Search Results (635)

Background: Meningiomas (MG) are the most common form of benign intracranial tumors. Neuropsychological deficits are often noticed preoperatively. After surgical removal, both improvements and persistent neuropsychological deficits have been reported. Here we present the neuropsychological characteristics of a larger patient group following acute treatment for meningioma. Methods: This retrospective study is part of an overall project investigating the postoperative characteristics and rehabilitation outcomes of 151 patients following surgical removal of MG. Patients were recruited at the neurological department of m&i-Fachklinik Enzensberg between 2019 and 2024. In addition to demographic data and tumor characteristics, the neuropsychological reports were evaluated by two experienced (neuro)psychologists. Results: 69 patients underwent standardized testing in the neuropsychology department and were thus included in the analysis. Upon admission, 52.2% of these patients exhibited attention deficits, 48% showed executive deficits, and 44% had memory impairments. No correlation was found between the extent of resection or the occurrence of complications during surgery and cognitive deficits. However, there was a trend showing that higher-grade tumors were more likely to cause cognitive impairment. The location of the tumor did not correlate with the impaired cognitive domains. At discharge, fewer patients exhibited attention deficits, and those that did had less severe symptoms. Conclusions: Meningiomas are considered to be easily treatable. However, our data show that neuropsychological impairments frequently occur after acute treatment, which may not be given sufficient attention in practice. Even mild cognitive impairments can lead to problems in everyday life or at work. We therefore recommend detailed neuropsychological diagnosis and, if necessary, therapy for all patients after acute treatment. Full article

Background: Airway mucus plugging is a key but long-overlooked mechanism of persistent airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Type 2 (T2) cytokines, particularly interleukin (IL)-4 and IL-13, drive goblet cell metaplasia, MUC5AC overexpression, and impaired mucociliary clearance, while eosinophil-derived products increase mucus viscosity and promote plug persistence. Methods: A comprehensive narrative review was conducted by searching PubMed and ClinicalTrials.gov databases from inception to February 2026. Search terms included “mucus plugs,” “mucus plugging,” “biologics,” “dupilumab,” “tezepelumab,” “mepolizumab,” “benralizumab,” “IL-4,” “IL-13,” “MUC5AC,” “quantitative CT,” “functional respiratory imaging,” “asthma,” and “COPD.” Studies were included if they reported original data or systematic evidence on mucus plug quantification, biologic-mediated changes in mucus plug scores, or imaging modalities for mucus assessment in asthma or COPD. Editorials, case reports with fewer than three patients, and studies not available in English were excluded. Two authors (P.-V.M. and A.C.) independently screened titles and abstracts; discrepancies were resolved by consensus. Randomized controlled trials, observational studies, and preclinical studies evaluating mucus plug outcomes and T2-targeted therapies were included. Reference lists of retrieved articles were hand-searched for additional relevant publications. Results: A recent systematic review identified multiple randomized controlled trials and observational studies that showed CT-assessed mucus plug scores go down with biologic therapies targeting the T2 pathway in asthma. Observational data extend this evidence to anti-IL-5/IL-5Rα agents. The VESTIGE trial provided the first functional respiratory imaging evidence of mucus plug resolution with dupilumab. In COPD, the BOREAS/NOTUS and MATINEE trials established the efficacy of dupilumab and mepolizumab in eosinophilic phenotypes; however, differences in inclusion criteria—particularly regarding FeNO thresholds and prior exacerbation burden—may explain divergent effects on lung function endpoints. Mucus plug outcomes have not been evaluated in COPD biologic trials. Quantitative imaging modalities, including HRCT mucus plug scoring, functional respiratory imaging, and hyperpolarized gas MRI, now enable objective assessment of mucus burden. Conclusions: Mucus plugging meets the definition of a treatable trait: it can be measured with CT scoring, it matters clinically, and it responds to T2 cytokine blockade. Adding mucus plug assessment to routine clinical evaluation, together with mucolytic strategies where needed, could move treatment decisions from empirical to biology-based across the asthma–COPD spectrum. Further studies are needed to confirm that mucus plug scoring works as a biomarker of treatment response in COPD and to test whether combining biologics with mucolytics improves outcomes. Full article

