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Inborn errors of immunity are rare, genetically heterogeneous disorders requiring coordinated clinical, laboratory, and genetic evaluation over time. Data are often fragmented across records, laboratory systems, and genomic reports, limiting longitudinal analysis and coordinated care, particularly in the Middle East and North Africa, where structured rare disease data infrastructures remain limited. To develop a Research Electronic Data Capture-based data management framework for inborn errors of immunity and demonstrate its use in a prospective multi-site setting. A Research Electronic Data Capture-based framework was developed at the College of Medicine and Health Sciences, United Arab Emirates University. Modular instruments captured consent, demographics, biospecimen processing, laboratory workflows, and genetic findings within a longitudinal structure. Data dictionaries, validation rules, and conditional logic ensured data quality. The framework was deployed across participating sites for prospective data collection. The framework enabled integrated longitudinal documentation of enrollment, biospecimens, and genetic testing. It was implemented across two clinical sites and used to enroll patients with suspected or confirmed inborn errors of immunity. The platform supported standardized cross-site data capture and monitoring of genetic findings, including automated flagging of variants of uncertain significance. This study demonstrates the development and early multi-site implementation of a Research Electronic Data Capture-based framework for inborn errors of immunity. By enabling standardized integration of clinical, laboratory, and genetic data, the platform supports data quality, cross-site collaboration, and tracking of evolving diagnoses. It provides a scalable foundation for rare disease research and may support improved clinical decision-making.

Calmodulinopathy is a rare CALM-related hereditary channelopathy presenting with long QT syndrome (LQTS), less commonly with catecholaminergic polymorphic ventricular tachycardia (CPVT) or LQTS/CPVT overlap. It carries high mortality and limited data from Chinese population. We reviewed two Chinese children with CALM2 mutation-related LQTS/CPVT overlap. Clinical data, genetic findings, and treatments were collected; outcomes were obtained via telephone follow-up. A systematic literature review was also performed. Case 1 was a 13-year-old girl with seven exercise-induced syncopal episodes. Sinus rhythm QTc 0.55 s, with bidirectional/polymorphic premature ventricular contractions, and ventricular tachycardia during exercise. A de novo CALM2 p.E140Q mutation was found. She remained event-free on propranolol and propafenone for two years. Case 2 was a 15-year-old boy with onset at 4 years. He experienced > 10 syncopal episodes triggered by recurrent exercise or emotional stress. Initial Holter monitoring revealed sinus bradycardia with a mean heart rate of 70 bpm and a maximum QTc of 0.51 s. A de novo CALM2 p.N98S mutation was found. Despite treatment with propranolol plus mexiletine, syncopal episodes continued, with the QTc interval further prolonged to 0.62 s. The p.E140Q variant is novel, whereas p.N98S has been previously reported. Literature suggests that β-blockers combined with Class Ic drugs may be more effective, and implantable cardioverter defibrillator (ICD) implantation should be considered in cases who respond poorly to medical therapy or survivors of aborted cardiac arrest. Patients who experience recurrent syncope coexisting with significant sinus bradycardia may have more severe phenotypes with higher risk of malignant arrhythmias, warranting earlier or more aggressive evaluation for device therapy. Genetic testing is recommended for suspected pediatric channelopathies with phenotype-guided individualized treatment.

