Biochemical and neuropathological findings in a Creutzfeldt-Jakob Disease patient with the rare Val180Ile-129Val haplotype in the prion protein gene

Genetic Creutzfeldt-Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease

IMPORTANCE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly lethal disease. Rapid, accurate diagnosis is imperative for epidemiological surveillance and public health activities to exclude treatable differentials and facilitate supportive care. In 2017, the International CJD Surveillance Network diagnostic criteria were revised to incorporate cortical ribboning on magnetic resonance imaging and the real-time quaking-induced conversion (RT-QuIC) assay, developments that require multicenter evaluation. OBJECTIVE: To evaluate the accuracy of revised diagnostic criteria through the retrospective diagnosis of autopsy-confirmed cases (referred to as in-life diagnosis). DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study used a 3-year clinicopathological series using all cases of autopsy-confirmed sCJD and a noncase group with alternative neuropathological diagnoses from national surveillance centers in the United Kingdom, France, Germany, and Italy. Data were collected from January 2017 to December 2019 and analyzed from January 2020 to November 2021. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of revised diagnostic criteria and diagnostic investigations. Secondary analyses assessing sCJD subgroups by genotype, pathological classification, disease duration, and age. RESULTS: A total of 501 sCJD cases and 146 noncases were included. Noncase diagnoses included neurodegenerative diseases, autoimmune encephalitis, and cerebral insults such as anoxia. Participants in the sCJD cases cohort were younger (mean [SD] age, 68.8 [9.8] years vs 72.8 [10.9] years; P  .99). Among 223 cases and 52 noncases with the full panel of investigations performed, sensitivity of revised criteria (97.8%; 95% CI, 94.9%-99.3%) was increased compared with prior criteria (76.2%; 95% CI, 70.1%-81.7%; P  .99). In 455 cases and 111 noncases, cortical ribboning was 67.9% sensitive (95% CI, 63.4%-72.2%) and 86.5% specific (95% CI, 78.7%-92.2%). In 274 cases and 77 noncases, RT-QuIC was 91.6% sensitive (95% CI, 87.7%-94.6%) and 100% specific (95% CI, 96.2%-100%). Investigation sensitivity varied with genetic and pathological features, disease duration, and age. CONCLUSIONS AND RELEVANCE: This diagnostic study demonstrated significantly improved sensitivity of revised sCJD diagnostic criteria with unaltered specificity. The revision has enhanced diagnostic accuracy for clinical care and surveillance

Prevalence and clinical correlates of dementia among COVID-19-related deaths in Italy

Introduction: We aimed at exploring the proportion of patients dying with COVID-19 and concomitant dementia in Italy, as well as their clinical characteristics and trajectories of care. Methods: The proportion of COVID-19-related deaths occurring in people with dementia and the clinical characteristics of deceased individuals according to their dementia status were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2621). Results: A total of 415 individuals with dementia were identified in the study population, accounting for 15.8% of overall COVID-19-related deaths. Patients with dementia less frequently presented with cough, had lower chance of receiving supportive therapies and intensive care approaches, and showed a faster clinical worsening as compared with individuals with intact cognition. Discussion: Dementia confers a relevant risk of adverse outcomes in case of SARS-CoV-2 infection and influences the clinical presentation, course and management of affected individuals

Spatial Epidemiology of Sporadic Creutzfeldt-Jakob Disease in Apulia, Italy

Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease caused by prions that is randomly distributed in all countries, with an overall yearly mortality rate of about 1-2 cases per million people. On a few occasions, however, sporadic CJD occurred with higher than expected rates, but further investigations failed to recognize any convincing causal link. In Italy, cluster analyses of sporadic CJD cases have not been performed previously

Clinical characteristics of hospitalized individuals dying with COVID-19 by Age Group in Italy

Background: Aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (≥ 65 years). Methods: Medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged ≥ 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. Results: Older adults (≥ 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 ± 1.9 vs. 2.5 ± 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (≥ 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (≥ 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%), and superinfections (30.9% vs. 9.8%). Conclusions: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications

Bleeding and thrombotic complications during treatment with direct oral anticoagulants or vitamin K antagonists in venous thromboembolic patients included in the prospective, observational START2-register

Objective The proportion and characteristics of Italian patients affected by venous thromboembolism (VTE) treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), and complications occurring during follow-up.Design A prospective cohort of 2728 VTE patients included in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) from January 2014 to June 2018 was investigated. Characteristics of patients, type of treatment and complications occurring during 2962 years of follow-up were analysed.Setting About 60 Italian anticoagulation and thrombosis centres participated in the observational START2-RegisterParticipants 2728 adult patients with VTE of a lower limb and/or pulmonary embolism (PE), with a follow-up after the initial phase treatment.Interventions Patients could receive DOACs or VKAs; both prescribed by the National and Regional Health Systems for patients with VTE.Outcomes measures Efficacy: rate of VTE recurrence (all thrombotic complications were also recorded). Safety: the rate of major and clinically relevant non-major bleeding events.Results Almost 80% of patients were treated with DOACs. The prevalence of symptomatic PE and impaired renal function was higher in patients receiving VKAs. Duration of anticoagulation was >180 days in approximately 70% of patients. Bleeding events were similar in both treatment groups. The overall eventuality of recurrence was significantly higher in DOAC cohorts versus VKA cohorts (HR 2.15 (1.14–4.06), p=0.018); the difference was almost completely due to recurrences occurring during extended treatment (2.73% DOAC vs 0.49% VKA, p<0.0001). All-cause mortality was higher in VKA-treated (5.9%) than in DOAC-treated patients (2.6%, p<0.001).Conclusion Italian centres treat most patients with VTE with DOACs and prefer VKA for those with more serious clinical conditions. Recurrences were significantly more frequent in DOAC-treated patients due to increased incidence after 180 days of treatment, probably due to reduced adherence to treatment. These results underline the importance of structured surveillance of DOAC-treated patients with VTE to strengthen treatment adherence during extended therapy

Microbiologically confirmed infections and antibiotic-resistance in a national surveillance study of hospitalised patients who died with COVID-19, Italy 2020-2021

Background: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19. Methods: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility. Results: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively. Conclusions: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance