Citations

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

Abstract The International League Against Epilepsy (ILAE) has updated the operational classification of epileptic seizures, building upon the framework established in 2017. This revision, informed by the implementation experience, involved a working group appointed by the ILAE Executive Committee. Comprising 37 members from all ILAE regions, the group utilized a modified Delphi process, requiring a consensus threshold of more than two thirds for any proposal. Following public comments, the Executive Committee appointed seven additional experts to the revision task force to address and incorporate the issues raised, as appropriate. The updated classification maintains four main seizure classes: Focal, Generalized, Unknown (whether focal or generalized), and Unclassified. Taxonomic rules distinguish classifiers, which are considered to reflect biological classes and directly impact clinical management, from descriptors, which indicate other important seizure characteristics. Focal seizures and those of unknown origin are further classified by the patient's state of consciousness (impaired or preserved) during the seizure, defined operationally through clinical assessment of awareness and responsiveness. If the state of consciousness is undetermined, the seizure is classified under the parent term, that is, the main seizure class (focal seizure or seizure of unknown origin). Generalized seizures are grouped into absence seizures, generalized tonic–clonic seizures, and other generalized seizures, now including recognition of negative myoclonus as a seizure type. Seizures are described in the basic version as with or without observable manifestations, whereas an expanded version utilizes the chronological sequence of seizure semiology. This updated classification comprises four main classes and 21 seizure types. Special emphasis was placed on ensuring translatability into languages beyond English. Its aim is to establish a common language for all health care professionals involved in epilepsy care, from resource‐limited areas to highly specialized centers, and to provide accessible terms for patients and caregivers.

ABSTRACT Background Membranous nephropathy (MN) is a leading cause of nephrotic syndrome (NS). Since the identification of anti–phospholipase A2 receptor (anti-PLA2R) antibodies in 2009, the use of laser microdissection and tandem mass spectrometry (LMD/MS) has allowed the discovery of several target antigens in MN. Methods In this retrospective cohort study, adult patients evaluated at the Division of Nephrology at Brotzu Hospital (Cagliari, Italy) with biopsy-proven MN and a negative serological test for anti-PLA2R antibody underwent LMD/MS, performed at the Department of Laboratory Medicine and Pathology of Mayo Clinic (Rochester, MN, USA). Results Twenty-four cases of biopsy-proven MN were available for antigen detection by LMD/MS studies. High total spectral counts of PLA2R were detected in 12 out of 24 (50%) cases. In addition, high spectral counts of THSD7A and NELL1 were detected in two cases each, and EXT1/EXT2 and NCAM1 in one case each. Five putative antigens have been detected: SULF1, PGLYRP, HYAL1, THBS and SEZ6L2. Conclusions Our study highlights at least two interesting considerations. First, the determination of PLA2R on renal tissue in the diagnosis of PLA2R-associated MN is emphasized since 50% of our cases were falsely diagnosed with PLA2R-negative MN based on the serum anti-PLA2R antibodies determination. Second, our study shows six patients with MN likely associated with putative antigens, two of them showing new antigens never described before in literature (HYAL1 and THBS1). This high prevalence of putative antigens in our cohort is not easily explainable and paves the way for evaluating specific factors in the Sardinian population that could explain this evidence.

Key Points In phospholipase A2 receptor-membranous nephropathy, clinical variables and antibody levels over 3 or 6 months of treatment were predictors of remission at 1 year. Prediction models at 3 and 6 months had similar performance predicting remission, with the 3-month model allowing for earlier assessment of response. The 3-month and 6-month prediction models could be applied in those treated with supportive therapy, rituximab, calcineurin inhibitors, or cyclophosphamide. Background In patients with antiphospholipase A2 receptor antibody–associated membranous nephropathy, there is currently no accepted method to predict an individual's probability of remission after treatment with immunosuppression or supportive therapy using changes in antibody levels and clinical variables during the first 3–6 months of therapy. Methods Using a cohort of 187 patients from the Glomérulopathie extramembraneuse rituximab, Membranous Nephropathy Trial of Rituximab, and Sequential Treatment with Tacrolimus and Rituximab Versus Alternating Corticosteroids and Cyclophosphamide in primary Membranous Nephropathy clinical trials with antibody levels at baseline ≥14 RU/ml, we derived logistic regression models to predict proteinuria remission at 12 months that can be used at baseline or after 3 or 6 months of treatment. Treatment exposures in the trials included supportive therapy, rituximab, calcineurin inhibitors, and cyclophosphamide. Predictors in the models included male sex and baseline and changes in serum albumin, proteinuria, and antibody levels, with or without changes in eGFR. Results Proteinuria remission at 12 months was achieved in 107 patients. Compared with the model at baseline, the 3-month and 6-month models had better model fit with lower Akaike information criterion (186/158 versus 225) and higher R 2 (52.7%/62.4% versus 25.8%), better discrimination with higher C-statistic (0.87 and 0.91 versus 0.75, P < 0.001), and better calibration with lower integrated calibration index (0.89%/2.22% versus 2.51%). The 3-month and 6-month models had no consistent difference in prediction performance, and decision curve analysis demonstrated similar net benefit for treatment decisions based on either model up to a threshold probability of 31%. Prediction performance was similar after internal validation using optimism correction. Prediction performance was maintained within subgroups of different treatment regimens, including supportive therapy, rituximab, calcineurin inhibitors, and cyclophosphamide. Conclusions Either the 3-month or 6-month models can be used in patients with antiphospholipase A2 receptor antibody associated membranous nephropathy after 3 or 6 months of treatment with a variety of immunosuppression or supportive therapy to predict remission status at 12 months.

