Early surgical fixation is the standard approach for intracapsular femoral neck (neck of femur; NOF) fractures. However, a small subgroup of patients is managed conservatively because operative risks outweigh benefits, or due to patient preference. We evaluated outcomes of initial nonoperative management in older adults and contextualised our findings through a structured literature review. We conducted a retrospective observational cohort study at a UK tertiary orthopaedic trauma unit (January 2018-August 2023). Patients with undisplaced or valgus-impacted NOF fractures initially managed nonoperatively, were included. The primary outcome was treatment failure, defined as conversion to operative fixation or arthroplasty. Secondary outcomes included 30- and 90-day mortality, and treatment-related complications. 38 patients were analysed. Most fractures were AO/OTA type 31-B1 (n = 29/38). The majority of patients were ASA class II-III (n = 14 and n = 15, respectively). 13 patients required delayed surgery (34%; 95% CI 21-50%), most commonly hemiarthroplasty (n = 9), followed by total hip arthroplasty (n = 3) and dynamic hip screw fixation (n = 1). The mean time from injury to surgery in those converted was 49 days (range 1-208). Of the 25 patients remaining nonoperative, 14 had no fracture-related readmissions, while two had persistent pain or poor mobility. 30-day mortality was 18% (7/38), and the 90-day mortality was 24% (9/38). Initial nonoperative management can avoid surgery in selected patients but carries a substantial risk of delayed conversion and prolonged time to definitive fixation. If chosen, a standardised pathway with close clinical and radiographic follow-up and clear escalation triggers is essential.
Biologic treatments demonstrate long-term clinical benefits for patients with osteoporosis, but their cost is prohibitive, and access can be limited, particularly in low-income countries. This analysis determined the cost impact of introducing biosimilar denosumab for the treatment of osteoporosis in Malaysia and Thailand. A budget impact model was developed to compare the cost of treating female patients aged ≥ 50 years with osteoporosis with biosimilar versus reference denosumab (60 mg/mL every 6 months) from a healthcare payer perspective in Malaysia and Thailand over 5-years. Model inputs included previously published, country-specific prevalence, incidence, mortality, and treatment data, supplemented by expert clinical advice where evidence was limited. Drug acquisition cost was assumed to cost 25% less than the reference product. Further assumptions included no change in osteoporosis incidence and mortality over the time horizon and consistent condition-related costs across both scenarios. Over 5 years, treatment with the reference denosumab was estimated to cost MYR ~ 864 million (USD ~ 217 million) in Malaysia and THB ~ 179.5 billion (USD ~ 5.2 billion) in Thailand. Biosimilar denosumab was estimated to cost MYR ~ 648 million (USD ~ 162 million) and THB ~ 134.6 billion (USD ~ 3.9 billion), resulting in potential savings of MYR ~ 216 million (USD ~ 54 million) and THB 44.8 billion (USD ~ 1.3 billion), respectively. The introduction of biosimilar denosumab in Malaysia and Thailand could yield significant cost savings and enhance access to biologic therapies for postmenopausal women with osteoporosis. The inclusion of biosimilar denosumab in national osteoporosis management programs could lead to increased uptake, but it is not explored in this analysis and requires further consideration.
Osteoporotic vertebral fractures (OVF) present varying treatment challenges depending on fracture severity, stability, and patient characteristics. While the OF classification system guides treatment decisions, gender differences in OVF management and outcomes remain underexplored. How do treatment strategies and clinical outcomes differ between genders? This secondary analysis utilized prospective data from the German multicenter EOFTT study, including 518 patients (390 females, 128 males) treated for thoracolumbar OVF. Outcomes assessed included adherence to OF score recommendations, pain levels, functional performance (Timed Up & Go test, Barthel Index, Oswestry Disability Index), and rates of anti-osteoporotic therapy (aoTh). Statistical analyses included generalized linear mixed models and repeated-measures general linear models, with therapy type as a covariate. Gender did not influence overall treatment choice; however, men more frequently underwent instrumentation, while women received augmentation procedures. AoTh administration was significantly lower in men at discharge (72% vs. 82%, p = 0.017) and follow-up (71% vs. 89%, p < 0.001). Both genders showed significant improvements in pain, mobility, and functional outcomes over time (p < 0.001), with no gender-specific differences. Adherence to OF score recommendations was 61% with no gender disparity. Although gender had minimal influence on pain and functional recovery, marked differences in surgical strategies and the administration of anti-osteoporotic therapy underscore potential disparities in the surgical treatment of women and the management of osteoporosis in men. Addressing these disparities through tailored screening, optimized adherence to guidelines, and individualized treatment strategies may improve outcomes in OVF management.
