Maladies orphelines

Neurophysiol Clin. 2026 Oct 24;56(6):103214. doi: 10.1016/j.neucli.2026.103214. Online ahead of print. ABSTRACT OBJECTIVES: To appraise the evidence on compound muscle action potential (CMAP) as a biomarker in spinal muscular atrophy (SMA): responsiveness to therapy, correlation with motor function, diagnosis and prognostic value, and patterns across SMA types. METHODS: Conducted per PRISMA 2020 (PROSPERO CRD420261476823). PubMed and Embase were searched to August 15, 2026 for studies reporting CMAP in genetically confirmed SMA. Findings were synthesized narratively across four pre-specified domains using a Synthesis Without Meta-analysis approach. Two reviewers independently assessed risk of bias with Joanna Briggs Institute tools. RESULTS: Sixty-two studies (2513 participants across reports) were included. Following disease-modifying therapy, CMAP increased in 22 of 33 contributing studies (66.7%), was stable in 9 (27.3%), and showed a mixed pattern in 2 (6.1%); none reported a net decrease. All three disease-modifying therapies were associated with CMAP increase. CMAP correlated moderately to strongly with motor function scales and discriminated diagnostic or severity categories in 6 of the 11 studies that formally tested this. Risk of bias was low or low-moderate in 27 studies; small sample size and absence of a concurrent control group were the most frequent limitations. DISCUSSION: CMAP rises in roughly two-thirds of treated cohorts and reflects disease severity, but floor, ceiling, and site-dependent effects limit its use as a standalone surrogate endpoint. Selecting the recording site by severity, adding a second site chosen on the same basis, and agreeing standardized acquisition and normative values would strengthen its role as a prognostic stratifier and a component of multimodal models. PMID: 42925809 | DOI: 10.1016/j.neucli.2026.103214

Muscle Nerve. 2026 Oct 26. doi: 10.1002/mus.70437. Online ahead of print. ABSTRACT INTRODUCTION/AIMS: Epidural spinal cord stimulation (SCS) has recently been explored in ambulatory individuals with spinal muscular atrophy (SMA), where an increase in muscle strength and endurance with concomitant reduced fatigability was observed. However, the underlying kinematic changes associated with these improvements remain poorly understood. This study aimed to examine whether previously documented improvements following SCS were associated with changes in joint kinematics and movement strategies. METHODS: A secondary kinematic analysis of previously collected 6-min walk test (6MWT) data using a 3D motion-capture system and subsequent principal component analysis (PCA) was completed on two ambulatory individuals with SMA. Speed as well as spatio-temporal gait variables and sagittal-plane joint kinematics were defined and compared before and after SCS intervention. RESULTS: After 4 weeks of SCS, participants walked farther and showed faster, more consistent speeds during the 6MWT. PCA revealed that these improvements were associated with changes in proximal joint velocity (SMA02 mean(L 2 ) = 0.45, SMA03 mean(L 2 ) = 0.54) and proximal joint mobility (SMA 02 mean(L 2 ) = 0.51, SMA03 mean(L 2 ) = 0.40) in both SMA participants. Consistent with these findings, hip range of motion, velocity, and acceleration increased by up to 48%, 44% and 28%, respectively, without evidence of exacerbated compensatory strategies. DISCUSSION: SCS may restore access to motor pathways selectively impaired in individuals with SMA. While confirmatory, larger cohort studies are needed, SCS has the potential to reduce intrinsic movement abnormalities and enhance treatment opportunities for SMA. PMID: 42934999 | DOI: 10.1002/mus.70437

