Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia.

Introduction: Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm. Methods: This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and ß-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality. Results: A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data. Conclusion: The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

Systemic Connective Tissue Disease and Neuromyelitis Optica Spectrum Disorder Coexistence: A Systematic Review and Meta-Analysis.

BACKGROUND: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. METHODS: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. RESULTS: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. CONCLUSIONS: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

Prevalence of hepatitis D virus infection in Central Italy has remained stable across the last 2 decades with dominance of subgenotypes 1 and characterized by elevated viral replication.

OBJECTIVES: Here we investigate Hepatitis D virus (HDV)-prevalence in Italy and its fluctuations over time and we provide an extensive characterization of HDV-infected patients. METHODS: The rate of HDV seroprevalence and HDV chronicity was assessed in 1579 hepatitis B surface antigen (HBsAg)+ patients collected from 2005 to 2022 in Central Italy. RESULTS: In total, 45.3% of HBsAg+ patients received HDV screening with an increasing temporal trend: 15.6% (2005-2010), 45.0% (2011-2014), 49.4% (2015-2018), 71.8% (2019-2022). By multivariable model, factors correlated with the lack of HDV screening were alanine-aminotransferase (ALT) less than two times of upper limit of normality (<2ULN) and previous time windows (P <0.002). Furthermore, 13.4% of HDV-screened patients resulted anti-HDV+ with a stable temporal trend. Among them, 80.8% had detectable HDV-ribonucleic acid (RNA) (median [IQR]:4.6 [3.6-5.6] log copies/ml) with altered ALT in 89.3% (median [IQR]:92 [62-177] U/L). Anti-HDV+ patients from Eastern/South-eastern Europe were younger than Italians (44 [37-54] vs 53 [47-62] years, P <0.0001), less frequently nucleos(t)ide analogs (NUC)-treated (58.5% vs 80%, P = 0.026) with higher HDV-RNA (4.8 [3.6-5.8] vs 3.9 [1.4-4.9] log copies/ml, P = 0.016) and HBsAg (9461 [4159-24,532] vs 4447 [737-13,336] IU/ml, P = 0.032). Phylogenetic analysis revealed the circulation of HDV subgenotype 1e (47.4%) and -1c (52.6%). Notably, subgenotype 1e correlated with higher ALT than 1c (168 [89-190] vs 58 [54-88] U/l, P = 0.015) despite comparable HDV-RNA. CONCLUSIONS: HDV-screening awareness is increasing over time even if some gaps persist to achieve HDV screening in all HBsAg+ patients. HDV prevalence in tertiary care centers tend to scarcely decline in native/non-native patients. Detection of subgenotypes, triggering variable inflammatory stimuli, supports the need to expand HDV molecular characterization.

Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study.

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era. Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used. To increase completeness of the recorded deaths and date correctness, a cross-check with the National Death Registry provided by the Ministry of the Interior was performed. We included in this study all patients infected by SARS-CoV-2 treated within 5 days after the test date and symptom onset between February 8 and April 30, 2022. All-cause mortalities by day 28 were compared between the two treatment groups after balancing for baseline characteristics using weights obtained from a gradient boosting machine algorithm. Findings: In the considered timeframe, 17,977 patients treated with molnupiravir and 11,576 patients with nirmatrelvir plus ritonavir were included in the analysis. Most patients (25,617/29,553 = 86.7%) received a full vaccine course including the booster dose. A higher crude incidence rate of all-cause mortality was found among molnupiravir users (51.83 per 100,000 person-days), compared to nirmatrelvir plus ritonavir users (22.29 per 100,000 person-days). However, molnupiravir-treated patients were older than those treated with nirmatrelvir plus ritonavir and differences between the two populations were found as far as types of co-morbidities were concerned. For this reason, we compared the weight-adjusted cumulative incidences using the Aalen estimator and found that the adjusted cumulative incidence rates were 1.23% (95% CI 1.07%-1.38%) for molnupiravir-treated and 0.78% (95% CI 0.58%-0.98%) for nirmatrelvir plus ritonavir-treated patients (adjusted log rank p = 0.0002). Moreover, the weight-adjusted mixed-effect Cox model including Italian regions and NHS centers as random effects and treatment as the only covariate confirmed a significant reduced risk of death in patients treated with nirmatrelvir plus ritonavir. Lastly, a significant reduction in the risk of death associated with nirmatrelvir plus ritonavir was confirmed in patient subgroups, such as in females, fully vaccinated patients, those treated within day 2 since symptom onset and patients without (haemato)-oncological diseases. Interpretation: Early initiation of nirmatrelvir plus ritonavir was associated for the first time with a significantly reduced risk of all-cause mortality by day 28 compared to molnupiravir, both in the overall population and in patient subgroups, including those fully vaccinated with the booster dose. Funding: This study did not receive funding.

