BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

• MeSH
• Crohn Disease * therapy   complications   MeSH
• Adult MeSH
• Remission Induction MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Rectal Fistula * therapy   etiology   MeSH
• Retrospective Studies MeSH
• Patient Satisfaction MeSH
• Mesenchymal Stem Cell Transplantation * methods   adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND & AIMS: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.

• MeSH
• alpha 1-Antitrypsin * genetics   blood   MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• alpha 1-Antitrypsin Deficiency * genetics   diagnosis   complications   MeSH
• Adult MeSH
• Elasticity Imaging Techniques MeSH
• Genotype MeSH
• Homozygote MeSH
• Liver Cirrhosis * genetics   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Mutation MeSH
• Lung physiopathology   pathology   diagnostic imaging   MeSH
• Lung Diseases genetics   etiology   diagnosis   MeSH
• Disease Progression * MeSH
• Risk Factors MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: Extensive surgical resection of the thoracic aorta in patients with type A aortic dissection (TAAD) is thought to reduce the risk of late aortic wall degeneration and the need for repeat aortic operations. OBJECTIVES: We evaluated the early and late outcomes after aortic root replacement and supracoronary ascending aortic replacement in patients with TAAD involving the aortic root. DESIGN: Retrospective, multicenter cohort study. METHODS: The outcomes after aortic root replacement and supracoronary ascending aortic replacement in patients with TAAD involving the aortic root, that is dissection flap located at least in one of the Valsava segments, were herein evaluated. In-hospital mortality, neurological complications, dialysis as well as 10-year repeat proximal aortic operation, and mortality were the outcomes of this study. RESULTS: Supracoronary ascending aortic replacement was performed in 198 patients and aortic root replacement in 215 patients. During a mean follow-up of 4.0 ± 4.0 years, 19 patients underwent 22 repeat procedures on the aortic root and/or aortic valve. No operative death occurred after these reinterventions. The risk of proximal aortic reoperation was significantly lower in patients who underwent aortic root replacement (5.5% vs 12.9%, adjusted subdistributional hazard ratio (SHR) 0.085, 95% CI 0.022-0.329). Aortic root replacement was associated with higher rates of in-hospital (14.4% vs 12.1%, adjusted odds ratio 2.192, 95% CI 1.000-4.807) and 10-year mortality (44.5% vs 30.4%, adjusted hazard ratio 2.216, 95% CI 1.338-3.671). Postoperative neurological complications and dialysis rates were comparable in the study groups. CONCLUSION: Among patients with TAAD involving the aortic root, its replacement was associated with a significantly lower rate of repeat proximal aortic operation of any type compared to supracoronary aortic replacement. Still, aortic root replacement seems to be associated with an increased risk of mortality in these patients. UNLABELLED: ClinicalTrials.gov: NCT04831073 (https://clinicaltrials.gov/study/NCT04831073).

• MeSH
• Aortic Aneurysm, Thoracic * surgery   mortality   diagnostic imaging   MeSH
• Time Factors MeSH
• Blood Vessel Prosthesis Implantation * adverse effects   mortality   MeSH
• Aortic Dissection * surgery   mortality   MeSH
• Adult MeSH
• Risk Assessment MeSH
• Middle Aged MeSH
• Humans MeSH
• Hospital Mortality * MeSH
• Postoperative Complications * epidemiology   etiology   mortality   MeSH
• Reoperation MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Comparative Study MeSH

PURPOSE: Carotid artery stenting with single-layer stents carries a risk of periprocedural cerebral embolization compared to carotid endarterectomy. Dual-layer micromesh stents were designed for improved plaque coverage and sustained embolic protection. This analysis aimed to confirm the Roadsaver dual-layer micromesh stent safety in a real-world carotid artery stenting cohort. MATERIALS AND METHODS: ROADSAVER was a prospective, single-arm, multicenter, observational study. Patients with carotid artery stenosis, eligible for elective stenting, were enrolled at 52 sites across 13 European countries. All procedures followed standard practice. The primary outcome was the 30-day major adverse event rate, defined as the cumulative incidence of any death or stroke. All deaths, strokes, and carotid artery revascularizations were independently adjudicated. RESULTS: In total, 1965 patients were analysed (mean age 70.6 ± 8.8 years). Cerebral ischaemia symptoms were present in 49.4% of participants. Radial/ulnar access was used in 26.3% of cases and embolic protection in 63.8%. The 30-day major adverse event incidence was 2.2% (1.6% in asymptomatic and 2.8% in symptomatic patients), with any stroke at 1.9%, any death at 0.8%, and stroke-related death at 0.5%. Predictors of higher 30-day major adverse event risk, identified through multivariable modelling, included residual stenosis ≥ 30%, thromboembolic venous disease, previous myocardial infarction, age ≥ 75 years, family history of atherosclerosis, non-insulin-dependent diabetes mellitus, symptomatic carotid stenosis, and stent length. CONCLUSION: Dual-layer micromesh carotid artery stenting is safe, with a low 30-day major adverse event incidence in real-world asymptomatic and symptomatic patients, supporting the sustained embolic protection design concept. LEVEL OF EVIDENCE: Level 2, observational study (with dramatic effect).

