Retrospective analysis of the role of Ulinastatin in reducing mortality in severe pancreatitis in critical care unit in Nepal

Background: Acute pancreatitis sequelae require a multidisciplinary approach and ICU care. Ulinastatin is a serine proteases inhibitor that reduces inflammation by suppressing the infiltration of neutrophils and elastase release and inflammatory mediators that help improve clinical symptoms and reduce mortality. This study aims to evaluate the clinical utility of Ulinastatin. Methods: Fifty-two patients admitted to ICU with acute pancreatitis were divided into; Ulinastatin group who received a 3 to 5 days course of 200,000IU, and Control Group who didn’t receive ulinastatin. Pearson's Chi-square and Fisher's exact test were used and a p-value < 0.05 was considered statistically significant. Results: Mean age was lower among the Ulinastatin group at 43 years (p-Value 0.014) and Hepatic dysfunction was more among this group (p-value 0.04). Among new onset of organ dysfunction, only CVS dysfunction was significant among the Control group ( p-value 0.044) while respiratory function recovery (p-value 0.04) and coagulation profile improvement (p-value 0.017) was statistically significant among the Ulinastatin group. The mean duration of hospital stay was shorter among control group, 9.65 days vs 14 days, a p-value of 0.05and also the average duration of stay in MDICU was lower, 4 days vs 8.5 days, p-value 0.0044 in comparison to Ulinastatin group. Overall mortality incidence was 15.38%, 19% in Ulinastatin group vs 11.5% in Control group. Conclusion: This retrospective study is our experience in the use of Ulinastatin which has shown little efficacy in declining mortality and/or hospital stay duration though it helps prevent new organ dysfunctions.

Indirect Impact of COVID-19 Vaccination on Weekly Trends in Morbidity and Mortality Indicators in Brazil, 2020 to 2021

Background: With the outbreak of the COVID-19 pandemic, safe and efficacious vaccines were quickly developed and made available to reduce its morbidity and mortality. This study aimed to describe the trends and evaluate the association of COVID-19 vaccination with indicators of morbidity and mortality due to the disease in Brazil.Methods: This was an ecological study whose unit of analysis was the time elapsed between February 16th, 2020, from the introduction of COVID-19 in Brazil and July 17th, 2021, six months after the start of vaccination in the country. From secondary databases, indicators of morbidity and mortality (incidence of hospitalization, proportion of severe cases, lethality and mortality) and vaccine coverage (doses 1, 2 or single dose) per epidemiological week (EW) and age groups were calculated (18 to 59 years and 60 years or older). Indicators of morbimortality were compared in the pre-vaccination (EW 8/2020 to EW 2/2021) and vaccination (EW 3/2021 to EW 28/2021) periods, analyzing the trends estimated using the JointPoint model and their associations using the Poisson model.Results: For individuals aged 60 years and over, during the period of COVID-19 vaccination there was a weekly trend towards a reduction in the incidence of hospitalizations (PMSV: -4.7%), severity (PMSV: -0.3%, lethality (PMSV: -2.0%) and mortality (PMSV: -2.8%); the increase in COVID-19 vaccination coverage was inversely associated with the incidence of hospitalizations (IRR: 0.969), lethality (IRR: 0.993), and mortality (IRR: 0.981). For individuals aged 18 to 59 years of age, during the period of COVID-19 vaccination there was a weekly trend towards a reduction in the incidence of hospitalizations (PMSV: -2.6%) and lethality (PMSV: -2.0%), while there was an increase in mortality (PMSV: 3.8%); the increase in COVID-19 vaccination coverage was inversely associated with the incidence of hospitalizations (IRR: 0.975) and lethality (IRR: 0.939). Conversely, it was directly associated with mortality (IRR: 1.054).Conclusions: it was demonstrated that COVID-19 vaccination had an indirect impact in reducing the morbidity and mortality trend from the disease in Brazil, especially in the elderly population, in which vaccination was prioritized and achieved greater coverage, when compared to individuals aged 18 to 59 years.

Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis

Aims: To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and incidence of QT prolongations. Results: Fifty-one studies (n = 61,221) were included. Hydroxychloroquine/chloroquine showed no efficacy in all primary efficacy outcomes, but was associated with increased odds of QT prolongations. Conclusion: Due to a lack of efficacy and increased odds of cardiac adverse events, hydroxychloroquine/chloroquine should not be used for treating hospitalized COVID-19 patients.

Estimating the impact of influenza on the epidemiological dynamics of SARS-CoV-2

As in past pandemics, co-circulating pathogens may play a role in the epidemiology of coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In particular, experimental evidence indicates that influenza infection can up-regulate the expression of ACE2—the receptor of SARS-CoV-2 in human cells—and facilitate SARS-CoV-2 infection. Here we hypothesized that influenza impacted the epidemiology of SARS-CoV-2 during the early 2020 epidemic of COVID-19 in Europe. To test this hypothesis, we developed a population-based model of SARS-CoV-2 transmission and of COVID-19 mortality, which simultaneously incorporated the impact of non-pharmaceutical control measures and of influenza on the epidemiological dynamics of SARS-CoV-2. Using statistical inference methods based on iterated filtering, we confronted this model with mortality incidence data in four European countries (Belgium, Italy, Norway, and Spain) to systematically test a range of assumptions about the impact of influenza. We found consistent evidence for a 1.8–3.4-fold (uncertainty range across countries: 1.1 to 5.0) average population-level increase in SARS-CoV-2 transmission associated with influenza during the period of co-circulation. These estimates remained robust to a variety of alternative assumptions regarding the epidemiological traits of SARS-CoV-2 and the modeled impact of control measures. Although further confirmatory evidence is required, our results suggest that influenza could facilitate the spread and hamper effective control of SARS-CoV-2. More generally, they highlight the possible role of co-circulating pathogens in the epidemiology of COVID-19.

High In-Hospital Mortality Incidence Rate and Its Predictors in Patients with Intracranial Hemorrhage Undergoing Endotracheal Intubation

(1) Background: The goal of this study was to determine the incidence of in-hospital mortality and to investigate its predictors in patients with a primary intracranial hemorrhage (ICH) undergoing endotracheal intubation. (2) Methods: This retrospective study, between July 2018 to July 2019, recruited patients who were diagnosed with a primary ICH and who were intubated during treatment in our institution. The outcome variable was in-hospital mortality, known as 30-day mortality, in patients with ICH undergoing endotracheal intubation. Multivariable analyses were performed to identify the prediction of in-hospital mortality. (3) Results: A total of 180 patients with ICH undergoing endotracheal intubation were included, with a mean (SD) age of 62.64 (13.82) years. A total of 73.33% were female, and 71.11% of the patients were indicated for intubation due to neurological reasons. The in-hospital mortality rate, following endotracheal intubation, was 58.33%. In a reduced model using a stepwise backward selection strategy with p values < 0.2, independent predictors of in-hospital mortality were brain herniations on cranial CT scans (OR: 10.268, 95% CI: 2.749–38.344), lower Glasgow coma scale (CGS) scores before intubation (OR: 0.614, 95% CI: 0.482–0.782), and the loss of the vertical oculocephalic reflex before intubation (OR: 6.288, 95% CI: 2.473–15.985). Conclusions: The in-hospital mortality rate was comparable to that in the early evidence, but was significantly higher compared to recent reports. We infer that brain herniations on cranial CT imaging, lower CGS scores before intubation, and the loss of the vertical oculocephalic reflex before intubation could be used to approximately predict in-hospital mortality in patients with primary ICH undergoing endotracheal intubation. These considerations can help guide clinical decisions and community stroke discussions.

