A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and Delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5,492 HBsAg-positive enrolled patients, 4,152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age≤40 years vs. 2.1%; p<0.001), more often females (males 43.0% vs. 68.6%; p<0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Effectiveness of test-and-treat model with direct-acting antiviral for hepatitis C virus infection in migrants: a prospective interventional study in Italy.

BACKGROUND: Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy. METHODS: A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021. After educational counseling on infectious diseases that are transmitted through blood or sexually pseudonymized HCV screening was offered to all undocumented migrants and low-income refugees observed at one of the 1st level clinical centers. The HCV-RNA-positive subjects were referred to one of the 3rd level units of Infectious Diseases (ID) and treated with a 12-week course of sofosbuvir-velpatasvir and observed for 12 weeks after the end of direct antiviral agents (DAA) treatment. STATISTICAL ANALYSIS: For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed. We used Pearson chi-square or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0. RESULTS: Of the 3501migrants observed in the study period, 3417 (97.6%) agreed to be screened; 185 (4.7%) were anti-HCV-positive and, of these, 53 (28.6%) were HCV-RNA-positive. Of these 53 subjects, 48 (90.5%) were referred to an ID unit and started DAA treatment. The HCV-RNA-positive-subjects were older [median 36 years (IQR: 32-21) vs 27.19 (IQR: 30.5-19.25); P = 0.001], and less frequently males [35 (66.03 %) vs 119 (90.1%), P < 0 .0001] than seronegative participants. They more frequently came from Eastern Europe (70.8%) stayed longer in Italy [months of stay in Italy, mean ± SD: 51.02 ± 52.84 vs 25.7 ± 42.65, P = 0.001], and had more years of schooling [years of schooling, mean ± SD: 9.61±2.81 vs 7.10 ± 4, P = 0.0001]. HCV-RNA-positive-subjects less frequently reported piercing, tattoos and tribal scars as risk factors (23.6%). Of these 48 HCV RNA positive subjects who started DAA, 47 (97.9%) showed a sustained virological response and one dropped-out in follow-up after DAA treatment. No subject had any adverse event. CONCLUSIONS: This model of HCV screening and linkage to care seems effective to eliminate HCV infectionin a difficult-to-reach and to-treat population, such as undocumented migrants and low-income refugees. The participation of cultural mediators in the study made possible a better interaction between migrants and physicians, as is evident from the large number of subjects enrolled. Eliminating HCV among migrants will have a long-term positive impact from a public health and healthcare perspective by reducing the number of individuals who potentially develop HCV-related complications such as liver cirrhosis and hepatocellular carcinoma and reducing the circulation of HCV in the regions that host them which often, as in the case of Italy, are low endemic for HCV infection.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Burden of Antimicrobial Resistance Among Women with Post-Partum Infections in Low-Middle Income Countries: A Systematic Review.

BACKGROUND: Due to the rising incidence of multidrug-resistant (MDR) pathogens, especially in Low-Middle-Income Countries (LMIC), post-partum infections represent a significant treatment challenge. METHODS: We performed a systematic review of the literature from January 2005 to February 2023 to quantify the frequency of maternal post-partum infections due to MDR pathogens in LMICs, focusing on methicillin-resistant Staphylococcus aureus (MRSA) and/or extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. SECONDARY OBJECTIVES: description of antimicrobials' prescriptions. FINDINGS: We included 22 studies with 14,804 total bacterial isolates from 12 countries, mostly from WHO African-Region. Twelve papers described wound- and 10 puerperal-infections. Seven were high-quality articles. Seventeen studies reported data on MRSA, and 18 on ESBL-producing Enterobacterales. Among high-quality studies, MRSA ranged from 9.8% in Ghana to 91.2% in Uganda; ESBL-producing Enterobacterales ranged from 22.8% in Ukraine to 95.2% in Uganda. Nine articles, mostly on C-sections, described different protocols for antibiotic prophylaxis and/or post-partum treatment. INTERPRETATION: We described a high burden of post-partum infections caused by MRSA and/or ESBL-producing Enterobacterales in LMICs, but only a few studies met quality standards. There is an urgent need for high-quality studies to better describe the real burden of antimicrobial resistance in low-resource settings and inform policies to contain the spread of multidrug-resistant organisms.

