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Long-term outcomes after a randomized phase II trial of nerve growth factor eye drops for optic pathway gliomas: four-year follow-up findings in children.

PURPOSE: A previous double-blind, randomized, placebo-controlled, phase II clinical trial reported beneficial effects of a short-term treatment (10 days) with murine nerve growth factor (mNGF) eye drops on visual function in children with optic pathway gliomas (OPG). The present study aimed to evaluate long-term changes in clinical and neuroradiological parameters in the cohort of OPG patients who had previously participated in the phase II mNGF trial. METHODS: Fifteen of the 18 patients originally enrolled in the phase II mNGF trial agreed to undergo clinical and neuroradiological monitoring over a 48-month follow-up period. Of these, 9 had originally been randomized to mNGF and 6 to placebo; no additional treatment (mNGF, chemotherapy, or radiotherapy) was administered during the extended follow-up. Every 6 months, patients underwent general clinical and neuro-ophthalmological examination, visual evoked potentials (VEP), and photopic negative response of the electroretinogram (PhNR). Brain MRI was performed every 12 months. RESULTS: Comparison of initial and final follow-up median values revealed no statistically significant changes in visual acuity, VEP amplitude, PhNR amplitude, or visual field radius. No significant differences were observed in any parameter relative to baseline values of the mNGF trial. Brain MRI demonstrated stable disease in all patients throughout the observation period. CONCLUSION: These findings, obtained in an observational extension of the original randomized cohort, indicate favorable long-term safety and tolerability of a short-term course of topical mNGF in children with OPG, with sustained visual and neuroradiological stability over four years, rather than evidence of persistent treatment efficacy. Further prospective, adequately powered and randomized clinical studies are needed to confirm both the short- and long-term clinical efficacy of NGF treatment in preventing OPG-induced visual loss.

Humans

Risk stratification in aortic stenosis: exercise haemodynamics to refine risk in early cardiac damage stages.

AIMS: To describe exercise haemodynamics across cardiac damage stages and evaluate the incremental prognostic impact of cardiac damage stage and exercise-induced pulmonary hypertension (exPHT) in patients with symptomatic moderate aortic stenosis (AS) and asymptomatic severe AS. METHODS AND RESULTS: A total of 436 consecutive patients with &#x2265; moderate AS (74 &#xb1; 10 years, 32% women, 56% severe AS) underwent cardiopulmonary exercise testing with echocardiography. The primary endpoint was heart failure (HF) death and HF hospitalizations. Cardiac damage stage was 0 in 93 patients, 1 (LV damage) in 135, 2 (LA/mitral damage) in 135, and 3-4 (pulmonary vasculature/tricuspid or RV damage) in 73. Higher stages were associated with worse exercise capacity and haemodynamics. Over a median follow-up of 37 months, 65 patients met the primary endpoint. After adjustment for age, AS severity, and aortic valve replacement, cardiac damage stage and exPHT were independently associated with HF outcomes [HR per stage increase 1.51 (1.26-1.82); P < 0.001; exPHT HR 2.36 (1.10-5.07); P = 0.03]. exPHT improved risk stratification in early-stage disease (stages 1-2), conferring an approximately five-fold higher risk of HF events in patients with exPHT [HR 4.45 (1.58-12.59); P < 0.01]. CONCLUSION: In patients with &#x2265; moderate AS and discordant symptoms, cardiac damage stage and exPHT independently refined HF risk stratification. ExPHT provides incremental prognostic value in early damage stages (1-2), representing over half of the cohort, supporting a stepwise approach of routine damage staging with selective with exPHT assessment with exercise echocardiography in this subgroup to guide more personalized management and potentially optimize AVR timing.

Humans

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20&#x2009;min of active or sham 6&#x2009;Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time&#x2009;&#xd7;&#x2009;group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time&#x2009;&#xd7;&#x2009;Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected &#x3b1;&#x2009;=&#x2009;0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (&#x3b2;&#x2009;=&#x2009;2.63, p=&#x2009;0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (&#x3b2;&#x2009;=&#x2009;1.99, p=&#x2009;0.037) and left medial amygdala (&#x3b2;&#x2009;=&#x2009;1.97, p=&#x2009;0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r&#x2009;=&#x2009;0.43, p=&#x2009;0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

The prevalence of isthmic and degenerative lumbar spondylolisthesis: an analysis of 1376 patients.

