37.5%), and cognitive deficits (24.4%). GTR was achieved in 56% of patients, while 32% underwent Subtotal Resection (STR), and 10% biopsy only. Kaplan-Meier analysis revealed a significant survival advantage for GTR, with a stable 5-year survival rate of 91.9% compared to 54.7% for STR (p = 0.0089). Molecular profiling identified PRKCA D463H as the predominant driver mutation, with BRAF V600E observed in a minority of cases. GTR is associated with superior long-term survival in the literature and may be considered when anatomically feasible. However, because this association may be confounded by tumor adherence and surgical selection, resection strategies must be strictly individualized to balance tumor control against hypothalamic morbidity.

Medicine

Corticosteroids in immunocompromised ICU patients with pneumonia: risks, evidence, and clinical practice.

Morales-Olivera JA et al. · Jun 25, 2026

Adjunctive corticosteroids are increasingly used in Severe Community-Acquired Pneumonia (sCAP) requiring admission to the intensive care unit (ICU), based on evidence derived largely from immunocompetent populations. Immunocompromised hosts, however, represent a distinct and growing subgroup among critically ill patients with sCAP, characterised by baseline immune defects, broader pathogen spectra, and a heightened susceptibility to treatment-related harm. Whether corticosteroid strategies validated in the general population can be safely and effectively extrapolated to immunocompromised ICU patients with sCAP remains uncertain, despite their growing use in contemporary ICU practice. Immunocompromised patients admitted to the ICU with sCAP experience compounded alterations in host defence, driven by pre-existing immune dysfunction and superimposed critical illness-associated immune dysregulation. In this setting, corticosteroids may attenuate inflammation-mediated lung injury, but may also deepen immune suppression, distort clinical evolution, and increase susceptibility to opportunistic superinfections and pathogen reactivation. Randomised trials and meta-analyses supporting corticosteroid use in sCAP have systematically excluded immunocompromised patients, treating immunosuppression as an exclusion criterion rather than a stratification variable, and commonly rely on short-term endpoints that fail to capture delayed infectious complications relevant to this population. Available observational data and pathogen-specific evidence suggest substantial heterogeneity of treatment effect (HTE) across immunocompromised subgroups, influenced by immune substrate, pathogen context, and cumulative immunosuppressive burden. Among the pathogen-specific contexts in which corticosteroids have the strongest evidence, Pneumocystis jirovecii pneumonia (PJP) stands out as the principal indication: adjunctive corticosteroids have demonstrated clear mortality benefit in AIDS-associated severe PJP, though this benefit does not extend uniformly to HIV-negative immunocompromised patients with PJP. Consequently, standard corticosteroid treatment in all CAP subgroups is unlikely to be appropriate. In immunocompromised ICU patients with sCAP, corticosteroid therapy should neither be routinely applied nor categorically avoided. Instead, decisions should be individualised, guided by a clearly defined therapeutic target, careful assessment of immune status, and consideration of the risk for opportunistic infections. When used, corticosteroids should be administered at the lowest effective dose and for the shortest feasible duration. Dedicated studies incorporating immune stratification, pathogen-informed approaches, and outcomes relevant to delayed infections are urgently needed. Until such evidence is available, careful risk-balance assessments to decide steroids in these patients.

Medicine

A Case Series Demonstrating the Spectrum of Invasive Methicillin-Sensitive Staphylococcus aureus (MSSA) Disease.

Mbombo E et al. · Jun 25, 2026

Introduction Staphylococcus aureus , although a common colonizer of skin and mucous membranes in humans, is associated with severe infections in both healthy and debilitated individuals. The mortality induced by invasive MSSA disease is high, especially in patients diagnosed late. In children, skin and joint manifestations are most common. Septic shock is a major contributing factor to early mortality. To date, reported cases of invasive MSSA disease in children are infrequent, especially in Sub-Saharan Africa. Case report We present 4 cases of previously healthy children who presented with various clinical manifestations, but skin lesions and fever were common in all of them. They had multisystem involvement and eventually required aggressive multifactorial therapy. Antibiotic treatment was tailored to the results of antimicrobial sensitivity tests following blood culture. Though the hospital stay was quite long, intensive care and appropriate antibiotics contributed to a good prognosis. Conclusion In children with invasive MSSA disease, early diagnosis and prompt management are key factors to improved prognosis. Skin lesions with tender joints in a febrile infant should raise suspicion for a staphylococcal infection. Intensive care and infection source control are the cornerstones of the management.

Medicine

Persistent Delirium in the Elderly: A Case Report and Review of Multifactorial Contributors and Management Challenges.

Salisbury T. · Jun 25, 2026

Introduction This case describes persistent delirium exceeding 18 months with prominent paranoid delusions in a 72-year-old woman with chronic hyponatremia, poststroke epilepsy, and alcohol use disorder. It highlights diagnostic and pharmacologic management challenges when standard agents carry prohibitive risks. Patient’s main concerns and important clinical findings A 72-year-old woman with a history of left hemispheric hemorrhagic stroke, poststroke epilepsy, and chronic alcohol use presented with acute confusion. Laboratory evaluation revealed severe hyponatremia (Na 122 mmol/L). Clinical findings included persecutory delusions, severe agitation with dangerous behaviors (attempting to leave moving vehicles, stabbing attempt), anxiety, insomnia, and fluctuating cognitive status with return to baseline between episodes. EEG demonstrated epileptiform discharges and generalized encephalopathy. Divalproex sodium levels at presentation were supratherapeutic (up to 127 mcg/mL). There was no evidence of prior dementia or progressive cognitive decline. Primary diagnoses interventions and outcomes The primary diagnosis was persistent delirium with multifactorial etiology. Interventions included hyponatremia correction, transition from divalproex to lacosamide, and initiation of mirtazapine, which was selected for its lower hyponatremia risk compared to other antidepressants, lower seizure risk compared to antipsychotics, and low deliriogenic potential. Sleep and anxiety improved with partial agitation reduction, though delirium persisted. Over 18 months, paranoid delusions evolved from episodic to continuous, creating treatment adherence barriers. Conclusion This case underscores the potential for exceptionally prolonged delirium in medically complex older adults, diagnostic complexity in differentiating persistent delirium from ictal-related psychosis and other conditions, and individualized pharmacotherapy considerations. Early multidisciplinary intervention, capacity assessments, and caregiver support are critical.