Breast cancer remains the most prevalent cancer among women in Jordan. Although national early detection efforts have expanded over recent years, opportunities remain to further improve timely diagnosis and screening uptake. Healthcare providers (HCPs) play a central role in influencing screening uptake, and strengthening their knowledge, attitudes, and practices (KAP) can support program effectiveness. To assess KAP of HCPs related to breast cancer early detection in Jordan and identify factors influencing their translation into practice. A nationally stratified cross-sectional study was conducted among 544 HCPs between January and June 2025 using a structured, interviewer-administered questionnaire. Composite scores for KAP were calculated and further dichotomized for multivariable logistic regression to identify predictors of KAP domains. The mean knowledge score was 57.0%, with high knowledge of signs and symptoms (78.1%) but substantially lower knowledge of screening recommendations, including clinical breast examination (27.4%) and mammography guidelines (28.6%). Attitudes were generally favorable (53.5%), with strong professional orientation (82.2%) and high perceived patient-level barriers (77.3%). Mean practice score was reflecting moderate implementation (49.0%). While most providers reported encouraging screening (98.9%) and appropriate case management (91.9%), correct screening practices were limited, including initiation age (30.3%) and screening intervals (20.8%). Female providers demonstrated higher odds of adequate knowledge (OR 1.78) and optimal practice (OR 1.93), while nurses had significantly lower knowledge (OR 0.46) and practice (OR 0.17). Regional disparities were observed, with lower knowledge but higher practice in southern regions. The findings indicate opportunities to better align provider knowledge, attitudes, and routine practice, particularly in screening-related competencies. Strengthening role-specific training, integrating guidelines into routine care, and addressing implementation and service-delivery factors are essential to improve early detection outcomes in Jordan and similar settings.

The incidence of tumour-positive surgical resection margins (TPRMs) after breast-conserving surgery (BCS) remains high, ranging from 10 to 40%. A TPRM, defined as breast cancer cells at the edge of the resected specimen at pathological evaluation, implies residual tumour and necessitates re-resection or boost radiation. To prevent these additional treatments, intraoperative near-infrared (NIR) fluorescence imaging with the topically applied, fluorescently quenched, cathepsin-activatable imaging agent AKRO-6qcICG might be used to detect residual cancer in the surgical cavity and guide additional resection during BCS. Cathepsins are proteolytic enzymes that are upregulated by breast cancer (associated) cells and therefore are suitable targets for tumour imaging. Ex vivo validation studies have shown that topically applied AKRO-6qcICG allows for clear breast cancer visualization and the detection of TPRMs. The proposed phase I/II study in healthy volunteers and breast cancer patients will assess the local and systemic safety of a single, topical dose of AKRO-6qcICG and its feasibility for intraoperative margin assessment during BCS. A total of six healthy volunteers (Part A) and 16 breast cancer patients (Part B) will be enrolled. In Part A, AKRO-6qcICG will be topically applied randomly on drawn blisters in two doses as will the vehicle compound, and one blister will be untreated functioning as a negative control. Physician and subject will remain blinded. In Part B, a single dose of AKRO-6qcICG will be topically applied in the surgical cavity. The primary objective is, with the occurrence of treatment-emergent (serious) adverse events as primary outcome measure. Secondary outcome measures include local and systemic tolerability parameters such as wound healing, numeric rating scales of pain and pruritus, vital signs, electrocardiogram parameters, clinical laboratory tests and pharmacokinetic parameters. Among the exploratory outcome measures are the diagnostic accuracy of the imaging agent to detect residual tumour in the surgical cavity and the tumour-to-background ratio of the fluorescent signal. This protocol has been approved by the Medical Ethical Committee Leiden-Den Haag- Delft (METC- LDD). The protocol is registered at EU Clinical Trials Register number 2025-523166-24-00. The results of this study will be reported through peer- reviewed publications and conference presentations. https://ctis.eu/trial/2025-523166-24-00?from=search.

