Search Results (117)

West Nile virus (WNV) is an arthropod-borne flavivirus first identified in 1937. Over time, WNV has spread globally and is now endemic in Italy. Although most human WNV infections are asymptomatic (80%), less than 1% progress to a neuroinvasive disease with high mortality rates. This case involves a 45-year-old woman with post-surgical hypoparathyroidism and Sjögren’s syndrome who developed severe encephalomyelitis linked to WNV, leading to ventilator-associated pneumonia and death. Neuropathological findings revealed a bilaterally cribriform thalamus and reddish punctate lesions near the dentate nucleus of the cerebellum. The trachea and bronchial hilum branches contained whitish foamy liquid. The left lung showed multiple brownish-violet areas, with whitish regions at dissection. The heart appeared unremarkable. A detailed neuropathological examination focused on areas involved in motor control pathways. Tissue samples were stained with hematoxylin and eosin and trichrome techniques, and immunohistochemistry was performed using CD68, CD3, and CD20. A significant damage was observed in the lenticular nucleus and motor thalamus, with prominent concentric vascular calcifications. The cerebellar cortex showed near-total depletion of Purkinje cells. In the spinal cord, CD68 and CD3 positivity was noted in the lateral funiculi, anterior horns, and Clarke’s column. Lung findings showed pulmonary edema, chronic emphysema, and bronchopneumonia. The observed CD3 and CD68 positivity confirms that WNV spreads trans-synaptically along motor control pathways. We speculate on the potential molecular mechanisms by which hypoparathyroidism and Sjögren’s syndrome may have played a role in the neuroinvasive progression of the disease. Full article

Background and Objectives: Infantile spasms (ISs), or West syndrome (WS), represent an early-onset epileptic encephalopathy in which diverse structural, genetic, metabolic, infectious, and neurocutaneous conditions converge on a shared pattern of hypsarrhythmia, clustered spasms, and later developmental impairment. Growing use of genomic diagnostics has revealed that variants in STXBP1, KCNQ2, GRIN2A, GRIN2B, and TSC-related genes are more common than previously recognized and can be linked to partially actionable pathways. This review aimed to synthesize current evidence on the multifactorial etiology, network-based pathogenesis, and evolving targeted therapies for ISs, with particular attention to TSC-related forms. Materials and Methods: A structured narrative review was undertaken of publications from 1990 to 2025 in PubMed, Scopus, Web of Science, and Embase using terms related to ISs, WS, genetics, mTOR, ACTH, vigabatrin, ketogenic diet, and precision therapies. Authoritative guidance from ILAE and AAN was incorporated. Clinical, molecular, and therapeutic data were grouped under etiological, pathogenetic, and management domains. Results: Structural causes remained the largest group, but combined genetic, genetic–structural, and metabolic etiologies accounted for about one third of contemporary cohorts. Early network disruption involving cortex, thalamus, basal ganglia, and brainstem, together with imbalances in NGF, BDNF, and IGF-1, explained why distinct primary insults produce a uniform electroclinical phenotype. Early treatment with ACTH or high dose prednisolone, with or without vigabatrin, was consistently associated with higher electroclinical remission and better developmental outcome. Everolimus and related mTOR inhibitors showed benefit in TSC-associated ISs, while agents directed at NMDA receptors or KCNQ channels are emerging for genotype defined subgroups. Conclusions: ISs should be approached as a heterogeneous but mechanistically convergent disorder in which rapid diagnosis, parallel genetic testing, and early disease modifying therapy improve prognosis. Integration of molecular profiling with standardized outcome monitoring is likely to move management from symptomatic seizure control to pathway-specific intervention. Full article

