γδ T cells are important for host defense at the respiratory mucosa, acting directly or through interactions with other cells. However, how γδ T cells influence other immune cells in the lung remains unclear. Using a genetically engineered mouse model of lung cancer, we show that tumors drive expansion of both CD27+ and CD27- γδ T cells. Advanced microscopy techniques indicated that CD27- γδ T cells are enriched in tumors, whereas CD27+ γδ T cells are more prone to interact with macrophages in tumor-associated adventitial cuffs. SiglecFlow profibrotic airway macrophages were more prevalent in lung tumor-bearing mice than tumor-free mice. This profibrotic subset was reduced in lungs when the cancer model was crossed to Tcrd knockout mice or treated with Vγ1-depleting antibodies but not in TcrgV4/6 knockout mice. Thus, our findings implicate Vγ1 γδ T cells in driving tumor-associated airway macrophage functional imprinting. Determining the translatability to human health may offer new avenues for refining patient management and immunotherapeutic strategies.

Marfan syndrome (MFS, OMIM #154700) is an autosomal dominant disorder that presents a challenging diagnosis due to its wide clinical variability. The prenatal diagnosis of the syndrome is rare and often associated with unfavourable prognoses, such as early mortality. This case report, written by scientist parents, aims to document the clinical journey, management, and development of a paediatric patient diagnosed with Marfan syndrome at 24 weeks of gestation. In the immediate postpartum period, the patient did not show any severe warning signs, such as tachypnoea or prostration. The initial findings included mild dilation of the aortic and pulmonary roots, funnel chest, downward-slanting palpebral fissures, and elongated fingers. Subsequent multidisciplinary follow-up revealed motor delays, hypotonia, and orofacial alterations. Despite the repercussions of Marfan syndrome, the patient's overall health is positive, and their development is consistent with what is expected for childhood. This case report offers a humanised and multidisciplinary perspective on the patient's journey, highlighting the importance of early diagnosis, access to healthcare services, and information to redefine the course of clinical histories, offering hope to other families.

Autism Spectrum Disorder (ASD) and Attention Deficit and Hyperactivity Disorder (ADHD) are two psychiatric disorders frequently encountered in children. ADHD is further categorized into three subtypes. The diagnostic processes for these conditions are complex and often prone to misclassification. We proposed a lightweight deep neural network, ADBrainNet, to differentiate ASD, ADHD combined, ADHD hyperactive/impulsive, ADHD inattentive and neurotypical individuals. Our methodology was benchmarked against prevalent ImageNet transfer learning methods, including AlexNet, MobileNet, ResNet18, and Xception, for training on resting-state fMRI images sourced from ABIDE and ADHD-200 datasets. ADBrainNet achieved superior performance on the independent external testing set through five-fold cross-validation, with a mean (± standard deviation) accuracy, precision, recall, and F1 score of 61.87% (± 5.59%), 65.72% (± 6.98%), 61.87% (± 5.59%), and 62.50% (± 5.78%), respectively. Furthermore, the explainable artificial intelligence algorithm LIME was employed to explore the most significant features during ADBrainNet's decision process. Our model provides an interpretable computational framework for neuroimaging-based classification between ASD and ADHD subtypes. This approach may inform future research and, upon further validation and comparison with clinician performance, could potentially aid in patient assessment, stratification, and management of psychiatric disorders.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging cardiovascular risk factor; evidence-based blood pressure (BP) management strategies for this population remain limited. We aimed to evaluate the efficacy and safety of a multifaceted intervention anchored by intensive BP control (< 130/80mmHg) in patients with MAFLD using data from the China Rural Hypertension Control Project (CRHCP) trial. This study is a post hoc analysis of the CRHCP trial, an open-label, cluster-randomized controlled trial conducted from 2018 to 2023 across 326 villages in China. Adults aged ≥ 40years with hypertension were eligible. Participants were randomized in a 1:1 ratio to receive either intensive BP control (target < 130/80mmHg) or usual care. MAFLD was diagnosed using the hepatic steatosis index (HSI ≥ 36) combined with metabolic criteria. The primary outcome was a composite of stroke, myocardial infarction, heart failure, or cardiovascular death; secondary outcomes included individual components of the primary outcome and all-cause death. The CRHCP trial is registered with ClinicalTrials.gov NCT03527719. A total of 29,624 participants (12,912 with MAFLD) were included in this analysis. The mean (SD) age was 63.2 (9.2) years, and 18,348 (61.9%) were female. During 48-month follow-up, risk reductions for composite CVD with intensive BP control were similar in patients with MAFLD (adjusted HR, 0.69; 95% CI, 0.61-0.78; P < 0.001) and those without MAFLD (HR, 0.70; 95% CI, 0.63-0.77; P < 0.001), with comparable reductions in stroke and cardiovascular death (adjusted HR for patients with MAFLD, 0.72; 95% CI, 0.55-0.95; P = 0.019; adjusted HR for patients without MAFLD, 0.63; 95% CI, 0.53-0.76; P < 0.001). All-cause mortality declined in patients without MAFLD (adjusted HR, 0.84; 95% CI, 0.76-0.93; P < 0.001) but not significantly in those with MAFLD (adjusted HR, 0.93; 95% CI, 0.79-1.09; P = 0.366), though the interaction was not significant (P for interaction = 0.601). There was an increased risk of hypotension in patients with or without MAFLD. Subgroup analyses confirmed consistent benefits. This study demonstrates that multifaceted intensive BP control at < 130/80mmHg significantly reduces the risk of cardiovascular disease in patients with MAFLD. These findings provide preliminary evidence for BP management in patients with MAFLD and require confirmation in future prospective clinical trials.

