Development and validation of a federated learning framework for detection of subphenotypes of multisystem inflammatory syndrome in children (preprint)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection. The highly diverse clinical features of MIS-C necessities characterizing its features by subphenotypes for improved recognition and treatment. However, jointly identifying subphenotypes in multi-site settings can be challenging. We propose a distributed multi-site latent class analysis (dMLCA) approach to jointly learn MIS-C subphenotypes using data across multiple institutions. Methods We used data from the electronic health records (EHR) systems across nine U.S. childrens hospitals. Among the 3,549,894 patients, we extracted 864 patients < 21 years of age who had received a diagnosis of MIS-C during an inpatient stay or up to one day before admission. Using MIS-C conditions, laboratory results, and procedure information as input features for the patients, we applied our dMLCA algorithm and identified three MIS-C subphenotypes. As validation, we characterized and compared more granular features across subphenotypes. To evaluate the specificity of the identified subphenotypes, we further compared them with the general subphenotypes identified in the COVID-19 infected patients. Findings Subphenotype 1 (46.1%) represents patients with a mild manifestation of MIS-C not requiring intensive care, with minimal cardiac involvement. Subphenotype 2 (25.3%) is associated with a high risk of shock, cardiac and renal involvement, and an intermediate risk of respiratory symptoms. Subphenotype 3 (28.6%) represents patients requiring intensive care, with a high risk of shock and cardiac involvement, accompanied by a high risk of >4 organ system being impacted. Importantly, for hospital-specific clinical decision-making, our algorithm also revealed a substantial heterogeneity in relative proportions of these three subtypes across hospitals. Properly accounting for such heterogeneity can lead to accurate characterization of the subphenotypes at the patient-level. Interpretation Our identified three MIS-C subphenotypes have profound implications for personalized treatment strategies, potentially influencing clinical outcomes. Further, the proposed algorithm facilitates federated subphenotyping while accounting for the heterogeneity across hospitals.

A Fuzzy Logic Scheme Based on Population and Spread Rate for the Management of Vaccination during Pandemics (preprint)

The pandemics like COVID-19 cause a massive shock to the global economy and its impacts are huge and endure across all domains of life. Effectively managing the limited vaccine supply is crucial in the fight against pandemics. A central issue in the management of pandemic vaccination is the allocation of vaccines from the central government to state authorities. The objective of this research was to make use of a fuzzy logic scheme for the management of vaccination to the local state authorities by a central Government based on population and spread rate. The proposed scheme utilizes a fuzzy logic inference system taking into account on population and spread rate to infer the vaccination rate. This scheme is in contrast to conventional approaches that often consider either a state's population or spread rate as the sole basis for vaccine allocation. The Covid-19 data of 6 southern states of India during the first week of October 2020 collected from the database maintained by the Ministry of Health and Family Welfare of Government of India was used for the verification of the proposed scheme. The proposed scheme was implemented using MATLAB/SIMULINK software and compared with the conventional schemes, one based on population and another based on spread rate. The results show that the proposed scheme ensures that sufficient doses of vaccines are allotted to the states on priority where spread rate is more and vaccines are not wasted in states where spread rate is less. At the same time, all states are eventually allotted sufficient vaccine doses to halt transmission. The proposed scheme ensures that sufficient vaccines are distributed in a quick, effective and unbiased way, and enhances the fight against pandemics.

Can We Use High-Frequency Yield Data to Better Understand the Effects of Monetary Policy and Its Communication? Yes and No! (preprint)

We examine the effects of three facets of monetary policy in Australia using high-frequency yield changes around RBA announcements: current policy; signalling/forward guidance; and changes in premia. Shocks to current policy have similar effects to those identified using conventional approaches, but the effects of signalling and premia shocks are imprecisely estimated. Still, the approach provides evidence that: forward guidance shocks raised future rate expectations in the mid-2010s as the RBA highlighted housing risks; Covid-era policy mainly affected term premia, unlike pre-COVID policy; shocks to the expected path of rates are predictable, suggesting markets misunderstand the RBA’s reaction to data.