Acute exacerbations of pediatric allergic rhinitis (AR) are difficult to anticipate, and individualized risk tools integrating clinical and environmental data are lacking. We developed an interpretable machine-learning model to predict 90-day AR exacerbation risk in children and conducted a preliminary transportability assessment in an independent cohort, following TRIPOD&#x2009;+&#x2009;AI guidelines. A development cohort (n&#x2009;=&#x2009;2,000) was assembled by linking NHANES (2005-2006 and 2011-2018 cycles) with EPA Air Quality System and NOAA meteorological data; an independent external cohort (n&#x2009;=&#x2009;50) was recruited at Wuhan Children's Hospital (2023-2024). Clinical predictors [Total Nasal Symptom Score (TNSS), total IgE, eosinophils, comorbidities] and environmental exposures (same-day and 0-7-day-lag PM2.5, PM10, O3, NO2, temperature, humidity) were analyzed. L2-regularized logistic regression (LR) was prespecified as the primary model and benchmarked against random forest, XGBoost, LightGBM, and SVM using nested 5-fold cross-validation and multiple imputation (m&#x2009;=&#x2009;5). Discrimination, calibration, decision-curve analysis, and SHAP interpretability were evaluated. Exacerbation occurred in 34.4% (687/2,000) of the development cohort and 36.0% (18/50) of the external cohort. The primary LR model achieved an internal AUC of 0.81 (95% CI: 0.74-0.88) and an external AUC of 0.71 (95% CI: 0.50-0.92); the wide confidence interval reflects the limited precision of the small validation sample. Baseline TNSS, same-day PM2.5, and total IgE were the most influential predictors across feature-selection and SHAP analyses. Children exposed to PM2.5&#x2009;>&#x2009;75 &#x3bc;g/m3 had approximately five-fold higher exacerbation odds than those exposed to <35 &#x3bc;g/m3 (OR&#x2009;=&#x2009;5.08, 95% CI: 3.45-7.47). A sensitivity model excluding TNSS retained moderate discrimination (external AUC 0.66, 95% CI: 0.49-0.83), supporting the independent contribution of environmental and immunologic factors. Decision-curve analysis showed positive net benefit across threshold probabilities of 0.10-0.35. An interpretable LR model integrating baseline symptom burden with ambient PM2.5 exposure demonstrated promising predictive performance for pediatric AR exacerbation. However, the small external cohort (n&#x2009;=&#x2009;50) yielded wide confidence intervals, and findings should be regarded as preliminary transportability evidence rather than definitive external validity. Larger multicenter prospective studies with site-specific recalibration are required before clinical implementation.

TP53 mutations are strongly associated with resistance to venetoclax in acute myeloid leukemia (AML) and represent a major challenge in current treatment strategies. Importantly, different TP53 mutants exhibit substantial functional heterogeneity, leading to distinct resistance phenotypes that are not adequately captured by conventional variant allele frequency (VAF)-based stratification. Emerging evidence suggests that TP53 mutations promote venetoclax resistance through multiple mechanisms, including apoptotic dysregulation, metabolic reprogramming, enhancement of leukemic stem cell properties, and epigenetic remodeling, with the relative contribution of each pathway varying among mutant types. This review systematically summarizes recent advances in the molecular mechanisms underlying TP53-mediated venetoclax resistance, with a particular focus on how mutant-specific functional differences shape therapeutic responses. Unlike previous broad reviews of TP53-mutated AML, this article specifically addresses venetoclax resistance as a clinically critical therapeutic challenge. We further discuss the limitations of current VAF-based classification systems and propose a practical framework that integrates mutant-specific resistance biology with precision therapeutic strategies.

Infection-induced bone defects are a challenging disease in orthopedic clinical practice. Traditional treatments face core problems such as limited bone sources, high risk of antibiotic systemic application-induced resistance, and difficulties in synchronizing infection control and bone regeneration. 3D printing technology, with its advantages of personalized customization, precise structural regulation, and compatibility and adaptability of multiple materials, has become the core preparation method for repair scaffolds for infection-induced bone defects. Constructing an integrated scaffold with three functions - antibacterial, osteogenic, and vascularization - that is temporally coupled and spatially stratified, and oriented towards clinical translation is a key direction to break through the treatment bottleneck of this disease. This review differs from existing reviews that only focus solely on antibacterial materials, 3D printing scaffold preparation, or bone regeneration mechanisms. It is the first to systematically construct a three-function collaborative framework of "infection control - angiogenesis - bone regeneration" with temporal coupling and spatial stratification. It deeply analyzes the adaptability of different material systems in the infection microenvironment, the logic of selecting anti-infection strategies, and the design rules of biomimetic structures. It comprehensively summarizes the key bottlenecks in clinical translation, real clinical case evidence, and industrialization paths, and clarifies the time-controlled regulatory mechanism and clinical translation targeting path of the three-function collaboration. 3D printed anti-infection bone scaffolds can achieve synchronous repair of infection clearance, bone regeneration, and angiogenesis. The three-function temporal and spatial collaborative design and integrated research for clinical translation are the core development directions in this field, providing theoretical support and practical guidance for the precise treatment of infection-induced bone defects.

