Maladies orphelines

Blood Coagul Fibrinolysis. 2026 Apr 3. doi: 10.1097/MBC.0000000000001423. Online ahead of print.ABSTRACTOBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal blood disorder due to deficiency of the enzyme ADAMTS13. Recombinant ADAMTS13 (rADAMTS13) is a new treatment aimed at restoring enzyme activity. This study aimed to evaluate the efficacy and safety of rADAMTS13 compared to standard therapy or placebo in patients with congenital or acquired TTP using a systematic review and meta-analysis.METHODS: This PRISMA-compliant review searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and others up to March 30, 2025. We included randomized controlled trials (RCTs) comparing rADAMTS13 to standard therapy or placebo in patients with TTP.RESULTS: Two RCTs (one phase 3, one phase 2) involving 129 patients (67 rADAMTS13, 62 placebo) met inclusion criteria. No significant differences were observed for the primary clinical outcomes of acute TTP events (risk ratio (RR) = 0.58 [95% CI, 0.20-1.70]) or serious treatment-emergent adverse events (RR = 0.64 [95% CI, 0.31-1.34]). However, rADAMTS13 significantly increased ADAMTS13 activity levels (MD, 0.92 IU/ml [95% CI, 0.59-1.26]; P < 0.0001). Urticaria was significantly lower in the rADAMTS13 group (RR = 0.25 [95% CI, 0.06-0.96]; P = 0.04). No significant differences were noted for other adverse events (all P > 0.05).CONCLUSION: rADAMTS13 significantly enhances ADAMTS13 activity but did not demonstrate a significant improvement in key clinical outcomes. These findings, based on two RCTs, are of moderate to low certainty per GRADE assessment. Larger trials are needed to confirm the clinical benefits of rADAMTS13.PMID:41934124 | DOI:10.1097/MBC.0000000000001423

Glob Med Genet. 2026 Mar 20;13(2):100099. doi: 10.1016/j.gmg.2026.100099. eCollection 2026 Jun.ABSTRACTBACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder primarily caused by pathogenic variants in PKD1 and PKD2. Although molecular testing has revolutionized diagnosis, variability persists in testing strategies and diagnostic yields. This review aims to evaluate molecular genetic techniques used in ADPKD diagnosis and summarize evidence on their diagnostic performance.METHOD: Following a predefined protocol and PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for studies published between January 2015 and August 2025. Eligible studies included ≥ 30 clinically diagnosed ADPKD participants and reported patient-level diagnostic data. Two investigators independently extracted information on testing methods, diagnostic yield, and identified genes.RESULTS: From 23,718 records, 20 studies met inclusion criteria, with sample sizes ranging from 32 to 634 participants. Diagnostic methods included Sanger sequencing (SS), multiplex ligand-probe amplification (MLPA), long-range PCR (LR-PCR), targeted next-generation sequencing (NGS) panels, whole-exome sequencing (WES), and whole-genome sequencing (WGS). Detection rates ranged from 61% (LR-PCR) to 92% (targeted NGS). PKD1 and PKD2 variants accounted for 79.9% and 15.9% of cases, respectively. Additional variants were identified in GANAB, HNF1B, IFT140, PRKCSH, and PKHD1.CONCLUSION: Targeted NGS panels provided the highest diagnostic accuracy and cost-effectiveness for ADPKD. Complementary use of MLPA and LR-PCR improved detection of complex variants. Further optimization of sequencing workflows and variant interpretation will enhance diagnostic precision and clinical application. This review provides an evidence-based foundation for current diagnostic practices in ADPKD.PMID:41938343 | PMC:PMC13050056 | DOI:10.1016/j.gmg.2026.100099

