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PubMed2026

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers.

The Magnolia study demonstrated that continuation of zoledronic acid (ZOL) beyond 2 years reduces the risk of progressive bone disease (PBD) in patients with multiple myeloma (MM). This follow-up study investigated the effects of ZOL in patients achieving very good partial response (VGPR) compared to patients who did not and whether bone turnover markers could identify patients at an increased risk of PBD following treatment cessation. Two Magnolia trial subgroups were analysed: patients with VGPR or better after 2 years of ZOL, randomized to either continued treatment or observation, and patients randomized to observation in whom serial bone markers (C-terminal cross-linked telopeptide of type I collagen [CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BAP], tartrate-resistant acid phosphatase isoform 5b [TRAcP]) were measured for up to 4 years. Continued monthly ZOL beyond 2 years significantly reduced the risk of PBD (hazard ratio 0.40; 95% confidence interval [CI] 0.16-0.92) in patients with VGPR or better (subgroup 1). After ZOL discontinuation, bone markers increased gradually. Elevated CTX (≥0.30 μg/L) and TRAcP (≥4 U/L) levels were associated with increased 6-month PBD risk (29% and 15% respectively) (subgroup 2). Continuation of ZOL beyond 2 years seems to reduce skeletal progression risk in patients achieving VGPR or better. Elevated CTX or TRAcP levels may help identify patients who could benefit from re-initiating ZOL.

Humans↗
PubMed2025

The wider erection angle in hypospadias: A neglected feature affecting surgical outcomes.

INTRODUCTION: Penile curvature often accompanies hypospadias, and numerous techniques have been described for its correction; however, in some cases, an abnormal erection angle may also be present, further exacerbating the perception of curvature. OBJECTIVE: This study investigates the significance of the erection angle in hypospadias cases and its correlation with the severity of the anomaly. STUDY DESIGN: A retrospective analysis of intraoperative photographs of hypospadias cases operated between 2019 and 2023 was performed. Erection angle was measured with a digital goniometer during a full artificial erection. Erection angles in proximal and distal hypospadias cases were analyzed and compared to data from Kinsey's subgroups representing healthy male erection angles. RESULTS: This study involved images of 68 patients, with 31 having proximal and 37 distal hypospadias. The median age of the whole group was 11 months (6-156, IQR 9). Median erection angle was 91 (63-119, IQR 11) for distal cases, whereas it was 96 (75-138, IQR 21) for proximal cases. The difference was statistically significant (p = 0.009). The erection angle distribution in our cohort, including both proximal and distal hypospadias cases, skewed toward wider angles, highlighting a distinct pattern compared to data constituted by Kinsey and Sparling. DISCUSSION: Our findings indicate that the erection angle in hypospadias is significantly wider in proximal cases, suggesting a correlation between erection angle and severity of the hypospadias. While we acknowledge the limitation of comparing our prepubertal cohort with Kinsey's adult data, the absence of evidence suggesting significant post-pubertal changes in erection angle justifies this approach. Additionally, the use of digital images for angle assessment is not a standardized technique in hypospadias evaluation; these images were initially captured for curvature assessment. Despite these limitations, our study provides novel insights into seldom mentioned association with hypospadias - a wide erection angle, emphasizing the need for further research on its implications for surgical planning and long-term outcomes. CONCLUSION: This study introduces a wider erection angle as an additional characteristic of hypospadias particularly pronounced in proximal cases. To our knowledge, this is the first focused investigation on addressing this aspect of the condition. It emphasizes the need for further research on adults with wide post-repair erection angles to explore its long-term impact on sexual function and aesthetics.

