Cardiovascular disease (CVD) and cancer share common risk factors, and cancer survivors experience elevated long-term cardiotoxicity. Traditional risk-based metrics require person-time denominators that are unavailable in aggregate public health databases. This study introduces a proportional co-listing framework to detect population-level cardiovascular surveillance signals on death certificates across cancer types and demographic strata. We conducted a national cross-sectional surveillance analysis using CDC WONDER Multiple Cause-of-Death data from 1999 to 2020 for decedents aged ≥ 15 years. Utilizing an "any-mention" framework, we calculated the Proportional Mortality Ratio (PMR), defined as the ratio of CVD co-listing on cancer-related death certificates to CVD listing on non-cancer certificates. Temporal trends were evaluated using joinpoint regression to estimate the average annual percent change (AAPC). Analyses were stratified by age, sex, race/ethnicity, geography, and index cancer subtypes (lung, colon, and leukaemia). Of 56,014,102 death certificates analyzed, 13,917,133 (24.8%) listed a malignant neoplasm, of which 3,997,238 (28.7%) co-listed CVD. Across the lifespan, the overall PMR followed a reverse J-shaped curve. Proportional co-listing was highest in the youngest cohort (ages 15-24: PMR 1.828, 95% CI: 1.778-1.879), declined to a nadir at ages 55-64 (PMR 0.336, 95% CI: 0.335-0.337), and rose modestly in older adulthood. From 1999 to 2020, PMRs increased significantly across all adult age groups, peaking at ages 55-64 (AAPC 1.69%, 95% CI: 1.52-1.83, p < 0.001). Young-adult PMR elevations were consistently higher in male, metropolitan, and Hispanic/Latino decedents. Among subtypes, leukaemia demonstrated the highest relative CVD co-listing in young adults (PMR 2.174), whereas colon cancer showed no statistically significant elevation (PMR 1.173, 95% CI: 0.951-1.447). Cardiovascular co-listing on US cancer death certificates is highly patterned by age, demographics, and cancer subtype. While elevated PMRs in young adults are consistent with patterns previously reported in cardio-oncology literature, sub-unity PMRs in middle-aged and older adults may reflect under-documentation of cardiovascular comorbidities in oncology settings alongside denominator effects arising from frequent CVD listing on non-cancer certificates. Improving comorbidity documentation on death certificates may enhance the utility of national administrative data for cardio-oncology surveillance and research.
Acute kidney injury (AKI) is a common complication in critically ill patients with decompensated cirrhosis who often require kidney replacement therapy (KRT) but prognostic uncertainty remains in critically ill ICU patients, particularly regarding short- and medium- term outcomes after KRT initiation. We conducted a retrospective, single center cohort analysis of critically ill patients with cirrhosis and AKI requiring KRT in the medical ICU of a tertiary care liver transplant center. We gathered data pertaining to CLIF-C ACLF and MELD-Na on the day of ICU admission. Survival outcomes of interest included days to death from the start of KRT, and at one- and six-month interval. 131 patients met the inclusion criteria of which 21 were listed for liver transplantation at time of ICU admission. 86.3% of patients were diagnosed with acute tubular necrosis (ATN) and the remaining with HRS-AKI. 69.5% of patients were prescribed Continuous Veno Venous Hemofiltration (CVVH) as initial KRT modality. Mean clinical severity scores were MELD-Na 33.1 (SD 8.3) and CLIF-C ACLF score 63.4 (SD 10.3). 21.4% and 15.3% of the 131 patients included, were alive at 1 and 6 months after ICU admission. Median survival time from KRT initiation in ICU was 5 days (IQR 3-12.5 days). Survival did not differ significantly by AKI etiology or transplant listing status although this is limited by small sample size and dynamic nature of transplant listing status. In unadjusted analyses, survival differed by initial KRT modality, with higher mortality among patients initiated on CVVH; however, in multivariable Cox regression, only CLIF-C ACLF score [HR 1.03 (1.00- 1.05), p = 0.04], platelets [HR 0.997 (0.994-0.999), p = 0.02] and INR [HR 1.22 (1.00-1.49), p = 0.05] were significantly associated with survival time. AKI requiring KRT in critically ill patients with cirrhosis is associated with limited survival. Mortality was primarily associated with overall severity of acute-on-chronic liver failure, as reflected by CLIF-C ACLF score, rather than MELD-Na. No clear differences were observed by AKI etiology or transplant listing status. Although unadjusted survival differed by initial KRT modality, this likely reflects confounding by illness severity rather than a modality-specific effect. Not applicable.