Invasive fungal disease (IFD) remains a life-threatening complication in patients with hematological diseases. Isavuconazole was approved by the FDA for primary treatment of invasive aspergillosis and mucormycosis. While clinical trials have demonstrated its efficacy, data on its use in hematology patients remain limited. This study aims to evaluate the real-world effectiveness and safety of isavuconazole in this population. We conducted a single-center, retrospective study of hematology patients who received isavuconazole for IFD between 1 June 2022, and 31 July 2024, at West China Hospital, Sichuan University. A total of 66 patients with proven (n = 9), probable (n = 17), or possible (n = 40) IFD were included in the study. Acute leukemia (AL) was the most common underlying disease, affecting 27 patients (40.9%), followed by non-Hodgkin’s lymphoma (NHL) and myelodysplastic syndrome (MDS). Over 80.0% of patients received oral isavuconazole. At 6 weeks of follow-up, a favorable response was observed in 57.6% of patients, increasing to 71.2% at 12 weeks. Factors associated with achieving complete response in isavuconazole treatment included receiving isavuconazole as primary treatment (OR = 0.10, p = 0.01) and reaching complete/partial remission (CR/PR) of the primary hematological disease (OR = 0.07, p = 0.003). The all-cause mortality rates were under 30.0%. The use of isavuconazole as primary antifungal therapy (p < 0.05) and achieving CR/PR in the underlying hematological disease (p < 0.05) were two independent predictors of improved clinical outcomes. Adverse events were reported in 33.3% of patients, and no adverse events led to discontinuation of treatment. Our study demonstrated that isavuconazole is an effective and well-tolerated treatment for IFD in hematology patients. The oral formulation provided comparable efficacy and enhanced compliance, potentially leading to improved outcomes and optimizing the management strategy. The generalizability of our findings may be limited by the single-center, retrospective nature; further validation through prospective, multi-center studies is needed. Full article

The coronavirus disease 2019 (COVID-19) pandemic in Tocantins, Brazil, exhibited distinct phases between 2020 and 2025, with high mortality concentrated in 2020–2021 and subsequent stabilization at residual levels. Using epidemiological data, statistical modeling, and genomic surveillance, we show that the crisis peaked in 2021, coinciding with the circulation of Gamma and Delta, when health system capacity was severely strained. From 2022 onwards, the spread of Omicron led to record incidence but proportionally low mortality, reflecting accumulated immunity, vaccination, and improved clinical management. Vaccination represented the turning point, reducing hospitalizations and deaths by over 90% and driving a clear decoupling between incidence and severity. Interrupted time-series and generalized additive model (GAM) analyses confirmed sustained reductions in transmission and severity associated with mass immunization. Genomic sequencing of 3941 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes identified 166 lineages and successive variant replacements, culminating in the predominance of LP.8.1.4 in 2025. To our knowledge, this is one of the few integrated, long-term analyses (2020–2025) combining epidemiological and genomic data, capturing the full succession of variants up to LP.8.1.4 and highlighting Tocantins as a strategic “variant corridor” linking Brazil’s North and Central-West regions. These findings underscore the dual role of vaccination and genomic surveillance in shaping the epidemic trajectory and the importance of sustaining both strategies to mitigate future health crises. Full article

Background: Developmental and Epileptic Encephalopathy (DEE) is a severe and heterogeneous neurological disorder in infancy/early childhood. DEE’s genetic and phenotypic variability complicates diagnosis and treatment. This retrospective study aimed to identify genetic variants and explore genotype–phenotype correlations in children with DEE using a targeted epilepsy gene panel (TGP) and Whole Exome Sequencing (WES). Patients and Methods: Medical records of children who underwent custom-designed 55-gene TGP and WES were reviewed. The diagnostic yield of each method was determined based on the detection of pathogenic (P) and likely pathogenic (LP) variants. Results: A total of 129 patients (66 males, 63 females) underwent TGP, which identified P/LP variants in 29 cases (22.48%). Variants were detected in SCN1A, KCNQ2, STXBP1, CDKL5, PCDH19, PLCB1, WWOX, SCN2A, FGF12, HCN1, SCN8A, and SLC35A2. WES further identified several variants in children with West syndrome. A TSC1 variant was detected in a patient without cutaneous stigmata of tuberous sclerosis complex. The NALCN variant in a patient was linked to Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies 1. A CTBP1 variant associated with extremely rare Hypotonia, Ataxia, Developmental Delay, and Tooth Enamel Defect Syndrome was detected in another patient. A PIEZO2 variant—associated with Marden–Walker syndrome—was found in a child with Early Infantile Developmental and Epileptic Encephalopathy. Conclusions: These findings highlight the extensive genetic heterogeneity and phenotypic variability of DEE. WES demonstrates substantial value in identifying novel gene-disease associations and may be considered as a first-tier diagnostic tool in epilepsy and DEE. Full article