Humans↗
PubMed2026

Elastic tape as an add-on strategy to potentiate pulmonary rehabilitation outcomes in nonobese males with moderate-to-very severe COPD: A randomised clinical trial.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) improves exercise capacity but has limited effects on ventilatory constraints in severe COPD. Application of elastic tape (ET) is a potential adjunctive strategy that improves ventilatory efficiency, but its effects during PR remain un lear. This study investigated whether ET potentiates PR benefits on exercise capacity, health status, psychological symptoms, and health-related quality of life (HRQoL) in individuals with COPD. METHODS: Forty-two nonobese men with moderate-to-very severe COPD were randomised to ET or Sham groups during an 8-week PR programme. The primary outcome was endurance shuttle walk test (ESWT) time; secondary outcomes included COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ), and Hospital Anxiety and Depression Scale (HADS). RESULTS: ESWT improved by +329s in the ET group, exceeding the MCID. Greater CAT improvements (p = 0.02), and a higher proportion achieving minimal clinically important difference (MCID) (48% vs. 29%; p = 0.02) were observed in the ET group. Only ET group achieved MCIDs for depression (p = 0.003) and anxiety (p = 0.02). HRQoL improved similarly in both groups. The only outcome with a significant time × group interaction was HADS-D (p = 0.001), improved by ET. Only This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Ethics Committee for Analysis of Research Projects (CAPPesq) of School of Medicine of the University of São Paulo - Hospital das Clínicas (approval 55 617 321.20000.0068). All adult participants provided written informed consent to participate in this study. Clinical Trial Registration number NCT05939999 (https://clinicaltrials.gov), registered on October 26th, 2025.ET group presented moderate-to-large effect sizes for ESWT (d = 0.89), HADS-A (d = 0.51) and HADS-D (d = 1.02). CONCLUSIONS: ET potentiates PR benefits on exercise capacity, health status, and psychological symptoms in individuals with moderate-to-very severe COPD.

Humans↗
PubMed2026

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5 years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult↗
PubMed2026

Pegcetacoplan Delivers Real-World Therapeutic Benefits and Reduces Disease Burden for Patients With Paroxysmal Nocturnal Haemoglobinuria: A Systematic Literature Review of Pegcetacoplan Real-World Clinical and Patient-Reported Outcomes.

AIMS: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired, non-malignant haematological disorder that, if left untreated, can lead to significant morbidity. This systematic literature review (SLR) summarized real-world evidence (RWE) for pegcetacoplan, a complement 3/3b inhibitor (C3i) available since 2021. METHODS: The SLR (PROSPERO-CRD420251043506) followed 2020 PRISMA guidelines and included RW studies of pegcetacoplan (n > 1 pts.; English; to April 2025) in adults (age ≥ 18 years) with PNH. RESULTS: Of 409 identified records, 39 qualified, representing 12 distinct studies. Six studies (n = 4-39) reported median haemoglobin (Hb) with baseline 8.1-9.6 g/dL. Ending median Hb and maximum pegcetacoplan durations were: 12.0 g/dL at 12 months, 11.1-12.1 g/dL at 6 months (3 studies), and 11.1 g/dL at 3 months (1 study). In 4 other studies (n = 48-70), ending mean Hb (maximum pegcetacoplan duration) was: 11.3 g/dL (7.2 months), 11.5 g/dL (6.6 months), 11.5 g/dL (5.9 months), and 11.58 g/dL (3 months). Six studies reported reduced absolute reticulocyte count (ARC; n = 4-39) from baseline median 155-301 × 109/L to median 56-106 × 109/L from 14 days of pegcetacoplan, maintained to maximum pegcetacoplan of 1-12 months. Three studies reported lactate dehydrogenase (LDH; n = 4-62); all showed reductions from baseline median 543.0 to 161.7 U/L after 3 months, and baseline median 299.5-316.0 U/L to 193.5-187.0 U/L after 6 months of pegcetacoplan. In complement 5 inhibitor-naïve, LDH reduced from 977.8 to 358.9 U/L after 8.4 months, and 503.6 to 292.5 U/L in C5i-experienced after 7.2 months. Three studies (n = 4-63) reported reduced LDH from above the upper limit of normal levels. Six studies (n = 23-70) reported reduced red blood cell transfusions (RBCt) after maximum pegcetacoplan durations of up to 12 months, and median durations of 3.0 and 10.2 months. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scores in 1 study increased from baseline (mean 28.4) to 38.6 at 3 months, 36.3 at 6 months, and 34.9 at 9 months of pegcetacoplan treatment. Two studies reported FACIT-Fatigue scores of 34.6-40.1 with pegcetacoplan for ≥ 1 month. EQ-5D mean utility scores (0.85-0.94) in 2 studies were comparable to population normative values. On the Short-Form 36 Health Survey, mental and physical component scores were slightly lower than US normative values. CONCLUSIONS: RWE indicates pegcetacoplan is associated with improved haematological outcomes, reduced RBCt dependence and fatigue, and enhanced HRQoL. These findings from real-world studies with diverse cohorts support generalizability and are broadly comparable with clinical trial evidence.

