Cold Plasma for Green Advanced Reduction/Oxidation Processes (AROPs) of Organic Pollutants in Water.

Cold plasma is gaining increasing attention as a novel tool to activate energy demanding chemical processes, including advanced reduction/oxidation processes (AROPs) of organic pollutants in water. The very complex milieu generated by discharges at the water/plasma interface comprises photons, strong oxidants and strong reductants which can be exploited for achieving the degradation of most any kind of pollutants. Despite the complexity of these systems, the powerful arsenal of mechanistic tools and chemical probes of physical organic chemists can be usefully applied to understand and develop plasma chemistry. Specifically, the added value of air plasma generated by in situ discharge with respect to ozonation (ex situ discharge) is demonstrated using phenol and various phenol derivatives and mechanistic evidence for the prevailing role of hydroxyl radicals in the initial attack is presented. On the reduction front, the impressive performance of cold plasma in inducing the degradation of recalcitrant perfluoroalkyl substances, which do not react with OH radicals but are attacked by electrons, is reported and discussed. The widely different reactivities of perfluorooctanoic acid (PFOA) and of perfluorobutanoic acid (PFBA) underline the crucial role played in these processes by the interface between plasma and solution and the surfactant properties of the treated pollutants.

Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism.

Recently, case series studies on patients with SARS-CoV-2 infection reported an association between remdesivir (RDV) administration and incidental bradycardia. However, the phenomenon has not yet been described in detail. We conducted a retrospective case-control study to evaluate the occurrence of RDV-related bradycardia in patients hospitalized for SARS-CoV2 pneumoniae. We retrospectively evaluated 71 patients, hospitalized in six internal medicine wards of the Milan area, affected by mild-to-moderate COVID-19 who received RDV (RDV group) and 54 controls, matched for sex, age and disease severity on admission (CTR group). The mean heart rate value recorded during the first two days of hospitalization was considered as baseline heart rate (HRb). Heart rate values relative to the 5-days treatment and the 5-days post-treatment were extracted for RDV group, while heart rate values relative to 10 days of hospitalization were considered for the CTR group. ΔHR values were calculated as maximum HR drop versus HRb. Possible associations between ΔHR and clinical-demographic factors were assessed through regression analysis. The RDV group experienced a significantly higher incidence of bradycardia compared to the CTR group (56% vs 33%, OR 2.6, 95% CI 1.2-5.4, p value = 0.011). Moreover, the RDV group showed higher ΔHR values than the CTR group. The HR progressively decreased with daily administration of RDV, reaching the maximun drop on day six (-8.6±1.9 bpm). In RDV group, patients who experienced bradycardia had higher drop in HR, higher alanine aminotransferase (ALT) values at the baseline (bALT) and during the RDV administration period. ΔHR was positively associated with HRb (ß = 0.772, p < 0.001) and bALT (ß = 0.245, p = 0.005). In conclusion, our results confirmed a significant association between RDV administration and development of bradycardia. This effect was proportional to baseline HR and was associated with higher levels of baseline ALT, suggesting a possible interaction between RDV liver metabolism and a vagally-mediated effect on HR due to increased availability of RDV metabolites.

Continuous Positive Airway Pressure in Elderly Patients with Severe COVID-19 Related Respiratory Failure.