J Cachexia Sarcopenia Muscle. 2026 Oct;17(5):e70413. doi: 10.1002/jcsm.70413. ABSTRACT BACKGROUND: Loss of ambulation (LOA) is a key milestone in Duchenne muscular dystrophy (DMD) with highly variable timing, complicating clinical counselling and trial design. Quantitative MRI non-invasively assesses muscle fat infiltration, yet few models have integrated MRI with clinical variables for individualized LOA prediction. We aimed to develop and validate a machine-learning model integrating quantitative MRI and clinical features to predict time to LOA and to derive interpretable, individualized risk estimates and candidate thresholds. METHODS: This prospective study enrolled 188 boys with DMD (median age 9.10 years). Quantitative MRI parameters (T1, T2, fat fraction [FF]) of 19 hip/thigh muscles and clinical variables were measured. Patients were randomly split into training (80%) and test (20%) sets. Feature selection used LASSO, Boruta and recursive feature elimination based on random survival forest (RSF). Three survival models were compared: RSF and a ridge-penalised Cox model (both integrating clinical and MRI-derived features) and a multivariable Cox model restricted to clinical variables. Performance was assessed by concordance index (C-index), time-dependent area under the curve (AUC), integrated Brier score (IBS) and decision curve analysis at 12, 24, 36 and 48 months. RESULTS: Over median 43.5 months follow-up, 66 patients (35.1%) experienced LOA. Six predictors were retained: NSAA score, MRC%, age and three FF parameters (rectus femoris, vastus lateralis, obturator internus). In the test set (n = 40, 15 events), RSF achieved a C-index of 0.870 (95% CI, 0.764-0.957), outperforming the clinical Cox (0.804) and ridge Cox (0.853) model. Time-dependent AUCs of the RSF model were 0.984, 0.971, 0.913 and 0.850 at 12, 24, 36 and 48 months. RSF showed the best calibration, with the lowest IBS (0.076, 95% CI: 0.052-0.111), followed closely by the ridge Cox model (0.078) and the clinical Cox model (0.109). RSF stratified patients into low-risk, intermediate-risk and high-risk groups; no LOA events occurred in the low-risk group, with annual event rates were 7.2% and 34.6% in the intermediate- and high-risk groups (log-rank p = 0.0025). SHAP analysis identified exploratory thresholds (NSAA < 14.55, MRC% < 68.36%, rectus femoris FF > 32.30%, vastus lateralis FF > 58.00%, obturator internus FF > 7.43%). An interactive web application enables individualized risk…

Zhongguo Dang Dai Er Ke Za Zhi. 2026 Oct 15;28(10):1289-1297. doi: 10.7499/j.issn.1008-8830.2606154. ABSTRACT Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder in which cardiac involvement is relatively insidious, and heart failure has become one of the major determinants of prognosis. Cardiac magnetic resonance imaging and speckle-tracking echocardiography provide a basis for the precise assessment of DMD-associated cardiomyopathy. At present, glucocorticoid therapy and cardiovascular drug therapy are the basic treatment approaches, and gene therapy, cell therapy, and molecularly targeted drugs are continually evolving. This review summarizes pathogenic mechanisms, diagnostic techniques, and therapeutic strategies for DMD-associated cardiomyopathy, with the aim of informing standardized clinical management and improving patient quality of life. PMID: 42902726 | DOI: 10.7499/j.issn.1008-8830.2606154

Clin Kidney J. 2026 Oct 9;19(10):sfag317. doi: 10.1093/ckj/sfag317. eCollection 2026 Oct. ABSTRACT OBJECTIVES: We aimed to appraise 11 currently available guidelines for ANCA-associated vasculitis (AAV), identify potential gaps, and provide recommendations for improvement. METHODS: The guidelines were appraised using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument consisting of 23 appraisal criteria/items across six domains (D). Four reviewers independently appraised guidelines and scaled domain scores were calculated. RESULTS: The average score of all guidelines was 4.5 ± 0.8 out of 7.0. Agreement between the reviewers was excellent. British Society for Rheumatology 2025 guidelines scored highest (5.8/7.0), being the only guideline unanimously recommended for use. In 'D1/Scope and purpose', all guidelines achieved high scores. In 'D2/Stakeholder involvement', major gaps were identified in the inclusion of the views and preferences of the target population (2c), with few guidelines including patient representatives, addressing patient participation, or considering patient views. In 'D3/Rigour of development', all but two guidelines received high scores. Implementation of the procedure for updating the guidelines (3 h) and for external review (3 g) was addressed poorly. In 'D4/Clarity of presentation', all guidelines except one received a high score. 'D5/Applicability' had the lowest scores due to gaps in the criteria for monitoring/auditing guideline implementation (5d), resource/cost implications (5c), lack of advice/tools for implementation (5a), and inadequate addressing of facilitators/barriers in guideline application (5a). 'D6/Editorial independence' was addressed well. CONCLUSIONS: Several aspects of AAV guidelines could be improved, including the inclusion of patient views and preferences, the processes for translating guidelines into clinical practice, and clearer criteria for monitoring guideline implementation and uptake. PMID: 42909277 | PMC: PMC13684405 | DOI: 10.1093/ckj/sfag317

