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Objective Despite the need for diagnostics and research, data on fluid biomarkers in hereditary spastic paraplegia (HSP) are scarce. We, therefore, explore Neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of patients with hereditary spastic paraplegia and provide information on the influence of demographic factors. Methods The study recruited 59 HSP cases (33 genetically confirmed) and 59 controls matched in age and sex. Neurofilament light chain levels were assessed by enzyme‐linked immunosorbent assay. The statistical analysis included the effects of age, sex, and genetic status (confirmed vs. not confirmed). Results Levels of CSF NfL were significantly increased in patients with hereditary spastic paraplegia compared to controls (median 741 pg/mL vs. 387 pg/mL, p < 0.001). Age (1.4% annual increase) and male sex (81% increase) impacted CSF NfL levels in patients. The age‐dependent increase of CSF NfL levels was steeper in controls (2.6% annual increase). Thus, the CSF NfL ratio of patients and matched controls—expressing patients’ fold increases in CSF NfL—declined considerably with age. Interpretation CSF NfL is a reliable cross‐sectional biomarker in hereditary spastic paraplegia. Sex is a relevant factor to consider, as male patients have remarkably higher CSF NfL levels. While levels also increase with age, the gap between patients and controls is narrowing in older subjects. This indicates distinct temporal dynamics of CSF NfL in patients with hereditary spastic paraplegia, with a rise around phenotypic conversion and comparatively static levels afterward.

Objective Neurological autoimmune peripheral and central nervous system disorders can be associated with anti-sulfatide antibodies. These antibodies are considered potential diagnostic biomarkers, although their additional diagnostic value in neurological fields has been increasingly questioned. Given the little evidence of anti-sulfatide antibodies’ frequency and diagnostic value in neurology, we aimed to fill this knowledge gap by investigating 10 years of data. Methods This retrospective study analyzed the results of the anti-ganglioside dot kits (GA Generic Assays GmbH) from 1318 serum samples and 462 cerebrospinal fluid (CSF) samples for the frequency, sensitivity, and specificity of anti-sulfatide antibodies in neurological disorders. Results Although anti-sulfatide antibodies are rarely present in neurological autoimmune disorders (serum IgM 2.5%, IgG 4.6%), they are also present in non-autoimmune diseases (serum IgM 1.2%, IgG 2.5%) and lack sensitivity and specificity towards being a diagnostic marker. Furthermore, anti-sulfatide antibodies are rarely found in CSF (e.g., no positive results for IgM), and including so-called borderline results ((+)) increases sensitivity and the false-positive rate in serum and CSF. Discussion While anti-sulfatide antibodies appear more frequently in neurological autoimmune diseases, they are rare overall and provide very limited diagnostic value in determining specific neurological diseases and—more importantly—if a neurological disease has a potential autoimmune etiology.

Background and purpose Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller–Fisher syndrome (MFS) and Guillain–Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross‐responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant. Methods In this 10‐year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti‐Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross‐responsiveness. Results Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross‐responsiveness was observed in 39.6% of all positive serum AGA. Conclusions Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross‐responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.

To evaluate the clinical outcomes of an antibiotic-loaded calcium sulphate-hydroxyapatite biocomposite (ALB) used specifically in staged surgical protocols for chronic osteomyelitis and nonunions, including large bone defects resulting from the necessary debridement of necrotic bone. This retrospective multicenter study analyzed 101 patients treated between 2013 and 2020. Inclusion criteria comprised adult patients with bone defects resulting from osteomyelitis, septic nonunion, or aseptic nonunion, treated with ALB (gentamicin or vancomycin) in a staged procedure. The primary outcome was treatment success, defined as infection eradication and stable bone consolidation without unplanned surgical revision. Secondary outcomes included revision rates, reinfection rates, and biomaterial-related side effects such as white drainage. Treatment success was achieved in 30.7% of patients. The overall revision rate was 58.4%, and the reinfection rate was 45.5%. The mean defect size was 4.1 cm. Statistical analysis identified larger defect sizes and higher volumes of implanted ALB as significant risk factors for failure. \"White drainage\" was observed in 13.9% of patients and was significantly associated with the use of larger material volumes. The use of ALB in staged protocols for large bone defects is associated with high revision and reinfection rates. These findings identify the limits of the technique and sharpen its indication spectrum, standing alongside the favorable outcomes reported for single-stage procedures in smaller defects. In large defects, the resorption of the carrier may outpace bone ingrowth, leading to recurrence of infection. Consequently, the use of ALB in large defects cannot be recommended based on these data.

The emergency obstetric care (EmOC) monitoring framework has been used for decades to monitor the availability and use of EmOC services in low- and middle-income countries (LMICs). EmOC monitoring is based around eight signal functions, a shortlist of key clinical interventions capable of averting deaths from the main direct causes of maternal mortality, categorised between two levels of care: basic and comprehensive, with a newborn resuscitation signal function added in 2009. The Re-Visioning Emergency Obstetric and Newborn Care (EmONC) Project (2020–2024) aimed to update the EmOC approach to reflect new knowledge in maternal and newborn health (MNH), and to expand the scope of the original EmOC monitoring framework. The project used technical workstreams and workshops to arrive at new proposals. This paper reports on the approach used to build consensus on a revised set of EmONC signal functions and levels of care. Using a three-round online Delphi approach, consensus (≥85%) was sought from a diverse panel of global MNH experts on EmONC signal functions and their placement at different levels of care, based on existing evidence-based guidelines. The process was iterative, each round building on the previous, and embedded in the wider Re-Visioning EmONC project; the output from each round involved coordination of inputs from multiple tiers of technical experts, including UN agencies, via technical expert groups, workstreams and workshops. The Delphi study recruited 113 experts in MNH from a range of geographic and economic settings, specialities and professions, including clinical, academic and programme expertise. The output from the three rounds included substantial convergence, resulting in set of 25 signal functions (11 obstetric, 13 neonatal and 1 referral) that reflect the spectrum of EmONC required for women and newborns. The revised EmONC signal functions are intended as a simple approach to allow health system managers to visualise their EmONC services, and as a means to hold health systems accountable to provide the main interventions to avert preventable maternal and newborn morbidity and mortality, and stillbirths.

Despite Domain-Driven Design's proven value in managing complex business logic, a fundamental semantic expressiveness gap persists between generic modeling languages and tactical DDD patterns, causing continuous divergence between design intent and implementation. We envision a constraint-based tactical modeling environment that transforms abstract architectural principles into explicit, tool-enforced engineering constraints. At its core is a DDD-native metamodel where tactical patterns are first-class modeling primitives, coupled with a real-time constraint verification engine that prevents architectural violations during modeling, and bidirectional synchronization mechanisms that maintain model-code consistency through round-trip engineering. This approach aims to democratize tactical DDD by embedding expert-level architectural knowledge directly into modeling constraints, enabling small teams and junior developers to build complex business systems without sacrificing long-term maintainability. By lowering the technical barriers to DDD adoption, we envision transforming tactical DDD from an elite practice requiring continuous expert oversight into an accessible engineering discipline with tool-supported verification.