COVID-19: The Development and Validation of a New Mortality Risk Score.

Background: The coronavirus disease 2019 (COVID-19) pandemic has found the whole world unprepared for its correct management. Italy was the first European country to experience the spread of the SARS-CoV-2 virus at the end of February 2020. As a result of hospital overcrowding, the quality of care delivered was not always optimal. A substantial number of patients admitted to non-ICU units could have been treated at home. It would have been extremely useful to have a score that, based on personal and clinical characteristics and simple blood tests, could have predicted with sufficient reliability the probability that a patient had or did not have a disease that could have led to their death. This study aims to develop a scoring system to identify which patients with COVID-19 are at high mortality risk upon hospital admission, to expedite and enhance clinical decision making. Methods: A retrospective analysis was performed to develop a multivariable prognostic prediction model. Results: Derivation and external validation cohorts were obtained from two Italian University Hospital databases, including 388 (10.31% deceased) and 1357 (7.68% deceased) patients with confirmed COVID-19, respectively. A multivariable logistic model was used to select seven variables associated with in-hospital death (age, baseline oxygen saturation, hemoglobin value, white blood cell count, percentage of neutrophils, platelet count, and creatinine value). Calibration and discrimination were satisfactory with a cumulative AUC for prediction mortality of 0.924 (95% CI: 0.893-0.944) in derivation cohorts and 0.808 (95% CI: 0.886-0.828) in external validation cohorts. The risk score obtained was compared with the ISARIC 4C Mortality Score, and with all the other most important scores considered so far, to evaluate the risk of death of patients with COVID-19. It performed better than all the above scores to evaluate the predictability of dying. Its sensitivity, specificity, and AUC were higher than the other COVID-19 scoring systems when the latter were calculated for the 388 patients in our derivation cohort. Conclusions: In conclusion, the CZ-COVID-19 Score may help all physicians by identifying those COVID-19 patients who require more attention to provide better therapeutic regimens or, on the contrary, by identifying those patients for whom hospitalization is not necessary and who could therefore be sent home without overcrowding healthcare facilities. We developed and validated a new risk score based on seven variables for upon-hospital admission of COVID-19 patients. It is very simple to calculate and performs better than all the other similar scores to evaluate the predictability of dying.

Systematic application of SICA-PED protocol for central venous catheterization in neonates: A prospective clinical study on 104 cases.

BACKGROUND: Catheterization of central vessels can be associated with early and late, potentially fatal complications. A proactive approach is imperative to reduce the frequency and magnitude of adverse events. Recently, the GAVeCeLT has proposed a protocol called SICA-PED (i.e. Safe Insertion of Central Access in Pediatric patients) and includes seven evidence-based strategies. METHODS: Through a single-center prospective observational study, the authors wanted to consolidate the efficacy and safety of these protocol in newborns. In a series of 104 newborns, the seven steps of the protocol were applied (1) pre-procedural ultrasound study of the RaCeVA veins, (2) correct aseptic technique, (3) ultrasound-guided venipuncture, (4) intraprocedural localization of the tip of the catheter with TTE (ECHO TIP) and (iECG) intracavitary electrocardiogram, (5) reasoned choice of the implant exit site with the RAVESTO Tunneling technique, (6) anchoring without stitches, and (7) exit point protection with the use of glue and transparent semipermeable membrane. The authors have included a further precaution in point (6) the subcutaneous anchoring system has added the counter-fixation of the catheter wings that we will call 6Plus Point. RESULTS: All infants requiring implantation of elective us-guided central venous access were enrolled in the study. None of the 104 implanted central venous catheters experienced early complications (accidental arterial puncture, PNX, primary malposition); rare late complications such as ecchymosis, CRBSI, exit site infection or dislodgement were observed, No catheter-related thrombotic phenomena were observed. The CRBSI catheter-related infection rate was 2.47 × 1000 days catheter cases. CONCLUSION: The results of this prospective study strengthen the feasibility and efficacy of the SICA-Ped Protocol. Demonstrating that the systematic application of the evidence-based seven-step implantation strategy increases the success rate, minimizes early and late complications, which result in increased patient safety.