Management of Pulmonary Thromboembolism

Pulmonary thrombo-embolism (PTE) is a major cause of cardiovascular morbidity and mortality. Incidence of PTE and its associated mortality is affected by the Prescence of associated risk factors, comorbid conditions and advancement in the treatment options. Clinical probability, D-Dimer, echocardiography and CT pulmonary angiography are used in the diagnosis. Management starts with stratification, with high-risk category being benefited from the thrombolytic therapy. Catheter directed therapy may be used in ineligible or failed cases with surgical embolectomy being used as final salvage therapy. Patients with persistent hemodynamic stability can be started on anticoagulation alone. Supportive therapy with fluid expansion and inhalational Nitric oxide may provide benefit in few. Patients with PTE should receive secondary preventive anticoagulation to prevent recurrences. High risk patients with sub-segmental PTE may benefit from anticoagulation. For early detection of long-term complications of PTE a patient cantered follow-up is needed. Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a dreaded complication with pulmonary end-arterectomy being a gold standard management option in eligible patients with non-surgical therapy (balloon pulmonary angioplasty and pulmonary vasodilators) also being used in many cases.

207. Ineffective Initial Antibiotics for Enteric Bacteremia: Does Every Hour Count with Rapid Diagnostics and Stewardship Intervention?

Background It has been a long-standing practice to administer broad-spectrum antibiotics early for sepsis as each hour delay is associated with increase in mortality. With increasing rates of antibiotic resistance fueled by unnecessary use of antibiotics, it is delicate to balance the benefits vs consequences of empiric carbapenem therapy. With rapid molecular blood culture diagnostics available, identification of extended-spectrum beta-lactamase (ESBL) producing bacteremia can occur within hours and therapy optimized with active stewardship intervention. With rapid diagnostics, does each hour of ineffective antibiotic therapy really count? Methods This multicenter, retrospective, cohort study compared adult inpatients with E. coli bacteremia from a urinary source who received initial effective (EA) vs ineffective antibiotics (IA). The primary outcome was clinical treatment success at day 4. Secondary endpoints included length of stay (LOS), infection-related mortality, incidence of C. difficile infection (CDI), and subgroup analysis of outcomes by ESBL (CTX-M type) vs non-ESBL. Associations with endpoints were assessed using Fisher’s Exact tests using R v. 4.0.3. Results Clinical treatment success at day 4 was higher in the EA (n = 488) vs IA (n = 119) groups (93.7% vs 86.6%, p = 0.01) and median LOS was shorter (5 [IQR 4-6] vs 5 [IQR 5-7] days, p &lt; 0.01). There were no differences in infection-related mortality (3.1% vs 3.4%, p = 0.8), 30-day mortality (2.5% vs 2.5%, p &gt; 0.9), or incidence of CDI (1.8% vs 0%, p = 0.3) in the EA vs IA groups, respectively. For patients on IA &lt; 24 h vs &gt; 24 h, there was no difference in clinical improvement at day 4 (86.7% vs 90.5%, p &gt; 0.9) nor 30-day mortality (2.4% vs 4.8%, p = 0.4). Clinical treatment success at day 4 was higher among non-CTX-M (n = 476) vs CTX-M (n = 131) patients (93.9% vs 86.3%, p = 0.01) even among those that received initial EA (94.5% vs 83.3%, p = 0.02). Median LOS was also shorter in CTX-M vs non CTX-M (5 [IQR 4-6] vs 5 [IQR 4-8] days, p &lt; 0.01). Conclusion There was no mortality difference among patients receiving initial EA vs IA for E. coli bacteremia with rapid molecular blood culture diagnostics with active stewardship. Therapy for patients on IE is rapidly corrected and stewardship programs can use this intervention to promote judicious use of carbapenems. Disclosures All Authors: No reported disclosures

Sex-differences in COVID-19 associated excess mortality is not exceptional for the COVID-19 pandemic

