Epidemiology and clinical course of severe acute respiratory syndrome coronavirus 2 infection in cancer patients in the Veneto Oncology Network: The Rete Oncologica Veneta covID19 study

Introduction: Coronavirus disease 2019 (COVID-19) pandemic started in Italy with clusters identified in Northern Italy. The Veneto Oncology Network (Rete Oncologica Veneta) licenced dedicated guidelines to ensure proper care minimising the risk of infection in patients with cancer. Rete Oncologica Veneta covID19 (ROVID) is a regional registry aimed at describing epidemiology and clinical course of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer. Materials and methods: Patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on cancer diagnosis, comorbidities, anticancer treatments, as well as details on SARS-CoV-2 infection (hospitalisation, treatments, fate of the infection), have been recorded. Logistic regression analysis was applied to calculate the association between clinical/laboratory variables and death from any cause. Results: One hundred seventy patients have been enrolled. The median age at time of the SARS-CoV infection was 70 years (25-92). The most common cancer type was breast cancer (n = 40). The majority of the patients had stage IV disease. Half of the patients had two or more comorbidities. The majority of the patients (78%) presented with COVID-19 symptoms. More than 77% of the patients were hospitalized and 6% were admitted to intensive care units. Overall, 104 patients have documented resolution of the infection. Fifty-seven patients (33%) have died. In 29 cases (17%), the cause of death was directly correlated to SARS-CoV-2 infection. Factors significantly correlated with the risk of death were the following: Eastern Cooperative Oncology Group performance status (PS), age, presence of two or more comorbidities, presence of dyspnoea, COVID-19 phenotype ≥ 3, hospitalisation, intensive care unit admission, neutrophil/lymphocyte ratio and thrombocytopenia. Conclusions: The mortality rate reported in this confirms the frailty of this population. These data reinforce the need to protect patients with cancer from SARS-CoV-2 infection

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

TOLLERABILITÀ ED EFFICACIA VIRO-IMMUNOLOGICA DI REGIMI IP-BASED VS NNRTI-BASED IN PAZIENTI LATE PRESENTER: UNO STUDIO RETROSPETTIVO

Premesse: la scelta del regime terapeutico nei Late Presenter (LP) deve contemplare un inizio precoce della terapia antiretrovirale (cART), evitando interazioni farmacologiche con altri farmaci e limitando gli effetti tossici. A tal riguardo, le linee guida internazionali non forniscono chiare indicazioni sul regime da adottare nei LP. Obiettivi: confrontare attraverso uno studio retrospettivo le differenze in termini di tollerabilità, efficacia virologica ed immunologica di regimi IP-based e NNRTI-based, in pazienti LP giunti alla diagnosi di HIV presso 2 Ospedali (Sant'Anna-Ferrara e S. Maria della Misericordia-Rovigo). Metodi: sono stati esaminati retrospettivamente pazienti con diagnosi di HIV e 0,05) nel Gruppo B. Un fallimento virologico si è verificato in 14 pazienti (29.1%) nel Gruppo A e in 2 (12.5%) nel gruppo B. (p>0,05). La mediana di cellule T CD4 al baseline era di 78/µL (IQR 49-148) nel gruppo A e di 150 cellule/µL (IQR 115-215) nel Gruppo B. Dopo 12 mesi di cART l'incremento di linfociti T CD4 è stato di 220 cellule/µL (IQR 152-370) nel Gruppo A e di 258 cellule/µL (IQR 164-329) nel Gruppo B.(p>0,05). Per 18 pazienti del Gruppo A (37.5%) è stata necessaria una modifica alla cART per intolleranza/tossicità terapeutica. Nel gruppo B, invece, si è resa necessaria per 3 pazienti (18,7%; p>0,05). Conclusioni: sebbene non emerga una differenza statisticamente significativa considerato l'esiguo numero di pazienti, i regimi NNRTI-based sembrerebbero conferire un miglior successo viro-immunologico dopo 12 mesi di terapia; inoltre, gli schemi NNRTI-based potrebbero rappresentare un migliore "approccio" alla cART per il paziente LP per la ridotta tossicità, garantendo quindi una maggiore aderenza alla terapia. Ulteriori studi saranno necessari per individuare schemi cART più appropriati per LP