Respirology. 2026 Apr 1. doi: 10.1002/resp.70246. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: High resolution computed tomography (HRCT) scan diagnostic classification for usual interstitial pneumonia (UIP) plays a critical role in therapeutic decision-making and clinical trial eligibility for interstitial lung disease (ILD) patients, but is subject to variability. A deep learning algorithm, the Systematic Objective Fibrotic Imaging Analysis Algorithm (SOFIA), has been validated to assist classification of HRCTs based on current guidelines. In this study, we evaluate the impact of SOFIA on inter-observer agreement for UIP classification and prognostic accuracy of clinicians' assessment of ILD HRCTs.METHODS: Radiologists and pulmonologists (reviewers) were invited to evaluate 203 HRCTs from a national fibrotic ILD registry, scoring each of four UIP categories (definite UIP, probable UIP, indeterminate, or alternative diagnosis). SOFIA outputs were then provided, and reviewers were able to reevaluate their scores. Changes in interobserver agreement for UIP classification and prognostic accuracy were calculated.RESULTS: Three hundred twelve reviewers (120 radiologists, 192 pulmonologists) from 49 countries evaluated 203 HRCT scans. Following SOFIA, inter-observer diagnostic agreement improved for definite UIP from moderate to good (ICCpre = 0.54[0.50-0.60]; ICCpost = 0.70[0.66-0.74]), and for probable UIP from fair to moderate (ICCpre = 0.30[0.27-0.35]; ICCpost = 0.53[0.49-0.58]). Following SOFIA, there was improved prognostic accuracy for reviewers' definite UIP, probable UIP, and indeterminate scores (significant change in c-index), and the proportion of reviewers whose probable UIP scores were significantly predictive of transplant-free survival increased by 42%.CONCLUSION: Providing SOFIA algorithm output to clinicians reviewing HRCT scans improved diagnostic agreement and prognostic accuracy for fibrotic ILD. SOFIA may be a useful automated assistive tool to support improved diagnostic consistency.PMID:41923409 | DOI:10.1002/resp.70246

JMIR Pediatr Parent. 2026 Apr 6;9:e76937. doi: 10.2196/76937.ABSTRACTBACKGROUND: Sickle cell disease (SCD) is a genetic blood disorder affecting millions globally, with life-threatening complications, and most patients live in sub-Saharan Africa. Particularly, children with SCD have a high risk of stroke. Although early screening for stroke could help prevent many cases, access to effective stroke screening remains limited in low-resource settings (LRS). Existing traditional approaches are highly operator-dependent, costly, resource-intensive, or difficult to deploy at scale in pediatric care. These limitations highlight the urgent need for accessible, scalable, and child-appropriate stroke screening and assessment tools suitable for low-resource health care contexts.OBJECTIVE: The aims of this systematic literature review are to (1) uncover system-level barriers affecting stroke screening accessibility for patients with pediatric sickle cell disease (PSCD) in LRS, including underserved contexts within high-income countries; (2) identify existing and emerging stroke screening and assessment technologies and their implementation characteristics, such as feasibility, scalability, portability, and training requirements; and (3) propose a user-centered mobile health (mHealth) framework for stroke screening that improves accessibility and feasibility in resource-constrained health care settings.METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to organize the search process. A systematic search was conducted using an advanced query and defined eligibility criteria in the academic databases of PubMed, IEEE Xplore, Wiley Online Library, and Google Scholar. Studies published in English between January 1, 2021, and October 31, 2025, were selected. Collected data were arranged in a preformatted Microsoft Excel spreadsheet for analysis. Risk-of-bias assessment was performed using various risk-of-bias assessment tools because of the heterogeneity of the included studies. Narrative synthesis was used for data synthesis.RESULTS: The literature search initially identified 1465 studies, of which 28 (2%) were selected for analysis. Among the 28 studies, 10 (36%) focused on stroke screening accessibility for patients with PSCD in either low- and middle-income countries or other income-level countries for LRS, and 18 (64%) outlined key features and the feasibility of stroke screening technologies. Identified […]