Europe experienced excess mortality from February through June, 2020 due to the COVID-19 pandemic, with more COVID-19-associated deaths in males compared to females. However, a difference in excess mortality among females compared to among males may be a more general phenomenon, and should be investigated in none-COVID-19 situations as well. Based on death counts from Eurostat, separate excess mortalities were estimated for each of the sexes using the EuroMOMO model. Sex-differential excess mortality were expressed as differences in excess mortality incidence rates between the sexes. A general relation between sex-differential and overall excess mortality both during the COVID-19 pandemic and in preceding seasons were investigated. Data from 27 European countries were included, covering the seasons 2016/17 to 2019/20. In periods with increased excess mortality, excess was consistently highest among males. From February through May 2020 male excess mortality was 52.7 (95% PI: 56.29; 49.05) deaths per 100,000 person years higher than for females. Increased male excess mortality compared to female was also observed in the seasons 2016/17 to 2018/19. We found a linear relation between sex-differences in excess mortality and overall excess mortality, i.e., 40 additional deaths among males per 100 excess deaths per 100,000 population. This corresponds to an overall female/male mortality incidence ratio of 0.7. In situations with overall excess mortality, excess mortality increases more for males than females. We suggest that the sex-differences observed during the COVID-19 pandemic reflects a general sex-disparity in excess mortality.

Sutureless aortic valve replacement: a meta-analysis

Background and objectives Sutureless aortic valves aim to achieve better outcomes and to aid and facilitate the minimally invasive aortic valve replacement procedure by tackling the issue of cross clamp time, which is an independent predictor of post-operative outcomes especially in patients with serious comorbidities. (2, 3) By reducing the number of sutures, the time for sutures placement is reduced. (1) Our Meta-analysis tries to assess the safety and hemodynamic performance of the sutureless aortic valve prosthesis’s in an attempt to ascertain their benefits as a viable alternative to current established measures. Methodology From their beginnings to February 2017, electronic searches were conducted using six databases. Relevant studies using commercially accessible suture-free valves to replace the aortic valve have been recognized. Based on the predefined endpoints, data were collected and analyzed. Results FC For incorporation in qualitative and quantitative analyses, twenty-four studies were recognized, with a total number of 5073 patients undergoing sutureless aortic valve replacement (SU-AVR). Mortality incidence at 30 days and 12 months follow-ups were 2.5% and 2.7%, respectively, while the incidence of thromboembolic events (1.6%) and paravalvular leak (PVL) (0.5%) were acceptable. Conclusion Current available evidence indicates that sutureless aortic valve replacement is a safe operation showing low mortality and complication rates, with satisfactory hemodynamic performance.

Lack of effect on in-hospital mortality of drugs used during COVID-19 pandemic: Findings of the retrospective multicenter COVOCA study

Introduction During COVID-19 pandemic, the use of several drugs has represented the worldwide clinical practice. However, though the current increase of knowledge about the disease, there is still no effective treatment for the usage of drugs. Thus, we retrospectively assessed use and effects of therapeutic regimens in hospitalized patients on in-hospital mortality. Methods COVOCA is a retrospective observational cohort study on 18 COVID centres throughout Campania Region Hospitals. We included adult patients with confirmed SARS-CoV-2 infection, discharged/dead between March/June 2020. Results 618 patients were included, with an overall in-hospital cumulative mortality incidence of 23.1%. Most prescribed early treatments were antivirals (72%), antibiotics (65%) and hydroxychloroquine/anticoagulants (≈50%). Tocilizumab, indeed, was largely prescribed late during hospitalization. Multivariable models, with a cut-off at day 2 for early COVID-19 therapy administration, did not disclose any significant association of a single drug administration on the clinical outcome. Discussion COVOCA represents the first multicenter database in Campania region. None drug class used during the pandemic significantly modified the outcome, regardless of therapy beginning, both overall and net of those already in non-invasive ventilation (NIV)/ orotracheal intubation (OTI) at hospitalization. Our cumulative incidence of mortality seems lower than other described during the same period, particularly in Northern Italy.