Feline infectious peritonitis (FIP) is a disease arising as a result of feline coronavirus infection. It used to be regarded a fatal disease, with euthanasia commonly recommended following diagnosis due to its very poor prognosis. The availability of effective antiviral therapies, particularly nucleoside analogues such as oral GS-441524, has fundamentally changed the outlook for cats with FIP. FIP is now a treatable and frequently curable disease. In these revised guidelines, the European Advisory Board on Cat Diseases (ABCD) presents an update on the treatment of FIP, incorporating the findings of new studies including the range of available treatments (such as GS-441524, remdesivir and molnupiravir (EIDD-2801) and its active metabolite EIDD-1931), which varies globally, as well as suggestions for monitoring and prognostic indicators. Tables are used to present easy-to-find information on antiviral and supportive treatments for cats with FIP. GS-441524 is the most extensively studied antiviral for FIP with treatment success rates often exceeding 90%. Remdesivir is primarily reserved as an injectable antiviral for severely affected cats unable to tolerate oral medication; it is usually replaced by oral medication as soon as, and when, possible. Although 84-day treatment courses have historically been used, emerging evidence suggests that shorter regimens of 42 days can be equally effective. Full article

Acid sphingomyelinase deficiency (ASMD) is currently treatable with olipudase alfa, increasing the need for early newborn screening (NBS). We conducted a two-center pilot cohort study to characterize dried blood spot (DBS) acid sphingomyelinase (ASM) activity in Japanese neonates in the neonatal intensive care unit (NICU). ASM activity was measured by flow injection-tandem mass spectrometry in 244 NICU-admitted neonates (gestational age 25–41 weeks; birth weight 773–4201 g); longitudinal paired samples were available in 34 neonates with birth weight < 2000 g and concurrent hematology in 43 neonates. The mean ASM activity was 3.7 ± 1.2 μmol/h/L (95% confidence interval, 3.54–3.84; range, 1.7–11.6), with a right-skewed distribution. ASM activity correlated positively with birth weight (r = 0.184, p = 0.0039), gestational age (r = 0.219, p = 0.0006), and lymphocyte count (ρ = 0.394, p = 0.0089) and negatively with hematocrit (ρ = −0.372, p = 0.014). In neonates with a birth weight < 2000 g, ASM increased significantly on repeat sampling (mean difference, 1.60 μmol/h/L; p < 0.0001; Cohen’s d = 0.912). These findings support NICU-specific reference ranges, hematology-informed interpretations, repeat testing after maturation, and the use of second-tier biomarkers for ASMD NBS implementation in Japan. Full article

Background/Objectives: Avoidable mortality—deaths before age 75 from preventable or treatable causes—is a key indicator of health system performance. In Mexico, nearly two-thirds of municipalities lack hospital beds, yet no study has examined the municipal-level association between healthcare infrastructure and avoidable mortality. This study assessed whether healthcare desert status is independently associated with avoidable mortality after adjusting for social deprivation. Methods: This ecological study analyzed 1891 Mexican municipalities (population ≥ 1000) over 2015–2024. Avoidable deaths were classified per OECD/Eurostat criteria (January 2022 revision). Healthcare desert status was defined by municipal hospital bed availability from 2019 facility data. Negative binomial mixed-effects regression estimated incidence-rate ratios (IRRs) adjusted for social deprivation, age structure, and state-level heterogeneity. Interrupted time-series analysis quantified pandemic disruption. Results: Of 4,960,244 deaths under 75 years, 81.2% were avoidable. Of 1891 municipalities, 1187 (62.8%) lacked hospital beds (healthcare deserts). Desert municipalities had 42.5% higher avoidable mortality (IRR = 1.425; 95% CI: 1.370–1.482; pre-pandemic 2015–2019), which attenuated to 1.353 after age-structure adjustment. Each standard-deviation increase in hospital beds (1 SD ≈ 2.2 beds per 1000) was associated with 7.9% lower mortality (IRR = 0.921). Avoidable mortality exhibited strong spatial clustering (Moran’s I = 0.382) in southern Mexico. By 2024, the desert–adequate mortality gap had widened by approximately five fold (from $\sim$12 to 69 per 100,000 population). Conclusions: Healthcare deserts are independently associated with substantially higher avoidable mortality in Mexico. The COVID-19 pandemic durably amplified pre-existing disparities associated with healthcare infrastructure deficits. Targeted hospital expansion in underserved municipalities is urgently needed, alongside investment in social determinants of health. Full article

