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PubMed2026

Investigating telomere length and hTERT-MNS16A VNTR polymorphism in Bipolar disorder: Insights into clinical features.

OBJECTIVE: To compare leukocyte telomere length (LTL; T/S ratio) and hTERT-MNS16A VNTR polymorphism between patients with bipolar disorder (BD) and healthy controls, and to examine their associations with clinical features in BD. METHODS: A total of 179 participants (100 BD patients, 79 healthy controls) were enrolled. Relative LTL was assessed by qPCR-based T/S ratio; hTERT-MNS16A VNTR genotyping by PCR and gel electrophoresis. Clinical variables including episode frequency, illness duration, age at onset, symptom severity scales, first episode polarity, and family history of mood disorder were evaluated. RESULTS: No significant differences were observed between BD patients and healthy controls in T/S ratio or hTERT-MNS16A VNTR genotype distributions (all p > 0.05). Within the BD group, S allele carriers (L/S or S/S) had significantly more depressive episodes than L/L homozygotes (1.45 ± 2.58 vs. 0.61 ± 1.52; p = .040). Significant inverse correlations were identified between T/S ratio and depressive episode count (ρ = -0.220, p = .028) and total mood episodes (ρ = -0.207, p = .039). Multivariable negative binomial regression revealed four independent predictors of depressive episode frequency: lower T/S ratio (p = 0.005), S allele carriage (L/S or S/S genotypes) (p = 0.001), first depressive episode polarity (p < 0.001), and family history of mood disorder (p = 0.035). CONCLUSION: Although LTL and hTERT-MNS16A VNTR genotype did not differ between BD patients and healthy controls, shorter telomere length and S allele carriage were independently associated with higher depressive episode frequency within the BD group, implicating telomere biology and hTERT genetic variation in the biological substrate of depressive illness burden.

Humans↗

PubMed2026

Ginkgo biloba versus desmopressin in treatment of children with monosymptomatic nocturnal enuresis: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) compared with Desmopressin and their combination in children with monosymptomatic nocturnal enuresis (MNE). METHODS: In this double-blind, randomized, placebo-controlled trial, 398 children aged 5-14 years with MNE were assigned to four groups: placebo, GBE (60 mg daily), Desmopressin (0.2 mg daily), or GBE plus Desmopressin for 3 months. Primary outcomes included the number of wet nights per week. Secondary outcomes assessed sleep quality using the Sleep Disturbance Scale for Children (SDSC), arousal by the Disorders of Arousal (DA) score, and quality-of-life using the Pediatric Incontinence Questionnaire (PinQ). RESULTS: After 3 months, the combination group demonstrated the greatest improvement in wet nights (median 0 [IQR 0-2]) compared to GBE (6 [0.5-6.5]) and Desmopressin (2 [0-6]) (p < 0.001). Full response rates (≥90% reduction in wet nights) were highest with combination therapy (88.3%), followed by Desmopressin (46.5%), GBE (24.8%), and placebo (9.5%) (p < 0.001). GBE-containing groups showed significantly increased DA and SDSC scores, indicating enhanced arousal and lighter sleep. Quality-of-life (PinQ) score decreased in all treatment groups denoting improvement, with the best outcomes observed in the combination arm. Adverse effects were mild and comparable across groups, and serum sodium levels remained stable. CONCLUSION: GBE is a safe and effective novel therapy for MNE, improving sleep arousal and symptom control. Its combination with Desmopressin offers superior efficacy, better quality of life, and lower relapse rates than either agent alone.

Humans↗

PubMed2026

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5 mg/kg/day, increased to 8 mg/kg/day if pain reduction was <30% after 24 h) or placebo for 48 h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a ≥30% reduction from baseline at 40 min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8 mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans↗

PubMed2025

Outcomes of Experiencing Interpersonal Violence in Autism: A Mixed Methods Systematic Review and Meta-Analysis.