Humans↗
PubMed2026

Unraveling the Clinical Spectrum of DNASE1L3 Deficiency: Insights from Case Series and Systematic Literature Review.

BACKGROUND: DNASE1L3 deficiency is a rare monogenic cause of lupus and lupus-like autoimmunity resulting from impaired extracellular DNA clearance and sustained immune activation. Although most reported patients present with early-onset systemic lupus erythematosus (SLE), emerging evidence suggests broader phenotypic variability, including vasculitic and overlap manifestations. Whether these presentations represent distinct clinical entities or a continuum of DNASE1L3-associated immune dysregulation remains unclear. We aimed to define the clinical spectrum of DNASE1L3 deficiency and examine the relationship between recurrent pathogenic variants and disease severity. METHODS: We conducted a combined pediatric case series and systematic literature review. Four children with genetically confirmed biallelic DNASE1L3 variants followed at a tertiary pediatric rheumatology centre were retrospectively analysed for clinical, immunological, genetic, treatment, and outcome data. In parallel, a systematic search of PubMed/MEDLINE, Scopus, and Web of Science identified previously reported patients with confirmed biallelic pathogenic or likely pathogenic DNASE1L3 variants and extractable patient-level clinical data. To facilitate cross-case comparison, we applied an exploratory three-tier descriptive framework reflecting increasing disease severity: vasculitic or organ-limited disease (G1), systemic lupus or overlap phenotypes without irreversible organ damage (G2), and severe systemic organ-damaging disease (G3). The assigned grades were descriptive rather than permanent categories, as some patients may meet the criteria for a higher grade if broader systemic manifestations or irreversible organ damage develop during follow-up. FINDINGS: Fifteen reports provided extractable patient-level data, corresponding to 45 unique previously reported patients after accounting for known or probable overlapping reports. Combined with four patients from our centre, the analysis included 49 genetically confirmed individuals. SLE-dominant disease was the most frequent phenotype (27 [60%] of 45), followed by hypocomplementaemic urticarial vasculitis/HUVS-dominant disease (10 [22.2%]) and overlap phenotypes (8 [17.8%]). Renal involvement was reported in 30 (66.7%) of 45 patients, and disease onset occurred by age 3 years in 20 (44.4%). Persistent hypocomplementemia affecting C3 and C4 was frequently reported across the spectrum. Recurrent DNASE1L3 variants were observed across multiple phenotypic and severity grades. Variants such as p.Asn191Ser and p.Thr97Ilefs*2 occurred in patients spanning organ-limited vasculitic disease, lupus overlap phenotypes, and severe multisystem lupus with major organ involvement. CONCLUSION: DNASE1L3 deficiency was associated with a broad clinical spectrum of immune-mediated disease rather than a single clinicopathological entity. The occurrence of identical pathogenic variants across distinct phenotypic and severity states argues against a simple genotype-phenotype model and suggests that additional modifiers influence disease expression.

Humans↗
PubMed2026

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans↗
PubMed2025

Prospective Longitudinal Associations Between Adverse Childhood Experiences and Adult Mental Health Outcomes: Systematic Review and Meta-Analysis.