Medicine

Incidental Breast Findings on Chest CT: Rates of Report and Follow-Up.

Hui J et al. · Jun 25, 2026

Objective This study aims to determine the incidence and types of breast findings detected on chest CTs at our institution and assess rates of subsequent follow-up imaging and breast cancer screening. Methods A retrospective review of all chest CTs performed at our institution over a 2-year period (1/1/2022-1/1/2024) was conducted, demonstrating 1540 patients above the age of 40 with incidental breast findings identified using a text search of the reports, and follow-up recommendations were documented. Clinical outcomes were analyzed for cases with recommended dedicated breast imaging. Results Incidental breast findings were detected in 14.3% of chest CTs in women above or at the age of 40. Further breast imaging was recommended in 54 cases, with 21 cases having associated dedicated breast imaging performed. Of these, corresponding dedicated workup revealed predominantly benign findings, with 82% representing benign or likely benign etiologies and only 4 cases representing malignancy. The likelihood of performing follow-up imaging was influenced by the language used in the report, with a 40% completion rate for studies using definitive wording as compared to 0% for optional wording. Conclusion There is a considerable rate of incidental breast findings visualized on chest CTs, which are predominantly benign. However, as there is a potential for visualization of malignant lesions, standardized reporting and follow-up protocols are essential to ensure proper evaluation and management. Further research is needed for evaluating and standardizing the potential use of chest CTs for assessing incidental breast lesions.

Medicine

DNA damage complexity as a predictor of cell survival: a microscopic Monte Carlo-based modeling framework for photon, proton and carbon ion irradiation.

Qi M et al. · Jun 25, 2026

Objective. Biological effect of charged particles characterized by cell surviving fraction (SF) depends on physical factors such as particle type, dose, beam quality descriptors, e.g. linear energy transfer or lineal energy. Driven by the crucial role of DNA double-strand breaks (DSBs) as indicators of cellular responses to ionizing radiation, this study aims to develop a cell-specific SF model based on the initial DSBs of varying complexities applicable to photon, proton, and carbon-ion irradiations across the investigated beam qualities. Approach. Microscopic Monte Carlo simulations were used to calculate DSBs for experiments measuring SF of H460 and H1437 lung cancer cells irradiated by proton (dose-mean lineal energyy¯d2.0-20.0 keV µ m -1 ), carbon ions (y¯d18.6-87.9 keV µ m -1 ) and reference 137 Cs photon beam. We modeled SF as a third-order polynomial function of DSBs of various complexities with two, three, and more strand breaks. The function was determined by a data fitting process. Main Results. For each cell line, a single model was able to accurately describe SF in experiments under all 19 irradiation conditions with different particle types andy¯dvalues. Root mean square errors were 0.218 for H460 cells and 0.170 for H1437 cells. When applying the model to a proton spread-out-Bragg-peak case, calculated relative biological effectiveness at SF = 0.1 were 1.01-1.42 for the H460 cells and 1.03-1.65 for the H1437 cells depending on the depth. Significance. We successfully developed an SF model using DSBs of various complexities as input variables. The model provides a unified description of photon, proton, and carbon-ion irradiations across investigated beam qualities.

Medicine

Influence of Ketogenic Diet Lipid Composition on Anxiety-Like Behavior and Neurometabolic Profile in Healthy Rats.

Gurgel GG et al. · Jun 25, 2026

Ketogenic diets (KDs) modulate brain function, but how their fatty acid composition impacts behavior remains poorly understood. Male Wistar rats were fed a control diet (CD, n = 6), a classic ketogenic diet (CKD, n = 6) rich in saturated fatty acids (SAFAs), or a modified ketogenic diet (MKD, n = 6) enriched with polyunsaturated fatty acids (PUFAs) and DHA. After 100 days, both KDs induced similar ketosis and increased brain glucose metabolism ( 1 ⁸F-FDG PET/CT), while reducing some cerebral pro-inflammatory cytokines (IL-1β, IL-6) and oxidized LDL. Notably, the CKD group exhibited an anxiety-like phenotype in the Elevated Plus Maze versus controls, significantly reducing open arm entries [1.58(0.60) vs. 5.08(1.03); p = 0.025], increasing closed arm time [3.33 min(0.22) vs. 1.70 min(0.19); p = 0.001], and elevating the Anxiety Index [0.92(0.04) vs. 0.70(0.07); p = 0.048], which correlated with SAFA incorporation in the frontal lobe. In contrast, the MKD group did not induce this anxiety-like effect, maintaining behavioral parameters comparable to the CD group, while showing an intense incorporation of omega-3 fatty acids and DHA in the hippocampus. These findings demonstrate that the behavioral divergence between KDs occurred despite shared reductions in the specific neuroinflammatory and oxidative markers evaluated. Overall, our results suggest that the dietary fatty acid profile, rather than the magnitude of systemic ketosis level, plays a critical role in modulating behavioral outcomes under ketogenic conditions.

Medicine