In this review and meta-analysis, we aimed to examine outcomes of interpersonal violence among autistic people. Intersectionality and minority theories suggest that negative outcomes are heightened among people with multiple marginalized identities. Thus, we also aimed to investigate gender-related outcomes of interpersonal violence among autistic people. We conducted a systematic database search with inclusion criteria including mixed methods, peer-reviewed research examining any harmful interpersonal act (e.g., physical, sexual, and psychological) experienced by autistic people. We undertook a random-effects meta-analysis with pooled data from 9 studies, comprising 3,647 autistic participants aged 1 to 80 years. Violence was associated with worsened mental health, with the strongest association for internalizing symptoms (d = 0.66, p < .001; 95% CI [0.51, 0.80]) and suicidal thoughts and behavior (d = 0.63, p < .001; [0.44, 0.82]). Narrative synthesis of 57 studies comprising 37,418 participants (13,127 autistic, 24,291 non-autistic) found violence was associated with numerous adverse health, development, and functional outcomes, including worsened mental health and behavioral difficulties compared to non-autistic controls from childhood. Females and gender minorities reported greater intra- and interpersonal health and development difficulties related to violence, emerging in early childhood and enduring into adulthood. Findings provide strong evidence of lifelong negative outcomes associated with interpersonal violence experienced by autistic people, providing evidence for the relevance of minority stress and intersectionality theories in understanding risk. Indeed, our results raise concerns that autistic people, and particularly non-male (female, gender diverse) individuals, have higher susceptibility for abuse from a young age, while being conditioned to respond with social desirability, superficial adaptivity, and dissociation.

Humans↗

PubMed2026

Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

Atomoxetine Hydrochloride↗

PubMed2026

Sustained effects of auricular point acupressure on chemotherapy-induced neuropathy: a randomized controlled trial follow-up study.

PURPOSE: Chemotherapy-induced neuropathy (CIN) is a persistent condition that impairs function and quality of life. Auricular point acupressure (APA) has shown short-term benefit for CIN, but the durability of these effects after treatment completion is unknown. This study evaluated the sustainability of symptom improvements for 3 months following a 4-week APA intervention. METHODS: This prespecified secondary analysis of a randomized wait-list controlled trial compared mobile-supported APA (mAPA) and virtual APA (vAPA) in adults with moderate or greater CIN who received APA during the initial treatment phase (mAPA, n = 80; vAPA, n = 75). Outcomes at 1, 2, and 3 months post-intervention were analyzed using generalized estimating equations with multiple imputation. The primary outcome was CIN severity, measured with an individualized composite outcome (ICO); the secondary outcome was CIN interference. RESULTS: Reductions in CIN severity and interference were maintained throughout follow-up in both groups (all p < .001). ICO scores decreased by 3.10, 3.36, and 3.61 points in mAPA and by 2.88, 2.90, and 3.21 points in vAPA at 1, 2, and 3 months, respectively. Benefits were maintained post-treatment, with higher retention in the mAPA group. CONCLUSIONS: Improvements in CIN severity and interference after APA were sustained for up to 3 months post-treatment, suggesting a durable benefit as a self-management strategy. Larger studies with longer follow-up and untreated comparison groups are needed. IMPLICATIONS FOR CANCER SURVIVORS: APA may offer survivors a durable, self-administered, nonpharmacologic option for managing CIN well beyond active treatment, without requiring ongoing clinical visits. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04920097 registered on 3 June 2021.

Acupressure↗

PubMed2026

Development of a core descriptor set for studies assessing interventions for diabetes-related foot ulceration.

AIMS/HYPOTHESIS: Foot ulceration is a common complication of diabetes and is associated with high mortality and costs. The quality of evidence to inform clinical practice is limited, partly because clinical studies do not consistently report baseline participant characteristics. This study aimed to develop a core descriptor set (CDS), a minimum set of descriptors to be measured in all studies evaluating interventions for people with diabetes-related foot ulceration. METHODS: A longlist of descriptors was generated through a systematic review of studies assessing interventions for diabetes-related foot ulcers, pre-registered with PROSPERO (CRD42019128250). The identified descriptors were then ranked based on perceived importance by healthcare professionals from different fields and geographical locations using a nine-point Likert scale in the first round of a Delphi survey. Using standardised criteria, descriptors without consensus were re-ranked in round two. Critical descriptors and those without consensus after the Delphi process were discussed in the consensus meeting to finalise the CDS. RESULTS: The systematic review yielded 95 candidate descriptors. The two Delphi rounds were completed by 102 and 69 healthcare professionals, respectively. The Delphi process identified 34 critically important descriptors and 13 descriptors without consensus, which were discussed in the consensus meeting. The ratified CDS included 28 descriptors across nine domains: demographic variables; individual factors; ulcer characteristics; limb characteristics; ongoing medical interventions; previous surgical interventions; medication history; biochemical measurements; and quality of life/function/symptoms. CONCLUSIONS/INTERPRETATION: This CDS reflects characteristics important to health professionals and researchers when reporting clinical studies on diabetes-related foot ulceration. Its use will aid the reporting of future studies.