Background: Chicken pox is a rare but serious condition in neonates—often regarded as a common childhood illness with mild symptoms—yet it can lead to severe complications, especially in the perinatal period. Neonatal varicella may present with fever occurring within the first 5–10 days of life, followed by a generalized vesicular eruption. The syndrome is uncommon, largely due to the widespread immunity in women of childbearing age, acquired through prior chicken pox infection or varicella immunization. However in Indonesia, a developing country without a national mandatory varicella vaccination program, the disease burden remains significant, and cases of neonatal varicella are still encountered. Neonates are at high risk of severe varicella infection, which, if untreated, has a reported mortality rate of up to 30%. Although varicella is rare in neonates, there are limited studies that have reported it. This study highlights the clinical presentations upon admission, diagnostic investigations, therapeutic management strategies, and potential complications of neonatal varicella. Methods: This study presents two cases of neonatal varicella that were managed at Hasan Sadikin General Hospital in West Java, Indonesia. Each patient underwent a clinical assessment and diagnostic evaluation upon arrival, followed by therapeutic management strategies, including the management of any complications that emerged during treatment. Results: The two cases of neonates presented with classic clinical features of neonatal varicella, including a generalized vesicular rash followed by fever within the first 10 to 12 days of life, without dermatological lesions or congenital malformations at birth. In both cases, maternal chicken pox developed within the first few days postpartum, suggesting postnatal transmission as the likely source of infection. Complications observed included respiratory failure and pneumonia, requiring respiratory support. However, both neonates recovered successfully without the administration of IVIG. Conclusions: Early initiation of antiviral therapy, timely administration of antibiotics, comprehensive supportive care, and monitoring for potential complications play a crucial role in managing neonatal varicella, even in the absence of IVIG. Full article

This report presents the case of a seven-year-old West Highland White Terrier diagnosed with relapsed and refractory multiple myeloma (MM), managed using multiple treatment approaches, including conventional chemotherapy (melphalan, vincristine, doxorubicin, and dexamethasone), radiation therapy (RT), and novel agents such as the selective inhibitor of nuclear export (verdinexor), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and tyrosine kinase inhibitors (TKIs; toceranib and sorafenib). Treatment response was monitored using serum globulin concentration and imaging studies. Verdinexor achieved the longest period of stable remission with minimal toxicity post-RT. Bortezomib + dexamethasone was effective in controlling hyperglobulinemia at doses ≥ 1.45 mg/m², although cumulative hematologic and gastrointestinal toxicity limited its prolonged use. Second-line proteasome inhibitors and TKIs demonstrated limited efficacy. Despite initial therapeutic response, the patient’s condition deteriorated due to persistent hyperglobulinemia and hyperviscosity syndrome. The absence of advanced supportive options, including plasmapheresis, contributed to a fatal outcome. This case highlights the potential utility of novel therapies such as verdinexor and bortezomib in managing refractory canine MM. Timely intervention, individualized dosing, and supportive care are essential for optimizing treatment outcomes. Further research is required to define effective combinations and integrate advanced care options, including stem cell transplantation and targeted antibody therapies, in veterinary MM. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

Orthohantavirus infection is a zoonotic disease transmitted to humans through contact with infected rodents. In Eurasia, Old World Orthohantaviruses can cause haemorrhagic fever with renal syndrome (HFRS), while in the Americas, New World Orthohantaviruses are responsible for hantavirus cardiopulmonary syndrome (HCPS). In Kazakhstan, the first recorded cases of HFRS appeared in the West Kazakhstan region in 2000, which has since then been established as an endemic area due to the presence of stable rodent reservoirs and recurring human infections. Routine diagnosis of HFRS in this region relies primarily on immunoassays. To enhance diagnostic precision, we aimed to implement both serological and molecular methods on samples from suspected HFRS cases in the endemic West Kazakhstan region and non-endemic Almaty City. A total of 139 paired serum, saliva, and urine samples were analysed using IgM/IgG ELISA, immunoblot assays, and qPCR. Our findings confirm that suspected HFRS cases in West Kazakhstan are associated with the Puumala virus serotype. Full article