Clin Oral Investig. 2026 Apr 15;30(5):177. doi: 10.1007/s00784-026-06865-0.ABSTRACTOBJECTIVE: Giant cell arteritis (GCA) is a granulomatous vasculitis affecting medium- and large-sized arteries, most commonly the temporal arteries. Delayed recognition can lead to severe complications, including irreversible vision loss and stroke. Dentists routinely obtain panoramic radiographs for dental assessment, where calcified carotid artery atheromas (CCAA) may appear as incidental findings in the cervical region. This study systematically evaluated the incidence of suspected CCAA detected on panoramic radiographs obtained for dental indications and considered the clinical relevance of these findings for dental practitioners.METHODS: A systematic search of MEDLINE, PubMed, and Embase databases was conducted to identify studies reporting calcified carotid artery atheromas detected on panoramic radiographs. Study selection followed PRISMA guidelines. Observational studies reporting CCAA on panoramic radiographs were included. Data extraction was performed independently, and pooled incidence estimates were calculated using a random-effects meta-analysis.RESULTS: Thirty-four cross-sectional studies met the inclusion criteria. The pooled incidence of suspected CCAA detected on panoramic radiographs was approximately 7% (95% CI 5-9%). Substantial heterogeneity was observed among studies. These findings indicate that incidental radiographic detection of cervical calcifications occurs in a measurable proportion of dental patients undergoing panoramic imaging.CONCLUSIONS: Although panoramic radiography is not a screening modality for carotid artery disease, dentists should recognize potential calcified carotid atheromas when interpreting images obtained for dental purposes. Identification of suspicious calcifications and appropriate referral for medical evaluation may support early assessment of patients with possible vascular risk factors.CLINICAL RELEVANCE: Routine dental examinations and panoramic radiography may allow early risk identification, underscoring the importance of interdisciplinary collaboration.PMID:41984118 | DOI:10.1007/s00784-026-06865-0

Leuk Lymphoma. 2026 Apr 16:1-10. doi: 10.1080/10428194.2026.2653811. Online ahead of print.ABSTRACTMyelodysplastic syndromes (MDS) are rare in women of reproductive age, and evidence regarding pregnancy outcomes remains limited. A systematic literature search identified 21 publications reporting MDS recognized before or during pregnancy, encompassing 69 pregnancies. The data were descriptively analyzed and stratified by timing of MDS diagnosis. Of the 69 pregnancies, 52% involved women diagnosed with MDS before conception, while 48% were diagnosed during pregnancy. Leukemic transformation occurred exclusively among cases diagnosed during pregnancy. The majority of pregnancies resulted in live births, with rates exceeding 93% in both groups, and neonatal complications being uncommon. MDS diagnosed during pregnancy appears to confer higher maternal risk, underscoring the need for early recognition and multidisciplinary management. This scoping review suggests that pregnancy can be successfully carried to term in selected women with MDS, particularly when disease stability is established prior to conception.PMID:41989197 | DOI:10.1080/10428194.2026.2653811

Semin Arthritis Rheum. 2026 Apr 8;78:152975. doi: 10.1016/j.semarthrit.2026.152975. Online ahead of print.ABSTRACTOBJECTIVE: To identify the most important and relevant items to consider when developing criteria to measure response to treatment in giant cell arteritis (GCA).METHODS: As part of an ongoing project to develop response criteria for GCA, a 4-round web-based Delphi exercise was conducted. Participants included patients with GCA and health professionals with expertise in GCA. Participants rated the importance (1=lowest, 9=highest) of 51 items selected based on a systematic literature review, grouped into six domains, and could suggest additional items. Items scored 7-9 by at least 70% of health professionals and 70% of patients were considered critically important and to have reached consensus. In the last round of the Delphi, participants ranked the top 10 most relevant items. A task force (n = 32 members) meeting followed to review the Delphi results, discuss rankings, and finalize the selection of items.RESULTS: One hundred eighty-seven physicians and 85 patients, from 38 countries, participated in the Delphi exercise. Twenty-four (75%) task force members participated in the virtual meeting. Thirteen new items were proposed in round 1. Twenty-four items were rated as critically important. No items were excluded during any round, and consensus was not reached for 40 items. The top 3 highest rated items by both patients and physicians were headache (ranked highest by 52%), amaurosis fugax (highest=10%), and jaw claudication (highest=7%). Twelve items were selected for the next phase of the project.CONCLUSION: Experts and patients identified 12 items considered important for measuring response to treatment in GCA.PMID:41985413 | DOI:10.1016/j.semarthrit.2026.152975