Can Assoc Radiol J. 2026 Oct 28:8465371261486850. doi: 10.1177/08465371261486850. Online ahead of print. ABSTRACT Fibrotic interstitial lung diseases (fILD) are a heterogeneous group of chronic diseases that require clinical, radiological and pathological correlation for diagnosis and management. In this setting, the role of radiologists is to define the ILD pattern using high-resolution CT (HRCT). These practice guidelines, developed by the Canadian Society of Thoracic Radiology (CSTR) and the Canadian Association of Radiologists (CAR), provide evidence-informed recommendations to assist practicing radiologists in standardizing HRCT acquisition and pattern recognition in fILD. Based on an integration of current evidence and expert consensus, it outlines core knowledge for identifying features of fibrosis and ancillary radiological findings that assist on pattern identification, providing a practical framework to imaging diagnosis. The document includes multidisciplinary correlation for the diagnosis of most common fibrotic ILDs and an updated review of specific clinical diagnoses relevant to the radiology practice. PMID: 42947619 | DOI: 10.1177/08465371261486850

Curr Neurol Neurosci Rep. 2026 Oct 24;26(1):62. doi: 10.1007/s11910-026-01533-y. ABSTRACT PURPOSE OF REVIEW: This narrative review aims to evaluate current literature on Dravet syndrome, integrating significant new findings into the existing knowledge of pathophysiology and disease course, and highlighting emerging treatments. RECENT FINDINGS: Beyond SCN1A pathogenic variants, recent findings implicate an expanding number of genes and polygenic interactions which may play a role in the pathophysiology of Dravet syndrome. Neuroimmune dysregulation during critical periods of early brain development may be an additional contributing factor. There is increased recognition of neurodevelopmental comorbidities and disease progression over the lifetime, with neurological decline in adulthood suggestive of a possible degenerative process. Emerging and investigational therapies, including gene-modulatory therapies, may provide improvement in seizures and other metrics. Along with an evolving understanding of Dravet syndrome, including its multifactorial disease mechanisms, clinical manifestations beyond seizures, and progression of disease, the advent of novel treatments offers the potential for improved care of patients across the lifespan. PMID: 42925451 | DOI: 10.1007/s11910-026-01533-y

Cent European J Urol. 2026;79(3):351-359. doi: 10.5173/ceju.2026.0108. Epub 2026 Jul 28. ABSTRACT INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with unclear pathophysiology and limited standardized treatments. This retrospective analysis evaluates the association of a combined approach including prolonged hydrodistension, intravesical instillation, and bilateral pudendal nerve block with symptom improvement. MATERIAL AND METHODS: Data from 64 patients, from December 2016 to June 2023, were analyzed, including demographic information, symptoms, intraoperative details, Interstitial Cystitis Symptoms Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Visual Analogue Scale (VAS) for pain, and daily frequencies at baseline, 1 and 6 months. Patients underwent prolonged hydrodistension with intravesical prednisolone followed by instillation of NaHCO₃, bupivacaine, prednisolone, and heparin sulphate. A bilateral pudendal nerve block was then performed under fluoroscopic guidance. RESULTS: Mean basal bladder capacity under general anaesthesia increased from 389.45mL to 537.34 ml and 629.91 ml after the first and second hydrodistension, respectively. Intravesical instillations and bilateral nerve block were performed in 90.6% and 95.3% of cases, respectively. ICSI decreased from 21.05 ±2.27 at baseline to 8.89 ±3.88 at 1 month and 13.87 ±5.42 at 6 months (p <0.0001). ICPI showed similar improvement. VAS pain scores significantly decreased at follow-up. Symptom improvement correlated with increased bladder capacity and higher baseline ICPI, while pain reduction was predicted by higher ICPI and diurnal frequency, lower baseline bladder capacity, and increased capacity after the second hydrodistension. CONCLUSIONS: The combined approach of prolonged bladder anti-inflammatory hydrodistension and bilateral pudendal nerve block shows a short-term association with improvement in the management of IC/BPS. The observed early improvements in symptoms warrant further prospective studies with larger cohorts to confirm durability and to evaluate the role of repeat procedures. PMID: 42904097 | PMC: PMC13681909 | DOI: 10.5173/ceju.2026.0108

