Citations

Background: Influenza-associated encephalopathy, encephalitis, and acute necrotizing encephalopathy (ANE) are rare but potentially life-threatening neurological complications of influenza. Adult cases remain poorly characterized because the available literature is largely limited to isolated case reports and small case series. Methods: A PRISMA-guided scoping review of the MEDLINE database was conducted through 31 May 2026. Published adult cases of influenza-associated encephalopathy, encephalitis, and ANE were identified and analyzed for demographic characteristics, clinical presentation, neuroimaging findings, treatment, and outcomes. Results: Eighty-three adult cases reported between 1958 and 2026 were included. The mean age was 45.6 ± 17.8 years, and 57.8% were male. Two-thirds did not have any underlying comorbidities. Neurological symptoms developed a mean of 4.6 days after influenza onset, with influenza A accounting for 80.7% of infections. Fever (91.6%), altered mental status (86.7%), and seizures (36.1%) were the most common manifestations. Encephalitis was the predominant presentation (44.5%), followed by encephalopathy (31.3%) and ANE (24.1%). MRI most frequently demonstrated cerebral hemispheric lesions (53.0%) and bilateral thalamic involvement (36.4%), while EEG abnormalities were reported in 69.6% of patients. Overall mortality was 22.9%, highest among patients with ANE (45.0%). Among survivors, 28.9% experienced persistent neurological sequelae. Conclusions: Influenza-associated encephalopathy, encephalitis, and ANE are rare in adults but are associated with substantial morbidity and mortality. This review represents the largest adult cohort reported to date and provides important insights into the clinical spectrum, neurodiagnostic findings, and outcomes of these uncommon complications. This review highlights significant gaps in knowledge and the need for collaborative multicenter studies to improve the diagnosis, treatment, and outcome of these severe complications of influenza infection.

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 < 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.

Suppurative portal vein thrombosis (pylephlebitis) is an uncommon condition usually associated with an intra-abdominal infection or inflammatory process. In this study, we aimed to synthesize data on previously published cases according to the PRISMA guidelines. A total of 103 patients were included. Patients were more commonly male (71.8%) and had a mean age of 49 years. The most common infection associated with pylephlebitis was diverticulitis (n = 29, 28.2%), and Escherichia coli was the most isolated pathogen (n = 21, 20.4%). Blood cultures were positive in 64 cases (62.1%). The most common site of thrombosis was the main portal vein (PV) in 59 patients (57.3%), followed by the superior mesenteric vein (SMV) in 40 patients (38.8%) and the right branch of the PV in 30 patients (29.1%). Sepsis developed in 60 patients (58.3%). The mortality rate in our review was 8.7%, and independent risk factors for mortality were the presence of pertinent comorbidities (OR 5.5, p = 0.02), positive blood cultures (OR 2.2, p = 0.02), and sepsis (OR 17.2, p = 0.049).

Anaplasma phagocytophilum is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and Borrelia burgdorferi was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% (n = 4/95) and 18.2% (n = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients.