OBJECTIVE:Alexithymia and depressive symptoms are common following acquired brain injury (ABI). However, their longitudinal relationship remains unclear. This study examined trajectories of alexithymia and depressive symptoms over 24 months post-injury and tested their temporal associations. METHODS:Adults with ABI (N = 116) (mean age = 44 years, 61% male, 82% moderate to severe ABI) were assessed at baseline (within two years post-injury), 3, 12, and 24 months using the Perth Alexithymia Questionnaire and the depression subscale of the Depression, Anxiety, Stress Scale. Bayesian latent growth models, and cross-lagged panel models were used to examine change, co-development, and directional relationships. RESULTS:Mean alexithymia scores remained stable across timepoints, whereas depressive symptoms showed modest improvement. Both constructs exhibited moderate temporal stability, and were associated at baseline, demonstrating co-occurrence in early recovery. No consistent directional relationship was observed, and overall model fit was poor. Additionally, there was substantial missingness at 24 months (75%). CONCLUSION:These findings suggest that alexithymia is relatively stable in the first two years following ABI and commonly co-occurs with depressive symptoms early after injury. However, there is no clear longitudinal direction association. Early assessment of emotional processing and mood may help identify individuals at risk for ongoing psychological difficulties.
BACKGROUND:Post-stroke dysphagia (PSD) remains prevalent after anterior circulation stroke treated with endovascular thrombectomy (EVT). We evaluated associations between ultrasound-derived hemodynamic indices and swallowing outcomes and their incremental prognostic value beyond clinical factors. METHODS:This retrospective cohort included 169 adults with anterior circulation stroke treated with EVT between November 2018 and November 2023. Transcranial Doppler and carotid ultrasonography measured intracranial pulsatility index (PI) and extracranial resistive index (RI). Outcomes included nasogastric (NG) tube dependence and Functional Oral Intake Scale (FOIS) at 4 and 12 weeks. RESULTS:Several RI and PI measures were associated with swallowing outcomes in univariable analyses. Basilar artery (BA) PI showed a weak correlation with time to NG tube removal (r = 0.160, p = 0.044). After adjustment for age, initial National Institutes of Health Stroke Scale (NIHSS), and 3-step swallowing screening, BA PI was not significantly associated with NG tube dependence at 4 weeks or 12 weeks (p = 0.134 and p = 0.064) and did not improve model discrimination (DeLong p = 0.281 and p = 0.362). CONCLUSIONS:Ultrasound-derived hemodynamic parameters were associated with swallowing outcomes after EVT, but the incremental prognostic value of BA PI beyond clinical factors was limited and requires prospective validation.
Louis XIV’s rapidly progressive terminal illness may be better explained by necrotizing soft-tissue infection than primary calciphylaxis. Severe distal pain, ascending gangrene, and fatal sepsis within three weeks suggest fulminant infection, plausibly arising from a diabetic foot lesion. Clinical chronology should remain central when evaluating competing retrospective clinicopathological hypotheses.
Robotic knee arthroplasty has shifted attention from whether a surgical plan can be executed accurately to which plan should be selected for each patient. This Collection examines robotic platforms, alignment strategies, safety, outcomes, and the evidence needed to translate technical precision into meaningful clinical benefit.
