Citations

Abstract Background: Spatial Reasoning AI (SRAI) systems are reshaping clinical practice by enabling real-time interpretation of complex anatomical structures in medical imaging, surgery, and chronic disease management (Lin et al., 2023, Qiao et al., 2021; Song et al., 2024) . Unlike traditional AI approaches that rely on tabular or 2D data, SRAI models incorporate geometric priors, multimodal fusion, and 3D anatomical reasoning to support high-impact tasks such as volumetric segmentation, disease localization, and intraoperative guidance (Milletari et al., 2016; Hatamizadeh et al., 2022; Zhang et al., 2022) . Objective: This scoping review aimed to (1) characterize the emerging landscape of spatial reasoning models in healthcare, (2) evaluate their clinical performance across diagnostic and prognostic applications, and (3) identify architectural trends that underpin successful translation into practice. Methods: Following PRISMA guidelines, we systematically screened PubMed to identify studies that implemented spatially aware AI models with real-time or clinically validated outcomes (Page et al., 2021) . Data extraction captured model architecture, modality, anatomical scope, clinical application, and performance metrics. Results: We identified 124 eligible studies across the clinical domains of oncology, neurology, cardiology, orthopedic surgery, and infectious diseases (Nie et al., 2019; Hao et al., 2020; Tasken et al., 2023) . SRAI systems consistently outperformed conventional methods in segmentation, lesion classification, and risk stratification. (Lin et al., 2023; Qiao et al., 2021; Mahootiha et al., 2024) . A paradigm shift from task-specific CNNs to foundation models that reason across spatial structures has emerged, beginning with adaptations of generalist models such as MedSAM and MedCLIP for zero-shot segmentation and cross-modal retrieval, and NeRF-based reconstruction for anatomically faithful 3D modeling (Ma et al., 2024; Mildenhall et al., 2020; Radford et al., 2021). Beyond technical performance, randomized evidence shows that SRAI systems can improve workflow efficiency without compromising outcomes (Lang et al., 2023) . Conclusion: SRAI models hold promise for enhancing diagnostic accuracy, prognostic precision, and clinical efficiency across diverse applications. Their successful integration will depend on standardized evaluation metrics, robust validation, and interpretable outputs. As foundation models evolve to better encode spatial priors, SRAI is poised to become a cornerstone of personalized and procedural medicine.

Abstract Background Progressive Supranuclear Palsy (PSP) is a rare and severe neurodegenerative tauopathy characterized by diverse clinical phenotypes, including Richardson's syndrome (PSP‐RS), PSP‐parkinsonism (PSP‐P), PSP‐progressive gait freezing (PSP‐PGF), and PSP‐corticobasal syndrome (PSP‐CBS). Significant geographic variation exists in prevalence, clinical presentations, and prognosis. Objectives This global review aims to systematically evaluate the epidemiological variation, clinical phenotypes, diagnostic practices, and management strategies for PSP, focusing on regional disparities and identifying influencing genetic and environmental factors. Methodology A comprehensive literature search following PRISMA guidelines was conducted, analyzing studies reporting PSP epidemiology, phenotypes, diagnostic criteria, risk factors, treatments, and prognoses. Data were categorized into epidemiology, risk factors, clinical presentations, diagnosis, treatment accessibility, and outcomes, considering geographic variation. Results Global PSP prevalence ranges between 5–6.4 per 100,000, influenced by diagnostic criteria and healthcare infrastructure. Clinical manifestations commonly include supranuclear gaze palsy, frequent falls, cognitive impairment, and motor dysfunction. Prognosis significantly varies with subtype; PSP‐RS shows rapid progression and shorter survival (5–7 years), whereas PSP‐P has a milder clinical course (8–12 years). Regional variations highlight differences in genetic predispositions, notably the MAPT H1 haplotype, environmental risk factors such as dietary neurotoxins and industrial pollutants, and accessibility to comprehensive healthcare services. Diagnostic accuracy has improved with the adoption of MDS‐PSP criteria, facilitating recognition of diverse phenotypes. Conclusions Regional disparities in PSP prevalence, phenotypic presentation, and healthcare accessibility underscore the importance of standardized diagnostic criteria, targeted genetic and environmental studies, and equitable healthcare strategies. Enhanced global collaboration is essential for improving PSP diagnosis, management, and patient outcomes worldwide.