SIGNIFICANCE OF PROGNOSTIC VALUE OF ANEMIA IN PREDICTING OPPORTUNISTIC INFECTIONS IN HIV-INFECTED LATE PRESENTER PATIENTS STARTING ANTIRETROVIRAL THERAPY

Introduction Anemia represents a well-known complication of HIV infection, especially in end-stage disease. Several factors could have an impact on Hemoglobin (HB) level in this disease, such as opportunistic infections, neoplasia and drugs. Many studies have demonstrated how developing of anemia is related with an higher incidence of AIDS, non-AIDS defining events or deaths, even if most of them concern to pre-HAART era; to our knowledge, few data examine the relationship between HB level at baseline and the risk of new AIDS events and new admissions to hospital among late presenters (LP) in the HAART-era. Methods We analyzed retrospectively patients’ data with new diagnosis of HIV and less than 350 T-CD4 cells/µL in period 2008-2013 in 2 HIV centers of North Italy; Santa Maria della Misericordia of Rovigo and Sant’Anna - University of Ferrara hospitals. Patients were sorted by HB level at baseline and divided in two groups: Group A and Group B, with and without anemia, respectively. Anemia was defined according the World Health Organization definition (Hb <13.0 g/dL in males, <12.0 g/dL in females). Chi-square Fisher’s exact test was emplojed to analyze differences among the two groups for new AIDS-events, new hospital admissions and virological failure. T-student test was used to evaluate differences among cell-T CD4+ in two groups. Results Of the 233 new diagnoses reported in 2008-2013 by the two centers, 47.6% were LP patients. Of these, 56 (71.8%) were males (22 Group A; 34 Group B) and 22 (28.2%) were females (12 Group A; 10 Group B). The median age of LP was 43 years (IQR 35-52) in Group A and 43 (IQR 36-52) in Group B. Risk factors related with HIV transmission were HET in 45 patients (20 Group A, 25 Group B), MSM in 12 (6 Group A, 6 Group B), IDU in 3 (2 Group A, 1 Group B), Other/Unknown 18 (6 Group A, 12 Group B). Of the 233 new diagnoses, 111 (47.6%) were LP; of these, (7.2%) died. Due to lack of data, 25 patients were excluded. 34 LP patients (43.6%) had anemia at diagnosis, compared to 44 (56.4%) patients without anemia. Total median values of T-CD4+-cells observed at the moment of diagnosis of HIV was 116/µL (IQR 59-217); in Group A, 74/µL (IQR 50-147) compared to 180/µL (IQR 76-245) (p0,05). Virological failure occurred in 11 patients (32.3%) in Group A, 9 (20.5%) in Group B (p>0,05). After beginning of HAART, 9 patients developed at least one new AIDS event (total number of new AIDS-events was 13) in Group A, 1 (1 new AIDS events) in Group B (p 0,05) Conclusion Despite beginning of HAART, patients who present late at diagnosis continue to have high risk of developing new AIDS-events or to be re-admitted at hospital. Both patient groups at moment of diagnosis had a median of T-CD4 cells count <200/µL, thus being at risk of developing AIDS. HB value before starting HAART seems to have an important prognostic role to pinpoint, among LP, who has an higher risk of new AIDS events. For this reason LP with anemia should be monitored with a closer follow-up to identify as soon as possible worsening of health-condition

Comparing imported malaria in adults and children presenting to an Italian teaching hospital: A 10-year retrospective study

Malaria is not endemic in Italy, but it still represents an important threat to the travelers' health. With this study we wanted to compare the characteristics of imported malaria between adults and children

COVID-19 Vaccination Limits Systemic Danger Signals in SARS-CoV-2 Infected Patients

Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns (DAMPs) have been clearly associated with severe illness and poor prognosis in COVID-19 patients. In this report, we revealed a significant reduction in the levels of IL-1ß and DAMPs molecules, as S100A8 and High Mobility Group Protein B1 (HMGB1), in vaccinated patients as compared to non-vaccinated ones. COVID-19 vaccination indeed prevents severe clinical manifestations in patients and limits the release of systemic danger signals in SARS-CoV-2 infected people