INTRODUCTION: Typically, spondylolisthesis is an asymptomatic spinal condition that is often captured accidently in radiographic studies. The limited studies reviewing incidence primarily used lateral radiographs, which lack the granularity of advanced imaging. In response, computed tomography (CT) has been recommended to enhance the accuracy of spondylolisthesis diagnosis (degenerative versus isthmic). In the present study, we sought to determine the prevalence of isthmic and degenerative spondylolisthesis using CT imaging. METHODS: We conducted a retrospective study of 1,680 patients who underwent abdominal/pelvic CT scans at a single level-1 trauma center from January 1, 2017, to January 31, 2017. RESULTS: A total of 1,680 CT scans were screened, of which 1,376 patient scans met the inclusion criteria of having undergone complete imaging (axial and sagittal images). The average age of the study population was 57.1 (standard deviation, 18.7) years; 51.1% were female, and 83.2% were Caucasian. The prevalence of isthmic spondylolisthesis was 5.4% (n&#xa0;=&#xa0;71): 3.6% of cases were at the L5-S1 level, 2.1% were at the L4-L5 level, and 0.6% were at the L3-L4 level. The female-to-male ratio was 0.73:1. The prevalence of degenerative spondylolisthesis was higher at 21.5% (n&#xa0;=&#xa0;285), and the level most commonly affected was L4-L5 (11.8%), followed by L5-S1 (9.7%) and L3-L4 (4.6%). The female-to-male ratio was 1.3:1. There was a higher prevalence of degenerative spondylolisthesis in women at L4-L5 (51.2% vs. 35.6%; P&#xa0;<&#xa0;0.001). CONCLUSION: We found that degenerative spondylolisthesis was more prevalent, occurring primarily in older women, between the L4-L5 vertebrae. On the other hand, isthmic spondylolisthesis more commonly occurred within male patients between the L5-S1 vertebrae. Our study is one of the first to recognize a high rate of degenerative spondylolisthesis within the L5-S1 region, highlighting the utility of CT scan to visualize spinal translation. LEVEL OF EVIDENCE: IV.

Humans

Efficacy of dapagliflozin on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: a pre-specified single-arm analysis from a randomized controlled trial.

AIM: To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12&#xa0;months. METHODS: This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10&#xa0;mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12&#xa0;months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS: Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7&#xa0;dB/m; mean change&#xa0;-&#xa0;71.02&#xa0;dB/m, 95% CI: -63.4 to&#xa0;-&#xa0;78.6; p&#xa0;<&#xa0;0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28&#xa0;kPa; mean change&#xa0;-&#xa0;1.31&#xa0;kPa, 95% CI: -0.92 to&#xa0;-&#xa0;1.70; p&#xa0;<&#xa0;0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS: Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12&#xa0;months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Humans

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

BACKGROUND: Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (LTE) studies (NCT01093326; up to 8 years). Current study evaluated safety and efficacy of ponesimod using combined core and LTE studies data for up to 13 years. METHODS: Of 393 participants completing the core study, 353 (90%) entered LTE, having 3 treatment periods (TP). In TP1 (&#x223c;1.85 years), participants continued core treatment (ponesimod: 10, 20, or 40&#x202f;mg QD) whereas placebo-treated participants were re-randomized (1:1:1) to respective ponesimod doses. In TP2 (TP2 and TP3 combined duration: &#x223c;10.4 years), participants on 40&#x202f;mg were re-randomized (1:1) to 10/20&#x202f;mg, while others continued same dose; in TP3 all participants received 20&#x202f;mg. Study outcomes included safety and efficacy (ARR, time-to 24-week confirmed-disability-accumulation [24-week CDA], total T1-weighted Gadolinium-enhanced (T1 Gd+) lesions, new/enlarging T2 lesions and Combined Unique Active Lesions [CUALs]). RESULTS: For 20&#x202f;mg dose, total 92.4% participants experienced &#x2265;1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study. Mean (95% CI) ARR=0.14 (0.10-0.20); Kaplan-Meier estimate (95% CI) of confirmed relapse and 24-week CDA=52.5% (42.3-63.5) and 31.3% (22.6-42.3). Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73). CONCLUSION: Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Humans

Physician-Modified Fenestrated Stent-Grafts Planned Using Three-Dimensional Techniques for Complex Aortic Pathology: A Systematic Review and Meta-Analysis.