Ann Hematol. 2026 Apr 17;105(5):249. doi: 10.1007/s00277-026-06900-w.NO ABSTRACTPMID:41995852 | DOI:10.1007/s00277-026-06900-w

J Comp Eff Res. 2026 Apr 17:e250206. doi: 10.57264/cer-2025-0206. Online ahead of print.ABSTRACTAim: To indirectly compare the efficacy and safety of elafibranor and seladelpar, as second-line treatments for primary biliary cholangitis. Materials & methods: Bayesian network meta-analyses compared data from randomized-controlled studies of elafibranor and seladelpar identified by a systematic literature review up to June 2024: (a) elafibranor (n = 108) versus placebo (n = 53; ELATIVE [NCT04526665]) and (b) seladelpar (n = 128) versus placebo (n = 65; RESPONSE [NCT03301506]). Patients from ELATIVE not meeting the RESPONSE upper limit of normal (ULN) criteria for alkaline phosphatase (ALP) and total bilirubin were excluded (n = 16); summary statistics for ELATIVE were recalculated using the new dataset. Random-effects models assessed the outcomes of cholestasis response (ALP <1.67 × ULN, ALP reduction ≥15% from baseline and total bilirubin ≤ULN), ALP normalization, change from baseline in ALP and pruritus, pruritus as a treatment-emergent adverse event and all-cause discontinuation. Results: Elafibranor-treated patients had greater odds of achieving cholestasis response than placebo- (median odds ratio [95% credible interval]: 84.79 [12.49, 2513.00]) or seladelpar-treated patients (13.02 [1.45, 420.20]), with posterior probabilities ≥99% that odds were higher with elafibranor than seladelpar or placebo. Among patients with ALP ≥350 U/l, the median odds ratio [95% credible interval] of cholestasis response for elafibranor-treated patients versus seladelpar-treated patients was 18.71 [0.65, 10,610.00], with a 95.2% posterior probability that odds were higher with elafibranor than seladelpar. For all other outcomes, there was no strong evidence of a difference between treatments. Conclusion: Bayesian network meta-analyses found strong probabilistic evidence supporting the treatment benefit of elafibranor compared with seladelpar for the achievement of cholestasis response at 52 weeks, while the treatment effect on other outcomes was uncertain. Head-to-head studies are needed to validate results of these indirect comparisons.PMID:41995445 | DOI:10.57264/cer-2025-0206

Epilepsy Behav. 2026 Apr 17;180:111050. doi: 10.1016/j.yebeh.2026.111050. Online ahead of print.ABSTRACTOBJECTIVE: Peri-ictal abnormalities on diffusion-weighted magnetic resonance imaging (DWI-PMA) are well established in patients with status epilepticus (SE). SE occurs in approximately 4-9% of patients with idiopathic generalized epilepsy (IGE), and outcomes are generally more favorable than in SE due to other causes. We investigated whether the rate of DWI-PMA differs between SE associated with IGE and SE due to other etiologies.METHODS: We performed a systematic review and individual patient meta-analysis of all studies published up to January 27th, 2025, reporting adult patients with non-anoxic SE and data on DWI-PMA.RESULTS: A total of 4,227 studies were screened, of which 185 met eligibility criteria (134 single case reports, 32 cohort studies, and 19 conference abstracts). Individual patient data were available for 531 patients from 17 studies. In addition, cumulative data from 326 patients with reported DWI-PMAs were available from 15 further studies. Among 38 patients with IGE who underwent peri-ictal MRI, none demonstrated DWI-PMAs associated with typical absence status or convulsive SE (estimated rate of 0%; one-sided 95% Clopper-Pearson confidence interval: 0%-10.0%). In contrast, 26.8% of patients with focal SE had DWI-PMAs (two-sided 95% Clopper-Pearson confidence interval: 24.8%-28.9%, p < 0.001, Fisher's exact test). Sensitivity analyses showed no major deviation from the expected prevalence of IGE based on population-based cohorts.CONCLUSION: SE associated with IGE is linked to a substantially lower risk of DWI-PMA as compared to SE due to other causes.PMID:42000483 | DOI:10.1016/j.yebeh.2026.111050