Newborn screening (NBS) bloodspots are primarily used to test for a defined panel of conditions, yet screening expansion has necessitated the implementation of new tests. Integral to test implementation across all clinical laboratories is the need to evaluate the method with clinical samples, and a common secondary use of residual bloodspots, which are samples that remain following conventional screening, is validating new testing methods by establishing “normal” analyte concentrations and setting action decision limits for NBS protocols prior to implementation. Analysis of de-identified residual bloodspots may potentially reveal an infant with a treatable condition, and re-identification and clinical notification of the infant may then be prudent. However, consent to test residual samples for conditions under implementation may not have been obtained. This ethical dilemma risks the inclusion of residual bloodspots in test development being declined by over-arching NBS authorities. Consequently, the Human Genetics Society of Australasia (HGSA) NBS Committee issued a survey to the Australasian NBS laboratories regarding the current practices of the use of residual bloodspots for new test implementation. The questionnaire revealed a consistent requirement for residual NBS bloodspot analysis to determine reference ranges and screening cutoffs for biochemical variants. If using de-identified residual samples as a component of test validation, re-identification of infants with out-of-range results for clinical referral was considered ethically justified for potentially treatable conditions. The survey results will be used to develop a consensus approach in the region that is both ethically and scientifically valid. Full article

Background: Vitamin B12 deficiency is a recognized but frequently under-integrated cause of global developmental delay (GDD) in infancy and early childhood. Early diagnosis is critical because neurological impairment may be partially or completely reversible with timely treatment. Objective: This narrative review aims to synthesize current evidence on the role of vitamin B12 deficiency in the diagnostic evaluation of GDD, with a focus on clinical phenotype, risk factors, biomarkers, treatment outcomes, and practical integration into contemporary diagnostic algorithms. Methods: A structured, non-systematic search of PubMed/MEDLINE, Embase, and Web of Science was performed to identify clinical studies, case series, reviews, and guideline documents addressing pediatric vitamin B12 deficiency and neurodevelopmental delay. Results: Vitamin B12 deficiency in early childhood is most commonly associated with maternal deficiency and exclusive breastfeeding without adequate supplementation. Evidence from recent clinical and observational studies indicates that vitamin B12 deficiency may present with nonspecific neurological symptoms, including developmental regression, hypotonia, and feeding difficulties. Incorporating vitamin B12 assessment—using serum vitamin B12, holotranscobalamin, methylmalonic acid, and homocysteine—into early diagnostic algorithms for GDD may facilitate timely identification of a treatable cause of neurodevelopmental impairment. The proposed diagnostic framework emphasizes early biochemical evaluation in infants with unexplained developmental delay, thereby supporting prompt treatment during a critical window of neurological reversibility. Conclusions: Targeted assessment of vitamin B12 status in children with GDD, together with evaluation of maternal status, represents a clinically relevant approach to identifying a potentially preventable and treatable cause of neurodevelopmental impairment. Integration of functional biomarkers into diagnostic pathways and the development of pediatric-specific reference standards are key priorities for future research and clinical practice. Full article

Background and Clinical Significance: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disorder that can mimic infection or malignancy. Spinal involvement is exceedingly rare and usually limited to pachymeningitis or epidural pseudotumors. True vertebral bone destruction has been reported only sporadically. Case Presentation: A 54-year-old man presented to our emergency department with severe neck pain after a fall. CT and MRI revealed extensive osteolysis of the C1 posterior arch and odontoid process with atlantoaxial subluxation. Following a second inpatient fall, he developed acute tetraparesis. Emergency posterior occipitocervical fusion (C0–C4) with C1–C2 laminectomy and foramen magnum decompression was performed. Histopathology demonstrated dense lymphoplasmacytic infiltration and fibrosis with up to 36 IgG4⁺ plasma cells per high-power field and an IgG4⁺/IgG ratio > 40%, confirming IgG4-RD. The patient recovered substantial motor function postoperatively and regained independent ambulation after neurological rehabilitation. Conclusions: IgG4-RD can rarely present as destructive craniovertebral osteolysis with neurological compromise. Unexplained C1–C2 osteolytic lesions should prompt evaluation for IgG4-RD, a rare but treatable cause of cervical instability. Full article