This study evaluated dental caries experience in individuals with neurofibromatosis type 1 (NF1) compared with matched controls and investigated its associations with salivary parameters, behavioral factors, and socioeconomic characteristics. In this case-control study, 42 individuals with NF1 and 42 controls matched for age and sex were included. Caries were diagnosed according to World Health Organization criteria, and the decayed, missing, and filled teeth (DMFT) index was used to assess caries experience. Oral hygiene was evaluated through the Simplified Oral Hygiene Index (OHI-S), tongue coating was quantified from standardized photographs, and questionnaires were used to assess cariogenic diet frequency and socioeconomic variables (educational level, housing status, and family income). Salivary assessments included unstimulated whole saliva flow rate (UWSFR), chewing-stimulated whole saliva flow rate (CSWSFR), pH, buffering capacity, viscosity, and levels of calcium, phosphorus, potassium, magnesium, amylase, and lipase. Participants with NF1 showed higher caries experience than matched controls (DMFT index: 18.5 ± 8.6 vs. 12.6 ± 7.4; p = 0.001). Hyposalivation (UWSFR: 57.1% vs. 2.4%; CSWSFR: 40.5% vs. 0%) and high salivary viscosity (71.4% vs. 11.9%) were significantly more frequent in NF1 (all p < 0.001). While bivariate analysis within the NF1 group showed no direct association between DMFT and salivary flow, post hoc power analysis indicated limited statistical power (20.4%) for this comparison. A significant positive correlation was found between DMFT and tongue coating index (ρ = 0.312; p = 0.044). In multivariable regression, NF1 was independently associated with higher DMFT compared to matched controls (p < 0.001). Additionally, lower family income (p < 0.001) and poorer oral hygiene (p = 0.016) were significantly associated with higher DMFT. A significant interaction between group and cariogenic diet (p < 0.001) was also observed, indicating that the association between dietary habits and DMFT differed between groups. Individuals with NF1 present significantly higher DMFT compared to matched controls. Our findings suggest that this is a multifactorial process, characterized by an independent association between NF1 status and DMFT, even after adjusting for salivary flow, oral hygiene, socioeconomic status, and dietary habits. Notably, the high prevalence of hyposalivation and altered salivary viscosity-combined with the significant positive correlation between tongue coating and DMFT-highlight a complex and compromised oral environment in NF1. These findings support that individuals with NF1 represent a high-risk group for dental caries and significant salivary impairment. This dual vulnerability necessitates specialized preventive protocols, including intensive biofilm control and regular dental monitoring, to reduce the high cumulative caries experience and its impact on oral health in this population.