Dental implants are a predictable treatment for tooth loss; however, infections extending into deep fascial spaces are rare and potentially life-threatening. This case highlights the importance of early diagnosis and multidisciplinary management of an implant-related submental abscess in a diabetic patient. A 33-year-old female with type 2 diabetes mellitus (HbA1c: 8.1%) presented with submental swelling five months after anterior mandibular implant placement. Clinical examination revealed erythema, tenderness, and purulent discharge around implant #41. Cone-beam computed tomography (CBCT) showed complete resorption of the lingual cortical plate and a radiolucent tract extending into the submental space, indicating abscess formation. The implant system used was Megagen AnyOne&#xae; (4.0&#xd7;10 mm). The patient was treated with amoxicillin-clavulanic acid 1 g every 12 hours for 5 days, and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control, followed by extraoral drainage with Penrose drain placement. The infected implant was removed surgically under local anesthesia, followed by thorough debridement of the cavity and local irrigation with rifamycin SV solution (250 mg/3 mL). The postoperative course was uneventful, and CBCT at the 3-month follow-up confirmed complete bone healing without recurrence. This case suggests that implant-related submental infections may result from a combination of surgical errors, anatomical factors such as lingual plate perforation, and systemic risk factors, including diabetes mellitus. CBCT plays a vital role in detecting cortical perforation and deep-space extension. Careful preoperative imaging, proper implant angulation, and timely combined medical-surgical management are critical for preventing serious complications and achieving favorable outcomes.

Esophageal cancer is commonly diagnosed at a locoregional stage and is typically treated with neoadjuvant chemoradiotherapy followed by esophagectomy. Despite advances in perioperative care, esophagectomy remains associated with substantial morbidity and mortality. Frailty assessment has been proposed as a tool for preoperative risk stratification, but its predictive value in patients undergoing esophagectomy remains uncertain. We conducted a retrospective cohort study of patients who underwent curative-intent esophagectomy between January 2012 and December 2024. The predictive performance of the 5-item Modified Frailty Index (mFI-5) was compared with the American Society of Anesthesiologists Physical Status (ASA-PS) classification. Receiver operating characteristic (ROC) curve analysis and exploratory multivariable logistic regression were performed to evaluate the predictive performance of mFI-5 and ASA-PS classification for 30-day mortality. A total of 123 patients underwent esophagectomy, with a 30-day mortality rate of 9.8%. Patients who died had significantly longer intensive care unit and hospital stays and a higher incidence of severe postoperative complications. ASA-PS demonstrated better discrimination than mFI-5 for predicting 30-day mortality (AUC 0.67 vs. 0.55), although the discriminatory performance of both tools remained limited. In the exploratory multivariable analysis, ASA-PS classification was independently associated with 30-day mortality, whereas mFI-5 was not. Although ASA-PS classification was independently associated with 30-day mortality, both ASA-PS and mFI-5 demonstrated limited predictive performance following esophagectomy. These findings suggest that mFI-5 and ASA-PS alone provide limited discrimination for predicting 30-day mortality and support the development of esophagectomy-specific risk prediction models incorporating objective clinical, physiological, functional, and procedure-specific variables.

Social anxiety disorder (SAD) is a common and often persistent mental health condition that typically emerges during adolescence and is associated with marked functional impairment. Although cognitive-behavioral therapy and selective serotonin reuptake inhibitors remain first-line treatments, many individuals experience incomplete response, poor tolerability, stigma-related concerns, or limited access to care. Against this background, exercise has attracted increasing interest as a low-cost, accessible, and scalable adjunctive intervention, although adherence and accessibility may vary across populations. In this mini-review, we synthesize current evidence on the role of physical activity and structured exercise in the management of SAD. Available findings suggest that higher levels of physical activity are generally associated with lower social anxiety symptoms, while emerging intervention studies indicate that aerobic exercise, climbing, and group-based exercise programs may confer psychological benefit. Exercise may complement mainstream therapies through partially overlapping yet distinct pathways, including enhancement of self-efficacy, resilience, body image, and social engagement, as well as modulation of cognitive bias, neuroplasticity, and stress-related physiological processes. Potential applications in adolescents, individuals with autism spectrum disorder and comorbid social anxiety, and performance-related anxiety contexts also warrant attention. However, the current evidence base remains limited by small samples, heterogeneous interventions, insufficient long-term follow-up, and a lack of large randomized controlled trials in clinically diagnosed SAD, and much of the available evidence derives from non-clinical or subclinical populations. Overall, exercise should be considered a promising adjunct rather than a replacement for established treatments, and future research should prioritize mechanism-informed, precision-based, and implementation-oriented intervention models.