BACKGROUND: Complex aortic pathology involving the visceral arteries remains a significant therapeutic challenge. Open repair is associated with considerable perioperative risk, particularly in patients with multiple comorbidities, while standard endovascular aneurysm repair (EVAR) is often not feasible because of inadequate proximal sealing zones. Fenestrated and branched endovascular repair (F/BEVAR) represents an established treatment strategy; however, the use of custom-made devices is limited by manufacturing time and availability. Physician-modified stent grafts (PMSGs) have therefore emerged as a pragmatic alternative. Three-dimensional planning techniques have been increasingly used to facilitate accurate graft modification. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of PMSG procedures planned with three-dimensional techniques. Technical success, target vessel patency, early mortality, endoleak occurrence, and reintervention rates were analyzed. METHODS: A systematic search was conducted in the PubMed/MEDLINE and Embase databases. Studies describing the use of physician-modified fenestrated stent grafts planned with three-dimensional tools were included. Meta-analyses were performed using a random-effects model with restricted maximum likelihood estimation. A logit transformation was used for the analysis of proportions. RESULTS: The analysis included five studies involving 172 patients. The estimated weighted mean follow-up duration was 14.9 months. The overall technical success rate was 92.9% (95% confidence interval [CI]: 84.5-96.9%), with low-to-moderate heterogeneity. Target vessel patency was 96.9% (95% CI: 93.6-98.5%). Early mortality was 5.5% (95% CI: 2.1-13.3%). The incidence of endoleaks was 13.3% (95% CI: 5.8-27.4%), with significant heterogeneity among studies. Reinterventions were reported in 6.6% of patients (95% CI: 2.3-17.5%). CONCLUSION: The results indicate that PMSG procedures planned with three-dimensional techniques are associated with a high rate of technical success and preserved patency of target vessels in patients with complex aortic pathology. The observed variability in endoleak and reintervention rates likely reflects differences in anatomical complexity and patient selection among studies. Further prospective studies are needed to confirm long-term outcomes.

Humans

Paramedian supracerebellar transtentorial approach for Ya&#x15f;argil T2 tentorial incisura meningiomas.

OBJECTIVE: Tentorial incisura meningiomas, particularly those arising from the middle incisural region (Ya&#x15f;argil T2), are surgically challenging because of their deep location and compression of critical neurovascular structures. These lesions typically have supratentorial or infratentorial extension but can also extend across both compartments. Although approach selection is often guided by the dominant compartment of tumor extension, for lesions with supratentorial-dominant extension, the optimal approach remains controversial, and a standardized strategy has not been established. Authors of this study evaluated the feasibility and outcomes of the paramedian supracerebellar transtentorial (PST) approach for Ya&#x15f;argil T2 tentorial incisura meningiomas with a supratentorial-dominant or combined extension. METHODS: The authors retrospectively reviewed data from consecutive patients with radiographic and intraoperative findings consistent with a Ya&#x15f;argil T2 tentorial incisura lesion treated via the PST approach from September 2005 through December 2025. Patients were placed in a semisitting position whenever feasible and in a semilateral position when semisitting was contraindicated. Collected data included demographics, tumor extension patterns, extent of resection on postoperative MRI, neurological outcomes, histopathology, rate of recurrence, and follow-up. RESULTS: Six patients, 1 male and 5 female, with an overall mean age of 43 years, underwent resection via the PST approach. Four lesions had predominantly supratentorial extension, and 2 had combined supra- and infratentorial growth, with no cases of isolated infratentorial extension. Five patients had been placed in the semisitting position and 1 in a semilateral position because of a cardiac contraindication to the semisitting position. No new permanent neurological deficits were observed. Postoperative MRI showed Simpson grade I resection in all 6 patients. The mean follow-up was 8.6 years. Histopathological analysis revealed 3 WHO grade 1 meningiomas, 1 WHO grade 2 meningioma (clear cell), and 2 solitary fibrous tumors (meningioma mimics). These diagnoses were evaluated according to the 2021 WHO classification. CONCLUSIONS: In this consecutive series, the PST approach was a viable single-corridor strategy for Ya&#x15f;argil T2 tentorial incisura lesions, including supratentorial-dominant tumors, achieving Simpson grade I resection with no permanent neurological deficits. By providing early devascularization at the tentorial attachment and a gravity-assisted, retractorless working corridor with favorable deep venous visualization, the PST approach challenges compartment dominance as the primary determinant of approach selection.