Thorac Cancer. 2026 Oct;17(20):e70408. doi: 10.1111/1759-7714.70408. ABSTRACT Patients with idiopathic pulmonary fibrosis (IPF) undergoing lung cancer surgery are at high risk of acute exacerbation of IPF (AE-IPF), which is associated with high mortality. Although antifibrotic therapy (AFT) has been proposed as a preventive strategy, evidence remains limited and heterogeneous, particularly regarding early postoperative outcomes. We systematically searched major databases, including PubMed and Ichushi-Web, through August 2025 to evaluate perioperative AFT in patients with IPF undergoing surgery. Eligible studies reported postoperative AE-IPF or mortality within 30-90 days. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using common- and random-effects models. Five retrospective cohort studies predominantly evaluating pirfenidone were included. AFT was associated with a lower incidence of postoperative AE-IPF both within 30 days (RR, 0.24; 95% CI, 0.07-0.76; I 2 = 0%) and 90 days (RR, 0.23; 95% CI, 0.09-0.57; I 2 = 0%). AFT was associated with lower mortality at 30 days (RR, 0.12; 95% CI, 0.02-0.91; I 2 = 0%) and 90 days (RR, 0.13; 95% CI, 0.02-0.76; I 2 = 0%). Sensitivity analyses, including a nationwide database study, supported the association, although the effect was attenuated. Evidence for nintedanib was limited to a small case series. Perioperative AFT, particularly with pirfenidone, was associated with lower rates of AE-IPF and mortality, including within 30 days post-lung cancer surgery. These findings underscore the clinical relevance of early postoperative outcomes and support further prospective studies to clarify the role of perioperative AFT. PMID: 42928436 | DOI: 10.1111/1759-7714.70408

PLoS One. 2026 Oct 22;21(10):e0360987. doi: 10.1371/journal.pone.0360987. eCollection 2026. ABSTRACT PURPOSE: For ten years, nintedanib and pirfenidone have been the only approved therapies for idiopathic pulmonary fibrosis (IPF), with nintedanib subsequently also approved for progressive pulmonary fibrosis (PPF). Previous studies demonstrate low antifibrotic (AF) uptake, but differences by site-of-care and AF uptake after seminal trials (IPF: INPULSIS/ASCEND; PPF: INBUILD) are not well characterized. We evaluated temporal trends in IPF and PPF diagnosis and AF use at academic (AC) versus non-academic (NonAC) centers. METHODS: Using the U.S. TriNetX Collaborative Network, we compared IPF and PPF incidence, prevalence, and AF use by center type using linear regression across post-trial and post-FDA-approval windows (IPF: 2015-2017, 2015-2024; PPF: 2020-2022, 2020-2024). Slope differences (Δslope) were calculated as AC minus NonAC annual slopes; therefore, positive values indicate faster increases at ACs, whereas negative values indicate faster increases at NonACs. RESULTS: Across both periods, IPF prevalence increased more rapidly at NonACs, while AF use was higher at ACs (2024: 33.5% vs 20.1%, p < 0.001). During the post-approval period (2015-2024), AF initiation and overall use rose faster at ACs: (AC-NonAC Δ slope +0.26 percentage points/year, p = 0.002; + 1.25 percentage points/year, p < 0.001). During the post-INPULSIS/ASCEND period (2015-2017), overall AF use rose faster at ACs (Δ slope +1.23 percentage points/year, p = 0.009), while AF initiation slopes did not differ significantly (Δ slope -0.22 percentage points/year, p = 0.155). PPF prevalence was similar across centers, with higher AF use at ACs in 2024 (17.1% vs 9.8%, p < 0.001). During the post-approval period (2020-2024), AF initiation and overall AF use increased faster at ACs (Δslope +1.16 percentage points/year, p < 0.001; + 1.94 percentage points/year, p = 0.009). During the post-INBUILD period (2020-2022), AF initiation rose faster at ACs (Δ slope +1.42 percentage points/year, p = 0.002), while overall AF slope differences were not significant. Outcome patterns for IPF revealed higher mortality and lung transplant in ACs, but lower respiratory failure and oxygen use. PPF showed higher respiratory failure and mortality in ACs, and no significant differences in lung transplant or oxygen use. CONCLUSIONS: AF use in IPF and PPF was higher and rose faster at ACs, suggesting faster AC adoption…