Cefiderocol either in monotherapy or combination versus best available therapy in the treatment of carbapenem-resistant Acinetobacter baumannii infections: A systematic review and meta-analysis.

BACKGROUND: The best treatment for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is still a matter of debate. OBJECTIVES: To describe the outcomes of patients treated with cefiderocol for CRAB infections, and to compare the efficacy of cefiderocol versus best available therapy (BAT). DATA SOURCES: We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to September 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies investigating 30-day mortality, clinical failure, microbiological failure or rate of adverse drug reactions of patients treated with cefiderocol or BAT. PARTICIPANTS: Patients with infections due to CRAB. INTERVENTIONS: Cefiderocol in monotherapy or in combination with other potentially active agents or BAT. ASSESSMENT OF RISK OF BIAS: We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies. METHODS OF DATA SYNTHESIS: We conducted a meta-analysis pooling risk ratios (RRs) through random effect models. RESULTS: We screened 801 original reports, and 18 studies (2 RCTs, 13 cohort studies and 3 case-series) were included in the analysis, for a total 733 patients treated with cefiderocol, and 473 receiving the BAT. Among patients receiving cefiderocol, the 30-day mortality rate was 42% (95% CI 38-47%), the rate of microbiological failure 48% (95% CI 31-65%), the clinical failure rate 43% (95% CI 32-55%), and the rate of ADRs was 3% (95% CI 1-6%). A lower mortality rate was observed among patients receiving cefiderocol monotherapy as compared to those treated with combination regimens (RR: 0.64; 95% CI: 0.43-0.94, p = 0.024). We found a significantly lower mortality rate (RR: 0.74; 95% CI: 0.57-0.95, p = 0.02) and a lower rate of ADRs (RR: 0.28; 95% CI: 0.09-0.91, p = 0.03) in the group treated with cefiderocol as compared to BAT. No difference was observed in microbiological and clinical failure rate. CONCLUSIONS: Our data strengthen the efficacy and safety profile of cefiderocol in CRAB infections.

Efficacy of sotrovimab on omicron BA.2, BA.4 and BA.5 subvariants of sars-cov-2 vs. other early therapies: a systematic review and meta-analysis of literature data.

Background: The aim of this meta-analysis was to ascertain whether sotrovimab was effective in reducing COVID-19 related hospitalization and mortality also in Omicron BA.2, BA.4 and BA.5 subvariants compared to other antivirals effective in index period. Methods: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) and observational studies comparing the efficacy of early treatment with sotrovimab compared to other early treatment effective in index period, antivirals or monoclonal antibodies (mAbs), in patients with COVID-19 during BA.2, BA.4, BA.5 waves, conducted in accordance with PRISMA guidelines. We searched MEDLINE, Google Scholar and the Cochrane Library. Mortality and hospitalization were defined as outcomes. Results: Four studies were included, allowing a meta-analysis of 8,041 patients. Meta-analysis showed no statistical difference between groups in hospitalization and mortality. Precisely, the RR of mortality showed no difference in the sotrovimab group compared to treatment with other drugs (OR 0.38, 95% CI 0.10-1.49, p<0.166). As regards the rate of hospitalization, no significant difference resulted between the patients treated with sotrovimab and those with other drugs (OR 1.66, 95% CI 0.41-6.66, p=0.477). Interpretation: In conclusion, this meta-analysis showed no significant difference between sotrovimab or other antivirals in reducing COVID-19 evolution in patients with a high risk of progression, considering both hospitalization and mortality.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Cognitive impairment after recovery from COVID-19: Frequency, profile, and relationships with clinical and laboratory indices.

