Lack of efficacy of convalescent plasma in COVID-19 patients with concomitant hematological malignancies: An Italian retrospective study

A multicenter retrospective study was designed to assess clinical outcome of COVID-19 in patients with hematological malignancies (HM) following treatment with anti-SARS-CoV-2 convalescent plasma (CP) or standard of care therapy. To this aim, a propensity score matching was used to assess the role of non-randomized administration of CP in this high-risk cohort of patients from the Italian Hematology Alliance on COVID-19 (ITA-HEMA-COV) project, now including 2049 untreated control patients. We investigated 30- and 90-day mortality, rate of admission to intensive care unit, proportion of patients requiring mechanical ventilatory support, hospitalization time, and SARS-CoV-2 clearance in 79 CP recipients and compared results with 158 propensity score-matched controls. Results indicated a lack of efficacy of CP in the study group compared with the untreated group, thus confirming the negative results obtained from randomized studies in immunocompetent individuals with COVID-19. In conclusion, this retrospective analysis did not meet the primary and secondary end points in any category of immunocompromized patients affected by HM

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

High-Frame Rate Vector Flow Imaging of the Carotid Bifurcation in Healthy Adults: Comparison With Color Doppler Imaging

To evaluate the carotid bifurcation in healthy adults using a commercial system equipped with high-frame rate vector flow imaging (VFI) based on the plane wave and to compare VFI with color Doppler imaging. METHODS: Carotid bifurcation diameters and flow characteristics of 60 vessels in 60 healthy volunteers were evaluated quantitatively and qualitatively to assess complex flow patterns and their extension and duration. RESULTS: Complex flow in the internal carotid artery (ICA) was associated with a statistically significant difference in the ΔICA sinus-to-common carotid artery (CCA) diameter ratio (the relative change in diameter between the CCA and ICA sinus.) Vector flow imaging and color Doppler imaging were in accordance when detecting complex flow in 96.7% of cases; in 3.3% of cases, only VFI identified small recirculation areas of short duration. Vector flow imaging highlighted a larger extension of the complex flow (mean ± SD, 47.7 ± 28.5 mm2 ; median, 45.5 mm2 ) compared with color Doppler imaging (mean, 29.2 ± 19.9 mm2 ; median, 29.5 mm2 ) and better depicted different complex flow patterns; a strong correlation (r = 0.84) was found between the ΔICA sinus-to-CCA diameter ratio and the complex flow extension. Vector flow imaging showed a longer duration of the flow disturbances (mean, 380 ± 218 milliseconds; median, 352.5 milliseconds) compared with color Doppler imaging (mean, 325 ± 206 milliseconds; median, 333 milliseconds), and there was a strong correlation (r = 0.92). CONCLUSIONS: Vector flow imaging is as effective as color Doppler imaging in the detection of flow disturbances, but it is more powerful in the assessment of complex flow patterns

Hepatitis C virus: determinants of patients' management costs

While Hepatitis C Virus (HCV) is a significant economic burden for healthcare providers, limited evidence is available on determinants of resources absorption, both in treatment-experienced and treatment-naïve HCV patients. The present study aimed to investigate the principal determinants of HCV management costs.4-8 November 201

Glia-derived D-serine control of synaptic plasticity in the nucleus accumbens: possible role for astrocytes in drug addiction.

