Background The safety and efficacy of cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in late-onset Pompe disease (LOPD) were established in the randomised, double-blind, 52-week PROPEL study (NCT03729362) conducted across 24 countries, including Japan. An open-label extension (OLE; NCT04138277) is evaluating long-term cipa+mig outcomes. In Japan, cipa+mig was also available before marketing authorisation in an expanded access study (ATB200-19). This case series summarises the efficacy and safety of cipa+mig in Japanese patients in PROPEL, PROPEL OLE and ATB200-19.Methods Endpoints included 6-minute walk distance (6MWD), forced vital capacity (FVC), biomarkers and safety. Cipa+mig (20 mg/kg intravenous cipa and 130–260 mg oral mig (weight-based dosing)) and alg+pbo (20 mg/kg intravenous alg and oral pbo) were given biweekly. Patients randomised to alg+pbo in PROPEL received cipa+mig in the OLE. Safety was assessed at every visit, and biomarkers at weeks 2, 4, 6, 12, 26, 38, 52 and every 26 weeks thereafter.Results Six patients from PROPEL/OLE (cipa+mig, n=2; alg+pbo, n=4; all enrolled in the OLE) and four from ATB200-19 were included. Two patients discontinued treatment: one in the OLE (anaphylactic reaction) and one in ATB200-19 (withdrawal of consent). For evaluable patients (n=8), 6MWD remained stable or improved from baseline to weeks 52 and 104. In PROPEL/OLE, FVC varied with most patients improving with cipa+mig treatment; in ATB200-19, FVC remained stable to week 104. In PROPEL/OLE and ATB200-19, biomarker levels improved or stabilised by week 104, including in the PROPEL switch group, where levels worsened at week 52 but improved after switching to cipa+mig. Seven patients experienced treatment-related adverse events. No deaths occurred.Conclusions Although the number of patients was small, the efficacy and safety of cipa+mig in Japanese patients from PROPEL/OLE and ATB200-19 were generally sustained and durable responses consistent with positive results in the overall PROPEL population.
Background The aim of this systematic review is to assess the evidence of the effect of cryotherapy on the development of chemotherapy-induced peripheral neuropathy (CIPN) in patients with breast cancer in neoadjuvant or adjuvant chemotherapy.Method Studies investigating the effect of cryotherapy as a preventive intervention for CIPN in patients with breast cancer treated with taxanes were eligible for inclusion. Non-English and non-German publications and studies inaccessible due to paywall restrictions were excluded. A systematic literature search was conducted in PubMed and Embase on 29 May 2026. The certainty of evidence was assessed using the GRADE method.Results Twenty-two studies involving 3369 participants were included.The included evidence suggests that cryotherapy may reduce the incidence and severity of CIPN in patients with breast cancer receiving taxanes. However, the certainty of the evidence was low overall because of study limitations such as small sample sizes, non-randomised study designs and heterogeneity.Conclusion The preventive effect of cryotherapy on the development of CIPN in patients with breast cancer receiving taxanes cannot be ruled out. The overall quality of evidence in the included studies is low. Therefore, it is not possible to conclude with certainty if cryotherapy can prevent the development of CIPN. Larger randomised controlled trials using objective measures such as nerve conduction studies are needed.
Background Progesterone signalling is a key determinant of meningioma behaviour, particularly in skull base tumours. Cyproterone acetate-associated meningiomas stabilise or regress after withdrawal Whether similar reversibility follows cessation of depot medroxyprogesterone acetate (DMPA), a widely used long-acting injectable contraceptive, is poorly characterised.Methods Retrospective case series of three women with intracranial meningiomas who discontinued DMPA following neurosurgical assessment, assessed with post-contrast CT (Cases 1 and 2) or magnetic resonance imaging (Case 3).Results All had prolonged DMPA exposure (approximately 14–27 years) and predominantly skull base disease with WHO grade I meningothelial histology. Each demonstrated measurable regression of enhancing soft-tissue tumour after cessation, despite marked heterogeneity in disease burden and chronicity, including one patient with multifocal meningiomatosis and more than a decade of documented progression. Hyperostotic bone showed no regression, and two patients required optic nerve and orbital decompression for progressive visual loss despite soft-tissue regression.Conclusion DMPA-associated meningiomas can regress following drug withdrawal, but the response is confined to the soft-tissue component. Persistent hyperostosis may continue to cause compression, and withdrawal should not be assumed to remove the need for surgery. These findings support routine assessment of progestin exposure in patients with meningioma.
Introduction Tubercular meningitis (TBM) is associated with high morbidity and mortality due to intense inflammatory responses causing basal exudates, vasculitic infarcts, hydrocephalus and cranial nerve palsies. Paradoxical reaction (PR) occurs in nearly 30% of patients and contributes to clinical deterioration during treatment. Dysregulated inflammatory mediators in serum and cerebrospinal fluid (CSF) have been implicated in PR and adverse outcomes in TBM. Objective This study evaluated baseline serum and CSF inflammatory biomarkers for predicting PR and vasculitic infarcts in newly diagnosed TBM patients. Methods In this prospective observational study, 151 treatment-naïve TBM patients fulfilling Marais consensus criteria were enrolled. Baseline clinical, radiological, serum and CSF inflammatory markers were assessed and repeated during PR/stroke. Serum markers included high-sensitivity C reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), ferritin, albumin, D-dimer, neutrophil–lymphocyte ratio (NLR) and systemic immune-inflammation index. CSF analysis included adenosine deaminase, NLR, protein, glucose and leucocyte count. Results Among 151 patients (mean age 32.7±14.5 years), 43 (28.4%) developed PR, most commonly within 1–2 months of antitubercular therapy initiation. Altered sensorium (58.1%) and progression of hydrocephalus (60.5%) were common manifestations. Higher baseline ESR, hsCRP, LDH, ferritin, D-dimer and lower serum albumin were significantly associated with PR. Serum ferritin showed the best predictive accuracy (area under the curve 0.910; cut-off ≥451 µg/L; sensitivity 88.4%, specificity 88.9%). On multivariable analysis, serum ferritin (OR 1.004; p=0.001) and ESR (OR 1.020; p=0.033) remained independent predictors. Conclusions Serum inflammatory markers, particularly ferritin and ESR, may serve as useful predictors of PR in TBM. These findings support an immune-mediated mechanism underlying paradoxical worsening and may help identify high-risk patients who could benefit from early anti-inflammatory or immune-modulatory therapy.