Actas Dermosifiliogr. 2026 Mar 20:104639. doi: 10.1016/j.ad.2026.104639. Online ahead of print.ABSTRACTHidradenitis suppurativa is a chronic inflammatory disease that typically presents with nodules, abscesses, tunnels, and scars in areas rich in pilosebaceous units, such as the axillae and the inguinal and anogenital regions. It is a condition with a high potential for progression, characterized by inflammation and pain, and has a significant psychological and social impact, markedly affecting quality of life. In addition, it is an underdiagnosed disease with a considerable diagnostic delay, which may lead to disabling situations.Therapeutic management is complex because it must be adapted to the clinical presentation and severity of the disease and often involves associated comorbidities. However, early management of the disease can prevent the progression of structural damage and improve both prognosis and patient quality of life.This article reviews the latest findings regarding the etiopathogenesis of the disease, diagnosis, and phenotyping models that assist in decision-making for disease management.PMID:41865977 | DOI:10.1016/j.ad.2026.104639

J Multidiscip Healthc. 2026 Jan 27;19:537644. doi: 10.2147/JMDH.S537644. eCollection 2026.ABSTRACTPURPOSE: This study aimed to illustrate the practical application and preliminary outcomes of a multidisciplinary team (MDT) approach in managing pediatric Fabry disease (FD), and provide a reference for the clinical management of this rare disease.METHODS: This single-center, prospective, observational case series was conducted at Beijing Children's Hospital. Between March 2021 and February 2024, five pediatric patients with FD who were managed by a dedicated MDT were enrolled. The MDT operated under a model of "identification and initiation in outpatient clinics, overall management by the core team, and specialist consultation as needed." The workflow covered a dual-path diagnostic pathway (MDT-initiated or external referral), pedigree screening, baseline assessment, individualized treatment, and long-term follow-up.RESULTS: Five pediatric FD probands were enrolled, with four diagnosed through the MDT-initiated pathway and one via external referral. For the four newly diagnosed patients, the MDT achieved a definitive diagnosis within 15-30 days of its engagement, despite a prior diagnostic odyssey of 2.0-5.9 years. Pedigree screening identified an asymptomatic sibling, enabling pre-symptomatic diagnosis. All patients commenced enzyme replacement therapy (ERT, agalsidase α) and did not develop adverse events. Through MDT coordination, they currently maintain continuous ERT at medical institutions with a travel time of 20 minutes to 2 hours. MDT-guided pain treatment, primarily with oxcarbazepine, effectively controlled neuropathic pain in most cases and improved quality of life. Psychosocial support alleviated family burdens, achieving treatment cost reimbursement rates of 60%-85%. At one-year follow-up, symptomatic improvement and significant reductions in globotriaosylsphingosine (Lyso-GL-3) levels were observed.CONCLUSION: The structured MDT approach facilitated accelerated diagnosis, early intervention, and comprehensive care in this pediatric FD cohort, yielding positive short-term outcomes and providing a practical reference for rare disease management.PMID:41877965 | PMC:PMC13006333 | DOI:10.2147/JMDH.S537644