The emergency department (ED) is an understudied route to cancer diagnosis. It is unclear how patients present to the ED at the time of suspected cancer diagnosis, and how physicians manage them. The objective of this study was to describe patient presentations and physician management for patients with a new suspected cancer in the ED. This was a prospective study at a tertiary care ED over a 1year period (Mar 2024-2025). Emergency physicians completed data collection form patients seen in the ED with suspected cancer. Charts were reviewed daily to identify missed patients and pertinent data were extracted. We described types of suspected cancers seen, patient presentation, disposition, and physician acceptability of the follow-up process for cancer workup. Over the 1year, 164 patients with suspected cancer diagnoses were seen in the ED, with the top suspected malignancies being gynecological (22.0%), head and neck (11.6%), breast (10.4%), and colorectal (6.7%).The majority of patients (90.2%) presented with symptoms suggestive of malignancy, and 46.3% came to the ED to expedite workup of an already suspected cancer. Approximately, half (52.4%) received a specialist consult in the ED, with 64.0% of those patients subsequently admitted. Among patients who received a consult in the ED, 62.8% were referred not because they were acutely unwell, but to expedite diagnostic workup or due to uncertainty about arranging appropriate follow-up. Physician acceptability of follow-up varied by cancer type. Patients with suspected cancer diagnoses are commonly seen in the ED. Many patients receive specialist consultations primarily to expedite diagnostic workup, which may not represent the most efficient use of already strained ED resources. Improved access to reliable and acceptable follow-up from the ED for further workup of patients with suspected cancer, regardless of cancer type, is needed.

The German-language, consensus- and evidence-based S3 guideline on lichen sclerosus (LS) was developed based on the European "EuroGuiDerm Guideline on lichen sclerosus" under the leadership of the German Dermatological Society (DDG) and the German Society for Gynecology and Obstetrics (DGGG). Particular emphasis was placed on adapting the recommendations to the healthcare conditions in German-speaking countries. The interdisciplinary guideline development group consisted of 24 experts from 16 medical societies and actively included patient representatives in the development process. The guideline provides comprehensive recommendations on diagnosis, patient management, follow-up care, and patient education, as well as the treatment of both genital and extragenital LS in women, men, girls, and boys. Regardless of age or sex, ultrapotent or potent topical glucocorticosteroids in combination with emollients remain the standard therapy for genital LS. In male patients with LS-associated phimosis who do not respond sufficiently to standard therapy, circumcision with complete removal of the foreskin is indicated. For extragenital LS, phototherapy with UV light is recommended as an adjunct to topical treatment. Topical calcineurin inhibitors are second-line therapy.