Cognitive impairment (CI) is regarded as a remarkable burden in COVID-19 survivors. Its prevalence and profile, and relationships with the disease clinical and laboratory indices, remain unclear. The present study investigated, in a large sample of patients recovered from COVID-19, the frequency of CI with both a face-to-face screening tool and comprehensive test battery (MCCB). The study also evaluated the profile of CI and its relationships with COVID-19 clinical and laboratory indices and with psychopathological features. Out of 1344 subjects assessed for eligibility, 736 completed the screening phase 11 months after the COVID-19 infection; 402 participated in the baseline phase and completed an in depth cognitive, clinical and laboratory assessment about one month later. More than one third of the screened subjects presented a CI (COG+); it was associated to age, education, male gender, COVID-19 severity, and presence of anosmia, dyspnea at rest and exertional dyspnea during the acute phase. COG+ subjects showed a higher severity of depression, anxiety and post-traumatic distress, and worse global functioning, than subjects without CI. The MCCB showed that 45% of the subjects had a CI involving attention, working memory, verbal learning, visual learning, and reasoning and problem solving. Finally, neurocognitive functioning was inversely correlated with LDH blood levels, a potential biomarker of disease severity. According to our findings, cognitive functioning should be routinely and periodically assessed in COVID-19 patients, especially in older subjects, who experienced more severe COVID-19 symptoms. In case of persisting dysfunctions cognitive training programs should be considered as treatment strategies.

Clinical and epidemiological factors causing longer SARS-CoV 2 viral shedding: the results from the CoviCamp cohort.

INTRODUCTION: The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. METHODS: We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. RESULTS: 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value < 0.001), Charlson comorbidity index (p = 0.009), arterial hypertension (p = 0.02), cardiovascular disease (p = 0.017), or chronic kidney disease (CKD) (p = 0.001). The multivariable analysis confers a leading role to CKD, with an odds ratio of 2.3 as factor influencing belonging to the groups showing a longer time-to-negative swab. Patients with CKD and diabetes were more frequently in the third group. DISCUSSION: Our analysis showed that CKD is a factor related to longer time-to-negative swab, probably because of immunosuppression related to this condition.

The impact of a non-restrictive Antimicrobial Stewardship Program in the emergency department of a secondary-level Italian hospital.

Evidence supporting the effectiveness of Antimicrobial Stewardship (AMS) Programs in the emergency department (ED) setting is limited. We conducted a prospective cohort study to assess the efficacy of an AMS program in an ED and a short-stay observation unit. The intervention included periodic prospective audits (twice a week), conducted by four infectious disease consultants. Primary outcomes included the difference in the hospital mortality rate, antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug resistant (MDR) bacteria, before March 2020-February 2021 and after March 2021-February 2022 when the program was implemented. Interrupted time-series analysis was performed to assess the effect of our program. During the 12-month program, we performed 152 audits and evaluated 366 antibiotic therapies out of a total of 853 patients admitted. In the intervention period, we observed a non-statistically significant decrease in total antibiotic consumption, with a change in level of - 31.2 defined daily dose/100 patient-days (PD) (p = 0.71). Likewise, we found no significant variations in the rate of BSI due to MDR Gram-positive (CT - 0.02 events/PD, p = 0.84), MDR Gram-negative bacteria (CT 0.08, p = 0.71), or Candida spp. (CT 0.008, p = 0.86). Conversely, we found a significant decrease in the mortality rate between the pre- and post-intervention periods (- 1.98 deaths/100 PD, CI - 3.9 to - 0.007, p = 0.049). The Antibiotic Stewardship Program in the ED was associated with a significant decrease in the mortality rate. More high-quality studies are needed to determine the most effective ASP strategies in this unique setting.

Predicting de-novo portal vein thrombosis after HCV eradication: A long-term competing risk analysis in the ongoing PITER cohort.

BACKGROUND & AIMS: Sustained virological response (SVR) by direct-acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non-tumoral PVT in patients with cirrhosis after HCV eradication. METHODS: Patients with HCV-related cirrhosis, consecutively enrolled in the multi-center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan-Meier and competing risk regression analyses were performed. RESULTS: During a median time of 38.3 months (IQR: 25.1-48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/µL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB-4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33-24.99) and pre-treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36-13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre-treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16-27.53 and subHR: 5.50; CI 95% 1.67-18.13, respectively). CONCLUSIONS: In patients with HCV-related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

Bidirectional Relationship between HIV/HBV Infection and Comorbid Depression and/or Anxiety: A Systematic Review on Shared Biological Mechanisms.