Thoracic aortic disease in young patients is often driven by congenital, syndromic, or heritable disorders. Risk for adverse events in these patients is not fully captured by aortic diameter alone. This mini-review describes the shift in management beyond a diameter-based framework to one that also incorporates body size, somatic growth, genotype, phenotype, family history, vascular distribution, and life-style context. We synthesized evidence across key disease groups illustrating distinct limitations of diameter-only assessment, including Marfan syndrome, Loeys-Dietz syndrome, Turner syndrome, bicuspid aortic valve-associated aortopathy, non-syndromic heritable thoracic aortic disease, and vascular Ehlers-Danlos syndrome. Across these conditions, aortic size remains clinically important, but its interpretation varies substantially by underlying disease biology. In some disorders, diameter remains central but is modified by growth and phenotype; in others, indexed measures are more informative in the setting of short stature or childhood growth; and in others, diffuse arteriopathy or vascular fragility may permit dissection at relatively small diameters or without substantial antecedent enlargement. These distinctions have implications for imaging strategy, genetic evaluation, family screening, prophylactic surgical thresholds, and counseling regarding pregnancy and lifestyle. Overall, the field is moving toward a more precise model of care in which surveillance and intervention are tailored not only to anatomy, but also to the patient's biological and familial risk profile.

Febrile neutropenia (FN) is a serious and potentially life-threatening complication in children with acute myeloid leukemia (AML), particularly during induction chemotherapy. However, data from low- and middle-income countries remain limited. We conducted a retrospective study including children and adolescents with newly diagnosed AML who experienced at least one FN episode during induction therapy at Aziza Othmana Hospital, Tunis, Tunisia. Among 63 patients with AML, 55 (87.3%) experienced 82 FN episodes. No patient received antibacterial or antifungal prophylaxis. Clinically documented infections (CDI) accounted for 53.6% of episodes, fever of unknown origin for 25.7%, and microbiologically documented infections (MDI) for 20.7%. The gastrointestinal tract was the most frequent site of infection (50%), followed by the respiratory tract (31.8%). Blood cultures yielded predominantly Gram-negative bacilli and Gram-positive cocci in similar proportions. Multidrug-resistant Gram-negative bacteria were identified in five episodes. Clinical outcomes were favorable in 77 episodes (94%), with a median time to defervescence of four days. Five patients died, resulting in a FN-related mortality rate of 9%. Intensive care unit (ICU) admission and presence of sepsis/septic shock were associated with mortality in univariate analysis. FN remains a major cause of morbidity and mortality during AML induction therapy. Early recognition, prompt antimicrobial treatment, and improved access to microbiological diagnostics may improve outcomes in resource-limited settings.