In 2024, the total number of heart transplants in the United States reached a record of 4,636, an 81.5% increase since 2013. Of these, 4,146 occurred in adults while 490 occurred in pediatric recipients (93.5% and 19.2% increases, respectively, since 2013). This growth has been insufficient to meet the demand, as the number of adult patients awaiting transplant has always far exceeded the number of transplants performed. This is compounded by increasing numbers of new listings, although new adult listings have increased to a lesser extent (by 57.0%) than adult transplants since 2013. Pediatric heart transplants have only increased 19.2% since 2013, with an apparent plateau since 2018. Except for pediatric candidates aged 12-17 years and those who turned 18 while waiting, there has been a decline in heart transplant rates since 2013: in candidates younger than 1 year, a 48.2% decrease (123.6 [in 2024] versus 238.5 [in 2013] transplants per 100 patient-years); in those aged 1-5 years, a 41.4% decrease (54.0 versus 92.1 transplants per 100 patient-years); and in those aged 6-11 years, an 18.2% decrease (71.0 versus 86.8 transplants per 100 patient-years). The prevalence of heart donors after circulatory death increased to 17.9%. Pretransplant mortality in adults declined slightly, to 8.4 deaths per 100 patient-years, and in pediatric candidates reached a 10-year low of 8.2 deaths per 100 patient-years. Most adult heart transplants (54.9%) were performed at adult status 2, while most pediatric heart transplants (88.8%) were performed at status 1A. There were 974 transplants performed in adults with Impella only, 716 with intra-aortic balloon pump only, and 189 with extracorporeal membrane oxygenation only. The 1- and 5-year survival after transplant remained stable (for transplants in 2017-2019): 91.2% and 80.1% in adults and 92.3% and 83.9% in pediatric recipients, respectively. Two-year survival was lowest in recipients listed at adult status 5 (79.3%) and highest in recipients listed at adult status 6 (91.1%).
Background: Nutrient-enriched sports foods can support efficient nutrient intake in specific circumstances in athletic nutrition management, such as during competition, when training away from the usual environment, or during periods of weight management. Despite their widespread availability, sports foods are not always used appropriately, necessitating tools to support informed product selection. Objective: This study aimed to characterize sports foods consumed by Japanese athletes and to develop a Japanese sports food exchange list to facilitate product selection based on target nutrient requirements. Methods: Seven sports food categories commonly used in Japanese sports settings were examined: sports drinks, energy jellies, energy bars, energy gels, protein drinks, protein bars, and protein powders. Following the methodology of Spain's sports food exchange list, development proceeded in two stages. First, suppliers were selected based on INFORMED CHOICE certification or listing on the Japan Anti-Doping Agency's product information website, with input from experienced sports dietitians. Subsequently, 523 products were classified into subcategories based on nutrient content per unit using established statistical criteria, including the mean, standard deviation, coefficient of variation, and z-values. Results: After excluding products with z-values outside ±2 or compositions deemed unsuitable for carbohydrate or protein supplementation, 498 products from 36 suppliers were classified into 24 subcategories. Japanese sports foods exhibited broad distributions in nutrient composition, variability derived from ingredient differences, and a high proportion of plant-based protein powders. Conclusions: This study developed a Japanese sports food exchange list comprising 498 products across 24 subcategories, enabling evidence-based product selection aligned with the nutrient intake goals of Japanese athletes.
Weaning failure from mechanical ventilation affects 10-20% of critically ill patients. Cardiovascular dysfunction-particularly diastolic dysfunction with elevated left atrial pressure (LAP)-underlies up to 50-60% of failed spontaneous breathing trials (SBTs) and frequently remains undetected without targeted echocardiographic assessment. This narrative review synthesises current evidence on the echocardiographic evaluation of weaning failure, with emphasis on LAP estimation, right ventricular (RV) dysfunction, and the integration of lung and diaphragm ultrasound. A structured literature search of PubMed/MEDLINE and EMBASE was performed for publications from January 2000 to April 2026, supplemented by hand-searching of reference lists and current society guidelines. This article is reported as a narrative review; no formal systematic review protocol was registered. A qualitative synthesis emphasising pathophysiological mechanisms, echocardiographic phenotypes, and clinical applicability was performed. Positive pressure ventilation with PEEP provides active LV afterload reduction; extubation abruptly removes this unloading and may precipitate acute filling pressure elevation in vulnerable patients. Multiparametric echocardiographic LAP assessment-integrating the E/e' ratio, deceleration time, and pulmonary vein flow-supports pre-extubation risk stratification. The dynamic PEEP reduction test, although not yet standardised or multicentre-validated, may identify patients with load-dependent cardiac decompensation before extubation. RV dysfunction is present in 20-50% of ventilated patients and worsens weaning outcomes through ventricular interdependence. Complementary lung ultrasound B-line quantification and diaphragm thickening fraction assessment together support a phenotype-specific diagnostic approach. A structured multimodal ultrasound framework integrating echocardiography, lung ultrasound, and diaphragm ultrasound may support identification and targeted treatment of the dominant mechanism of weaning failure before extubation. Prospective multicentre validation of the integrated protocol as a whole remains a priority research need.