Predictors of bacteremia and death, including immune status, in a large single-center cohort of unvaccinated ICU patients with COVID-19 pneumonia.

BACKGROUND: We investigated the possible role of the immune profile at ICU admission, among other well characterized clinical and laboratory predictors of unfavorable outcome in COVID-19 patients assisted in ICU. METHODS: Retrospective analysis of clinical and laboratory data collected for all consecutive patients admitted to the ICUs of the General Hospital of Pescara (Abruzzo, Italy), between 1st March 2020 and 30th April 2021, with a confirmed diagnosis of COVID-19 respiratory failure. Logistic regressions were used to identify independent predictors of bacteremia and mortality. RESULTS: Out of 431 patients included in the study, bacteremia was present in N = 191 (44.3%) and death occurred in N = 210 (48.7%). After multivariate analysis, increased risk of bacteremia was found for viral reactivation (OR = 3.28; 95% CI:1.83-6.08), pronation (3.36; 2.12-5.37) and orotracheal intubation (2.51; 1.58-4.02). Increased mortality was found for bacteremia (2.05; 1.31-3.22), viral reactivation (2.29; 1.29-4.19) and lymphocytes < 0.6 × 103c/µL (2.32; 1.49-3.64). CONCLUSIONS: We found that viral reactivation, mostly due to Herpesviridae, was associated with increased risk of both bacteremia and mortality. In addition, pronation and intubation are strong predictors of bacteremia, which in turn together with severe lymphocytopenia due to SARS-CoV2 was associated with increased mortality. Most episodes of bacteremia, even due to Acinetobacter spp, were not predicted by microbiological evidence of colonization.

Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies.

Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005-2009 to 3.0% in 2010-2014 and 5.1% in 2015-2019 (P = 0.007) (OR[95%CI]:11.04[1.42-85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0-2905]IU/mL for complex profiles vs 2078[115-6037]IU/ml and 1881[410-7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.

Severe Streptococcus equi Subspecies zooepidemicus Outbreak from Unpasteurized Dairy Product Consumption, Italy.

During November 2021-May 2022, we identified 37 clinical cases of Streptococcus equi subspecies zooepidemicus infections in central Italy. Epidemiologic investigations and whole-genome sequencing showed unpasteurized fresh dairy products were the outbreak source. Early diagnosis by using sequencing technology prevented the spread of life-threatening S. equi subsp. zooepidemicus infections.

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study.

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients' decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions.

SOX-1 antibodies in a patient with Crohn's disease: a case report.

BACKGROUND: The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms. CASE PRESENTATION: A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure. CONCLUSIONS: Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.

Monocyte Distribution Width as a predictor of community acquired sepsis in patients prospectively enrolled at the Emergency Department.

BACKGROUND: Monocyte Distribution Width (MDW), a simple cellular marker of innate monocyte activation, can be used for the early recognition of sepsis. We performed an observational prospective monocentric study to assess the predictive role of MDW in detecting sepsis in a sample of consecutive patients presenting at the Emergency Department. METHODS: Prospective observational study using demographic and clinical characteristics, past medical history and other laboratory measurements to predict confirmed sepsis using multivariate logistic regression. RESULTS: A total of 2724 patients were included in the study, of which 272 (10%) had sepsis or septic shock. After adjusting for known and potential risk factors, logistic regression found the following independent predictors of sepsis: SIRS equal to 1 (OR: 2.32, 1.16-4.89) and 2 or more (OR: 27.8, 14.8-56.4), MDW > 22 (OR: 3.73, 2.46-5.70), smoking (OR: 3.0, 1.22-7.31), end stage renal function (OR: 2.3, 1.25-4.22), neurodegenerative disease (OR: 2.2, 1.31-3.68), Neutrophils ≥ 8.9 × 103/µL (OR: 2.73, 1.82-4.11), Lymphocytes < 1.3 × 103/µL (OR: 1.72, 1.17-2.53) and CRP ≥ 19.1 mg/L (OR: 2.57, 1.63-4.08). A risk score derived from predictive models achieved high accuracy by using an optimal threshold (AUC: 95%; 93-97%). CONCLUSIONS: The study suggests that incorporating MDW in the clinical decision process may improve the early identification of sepsis, with minimal additional effort on the standard procedures adopted during emergency care.

A NLP Pipeline for the Automatic Extraction of a Complete Microorganism's Picture from Microbiological Notes.