Humans

Efficacy of current approaches to non-invasive diagnosis of skin cancer and the potential impact of artificial intelligence: A systematic review and meta-analysis.

BACKGROUND: Skin cancer is one of the most prevalent malignancies worldwide, particularly within Caucasian populations. This systematic review and meta-analysis aimed to quantitatively review the current literature on non-invasive diagnosis of skin cancer and evaluate the current evidence to support the use of tools in addition to, or in replacement of clinician face-to-face assessment. METHODS: A literature search was conducted for publications in PubMed, Medline and Embase databases. Articles describing accuracy, sensitivity, specificity and outcomes of their mode of assessment were included. A total of 208 articles met the inclusion criteria. RESULTS AND CONCLUSION: This systematic review and meta-analysis showed that the diagnostic performance of artificial intelligence (AI) in the interpretation of dermatoscopic images was high for melanoma diagnosis, basal cell carcinoma or malignancy, in comparison to dermatoscopic assessment alone by clinicians and experts. Although AI interpretation of images demonstrated higher sensitivity for melanoma diagnosis in comparison to clinical assessment combined with dermatoscopic assessment, it is unclear if this is also the case for basal cell carcinoma and squamous cell carcinoma diagnosis. Reflectance confocal microscopy, a non-invasive high resolution imaging technique, is known to have a high sensitivity for diagnosing cutaneous malignancy, and this may have applications within secondary care. Therefore, AI could help reduce resource burden and aid in clinical assessment, particularly within primary care settings.

Humans

Depression and amyloid-&#x3b2; across CSF, PET, and plasma biomarkers: a systematic review and meta-analysis.

Alzheimer's disease is increasingly defined by biomarker evidence of amyloid-&#x3b2; and tau pathology, sharpening questions about whether late-life depression contributes to, or instead reflects, this pathology. We conducted a systematic review and meta-analysis of studies published between 2000 and 2025 that compared amyloid-&#x3b2; biomarkers in adults with and without depression, with depression defined by validated clinical diagnoses or symptom rating scales. Twenty-four studies were included, spanning three biomarker sources: cerebrospinal fluid, positron emission tomography imaging, and plasma. Across all sources, the pooled difference in amyloid-&#x3b2; burden between depressed and non-depressed individuals was small and clustered near zero, indicating only a weak, statistically non-significant tendency toward higher amyloid in depression. When the three sources were examined separately, each yielded a similar near-null result, although between-study heterogeneity was considerable for cerebrospinal fluid and plasma and moderate for imaging. Importantly, a prespecified subgroup analysis showed that imaging results diverged by quantification method: studies using the simpler standardized uptake value ratio clustered around zero, whereas the smaller group of studies using kinetic distribution volume ratio modelling showed a significant positive association, suggesting that methodological choices critically influence the observed relationship. Taken together, these findings indicate that depression is not consistently accompanied by greater amyloid-&#x3b2; burden across widely used biomarker platforms. The distribution volume ratio signal nonetheless raises the possibility of subtle associations that cruder methods may obscure, and suggests that depression may shape Alzheimer's disease trajectories more by modifying the clinical impact of amyloid than by altering its amount.

Humans

Artificial intelligence-supported double reading in European population breast cancer screening: A systematic review and meta-analysis of prospective programs.