BACKGROUND: Mental disorders that are comorbid with chronic infectious diseases may worsen clinical outcomes and patients' quality of life. We hypothesized that depression and/or anxiety syndromes or symptoms comorbid with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) infection might stem from shared biological mechanisms. METHODS: We conducted a systematic review applying the PRISMA statement by searching into the PubMed, APA PsycInfo, and Scopus databases. We examined the literature on HIV/HBV infection comorbid with depression and/or anxiety in adults ≥18 years. RESULTS: Thirty-one studies on HIV and three on HBV were analyzed. The Tat protein contributed to HIV-associated mood disorders due to the protein's ability to cause neurodegeneration and induce hypothalamic-pituitary-adrenal (HPA) axis dysregulation in response to natural stressors. The decreased brain-derived neurotrophic factor (BDNF) levels also emerged as a mechanism involved in HIV neuropathogenesis and the associated mood symptoms. Neuroinflammation was implicated in depression and/or anxiety onset in patients with HIV/HBV infections. Microglial activation and release of cytokines, in particular, appeared as potential pathogenetic mechanisms. Furthermore, an altered balance between quinolinic acid and kynurenic acid production emerged in HIV patients with comorbid depression, indicating a glutamatergic dysfunction. Inflammatory cytokine production and the downregulation of cellular immune responses contributed to persisting inflammation, delayed healing, and functional decline in patients with chronic hepatitis B (CHB) infection. A shift in type 1-type 2 cytokine balance might be implicated in HBV-related immune pathogenesis, and depression and anxiety might be considered immunomodulatory factors. Cytokines also caused HPA axis hyperactivity, frequently observed in HIV/HBV patients with comorbid depression/anxiety. CONCLUSIONS: The present systematic review showed, for the first time, that HIV/HBV and depression and/or anxiety might have several biological mechanisms as common denominators. The longitudinal course of the highlighted biological mechanisms should be explored to establish the causative interrelationship among the involved mechanisms. In addition, future research should investigate the possibility that a patient's clinical outcome might improve using pharmacological treatments acting on the biological mechanisms we described as common denominators of chronic inflammatory infective diseases and depression/anxiety.

Genomic epidemiology of the main SARS-CoV-2 variants in Italy between summer 2020 and winter 2021.

Since the beginning of the pandemic, SARS-CoV-2 has shown a great genomic variability, resulting in the continuous emergence of new variants that has made their global monitoring and study a priority. This work aimed to study the genomic heterogeneity, the temporal origin, the rate of viral evolution and the population dynamics of the main circulating variants (20E.EU1, Alpha and Delta) in Italy, in August 2020-January 2022 period. For phylogenetic analyses, three datasets were set up, each for a different main lineage/variant circulating in Italy in that time including other Italian and International sequences of the same lineage/variant, available in GISAID sampled in the same times. The international dataset showed 26 (23% Italians, 23% singleton, 54% mixed), 40 (60% mixed, 37.5% Italians, 1 singleton) and 42 (85.7% mixed, 9.5% singleton, 4.8% Italians) clusters with at least one Italian sequence, in 20E.EU1  clade, Alpha and Delta variants, respectively. The estimation of tMRCAs in the Italian clusters (including >70% of genomes from Italy) showed that in all the lineage/variant, the earliest clusters were the largest in size and the most persistent in time and frequently mixed. Isolates from the major Italian Islands tended to segregate in clusters more frequently than those from other part of Italy. The study of infection dynamics showed a positive correlation between the trend in the effective number of infections estimated by BSP model and the Re curves estimated by birth-death skyline plot. The present work highlighted different evolutionary dynamics of studied lineages with high concordance between epidemiological parameters estimation and phylodynamic trends suggesting that the mechanism of replacement of the SARS-CoV-2 variants must be related to a complex of factors involving the transmissibility, as well as the implementation of control measures, and the level of cross-immunization within the population.