Aging Cell. 2026 Nov;25(11):e70763. doi: 10.1111/acel.70763. ABSTRACT Patients with idiopathic pulmonary fibrosis (IPF) are highly vulnerable to respiratory virus infections, but the cellular mechanisms linking fibrotic remodeling to impaired local antiviral defense remain unclear. Here, we investigated how cellular senescence shapes the response of patient-derived healthy (HLF) and IPF primary lung fibroblasts to influenza A virus (IAV) infection. Transcriptomic profiling identified infection as the driver of gene expression in both DNA damage-induced senescent HLF and IPF fibroblasts and revealed induction of canonical antiviral pathways in both cell states. However, senescent IPF fibroblasts adopted a distinct antiviral response state characterized by a broader set of uniquely induced genes and differential coordination of antiviral transcriptional networks. Functionally, senescence increased viral titers in HLF and IPF fibroblasts, while senescent IPF fibroblasts displayed an altered inflammatory response. Network analysis linked viral response- and cell cycle-associated modules specifically to the senescent HLF infected state, whereas these programs were weaker in senescent IPF fibroblasts. Transcription factor inference identified IRF3 and STAT1 as candidate regulators of this altered antiviral state in both senescent HLF and IPF fibroblasts. Consistent with the network and transcription factor analyses, siRNA-mediated depletion of IRF3 or STAT1 significantly reduced IFN-β secretion in senescent HLF fibroblasts, whereas IPF fibroblasts showed only milder effects, indicating a disease-specific dependence on these pathways for antiviral control. Together, these findings show that the combination of cellular senescence and fibrotic fibroblast identity creates a dysfunctional antiviral state that may help explain the high susceptibility of IPF patients to virus-associated acute exacerbations and disease worsening. PMID: 42902866 | DOI: 10.1111/acel.70763

J Neuropathol Exp Neurol. 2026 Oct 22:nlag112. doi: 10.1093/jnen/nlag112. Online ahead of print. ABSTRACT Amyloid myopathy is an etiologically heterogeneous group of disorders associated with amyloid deposition in skeletal muscle. The great majority of cases reflect muscle involvement in systemic amyloidosis, particularly immunoglobulin light-chain amyloidosis and hereditary amyloidosis. Occasionally, amyloid myopathy presents as an isolated myopathy associated with muscle proteinopathies. Clinical manifestations are generally nonspecific. Muscle weakness is the most common presentation; however, many patients with biopsy-confirmed amyloid deposition lack objective weakness, as amyloid within muscle does not necessarily equate to clinically significant myopathy. Amyloid myopathy is probably underdiagnosed due to the limited use of muscle biopsies and potential under-detection of amyloid deposition in muscle specimens. Histopathologically, it is characterized by amyloid deposition predominantly within the perimysial and endomysial blood vessel walls and perivascular regions. Neurogenic features are also frequently observed in muscle biopsies from patients with systemic amyloidosis-associated or isolated myopathy. While amyloid microangiopathy and neurogenic features seem to dominate amyloid myopathy pathology, the pathogenesis remains elusive. In this article, we comprehensively review amyloid myopathy pathogenesis and histopathological correlates including specific workup for detection of amyloid deposition, as well as clinical manifestations, diagnostic approach, and management. This review reveals that amyloid myopathy may represent a microangiopathic-neurogenic-myopathic process. PMID: 42911938 | DOI: 10.1093/jnen/nlag112