The elderly population represents a high percentage of patients hospitalized for COVID-19 pneumonia and severe respiratory failure, for whom CPAP may be a treatment option. The aim of this study was to describe the CPAP support modalities and to explore factors associated with CPAP failure. In this retrospective study, 110 consecutive patients aged ≥ 75 years were enrolled. Median frailty score, baseline partial arterial pressure of oxygen to fraction of inspired oxygen ratio (P/F), and respiratory rate (RR) were 5, 108, and 30 cycles/min, respectively. Of the 110 patients that began CPAP treatment, 17 patients died within 72 h from baseline, while in 2 patients, CPAP was withdrawn for clinical improvement. Thus, of the 91 patients still on CPAP at day 3, 67% of them needed continuous CPAP delivery. Patients with RR ≥ 30 and with frailty score ≥ 5 had an odds ratio of continuous CPAP needing of 3 and 4, respectively. Patients unable to tolerate CPAP-free periods demonstrated higher mortality risk as compared to those able to tolerate intermittent CPAP (OR: 6.04, 95% CI 2.38−16.46, p < 0.001). The overall in-hospital mortality was 63.6%. Delirium occurred in 59.1%, with a mortality rate in this subgroup of 83.1%. In a time-varying Cox model, the hazard ratio of death was 2.9 in patients with baseline RR ≥ 30 cycle/min, 2.4 in those with baseline P/F < 100. In the same model, the hazard ratio of death was 20 in patients with delirium and a frailty score < 5 and 8.8 in those without delirium and with frailty ≥ 5, indicating a competitive effect between these two variables on the death risk. Conclusions: Respiratory impairment, frailty, and delirium predict treatment failure, with the latter two factors demonstrating a competitive effect on mortality risk. CPAP support may represent a feasible therapeutic option in elderly patients, although chances of a therapeutic benefit are markedly reduced in case of severe respiratory impairment, very frail baseline condition or delirium occurrence.

Pulsed-wave Doppler for ultrasound-based tip location using bubble test: A pilot study.

BACKGROUND: MicroBubbles Time test (MBT), consisting in the rapid infusion of saline with addition of air microbubbles, visualized by B-mode echocardiography, represents a potential alternative to Intracavitary ECG (IC-ECG) and chest X-ray for central venous catheters (CVCs) tip location. Even if promising, this technique lacks of standardization: a clear time cut-off between bubble infusion and their detection in heart's right chambers hasn't been yet established. At these regard, microbubbles could be also detected as microembolic signals (MES) with an alternative ultrasound technique: the pulse wave Doppler (PW). OBJECTIVE AND METHODS: The first aim of this pilot study is to establish agreement of MBT with PW test (MBT-PW) compared with reference standard IC-ECG and normal MBT for tip location on CVCs. Corrected tip's position was established through reference standard IC-ECG, afterward MBT-PW was performed, with the sample volume placed at tricuspid valve to detect MES simultaneously with micro-bubbles injection in CVCs. The second aim was to evaluate inter-observer variability for MES detection and grading. RESULTS: Eight patients were enrolled; we obtained three records for each patients (24 with MBT and 24 with MBT-PW, the two techniques were acquired simultaneously). Inter-methods agreement through reference standard IC-ECG versus MBT-PW and MBT versus MBT-PW methodic was satisfying (Cohen's kappa value = 1). MBT-PW and MBT signals were recorded within the first heart beat after microbubble infusion in all patients. Mean time delay thorough MBT-PW and MBT was 0.76 ±0.07 and 0.78 ± 0.07 s respectively; Intraclass correlation coefficient was 0.992 (95% CI: 0.981-0.996) suggesting excellent correlation. Inter-observer variability for positive MBT-PW evaluation was optimal (Cohen's kappa value was 1), while indicated substantial agreement for MES grade evaluation (Fleiss' Kappa value was 0.704; 95% CI: 0.328-1.000). CONCLUSIONS: Our study supports agreement between MBT-PW and reference standard IC-ECG for tip location. Satisfactory agreement was observed also for MBT-PW and MBT.

Early echocardiographic findings in patients hospitalized for COVID-19 pneumonia: a prospective, single center study.