Acute-on-chronic liver failure (ACLF) has been associated with excellent post-liver transplant (LT) outcomes at 1 year; however, the impact of alcohol as ACLF precipitant, specifically alcohol-associated hepatitis (AH), and as etiology of chronic liver disease remains uncertain. This study aimed to assess the effect of alcohol as ACLF precipitant and chronic liver disease etiology (alcohol-associated liver disease vs. non–alcohol-associated liver disease) on posttransplant outcomes. We performed a retrospective study using the Multi-Organ Dysfunction and Evaluation for LT Consortium database and included 640 patients with ACLF who underwent LT across 15 transplant centers in North America. The primary outcome was 1-year posttransplant survival. We used logistic regression and Cox proportional hazards to compare posttransplant survival, mortality risk, and health care utilization, adjusting for age, ACLF grade, comorbid diabetes mellitus, chronic kidney disease, and HCC. The median follow-up from LT was 2.8 years (P25–P75, 2.2–5.5 y) for patients with AH-ACLF (n=42) and 3.1 years (P25–P75, 1.6–4.9 y) for patients without AH (n=598). No significant difference was observed in 1-year survival after LT in patients with AH-ACLF versus those without AH ( p =0.36). Patients with AH had significantly higher health care utilization evidenced by greater length of stay (28.5 vs. 19.0 d, p =0.004; adjusted linear estimate 16.89, 95% CI: 7.66–26.11, p <0.001), higher rates of rehabilitation placement (71.4% vs. 41.8%, p =0.002; adjusted odds ratio: 4.13, 95% CI: 2.04–8.89, p <0.001), and non-ambulatory status (39.0% vs. 21.0%, p =0.005; adjusted odds ratio: 4.54, 95% CI: 1.90–10.79, p <0.001). Compared with other etiologies, alcohol-associated liver disease was not associated with differences in 1-year mortality, mortality risk over time, or health care utilization, after excluding patients with AH as ACLF precipitant. While there were no differences in 1-year survival, AH-ACLF was associated with higher health care resource utilization compared with other ACLF precipitants. LT centers should ensure adequate resources are allocated for the management of these patients.

ABSTRACT Objective Sacrifice of pterygopalatine fossa (PPF) neurovascular structures during endoscopic endonasal transpterygoid approach (EETPA) may impact a patient's comorbidity. We present anatomical and surgical techniques for maximizing PPF transposition while preserving its neurovascular structures through orbito‐pterygo‐sphenoidal (OPS) ligament release and descending palatine canal (DPC) decompression. Methods The EETPA was performed on six specimens. Two measurements were obtained to assess PPF transposition: (1) Inferior transposition (distance between the superior margins of the base of the pterygoid process and PPF); (2) lateral transposition (distance from Eustachian tube lateral margin to PPF medial margin). Results After incising the OPS ligament, a mean gain of PPF inferior transposition of 7 mm (4–11 mm, p = 0.03) was observed, with a total inferior transposition of 12 mm (6–15 mm). Subsequently, the posterior half of the inferior turbinate was removed and the DPC was decompressed, with a mean gain of PPF lateral transposition of 12 mm (range 8–15 mm, p = 0.01). Conclusion The OPS ligament release offers a significant advantage for the PPF inferior transposition, allowing access to the inferolateral recess of the sphenoid sinus, cavernous sinus, and paramedian middle cranial fossa, while the DPC decompression provides a significant advantage for the PPF lateral transposition, granting access to the Eustachian tube and ITF. Level of Evidence N/A.

Abstract Hereditary adult-onset ataxias are a heterogeneous group of phenotypically overlapping conditions, often caused by pathogenic expansions of short tandem repeats. Currently, 18 repeat disorders with a core phenotype of adult-onset ataxia are known. Diagnosis typically relies on sequential PCR-based methods, which are labour-intensive and lack precision. Long-read sequencing (LRS) has the potential to overcome these limitations and is currently implemented and validated in clinical genetics. Using clinical nanopore Cas9-targeted sequencing (Clin-CATS) for parallel in-depth repeat analysis, we evaluated a diagnostic cohort of 513 adult-onset ataxia patients, determining frequencies of all known repeat-associated ataxias except Spinocerebellar ataxia 4 (SCA4), as well as the carrier frequencies for autosomal-recessive disorders, RFC1 spectrum disorder and Friedreich’s ataxia (FRDA). Additionally, phenotypes of patients with established genetic diagnoses were characterized, especially those of patients living with RFC1 spectrum disorder and SCA27B. Repeat-associated ataxias were confirmed in 33.3% of cases, including rare ataxias, such as SCA10, SCA36 and SCA37, alongside as the most prevalent conditions SCA27B and RFC1 spectrum disorder. Potentially pathogenic expansions in FGF14 were identified in an additional 4.7% of patients. Testing of another 347 patients for ZFHX3 expansions linked to SCA4 did not identify any cases. Dual diagnoses were frequent, occurring in 6.4% of patients with repeat-associated ataxia. We confirmed a high RFC1 spectrum disorder carrier frequency (7.2%) and reclassified certain FXN expansions as likely non-pathogenic, resulting in a lower than estimated carrier frequency for FRDA of 0.8%. We also identified novel repeat configurations in several loci and illustrated the high heterogeneity of repeat expansions in RFC1, highlighting it as a potential source of false results when using PCR-based methods. This study underscores the diagnostic advantages of LRS for comprehensive repeat analysis and recommends its adoption as a standard in clinical genetics, replacing Southern blot and PCR-based approaches. Furthermore, based on our findings in a large patient cohort a re-evaluation of existing phenotype-genotype correlations is recommended as well as evaluating additional parameters alongside the repeat length to improve diagnostic precision of repeat analysis.