Pediatr Blood Cancer. 2026 Aug 3:e70607. doi: 10.1002/1545-5017.70607. Online ahead of print. ABSTRACT BACKGROUND: Sickle cell disease (SCD) has undergone major changes in the last decades. Its prevalence has been steadily increasing and numerous advances have been made in the management of the disease. However, the effect in real-life setting of these major changes is unknown, particularly in a Canadian environment. PROCEDURE: We aimed to assess the impact of these changes on the evolution in the healthcare utilization (HCU) of children with SCD in a Canadian pediatric tertiary center from 2009 to 2024. RESULTS: The number of children with SCD followed at our center more than doubled (221 to 499 patients). Practice changes reduced mean time to hydroxyurea introduction, resulting in a steady annual increase in mean fetal hemoglobin across the patients with HbSS. Reflecting the number of patients followed, the absolute number of annual outpatient and ED visits increased significantly (1207 to 1769 and 192 to 526, respectively). However, there was a significant decrease in the mean number of outpatient visits (5.46 to 3.55 [p = 0.03]) and hospitalizations (1.18 to 0.58 [p<0.0001]) by patient annually. There was also a reduction in the percentage of admissions after an ED visit (62.5% to 42.6% [p<0.0001]). CONCLUSION: Although the number of patients with SCD followed at our institution drastically increased in 15 years, the practice changes were effective and likely mitigated the impact on admissions. It illustrates the significant impact of improved management in the care of patients with SCD. Allocated resources need to reflect the overall increase in HCU to allow for continuous optimal care of this vulnerable population. PMID: 42544872 | DOI: 10.1002/1545-5017.70607

Chest. 2026 Jul 30:S0012-3692(26)00952-9. doi: 10.1016/j.chest.2026.05.051. Online ahead of print. ABSTRACT BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is an important phenotype in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION: What is the prevalence of CPFE? What is the predictive performance of the CPFE index and of physiologic airflow obstruction for CT imaging emphysema extents? Is the extent of emphysema on CT imaging associated with outcomes in patients with fibrotic ILD? STUDY DESIGN AND METHODS: Consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who underwent a standardized visual assessment of the baseline high-resolution CT imaging of the chest from a prospective registry were included. CPFE was defined as emphysema extent of ≥ 15% on CT imaging, with sensitivity analyses using different thresholds: ≥ 5%, ≥ 10%, and ≥ 20%. Emphysema subtypes were categorized based on their predominant distribution: centrilobular, paraseptal, or panlobular. The CPFE index was derived using measurements of spirometry and diffusion capacity of the lungs for CO 2 . RESULTS: The prevalence of CPFE at baseline was 20% for IPF (92/455) and 7% in non-IPF fibrotic ILD (84/1121). Both FEV 1 to FVC ratio less than the lower limit of normal and < 0.70 showed poor sensitivity (IPF, 11.1%-18.9%; non-IPF fibrotic ILD, 13.1%-23.7%) for detecting emphysema on CT imaging, although high specificity (IPF, 96.2%-98.8%; non-IPF fibrotic ILD, 92.8%-95.8%). The CPFE index was correlated moderately with extent of emphysema on CT imaging in both IPF (r = 0.48) and non-IPF fibrotic ILD (r = 0.41), but with poor agreement and wide limits of agreement on Bland-Altman analysis. Extent of emphysema on CT imaging of ≥ 20% was associated consistently with differences in lung function trajectories and worse transplant-free survival in IPF and non-IPF fibrotic ILD. No significant relationships were noted between emphysema subtypes and health outcomes. INTERPRETATION: Our results show that coexisting emphysema is important in both IPF and non-IPF fibrotic ILD, with extent of emphysema on CT imaging of ≥ 20% being associated with worse health outcomes. Both physiologic and radiologic assessments are needed to identify coexistent emphysema in patients with fibrotic ILD. PMID: 42413722 | DOI: 10.1016/j.chest.2026.05.051