BACKGROUND: Cardiac dysfunction, mainly assessed by biomarker alterations, has been described in COVID-19 infection. However, there are still areas of uncertainty regarding its effective role in disease evolution. Aim of this study was to evaluate early echocardiographic parameters in COVID pneumonia and their association with severity disease and prognosis. METHODS: An echocardiographic examination was performed within 72 h from admission in 64 consecutive patients hospitalized for COVID-19 pneumonia in our medium-intensity care unit, from March 30th to May 15th 2020. Six patients were excluded for inadequate acoustic window. RESULTS: Fifty-eight consecutive patients were finally enrolled, with a median age of 58 years. Twenty-two (38%) were classifiable as severe COVID-19 disease. Eight out of 58 patients experienced adverse evolution (six died, two were admitted to ICU and received mechanical ventilation), all of them in the severe pneumonia group. Severe pneumonia patients showed higher troponin, IL-6 and D-Dimer values. No significant new onset alterations of left and right ventricular systolic function parameters were observed. Patients with severe pneumonia showed higher mean estimated systolic pulmonary artery pressure (sPAP) (30.7 ± 5.2 mmHg vs 26.2 ± 4.3 mmHg, p = 0.006), even if in the normality range values. No differences in echocardiographic parameters were retrieved in patients with adverse events with respect to those with favorable clinical course. CONCLUSION: A mild sPAP increase in severe pneumonia patients with respect to those with milder disease was the only significant finding at early echocardiographic examination, without other signs of new onset major cardiac dysfunction. Future studies are needed to deepen the knowledge regarding minor cardiac functional perturbation in the evolution of a complex systemic disorder, in which the respiratory involvement appears as the main character, at least in non-ICU patients.

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.

Non-invasive hemodynamic profile of early COVID-19 infection.

INTRODUCTION: Little is known about the systemic and pulmonary macrohemodynamics in early COVID-19 infection. Echocardiography may provide useful insights into COVID-19 physiopathology. METHODS: Twenty-three COVID-19 patients were enrolled in a medical ward. Gas exchange, transthoracic echocardiographic, and hemodynamic variables were collected. RESULTS: Mean age was 57 ± 17 years. The patients were hypoxemic (PaO2 /FiO2  = 273.0 ± 102.6 mmHg) and mildly hypocapnic (PaCO2  = 36.2 ± 6.3 mmHg, pH = 7.45 ± 0.03). Mean arterial pressure was decreased (86.7 [80.0-88.3] mmHg). Cardiac index was elevated (4.32 ± 0.90 L∙min-1 ∙m-2 ) and the resulting systemic vascular resistance index low (1,458 [1358-1664] dyn∙s∙cm-5 ∙m-2 ). The right heart was morphologically and functionally normal, with pulmonary artery pressure (PAPm, 18.0 ± 2.9 mmHg) and Total Pulmonary Resistances (TPR, 2.3 [2.1-2.7] mmHg∙l-1 ∙min-1 ) within normal limits. When stratifying for SVRI, patients with an SVRI value below the cohort median had also more severe oxygenation impairment and lower TPR, despite a similar degree of CXR infiltrates. Oxygen delivery index in this group resulted supranormal. CONCLUSIONS: In the early stages of COVID-19 infection the hemodynamic profile is characterized by a hyperdynamic circulatory state with high CI and low SVRI, while the right heart is functionally unaffected. Our findings suggest that hypoxemia, viral sepsis or peripheral shunting are possible mechanisms for the vasodilation that dominates at this stage of the disease and may itself worsen the gas exchange.

I Will Be at Your (Bed)Side - The Role of Bedside Echocardiography for Non-Cardiologists.

As the availability of portable echocardiographic equipment is becoming more and more widespread, physicians can add a powerful tool to their bedside examination skills, thus helping them to more effectively face the growing complexity of patients admitted to internal medicine departments or the emergency room. Focused cardiac ultrasound (FoCUS) can be defined as a goal-directed, simplified, qualitative examination performed at the bedside using portable echocardiographic devices. FoCUS is not meant to be a substitute for a standard 2D color Doppler echocardiographic examination. Nevertheless, it can provide rapid and reliable information when limited to basic questions, even when performed by non-cardiologists with brief training. Furthermore, a focused cardiac ultrasound examination maximizes its diagnostic role when integrated with an ultrasonographic assessment of the lung, abdomen and deep veins, in a multisystem approach that is particularly dear to internists. In this article, we will focus on the specific targets of a focused cardiac ultrasound examination, as well as the most common pitfalls that can be encountered in ultrasonographic practice. We will also address the application of FoCUS in the management of two typical scenarios in clinical practice, such as dyspnea and non-post-traumatic hypotension.

Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients.