To assess the clinical characteristics, disease activity, functional status, and quality of life of Egyptian patients with axial spondyloarthritis (axSpA), and to evaluate differences according to sex and HLA-B27 status. This cross-sectional study included 256 patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA. Clinical, laboratory, imaging, and treatment data were collected. Disease activity was assessed using ASDAS-CRP and BASDAI, functional status using BASFI, spinal mobility using BASMI, and quality of life using ASQoL. Comparisons were performed according to sex, HLA-B27 status, and combined sex/HLA-B27 subgroups. Of 256 patients, 57.4
Abstract Background Patients with primary membranous nephropathy (PMN) and high anti-PLA2R antibody titers (> 150 RU/mL) often respond poorly to conventional treatments, and the optimal immunosuppressive regimen remains unclear. We conducted a retrospective study to compare the efficacy and safety of four regimens in this high-risk population: rituximab monotherapy (RTX regimen), tacrolimus plus glucocorticoids (TAC regimen), rituximab plus cyclosporine (RTX plus CsA regimen), and cyclophosphamide plus glucocorticoids (CTX regimen). Methods We retrospectively enrolled 185 patients with biopsy-proven PMN and anti-PLA2R titers > 150 RU/mL. All patients completed the full treatment course and the 24-month follow-up period. The primary outcome was total remission (TR) at 24 months, and the secondary outcomes included complete remission (CR), partial remission (PR), immunological remission (IR), relapse rate, time to remission, and adverse events. Results At 24 months, the TR rates were 54.5% (24/44) for the RTX regimen, 52.2% (24/46) for the TAC regimen, 76% (38/50) for the RTX plus CsA regimen, and 73.3% (33/45) for the CTX regimen. Kaplan–Meier analysis revealed significant differences in cumulative IR rate (log-rank P = 0.0009), cumulative CR rate (log-rank P = 0.0072), and cumulative TR rate (log-rank P = 0.0005) among the four regimens. The TAC regimen had a significantly higher relapse rate (36.8%, 14/38) than the RTX plus CsA regimen (13.6%, 6/44) (log-rank P = 0.013). Conclusion In this retrospective cohort, the RTX plus CsA regimen demonstrated durable efficacy, with a more favorable safety profile and a lower relapse rate. These preliminary findings support formal comparison of this regimen with current therapies in randomized controlled trials (RCTs).
Randomized studies have demonstrated that high-volume hemodiafiltration results in reduced mortality compared to conventional hemodialysis treatment. However, eligibility criteria in these trials may limit generalizability to routine clinical practice. Some of these trials reported a limited number of events, underscoring the need to further evaluate the effect of hemodiafiltration on mortality. We will conduct a target trial emulation study using data from routine clinical practice. The primary aim of this study is to evaluate whether high-volume hemodiafiltration reduces all-cause mortality. The secondary aim is to assess cause-specific mortality. Other aims include assessing all-cause and cause-specific hospitalizations, as well as cumulative length of hospital stay and the dose–response relationship between convection volume in hemodiafiltration and the outcomes. Data will be obtained from the second version of ApolloDialDb (Apollo), an anonymized dialysis dataset capturing over 1000 variables from patients from all over the world. For this study, we will include adult patients from European countries with kidney failure who initiated with at least one treatment of high-flux hemodialysis or hemodiafiltration between 01 January 2018 and 30 June 2024, and who were prescribed a thrice-weekly dialysis schedule at the start. Patients starting with home dialysis will be excluded. We will use a target trial emulation approach with a clone-censor-weight design and marginal structural models, controlling for selection bias, survivor bias, and competing risk bias. Sub-analyses will be performed to investigate the effect of high-volume hemodiafiltration (≥ 23 L of convection volume). Inverse probability weighting will be applied to adjust for predefined confounders including sociodemographic, clinical, and anthropometric factors, as well as comorbidities to achieve balance between treatment groups. In addition to randomized studies, prior large observational studies have indicated a survival benefit for hemodiafiltration, as well as a possible reduction of hospitalizations. The target trial emulation study outlined in this protocol will expand this knowledge and provide generalizable insights on the effects of hemodiafiltration on outcomes by using real-world data representative of routine clinical practice while appropriately addressing sources of bias. This protocol outlines a study in which we will examine the effects of hemodiafiltration (HDF) compared with high flux hemodialysis (HD) using data from standard day-to-day dialysis care, collected from across Europe. Clinical trials have previously shown that HDF provides benefits for survival and quality of life. However, it remains uncertain whether these benefits apply to all patients or only in healthier patients, who meet the eligibility criteria to participate in a clinical trial. We will use advanced statistical methods, specifically target trial emulation, to closely mimic a randomized clinical trial using real-world data and thereby reduce bias. The study will evaluate overall 5-year survival, causes of death, hospitalizations, and the impact of higher HDF convection volumes to help guide future dialysis care decisions.