Abstract Psoriasis is a chronic, debilitating disease of inflammatory dermatoses. IL-17 plays a pivotal role in the pathogenesis of psoriasis. It acts as a driving force in psoriasis and has a significant role in keratinocyte proliferation, plaque progression, neutrophil recruitment, forming an amplification loop, and formation of tissue-resident memory T helper cells causing relapse. Ixekizumab is a humanized IgG4 monoclonal anti-IL-17 antibody approved for psoriasis in 2016. We are reporting a series of 22 patients presented with moderate to severe psoriasis treated with ixekizumab. 31.8% of patients had pre-existing comorbidities like Hypertension, diabetes, or hypertriglyceridemia. After 14 weeks of treatment, the Mean ± SD PASI improved from 30.82 ± 7.06 to 2.82 ± 3.12. At the end of treatment (14 th week), PASI75, PASI 90, and PASI 100 were achieved by 95.45%, 68.18%, and 27.27% of patients, respectively. Friedman’s ANOVA shows a significant decrease ( P &lt; 0.05) in PASI, BSA, and sPGA scores starting from the 1 st follow-up (2 weeks) onwards. Paired t -test shows a significant decrease in PAsI, BSA, and sPGA reduction, P &lt; 0.0001 between baseline and 7 th follow-up visit (14 weeks). No significant side effects were noted in this period. The present study illustrates the experience with ixekizumab in real-world clinical practice, confirming its effectiveness and safety in the management of plaque psoriasis patients.

Biliary tract cancers, encompassing intrahepatic, perihilar and distal cholangiocarcinoma and gallbladder cancer, are a heterogeneous group of highly aggressive malignancies. Most patients have unresectable disease at first presentation, and even those who undergo surgery are likely to have disease recurrence. Newer approaches have included liver transplantation for selected patients, and the integration of locoregional and systemic therapies has expanded the number of patients who can benefit from surgery. The advent of immune-checkpoint inhibitors and targeted therapies for patients with advanced-stage disease has prompted the exploration of these agents in earlier-stage disease settings. Despite this progress, treatment algorithms remain complex, necessitating a multidisciplinary and individualized approach to patient management. Future research should focus on optimizing patient selection through biomarker-driven strategies, including the integration of molecular profiles to guide the selection of systemic therapy, as well as refining the criteria for surgery and transplantation. These improvements will require global collaboration and novel clinical trial designs. In this Review, we describe evolving perioperative strategies for the management of patients with biliary tract cancers and highlight emerging directions in the field.

Amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) are closely related. While some aMCI patients convert to AD (conversion), some revert to age-appropriate cognitive functioning (reversion). Early identification of these bidirectional trajectories informs aMCI-AD pathology and aids patient management. Data from 129 aMCI participants in the Alzheimer's Disease Neuroimaging Initiative, who either converted or reverted, were analyzed. Baseline and longitudinal data relative to exact conversion and reversion times were incorporated to evaluate predictive power using support vector machine analysis. The accuracy of three models, each utilizing different data modalities, was compared. Neurobiological markers associated with these clinical trajectories were examined. The model incorporating brain volumetric changes achieved 92.31% accuracy in classifying conversion vs. reversion. Key neural markers included left inferior lateral ventricle volume for conversion times, left inferior temporal gyrus volume for cognitive status at conversion, and hippocampal and amygdala volumes for memory performance at conversion. The models offer bidirectional, prognostic predictions in aMCI patients. Identified markers provide valuable insights for early intervention. This study informs strategies to reduce AD incidence and optimize resource allocation, contributing to a more comprehensive understanding of disease trajectories and effective management.