A single-nucleotide polymorphism causing a C to G change in the PNPLA3 gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17ß-hydroxysteroid dehydrogenase type 13 (HSD17B13) mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for PNPLA3 and HSD17B13 gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of PNPLA3 G∗ allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC (p = 0.007). When the HSD17B13:TA status of these patients was taken into account, the abovementioned trend was strengthened among HSD17B13 major allele homozygotes and completely blunted among carriers of the minor allele (p = 0.0003 and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the PNPLA3 minor allele and HSD17B13 major allele (vs. all other possible combinations) was an independent risk factor for HCC (OR = 2.00, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination PNPLA3 minor allele and HSD17B13 major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C.

Diagnostic Accuracy of Carotid Doppler Ultrasound for the Detection of Right-to-Left Cardiac Shunt.

BACKGROUND: Right-to-left cardiac shunt is a condition anatomically related to patent foramen ovale (PFO) and potentially related to cryptogenic cerebrovascular events. As recent studies demonstrated a reduction of recurrent stroke in patients undergoing percutaneous PFO closure after a cryptogenic cerebrovascular event, it is now of pivotal importance to screen these patients for Right-to-left shunt(RLS) presence. At this regard, transcranial color Doppler (TCCD) with contrast has a good sensitivity (97%) and specificity (93%) compared to transesophageal echocardiography and became the test of choice to assess RLS presence, thanks to its noninvasive nature. However, temporal bone window is not accessible in 6%-20% patients. Several approaches have been explored to overcome this limitation with encouraging but not definitive results for extracranial internal carotid artery (ICA) approach, proposed in previous pivotal studies. Aims of this study were to further assess the diagnostic accuracy of ICA Doppler ultrasound with contrast for RLS detection compared to TCCD, with the two tests performed simultaneously. MATERIALS AND METHODS: Sixty-four patients underwent simultaneously to TCCD and ICA Doppler ultrasound, both performed at rest and after Valsalva maneuver. Diagnosis of RLS was made, both for TCCD and ICA ultrasound, if=1 microembolic signals (MES) were detected during the examination (either at rest or after Valsalva maneuver). RESULTS: ICA Doppler ultrasound sensitivity and specificity resulted respectively of 97% (confidence interval [CI] 95%) and 100% ([CI] 95%), while negative likelihood ratio was 0.03 (CI 95%). CONCLUSIONS: ICA Doppler ultrasound represents a valid alternative to TCCD for RLS screening in patients without adequate transcranial acoustic window.

Diagnostic accuracy of transthoracic echocardiography to identify native valve infective endocarditis: a systematic review and meta-analysis.

Infective endocarditis (IE) is a serious and potentially life-threatening disease, and accurate diagnosis is essential. We performed a systematic review and meta-analysis to assess the diagnostic accuracy of transthoracic echocardiography (TTE), with transesophageal echocardiography (TEE) as the reference standard, in patients with suspected IE of the native valves. We performed a systematic search in MEDLINE, EMBASE and Cochrane Library searching for studies that enrolled adult patients with suspected native valves IE where data about both TTE and TEE could be extracted. We included 11 studies, for a total of 2209 patients. The overall sensitivity, specificity, negative and positive likelihood ratios (LR) of TTE are 0.71 (95% CI 0.56-0.82), 0.80 (95% CI 0.58-0.92), 0.37 (95% CI 0.20-0.68) and 3.56 (95% CI 1.3-9.72), respectively. The subgroup analyses of the studies considering different cut-off levels show that the strict negative criteria (i.e., managing indeterminate results as positive) have the highest sensitivity and the lowest LR-. On the contrary, when managing indeterminate results as negative (standard criteria), the specificity and LR+ are the highest. We observed no differences between the studies performed with older and more recent technologies. In conclusion, our study results support the use of a negative TTE as a single rule-out test in patients with a low pre-test probability. In selected cases, the use of strict negative criteria might exclude IE in intermediate-risk patients, and a positive TTE might be considered as a single rule-in test with no need for TEE if TEE results would not change the patient's management.