In the search for more effective ways to treat atrial fibrillation and other cardiac arrhythmias, Pulsed Field Ablation has emerged as a way to achieve better outcomes for more patients in a shorter time. Jim Banks looks at its rollout in the U.K., where its dramatic effect on waiting lists is laying the groundwork for much wider use in the National Health Service.
Emotional events are often remembered more vividly than neutral ones, and unexpected events also tend to receive enriched encoding. However, little is known about how emotional valence and expectation violations jointly shape episodic memory. This study examined their combined influence by orthogonally manipulating emotional content and expectation during encoding. Participants first learned predictive contingencies in a rule-learning task. An encoding phase followed, in which some stimuli violated established expectations, while emotional content was manipulated orthogonally to expectation. Recognition memory was then tested for expected and unexpected stimuli. In mixed-valence lists (Experiment 1), unexpected stimuli enhanced recollection for negative and neutral items but not for positive ones. When arousal was matched across valence (Experiment 2), the benefit shifted to unexpected positive and neutral stimuli. In purely emotional lists (Experiment 3), the effect of expectation violations on recollection was diminished, and memory was shaped primarily by valence, with negative stimuli eliciting greater recollection than positive ones. These findings show that the mnemonic benefit of unexpected events is not uniform but varies with valence, arousal, and list composition. They support layered models of distinctiveness, suggesting that memory emerges from the interaction of item-level expectancy, emotional salience, and contextual variability.
Chronic musculoskeletal pain (CMP) is a major cause of disability, with biopsychosocial effects that may be worsened by long waiting times for care. This study aimed to describe the profile of patients with CMP on the waiting list for physiotherapy. We conducted a cross-sectional study using an online survey distributed via telephone. Participants' information was obtained from the Municipal Health Department. The survey assessed data on clinical, physical and psychosocial characteristics. Overall, we contacted 1208 individuals, and 134 completed the survey. The most common pain sites were the right shoulder (44.0%), lower back (42.5%), right hand (38.8) and right knee (38.8). Nearly half of the participants reported pain in 4 or more pain sites in the last seven days (49.3%) and use of antidepressants (48.5%) or analgesics (45.5%). Symptoms of anxiety and depression were present in 45.5% and 35.8% of participants, respectively. One out of five participants reported being unable to work in the last 30 days due to their health conditions. Only 23.9% had previously received physiotherapy care, and among these, 68.7% waited one year or longer for treatment. Patients on the waiting list for physiotherapy commonly report pain, psychosocial symptoms and functional disability. Strategies to improve timely access for physiotherapy are needed to reduce the burden of CMP.
Dual-use research of concern (DURC) refers to legitimate scientific research that, if misapplied, could cause significant harm. Journal editors play an important role in ensuring that disseminated research does not pose unacceptable risks to society. We conducted a thematic analysis of DURC policies adopted by life science journals. Top 10 journals listed in Google Scholar Metrics (February 2026) across 15 life science categories yielded 133 journals after de-duplication. Each journal's website was screened for a policy addressing DURC, biosafety, or biosecurity. Following de-duplication of policies, a set of unique DURC policies was established. Policies were coded using color-coded identifiers for key stakeholders and actions, and themes were identified through reviewer consensus. Fifty-nine journals (44.36%) had a clear policy addressing DURC, biosafety, or biosecurity. De-duplication yielded 11 distinct policy documents. Thematic analysis revealed five themes: (1) transparency and disclosure; (2) regulatory compliance; (3) editorial oversight and gatekeeping; (4) distributed responsibility; and (5) different definitions of DURC. Many life science journals continue to lack explicit DURC policies. Among those with policies, there is a shared expectation that authors, reviewers, and editors are adequately trained to recognize and manage DURC-related risks, an assumption that may be unwarranted.