A case of fulminant myocarditis associated with a novel coronavirus infection (preprint)

Background COVID-19 patients mainly have the high incidence and mortality of major cardiovascular diseases in the acute phase. However, fulminant myocarditis and cardiogenic shock are rare in the post-acute phase, and the prognosis is very poor.Case presentation Here, we report a case of a 43-year-old young man with fulminant myocarditis and cardiogenic shock in the acute phase after coronavirus infection, with timely extracorporeal membrane oxygenation and intra-aortic balloon application in respiratory failure, which improved the prognosis of fulminant myocarditis and saved the lives of COVID-19 patients. After active anti-shock, mechanical ventilation, anti-inflammation, and organ support and other treatments, the patient was discharged after a stable condition and stable vital signs. The patient was followed up weekly after discharge and showed good cardiopulmonary recovery.Conclusions In critically ill patients with severe myocarditis, cardiogenic shock, arrhythmia, respiratory and circulatory failure, ECMO and IABP in patients with explosive myocardial inflammatory cardiogenic shock have achieved better results.

[Kawasaki disease cytokine release syndrome and Kawasaki disease shock syndrome: A case report]. / Síndrome de tormenta de citocinas y síndrome de choque por enfermedad de Kawasaki: reporte de un caso.

BACKGROUND: Kawasaki disease is a vasculitis of small and medium vessels, with a high prevalence throughout the world. In addition to coronary aneurysms, this vasculitis can lead to a number of systemic complications, including Kawasaki disease shock syndrome and Kawasaki disease cytokine storm syndrome. CASE REPORT: : Case report: A 12-year-old male patient, who began his condition with heartburn, sudden fever of 40 ºC and jaundice, for which he was prescribed treatment with antipyretics and bismuth subsalicylate, without satisfactory reaction. Gastroalimentary content was added three times, and centripetal maculopapular dermatosis. After 12 hospital stays, he was evaluated by personnel from the Pediatric Immunology service, who reported data on hemodynamic instability due to persistent tachycardia for hours, immediate capillary refill, intense pulse, oliguria of 0.3 mL/kg/h of partial urinary output with condensed urine; the systolic blood pressure figures were below the 50% percentile, and there was polypnea and limit saturation in 93%. In the paraclinical studies, the rapid decrease in platelet count (from 297,000 to 59,000 in 24 hours), as well as a neutrophil-lymphocyte index of 12, drew attention. The concentrations of NS1 size, IgM and IgG for dengue and PCR for SARS virus were determined. -CoV-2, which were negative. The definitive diagnosis of Kawasaki disease was established with Kawasaki disease shock syndrome. The evolution of the patient was satisfactory, with a decrease in fever after the administration of gamma globulin on the tenth day of hospitalization, and a new protocol with prednisone (50 mg/day) was started, when the cytokine storm syndrome due to illness was integrated. Kawasaki syndrome simultaneous with pre-existing disorders, that is, Kawasaki disease and Kawasaki disease shock syndrome due to thrombocytopenia, hepatosplenomegaly, fever, lymphadenopathy; in addition, ferritin of 605 mg/dL and transaminasemia. The control echocardiogram did not show coronary abnormalities and hospital discharge was granted 48 hours after starting treatment with the corticosteroid, with a 14-day follow-up plan. CONCLUSIONS: Kawasaki disease is an autoimmune vasculitis that can worsen with simultaneous syndromes associated with high mortality. It is important to know this type of alterations and their differences to properly discern and implement effective and timely treatment.