BACKGROUND: Most European population mammography screening programs rely on double reading with arbitration, a model that delivers mortality benefit but is increasingly challenged by radiologist workload, variable specificity, and interval cancers. Artificial intelligence (AI) is being evaluated to support or optimize these established European screening pathways. PURPOSE: To synthesize prospective or program-embedded evaluations of AI conducted within European-style population screening programs and to estimate exploratory program-level absolute risk differences (RDs) per 1000 examinations for cancer detection rate (CDR) and recall. MATERIALS AND METHODS: We performed a prespecified, focused evidence synthesis of three large studies embedded within routine population screening programs operating under European-relevant workflows: MASAI (randomized AI-supported risk triage within a national program), ScreenTrustCAD (prospective paired-reader evaluation with AI as an independent reader in a double-reading framework), and PRAIM (nationwide decision-referral implementation). Outcomes were harmonized as AI-control RDs per 1000 examinations. Random-effects pooling used Hartung-Knapp-Sidik-Jonkman models. For the paired-reader design, sensitivity analyses applied a Kish effective sample-size approach across plausible within-examination correlations (&#x3c1;&#xa0;=&#xa0;0.3-0.8). Positive predictive value (PPV) and workflow/time outcomes were summarized descriptively. RESULTS: Across 597,419 examinations, the pooled CDR RD was +0.9 per 1000 (95% CI -0.0 to +1.8; I2&#xa0;&#x2248;&#xa0;12%), consistent with a modest directional increase with borderline statistical uncertainty. The pooled recall RD was -0.6 per 1000 (95% CI -3.1 to +2.1; I2&#xa0;&#x2248;&#xa0;41-43%), indicating no consistent recall increase across screening programs. Where reported, PPV was higher with AI-supported screening. Efficiency signals included 44.3% fewer total readings in MASAI and shorter reading times for AI-normal examinations in PRAIM; in PRAIM, a program-level safety-net mechanism recovered 204 cancers that would otherwise have been missed. CONCLUSION: In European population screening programs characterized by double reading and arbitration, prospective program-embedded evidence suggests that AI integration may yield a small absolute increase in cancer detection (&#x2248;1/1000) without a consistent increase in recall, alongside improved PPV and efficiency signals. These findings suggestAI primarily as a complementary reader within European screening workflows, with implementation requiring explicit quality assurance and monitoring of interval cancers and stage distribution.

Humans

IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature.

IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n&#x2009;=&#x2009;16) or vascular imaging (n&#x2009;=&#x2009;14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.

Humans

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50&#x202f;aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT&#xd7;diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F&#x202f;=&#x202f;4.322, P&#x202f;=&#x202f;0.041); this interaction was driven by CCT specifically in aMCI (F&#x202f;=&#x202f;4.465, P&#x202f;=&#x202f;0.038). Significant CCT&#xd7;diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F&#x202f;=&#x202f;5.429, P&#x202f;=&#x202f;0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F&#x202f;=&#x202f;6.587, P&#x202f;=&#x202f;0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F&#x202f;=&#x202f;6.550, P&#x202f;=&#x202f;0.013; F&#x202f;=&#x202f;7.097, P&#x202f;=&#x202f;0.010). No significant interaction effect on the change in hippocampal GMV was noted (P&#x202f;>&#x202f;0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans

The Role of Artificial Intelligence Combined With Digital Cholangioscopy for Indeterminant and Malignant Biliary Strictures: A Systematic Review and Meta-analysis.

BACKGROUND: Current endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopic-based diagnostic sampling for indeterminant biliary strictures remain suboptimal. Artificial intelligence (AI)-based algorithms by means of computer vision in machine learning have been applied to cholangioscopy in an effort to improve diagnostic yield. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic performance of AI-based diagnostic performance of AI-associated cholangioscopic diagnosis of indeterminant or malignant biliary strictures. METHODS: Individualized searches were developed in accordance with PRISMA and MOOSE guidelines, and meta-analysis according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve (SROC). RESULTS: Five studies (n=675 lesions; a total of 2,685,674 cholangioscopic images) were included. All but one study analyzed a deep learning AI-based system using a convoluted neural network (CNN) with an average image processing speed of 30 to 60 frames per second. The pooled sensitivity and specificity were 95% (95% CI: 85-98) and 88% (95% CI: 76-94), with a diagnostic accuracy (SROC) of 97% (95% CI: 95-98). Sensitivity analysis of CNN studies (4 studies, 538 patients) demonstrated a pooled sensitivity, specificity, and accuracy (SROC) of 95% (95% CI: 82-99), 88% (95% CI: 72-95), and 97% (95% CI: 95-98), respectively. CONCLUSIONS: Artificial intelligence-based machine learning of cholangioscopy images appears to be a promising modality for the diagnosis of indeterminant and malignant biliary strictures.