Fistula laser closure (FiLaC) is a minimally invasive treatment option for perianal fistulas with acceptable healing rates. We report implementation and include short-term results in line with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) 2A framework in patients with complex fistulas and previous surgical repair attempts. Prospective audit data from 56 consecutive patients with perianal fistulas treated between June 2024 and January 2025. The FiLaC procedure included cleaning the fistula tract, application of approximately 100 J/cm fistula length and closing of the internal opening with a stitch. All patients refused more invasive operations and/or were not suitable for advanced repair. Patients were diagnosed with fistulas after a median of 34.5 months (interquartile range, IQR 13.8-54.2 months), with a median of 3 months (IQR 1.8-4.0 months) following previous fistula-related surgery. Most patients had cryptoglandular fistulas (80.4%) while 19.6% had inflammatory bowel disease-related fistulas. Most fistulas were transsphincteric (69.6%), and only 32.1% of patients were seton-free before the procedure. During the first postprocedural outpatient visit at 7.9 weeks (median; IQR 6.4-10.9 weeks), clinical healing was evident in 14 (24.1%) cases, and 23 (39.7%) patients reported relevant symptomatic improvement. A total of 21 patients (36.2%) did not report any improvement, 3 patients (5.2%) experienced a postoperative complication, with 1 (1.7%) requiring a return to theatre due to an abscess. After a median of 10.4 months, the "seton-free rate" was 67.9%, This represents a relevant improvement to 32.1% before FiLaC. The use of FiLaC is a safe, sphincter-preserving treatment for complex perianal fistulas and was associated with a marked increase in the seton-free rate. While complete fistula healing rates were lower than previously reported, FiLaC remains an option for patients with complex disease.
The present study aimed to identify novel risk factors that influence buccal and lingual split patterns by focusing on individual mandibular ramus patterns in sagittal split ramus osteotomy (SSRO) cases. This retrospective cohort study analyzed 658 splits from patients who underwent an SSRO with the Hunsuck technique. Predictor variables included demographic and mandibular anatomy factors, while split patterns were used as outcome variables. Posterior ramus length and buccal horizontal osteotomy (BHO)-buccal type showed significant correlations with buccal bad split patterns. A 1-mm decrease in posterior ramus length increased the risk by up to 25%. As compared with the BHO-caudal type, BHO-buccal type had up to a 22-fold greater likelihood of pattern induction. For lingual split patterns, age, gender, transverse ramus width, posterior ramus length, and BHO were significant factors, with younger age, male gender, wider transverse ramus width, and BHO-buccal type associated with a higher incidence of long lingual splits, while shorter posterior ramus length and BHO-lingual type were linked to increased incidence of short lingual splits. Buccal and lingual split patterns are associated with patient demographics, and considered to be mandibular anatomical risk factors. While posterior ramus length, age, gender, and transverse ramus width are congenital and uncontrollable, BHO type can be adjusted to prevent complications. The anatomical risk factors identified in this study can help surgeons evaluate individual patients received SSRO for risk as well as treatment planning to prevent complications associated with split patterns.
This substudy of the OPTIC-J trial analyzed magnetic resonance imaging (MRI) scans from a subset of Japanese patients to examine changes in orbital tissues after teprotumumab treatment vs placebo for active thyroid eye disease (TED). Post hoc exploratory. Volumes and inflammation/edema of extraocular muscles (EOMs) and orbital fat were measured before and after 24 weeks of teprotumumab treatment or placebo using MRI in patients enrolled at four of the 16 trial sites. Inflammation/edema in EOM and orbital fat were evaluated using the signal intensity ratio, based on T2 intensity in the cerebral white matter, and an ordinal grading scale (0-3), respectively. Key clinical outcomes included proptosis, diplopia, and clinical activity score (CAS). Mean (%) changes in total EOM and orbital fat volumes in study eyes treated with teprotumumab (n = 6) and placebo (n = 8) were -1,022 mm3 (-31%; P = 0.007) and -348 mm3 (-11%; P = 0.039), and -771 mm3 (-6%; P = 0.120) and 418 mm3 (4%; P = 0.084), respectively. Reductions were significantly greater with teprotumumab vs placebo (EOM, P = 0.021; fat, P = 0.016). Mean (%) changes in total EOM and orbital fat inflammation/edema grading of study eyes treated with teprotumumab were -1.82 (-31%; P = 0.005) and -1 (P = 0.031), respectively. Patients administered teprotumumab exhibited improvements in proptosis (83%), diplopia (67%), and resolution of activity determined by CAS (50%). In this OPTIC-J trial substudy, reductions in orbital soft tissue volumes and inflammation/edema were observed with MRI after teprotumumab treatment vs placebo; corresponding improvements in TED clinical outcomes were also observed.