Mitotane remains the cornerstone of adrenocortical carcinoma. However, its real-world safety profile is poorly defined. This study systemically evaluated mitotane-associated adverse events (AEs) and characterized multivariable patterns of serious outcomes using a combined pharmacovigilance and machine learning approach. Mitotane-related AE reports (2004-2025) were extracted from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses were performed via four algorithms. Detected signals were categorized using a clinical priority scoring system based on signal strength, mortality, seriousness, and existing evidence. Time-to-onset was evaluated utilizing Kaplan-Meier methods. Elastic net logistic regression and Extreme Gradient Boosting (XGBoost) models characterized features associated with serious outcomes, with performance assessed by the area under the receiver operating characteristic curve (AUROC). Among 870 identified reports, 45.7% involved serious outcomes. We detected 75 safety signals, predominantly involving gastrointestinal, neurological, endocrine, and metabolic systems. Notably, 21 signals (28.0%) were assigned moderate clinical priority, with adrenal insufficiency as the highest-priority signal. Time-to-onset analysis showed that endocrine AEs had a significantly longer onset time than non-endocrine AEs. Both models demonstrated consistent characterization of multivariable patterns associated with serious outcomes (elastic net AUROC&#xa0;=&#xa0;0.830, XGBoost AUROC&#xa0;=&#xa0;0.869). Key contributors to serious outcomes included reporting country, medical event designation, organ system involvement, and medication complexity. This large-scale study provides a real-world safety assessment of mitotane. Integrating signal detection, clinical prioritization, and interpretable machine learning reveals multivariable patterns underlying serious AEs. These findings support a risk-stratified monitoring approach to enhance the clinical safety of mitotane therapy.

Endometriosis is a chronic disease associated with pain, fertility difficulties, and reduced quality of life (QoL). Beyond clinical symptoms, health-related and lifestyle behaviors may influence the long-term impact of the disease. This study aimed to assess multiple QoL dimensions in women with endometriosis and examine their associations with disease-related symptoms, body mass index (BMI), and lifestyle characteristics. A cross-sectional online survey was completed by 153 women aged&#x2009;&#x2265;&#x2009;18 years with self-reported endometriosis. Data included sociodemographic characteristics, body weight, physical activity, diet, smoking, and digestive symptoms, including painful defecation. The Endometriosis Impact Questionnaire evaluated physical, psychological, social, sexual and intimate, fertility, educational, employment and financial, and lifestyle QoL across three recall periods. Non-parametric tests and multivariate linear regression models assessed group differences and factors associated with QoL dimensions and overall impact. The greatest burden was observed in fertility, physical, and psychological dimensions, particularly during the previous 12 months. Body-weight change since symptom onset was associated with poorer outcomes across all QoL domains. BMI showed coding-dependent associations: continuous BMI predicted greater physical and psychological impact, whereas BMI&#x2009;&#x2265;&#x2009;25.0&#x2005;kg/m2 was linked to lower impact in physical (&#x3b2;=-0.42; p&#x2009;=&#x2009;0.005), sexual and intimate (&#x3b2;=-0.31; p&#x2009;=&#x2009;0.044), and employment and financial QoL (&#x3b2;=-0.31; p&#x2009;=&#x2009;0.049). Painful defecation was associated with greater psychological and sexual and intimate impact and higher overall impact. Smoking was associated with greater lifestyle impact (&#x3b2;=0.38; p&#x2009;<&#x2009;0.001) and higher overall impact (&#x3b2;=0.17; p&#x2009;=&#x2009;0.042). Dietary supplement use was associated with lower fertility impact (&#x3b2;=-0.18; p&#x2009;=&#x2009;0.049), whereas following a dietary regimen was associated with higher fertility impact (&#x3b2;=0.22; p&#x2009;=&#x2009;0.014). Endometriosis substantially affects multiple life domains, particularly fertility and physical and psychological well-being. Weight change, painful defecation, and smoking were linked to poorer QoL, while BMI demonstrated complex domain-specific associations. Integrated medical and lifestyle approaches may improve long-term disease impact.