Humans

Robotic-assisted transbronchial biopsy versus computed tomography-guided transthoracic needle biopsy for peripheral pulmonary lesions: a systematic review and meta-analysis of direct comparative studies.

Robotic-assisted bronchoscopy (RAB) and computed tomography-guided transthoracic biopsy (CTTB) are competing strategies for sampling peripheral pulmonary lesions (PPLs). Whether they differ in yield or safety is uncertain. To our knowledge, this is the first systematic review restricted to direct comparisons. We searched MEDLINE, Europe PMC, Scopus, Web of Science and ClinicalTrials.gov from inception to 7 July 2026 for studies directly comparing RAB with CTTB in adults with PPLs. The primary outcome was strict 2024 American Thoracic Society/American College of Chest Physicians diagnostic yield. Risk of bias was assessed with ROBINS-I and certainty with GRADE. A cohort-genealogy step identified, per outcome, the largest set of cohorts sharing no patients; only that set was pooled, with Hartung-Knapp and Mantel-Haenszel sensitivity analyses. Five retrospective studies from one US health system were eligible. Four share patients; at most three cohorts are mutually independent. Across those three, diagnostic yield was comparable (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; I&#xb2;=24%; Hartung-Knapp 0.87-1.13), with an identical relative effect under strict and intermediate definitions although absolute yields fell from 88% to 74-84% under strict criteria. Pneumothorax requiring a chest tube and/or admission was about three-quarters less frequent with RAB across all three cohorts (RR 0.25, 95% CI 0.14-0.46; I&#xb2;=0%; Hartung-Knapp 0.07-0.96). Strict yield (RR 0.99) and any pneumothorax (RR 0.06) were reported by two cohorts each and neither survives the few-studies correction. RAB took about 50&#xa0;min longer than CTTB where same-session staging endobronchial ultrasound was counted in the robotic time, but only about 8&#xa0;min longer than CTTB where it was not. Only one cohort reported yield by lesion size category and none reported yield by bronchus sign or lung zone, so lesion-level subgroups could not be pooled. Certainty was low for pleural complications and very low elsewhere. Low-certainty evidence indicates that RAB is associated with fewer pleural complications, with no statistically detectable difference in diagnostic yield; equivalence was not formally established. Because all evidence is retrospective, confined to one health system, and almost never stratified by lesion size or accessibility, these findings are hypothesis-generating and require a multicenter randomized trial.

Humans

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66&#xa0;years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans

An Overview of Red Breast Syndrome: A Qualitative Systematic Review of the Literature and a Single-Center Case Series.

Red breast syndrome (RBS) is an uncommon inflammatory complication that may occur following implant-based breast reconstruction and can clinically mimic surgical-site infection. This qualitative systematic review, based on comprehensive PubMed and Scopus searches, summarizes the existing literature on RBS, focusing on its etiology, clinical presentation, diagnostic characteristics, and therapeutic approaches following breast reconstruction using acellular dermal matrices (ADMs). A management protocol is proposed based on available data, and a single-center case series is presented from our Hospital, including patients who developed RBS after direct-to-implant reconstruction with ADM between January 2022 and December 2024. Twenty-nine studies met the inclusion criteria, comprising case reports, case series, and retrospective or prospective cohort studies. The reported incidence of RBS ranged from 0% to 29.6%. Proposed etiologies include endotoxin contamination, residual cellular debris, delayed hypersensitivity reactions, and lymphatic or vascular impairment of mastectomy flaps. Most reports described localized erythema confined to the area of the ADM, with normal inflammatory markers and negative imaging findings, whereas antibiotic therapy frequently failed to achieve improvement. Corticosteroids represented the most consistently effective treatment, although some cases required ADM removal or replacement. In our institutional case series (n = 8), symptom onset occurred between 4 weeks and 7 months postsurgery. Inflammatory markers remained within normal limits, imaging rarely demonstrated fluid collections, and symptoms resolved within days to weeks with corticosteroid therapy or conservative management. This review consolidates current evidence, proposes a diagnostic-therapeutic algorithm and highlights the need for prospective investigations and manufacturer-level endotoxin testing to elucidate pathogenesis and optimize clinical management. Level of Evidence: 2 (Risk) For image description, please refer to the figure legend and surrounding text.

Humans