Humans↗

PubMed2026

Therapeutic approaches for the treatment of bovine metritis: a systematic review of clinical, reproductive and productive outcomes.

Bovine metritis is a complex multifactorial disease associated with substantial clinical and economic impact due to reduced milk production, subfertility, and increased culling rates. Considerable uncertainty remains regarding the comparative efficacy of the many therapeutic strategies used to manage it. This systematic review aimed to summarize and critically evaluate the available evidence on therapeutic approaches for bovine metritis, with respect to clinical cure, reproductive performance, productive performance, and culling. A literature search conducted in PubMed, Web of Science and CABI Digital Library (2010-2025) identified 18 randomized controlled clinical trials eligible for inclusion. Risk of bias was assessed independently by two reviewers using the Cochrane RoB 2 tool. Given substantial clinical and methodological heterogeneity across studies, findings were synthesized narratively by outcome, without meta-analytic pooling, and the certainty of evidence was assessed using GRADE for the comparisons supported by more than one study. Overall, systemic antimicrobial therapies consistently improved short-term clinical cure rates, although their effects on long-term reproductive and productive performance remained inconsistent. In selected cases, nonsteroidal anti-inflammatory drugs (NSAIDs) showed clinical outcomes comparable to antimicrobial treatments, allowing reductions in antimicrobial use ranging from 50% to 92%. Alternative approaches, such as intrauterine flavonoid, chitosan or dextrose-based therapies, produced inconsistent results that appeared to correlate with disease severity and treatment protocol. The evidence base is limited by substantial heterogeneity in disease definitions, postpartum timing of diagnosis, and cure criteria across studies, and by the near-universal absence of allocation concealment in the primary literature; these limitations restrict the certainty of most conclusions to low or moderate. Therefore, effective metritis control should move beyond symptom resolution and incorporate integrated and preventive strategies targeting inflammatory and metabolic dysregulation during the transition period.

Animals↗

PubMed2026

Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.

BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (0.9% saline) 24 h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96 h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n = 73) or placebo (n = 83). Psychological pain decreased in both groups but was lower with ketamine during the first 96 h. Pointwise scores were lower with ketamine from 40 min to 96 h, largest at 40 min, 2 h, 4 h, and 24 h (all p < 0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96 h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.

Humans↗

PubMed2026

A systematic review and meta-analysis of radiation-induced oral complications in head and neck cancer: Prevalence and clinical outcomes.

BACKGROUND: Radiation-induced oral complications, notably xerostomia and oral mucositis (OM), are common and debilitating in patients with head and neck cancer (HNC), adversely affecting swallowing, nutritional intake, and overall quality of life (QoL). OBJECTIVES: This review aimed to quantify the prevalence of radiation-induced xerostomia and OM and synthesize their impact on dysphagia and nutritional status among HNC patients undergoing radiotherapy (RT). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive searches were performed in MEDLINE, Scopus, SciFinder, Embase, and PubMed for studies published between January 2019 and December 2025. Data from 51 studies were extracted and synthesized. RESULTS: The pooled prevalence was 85% (95% CI: 81.6-87.9%) for xerostomia and 88.3% (95% CI: 73.9-95.3%) for any-grade OM. Severe OM (Grade 3-4) had a prevalence of 39.5% (95% CI: 23.1-58.8%). These complications were strongly interrelated and significantly associated with dysphagia (69.8%; 95% CI: 53.1-83.7%), malnutrition (66.6%; 95% CI: 37.3-95.9%), and poor QoL (pooled mean QoL score: 64.13/100). Studies employing advanced radiation techniques (e.g., IMRT) demonstrated a lower prevalence of xerostomia (OR = 0.58, 95% CI: 0.42-0.80) compared to conventional RT. CONCLUSION: Radiation-induced oral complications (xerostomia & OM) remain prevalent and clinically significant burden in HNC patients, contributing to a cascade of functional impairments and diminished QoL. These findings highlight the need for preventive strategies, symptom management interventions, and the broader adoption of advanced RT techniques. Longitudinal research is warranted to further evaluate long-term outcomes and guide patient-centered care models.