The albumin redox status (ARS) is altered in patients with chronic kidney disease (CKD), shifting towards a higher degree of oxidation. Oxidative Stress leads to persistent microinflammation and increased morbidity and mortality. An improvement in renal function following kidney transplantation (KTX) could lead to an improvement in ARS. Aim of this study was to evaluate the effects of KTX on ARS. In an observational, monocentric feasibility study design, ARS was determined before and eight times up to 180 days after KTX by fractionation of albumin into reduced human mercaptalbumin (HMA), reversibly oxidized human nonmercaptalbumin 1 (HNA-1) and irreversibly oxidized human nonmercaptalbumin 2 (HNA-2) by high-performance liquid chromatography (HPLC) with fluorescence detection. In healthy individuals, HMA accounts for 70–80
Real-world evidence describing the early laboratory course after finerenone initiation in contemporary nephrology practice remains limited, particularly in cohorts with high background use of sodium-glucose co transporter 2 inhibitors (SGLT2i). We evaluated early kidney-function, potassium, and albuminuria trajectories and short-term treatment tolerability. FINE-TURK was a multicenter retrospective cohort study without a comparator group. Adults with diabetes and chronic kidney disease who initiated finerenone in routine care were evaluated at baseline and using the first available values recorded in the 1–3-month follow-up fields. Primary outcomes were within-patient changes in estimated glomerular filtration rate (eGFR), serum potassium, and urinary albumin-to-creatinine ratio (UACR). Complete and incomplete follow-up groups were compared, UACR responder analyses were performed, and exploratory multivariable and subgroup models were fitted. The analytic cohort contained 1,091 patients (mean age 60.6 ± 11.5 years; 55.0
PURPOSE:Acquired brain injuries (ABI) frequently lead to cognitive impairments, which can be challenging to detect and persist for years, negatively impacting patient outcomes. Timely and specific screening is crucial for proper management. Cog-First is a tablet-based self-assessment of executive functions, memory, and attention lasting approximately 20 min. This study aimed to develop the English version of Cog-First and evaluate its feasibility. MATERIALS AND METHODS:A two-phase study was conducted. Phase 1 involved a rigorous translation and cultural adaptation process, following established guidelines. Phase 2 consisted of an exploratory comparison between MoCA and Cog-First scores in individuals with ABI. RESULTS:The English version of Cog-First was developed. Practitioners highly rated the relevance and applicability. Strong agreement (90%) was observed for memory, attention and inhibition sub-tests. About 90% of ABI participants expressed a high level of satisfaction. Exploratory analyses showed an association between MoCA and Cog-First scores (p = 0.037, r = .46). CONCLUSION:This study successfully translated and culturally adapted Cog-First into English and demonstrated its feasibility and acceptability in English-speaking individuals with ABI. While further research is required to explore its psychometric properties, normative values and clinical utility comprehensively, Cog-First might enhance the detection of subtle cognitive deficits and inform targeted rehabilitation strategies.
BACKGROUND:Concussions often result in psychophysiological symptoms that reflect disruptions in brain-body systems, yet objective biomarkers remain limited. Heart rate variability (HRV) has emerged as a promising biomarker of autonomic adaptability and rehabilitation, including as an index of physiological recovery following concussion. However, concussion literature has predominantly emphasized HRV responses to physiological stressors, rather than psychological tasks that engage impaired domains such as attention, emotion regulation, and executive function. OBJECTIVES:We systematically mapped the use of HRV during emotional and cognitive paradigms in adult concussion populations clarifying rationales for its application, the stimuli and measures employed, and state of science. RESULTS:We identified 6,791 records, four meeting inclusion criteria. Paradigms included emotional film clips and cognitive tasks, with HRV indices spanning time-, frequency-, and nonlinear domains. Across studies, individuals with concussion demonstrated altered autonomic flexibility compared to control subjects, including blunted modulation, atypical valence-related responses, and compensatory increases in vagal activity. Methodological heterogeneity limited cross-study comparability. CONCLUSION:This review highlights a critical evidence gap regarding HRV measurement in psychological contexts after adult concussion. Standardized HRV protocols, diverse samples, and longitudinal designs are needed to clarify recovery trajectories and further assess the value of HRV as a recovery biomarker after concussion.