This study aimed to examine: (a) behavioral and emotional problem trajectories of children (in middle and late childhood) and adolescents with intellectual disability, and (b) the influence of parenting behaviors and the parent-child relationship on these trajectories. Participants were primary caregivers (N = 350) of children/adolescents with intellectual disability who were 10 years or older in Wave 1, 2, or 3 and under 16 years by Wave 3 of a longitudinal families study. Measures of child behavioral and emotional problems, parenting behavior, the parent-child relationship, and parent psychological distress were included. Using linear mixed modeling, behavioral and emotional problems declined slightly over time but remained high. Parenting behaviors and parent psychological distress did not affect trajectories. However, conflict (but not closeness) in the parent-child relationship was associated with increased behavioral and emotional problems over time. Higher levels of family financial hardship and an autism diagnosis were associated with increased behavioral and emotional problems. Child sex differences were also identified. Despite small improvements, individuals with intellectual disability exhibit high levels of behavioral and emotional problems into and during adolescence. Parent-child conflict may be an important focal point for interventions to reduce behavioral and emotional problems in young people with intellectual disability.
Regional differences affect the reliability of the AO Spine-DGOU Osteoporotic Fracture Classification. European participants showed the highest agreement. This study underscores the need for addressing regional factors to improve the system's global clinical utility. To evaluate the influence of geographic region on the reliability and reproducibility of the AO Spine-DGOU Osteoporotic Fracture Classification System. This study included 320 participants from various global regions who classified 27 cases of osteoporotic vertebral fractures using the AO Spine-DGOU system which categorizes the fractures to 5 subtypes (OF 1-OF 5). Participants underwent training via an online webinar. Interobserver reliability and intraobserver reproducibility were assessed using Fleiss' kappa coefficient, and agreement with a gold standard committee was evaluated. The classification system showed moderate to substantial agreement with the gold standard globally (initial kappa 0.58, improving to 0.61). European participants had the highest agreement (kappa 0.64 and 0.66). OF4 fractures were most accurately classified, while OF3 fractures showed the least agreement. Intraobserver reliability was highest among European participants. Post hoc analysis indicated significantly better reliability among German-speaking participants compared to other Europeans (kappa 0.79 vs. 0.70, p = 0.0026). The AO Spine-DGOU Osteoporotic Fracture Classification System demonstrates moderate to substantial reliability and reproducibility, with regional differences influenced by factors such as training and clinical experience. This underlines the necessity of proper education adapted to the regional particularities.
Early breast cancer risk identification is essential for targeted screening and prevention. Provider uptake of risk-stratified screening remains low, often due to limited education on risk assessment, clinical time restrictions, and limited resources for systematic implementation. Patient perspectives on incorporating screening tools into routine care are not well understood. This study elicited patient experiences and preferences regarding risk assessment and genetic testing in primary care. Twenty semi-structured interviews were conducted with individuals at average and high breast cancer risk. The interview guide was developed using the informed decision-making framework. Participants reviewed a decision aid and provided feedback on risk and genetic testing communication. Interviews were transcribed and thematic analysis was conducted by two independent coders. Study participants had an average age of 44 with 45% of individuals self-reporting high-risk for breast cancer. Women across risk levels desired clear, empathetic communication with detailed screening and genetic testing information. Financial constraints, fear of results, and confidentiality were perceived barriers. Key benefits included informed decision-making and prevention potential. Participants emphasized accessible information, personalized communication, and clear follow-up plans. High-risk participants demonstrated more active information-seeking, desired ongoing support after testing, and emphasized family. Most found the communication guide and decision aid supportive for informed decision-making. Patient-centered communication and accessible, comprehensive information are key for communication of breast cancer risk. Addressing financial barriers and anxieties surrounding genetic testing will be critical for equitable uptake. Future work should consider these patient preferences in designing interventions to improve risk-aligned care.