Background: Idiopathic pulmonary fibrosis (IPF) and emphysema often coexist in patients with lung cancer (LC), forming a syndrome with combined pulmonary fibrosis and emphysema (CPFE). The three share the pathogenic mechanisms of smoking, chronic inflammation, and oxidative stress. The clinical management of CPFE patients is challenging, but its impact on tumor characteristics, acute exacerbation (AE), and prognosis is still controversial. The purpose of this study was to clarify the effect of CPFE on tumor biological behavior, AE risk, and survival outcome in patients with IPF-LC so as to optimize individualized treatment strategies. Methods: This was a retrospective and single-center study. Newly diagnosed LC patients with IPF, COPD, and normal lungs were recruited in the west China hospital. Patients with IPF were further categorized into CPFE-LC and isolated IPF-LC groups based on the presence of emphysema. Clinical and tumor features, lung function parameters, and prognosis were obtained and compared. Results: Patients with IPF and LC were more common in older men and heavy smokers. IPF-associated tumors had a higher proportion of carrying EGFR wild-type, occurring in the lower lobe of the lung and developing adenocarcinoma and squamous cell carcinoma. Among IPF-LC patients, 68.2% (103/151) met CPFE criteria. Pulmonary function tests demonstrated preserved VC% but significantly reduced FEV1/FVC in CPFE versus non-emphysema IPF (76.3% vs. 80.7%, p = 0.004), alongside elevated CPI and impaired DLCO. CPI ≥ 40 (HR = 2.087, 95%CI: 1.715–6.089, p = 0.012), combined with COPD (HR = 2.281, 95%CI: 1.139–4.569, p = 0.040), isolated IPF (HR = 5.703, 95%CI: 2.516–12.925, p < 0.001), and CPFE (HR = 6.275, 95%CI: 3.379–11.652, p < 0.001), were independent prognostic risk factors in LC patients. The incidence of treatment-induced AEs (49.5% vs. 29.2%, p = 0.038) and AE-related mortality (28.0% vs. 11.8%, p = 0.045) were significantly higher in the CPFE group than in the isolated IPF group. Logistic regression analysis showed that CPFE (OR: 3.494, 95%CI: 2.014–6.063, p = 0.001) was independently associated with the risk of AE-related mortality in patients with LC and IPF. Conclusions: Compared to LC patients with solely IPF, the presence of emphysema had no significant impact on overall survival, but CPFE increased the risk of treatment-triggered AE and was associated with AE-related mortality. In patients with LC, CPFE with AEs had a worse prognosis than IPF with AEs. Full article

Familial adenomatous polyposis (FAP) is the most common hereditary colorectal adenomatous polyposis and cancer syndrome which has historically been associated with a near absolute risk of colorectal cancer. However, the morbidity and mortality from colorectal cancer has been greatly diminished by pre-symptomatic genetic testing which identifies affected individuals and by appropriately timed, risk-reducing surgery of the colorectum. Following colorectal surgery, cancer risk beyond the retained rectum or ileal pouch includes other gastrointestinal organs, especially those of the upper gastrointestinal tract. While genotype–phenotype correlations exist for the severity of colonic polyposis, they have not been demonstrated for upper gastrointestinal tract manifestations. We reviewed the impact of ethnicity on the upper gastrointestinal manifestations of FAP by a comparison of published data in patients with FAP from Asian and Western countries. Our main findings demonstrate that following risk-reducing surgery to mitigate colorectal cancer risk, patients with FAP remain at increased risk for upper gastrointestinal polyposis and cancer. The duodenal and gastric phenotype differs between patients with FAP from the West and the East, and all should be followed in a multidisciplinary surveillance program. Following risk-reducing surgery to mitigate colorectal cancer risk, patients with familial adenomatous polyposis remain at increased risk for upper gastrointestinal polyposis and cancer. The duodenal and gastric phenotype differs between patients with FAP from the West and the East, and all should be followed in a multidisciplinary surveillance program. Full article

Tools for measuring the likelihood of relapse in infantile epileptic spasms syndrome (IESS) treatment could aid clinicians in making critical management decisions. High-frequency oscillations (HFOs), transient bursts of electroencephalography (EEG) activity with frequencies beyond 80 Hz, are a new and promising noninvasive biomarker. The present study aimed to investigate the association between the Burden of Amplitudes and Epileptiform Discharges (BASED) scores, an interictal EEG grading scale for IESS, and scalp HFOs in patients with IESS. The study enrolled 50 patients, 25 with a clinical diagnosis of IESS and 25 without epilepsy. The percentage of patients with at least one scalp HFO detected, stratified by BASED scores, differed significantly: for BASED scores ≤ 2, 7.7%; for 3, 16.7%; for 4, 87.5%; and for 5, 100% (p < 0.001). Compared with BASED scores ≤ 2, the median scalp HFO detection rate was significantly highest for BASED scores of 5 (median [IQR]: 6.24 [2.25–8.32], p < 0.001), followed by BASED scores of 4. The scalp HFO detection rates showed a better performance in estimating patients with BASED scores of 4 and 5. It is hoped that scalp HFOs can be used as an objective indicator to validate the results of BASED scores. Full article