Humans↗

PubMed2026

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans↗

PubMed2026

Bacterial Lysates Add-On Therapy to Reduce Postoperative Recurrence in Nasal Polyps.

OBJECTIVE: This study aimed to investigate the potential role of OM-85 in reducing polyp recurrence (PR). METHODS: A single-center randomized, prospective study was performed to compare the inter-group PR rate, patient-reported outcome measures (PROMs), CT and endoscopic scores. Hundred patients were randomized to receive either add-on OM-85 (34/50) or control group (43/50); 77 participants completed the 12-month follow-up. The OM-85 group received oral treatment for 10 days, followed by a 20-day washout (Months 1-3 and 7-9). Primary outcome was the PR rate. Secondary outcomes included PROMs, Lund-Kennedy (L-K) scores, Lund-Mackay (L-M) scores, and complete blood count (CBC) parameters. RESULTS: The PR rate was significantly lower in the OM-85 group (8.82%) than in the control group (27.91%, χ 2 = 4.408, p = 0.036). Univariable analysis identified pre-operative Lund-Mackay (L-M) score (p = 0.008) and hyposmia VAS score (p = 0.031) as significant predictors of PR. In multivariable analysis, the L-M score remained an independent predictor (OR = 1.15, p = 0.012), with an optimal cutoff of 10. The OM-85 group showed significant improvements in nasal obstruction, olfactory dysfunction, and mucopurulent discharge at 6 and 12 months (p < 0.05). Lund-Kennedy (L-K) score and 22-item Sinonasal Outcome Test (SNOT-22) score were also significantly improved (p < 0.05). Furthermore, the OM-85 group exhibited elevated white blood cell counts and lymphocyte percentages from 6 months onward (p < 0.05). CONCLUSION: Adjuvant OM-85 may reduce postoperative PR, with improved endoscopic and symptom scores, potentially mediated by enhanced systemic immune function.

Humans↗

PubMed2026

Online Social Anxiety in the Digital Age: Transitions, Predictors, and Mental Health Associations in Emerging Adulthood.

BACKGROUND: Online social anxiety (OSA), a multidimensional form of social evaluative anxiety in online social contexts, disproportionately affects emerging adults who constitute the largest active group of media users and face heightened psychological sensitivity due to growing pressures and immature sociocognitive regulation during the transition to adulthood. However, its heterogeneity, transitions, and longitudinal associations with mental health outcomes remain underexplored. METHODS: This study utilized data from two waves of a three-wave longitudinal survey, with 849 Chinese participants (Meanage = 21.6 years; 50.4 percent female) assessed at 4-month intervals. Individuals were classified using latent profile analysis and the stability and changes of profiles were assessed via latent transition analysis (LTA). Multinomial logistic regressions were conducted separately at baseline and follow-up to identify correlates of profile membership. Predictors of profile transitions were examined using manual three-step LTA models, and associations between latent transition patterns and follow-up mental health outcomes were examined using BCH-LTA distal outcome analyses controlling for the corresponding baseline symptom level. RESULTS: Four profiles of OSA were identified: low, privacy-sensitive, moderate-high, and high OSA. Extreme profiles (low/high OSA) showed high stability (80.4 percent and 79.1 percent), while privacy-sensitive OSA exhibited the lowest stability (55.1 percent). Profile memberships were influenced by social-cognitive biases and digital interaction, particularly fear of negative evaluation and online interpersonal trust, whereas profile transitions were mainly associated with anxiety. Transitions toward less severe OSA profiles were generally associated with better subsequent mental health, whereas transitions toward more severe profiles corresponded to poorer outcomes, particularly for offline social anxiety. CONCLUSION: OSA was heterogeneous in its manifestation, severity and transitions. Personalized and early interventions targeting profile-specific vulnerabilities are critical to prevent the worsening of OSA and mitigate its psychological burden.

Humans↗

PubMed2026

Home-Based Cardiac Rehabilitation Using a Smart Ring and Telephone Counselling: A Randomized Controlled Trial.