Abstract Background Post-transplant Immunoglobulin A Nephropathy (IgAN) is an important cause of premature graft loss. Management strategies are often extrapolated from native IgAN, with available evidence limited to heterogeneous, predominantly small retrospective studies. Objectives To characterise diagnostic criteria, map management strategies, and summarise associated clinical outcomes in post-transplant IgAN. Methods A literature search was performed in MEDLINE, Embase, Web of Science, and Scopus (1st January 2000–11th December 2025) following Joanna Briggs Institute (JBI) and PRISMA-ScR guidelines. English-language studies of adult kidney transplant recipients with biopsy-proven post-transplant IgAN and documented management strategies were included. Data on study design, cohorts, diagnostic criteria, interventions, and outcomes were charted and narratively described. Results Twenty-seven studies met the inclusion criteria. Most were single-centre retrospective cohorts. Diagnostic criteria varied, but typically histological evidence of IgA deposition alone was sufficient. IgAN was often clinically relevant, with proteinuria > 1 g/day frequently reported. Reported treatments included renin-angiotensin-aldosterone system (RAAS)-blockade, immunosuppression adjustment, rituximab, tonsillectomy and pulsed corticosteroids. Several small case series explored emerging therapies (iptacopan, budesonide, telitacicept). Study heterogeneity precluded quantitative data synthesis. Conclusions RAAS-blockade was the most commonly used intervention and was associated with benefit in several studies. Tonsillectomy was associated with improved outcomes but reported only in Japanese cohorts. Other interventions (rituximab, pulsed steroids, emerging therapies) warrant prospective clinical trials. Amid evolving paradigms in native IgAN management, this review highlights heterogeneity in diagnostic criteria, outcome reporting, and interventions for the management of post-transplant IgAN. Robust prospective, multicentre studies are urgently required to define optimal management in this high-risk population.
Self-limiting or degenerative upper extremity musculoskeletal conditions (UEMSCs) are common and often managed without medical intervention. This study aims to identify latent subgroups of these conditions in individuals who do not seek care, by examining a range of biopsychosocial factors. Understanding these patterns, can provide insights to inform personalized and comprehensive care strategies for individuals who do seek medical attention for musculoskeletal illnesses. A total of 4,635 healthcare staff who provided consent were included in a within cohort-cross-sectional study. We conducted interviews and physical examinations to screen participants for common UEMSCs. Two latent class analyses (LCA) identified statistical groupings of the following upper extremity conditions diagnosed based on symptoms and signs: carpal tunnel syndrome (CTS), lateral epicondylitis (LE), trapeziometacarpal osteoarthritis (TMC OA), DeQuervain tendinopathy (DEQ), trigger digit (TD), ganglion cyst (GAN), and rotator cuff tendinopathy (RCT). One LCA among the 4635 people screened and the other LCA among the 713 people with at least one UEMSC. We then analyzed the association of several biopsychosocial factors with the specific classes identified. Among the 4635 workers, 3 latent classes were identified: (1) All UEMSCs except GAN, high distress, lower socioeconomic status, and limited strength (0.4
‘Gender’ as a social construct is increasingly recognized as a determinant of care inequity in chronic kidney disease (CKD). However, a systematic analysis of gender-based disparity in access to care across the continuum of CKD care is lacking. This systematic review aimed to synthesize the global evidence on gender-based disparities in access observed across sequential steps of CKD care. The review was registered in PROSPERO (CRD420251091356) and conducted following PRISMA guidelines. Four databases (PubMed, Cochrane, HINARI, Embase) were searched for publications from 2000–July 2026. Two reviewers independently screened 1,140 articles and risk of bias was assessed using ROBINS-E. Data were extracted across four aspects of CKD care: (1) diagnosis, monitoring and prescription of guideline-recommended treatment, (2) vascular access, (3) initiation and maintenance of dialysis, and (4) transplantation. Thirty-five studies were included, spanning diverse geographical regions. Women faced consistent disadvantages across the continuum of CKD care. They had lower odds of receiving a diagnosis of CKD or nephrology referral, less frequent monitoring of kidney function, and lower prescription rates of guideline-recommended medications. Among those with kidney failure, women comprised only 38–41
BACKGROUND:Oxidative stress, inflammation, and apoptosis following traumatic brain injury (TBI) cause secondary damage that leads to long-term neurological impairments. Though its effectiveness in TBI remains largely underexplored, the natural polyphenol resveratrol (RES) shows neuroprotective effects. This meta-analysis assesses RES's therapeutic potential in rodent TBI models. METHODS:Medline, Embase, Scopus, and Web of Science (up to April 2025) were searched for studies evaluating RES in rodent TBI using PRISMA recommendations. Inclusion criteria were satisfied by 10 studies. Outcomes included cerebral edema, autophagy, inflammation, apoptosis, neuronal density, and neurological status. With 95% confidence intervals, random-effects models computed standardized mean differences. We looked at publication bias (Egger's test) and heterogeneity (I2). RESULTS:RES notably lowered autophagy markers (Beclin-1; LC3II) and cerebral edema. It decreased apoptosis (caspase-3) and inflammation (IL-1β; TNF-α). In CA1 and CA3 areas, hippocampal neuron density increased. With lower escape latency in the Morris water maze and Neurological Severity Score, memory and neurological status improved. CONCLUSION:By reducing edema, inflammation, and apoptosis, RES shows strong neuroprotection in rodent TBI models while maintaining neurons and improving recovery. RES is a reasonable contender for supplementary TBI treatment.