Acute traumatic spinal cord injury (SCI) is a devastating neurological condition with limited reliable blood-based biomarkers for assessing injury severity and recovery. Taurine, a neuroprotective amino acid with antioxidant and anti-inflammatory properties, has shown promising effects in experimental studies, but clinical evidence remains limited. To investigate longitudinal changes in serum taurine concentrations following acute traumatic SCI, evaluate their diagnostic performance, and examine their association with functional recovery. This prospective case-control pilot study included 60 patients with acute traumatic SCI and 60 age- and sex-matched healthy controls. Serum taurine concentrations were measured by enzyme-linked immunosorbent assay within 24 h of injury and at 6 months. Patients were classified as complete (n = 30) or incomplete (n = 30) paraplegia. Functional outcomes were assessed using the Spinal Cord Independence Measure (SCIM). Non-parametric tests, receiver operating characteristic (ROC) curve analysis, multivariable linear regression, and Spearman's correlation were performed. Baseline serum taurine concentrations were significantly lower in patients with SCI than in healthy controls (94.80 [56.95-217.30] vs. 478.60 [272.70-985.02] ng/mL; P < 0.001). Taurine concentrations increased significantly at 6 months but remained below control levels (P < 0.001). Patients with incomplete paraplegia had significantly higher taurine concentrations than those with complete paraplegia at both time points (P < 0.001). Baseline serum taurine showed good diagnostic performance (AUC 0.880, 95% CI 0.813-0.933), with 71.2% sensitivity and 89.8% specificity. Serum taurine correlated positively with SCIM self-care, mobility, and total SCIM scores. Serum taurine decreases following acute traumatic SCI, increases during recovery, and demonstrates good diagnostic performance with significant associations with functional outcomes, supporting its potential as a biomarker for injury severity and neurological recovery.
Von Hippel-Lindau disease (VHLD) is a rare autosomal dominant disease, occuring in ~ 1 in 35,000 individuals. Overall, individuals with inherited mutations in the VHL tumor suppressor gene are predisposed to a variety of cancer, including high frequencies of clear cell renal cell carcinoma (ccRCC), pancreatic neuroendocrine tumors, and hemangioblastomas, as well as benign cystic conditions and other cancers. The degree of risk for each of these pathological conditions depends on the location and severity of the inherited germline mutation, and the specific VHL protein interactions and functions disrupted. A core VHL protein function is as the targeting subunit of an E3 ligase complex, with protein degradation activity based on interactions with elongins (ELOB, ELOC), Cullin 2 (CUL2), and RBX1. For ccRCC and some other cancers, loss of VHL-dependent degradation of key substrates-the transcription factors hypoxia-inducible factor alpha (HIF-1α and HIF-2α)-and upregulation of HIF-dependent transcripts are critical to promote tumor formation. For this reason, drugs such as the HIF signaling inhibitor belzutifan have emerged as promising clinical agents for treatment of VHLD patients prone to ccRCC. However, other biological consequences of VHL loss are independent of HIFα degradation, and in some cases independent of the VHL ubiquitin ligase activity. Non-canonical activities of VHL include regulation of microtubule stability, mitotic progression, and ciliation, as well as formation of the extracellular matrix (ECM); the degree to which disruption of these activities contributes to VHLD is currently not well understood. This review provides a concise update of the current literature on VHLD pathogenesis, the relationship of VHL structure and protein interactions to the spectrum of phenotypes associated with VHLD, and current and proposed treatment, prevention, and interception of cancer formation for VHLD patients.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors confer cardiovascular and renal benefits that exceed those attributable to glycemic control alone, prompting interest in pleiotropic mechanisms, including immunomodulation. While prior research has largely focused on innate inflammatory pathways, emerging evidence suggests that SGLT2 inhibition may also influence adaptive immunity through immunometabolic reprogramming. Recent findings demonstrate functional SGLT2 expression in activated human cluster of differentiation 4 (CD4⁺) T cells and responsiveness to pharmacological inhibition, raising the possibility that both systemic metabolic remodeling and direct cellular effects contribute to immune regulation. This review examines the immunometabolic pathways linking SGLT2 inhibition to adaptive immune regulation and critically synthesizes the mechanistic, preclinical, and clinical evidence supporting effects on the T helper 17 (Th17)/regulatory T-cell (Treg) axis, the most extensively studied adaptive immune pathway in this field. Proposed mechanisms include AMP-activated protein kinase (AMPK) activation, suppression of mechanistic target of rapamycin complex 1 (mTORC1) and serum/glucocorticoid-regulated kinase 1 (SGK1), ketone-associated signaling, and broader fasting-mimetic metabolic remodeling that may favor regulatory over pro-inflammatory T-cell responses. Experimental studies frequently report attenuation of Th17-associated responses and restoration of Th17/Treg balance, whereas human evidence remains limited. However, current data support adaptive immune modulation as a biologically plausible but incompletely validated component of SGLT2 inhibitor biology. Further translational and clinical studies are required to clarify its contribution to cardiorenal benefits and its potential relevance to therapeutic repurposing in immune-mediated diseases.