Objective: To determine the prevalence of generalized anxiety disorder (GAD) in patients (aged 18-86 years, not under treatment, and with no prior diagnosis of GAD) attending an underserved primary care outpatient clinic in Higuerote, Venezuela, between October and December 2023. Methods: A descriptive, cross-sectional, quantitative, population-based study was conducted. Data were collected via a 49-item closed-question survey that included the Hamilton Anxiety Rating Scale, Perceived Stress Scale, and 16 author-designed yes/no questions on GAD-related risk factors. Statistical analysis was performed using SPSS V26; P < .01 was considered statistically significant. Results: The study included 440 patients (mean age of 33.8± 15.3 years; 70.2% female); 50.0% of participants presented with mild anxiety, 6.0% with mild-to-moderate anxiety, and 44.0% with moderate-to-severe anxiety. Psychosocial stress, reported by 299 patients (67.9%), was strongly associated with anxiety severity (odds ratio [OR] =124.6; 99% CI, 29.3-529.6; P<.001). Among those with moderate-to-severe anxiety, 85.7% (n=192; OR= 641.0; 99% CI, 138.5-2,966.8; P<.001) reported anxiety episodes, and 90.0% (n= 180; OR= 74.9; 99% CI, 30.2-185.7; P<.001) reported panic attacks. Alcohol consumption (71.8%, n=316) was significantly associated with anxiety severity (P<.001). Family history of anxiety (60.0%, n=264) and depression (51.8%, n=228) were also significantly associated with anxiety severity (P<.01). While SARS-CoV-2 was infection was significantly associated with anxiety severity (OR=1.9; 99% CI, 1.2-3.1; P<.001), history of traumatic brain injury was not (P = .12). Conclusions: This study revealed a statistically significant high prevalence of GAD in the underserved population of Higuerote, Venezuela. These results show the need for updated mental health epidemiologic data, surveillance, and individualized community-based strategies in disadvantaged/marginalized populations, by empowering local psychiatric workforces through data-driven, context-specific care initiatives. Prim Care Companion CNS Disord 2026;28(3):25m04168. Author affiliations are listed at the end of this article.
Post-stroke apathy (PSA) is a common, disabling syndrome with few evidence-based treatment options. We evaluated the safety, feasibility, acceptability, and evidence of effects of a three-day accelerated intermittent theta burst stimulation-repetitive transcranial magnetic stimulation (iTBS-rTMS) protocol targeting the left dorsomedial prefrontal cortex (dmPFC) in chronic stroke survivors with apathy. Stroke survivors with symptomatic apathy received open-label iTBS-rTMS at the left dmPFC (21,600 pulses across 36 sessions; 3 treatment days; 12 sessions/day within one week). Safety endpoints included adverse events, neuroradiological findings, and objective cognitive performance. Secondary outcomes included measures of apathy and other neuropsychiatric symptoms, as well as psychosocial functioning, including quality of life and caregiver burden. Participants were followed up for one month. Fourteen participants (mean age = 61.8 ± 14.0 years; mean time since stroke = 55.6 ± 31.6 months) completed the iTBS-rTMS treatment course. No serious adverse events occurred. Participants rated the treatment as highly acceptable, and cognitive performance was stable from pre- to post-rTMS, with no treatment-related changes on structural MRI. Regarding apathy, participants had significant improvements with moderate to large effect sizes on the Lille Apathy Rating Scale (LARS), on both self ( d = 0.78) and caregiver-rated versions ( d = 1.28), p<0.05 pretreatment-to-one-month follow-up. In addition, secondary measures of psychosocial function also showed improvement with moderate to large effect sizes (Stroke Specific Quality of Life Scale: d = 0.62; Zarit Burden Interview: d = 0.72), and the Brief Inventory of Psychosocial Function: d = 0.89). In chronic stroke survivors with PSA, accelerated iTBS-rTMS targeting the left dmPFC appears to be safe, feasible, tolerable, and highly acceptable, with preliminary evidence suggesting a potential role in reducing apathy and secondarily promoting improvements in quality of life, caregiver burden, and broader psychosocial function. Clinical Trial Registration ID: NCT05878457 , listing: https://clinicaltrials.gov/study/NCT05878457. none. What Is New?: Dorsomedial prefrontal cortex (dmPFC) holds promise as a network-informed target capable of stimulation with transcranial magnetic stimulation for reducing apathy.High dose of intermittent theta burst (iTBS) stimulation administered to date in a chronic stroke population to dmPFC appears safe, well-tolerated, and feasible with a novel accelerated protocol.What Are the Clinical Implications?: Accelerated iTBS at the left dmPFC appears to be a feasible and potentially efficacious target for apathy in chronic stroke-a patient group with limited evidence-based intervention options.