INTRODUCCIÓN: La enfermedad de Kawasaki es una vasculitis de pequeños y medianos vasos, con elevada prevalencia en todo el mundo. Además de los aneurismas coronarios, esta vasculitis puede generar diversas complicaciones sistémicas, como el síndrome de choque por enfermedad de Kawasaki y el síndrome de tormenta de citocinas por enfermedad de Kawasaki. REPORTE DE CASO: Paciente masculino de 12 años de edad, que inició su padecimiento con pirosis, fiebre súbita de 40 ºC e ictericia, por lo que se le prescribió tratamiento con antipiréticos y subsalicilato de bismuto, sin reacción satisfactoria. Se agregó vómito de contenido gastroalimentario en tres ocasiones y dermatosis maculopapular centrípeta. Después de 12 horas de estancia intrahospitalaria fue valorado por personal del servicio de Inmunología Pediátrica, quienes informaron datos de inestabilidad hemodinámica por taquicardia persistente, llenado capilar inmediato, pulso intenso, oliguria de 0.3 mL/kg/h de gasto urinario parcial con orina condensada; las cifras de tensión arterial sistólica se encontraban debajo del percentil 50%, y había polipnea y saturación limítrofe en 93%. En los estudios paraclínicos llamó la atención el rápido descenso del conteo plaquetario (de 297,000 a 59,000 en 24 horas), así como el índice neutrófilo-linfocito de 12. Se determinaron las concentraciones de antígeno NS1, IgM e IgG para dengue y PCR para virus SARS-CoV-2, que resultaron negativas. Se estableció el diagnóstico definitivo de enfermedad de Kawasaki con síndrome de choque por enfermedad de Kawasaki. La evolución del paciente fue satisfactoria, con disminución de la fiebre luego de la administración de gammaglobulina en el décimo día de hospitalización, y se inició un nuevo protocolo con prednisona (50 mg/día), al integrarse el síndrome de tormenta de citocinas por enfermedad de Kawasaki simultáneo con las alteraciones preexistentes, es decir: enfermedad de Kawasaki y síndrome de choque por enfermedad de Kawasaki por trombocitopenia, hepatoesplenomegalia, fiebre, adenopatías; además, ferritina de 605 mg/dL y transaminasemia. El ecocardiograma de control no mostró modificaciones coronarias y se otorgó el alta hospitalaria después de 48 horas de iniciar el tratamiento con el corticosteroide, con plan de seguimiento en 14 días. CONCLUSIONES: La enfermedad de Kawasaki es una vasculitis autoinmunitaria que puede agravarse con síndromes simultáneos asociados y generar elevada mortalidad. Es importante conocer este tipo de alteraciones y sus diferencias para discernir de forma adecuada e implementar el tratamiento eficaz y oportuno.

Governing the Varieties of Sovereign Risk in EMU: The Rise of State-Contingent Common Public Policies (preprint)

The 30-year old Maastricht Treaty on European Union (EU) is based on the political vision that a stable euro requires sound budgetary policies and sustainable public finances in all the participating countries. This paper reviews the evolving European framework for governing the varieties of sovereign risk in the Economic and Monetary Union (EMU). The main finding is that a growing body of EU/EMU public policies with provisions contingent on the state of national economies, sustainable financial integration, or effective monetary transmission, works against fiscal discipline. EU fiscal rules allow for state-contingent compliance and include ample flexibility to account for mitigating relevant factors. EU financial governance provides public entities with a privileged access to private finance contingent on prudential considerations. The European Central Bank introduced contingent monetary policy tools for managing government bond spreads. Member States draw on EU/EMU quasi-fiscal agencies to create common contingent liabilities which escape EU fiscal oversight. The European response to the economic fallout from the Covid-19 pandemic added an EU-debt financed fiscal redistribution scheme contingent on national funding needs. Member States can also draw on this public risk-sharing tool to absorb the energy shock following the Russian invasion of Ukraine. The rise of state-contingent governance to suppress the varieties of sovereign risk in EMU marks the political transition from the Maastricht Treaty’s focus on public risk reduction to a ‘Next Generation EMU’ which favours public risk-sharing. The challenge for the future will be to balance the need to stabilise the eurozone with the need for fiscal discipline.

TNF/iNOS/NO pathway mediates host susceptibility to endothelial-dependent circulatory failure and death induced by betacoronavirus infection.