Shoulder arthroplasty has become an established treatment option for displaced and complex proximal humeral fractures, particularly in elderly patients. Fracture-specific stems are increasingly used in clinical practice; however, early data on surgeon experience with newly introduced convertible stem designs remain limited. This study aimed to assess orthopedic surgeons’ early intraoperative experience with a newly developed humeral fracture system (Tornier Perform Humeral System – Fracture, Tornier Inc., a wholly owned subsidiary of Stryker, Bloomington, MN, USA) using a structured survey as part of an early product surveillance program. A prospective observational survey was conducted among orthopedic surgeons in the United States and Canada who had performed surgery using the fracture stem. Case-level evaluations of intraoperative handling, technical features, and surgeon-reported comparisons with routinely used implant systems were collected. Descriptive statistics were used to summarize survey responses. Twenty-six orthopedic surgeons submitted feedback on 47 surgical cases (45 primary cases, 2 revisions), including predominantly reverse configurations (46/47) and one hemiarthroplasty construct. All available stem fixation methods were used: cementless without interlocking screws (n = 24), cementless with interlocking screws (n = 14), and cemented (n = 9). Surgeons reported high levels of satisfaction and favorable ratings for ease of use. Across multiple comparative dimensions, the fracture system was frequently rated favorably compared with surgeons’ routinely used systems. Twenty-five of 26 participating surgeons indicated that they would consider using the system in future cases and would recommend it to others (missing data for one surgeon). Qualitative feedback described perceived benefits related to specific design features, including press-fit capability, bone graft window, proximal stem design, and the option for interlocking screw fixation. Surgeons reported favorable early intraoperative impressions of this fracture system. These findings provide exploratory insights into surgeon-reported usability and perceived design characteristics under early real-world use. Further studies are required to evaluate the clinical relevance of these surgeon-reported perceptions. IV.
BACKGROUND:Neurostimulants are commonly used after traumatic brain injury (TBI) to improve arousal, attention, and participation in rehabilitation. However, little is known about stimulant use among pediatric patients with preexisting attention-deficit/hyperactivity disorder (ADHD). We describe stimulant use to facilitate emergence from post-traumatic amnesia (PTA) in an adolescent with severe TBI and preexisting ADHD. CASE PRESENTATION:A 14-year-old male with ADHD sustained a severe TBI with diffuse axonal injury following an electric scooter crash. He experienced prolonged PTA, severe agitation, and motor restlessness despite multimodal pharmacologic management and environmental interventions. On post-injury day 17, a trial of methylphenidate produced rapid improvements in attention and agitation. Agitated Behavior Scale scores subsequently decreased, and he emerged from PTA by post-injury day 23. DISCUSSION:This case highlights a potential role for individualized neurostimulant therapy in facilitating recovery after severe TBI among adolescents with preexisting ADHD. To our knowledge, this is the first pediatric case in the literature describing stimulant use to facilitate emergence from PTA in a patient with preexisting ADHD. Further research is needed to establish evidence-based guidance for stimulant selection, dosing, and timing of re-initiation after pediatric TBI.