Corticosteroids modulate key inflammatory and fibroproliferative pathways involved in ARDS through genomic and non-genomic glucocorticoid receptor signaling. Advances in ARDS pathophysiology have highlighted the importance of timing, inflammatory burden, and host response in determining treatment efficacy. Clinical evidence supports corticosteroid use in moderate-to-severe ARDS, particularly in COVID-19 ARDS and severe community-acquired pneumonia, with reductions in mortality and duration of mechanical ventilation. However, treatment effects remain heterogeneous across etiologies and biological subphenotypes. Recent identification of hyperinflammatory and hypoinflammatory ARDS phenotypes suggests that corticosteroid responsiveness is not uniform. Hyperinflammatory phenotypes and septic ARDS appear more likely to benefit, whereas evidence remains limited or conflicting in influenza-associated and non-septic ARDS. Long-term effects and adverse outcomes, including metabolic complications and ICU-acquired weakness, remain insufficiently characterized. Future research is increasingly focused on precision medicine approaches integrating biomarkers, adaptive platform trials, and phenotype-guided strategies. Emerging developments include lung-targeted corticosteroid delivery systems and selective glucocorticoid receptor modulators designed to improve efficacy while reducing systemic toxicity. Corticosteroids should therefore be considered a context-dependent therapy whose benefit is influenced by etiology, disease stage, inflammatory phenotype, and timing of administration.
COVID-19 is still a potentially serious infection in immunocompromised individuals, with a significant risk of respiratory failure; nevertheless, the optimal treatment strategy is uncertain. Herein, the impact of combination therapy versus monotherapy on risk of respiratory failure was evaluated. This study is a pragmatic target trial emulation performed on observational data collected between 01/01/2022 and 31/03/2024 in 4 tertiary-care hospitals. immunocompromised patients with mild/moderate COVID-19. (arm A) monotherapy with antivirals (DAAs) or monoclonal antibodies (MoAbs) versus (arm B) combination therapy of MoAbs plus DAAs. COVID-19-related acute respiratory failure on day 28 post-randomization. Secondary aims: adverse events to therapy, 90-day mortality, 90-day COVID-19 recurrence/complications, and duration of viral shedding. Overall, 1,035 subjects were screened, and 303 immunocompromised patients were included; main immunodeficiencies were hematologic cancer (71%), exposure to anti-CD20 (36%), solid organ transplantation (15%) and solid cancer (13%). After enrollment, 189 and 114 received mono- or combination therapy, respectively. Of them, 99 patients (33%) met the primary outcome, with a lower incidence in combination therapy group (17% vs. 42%, p < 0.001). In the IPCW-adjusted population, use of combination therapy was associated with a 23.7% (95%CI = 12.4% - 35.1%) reduced risk of developing acute respiratory failure if compared with monotherapy. Results were confirmed at IPCW-adjusted Cox multivariable model: combination therapy was independently associated with a protective effect (aHR = 0.40, 95%CI = 0.22-0.70). In immunocompromised patients with COVID-19, combination therapy appears associated with a lower risk of respiratory failure and may be preferred, when possible, over monotherapy.