Introduction: Drugs of abuse usurp learning and memory mechanisms normally related to neuronal rewards producing long-lasting neuroadaptation that underlies drug-seeking behavior and relapse. These alterations involve NMDA-dependent long-term plasticity in neural structure related to addiction such as the nucleus accumbens (NAc). Objectives: Aim of the present study was to investigate whether D-serine, released by astrocytes and/or neurons, may be involved in regulating synaptic activity and plasticity in the NAc. Methods: Experiments have been performed by using electrophysiological and immunohistochemical techniques. Coronal brain slices containing the NAc were prepared from Wistar rats (28 days old). Results: Pre-incubation of slices with D-amino acid oxidase (DAAO; 0.2 U/mL), a D-serine degrading enzyme, induced a significant increase of the AMPA/NMDA ratio at prefrontal cortex-medium spiny neuron synapses (from 1.3\ub10.2 to 5.8\ub11.5). This result suggests that D-serine modulates the NMDA component of the EPSCs. Therefore we tested the hypothesis that this amino acid may contribute to the NMDAdependent synaptic plasticity in the NAc. LTP and LTD induction requires the activation of NMDARs; as expected perfusion of the slices with D-AP5, a NMDAR antagonist, abolished these forms of synaptic plasticity. We then compared the amplitude of LTP and LTD in control and in DAAO-treated slices. The results of this set of experiments showed that D-serine degradation strongly reduced LTP and LTD (90.4% and 99.2%, respectively) thus indicating that this amino acid is required for these forms of plasticity. As for the cellular origin of D-serine, preliminary results from immunohistochemical experiments suggest a prevalent astrocytic site of production. Conclusions: These data suggest that astrocytic D-serine regulates NMDARs function and synaptic plasticity in the NAc. Ongoing experiments will address whether this signaling is impaired in cocaine model of drug addiction

Delirium and risk factors in patients undergoing non-invasive ventilation for de novo acute respiratory failure: an observational multicenter trial.

Background- Noninvasive ventilation (NIV) still has high failure rate when used for de novo acute respiratory failure (ARF). Delirium may impact the outcome, however data regarding its incidence, timing of occurrence and clinical predictors in this subset of patients are scarce. Methods- Consecutive patients with de novo ARF subjected to NIV were recruited in 10 Italian Respiratory Intensive Care Units (RICUs) and Intensive Care Units (ICUs). Demographics and clinical features, including tolerance to interface and NIV setting were recorded on admission and during stay, whereas delirium onset and type was assessed by the (Confusion Assessment Method for ICU (CAM-ICU)-7 scale and Richmond Agitation Sedation Scale (RASS) twice/per day up to a week. The association between clinical variables and the occurrence of delirium and its influence on NIV failure and other clinical outcomes were analyzed. Results- Thirty-two out of 90 enrolled patients (36%) developed delirium over 7 days upon admission; median time to onset was 48 hours (24–60). Older age (OR=2.7 [1.9–9], p=0.01), the presence of cancer OR=3.7 [2–5.4], p=0.002), sepsis (OR=1.7 [1.1–3.4], p=0.01), SOFA score (OR=1.8 [1.1–3.1], p=0.01), low tolerance to interface (OR=3.2 [2.1–5], p=0.002), use of helmet (OR=1.9 [1.2–4.3] p=0.04), and higher pre-DELIRIC (OR=3.5 [1.3–15], p=0.03) and BORG (OR=1.7 [1.1–4.6], p=0.02] scores were significantly associated with delirium. Delirium had high risk for NIV failure (HR = 3.5 95%CI [1.4–8.6], p=0.0002) and it significantly associated with longer RICU/ICU stay and higher mortality. Conclusion- Delirium onset in acute hypoxic patients undergoing NIV is frequent and negatively affects the outcome. Multiple related clinical factors should be addressed early on admission to prevent the delirium-related risk of NIV failure in these patients

Reduced D-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA-dependent synaptic plasticity

Cocaine seeking behavior and relapse have been linked to impaired potentiation and depression (LTP and LTD) at excitatory synapses in the nucleus accumbens (NAc), but the mechanism underlying this process is poorly understood. We show that, in the rat NAc core, D-serine is the endogenous coagonist of synaptic N-methyl D-aspartate receptors (NMDARs), and its presence is essential for NMDA-dependent LTP and LTD. NAc core slices obtained from cocaine-treated rats after 1 day of abstinence presented significantly reduced D-serine concentrations, increased expression of the D-serine degrading enzyme, D-amino acid oxidase, and downregulated expression of serine racemase, the enzyme responsible for D-serine synthesis. The D-serine deficit was associated with impairment of LTP and LTD that was restored by slice perfusion with exogenous D-serine. Furthermore, in vivo administration of D-serine prevented behavioral sensitization to cocaine. These results provide evidence for a critical role of D-serine signaling in synaptic plasticity relevant to cocaine addictio