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.

Perceptions of U = U Among Italian Infectious Diseases Specialists: A Nationwide Survey on Providers' Attitudes Toward the Risk of HIV Transmission in Virologically Suppressed Patients.

This survey aimed to understand how far the Italian infectious diseases (ID) specialists are confident in the "Undetectable = Untransmittable" (U = U) message and translate this concept into clinical practice. An anonymous survey was distributed by e-mail to 286 clinicians to collect their opinions regarding six situations potentially at risk of HIV transmission between virologically suppressed patients and seronegative individuals who possibly require postexposure prophylaxis (PEP). Overall, 51% of ID specialists deemed zero risk of HIV transmission through condomless sex for undetectable patients. This answer was more frequent among HIV specialists (30% vs. 21%, p = .01) and clinicians working in teaching hospitals (35% vs. 16%, p = .03). Remarkably, 61% of participants would advise taking PEP for the HIV-negative partner in case of sexual intercourse with a seropositive person with a recent blip occurrence or absence of an HIV RNA test performed within the last 6 months (63%). Seventy-three percent of respondents deemed it essential to know patients' history of adherence to interpreting an HIV RNA test, regardless of its timing. When applying the U = U concept to daily clinical decisions, we observed an overall cautious attitude among physicians. Concerns mainly regarded the timing of the last HIV RNA test to the exposure event, especially in the absence of details on the patient's adherence. Wider diffusion and application of the U = U message are needed.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients.

PURPOSE: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. METHODS: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves. RESULTS: 238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40 IU/L, ALT < or ≥ 80 IU/L, and presence/absence of a bright liver echo pattern on ultrasonography. CONCLUSIONS: Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection.

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

Behavioral and clinical characteristics of people receiving medical care for HIV infection in an outpatient facility in Sicily, Italy.

AIM: The authors examined a cohort of HIV-positive outpatients at the AIDS Center of Palermo University in Italy in order to identify factors related to the frequency of their visits to the outpatient facility for health care services. METHODS: Two hundred and twenty-four HIV-infected subjects were enrolled in the study. Demographic and HIV disease characteristics were recorded and assessed with the number of days accessed to our outpatients unit in univariate and multivariate analyses. The potential relationship with immunological status was also analyzed stratifying the patients into groups according to their CD4(+) T-cell counts (≥500 vs <500/mm(3), and ≥200 vs <200/mm(3)). RESULTS: Both univariate and multivariate analyses showed that duration of antiretroviral therapy <5 years and hypertension were significantly associated with a CD4(+) T-cell count of <500/mm(3), whereas geographic origin (Africa) was associated with a CD4(+) T-cell count of <200/mm(3). Mean number of days the patients sought access to day-care services for laboratory tests was negatively associated with CD4(+) T-cell count. CONCLUSION: Patients with low CD4(+) T-cell counts showed higher use of health care services, demonstrating how early HIV diagnosis can help to reduce health care costs. The CD4(+) T-cell cut-off of 200 cells emphasizes the importance of identifying and managing HIV infection among hard-to-reach groups like vulnerable migrants. In our sample, the illegal status of immigrants does not influence the management of their HIV/AIDS condition, but the lack of European health card that documents the current antiretroviral status, could interfere with the efforts to eradicate AIDS. A better understanding of the major determinants of HIV treatment costs has led to appropriate large-scale actions, which in turn has increased resources and expanded intervention programs. Further guidance should be offered to hard-to-reach groups in order to improve early AIDS diagnosis, and procedures for identifying and managing these vulnerable subjects should be made available to care commissioners and service providers.

Determinants of HIV outpatient service utilization according to HIV parameters.

INTRODUCTION: The increased life expectancy of HIV patients in the era of highly active antiretroviral therapy has had profound consequences for the healthcare systems that provide their care. It is useful to assess whether healthcare resources need to be adapted to the different stages of HIV infection or to patient characteristics [1]. To study how patient features influence utilization of out patient services, we retrospectively analyzed the electronic health record of HIV-positive patients who had followed day-care programs at the AIDS Center of the University of Palermo, Italy. MATERIALS AND METHODS: 223 HIV-infected subjects were recruited and divided into two groups according to CD4 cell counts (117 with a CD4 count ≤500/mm(3) and 106 with CD4 count ≥500/mm(3)). Data on age, gender, race, lifestyle habits (including educational level, drug abuse history, smoking status, alcohol consumption, sexual behaviour) BMI, HIV-RNA, CD4+ T-cell count, antiretroviral therapy (ART), comorbidities such as HCV co-infection, osteoporosis biomarker, dyslipidemia, diabetes, renal function and systolic and diastolic blood pressure were recorded in a purposely designed database and were analyzed in relation to AIN by uni- and multivariable logistic regression. RESULTS: Table 1 shows the characteristics of enrolled patients; the average age of the recruited patients was 45.4±9.5 years. 163 individuals were male (73%), 26 were immigrants (12%) and 91 (40%) were treatment-naïve. Mean day care access for laboratory tests to evaluate stage of HIV and for treatment monitoring was 6.5 days for CD4 cell count measurements and 9.6 for HIV RNA/drug-resistance testing. When patients were stratified according to CD4 count, mean day care access for laboratory tests to evaluate HIV stage and to monitor treatment was negatively correlated with CD4 cell counts. CONCLUSIONS: Only patients with CD4 counts ≤500/mm(3) showed higher rates of healthcare utilization; these data may be useful for monitoring and revising implementation plans for the different phases of HIV disease.

Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients.

BACKGROUND: Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection. AIM: The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness ≥ 9.5 kPa and FIB-4 values ≥ 3.25. The optimal stiffness cut-off according to FIB-4 ≥ 3.25 was evaluated by ROC analysis. RESULTS: No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness ≥ 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79-0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03). CONCLUSION: Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.

Prospective evaluation of hepatic steatosis in HIV-infected patients with or without hepatitis C virus co-infection.

BACKGROUND: Limited data are available on hepatic steatosis (HS) in HIV patients who are not infected with hepatitis C virus (HCV). The aims of this study were to assess the prevalence of HS and its risk factors in HIV patients with and without HCV infection, and to evaluate whether HS correlates with advanced liver fibrosis and/or cardiovascular disease risk. METHODS: Fifty-seven HIV mono-infected and 61 HIV/HCV co-infected patients were enrolled consecutively. All patients underwent liver ultrasound and transient elastography. The main parameters of liver function, HIV and HCV viral loads, CD4+ cell counts, and data on highly active antiretroviral therapy (HAART) were recorded. Cardiovascular disease risk was evaluated using the 10-year Framingham risk score. RESULTS: HS prevalence in the whole HIV population was 53% (54% in mono-infected patients and 51% in co-infected patients). HS was associated with lipodystrophy and triglyceride values (p<0.0001), metabolic syndrome (p<0.0004), and total cholesterol levels (p<0.001) in both HIV groups. In HIV mono-infected patients, HS was linked with HAART exposure of >1 year (p<0.01). By multivariate analysis, only triglyceride levels (p<0.02) and Framingham risk score (p<0.05) were independently associated with HS in both HIV groups. No correlation was observed between HS and advanced liver fibrosis, measured by transient elastography. CONCLUSIONS: HS was common in HIV patients, occurring in about half of the population. HS was found to be linked with the Framingham risk score, but was not correlated with advanced liver fibrosis. We suggest that in our HIV population with HS, the burden of cardiovascular disease risk is greater than that of liver disease progression.

Transient elastography: a non-invasive tool for assessing liver fibrosis in HIV/HCV patients.

AIM: To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF. METHODS: Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviral therapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used. RESULTS: LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (χ(2)(MH) = 4, P < 0.04). In fact, LS ≥ 9.5 was significantly higher in co-infected than in HIV and HCV mono-infected patients (χ(2) = 5, P < 0.03). Also APRI and the FIB-4 index showed more LF in co-infected than in HIV mono-infected patients (P < 0.0001), but not in HCV mono-infected patients. In HIV/HCV co-infected patients, the extent of LS was significantly associated with alcohol intake (P < 0.04) and lower CD4+ cell count (P < 0.02). In HCV patients, LS was correlated with alcohol intake (P < 0.001) and cholesterol levels (P < 0.03). Body mass index, diabetes, HCV- and HIV-viremia were not significantly correlated with LS. In addition, 20% of co-infected patients had virologically unsuccessful HAART; in 50% compliance was low, CD4+ levels were < 400 cells/mm(3) and LS was > 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues. CONCLUSION: ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects.

[The return of anthrax. From bioterrorism to the zoonotic cluster of Sciacca district]. / Il ritorno del carbonchio. Dal bioterrorismo al focolaio zoonotico del distretto di Sciacca.

Anthrax is a disease caused by Bacillus anthracis which affects herbivorous animals. Humans acquire the disease incidentally by exposure to infected animals, animal products or spores on soil. The infection is still endemic in many regions in developing countries. In Italy animal clusters are very rare and human cases are exceptional. Bacillus anthrax is also a potential source for acts of bioterrorism. In the natural human infection, cutaneous anthrax is the most widespread, while the other two, pulmonary and gastrointestinal anthrax, are very rare forms. We describe the first case of human anthrax occurring in western Sicily in the last twenty years. The cutaneous lesion healed without significant scarring after antibiotic treatment with tigecycline, rifampin and ciprofloxacin. Following our diagnosis, a cluster of bovine anthrax was detected in the district of Sciacca, causing the death of 13 animals. A larger outbreak was avoided by the vaccination of over 5000 herbivores.

Atrial fibrillation in Mediterranean spotted fever.

Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii and characterized by fever, maculo-papular rash and a black eschar at the site of the tick bite ('tache noir'). We describe the case of a 58-year-old man affected by MSF who developed atrial fibrillation. The patient presented himself to the hospital after 7 days of fever, malaise and severe headache. Cardiac auscultation revealed a chaotic heart rhythm and an electrocardiogram confirmed atrial fibrillation with a fast ventricular response. Diagnosis of MSF was made after the appearance of a maculo-papular skin rash, and treatment with oral doxycycline was started. An immunofluorescence antibody test confirmed R. conorii infection. The patient recovered after 7 days of treatment. Cardiac arrhythmia is a rare complication of MSF. Inflammation may play a role in the pathogenesis of atrial fibrillation. R. conorii is an intracellular bacterium which could trigger atrial fibrillation. Our patient was previously healthy and had no reported history of cardiac disease. This suggests that heart function should be monitored in MSF patients even in the absence of underlying risk factors.