BACKGROUND: Home-based cardiac rehabilitation (HB-CR) is a promising alternative to center-based cardiac rehabilitation as it can address several barriers impeding CR implementation because of its enhanced accessibility. However, to date, HB-CR has not garnered adequate attention due to a lack of communication between patients and medical staff. In this study, we aimed to investigate the effectiveness of HB-CR by monitoring the pulse rate (PR) using a smart ring equipped with photoplethysmography. METHODS: Patients with cardiovascular disease were educated on structured HB-CR methods following a symptom-limited cardiopulmonary exercise test (CPET), and were instructed to wear the device during the exercise session. The recorded PR was uploaded to a website via a smartphone and monitored by medical staff. Patients were randomly assigned to one of two groups: intervention or control group. The intervention group received weekly telephone counselling and was encouraged to maintain optimal levels of physical activity. In contrast, the control group only recorded their exercise data without additional interventions. After 3 months of training, the CPET was performed. RESULTS: Among the 64 randomized patients (32 in each group), an intention-to-treat analysis showed that peak oxygen consumption increased over time in both the groups, with a significantly greater improvement in the intervention group. The group-by-time interaction for peak oxygen consumption was statistically significant (estimated mean difference, 2.0 mL/kg/min; 95% confidence interval, 0.7-3.3; P = 0.004). CONCLUSION: HB-CR using a smart device was effective in improving oxygen consumption. However, appropriate monitoring and timely counselling by medical professionals are important for improved outcomes. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005893.

Humans↗

PubMed2026

Long-term outcomes of surgical correction of ventral penile curvature in children: Patient-reported measures, surgical results, and decisional regret.

INTRODUCTION: There is a dearth of data on long-term outcomes, including patient-reported outcomes (PROMs), decisional regret, and complication rates for surgical correction of isolated ventral penile curvature in childhood. PATIENTS AND METHODS: Twenty-six children treated for ventral curvature between 1993 and 2008 were identified; 24 met inclusion criteria (isolated ventral curvature without hypospadias or need for urethral reconstruction). Surgical correction consisted of degloving alone or degloving with Nesbit-like dorsal plication when residual curvature >20° persisted after degloving. PROMs were collected via pre-mailed validated questionnaires after puberty: Danish Prostatic Symptom Score (DAN-PSS) for LUTS, Erection Hardness Score (EHS) for erectile function, Penile Perception Score (PPS) for cosmetic perception, and items assessing decisional regret and perceived appropriateness of surgical timing. RESULTS: Curvature was corrected intraoperatively in all 24 patients. Twelve underwent degloving alone and 12 required additional dorsal plication. During long-term follow-up (median 14.2 years), one patient (4%) underwent re-operation for residual curvature, and three (13%) underwent cosmetic revisions; two (8%) underwent cystoscopy for flow concerns. 71% returned PROMs at a median age of 16.2 years. LUTS were uncommon, with low bother scores. Erectile function was favorable: 87% (13/15) reported EHS 4 and 93% (14/15) reported ejaculation. Cosmetic outcomes were favorable, with PPS dissatisfaction rates comparable to controls. Two patients reported dissatisfaction with overall appearance, and one with residual subjective curvature. No patient expressed decisional regret, and 88% felt timing of surgery was appropriate. CONCLUSION: Early surgical correction of isolated ventral penile curvature using degloving with or without dorsal plication provided durable anatomical correction and favorable long-term functional and cosmetic outcomes. These findings support early intervention as an effective approach with sustained patient-perceived benefits.

Humans↗

PubMed2026

Exercise-induced chronic adaptations and pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in patients with depression: A systematic review and exploratory meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a leading cause of disability worldwide. Although exercise has been shown to alleviate depressive symptoms, potentially by affecting the body's inflammatory response, evidence in this area remains inconsistent. This study synthesized the most recent evidence from randomized controlled trials (RCTs) on the relationship between exercise-induced chronic adaptations and pro-inflammatory cytokine levels in patients with depression. METHODS: Eligible RCTs were identified from six electronic databases. Effect sizes were pooled using mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Two independent researchers assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: The review included 21 RCTs involving 1572 participants, six of which were included in the meta-analysis. No evidence of efficacy was observed for the chronic effects of exercise on the levels of the pro-inflammatory cytokines interleukin-1-beta (IL-1β) (MD = -0.01, 95% CI [-0.06, 0.04], p = 0.79), interleukin-6 (IL-6) (SMD = -0.30, 95% CI [-0.64, 0.04], p = 0.08), and tumor necrosis factor-alpha (TNF-α) (SMD = -0.18, 95% CI [-0.50, 0.14], p = 0.27) in patients with depression. However, the pooled results for certain markers were not robust. The certainty of evidence for each outcome was very low owing to inconsistency, indirectness, and imprecision. CONCLUSIONS: Evidence for exercise improving pro-inflammatory cytokine levels in patients with depression during the chronic phase remains exploratory and uncertain. Well-designed, adequately powered studies incorporating a broader range of immune biomarkers and dynamic multi-time-point assessments are urgently needed to determine whether exercise-induced chronic adaptations can modulate inflammatory pathways in depression.