The Italian "Istituto Superiore di Sanità" (ISS) identifies hospital-acquired infections (HAIs) as the most frequent and serious complications in healthcare. HAIs constitute a real health emergency and, therefore, require decisive action from both local and national health organizations. Information about the causative microorganisms of HAIs is obtained from the results of microbiological cultures of specimens collected from infected body sites, but microorganisms' names are sometimes reported only in the notes field of the culture reports. The objective of our work was to build a NLP-based pipeline for the automatic information extraction from the notes of microbiological culture reports. We analyzed a sample composed of 499 texts of notes extracted from 1 month of anonymized laboratory referral. First, our system filtered texts in order to remove nonmeaningful sentences. Thereafter, it correctly extracted all the microorganisms' names according to the expert's labels and linked them to a set of very important metadata such as the translations into national/international vocabularies and standard definitions. As the major result of our pipeline, the system extracts a complete picture of the microorganism.

Reliability of predictive models to support early decision making in the emergency department for patients with confirmed diagnosis of COVID-19: the Pescara Covid Hospital score.

BACKGROUND: The hospital management of patients diagnosed with COVID-19 can be hampered by heterogeneous characteristics at entry into the emergency department. We aimed to identify demographic, clinical and laboratory parameters associated with higher risks of hospitalisation, oxygen support, admission to intensive care and death, to build a risk score for clinical decision making at presentation to the emergency department. METHODS: We carried out a retrospective study using linked administrative data and laboratory parameters available in the initial phase of the pandemic at the emergency department of the regional reference hospital of Pescara, Abruzzo, Italy, March-June 2020. Logistic regression and Cox modelling were used to identify independent predictors for risk stratification. Validation was carried out collecting data from an extended timeframe covering other variants of concern, including Alpha (December 2020-January 2021) and Delta/Omicron (January-March 2022). RESULTS: Several clinical and laboratory parameters were significantly associated to the outcomes of interest, independently from age and gender. The strongest predictors were: for hospitalisation, monocyte distribution width ≥ 22 (4.09; 2.21-7.72) and diabetes (OR = 3.04; 1.09-9.84); for oxygen support: saturation < 95% (OR = 11.01; 3.75-41.14), lactate dehydrogenase≥237 U/L (OR = 5.93; 2.40-15.39) and lymphocytes< 1.2 × 103/µL (OR = 4.49; 1.84-11.53); for intensive care, end stage renal disease (OR = 59.42; 2.43-2230.60), lactate dehydrogenase≥334 U/L (OR = 5.59; 2.46-13.84), D-dimer≥2.37 mg/L (OR = 5.18; 1.14-26.36), monocyte distribution width ≥ 25 (OR = 3.32; 1.39-8.50); for death, procalcitonin≥0.2 ng/mL (HR = 2.86; 1.95-4.19) and saturation < 96% (HR = 2.74; 1.76-4.28). Risk scores derived from predictive models using optimal thresholds achieved values of the area under the curve between 81 and 91%. Validation of the scoring algorithm for the evolving virus achieved accuracy between 65 and 84%. CONCLUSIONS: A set of parameters that are normally available at emergency departments of any hospital can be used to stratify patients with COVID-19 at risk of severe conditions. The method shall be calibrated to support timely clinical decision during the first hours of admission with different variants of concern.

Whole-Genome Sequencing of ST2 A. baumannii Causing Bloodstream Infections in COVID-19 Patients.

A total of 43 A. baumannii strains, isolated from 43 patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and by bacterial sepsis, were analyzed by antimicrobial susceptibility testing. All strains were resistant to almost three different classes of antibiotics, including carbapenems and colistin. The whole-genome sequencing (WGS) of eight selected A. baumannii isolates showed the presence of different insertion sequences (ISs), such as ISAba13, ISAba26, IS26, ISVsa3, ISEc29, IS6100 and IS17, giving to A. baumannii a high ability to capture and mobilize antibiotic resistance genes. Resistance to carbapenems is mainly mediated by the presence of OXA-23, OXA-66 and OXA-82 oxacillinases belonging to OXA-51-like enzymes. The presence of AmpC cephalosporinase, ADC-25, was identified in all A. baumannii. The pathogenicity of A. baumannii was exacerbated by the presence of several virulence factors. The multi-locus sequence typing (MLST) analysis showed that all strains belong to sequence type 2 (ST) international clone.

COVID-19 and first manic episodes: a systematic review.