Objectives: West syndrome (WS) is a rare disorder with an estimated prevalence of 1 in 4000 live births, characterized by infantile spasms, hypsarrhythmia, and psychomotor developmental impairment. The available information on dental care forWS patients remains limited. The aim of this study was to describe oral manifestations and dental management in a series of WS patients. Methods: Fourteen patients diagnosed with WS were evaluated, including 10 males and 4 females, aged 12–41 years. Medical and dental variables were collected for all patients. Results: The most frequent oral findings were poor oral hygiene (64.2%), gingivitis (64.2%), dental caries (57.1%), and bruxism/tooth wear (28.5%). Only one patient had dental fractures (due to trauma), and none exhibited drug-induced gingival enlargement. Initial dental treatment was carried out under general anesthesia in 42.3% of the patients. However, following desensitization, half of the patients showed improved behavior and were ultimately treated using non-pharmacological behavioral support techniques. Conclusions: This series represents the largest published to date on the dental aspects of WS. Dental treatment needs of WS patients are considerable, and their management is primarily determined by the degree of epilepsy control, the presence of comorbidities, and the level of cooperation. Nevertheless, these patients may benefit from desensitization strategies to improve their behavior. As subsequent sessions were conducted, the behavior of 1 in every 3 initially non-compliant patients showed significant improvement. Full article

HIV testing is crucial towards the control of the Acquired Immune Deficiency Syndrome (AIDS) epidemic. Monitoring trends of human immunodeficiency virus (HIV) testing over time may help interpret the incidence of new HIV diagnoses and effectiveness of HIV testing strategies. We started a research project aimed at assessing testing rates for HIV infection among Italian outpatients in 2018–2023. Numeric data for screening, confirmatory, and monitoring tests obtained by a national register were compared with the numbers of adult residents, newly diagnosed HIV infections, and patients undergoing treatment. The number of screening tests declined from 1,133,377 in 2018 to 889,972 in 2020 and increased to 1,096,822 in 2023. HIV-RNA tests showed a similar pattern, whereas confirmatory immunoblots did not vary significantly over time. The ratio of screening tests to adult residents was higher in North-West (2.87%) and North-East (2.31%) Italy compared to South Italy and the islands (1.47%), indicating that screening should be enhanced in the latter area. We observed differences between the ratio of screening tests and the incidence of newly diagnosed HIV infections by geographic area. Discrepancies in the number of screening and confirmatory tests needed for each new diagnosis suggest repeated testing on people already diagnosed and possible data reporting issues. The monitoring of HIV screening tests at the national and regional levels can provide essential data to interpret trends in HIV epidemiology and plan relevant testing strategies over time. Full article

Arboviruses pose significant public health challenges globally, particularly in Pakistan, where deforestation, climate change, urbanization, inadequate sanitation, and natural disasters have all contributed to the spread of mosquito-borne flavivirus diseases like dengue fever. The lack of a thorough national surveillance system has made it difficult to determine the extent and distribution of these diseases. Concern has been raised by recent outbreaks of West Nile virus (WNV) and chikungunya (CHIKV) epidemics, which may lead to Zika virus (ZIKV) outbreaks in the future. Additionally, hospital-based surveillance has detected the Japanese encephalitis virus (JEV) in the region. Evidence also points to the presence of additional arboviruses in healthy populations, such as the Karshi virus (KSV), Tamdy virus (TAMV), Crimean–Congo hemorrhagic fever virus (CCHFV), and severe fever with thrombocytopenia syndrome virus (SFTSV). This review aims to address the risk factors linked to these diseases, provide specific policy recommendations for efficient disease prevention and control, and describe the epidemiological trends of these diseases in Pakistan while emphasizing the critical need for improved surveillance and thorough epidemiological investigations. Full article