Objective: Physicians inevitably face illness; yet, occupying the role of patient poses distinct psychological and professional challenges. To elucidate the unique challenges and strengths physicians may experience as patients, this study examines how popular media portrays physicians, highlighting common themes and their implications for clinical practice and medical education. Methods: Literature was reviewed on the unique experiences of physicians in the role of patient. Searches were conducted on Google and ChatGPT using the terms movies + physician as patients, television + physician as patients, and popular media + physician as patients. Additional examples were drawn from the authors' media knowledge base. Retrieved results were reviewed for depictions that exemplify the challenges and strengths unique to physician patients. Scenes from widely recognized films and television shows were discussed to illustrate key themes. Results: Six recurring themes emerged: (1) shame and loss of professional identity, (2) interference in one's own care through self-diagnosis, (3) fear of burdening colleagues, (4) difficulty relinquishing control, (5) curbside consultations with blurred boundaries, and (6) health literacy as a strength. These narratives reflect the physician health literature and offer resonant vignettes of the tensions physician patients face. Conclusion: Physicians who become patients balance vulnerability with unique strengths, yet their professional identity often complicates care. Clinicians should anticipate these dynamics, set clear boundaries, and normalize help-seeking to ensure safe and dignified treatment. Media-based narratives can serve as powerful teaching tools, fostering empathy and preparing clinicians to navigate the complexities of caring for or assuming the role of physician patients. Prim Care Companion CNS Disord 2026;28(3):26m04196. Author affiliations are listed at the end of this article.
Non-communicable diseases (NCDs), such as hypertension, diabetes, and asthma, require continuous medication management. However, medication adherence remains suboptimal. Telepharmacy-defined as pharmacist-led care delivered remotely via telephone, video, or digital platforms-may improve adherence and clinical outcomes while addressing access barriers, but uncertainty remains regarding clinical effectiveness and generalisability. A systematic review is warranted to assess whether telepharmacy improves medication adherence, safety, and other key outcomes compared with usual care. To assess the clinical effectiveness of telepharmacy services, compared with usual care, on medication adherence and clinical outcomes in patients with NCDs in ambulatory care settings. We searched CENTRAL, MEDLINE, Embase, Global Index Medicus, and two trial registries up to 15 December 2025. We also assessed the reference lists of included studies and relevant reviews, conducted citation searching, and contacted study authors to clarify information and identify additional data. No language or publication status restrictions were applied. We included individually randomised controlled trials (RCTs) and cluster-RCTs comparing pharmacist-led telepharmacy with usual care for people with NCDs (e.g. cardiovascular disease, diabetes, and cancer) in ambulatory care settings. Critical outcomes were medication adherence, patients' satisfaction, and drug-related problems (DRPs). Important outcomes included mortality rate, worsening of NCDs, clinical measurements, laboratory values, patients' quality of life, healthcare use, and economic outcomes. We included seven outcomes in the summary of findings table. We assessed the risk of bias for the seven outcomes in the summary of findings table using the Cochrane RoB 2 tool, incorporating both individually RCTs and cluster-RCTs. We conducted synthesis analyses using random-effects models, calculating summary risk ratios or mean differences (MDs)/standardised mean differences (SMDs) with 95% confidence intervals (CIs). For cluster-RCTs, we used adjusted estimates or applied design effect corrections. Where meta-analysis was not feasible, we used narrative synthesis. We assessed the certainty of the evidence using GRADE. We included 21 trials (17 individually RCTs and 4 cluster-RCTs) involving a total of 5440 participants with NCDs. Sample sizes ranged from 20 to 1400 participants. Studies were conducted in high-, upper-middle-, and lower-middle-income countries, across hospital, clinic, pharmacy, or insurer-based settings. Interventions targeted conditions such as diabetes, hypertension, and asthma. Telepharmacy interventions varied in delivery modes (e.g. telephone, video, and app), intensity, and components (e.g. adherence support, monitoring, and education). Follow-up durations ranged from one to 18 months, with most studies lasting 12 months or less. Telepharmacy interventions may improve medication adherence compared with usual care (SMD 0.32, 95% CI 0.10 to 0.55; 10 studies, 2978 participants; low-certainty evidence). For patients' satisfaction, the evidence is very uncertain about the effect of telepharmacy interventions compared with usual care (SMD 0.37, 95% CI -0.11 to 0.85; 3 studies, 422 participants; very low-certainty evidence). One additional study using a 5-point Likert scale reported little to no difference between groups (96.5% versus 97.5%; P = 0.68). Another study lacked a comparator group, and we excluded it from the synthesis. We did not pool the evidence for DRPs due to clinical and methodological heterogeneity. Narrative findings from individual studies showed that one study reported increased detection of DRPs. Other studies reported fewer adverse events, suggesting prevention of DRPs, while the remaining studies found no clear differences. The certainty of the evidence was low. Regarding important outcomes, two studies reported worsening of NCDs. Due to clinical heterogeneity, we did not pool the results and presented them narratively. The effect of telepharmacy on worsening of NCDs remains uncertain. For asthma control, no clear difference was observed (SMD 0.23, 95% CI -0.34 to 0.80; 2 