Poor disease outcomes and lethality are directly related to endothelial dysfunction in betacoronavirus infections. Here, we investigated the mechanisms underlying the vascular dysfunction caused by the betacoronaviruses MHV-3 and SARS-CoV-2. Wild-type C57BL/6 (WT) and knockout mice for inducible nitric oxide synthase (iNOS-/-) or TNF receptor 1 (TNFR1-/-) were infected with MHV-3, and K18-hACE2 transgenic mice expressing human ACE2 were infected with SARS-CoV-2. Isometric tension was used to evaluate vascular function. Protein expression was determined by immunofluorescence. Tail-cuff plethysmography and Doppler were used to assess blood pressure and flow, respectively. Nitric oxide (NO) was quantified with the DAF probe. ELISA was used to assess cytokine production. Survival curves were estimated using Kaplan-Meier. MHV-3 infection reduced aortic and vena cava contractility, arterial blood pressure, and blood flow, resulting in death. Resistance mesenteric arteries showed increased contractility. The contractility of the aorta was normalized by removing the endothelium, inhibiting iNOS, genetically deleting iNOS, or scavenging NO. In the aorta, iNOS and phospho-NF-kB p65 subunit expression was enhanced, along with basal NO production. TNF production was increased in plasma and vascular tissue. Genetic deletion of TNFR1 prevented vascular changes triggered by MHV-3, and death. Basal NO production and iNOS expression were also increased by SARS-CoV-2. In conclusion, betacoronavirus induces an endothelium-dependent decrease in contractility in macro-arteries and veins, leading to circulatory failure and death via TNF/iNOS/NO. These data highlight the key role of the vascular endothelium and TNF in the pathogenesis and lethality of coronaviruses.

Characteristics and Outcomes of Multisystem Inflammatory Syndrome in Children: A Multicenter, Retrospective, Observational Cohort Study in Mexico (preprint)

Multisystem inflammatory syndrome in children temporally associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysm were found in 5.7% and 13.2% of the patients, respectively. The rate of mortality due to SARS-CoV-2-related factors was 4.6%. Delay of [≥]10 days in hospital admission was associated with coronary artery aneurysm or dilatation (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2- 2.0). Age [≥] 10 years (OR 5.6, 95% CI 1.4- 2.04), severe underlying condition (OR 9.3, 95% CI 2.8- 31.0), platelet count < 150,000/mm3 (OR 4.2, 95% CI 1.2- 14.7), international normalized ratio > 1.2 at admission (OR 3.8, 95% CI 1.05- 13.9), and serum ferritin concentration > 1500 mg/dL (OR 52, 95% CI 5.9- 463) were risk factors for death.

Capillary Leak Syndrome after SARS-CoV-2 Infection and COVID-19 Vaccines: A Comparative Review (preprint)

Systemic capillary leak syndrome (SCLS) is an uncommon, potentially life-threatening disorder defined as recurrent attacks of pseudo-shock. This syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space. SCLS can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency. The syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolemia, hemoconcentration, prerenal azotemia, shock, and syncope. After ruling out other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the classical triad of hypotension, hemoconcentration, and hypoalbuminemia. Eliminating the precipitating factors is the cornerstone of SCLS management. It is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this condition. This review will discuss and compare different aspects of SLCS after SARS-CoV-2 infection and COVID-19 vaccination.

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

The Prediction Value of D-Dimer on Prognosis in Intensive Care Unit among Old Patients ( ≥65 Years): A 9-Year Single-Center Retrospective Study of 9261 Cases.

Background: D-dimer (DD) has been indicated as a potential indicator due to its connection with the prognosis of the COVID-19 pandemic. Aging is linked to elevated DD levels in coagulation activation. However, few studies have investigated the correlation of DD with prognosis, especially in the old population. Therefore, this study aims at investigating the correlation of DD with prognosis in shock and perioperative populations over 65 years of age. Methods: We analyzed 9261 old patients admitted to intensive care units (ICUs) with either confirmed shock or in perioperative period of high-risk surgery, with 8813 of them had DD levels determined on admission. In-hospital mortality, length of ICU stay and ventilation time (VT) associated variables were assessed using generalized linear models. Results: Although DD levels had no positive correlations with in-hospital mortality (RR, 1.006; 95% CI, 0.998-1.014) and length of ICU stay (RR, 1.012; 95% CI, 0.997-1.028) in Model 3, they were strongly correlated with VT (RR, 1.577; 95% CI, 1.024-2.064). Higher DD levels in females (RR, 1.804; 95% CI, 1.116-2.602), those who used antibiotics (RR, 1.736; 95% CI, 1.092-2.453), those with surgery (RR, 1.640; 95% CI, 1.273-2.114), and those with shock (RR, 1.740; 95% CI, 1.001-2.687) had stronger correlation with longer VT than the counterparts. While patients who were between 65 and 74 years old (RR, 1.023; 95% CI, 1.003-1.043), with no use of antibiotics (RR, 1.007; 95% CI, 1.001-1.013) nor shock (RR, 1.011; 95% CI, 1.002-1.021), but had undergone surgical procedures (RR, 1.030; 95% CI, 1.012-1.048) were correlated with a longer ICU length of stay. Conclusion: DD levels at ICU admission are highly related to increased VT and length of ICU stay in the old population with either confirmed shock or after high-risk surgery, indicating the strong potential of DD as a marker with prognostic utility for all ICU patients in the future.