Sars-CoV-2 is a respiratory virus that can access the central nervous system, as indicated by the presence of the virus in patients' cerebrospinal fluid and the occurrence of several neurological syndromes during and after COVID-19. Growing evidence indicates that Sars-CoV-2 can also trigger the acute onset of mood disorders or psychotic symptoms. COVID-19-related first episodes of mania, in subjects with no known history of bipolar disorder, have never been systematically analyzed. Thus, the present study assesses a potential link between the two conditions. This systematic review analyzes cases of first appearance of manic episodes associated with COVID-19. Clinical features, pharmacological therapies, and relationships with pre-existing medical conditions are also appraised. Medical records of twenty-three patients fulfilling the current DSM-5 criteria for manic episode were included. Manic episodes started, on average, after 12.71±6.65 days from the infection onset. Psychotic symptoms were frequently reported. 82.61% of patients exhibited delusions, whereas 39.13% of patients presented hallucinations. A large discrepancy in the diagnostic workups was observed. Mania represents an underestimated clinical presentation of COVID-19. Further studies should focus on the pathophysiological substrates of COVID-19-related mania and pursue appropriate and specific diagnostic and therapeutic workups.

Reversibility of Central Nervous System Adverse Events in Course of Art.

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19−0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts.

Prevalence of HEV infection in acute non-ABC hepatitis and prognostic role of extrahepatic manifestations.

Background: HEV-3 and HEV-4 are emerging cause of zoonotic acute hepatitis in high-income countries. In Europe the disease is underdiagnosed but hyperendemic areas have been identified. We describe a population with acute non-ABC (n-ABC) hepatitis in Abruzzo, the Italian region with the highest seroprevalence reported. The study was included in the surveillance of acute hepatitis E by the Italian Institute of Public Health started in 2004 and implemented in 2015. Methods: Patients with n-ABC hepatitis during 2004-2018 in all Abruzzo Infectious Disease Departments were tested for HEV-IgM (Wantai®) and HEV-RNA (ORF3). Positive samples were sequenced (Beckman Coulter®) and phylogenetic tree (MEGA 6.06 software) obtained. Clinical data were retrospectively collected and an alimentary risk factors-questionnaire was administered. Categorical and quantitative variables were compared (Chi square test or Fisher test and Wilcoxon test). Results: 97 hospitalized patients were tested, most cases (91.7%) after 2015. Overall, HEV-IgM resulted positive in 36% and HEV-RNA detectable in 33.3%. All 24 sequences obtained were HEV-3, with two small groups of closely related strands. L'Aquila was the Province with higher positivity rate (44%). Retrospective clinical data were acquired in 86.5% of patients, no one having liver failure. Higher ALT-levels (1282.34 vs 893.25, p=0.0139) and extrahepatic symptoms (OR 16.69, p=0.0018) were strongly associated with HEV-IgM presence. Two small outbreaks are described. Conclusions: More than one third of n-ABC hepatitis in all Abruzzo are HEV-related. Extrahepatic symptoms correlate with HEV aetiology. Implementing surveillance is mandatory to really understand the extent of the disease.

A 5-Year-Old Child with a Deep Neck Abscess Complicated by Laryngeal Obstruction.

Deep neck space infections (DNSI) are defined as infections in the potential spaces and fascial planes of the neck. We show the clinical case of a retro and para-pharyngeal abscess in a healthy 5-year-old child complicated by compression and dislocation of the larynx with marked airway caliber reduction and potentially fatal extension up to the mediastinal aditus. DNSI can occur at any age and, due to its rapid progression, requires immediate treatment in children. In healthy children, concurrent abscesses in separate neck spaces are rare. DNSI recurrence should alert the physician to the possibility of a congenital problem, and if imaging fails, laryngoscopy may be the best diagnostic technique.

COVID-19 Vaccination Did Not Increase the Risk of Potentially Related Serious Adverse Events: 18-Month Cohort Study in an Italian Province.

This cohort study on the entire population of an Italian Province assessed the incidence of potentially vaccine-related serious adverse events (PVR-SAEs) by COVID-19 vaccination status. From January 2021 to July 2022, we extracted all deaths and hospitalizations due to several cardiovascular diseases, pulmonary embolism, and deep vein thrombosis from National Healthcare System official data. During the follow-up, 5743 individuals died, and 2097 were hospitalized for PVR-SAEs. Vaccinated subjects (n = 259,821) did not show an increased risk of all-cause death, non-COVID death, or any PVR-SAEs, as compared to the unvaccinated (n = 56,494). These results were consistent across genders, age-classes, vaccine types, and SARS-CoV-2 infection status and did not vary in Cox models adjusting for age, gender, SARS-CoV-2 infection, and selected comorbidities. In the infected population, any dose of vaccine was associated with a lower likelihood of death and PVR-SAE. In the uninfected population, subjects who received one or two doses showed a significantly higher incidence of most outcomes, likely due to a large selection bias introduced by the Italian restriction policies targeting uninfected subjects who received less than three doses. In conclusion, COVID-19 vaccination was not associated with an increase of mortality or selected PVR-SAEs incidence. Further research is warranted to evaluate the long-term safety of COVID-19 vaccines.