studies, 318 participants). Telepharmacy interventions may reduce systolic blood pressure (SBP) (MD -6.82 mmHg, 95% CI -12.16 to -1.48; 5 studies, 1254 participants; low-certainty evidence) and may reduce diastolic blood pressure (DBP) (MD -2.50 mmHg, 95% CI -4.80 to -0.20; 5 studies, 1254 participants; low-certainty evidence) compared to usual care. Two additional studies reporting clinical measurements found more pain relief with telepharmacy in one study, and no clear difference in thromboembolic events in the other. For glycated haemoglobin (HbA1c), telepharmacy interventions probably have little or no effect (MD -0.10%, 95% CI -0.25 to 0.05; 5 studies, 1771 participants; moderate-certainty evidence). For LDL cholesterol, a meta-analysis of two studies showed no clear difference between the groups (MD -0.84 mg/dL, 95% CI -4.70 to 3.02; 2 studies, 444 participants). One study reported better prothrombin time-international normalised ratio (INR) control in the intervention group. Three studies assessed quality of life using different tools, but did not show consistent evidence of benefit. Hospital admissions and emergency department visits showed no clear differences between groups. Two studies evaluated economic outcomes, with one reporting cost savings and the other showing no difference in total or disease-related costs. No included studies reported data on mortality rate or adverse events attributable to telepharmacy, so potential harms remain uncertain. Low-certainty evidence suggests that telepharmacy interventions may improve medication adherence, and may reduce both SBP and DBP in patients with NCDs in ambulatory care settings compared to usual care. Moderate-certainty evidence indicates telepharmacy interventions probably have little or no effect on HbA1c. The evidence is very uncertain about the effect of telepharmacy interventions on patients' satisfaction. The evidence base is limited by short follow-up periods, variation in interventions and outcome measures, and lack of equity-related data. Telepharmacy appears promising for ambulatory care, but further high-quality trials with standardised adherence measures and longer follow-up are needed to clarify effectiveness, implementation potential, and equity impacts. Takeshi Hasegawa and Hisashi Noma were supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: JP24K06239 and JP23K24811). Protocol (2023): DOI 10.1002/14651858.CD015136.
Reactive neutrophil infiltration can restrain CD8+ T cell expansion in lymph nodes during adoptive T cell therapy (ACT), yet its spatiotemporal regulation remains incompletely understood. Levaraging flow cytometry and multiplex immunofluorescence data, we performed a time-resolved quantitative assessment of immune cell dynamics in tumor-draining lymph node (tdLN) and non-tumor-draining lymph node (non-tdLN) in a melanoma mouse model receiving ACT. Transferred tumor-reactive CD8+ T cells accumulated and expanded early after treatment initiation, showing the highest frequency of a favorable central memory 13 CD8+ T cell phenotype in the tdLN. Enhancing innate immune signaling in melanomas increased neutrophil influx into lymph nodes, particularly the non-tdLN; however, within the tdLN, neutrophils were enriched in the T cell zone, which also contained the largest absolute reservoir of transferred CD8+ T cells. Together, these findings indicate that tdLN and non-tdLN differ in early neutrophil dynamics and compartmentalization during ACT, influenced by the strength of innate immune signaling in the tumor.
To characterize the demographic characteristics, clinical features, and severity of thyroid eye disease (TED) in paediatric patients with Graves' disease for comparison with an adult cohort in the Kingdom of Bahrain. Paediatric patients (≤ 18 years) with Graves' disease were screened for TED in Bahrain between October and December 2025. Paediatric endocrinologists across government, military, university, and private sectors participated. Patients were identified from physician-provided lists and verified using diagnostic codes and medical records from four nationwide centres. Comprehensive ophthalmic and orbital examinations were performed, and patients were classified into TED and non-TED groups. TED was diagnosed using the Bartley criteria and graded according to the European Group on Graves' Orbitopathy (EUGOGO) classification. Findings were compared with an adult Graves' disease cohort (> 18 years) from the same population referred between September 2023 and December 2025. Among 22 paediatric patients with Graves' disease (median age 14 years, interquartile range [IQR] 10-16 years; female-to-male ratio 4:1), 11 (50%) were diagnosed with TED. No statistically significant differences were observed between patients with and without TED regarding demographic characteristics, smoking exposure, Graves' disease duration, family history of autoimmune thyroid disease, or hyperthyroidism treatment. However, parental consanguinity was significantly more common among patients with TED. Among paediatric TED patients, 54.5% had bilateral disease and 81.8% had mild TED. None had sight-threatening disease or diplopia. All patients were symptomatic, most commonly with periorbital bulging or swelling (81.8%). Lid retraction (72.7%) and proptosis (63.6%) were the most frequent objective findings, whereas extraocular motility restriction was uncommon (18.2%). Compared with adults (n = 81), mild disease was more frequent in paediatric patients (81.8% vs 48.1%; P = 0.04), whereas lid lag was more common in adults (64.2% vs 18.2%; P = 0.01). This study provides the first regional data on paediatric TED in the Gulf region, demonstrating that TED is common among children with Graves' disease and is predominantly mild in severity. Eyelid involvement and proptosis were the most frequent manifestations. Parental consanguinity was more common among children with TED, suggesting a possible genetic contribution. These findings emphasize the importance of routine ophthalmic screening in paediatric Graves' disease and highlight age-related differences in clinical presentation.
Chronic pain and substance use disorders (SUD) frequently co-occur and are associated with poorer treatment outcomes. The way pain is measured affects which patients are identified as having clinically meaningful pain, which functional consequences are linked to substance use outcomes, and whether findings can be compared across studies or translated into care. Pain measurement practices in SUD research have not been systematically mapped. We conducted a systematic scoping review of studies from 1990 to 2025 that reported pain assessment in SUD populations, including opioid, alcohol, tobacco, stimulant, and polysubstance use disorders. We searched PubMed, MEDLINE, Embase, CINAHL and PsycINFO. We extracted data on pain assessment tools, substance use categories, SUD-specific psychometric evaluation, and coverage of eight NIH HEAL Pain Common Data Element domains: intensity, interference, location, physical functioning, quality of life, psychological factors, sleep disturbance, and treatment satisfaction. Ninety-six studies (25,872 participants; mean per study 269, median 113) met inclusion criteria. Most used unidimensional pain intensity measures. Pain intensity scales appeared in 91% of studies, but only 14.6% reported SUD-specific psychometric evaluation. Pain interference, location, and treatment satisfaction were assessed in fewer than 60% of studies, and 11.5% assessed at least six of the eight NIH HEAL domains. Randomized controlled trials assessed more domains on average than cross-sectional studies. Studies focusing on opioid use disorder (OUD) more often used multidimensional tools than studies of alcohol, tobacco, stimulant, or polysubstance use. In the subset of studies that examined pain-substance use relationships, pain interference more often showed stronger associations with substance use outcomes than pain intensity alone. Pain assessment in SUD research relies largely on unidimensional intensity scales. Substance Use Disorder specific validation is infrequent, and multidimensional pain domains are not consistently used. Brief multidimensional assessment approaches and systematic psychometric evaluation of pain measures in SUD populations are needed to improve the accuracy and clinical usefulness of pain measurement in research and treatment. We propose a candidate framework and minimum set for such studies.
To evaluate how primary endpoint selection influences patient eligibility, enrolment, and detection of treatment efficacy in RPGR gene therapy trials, comparing low luminance visual acuity (LLVA) with microperimetry-based outcome measures. Retrospective analysis of a phase 1/2-3 interventional clinical trial. Fifteen patients were included in this study. Each was administered with gene therapy in one with the other eye serving as control. Month 12 data from patients with RPGR-associated retinopathy enrolled at a single centre in the XIRIUS trial (NCT03116113) were retrospectively analysed. FDA-aligned low-luminance visual acuity (LLVA) responder criteria (≥15-letter gain) and EMA-aligned significant change from baseline in microperimetry mean sensitivity, were applied. Microperimetry outcomes were evaluated across the full 68-point MAIA grid and within a central 16-point subset. Minimal baseline inclusion thresholds were used. The proportion of gene therapy-treated patients meeting FDA- and EMA-aligned (≥2.5 dB improvement in mean sensitivity) responder criteria was determined. Proportion of patients meeting the responder criteria in either microperimetry or LLVA. At baseline, LLVA excluded more patients from study inclusion due to floor effects than microperimetry. At month 12, 2 of 10 patients (20%) met LLVA responder criteria. In contrast, 5 of 11 patients (45%) met EMA-aligned whole-grid microperimetry responder criteria, including all LLVA responders and three additional patients with clear functional improvement not captured by LLVA. Restricting analysis to the central 16 microperimetry points further increased responder detection, identifying 7 of 11 patients (64%). Improvements in microperimetry mean sensitivity of at least 2.5 dB, exceeding expected test-retest variability. No responders were identified for any endpoint in untreated fellow eyes. Primary endpoint choice substantially affects efficacy detection and patient inclusion in RPGR gene therapy trials. LLVA demonstrated limited sensitivity and restricted eligibility to a narrow disease window, risking underestimation of treatment benefit. Microperimetry mean sensitivity, particularly when spatially aligned with the treated retinal area, detected functional improvement in a substantially larger proportion of patients and supports broader enrolment. Microperimetry-based endpoints provide a more sensitive and inclusive primary outcome measure for RPGR gene therapy trials.
The flavin-dependent N-monooxygenase SidA from Aspergillus fumigatus catalyzes the conversion of L-ornithine to N5-hydroxy-L-ornithine. This product is incorporated into hydroxamate containing siderophores, which are iron chelators required for growth during A. fumigatus infection in mammals. The activity of SidA has been shown to be required for siderophore biosynthesis. Here, we used a colorimetric product formation assay to screen a small-molecule library for the identification of potential inhibitors of SidA. Ebselen, an organoselenium compound, was identified as an inhibitor of SidA. This compound inhibited SidA with an IC50 value of 11 ± 1 μM. Ebselen derivative, ebsulfur, was also found to inhibit SidA with an IC50 value of 40 ± 13 μM. These compounds represent a new type of inhibitors of siderophore biosynthesis.
Problematic pornography use (PPU) and other compulsive sexual behaviors (CSBs) are associated with numerous psychosocial consequences, with a higher frequency in men than women. However, less is known about the frequency and relationship between PPU, CSBs, depression, and alcohol use problems, especially among college students who may endorse these behaviors at higher rates. This study sought to identify the relationship between co-occurring CSBs, PPU, alcohol use problems, and depression across gender (77% women, 23% men) in a sample of college students (N = 1126). Participants completed an anonymous online survey. Categorical modeling (i.e., chi-square tests and binary logistic regressions) was utilized to identify base rates and odds ratios of clinically significant PPU and CSBs among individuals with alcohol use problems and depression. Men, relative to women, reported PPU and co-occurring alcohol use problems and depression at higher rates. Less significant gender differences were observed across co-occurring CSBs, alcohol use problems, and depression. Alcohol use problems were moderately to strongly associated with CSBs. Depression was associated with PPU in women. Co-occurring alcohol use problems and depression were moderately associated with CSBs. This study highlights the role of gender in potential comorbidities between PPU and CSBs in young adults, as well as the need for greater research examining the consequences of PPU, CSBs, and co-occurring disorders.
Patellofemoral pain (PFP) is a common cause of anterior knee pain, particularly among physically active individuals. High-intensity laser therapy (HILT) has shown analgesic effects in several musculoskeletal conditions; however, its role in PFP remains unclear. To evaluate the effects of HILT in people with PFP. Randomized controlled trials (RCTs) evaluating HILT for PFP were identified through searches in PubMed, Scopus, Web of Science, CINAHL, MEDLINE, ScienceDirect, the Cochrane Library, and PEDro, with additional screening of reference lists and gray literature (last search: May 1, 2026). The primary outcome was pain intensity, while functional outcomes were considered secondary. Risk of bias was assessed using the Cochrane RoB 2 tool. Meta-analyses were conducted using standardized mean differences (SMDs) with 95% confidence intervals under a random-effects model. Certainty of evidence was evaluated using the GRADE framework. Four RCTs were included, with 77 participants allocated to HILT combined with exercise and 92 to control groups. The overall RoB was assessed as high across all included trials, primarily driven by concerns related to outcome measurement and selective reporting. All HILT protocols were delivered alongside therapeutic exercise (strengthening and/or stretching), and no included trial evaluated HILT as a standalone intervention. HILT resulted in a statistically significant reduction in pain at post-treatment (SMD = - 0.66; 95% CI - 0.98 to - 0.35; p < 0.01) and at follow-up (SMD = - 1.08; 95% CI - 1.89 to - 0.26; p < 0.01); however, the certainty of evidence was rated as very low due to high RoB across included trials, substantial heterogeneity (I2 > 50%), and imprecision related to small sample sizes. No significant between-group differences were observed for functional outcomes (Kujala scale), for which the certainty of evidence was also very low due to similar methodological limitations. HILT combined with therapeutic exercise may reduce pain in individuals with PFP; however, its independent effect cannot be determined. The very low certainty of the evidence limits confidence in these findings, and improvements in functional outcomes remain unclear. High-quality randomized controlled trials are required to clarify the role of HILT in PFP rehabilitation and to determine its potential contribution within multimodal treatment approaches. CRD42025631248 (PROSPERO) (December 24, 2024).