• MeSH
• Stroke prevention & control   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Prosthesis Design MeSH
• Aged MeSH
• Carotid Stenosis * therapy   surgery   diagnostic imaging   MeSH
• Stents * MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Geographicals
• Europe MeSH

PURPOSE: This study aimed to compare general ophthalmologists, retina specialists, and Aireen AI screening system with the clinical reference standard of a three-member high-level expert committee for diabetic retinopathy (DR) in the evaluation of fundus images for DR. PATIENTS AND METHODS: The study was designed as a diagnostic, multicenter, cross-sectional, non-randomized diagnostic study. The cohort included in the clinical investigation consisted of 1274 patients with diabetes mellitus (DM) type I or II. Each patient underwent one-field fundus photography using a non-mydriatic camera to assess findings of DR. One hundred and nineteen subjects (9.3%) were excluded from the clinical investigation based on Aireen system assessment. In the clinical investigation, all images were assessed at three independent levels of evaluation: 1) general ophthalmologists (GO) - without subspecialty training in the retina; 2) retina specialists (RS); and 3) system Aireen. In cases where there may be disagreements amongst groups, the image is referred for assessment by the Diabetic Retinopathy Board (DRB). RESULTS: The overall prevalence of any DR was 31.9% (368 cases out of 1154 DM), according to the DRB. Overall concordance between AI system Aireen and GO and RS assessments in the detection of DR from fundus photography occurred in 734 cases (63.6%). The number of disagreements between Aireen system, GO and RS evaluation occurred in 420 (36.4%) cases. Sensitivity for GO was 87.0% (95% CI: 83.6; 90.4), for RS was 82.9% (95% CI: 79.1; 86.7), and for AI system Aireen was 92.1% (95% CI: 89.3; 94.9). Specificity was 76.5% (95% CI: 73.5; 79.5), 81.2% (95% CI: 78.5; 83.9), and 90.7% (95% CI: 88.7; 92.7) for GO, RS and AI system Aireen, respectively. CONCLUSION: This real-world study illustrates the potential use of AI system Aireen in screening for DR. It exhibits higher sensitivity and specificity compared to telemedicine evaluation of one field fundus image.

• Publication type
• Journal Article MeSH

DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment. DDC levels increased over time in PD, being significantly associated to higher dosages of dopaminergic treatment. This emphasizes the need to consider treatment effect when analyzing plasma DDC, and suggests that plasma DDC, in contrast to CSF DDC, is of limited use as a diagnostic biomarker for LBD, but could be valuable for treatment monitoring.

• MeSH
• Biomarkers * blood   cerebrospinal fluid   MeSH
• Lewy Body Disease * drug therapy   blood   cerebrospinal fluid   MeSH
• Dopa Decarboxylase * metabolism   MeSH
• Dopamine Agents therapeutic use   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Parkinson Disease * drug therapy   blood   cerebrospinal fluid   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

• MeSH
• Adult MeSH
• Intracranial Arteriovenous Malformations * surgery   radiotherapy   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Radiosurgery * methods   MeSH
• Reoperation MeSH
• Retrospective Studies MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.

• MeSH
• COVID-19 * MeSH
• Adult MeSH
• Hematologic Neoplasms * complications   drug therapy   epidemiology   MeSH
• Humans MeSH
• Antibodies, Monoclonal MeSH
• Pre-Exposure Prophylaxis * MeSH
• Retrospective Studies MeSH
• SARS-CoV-2 MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Czech Republic MeSH

OBJECTIVE: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years. RESULTS: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17). INTERPRETATION: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543.

• MeSH
• Dementia * MeSH
• Cognitive Dysfunction * diagnosis   MeSH
• Humans MeSH
• Neurodegenerative Diseases * MeSH
• Parkinsonian Disorders * MeSH
• REM Sleep Behavior Disorder * diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

IMPORTANCE: Since 2005, a total of 50 face transplants have been reported from 18 centers in 11 countries. The overall survival of the grafts has not yet been established. OBJECTIVE: To assess the survival of the face transplant grafts and evaluate factors potentially influencing it. DESIGN, SETTING, AND PARTICIPANTS: Data on all the transplants included in this multicenter cohort study were collected at participating transplant centers for updated nonpublished data, supplemented with literature review for nonparticipating centers. Data from 2005 until September 2023, were included. Data were analyzed from November 11, 2005, through September 18, 2023. Patients included the first 50 patients in the world to have received a face transplant. EXPOSURE: Face transplant graft. MAIN OUTCOMES AND MEASURES: The primary outcome was the overall survival of the face transplant graft, defined as either transplant loss or patient death. The secondary outcome was the number of acute rejection episodes per year. RESULTS: The 50 transplants were performed on 39 men (81%) and 9 women (19%) with a median age of 35 (range, 19-68) years at the time of the transplant. The median follow-up time was 8.9 (range, 0.2-16.7) years. During the follow-up, 6 transplants were lost with 2 patients retransplanted. There were 10 patients who died, 2 of whom had lost a transplant. The 5- and 10-year survival of the transplants was 85% (SD, 5%) and 74% (SD, 7%), respectively. The sequential number of the transplant in the world was a significant predictor of survival (hazard ratio, 95; 95% CI, 90-100; P < 05). The median number of acute rejection episodes per year was 1.2 (range, 0-5.3) for the transplants that were lost and 0.7 (range, 0-4.6) for the transplants that survived. No correlation with patient and transplant variables was detected for either the transplant survival or the number of rejection episodes. CONCLUSIONS AND RELEVANCE: In this study, the overall survival of the face transplants is encouraging. These data suggest that the acceptable long-term survival of face transplants makes them a reconstructive option for extensive facial defects.

• MeSH
• Global Health MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Graft Survival * MeSH
• Graft Rejection * MeSH
• Aged MeSH
• Facial Transplantation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comment MeSH
• Multicenter Study MeSH