B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) drive the galactose-deficient IgA1 (Gd-IgA1) production that underlies IgA nephropathy (IgAN). Several BAFF/APRIL-pathway inhibitors have entered randomized testing, but none has been compared head-to-head. We systematically searched MEDLINE, Scopus, the Cochrane Central Register, Web of Science, and Embase to July 2026 for randomized, placebo-controlled trials of BAFF/APRIL-pathway inhibitors in adults with biopsy-proven IgAN. Random-effects pairwise meta-analysis used the standardized mean change for proteinuria and estimated glomerular filtration rate (eGFR), change-score standardization for biomarkers, and risk ratios (RR) for safety, and a frequentist star network meta-analysis with placebo as reference ranked agents by P-score. Seven trials (1,590 adults) evaluating telitacicept, atacicept, and sibeprenlimab were included. Versus placebo, BAFF/APRIL-pathway inhibition reduced proteinuria (SMCR −0.73, 95
Abstract Background Hyperbaric oxygen therapy (HBOT) has gained increasing interest in regenerative medicine for its capacity to enhance tissue oxygenation, reduce inflammation, and accelerate healing. While its use in musculoskeletal medicine is expanding, particularly among athletes and in sports orthopaedics, the clinical evidence base remains fragmented across indications and has not been systematically evaluated. Purpose The aim of this systematic review was to synthesize the available clinical evidence for HBOT in human musculoskeletal pathologies, with focus on its application in orthopaedic medicine. Methods A systematic PubMed and LIVIVO search identified clinical studies (January 1996 - January 2026) investigating intervention-based studies using HBOT for musculoskeletal conditions in humans. Exclusion criteria were combinatory therapies, transplantations, radiation injuries, osteomyelitis, spine and oral surgery. Data on study design, HBOT protocols and their outcomes was collected. A qualitative synthesis was performed due to heterogeneity in study designs and outcome measures. Risk of bias was assessed using Cochrane RoB 2 tool (RCTs) and ROBINS-I V2 (non-RCTs). Studies were categorized by pathology (muscle/tendons/ligament injury; avascular necrosis (AVN) and bone marrow edema (BME)). Results Nineteen studies involving 612 patients met our inclusion criteria. Conditions included exercise-induced muscle damage (EIMD) and its symptomatic manifestation delayed onset muscle soreness (DOMS), ligament injuries, AVN, BME, and tendon perfusion. Evidence for HBOT’s effects in DOMS/EIMD was limited, with RCTs showing no significant benefit. Conversely, AVN and BME studies reported consistent improvements in imaging, pain and functional scores, particularly with prolonged protocols. Limited evidence suggested potential benefits in ligament healing; tendon oxygenation effects were inconclusive. HBOT protocols ranged from 1 - 12 sessions for soft-tissue and 20 - 80 sessions for bone injuries, mainly using 60 to 90 minute sessions with 100% oxygen. Adverse events were rare and mild. Most RCTs showed low risk of bias; non-randomized studies had serious-to-critical bias due to confounding and measurement issues. Conclusions HBOT may have a role as an adjunctive therapy for musculoskeletal pathologies, especially AVN and BME, where the most consistent evidence was observed, while its benefit in ligament injuries, muscle recovery, and tendon pathology remains inconclusive and requires higher-quality trials to substantiate. Clinical relevance This topic is directly relevant to orthopaedic and sports medicine practitioners considering its off-label use. This review identifies conditions with the most consistent clinical benefit, highlights the limitations of current evidence, and defines priorities for future high-quality trials to guide safe and effective clinical implementation. Study design Systematic review.
Skeletal fragility in type 2 diabetes mellitus (T2DM) is incompletely represented by areal bone mineral density (BMD). We defined an operational reduced-BMD subgroup using routine hospital information-system data and examined whether routinely available clinical variables showed incremental associations and whether complex classifiers improved internal discrimination beyond age and sex. This single-center retrospective cross-sectional analysis included 329 de-identified analytical records from adults with T2DM who underwent routine dual-energy X-ray absorptiometry. The operational reduced-BMD subgroup was defined by the lowest T-score among the lumbar spine L1-L4, femoral neck, and total hip: records with at least one site-specific T-score ≤ − 1.0 were classified into the subgroup, and a stricter < -1.0 definition was examined as a boundary sensitivity analysis. Because menopausal status and Z-scores were unavailable, this rule was treated as an operational subgroup definition rather than a universal clinical diagnosis. Descriptive analyses, deliberately parsimonious Jeffreys-prior bias-reduced logistic models, fixed-unit age sensitivity analyses, and repeated nested internal classification were performed. Twenty-six records (7.9