ABSTRACTBackgroundAchalasia is associated with an increased risk of esophageal cancer; though reported incidence rates vary widely (0.4% to 9.2%) due to differences in demographics, follow‐up duration, and diagnostic methods. This study evaluates the risk of esophageal cancer and Barrett's esophagus (BE) in achalasia using a large national database and a propensity‐matched control cohort.MethodsAchalasia patients were identified utilizing the TriNetX database based on International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes for diagnostic procedures and lower esophageal sphincter (LES) directed therapies, including Heller myotomy, peroral endoscopic myotomy, and pneumatic dilation. A matched control group of celiac disease patients was used. A 1‐year lead time was applied to exclude secondary malignant achalasia. Outcomes included the incidence of esophageal cancer and BE, with subgroup analysis in patients following therapy.ResultsAmong 7863 achalasia patients (mean age 58.0, 51.9% female), the esophageal cancer risk was significantly higher than control (risk ratio 2.87, 95% CI: 1.56–5.27, p < 0.001). The absolute risk was low, with 40 cases (0.51%) over a mean follow‐up of 3.18 years. BE risk was also higher in achalasia (risk ratio 1.54, 95% CI: 1.24–1.90, p < 0.001), with 220 cases (2.80%). Subgroup analysis revealed no significant difference in BE risk between POEM and Heller myotomy (risk ratio 1.0, 95% CI: 0.42–2.40, p > 0.99).DiscussionThe elevated cancer risk in achalasia over a short follow‐up period warrants reconsideration of current endoscopic surveillance guidelines, despite the low absolute risk of esophageal cancer and BE.

Our study examined healthy human MASH and MASH-associated hepatocellular carcinoma (MASH-HCC) livers using bulk and scRNA sequencing, spatial transcriptomics, and immunohistochemistry. We found that ACSLs displayed differential and spatially heterogeneous expression. ACSL4 was abundant in tumor tissues, whereas ACSL5 was elevated in noncancerous MASH tissues. ACSL4 was mainly found in immune cells like natural killer cells and natural killer T cells in murine MASH-HCC, suggesting its role in tumor immune microenvironment modulation.

Acute respiratory distress syndrome (ARDS) is a common and highly heterogeneous condition in the critically ill. The association between hyper- and hypo-inflammatory subphenotypes and clinical outcomes has generated significant interest in precise ARDS management. The value of identifying biomarkers to guide treatment and enrollment in future ARDS trials is undisputable. We describe multiple factors complicating the search for subphenotypes and their treatable traits. The observed heterogeneity seen in the clinical course of ARDS is dynamic and influenced by factors beyond lung pathophysiology, including variations in the delivery of best critical care practices, patient comorbidities, and functional status, and patient or family preferences. Current subphenotype definitions lack strong biological plausibility and without clear evidence of benefit from targeted treatments, their use in clinical practice is currently unwarranted.

BACKGROUND: The purpose of this study was to assess the feasibility and prognostic value of cardiac output (CO) reserve assessment using exercise echocardiography in Fontan patients. We hypothesized that adults with Fontan palliation had lower CO reserve compared with controls, and impaired CO reserve was associated with greater congestion (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) and cardiovascular events (death/transplant/heart failure hospitalization) in Fontan patients. METHODS: Thirty-seven Fontan patients and 61 controls underwent exercise echocardiography using a supine cycle ergometer. Doppler-derived CO and oxygen consumption (VO 2 ) were assessed at rest and every stage of exercise. CO reserve was calculated as ∆CO/Watt (∆CO/W) and ∆CO/∆VO 2 . RESULTS: Assessment of CO reserve was feasible in 95% of the Fontan group with modest reproducibility. Although both groups had similar CO at rest, the Fontan group had lower CO reserve with exercise as evidenced by lower ∆CO/W ratio (46±17 versus 57±19 mL/W; P <0.001) and lower ∆CO/∆VO 2 ratio (4.48±1.02 versus 5.37±2.18 mL/mL; P =0.03). There was a correlation between ∆CO/W ratio and log NT-proBNP (r=0.65; P <0.001), and between ∆CO/∆VO 2 ratio and log NT-proBNP (r=0.53; P =0.009). Impaired CO reserve was associated with congestion and cardiovascular events and provided improved prognostication (higher area under the curve and C statistics) above conventional echocardiographic indices and treadmill peak VO 2 . CONCLUSIONS: Patients with Fontan palliation had lower CO reserve, and impaired CO reserve was associated with congestion and cardiovascular events. Further studies are required to determine whether cardiac interventions can improve CO reserve and whether changes in CO reserve can be used as a surrogate end point for therapeutic response.