Pyridoxine-dependent epilepsy due to ALDH7A1 deficiency (PDE-ALDH7A1) is a rare but treatable epileptic encephalopathy caused by disruption of lysine catabolism and secondary depletion of pyridoxal-5′-phosphate (PLP). Although seizures are often controlled with pyridoxine supplementation, many patients continue to experience neurodevelopmental impairment, underscoring the importance of early diagnosis and improved therapeutic strategies. Central to both diagnosis and pathophysiology is the accumulation of lysine-derived metabolites, most notably α-aminoadipate semialdehyde (α-AASA), its cyclic Schiff base Δ¹-piperideine-6-carboxylate (P6C), and pipecolic acid. These metabolites have become the biochemical hallmarks of PDE-ALDH7A1, linking ALDH7A1 pathogenic variants to PLP inactivation and neuronal dysfunction. However, their chemical instability and analytical requirements pose challenges for universal diagnostics and newborn screening. This review summarizes current understanding of lysine catabolism in health and disease, critically evaluates the diagnostic utility and limitations of classical biomarkers, and discusses emerging insights into their pathophysiological roles. We further highlight recent discoveries of novel, chemically stable biomarkers, including 6-oxopiperidine-2-carboxylic acid (6-oxo-PIP), 2-oxopropylpiperidine-2-carboxylic acid (2-OPP), and 6-hydroxy-2-aminocaproic acid (HACA), identified through advanced metabolomics approaches. These metabolites show promise for newborn screening and provide new mechanistic links between metabolic stress, seizure susceptibility, and ongoing neurological morbidity despite pyridoxine treatment. Collectively, advances in biomarker discovery are reshaping diagnostic strategies for PDE-ALDH7A1 and offering new perspectives on disease mechanisms, paving the way for earlier detection and the development of more effective, mechanism-based therapies. Full article

Background/Objectives: Paediatric cataract is among the most common treatable causes of childhood blindness, caused by a genetically diverse disorder with variable clinical features. Although genetic factors significantly contribute to the development of paediatric cataracts, recent data on their genetic makeup and genotype–phenotype relationships in Saudi Arabia is limited. This study aims to investigate the genetic spectrum, inheritance patterns, and genotype–phenotype correlations of paediatric cataract in a Saudi population over twenty years. Methods: We conducted a retrospective cohort study of children diagnosed with congenital or juvenile cataracts between 2000 and 2019 at two major referral centres in Riyadh. Clinical, ocular, and systemic data were collected through multidisciplinary evaluations. Genetic analysis involved whole-exome and whole-genome sequencing performed at College of American Pathologists (CAP)-accredited laboratories. Variant interpretation was supported by bioinformatic and Artificial Intelligence (AI) prediction tools. Genotype–phenotype relationships were systematically analysed. Results: The study included 28 cases of genetically confirmed paediatric cataracts. Variants classified as pathogenic or likely pathogenic were identified in 13 genes. Autosomal recessive inheritance was predominant, with many patients exhibiting homozygous variants, often due to consanguinity. Two novel variants were identified in the Collagen Type XVIII Alpha 1 Chain (COL18A1) and the RAB3 GTPase-activating protein catalytic subunit 2 (RAB3GAP2) genes. Considerable phenotypic variability was observed, even among patients with the same mutation, particularly those with the recurrent CRYBB1 c.171del (p.Asn58fs) mutation. Syndromic cataracts were more frequently associated with loss-of-function variants and multisystem features. Conclusions: This study offers updated insights into the genetics and clinical presentation of paediatric cataract in Saudi Arabia. It highlights high genetic diversity, unique inheritance patterns, and notable genotype–phenotype variability, emphasising the importance of early genetic testing and multidisciplinary assessment for improved diagnosis, management, and counselling. Full article

Chronic obstructive pulmonary disease (COPD) represents an escalating global health challenge characterized by profound clinical and biological heterogeneity. Conventional diagnostic paradigms, primarily reliant on spirometric criteria and broad phenotypic labels, often fail to capture the complex molecular mechanisms underlying effective precision medicine. This narrative review synthesizes the evolving landscape of COPD characterization, analyzing the integration of biomarkers, advanced quantitative imaging, and multi-omics technologies. Key developments highlighted include the clinical validation of biologics targeting type 2 inflammation, which reinforce the paradigm shift from generic symptomatic management toward the identification of specific treatable traits. We further explore the role of artificial intelligence and deep learning in enhancing radiological precision and body composition analysis. Ultimately, this work proposes a transition toward a GETomics (Genetics, Environment, and Time) framework as a fundamental prerequisite for transcending the limitations of traditional classification systems and delivering truly personalized care in the 21st century. Full article