In this exploratory case-control study, we investigated the potential associations of pregnancy-associated plasma protein-A (PAPP-A), &#x3b2;-human chorionic gonadotrophin (&#x3b2;-HCG), vascular endothelial growth factor (VEGF), and leukemia inhibitory factor (LIF) with ectopic pregnancy (EP), using logistic regression to describe unadjusted associations and receiver operating characteristic (ROC) curve analysis to characterise exploratory biomarker performance. We conducted a case-control study including 48 patients with EP and 46 patients with normal intrauterine pregnancy as controls, recruited between October 2022 and May 2024 at a single center. Logistic regression was applied to describe associations between each biomarker and EP. ROC curves were derived from these models to explore discrimination, and an exploratory threshold was identified using the Youden index. The area under the curve (AUC) for &#x3b2;-HCG and PAPP-A were the highest (0.85 and 0.84, respectively), compared with VEGF (0.73) and LIF (0.54). PAPP-A showed the strongest association among the candidate markers (OR&#x2009;=&#x2009;0.774), with an exploratory sensitivity of 0.77. VEGF had the highest specificity (0.96). The combined exploratory AUC of PAPP-A and &#x3b2;-HCG (0.89) was similar to that of PAPP-A and VEGF (0.88). This exploratory study suggests that PAPP-A may be a promising candidate biomarker for early EP detection in the context of an exploratory case-control comparison with normal intrauterine pregnancy, with performance comparable to &#x3b2;-HCG. Further prospective studies with external validation in clinically relevant populations are needed to confirm these preliminary findings and assess clinical potential.

Emaciated oncology patients present unique challenges for totally implantable venous access port (TIVAP) implantation because of limited subcutaneous tissue coverage over the anterior chest wall. Conventional subcutaneous port placement in this population may increase the risk of local complications, including skin erosion, port exposure, and pocket infection. This study aimed to evaluate the feasibility, safety, and short-term clinical outcomes of supra-pectoralis major TIVAP implantation in emaciated oncology patients. This retrospective single-center study included 188 consecutive emaciated oncology patients who underwent TIVAP implantation using the supra-pectoralis major technique at the Changshu Hospital Affiliated to Nanjing University of Chinese Medicine between January 2023 and June 2024. Emaciation was defined as a body mass index (BMI) <18.5 kg/m&#xb2; and subcutaneous fat thickness &#x2264;5 mm at the intended implantation site. All procedures were performed under ultrasound guidance, and catheter tip position was confirmed by fluoroscopy. Technical success, operative time, postoperative complications, and functional port retention during 6-12 months of follow-up were evaluated. A total of 188 patients were included. The mean age was 70.2 &#xb1; 7.8 years, and the mean BMI was 16.3 &#xb1; 1.1 kg/m&#xb2;. Technical success was achieved in all patients (100%) with a mean operative time of 24.8 &#xb1; 5.8 minutes. During follow-up, device-related complications occurred in 11 patients (5.85%), including port exposure in 2 (1.06%), pocket infection in 4 (2.13%), catheter malposition in 3 (1.60%), and fibrin sheath formation in 2 (1.06%). Four patients (2.13%) required port removal because of complications, while the remaining 184 patients (97.87%) retained a functional port until the end of follow-up or until death from underlying malignancy. During the observation period, 82 patients (43.62%) died from progression of the primary disease. In this single-center retrospective series, supra-pectoralis major implantation of TIVAPs was technically feasible in emaciated oncology patients and was associated with a high technical success rate and an acceptable short-term complication profile. These preliminary observations suggest that the technique may represent a practical implantation option in this vulnerable population.

Antibody-based therapeutics are a rapidly expanding class of treatments, with over 200 approved candidates and thousands in clinical trials. Computational pre-filtering using protein structure prediction models has the potential to reduce the cost of wet-lab screening, yet the relationship between model confidence measures and functional binding properties remains incompletely understood. Here, we evaluate whether confidence measures produced by contemporary open-source protein structure prediction models are suitable for in silico screening of nanobody-antigen interactions. We benchmark Boltz-2, Chai-1, IntFold, and AlphaFold3 using two complementary tasks: (i) ranking true nanobody-antigen binding complexes above non-binding bait pairs across 17 antigens, and (ii) detecting out-of-distribution sequences generated by alanine substitution of all complementarity-determining region residues. We further assess confidence measure sensitivity through progressive alanine mutagenesis on 13 nanobody-antigen complexes spanning the range of CDR3 lengths in our dataset and evaluate generalizability using data from a camelid immunization campaign against CD33. Boltz-2-derived confidence measures achieved the highest median performance for identifying true binders. Local confidence measures, including pLDDT and interface- or CDR-focused metrics, were most effective at detecting out-of-distribution sequences and exhibited the greatest sensitivity to mutations. No single confidence measure performed best across both tasks, and all evaluated protein structure prediction models showed limited generalization to previously unseen antigens. Our results suggest that robust in silico nanobody candidate selection should combine complementary global and local confidence measures rather than relying on a single metric. These findings provide practical guidance for integrating open-source protein structure prediction models into AI-driven nanobody discovery pipelines while highlighting the need for improved generalization across antigens.