Efficacy and Safety of Reparixin in Patients with Severe COVID-19 Pneumonia: A Phase 3, Randomized, Double-Blind Placebo-Controlled Study.

INTRODUCTION: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. METHODS: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. RESULTS: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. CONCLUSIONS: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51.

An Unusual Case of a Double Tricuspid and Mitral Valves Infective Endocarditis Complicated by Multiple Septic Embolisms Secondary to an Atrial Septal Defect: A Case Report and Review of Literature.

Multivalvular endocarditis (MVE) is an uncommon infection that mostly involves mitral and aortic valves, and it is related to a higher risk of congestive heart failure and a higher mortality. We described a case of a bilateral MVE and performed a review of the literature on similar clinical cases. We reported an unusual case of a 68-year-old male patient with a tricuspid and mitral infective endocarditis due to a methicillin-resistant Staphylococcus aureus complicated by multiple right- and left-sided septic embolization (lungs, brain, spleen, L2-L3 vertebral bones) due to an unknown atrial septal defect identified and repaired during cardiac surgery. Despite the severity of the clinical case, the patient experienced a good clinical outcome also thanks to a multidisciplinary approach. We identified 21 case reports describing bilateral MVE. A multidisciplinary approach is essential in the management of valve diseases to improve the prognosis of patients, especially in bilateral MVE.

Prognostic Value of Creatinine Levels at Admission on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The aim of the study was to assess the impact of creatinine levels at hospital admission on COVID-19 progression and mortality. METHODS: We performed a multicenter, observational, retrospective study involving seventeen COVID-19 Units in the Campania region in southern Italy. All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction on a naso-oropharyngeal swab, from 28 February 2020 to 31 May 2021, were enrolled in the CoviCamp cohort. RESULTS: Evaluating inclusion/exclusion criteria, 1357 patients were included. Considering in-hospital mortality and creatinine value at admission, the best cut-off point to discriminate a death during hospitalization was 1.115 mg/dL. The logistic regression demonstrated that factors independently associated with mortality were age (OR 1.082, CI: 1.054-1.110), Charlson Comorbidity Index (CCI) (OR 1.341, CI: 1.178-1.526), and an abnormal creatinine value at admission, defined as equal to or above 1.12 mg/dL (OR 2.233, CI: 1.373-3.634). DISCUSSION: In conclusion, our study is in line with previous studies confirming that the creatinine serum level can predict mortality in COVID-19 patients and defining that the best cut-off of the creatinine serum level at admission to predict mortality was 1.12 mg/dL.

Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens.

BACKGROUND: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. The aim of our study was to evaluate whether patients treated with PIs have both greater dyslipidemia and increased intima media thickness (IMT) and atheromatous plaques compared to patients treated without PIs. MATERIALS AND METHODS: A total of 110 HIV-experienced patients screened with Doppler ultrasonography of the supra-aortic trunks in December 2019 were enrolled in a retrospective cross-sectional observational study. Patients were divided into two groups: 59 in the PI-based group, treated with PIs, and 51 in the PI-sparing group. In the two groups, we evaluated lipids, cardiovascular risk factors (smoking, BMI, age, hypertension), increased pathological IMT (a value > 1 mm), and possible atheromatous plaque. RESULTS: Serum LDL (p 0.04) and percentage of patients with hypercholesterolemia (p 0.03) were higher in the PI-based than in the PI-sparing group. Doppler data showed a trend in increase of IMT > 1 in the PI-based group, which appeared statistically significant for the section of the left common carotid artery (p 0.03). However, in multivariate logistic regression models, none of the evaluated variables were significantly associated with IMT > 1. CONCLUSIONS: Our real-life data show that patients treated with PIs have a trend of developing both greater dyslipidemia and increased pathological IMT and atheromatous plaques These findings may be useful to optimize antiretrovirals for patients with cardiovascular risk factors.