The removal of cadmium from contaminated water remains a critical challenge due to its high toxicity, persistence, and limited treatability at low concentrations. In this study, we propose a novel algal–nanoparticle system that integrates cadmium adsorption by Chlorella vulgaris with zinc ferrite (ZnFe₂O₄) nanoparticle-assisted sedimentation, with the aim of addressing a significant operational challenge in algal remediation. The microalgal biomass demonstrated the capacity to remove cadmium with efficiencies exceeding 90%, facilitated by adsorption through surface functional groups. The incorporation of ZnFe₂O₄ nanoparticles promoted the formation of dense, magnetically responsive aggregates, significantly accelerating biomass settling without the necessity for additional chemical flocculants. The strategy’s efficacy is evidenced by its enhancement of metal removal and solid–liquid separation processes, which renders it a potentially scalable and environmentally sustainable approach for the treatment of cadmium-contaminated wastewater. The strategy holds relevance for effluents derived from mining, electroplating, fertilizer production and battery manufacturing. Full article

Pediatric (neonatal and infantile) jaundice resulting from underlying cholestasis (caused by conjugated hyperbilirubinemia) is always pathological and requires prompt evaluation. Pediatric cholestasis can be caused by medical or surgical factors and, if left untreated, can lead to irreversible liver damage. Timely recognition of pediatric cholestasis and identification of the underlying etiology are paramount to improve outcomes. The broad spectrum of causes potentially underlying pediatric cholestasis requires a multidisciplinary diagnostic approach, and each aspect must be interpreted in the concomitant clinical picture. A liver biopsy is one component of a complex diagnostic puzzle. However, interpreting a liver biopsy performed on a newborn/infant with conjugated/direct hyperbilirubinemia can be a challenging task, as these biopsies are rarely encountered in general hospitals. The aim of this review is to provide a practical and simplified approach to pediatric cholestasis with examples of real clinical cases we have encountered and discuss key features, both histological and clinical, that can help narrow the differential diagnosis and identify treatable causes. Full article

Warm forming of heat-treatable aluminium alloys can induce significant changes in their initial heat treatment, affecting both the forming process and the final in-service properties. This work aims to systematically investigate the influence of heat-holding time on the thermo-mechanical behaviour and post-forming properties of Al–Mg–Si alloys (EN AW 6016-T4 and EN AW 6061-T6), with a focus on optimizing process parameters to enhance formability and minimize springback. The study combines uniaxial tensile tests, cylindrical cup forming, hardness measurements, and springback evaluation, at room temperature (RT) and 200 °C, for different heat-holding times. The results show that short heat-holding times improve formability and reduce springback, while longer times promote artificial ageing, increasing strength and hardness but reducing ductility, especially in the EN AW 6016-T4 alloy. The EN AW 6061-T6 alloy exhibits greater thermal stability. The findings provide practical guidelines for industrial warm forming of Al–Mg–Si alloys, highlighting the critical role of heat-holding time in balancing formability, strength, and dimensional accuracy. Full article

This study assesses the technical, operational, environmental, and economic feasibility of integrating alkaline water electrolysis (AEL) using on-site measured surplus electricity from two 20 MW natural-gas turbogenerators installed at a Central Processing Facility (CPF) in a Colombian oilfield. Unlike approaches based on modeled profiles, the analysis relies on more than 31,000 experimental records of gas consumption and active power, enabling an accurate characterization of the structural availability of energy surpluses under real operating conditions. A specialized industrial water treatment and purification company was consulted and provided with the physicochemical characterization results obtained from process water samples analyzed by an accredited laboratory. Based on these parameters, the technical supplier confirmed the feasibility of designing a multistage treatment train, including equalization, filtration, clarification, activated carbon, ultrafiltration, and reverse osmosis, capable of achieving final conductivities at or below 5 µS/cm. This water quality level is compatible with typical industrial alkaline electrolysis requirements and in line with technical specifications commonly aligned with ASTM and ISO standards for pressurized AEL systems. A strategic comparison between PEM and AEL technologies, supported by IFE/EFE matrices and sensitivity analyses, identified alkaline electrolysis as the optimal alternative under a stable electrical profile and capital expenditure constraints. Energy sizing for scenarios between 1.5 and 10 MW, assuming continuous 24 h operation and an average specific consumption of 50 kWh/kg H₂, yields productions between 0.5 and 3.5 t H₂/day, with electrical efficiencies above 70%. A 20-year financial analysis indicates a techno-economic threshold near 3 MW (NPV > 0; IRR > WACC), with optimal performance in the 6.5–10 MW range and payback periods between 2 and 4 years under internal valorization of the surplus electricity. From an environmental perspective, the produced hydrogen is classified as low-carbon rather than “green” due to its thermal origin; however, the integration improves the turbines’ operating regime and valorizes surplus electrical exergy that was previously unused, providing a replicable strategy for industrial assets with self-generation and treatable water availability. Full article