Research suggests a strong, dose-response relationship between adverse childhood experiences (ACEs) and poor adult mental health outcomes. This systematic review and meta-analysis aimed to systematically investigate the existence and strength of prospective associations between ACEs and adult mental health outcomes: anxiety, depression, psychotic-like experiences, post-traumatic stress disorder (PTSD), self-harm, and suicidality. We searched 12 electronic databases for publications after 1990. A narrative synthesis of included studies and random-effects meta-analyses with moderation were completed for all outcomes, excluding self-harm. In total, 62 studies from 15 countries were included. Most studies were from the United States; 95% of publications (N = 59) came from high-income countries (HICs) and 5% (N = 3) from upper-middle-income countries. Pooled associations between ACEs and adult mental illness were strongest for PTSD (OR = 2.26; 95% CI [1.75, 2.77]), followed by anxiety (OR = 1.78; 95% CI [1.45, 2.11]), depression (OR = 1.61; 95% CI [1.45, 1.76]), psychotic-like experiences (OR = 1.34; 95% CI [1.13, 1.54]), and suicidality (OR = 1.28; 95% CI [1.13, 1.43]). Moderation analyses suggested ACEs with a violence or maltreatment component were significant risk factors for adult depression compared to household ACEs, and that study location was a significant moderator in the depression, anxiety, and PTSD models. Further moderation effects will be discussed. Findings confirm ACEs are a significant risk factor for mental ill-health in adulthood. Our review highlights the urgent need for research exploring associations between ACEs measured in childhood and adult mental illness outside of HIC settings.

Humans↗
PubMed2026

Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.

STUDY OBJECTIVES: To evaluate the effect of daridorexant on nighttime respiratory function and sleep in adults with severe obstructive sleep apnea (OSA) without insomnia. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, two-period, crossover trial was conducted at a single sleep center in 16 adults (≥18 years) with severe OSA without insomnia. In each period, daridorexant 50 mg or placebo was administered every evening for 5 days. Primary and secondary endpoints were the treatment differences (daridorexant-placebo) for apnea/hypopnea index (AHI) and oxygen saturation (SpO2) during total sleep time (TST), respectively, after last dosing. A mean increase in AHI ≥10 events/h and mean decrease in nocturnal SpO2 ≤-2% were the minimum changes considered to be clinically meaningful negative effects. Other endpoints included TST, latency to persistent sleep (LPS), and wake after sleep onset (WASO). RESULTS: Mean baseline AHI was 51.2 events/h (range 30.8, 82.2) and mean SpO2 during TST was 92.1% (range 88.5, 94.3). No clinically meaningful effect of daridorexant on AHI or SpO2 during TST was detected. Treatment differences were -3.7 events/h (one-sided 95% CI ≤ +4.2) and - 0.12 % (one-sided 95% CI ≥ -0.6), respectively. Compared with placebo, daridorexant increased TST by 32.5 min (90% CI: 6.9, 58.2), associated with shorter LPS (-10.3 min [90% CI: -20.6, -0.02]) and a trend towards reduced WASO (-15.2 min [-31.2, 0.9]). Four adverse events were reported (daridorexant n = 3; placebo n = 1), all of mild intensity and none related to respiratory function. CONCLUSION: Short-term treatment with daridorexant does not impair sleep-disordered breathing and may improve sleep in patients with severe OSA. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05458193, NCT05458193. Statement of Significance Obstructive sleep apnea (OSA) is highly prevalent and associated, in 30%-50% of cases, with insomnia-related symptoms, yet the safety of insomnia medications in OSA remains unclear. Daridorexant, a dual orexin receptor antagonist for the treatment of adults with insomnia disorder, previously showed no negative effect on sleep-disordered breathing in participants with mild/moderate OSA. This randomized, double-blind, placebo-controlled, crossover trial evaluates daridorexant 50 mg (maximum therapeutic dose) in participants with severe OSA without insomnia. Repeated dosing (5 nights) did not impair nighttime respiratory function, as assessed by apnea/hypopnea index and nocturnal oxygen saturation. Moreover, improvements in sleep characteristics were observed with daridorexant, extending evidence that daridorexant 50 mg is safe and well-tolerated and may improve sleep in adults with severe OSA.