Int Urogynecol J. 2026 Apr 1. doi: 10.1007/s00192-026-06532-8. Online ahead of print.ABSTRACTINTRODUCTION AND HYPOTHESIS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by bladder pain and lower urinary tract symptoms, predominantly affecting women and significantly impairing quality of life. Particularly in the absence of reliable knowledge about etiology and appropriate treatment of IC/BPS, clinical practice guidelines (CPGs) emphasize self-management as a key element of care. This review was aimed at comparing recommendations from CPGs, focusing on interventions to facilitate the self-management of women with IC/BPS.METHODS: A systematic review was conducted following a preregistered protocol. Databases and libraries MEDLINE, Guidelines International Network, Cochrane Library, National Institute for Health and Care Excellence, and Scottish Intercollegiate Guidelines Network were searched. Data extraction focused on interventions facilitating self-management, following the definition according to Corbin and Strauss. Recommendations were categorized and presented with grade of recommendation and level of evidence. CPG quality was appraised using the Appraisal of Guidelines for Research & Evaluation II instrument.RESULTS: Eight CPGs from Europe, North America, and Asia were included. All emphasized self-management as essential for IC/BPS care and contained recommendations across ten core categories, including dietary modification, bladder training, multimodal pain management, stress management, sexual health, and others. Although certain interventions such as physiotherapy referral and bladder diaries were frequently recommended, overall consistency and strength of evidence were limited.DISCUSSION: Although some consensus exists, recommendations vary in focus and often lack strong evidence. Gender-specific aspects are rarely addressed. These findings highlight the need for more consistent, evidence-informed, and patient-centered CPGs that explicitly account for the gendered and biographical dimensions of living with IC/BPS.PMID:41920328 | DOI:10.1007/s00192-026-06532-8

Anal Biochem. 2026 Mar 31:116120. doi: 10.1016/j.ab.2026.116120. Online ahead of print.ABSTRACTGaucher disease is a rare lysosomal storage disorder characterized by lipid accumulation. Emerging evidence suggests that patients with gaucher disease are at an increased risk of developing melanoma, yet the shared molecular mechanisms remain unclear. This study aimed to investigate and validate potential biomarkers commonly expressed in gaucher disease and melanoma through an integrated approach combining bioinformatics, in silico, and in vitro analyses. Gene expression profiles of gaucher disease and melanoma were downloaded from the Gene Expression Omnibus (GEO). Webgestalt was used to identify key pathways and genes. Enriched pathways and genes were detected using the Enrichr platform for commonly expressed genes. Cytoscape software identified 14 hub genes, from which one key gene was selected using a validation dataset from GEO. SwissADME was used to predict 8 drug candidates. Docking analysis was performed to validate the binding capacity of protein and drug candidates. Among them, colchicine exhibited lipid accumulation-inhibiting effects in a gaucher cell model, suggesting it as a potential therapeutic candidate.PMID:41933778 | DOI:10.1016/j.ab.2026.116120

Urologie. 2026 Apr 13. doi: 10.1007/s00120-026-02812-9. Online ahead of print.ABSTRACTBACKGROUND: In July 2025, the S2k guideline on the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS), developed under the auspices of the German Society of Urology (DGU), was published via the Association of the Scientific Medical Societies in Germany (AWMF) following comprehensive revision. The update aimed to improve diagnostic and therapeutic clarity and clinical applicability.OBJECTIVE: This article summarizes the key updates of the revised guideline and provides practical guidance for the clinical management of patients with IC/BPS.RESULTS: Major revisions include an updated definition and classification of IC/BPS in accordance with the WHO ICD-11 framework and an expanded overview of current pathogenetic concepts. A clearly structured, multimodal treatment algorithm has been implemented, integrating pharmacological, intravesical, interventional, neuromodulatory, and nonpharmacological therapies. Particular focus is placed on psychosocial comorbidities, individualized dietary management, pelvic floor physiotherapy, pain medicine, and urological rehabilitation.CONCLUSION: The updated S2k guideline provides an evidence-informed, interdisciplinary, and clinically applicable framework for the management of IC/BPS. Careful diagnostic evaluation and individualized multimodal treatment strategies are essential to improve symptom control and long-term quality of life in affected patients.PMID:41974934 | DOI:10.1007/s00120-026-02812-9