Background/Objectives: Isolated methylmalonic acidemia (iMMA) is a rare autosomal recessive metabolic disorder caused by defects in methylmalonyl-CoA mutase (MCM) activity or in the biosynthesis of its cofactor, adenosylcobalamin. Mutations in five genes—MMUT, MMAA, MMAB, MMADHC, and MCEE—are known to underlie this condition. This study aimed to characterize the clinical features and molecular spectrum of iMMA in Malaysian patients of diverse ethnic backgrounds. Material and Methods: Patients with biochemical evidence suggestive of iMMA, including elevated propionylcarnitine (C3), increased C3/C2 ratio, and raised urine methylmalonic acid levels in the absence of hyperhomocysteinemia, were selected for genetic testing. Sanger sequencing was performed to identify pathogenic variants in the MMUT, MMAA, MMAB, MMADHC, or MCEE genes. Results: The cohort consisted predominantly of Iban patients (n = 5), with the remaining cases comprising one Malay and one Thai–Malay individual. Age at diagnosis ranged from Day 1 of life to 6 years. All 7 patients were confirmed to have iMMA through molecular analysis. A total of seven pathogenic or likely pathogenic variants were identified, including two novel MMUT variants (c.246_250delinsGA and c.1358G&gt;C), four known MMUT variants (c.560C&gt;G, c.693C&gt;G, c.982C&gt;T, c.1106G&gt;A), and one known MMAB variant (c.644+1G&gt;A). Clinical presentation and disease severity varied across cases, reflecting underlying genotypic heterogeneity. Conclusions: This study highlights the molecular diversity and clinical variability of iMMA in Malaysia. Our findings reinforce the importance of integrating metabolic screening with molecular diagnostics to identify disease-causing variants and guide patient management strategies effectively.

Introduction and Importance: Metacarpal head fractures are rare intra-articular injuries categorized into 10 types by McElfresh and Dobyns. This report discusses the first reported case of simultaneous coronal head-split fractures of the fourth and fifth metacarpals, the unusual mechanism of injury, and our surgical management of this never-seen type of fracture. Case Presentation: We describe the case of a coronal head split fracture of the fourth and fifth metacarpals in an 18-year-old male who presented with severe pain in the knuckles following a punch. Radiographs of the left hand showed intra-articular fractures of the heads of his fourth and fifth metacarpals step-off of 3 mm. Fixation was performed using two crossed 1.2-mm headless compression screws, each inserted dorsal to palmar to restore articular surface integrity and congruency. A full active range of motion was achieved at 8 weeks postoperatively without rotational deformity. Clinical Discussion: We present our approach to patient management, comparing it to the existing literature. Given the articular step-off and the patient’s young age, open reduction and internal fixation with headless compression screws was performed. To the best of our knowledge, this is the first documented case of surgical management for this specific fracture pattern, highlighting our successful approach in achieving anatomical reduction and stable fixation, which facilitated early mobilization and a favorable outcome. Conclusion: This report highlights a viable surgical approach and major take-away points for this rare intra-articular injury, namely fracture pattern recognition, adherence to surgical principles, and achieving appropriate anatomical reduction and stable fixation to promote faster and successful recovery.