Humans↗

PubMed2026

Enhanced risk stratification in hypertrophic cardiomyopathy through the integration of extracellular volume fraction on cardiovascular magnetic resonance.

AIMS: This study investigated the incremental prognostic value of cardiovascular magnetic resonance (CMR)-derived extracellular volume fraction (ECV), a marker of diffuse interstitial fibrosis, beyond late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analysed 990 consecutive HCM patients (median age 58 years, male 68.3%) who underwent CMR between 2012 and 2024. LGE and global ECV were quantified, and their associations with the primary endpoint of HCM-related events-a composite of sudden cardiac death (SCD) events, heart failure (HF) events, and HCM-related death-were assessed. During a median follow-up of 3.2 years, 64 (6.5%) patients experienced the primary endpoint. While LGE (median 7.1%, IQR 2.3-16.9%) and ECV (median 29.0%, IQR 26.6-32.0%) were moderately correlated (R = 0.604, P < 0.001), both were significantly associated with increased risk of the primary endpoint and individual outcomes of SCD and HF events, and optimal cutoffs were determined as LGE ≥ 27% and ECV ≥ 35%. Patients with ECV ≥ 35% had more symptoms, a more severe phenotype with greater systolic and diastolic dysfunction, and more pathogenic gene variants. Notably, ECV remained a significant predictor of the primary endpoint (adjusted HR 1.08, 95% CI 1.02-1.15, per 1%) after adjustment for key disease variables, including left ventricular ejection fraction and LGE. Elevated ECV effectively identified high-risk individuals even among lower-risk subgroups, including those with low LGE burden. CONCLUSION: Increased ECV is an independent predictor of HCM-related outcomes. ECV may serve as a novel imaging biomarker to refine risk stratification in HCM patients who do not meet traditional LGE-based high-risk criteria.

Humans↗

PubMed2026

Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin.

Anhedonia is a core feature of depression that reflects reward system dysfunction. Acute inflammatory challenge has been shown to induce transient anhedonia and reward processing deficits, but its effects on distinct components of social reward processes remain poorly understood. This randomized, double-blind, placebo-controlled study evaluated anhedonia and social reward responsivity following acute inflammatory challenge. Low-dose endotoxin (0.8 ng/kg body weight; n = 18) or placebo (same volume of 0.9% saline; n = 22) was administered to female adults (ages 25-44). Anhedonia (Snaith-Hamilton Pleasure Questionnaire) and blood samples for cytokine assessment were collected pre-infusion and 2 and 4 h post-infusion. Social reward motivation (wanting to engage in a social task) was assessed at a baseline eligibility visit and 2 h post-infusion. Sensitivity to positive social cues (attentional bias toward and recognition of happy faces) was assessed pre-infusion and 2 h post-infusion. Results showed that endotoxin increased anhedonic symptoms (p = .005) and decreased social motivation by 2 h post-infusion (p = .001); within the endotoxin condition, changes in both outcomes were associated with increases in TNF-α (p's < .04). A significant condition-by-time interaction for happy-face recognition (p = .011) was driven by increased accuracy in the placebo (p = .04) but not endotoxin (p = .43) condition. Endotoxin administration did not affect attentional bias toward happy faces. Findings suggest that acute inflammatory challenge induces anhedonia and reduces social motivation, with more limited effects on sensitivity to positive social cues, highlighting specific reward-related pathways through which immune activation may contribute to inflammation-associated depression. Future work could examine whether immune-related changes in social motivation contribute to motivational deficits in depression.

Humans↗