Humans↗
PubMed2026

Smoke-Free Home Intervention in Permanent Supportive Housing: A Cluster Randomized Clinical Trial.

IMPORTANCE: Chronic diseases related to tobacco use and secondhand smoke exposure are the leading causes of death among formerly homeless adults living in permanent supportive housing (PSH) in the US. OBJECTIVE: To evaluate the efficacy of a brief, smoke-free home intervention in promoting voluntary smoke-free home adoption among PSH residents. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial, data collection occurred from January 11, 2022, to March 31, 2025. Participants were residents aged 18 years or older who smoked cigarettes at home in 40 multiunit PSH sites in the San Francisco Bay area, randomized to intervention or waiting list control clusters, and housing staff who worked at the study sites. INTERVENTION: Residents in intervention sites received one-on-one in-person coaching from research staff on adopting a smoke-free home; waiting list control site residents received no interventions during the study but were offered the intervention once the intervention group completed follow-up. Staff in both intervention and control sites received training on providing brief tobacco cessation coaching. MAIN OUTCOMES AND MEASURES: Primary outcomes were smoke-free home adoption for at least 90 days and 7-day carbon monoxide-verified point prevalence abstinence (PPA; expired carbon monoxide level ≤5 ppm) at 6 months. Secondary outcomes were any adoption (≥1 day) of a smoke-free home in the past 90 days among residents and changes in Smoking Knowledge, Attitudes, and Practices (S-KAP) scores among staff. RESULTS: The trial enrolled 400 residents (mean [SD] age, 54.5 [10.7] years; 251 [63.1%] male), 191 in the intervention and 209 in the control cluster. At 6 months, 13 residents (6.8%) in the intervention and 10 (4.8%) in the control group adopted a smoke-free home for at least 90 days (odds ratio [OR], 1.45; 95% CI, 0.69-3.07). Few residents achieved 7-day PPA, though more intervention residents (12 [6.3%]) achieved it compared with controls (2 [1.0%]) (OR, 6.94; 95% CI, 1.69-28.45). Intervention residents had greater odds than control residents of any smoke-free home adoption of at least 1 day (121 [63.4%] vs 77 [36.8%]; adjusted OR, 3.83 [95% CI, 2.63-5.57]). Among staff, mean (SD) S-KAP scores increased at 6 months vs baseline for beliefs (by 0.21 [0.55] points) and practices (by 0.24 [0.61] points) pertaining to providing cessation treatment. CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, the brief intervention did not result in a significant increase in smoke-free home adoption for at least 90 days, though more residents in the intervention than the control group attempted adoption for at least 1 day. These findings support the scalability of this approach to reduce smoking in PSH, but more intensive interventions may be needed to sustain intervention effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04855357.

Humans↗
PubMed2026

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult↗
PubMed2026

Understanding Suicide through Coroners' Narratives: implications for primary care from a mixed‑methods study of 157 Coroners' reports.

Suicide is a major public health concern, and general practice is often a recent point of contact before death. While mental illness is well recognised, the broader social and contextual factors influencing suicide risk remain under-reported in primary care and epidemiological research Aim To describe the demographic, clinical, and psychosocial characteristics of individuals who died by suicide, integrating coronial quantitative data with qualitative narrative accounts to identify implications for primary/ secondary care and public health. Design and setting Explanatory sequential mixed‑methods study of 157 consecutive deaths by suicide recorded by coroners (2018-19) across five English local authorities. Method Demographic, clinical, and social data were extracted from coroners' records and summarised descriptively. Narrative case summaries were coded and analysed thematically to identify contextual, relational, and service factors preceding death. Results Of 157 individuals: 79% were male; 65% lived in the most deprived IMD quintile; 85% had a diagnosed mental health condition; 62% had a long‑term physical illness; 41% had a previous suicide attempt. About half consulted a GP in the preceding three months; mental health featured in about half of those consultations. Common stressors were relationship breakdown (37.2%), housing instability (22.1%), and work pressures (18.2%). Seven interlinked themes were identified: Mental health; Alcohol/Substance use, Physical health; Social connectedness; Life course trauma, Socioeconomic and Structural Vulnerability; Healthcare access. Service transitions were key vulnerability points Conclusion Coroners' records offer important insights into the complex circumstances preceding suicide and highlight opportunities for GPs to recognise intersectional complexity and support integrated, cross-sector suicide prevention approaches.