The primary aim of a cytogenetics laboratory is to define the most appropriate diagnostic strategies in order to provide clinicians with relevant and actionable information for optimal patient management. Together with molecular biology data, these findings represent an essential and indispensable component for the diagnosis, prognosis and treatment of onco-hematological diseases. Optical genome mapping (OGM) is an emerging genome-wide cytogenomic technology that enhances the detection of structural and copy number variants compared with conventional cytogenetic methods through the analysis of ultra-high molecular weight DNA molecules linearized in nanochannels. OGM improves the identification of cryptic and complex genomic rearrangements and facilitates the discovery of novel cytogenomic biomarkers, with a significant impact on risk stratification and therapeutic targeting. Recent expert recommendations support its integration into the cytogenomic and molecular work-up of hematological malignancies in the context of the updated WHO and ICC classifications. In hematological malignancies, chromosomal aberrations represent key diagnostic and prognostic biomarkers. Standard cytogenetic approaches, including chromosome banding analysis, fluorescence in situ hybridization and chromosomal microarrays, remain the current diagnostic backbone but are limited by resolution, culture dependency and target-restricted analysis. OGM has demonstrated high concordance with standard methods while providing additional clinically relevant information, particularly in cases with complex karyotypes and cryptic rearrangements, leading to a more accurate prognostic stratification. When integrated with targeted next-generation sequencing, OGM enables a comprehensive genomic characterization within a single workflow. Despite its clear advantages, OGM does not fully replace conventional techniques and its application must be guided by disease-specific clinical indications. Expert consensus recommends OGM as a first-line or second-line tool depending on the diagnostic setting, particularly in cases with failed karyotypes, normal cytogenetics with suspected cryptic aberrations, and entities requiring genome-wide structural variant assessment The presentation will briefly outline the technical basis of OGM and, through selected representative clinical cases, will highlight its major advantages in improving diagnostic precision and prognostic stratification, as well as its current limitations and optimal positioning in routine diagnostic practice. References Kanagal-Shamanna R et al. — Am J Hematol. 2025;100(6):1029-1048. https://doi.org/10.1002/ajh.27688 Levy B et al. — Am J Hematol. 2024;99(4):642-661. https://doi.org/10.1002/ajh.27175 Puiggros A et al. — Optical genome mapping: a promising new tool to assess genomic complexity in chronic lymphocytic leukemia (CLL). Cancers. 2022. https://doi.org/10.3390/cancers14143376 Puiggros A et al. — Optical genome mapping: technical basis and applications in hematological malignancies. Sangre. 2023. https://doi.org/10.1016/j.sang.2023.05.001 Ramos-Campoy S et al. — TP53 abnormalities are underlying the poor outcome associated with chromothripsis in chronic lymphocytic leukemia patients with complex karyotype. Cancers. 2022. https://doi.org/10.3390/cancers14133217

Optimizing diagnosis and management of patients with ENPP1 deficiency: an expert opinion.

Management and work-up procedures of patients with head and neck malignancies treated by radiation: 2025 update.

Objective: An important characteristic of Hepatocellular carcinoma (HCC) is that it features multicentric recurrences that can recur after curative treatment. Current recommended curative treatments for HCC include liver transplantation (LT), and prognostic evaluation and appropriate treatment selection are crucial in the management of HCC patients. Factors considered tend to include tumor size and number, lobar distribution, multinodularity, α-fetoprotein (AFP) level, degree of tumor differentiation, vascular invasion, and satellite nodules. However, the prognostic value of intrahepatic lymphatic vessel invasion (LVI) has rarely been reported for liver cancers. Methods: From January 2012 to December 2020, a total of 178 HCC patients who underwent liver transplantation consecutively were retrospectively enrolled. Those who underwent liver transplantation were divided into two groups based on the presence or absence of lymphatic vessel invasion. The primary aim was to compare the two groups for overall survival (OS), disease free survival (DFS), and recurrence rates, as well as to evaluate the prognostic effect of LVI after transplantation. Results: Poor tumor characteristics such as high tumor differentiation grade and MVI were significantly higher in the patient group with LI. Tumor recurrence and mortality rates were significantly higher in LI-positive recipients. Conclusions: The lymphatic invasion (LI) group displayed higher rates of recurrence and mortality. The findings emphasize the need to incorporate LI assessment into prognostic evaluations to enhance the management and outcomes of individuals with Hepatocellular carcinoma.

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform nonbinding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses Daridorexant (Quviviq), 25 mg oral tablet, 50 mg oral tablet. Indication: Quviviq (daridorexant) is indicated for the management of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

Implications of Sarcopenia in Patients with Structural Valve Pathology.