To investigate the changes, bidirectional relationships, and moderating factors of illness perception and intrinsic capacity in older adults with COPD and Type 2 Diabetes Mellitus (T2DM) during the hospital-to-home transition. A prospective cohort study was conducted from April 2024 to September 2025, conveniently enrolling 232 older adults with COPD and T2DM from the Sixth People's Hospital of Nantong. Participants were assessed at three time points: at discharge (T0), 1&#x202f;month (T1), and 3&#x202f;months (T2) post-discharge, using the Brief Illness Perception Questionnaire (BIPQ) and a WHO framework-based intrinsic capacity assessment tool. A Random-intercept cross-lagged panel model (RI-CLPM) was used to analyze the dynamic cross-lagged relationships, a Latent growth model (LGM) was used to analyze the association of their change trajectories, and exploratory subgroup analyses were performed. (1) Trajectory analysis: Illness perception total scores showed a consistent and significant decreasing trend across the three time points (p <&#x202f;0.001), while intrinsic capacity total scores exhibited a slight but significant linear decline (p =&#x202f;0.010). (2) Dynamic associations: The RI-CLPM revealed significant bidirectional negative associations between illness perception and intrinsic capacity during the T0-to-T1 phase (&#x3b2; =&#x202f;-0.21, &#x3b2; =&#x202f;0.18, both p <&#x202f;0.05). During the T1-to-T2 phase, only intrinsic capacity was positively associated with subsequent higher negative illness perception (&#x3b2; =&#x202f;0.15, p =&#x202f;0.047). (3) Trajectory association: The parallel process LGM indicated a moderate-to-strong positive correlation between the rate of improvement in illness perception and the rate of decline in intrinsic capacity (r =&#x202f;0.32, p =&#x202f;0.008). (4) Subgroup differences: Exploratory analyses showed that COPD severity (GOLD stage 3-4) and impaired baseline vitality significantly strengthened the negative association between illness perception and intrinsic capacity (between-group comparison p <&#x202f;0.05). During the hospital-to-home transition, illness perception and intrinsic capacity in older adults with COPD and T2DM exhibit a dynamic interaction, characterized by bidirectional influences in the early stage and a more sustained effect of intrinsic capacity on perception later. COPD severity and baseline vitality status are important clinical moderators of this relationship. The findings provide a basis for developing targeted transition care strategies that integrate psychological and functional interventions for high-risk subgroups.

The direct anterior approach (DAA) for total hip arthroplasty (THA) is increasingly adopted due to faster postoperative recovery. However, rare intraoperative complications such as intrapelvic migration of a trial femoral head remain poorly characterized, and optimal management strategies are not well established. This study aimed to describe a novel intraoperative retrieval technique and evaluate its feasibility and safety. We report a single case of intrapelvic trial femoral head migration occurring during primary THA performed via the DAA at our institution. Intraoperative findings, decision-making, and surgical management were documented. A modified approach involving partial transection of the rectus femoris muscle was employed to facilitate manual retrieval of the migrated component. The migrated trial head was successfully retrieved manually after approximately 30&#x2005;min. No laparotomy or additional surgical intervention was required, and no neurovascular or visceral injury was identified. The patient subsequently underwent postoperative rehabilitation, with the Harris Hip Score (HHS) was 77 points at discharge (week 4), and the latest HHS score was 83 point after 7-months follow-up (May 2026). This case demonstrates that a minimally invasive, direct retrieval strategy may be a feasible alternative to conventional approaches such as laparotomy or laparoscopy, which carry higher risks of morbidity. The technique expands current management options for this rare complication and may help improve intraoperative safety. Further studies are needed to validate its generalizability and establish standardized treatment algorithms.