to reassess the prognostic value of positive surgical margins (PSM) after partial nephrectomy (PN) in terms of relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and cancer-specific mortality (CSM) within a large cohort spanning changing surgical eras, including the progressive adoption of minimally invasive approaches. We retrospectively analyzed 1441 patients who underwent PN for cM0 renal tumors between 2000 and 2024 at a tertiary referral center. Patients were stratified according to margin status (PSM vs. negative surgical margins, NSM). Kaplan-Meier analyses estimated RFS, PFS, and OS, while uni (UVA)- and multivariable (MVA) Cox regression models stratified by surgical era (2000-2011 vs. 2012-2024) tested the association between PSM and local relapse, progression, and all-cause mortality. Fine-Gray regression tested PSM impact on CSM. Then, exploratory interaction and subgroup analyses according to surgical approach were also performed. Of 1441 included patients, 81 (5.6%) had PSM on final pathology. Apart from a higher proportion of females in the PSM group (42% vs. 31%, p = 0.03), no clinical or pathological differences were observed between PSM and NSM (all p > 0.1). At 5-year follow-up, RFS, PFS, and OS were 90.5% vs. 96.7% (p = 0.003), 94.9% vs. 94.4% (p = 0.7), and 91.3% versus 94.4% (p = 0.1) for PSM vs. NSM, respectively. After adjustment for the selected clinical variables, PSM were associated with higher hazard of local relapse (HR: 4.03, 95% CI: 1.64-9.87; p = 0.002). No statistically significant association was observed between PSM and systemic progression (HR: 1.15, 95% CI: 0.35-3.74; p = 0.8), all-cause mortality (HR: 1.96, 95% CI: 0.82-4.72; p = 0.1), or CSM on Fine-Gray analysis (SHR: 2.66, 95% CI: 0.58-12.1, p = 0.2). However, the number of progression and mortality events in the PSM group was limited, resulting in wide CIs. PSM after PN were independently associated with a higher risk of local recurrence. No statistically significant association was observed with systemic progression, CSM, or OS; however, these analyses were limited by the small number of events, and clinically meaningful effects cannot be excluded. These findings support careful postoperative surveillance while larger contemporary studies are needed to better define the long-term prognostic impact of PSM.
BLABEL was set up to collect data on the first-line treatment patterns and 5-year disease-evolution of non-muscle invasive bladder cancer (NMIBC) in Belgium. The primary objective was to describe treatment regimens following diagnosis, with patient and disease characteristics and 5-year disease evolution as secondary objectives. This retrospective chart review included 232 NMIBC patients diagnosed (Ta, T1, Tis) between January 1, 2016, and December 31, 2017, across eight centres. At diagnosis, 86.6% (N = 201) had Ta/T1 disease without carcinoma in situ (CIS). After transurethral resection of the tumour, 42.2% of all patients were monitored through observation after TURB, 44.4% received Bacillus Calmette-Guérin (BCG) instillations and 10.8% received intravesical chemotherapy. 90.9% had a complete response (CR) to their initial treatment. During the 5-year follow-up 28.4% experienced NMIBC recurrence, 7.3% progressed to muscle-invasive bladder cancer (MIBC), 3% to metastatic disease and 3% died due to bladder cancer. At 5 years, 65.5% remained disease-free, indicating that 34.5% experienced some form of recurrence. Among CIS patients, 77.4% had an initial CR, 29% experienced NMIBC recurrence and 12.9% progressed to MIBC. This Belgian real‑world study provides insight into first‑line treatment patterns and long‑term outcomes of NMIBC following diagnosis. Most patients underwent observation or BCG instillations after TURB. While the initial response to intravesical treatment is high, approximately one-third of patients recurred within 5 years. High-risk NMIBC patients, particularly those with CIS, had worse outcomes, demonstrating an unmet need.