DELAY IN DIAGNOSIS AMONG AIDS-PRESENTER IN TWO HOSPITALS IN THE NORTH EAST OF ITALY

Introduction. Most common causes of death in HIV patients in high income countries are related to late presentation (LP), defined as presenting for care with a CD4 count <350 cell/µL or with an AIDS-defining event. Data by ECDC illustrate that during years 2008-2012 in Italy, 5382 AIDS cases occurred with 2307 AIDS-related death. LP is associated to reduced life expectancy, higher risk of HIV transmission and economic implications. In this preliminary study we aimed to calculate the delay in HIV diagnosis in patients with symptoms of AIDS-disease and to characterize AIDS-events more frequently related to delay. Methods We retrospectively analyzed data of patients with new HIV diagnosis and less than 350 T-CD4 cells/µL in period 2008-13 in Rovigo and Ferrara hospitals; furthermore, we calculated the days between the first contact with any health care provider because of onset of AIDS-disease symptoms and diagnosis of HIV/AIDS. We also evaluated risk factors for delay in diagnosis. Results. An overall of 233 new diagnoses was recorded by the two centers and 47.6% were LP. Of these, 33.3% were AIDS-presenter and 7.2% died. Median age of LP was 43 ys (IQR 35-52); 72.1% males; 18.9% non-nationals. Risk factors related with HIV transmission were HET 55% (n.45), MSM 18.9% (n.12), IDU 5.4% (n.3), unknown, 20.7% (n. 18). Among 37 AIDS-presenters (M 76%, F 24%; HET 60%, MSM 16.5%, unknown, 23.5%), we recorded the following AIDS events: 10 wasting syndromes, 9 PCP, 7 esophageal candidiasis, 6 Kaposi’s Sarcoma (KS), 5 CMV disease, 3 neurotoxoplasmosis (NT), 3 Non Hodgkin Lymphomas, 3 Progressive Multifocal Leukoencephalopathy, 2 TB, 1 AIDS dementia complex (ADC), 1 Atypical mycobacteriosis, 1 Candida pneumonia, 1 Cryptococcosis*. Of these patients, 24,5% had more than 1 AIDS event at diagnosis. We found a median delay of 48,5 days (IQR 16-154), which was maximum in patients with (180 days) and KS (150 d) and minimum in those with NT, (10 d) and TB (9 d). Mortality among AIDS presenters was 23%. There were no significant differences in delay of diagnosis between national and non-national, male and female and risk factors. Conclusions In our centers, LP demographic features agree with national data. Despite the presence AIDS events, HIV test was performed with a median delay of more than 45 d; some conditions such as ADC or KS were associated with a lateness of 6-5 months respectively. By contrast, TB seemed to be linked with a quicker HIV-test performance, probably due to physicians’ awareness of the epidemiological relevance of coinfection TB-HIV. Typical AIDS events, as KS and esophageal candidiasis, were associated with a relevant delay. “Late testing” even in presence of an AIDS event shows how nowadays HIV is a less perceived issue. Our study points out the need of improving physicians’ consciousness about AIDS to detect it and starting HAART together with other specific therapy as soon as possible

Evaluation of adherence to antiretroviral therapy in Italian HIV patients

We studied factors associated with treatment adherence in 88 male and 21 female adults (age range, 24-65 years) with HIV infection undergoing therapy with HIV-1 protease inhibitors (PIS) in Italy. Data on sociodemographic variables, clinical and psychological symptoms, treatment compliance, physician/patient relationship, and psychosocial characteristics were obtained by means of semistructured interviews. Every subject also compiled two self-report questionnaires: Coping Orientations to Problem Experiences (COPE) and Medical Outcomes,Study-HIV (MOS-HIV) in order to evaluate the use of coping strategies and quality of life. We found a high rate of adherence to HIV therapies (almost 90% of patients had taken at least 80% of medication in the previous 7 days). No significant differences were found between adherence and nonadherence groups as measured by self-report. Few significant differences were found when data laboratory were used. When a Bonferroni corrected p level, of <0.001 was used, only a comparison on Mental Disengagement subscale of COPE was statistically significant