Nonacute subdural hematoma (NASDH) is associated with cognitive dysfunction and decline. Middle meningeal artery embolization (MMAE) has shown efficacy in reducing NASDH recurrence and promoting hematoma resorption, but its potential impact on long-term cognitive outcomes is unexplored. This study aims to determine whether standalone MMAE is associated with reduced dementia risk compared with conservative management (CM) in dementia-free patients with nonsurgical NASDH. This was a multicenter retrospective cohort study using the TriNetX US collaborative research network database. Adult patients with newly diagnosed NASDH who did not undergo surgical drainage were included. Patients with known dementia at the time of NASDH diagnosis were excluded. Patients who underwent standalone MMAE were compared with those who underwent CM only. The primary outcome was new-onset dementia during a 5-year study follow-up period. Secondary outcomes included all-cause mortality. One-to-one propensity score matching was performed to account for confounding and indication bias. Outcomes were compared using time-to-event analyses with Kaplan-Meier curves and Cox proportional hazards models. Of 175 868 patients with nonsurgical NASDH, 1991 underwent MMAE. After propensity score matching, 1972 patients remained in each group with similar baseline characteristics (all absolute standardized differences <0.10). Mean follow-up was 704 days for MMAE patients and 818 days for CM patients. Compared with CM, MMAE was associated with significantly lower 5-year probability of incident dementia (6.0% versus 11.4%; P<0.001; hazard ratio 0.55 [95% CI, 0.40-0.77]), representing a 45% reduction in risk. MMAE was also associated with significantly lower all-cause mortality (25.1% versus 32.1%; P=0.001). Among nonsurgical, dementia-free patients with NASDH, standalone MMAE was associated with significantly reduced incident dementia risk compared with CM. These findings suggest MMAE may provide neurocognitive benefits beyond preventing hematoma progression, potentially through promoting hematoma resorption and preserving cortical integrity. Prospective studies are needed to confirm these hypothesis-generating observations and establish causality.

Since its introduction in 1974, the artificial urinary sphincter (AUS) has been considered the gold standard for treatment of moderate to severe male stress urinary incontinence. This article provides an overview of perioperative management and long-term outcomes, offering an evidence-based foundation for clinical practice. Current evidence on patient selection, preoperative diagnostics, surgical techniques, long-term outcomes, and management of complications was reviewed, based on recent studies, multicenter cohorts, and registry data. The implantation of an AUS generally results in high continence rates and substantial improvement in quality of life. Perioperative risk factors, including prior radiotherapy, diabetes mellitus, or previous urethral procedures, increase the likelihood of postoperative complications such as infections, urethral erosions, or mechanical failure. Specialized centers with extensive experience achieve better functional outcomes and lower revision rates. Despite potential complications, most patients report sustained satisfaction and an improved quality of life following AUS implantation. The AUS is an effective treatment option for moderate to severe stress urinary incontinence. Perioperative risk assessment, specialized implantation techniques, and treatment in experienced centers are crucial for therapeutic success. Prospective registry and multicenter data provide valuable guidance for evidence-based patient selection, complication management, and of long-term outcome optimization.

Pediatric acromioclavicular (AC) joint injuries are rarely reported, and data on return-to-sport rates (RTS) in this population are limited. This study aims to characterize management strategies and return-to-sport outcomes following AC joint injuries in pediatric athletes, addressing a gap in the current literature. Patients under 18 years of age who sustained an AC joint injury between March 1, 2014, and March 1, 2024, were identified using databases from a large tertiary referral hospital and a large children's hospital. Extracted data included patient demographics, injury patterns, management approaches, and RTS status. A total of 108 patients (110 shoulders) were included (74% male; mean age, 12.77±2.13​​​​​y; range 8 to 17 years). Low-grade injuries accounted for 95% of cases, and all injuries were managed nonoperatively. Sling immobilization was used in 40%, physical therapy (PT) in 29%, rest in 17%, and a combination of sling and PT in 15%. The most common mechanisms were football (29, 26%), motor vehicle collisions (11, 10%), and soccer (10, 9%). At least 48% (52) of patients had documented return-to-sport dates, with the median RTS time being 21 days (IQR 14 to 49.45​​​​​d). Concomitant injury was associated with a longer RTS time (HR 0.33, 95% CI 0.16-0.69, P=0.003). In this cohort of pediatric athletes, AC joint injuries were predominantly low-grade and managed nonoperatively. Of the patients with documented follow-up and RTS, the median RTS time was 3 weeks. These findings reinforce the favorable prognosis of nonoperative treatment for low-grade injuries in this population. Given the rarity of pediatric AC joint injuries and the limited published data, reporting these outcomes is essential to guide evidence-based management in pediatric sports medicine. IV: retrospective cohort study.