The clinical spectrum and management of infective endocarditis (IE) in non-referral centers are poorly characterized. We aimed to analyze long-term trends in IE in a university hospital without on-site cardiac surgery. Retrospective analysis of prospectively collected population-based data from IE patients across four time periods (1988-2024) at Hospital Universitario Lucus Augusti. 698 episodes were included (86.5% definite IE). 75.4% occurred in men. Median age was 72.5 years (IQR 63-80) and increased significantly over time (63 to 77 years; p < 0.001). Incidence rose from 3.5 to 16.9 cases per 100 000 inhabitants (overall 9.2/100 000). Age-adjusted Charlson Comorbidity Index (CCI) increased from 3 (IQR 1-4) to 6 (IQR 4-7) (p < 0.001). Degenerative valvular disease-related IE and prosthetic valve IE increased significantly. The Streptococcus bovis group was the most frequent etiology (23.1%), with a rise in Enterococcus spp. and coagulase-negative staphylococci (p < 0.001). Non-paravalvular complications occurred in 76.2%, with increasing rates of heart failure. Transfer to a referral center remained stable (20.5%) and was more frequent in younger, less comorbid patients. Cardiac surgery was indicated in 31% and performed in 15.6%; overall in-hospital mortality was 19.9%, unchanged over time. The incidence of IE increased markedly in parallel with aging, rising comorbidity, and degenerative and prosthetic valve disease. Despite these changes, surgical rates and mortality remained stable, suggesting that referral patterns and local population characteristics should be considered when interpreting the clinical spectrum and outcomes of IE.
Blood flow restriction (BFR) training induces beneficial adaptations at low exercise intensities. However, studies on its effects during walking exercise in individuals with Parkinson's disease (PD) remain limited. Twenty-four individuals with PD (Hoehn and Yahr stages 2-3) were randomly assigned to a walking exercise (WALK, n = 8), walking with BFR (WALK-BFR, n = 8), or control group (CON, n = 8). Both exercise groups performed supervised training twice weekly for 8 weeks; the WALK-BFR group was trained with BFR applied at 40-60% of the arterial occlusion pressure. The outcomes included vascular, neurotrophic, functional, and quality-of-life parameters. Exercise-related adverse events were recorded. The WALK group did not show significant improvements in brain-derived neurotrophic factor (BDNF), flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), Five Times Sit-to-Stand Test, Timed Up and Go Test (TUGT), or 10-Meter Walk Test (10MWT) [all p > 0.05]. Although total Unified Parkinson's Disease Rating Scale (UPDRS) scores decreased in the WALK group, a similar reduction was observed in the CON group, with the only distinct improvement observed in UPDRS Part I. In contrast, WALK-BFR demonstrated significant improvements in BDNF and FMD (both p < 0.05), as well as functional performance (TUGT and 10MWT), quality of life (PDQ-8), and total UPDRS scores, with additional reductions in UPDRS Parts II-IV. However, baPWV did not significantly change in any group (p > 0.05). Both interventions were well tolerated, with a similar incidence of mild and transient lower-extremity muscle soreness in WALK and WALK-BFR groups. WALK-BFR was associated with concurrent improvements in neurotrophic, vascular, and functional outcomes and quality of life in individuals with PD. Furthermore, the intervention was well tolerated and may represent a feasible rehabilitation strategy.
Device deactivation in patients with heart failure is an increasingly relevant clinical and ethical challenge as the use of cardiovascular implantable electronic devices expands. Current guidelines affirm the ethical and legal permissibility of deactivating life-sustaining devices, including implantable cardioverter-defibrillators, pacemakers, and mechanical circulatory support systems, when requested by patients or surrogates with decision-making capacity. Importantly, guidelines from professional societies recommend that discussions about device deactivation be included in the pre-implantation consent process. However, clinical practice reveals persistent gaps in advance care planning, with device deactivation discussions remaining infrequent. Deactivating implantable cardioverter defibrillators can prevent painful and unnecessary shocks at the end of life, which may otherwise prolong dying without improving quality of life. Multidisciplinary involvement, including palliative care consultation, is essential to support patient-centered decision-making and symptom management. This review synthesizes the latest evidence and consensus on device deactivation in heart failure, emphasizing the need for communication, initiated early in the disease course, as well as individualized care, and integration of patient preferences throughout the disease trajectory.