Abstract Background The Global Leadership Initiative on Malnutrition (GLIM) introduced an approach for malnutrition diagnosis in 2019 that comprised screening followed by assessment of three phenotypic criteria (weight loss, low body mass index [BMI], and low muscle mass) and two etiologic criteria (reduced food intake/assimilation and inflammation/disease burden). This planned update reconsiders the GLIM framework based on published knowledge and experience over the past 5 years. Methods A working group ( n = 43 members) conducted a literature search spanning 2019–2024 using the keywords “Global Leadership Initiative on Malnutrition or GLIM.” Prior GLIM guidance activities for using the criteria on muscle mass and inflammation were reviewed. Successive rounds of revision and review were used to achieve consensus. Results More than 400 scientific reports were published in peer‐reviewed journals, forming the basis of 10 systematic reviews, some including meta‐analyses of GLIM validity that indicate strong construct and predictive validity. Limitations and future priorities are discussed. Working group findings suggest that assessment of low muscle mass should be guided by experience and available technological resources. Clinical judgment may suffice to evaluate the inflammation/disease burden etiologic criterion. No revisions of the weight loss, low BMI, or reduced food intake/assimilation criteria are suggested. After two rounds of review and revision, the working group secured 100% agreement with the conclusions reported in the 5‐year update. Conclusion Ongoing initiatives target priorities that include malnutrition risk screening procedures, GLIM adaptation to the intensive care setting, assessment in support of the reduced food intake/assimilation criterion, and determination of malnutrition in obesity.

Abstract Hereditary tumor predisposition syndromes pose a challenge for early detection and timely treatment of tumors. In von Hippel–Lindau disease, desirable personalized surveillance programs are lacking due to insufficient data on genotype-specific risk profiles of individual mutations. To describe neoplastic risk profiles for carriers of pathogenic and likely pathogenic VHL germline mutations, our observational study recruited 1,350 participants from 40 centers worldwide. 432 different VHL germline mutations were observed, with p.Asn78Ser, p.Arg161Ter, p.Arg161Gln, p.Arg167Gln, p.Arg167Trp and p.Tyr98His being the six most frequent, occurring in a total of 493 carriers (36.5%) and in ≥30 patients each. Age-related penetrance risks for retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine tumors and pheochromocytoma/paraganglioma in carriers of the most frequent VHL mutations were assessed. In addition, the number of organs affected, the frequency of surgery and the outcome are reported. Pairwise comparisons of the age-dependent tumor penetrance of these six mutations showed that 47 out of 90 pairs were significantly different. The most significant associations were found in p.Tyr98His (n = 19), followed by p.Arg161Ter (n = 10). All pairwise comparisons of mutations affecting different codons showed at least one significant (P &lt; 0.05) difference, except for p.Asn78Ser vs p.Arg161Ter. Thus, tumor risk varied by VHL mutation type and location, but did not differ between the truncating mutation p.Arg161Ter and the missense mutation p.Asn78Ser. Our study demonstrates the importance of mutation-specific phenotype prediction. With appropriate validation, the data have important implications for risk assessment and decision making in tumor prevention for carriers of the respective VHL mutations.

OBJECTIVE Core outcome sets (COSs) are needed to promote data consistency across studies as well as data synthesis and comparability. The goal of the current study was to utilize a modified Delphi process to develop a COS–sciatic injury and neuropathy evaluation (COS-SINE). METHODS A five-stage approach was utilized to develop the COS-SINE: stage 1, consortium development; stage 2, literature review to identify potential outcome measures; stage 3, Delphi survey to develop consensus on outcomes for inclusion; stage 4, Delphi survey to develop definitions; and stage 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set–STAndards for Development recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. Three participants were excluded on the basis of agreed upon participation rules. The final COS-SINE consisted of 36 data points/outcomes covering the domains of demographics, diagnostics, patient-reported outcomes, motor and sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with consensus optimal time points for assessment identified as preoperatively and 3, 6, 12, 24, and 36 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-SINE should serve as a minimum set of data that should be collected in all future neurosurgical studies on sciatic nerve injury and neuropathy. Incorporation of this COS should help improve consistency in reporting and data synthesis and comparability and should minimize outcome-reporting bias.

Abstract “Nonclassical” myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) represent a heterogeneous group of malignancies characterized by a wide range of clinical manifestations. Unlike classical MPNs, there is no standardized management approach for these conditions, particularly concerning the indications for and management of allogeneic hematopoietic cell transplantation. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) have collaborated to develop shared guidelines aimed at optimizing the selection and management of patients with these rare forms of neoplasms. A comprehensive review of the literature from the publication of the revised fourth edition of the (2016) World Health Organization classification onward was conducted. A multidisciplinary group of experts in the field convened to produce this document, which was developed through multiple rounds of draft circulation. Key recommendations include the early identification of potential transplant candidates, particularly in cases of chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL)/CEL, not otherwise specified (CEL-NOS), myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions with FGFR1, JAK2, ABL1, and FLT3 rearrangements, MDS/MPN with neutrophilia/atypical chronic myeloid leukemia, and MDS/MPN, NOS. For patients with MPN, NOS/MPN unclassifiable, standard recommendations for myelofibrosis should be applied. Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended on the basis of established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.