General Practice↗
PubMed2026

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the subset of individuals with major depressive disorder for whom depression has been labeled as "treatment resistant". Understanding the impact of this diagnostic label on illness identity and attitudes towards new therapies is important as genomic technology expands and rates of depression increase. We sought to explore perceptions and attitudes towards pharmacogenomic testing among individuals who had received a diagnosis of treatment resistant depression. We conducted a qualitative study with a constructivist orientation. Participants were recruited from a larger genomic research study and interviewed by phone or video call. We took an inductive approach to coding guided by reflexive thematic analysis. Themes were then organized into a relational framework following principles of interpretive description. Twelve individuals were interviewed. Key themes included internalized acceptance/hopelessness, and external validation/frustration, which were cyclically interconnected. These themes were situated within a larger framework illustrating the ways that illness identity and modifying factors such as relief of guilt, social support, pharmacogenomic testing and depressive symptoms can either facilitate acceptance and validation or contribute to feelings of hopelessness and frustration. Though participants expressed some skepticism around its effectiveness, pharmacogenomic testing may contribute to the shift towards acceptance and validation by legitimizing individuals' experiences with lack of treatment response. Genetic counselors and other healthcare providers should be aware of the complex balance between hope and frustration underlying conversations around pharmacogenomic testing, and factors that are more likely to foster self-acceptance.

Humans↗
PubMed2026

[Specificity in the management of gynecological cancers in French overseas departments].

The five overseas departments and regions (DROMs) are Guadeloupe, French Guiana, Reunion, Martinique and Mayotte. In the DROMs, certain areas show significantly higher incidence rates for certain cancers, particularly gynaecological cancers; overall, the 5-year net standardised survival rates are lower than those observed in mainland France. Here, we present an overview of the management of gynaecological cancers in each DROM.

Humans↗
PubMed2026

Peptide molecular lock-engineered nanobodies enable an oriented dual-modal immunoassay for reliable detection of Cronobacter sakazakii.

Conventional nanobody ELISAs for trace Cronobacter sakazakii in powdered infant formula suffer from random orientation and low signal output. We developed an oriented dual-modal immunoassay that combines site-specific biotinylation via a C-terminal AviTag and a peptide molecular lock, enabling controlled surface orientation while preserving nanobody structural integrity. This strategy was further integrated with phage-displayed nanobodies for multivalent amplification and both fluorescent and colorimetric readouts. The assay exhibited a broad linear range of 103-106 CFU/mL, with limits of detection (LODs) of 6.70 × 102 CFU/mL for fluorescence and 1.55 × 103 CFU/mL for colorimetry, showing improved sensitivity compared with the conventional passive adsorption-based Nb-ELISA evaluated in this study. XGBoost-based multimodal fusion improved quantitative accuracy, and SHAP analysis elucidated modality contributions. In spiked powdered infant formula samples, recoveries ranged from 92.1% to 118% with coefficients of variation below 5.98%, confirming acceptable matrix tolerance and analytical reliability.

Cronobacter sakazakii↗
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 &#xb1; 2.58 vs. 0.61 &#xb1; 1.52; p = .040). Significant inverse correlations were identified between T/S ratio and depressive episode count (&#x3c1; = -0.220, p = .028) and total mood episodes (&#x3c1; = -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↗