The Impacts of COVID-19 Shock on Intergenerational Income Mobility: Evidence from China.

The COVID-19 crisis has caused a huge negative shock to economic activities worldwide, leading to a reduction in income and changes in income distribution. Intergenerational mobility is an important indicator of sustainable social development. This paper explores the short-term impacts of the sudden COVID-19 pandemic on intergenerational income mobility and personal income in China. Using the variation in the number of confirmed cases across provinces, we construct a province-level pandemic intensity index and combine it with individual data from the China Family Panel Studies (CFPS). We apply a general difference-in-difference strategy to identify the causal effect of the pandemic on intergenerational income mobility. We find that personal income is positively related to parental income, and that the COVID-19 crisis has caused a decline in individual income and exacerbated intergenerational income persistence. A more intense COVID-19 pandemic shock is associated with a larger increase in intergenerational income elasticity and intergenerational income rank-rank slope. We found that with one standard deviation increase in local pandemic intensity, the intergenerational income elasticity increases by 0.315 and the intergenerational income rank-rank slope increases by 0.198 on average. The mechanism testing suggests that heterogeneous effects among different groups are the force underlying the results. Low-income, low-skilled, and low-parental-income individuals have suffered a more severe impact from the pandemic shock.

Deep immune profiling uncovers novel associations with clinical phenotypes of Multisystem Inflammatory Syndrome in Children (MIS-C) (preprint)

Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory condition that follows SARS-CoV2 infection or exposure in children. Clinical presentations are highly variable and include fever, gastrointestinal (GI) disease, shock, and Kawasaki Disease-like illness (MIS-C/KD). Compared to patients with acute COVID, patients with MIS-C have a distinct immune signature and expansion of TRVB11 expressing T cells. However, the relationship between immunological and clinical phenotypes of MIS-C is unknown. Here, we measured serum biomarkers, TCR repertoire, and SARS-CoV2-specific T cell responses in a cohort of 76 MIS-C patients. Serum biomarkers associated with macrophage and Th1 activation were elevated in patients with shock, consistent with previous reports. Significantly increased SARS-CoV-2-induced IFN-{gamma}, IL-2, and TNF- production were seen in CD4+ T cells from patients with neurologic involvement and respiratory failure. Diarrhea was associated with a significant reduction in shock-associated serum biomarkers, suggesting a protective effect. TRVB11 usage was highly associated with MIS-C/KD and coronary aneurysms, suggesting a potential biomarker for these manifestations in MIS-C patients. By identifying novel immunologic associations with the different clinical phenotypes of MIS-C, this study provides insights into the clinical heterogeneity of MIS-C. These unique immunophenotypic associations could provide biomarkers to identify patients at risk for severe complications of MIS-C, including shock and MIS-C/KD.

Incidence of and risk factors for postintubation hypotension in critically ill patients with COVID-19. / Incidência e fatores de risco para hipotensão pós-intubação em pacientes críticos com COVID-19.

OBJECTIVE: To evaluate the incidence of risk factors for postintubation hypotension in critically ill patients with COVID-19. METHODS: We conducted a retrospective study of 141 patients with COVID-19 who were intubated in the intensive care unit. Postintubation hypotension was defined as the need for any vasopressor dose at any time within the 60 minutes following intubation. Patients with intubation-related cardiac arrest and hypotension before intubation were excluded from the study. RESULTS: Of the 141 included patients, 53 patients (37.5%) had postintubation hypotension, and 43.6% of the patients (n = 17) were female. The median age of the postintubation hypotension group was 75.0 (interquartile range: 67.0 - 84.0). In the multivariate analysis, shock index ≥ 0.90 (OR = 7.76; 95%CI 3.14 - 19.21; p < 0.001), albumin levels < 2.92g/dL (OR = 3.65; 95%CI 1.49 - 8.96; p = 0.005), and procalcitonin levels (OR = 1.07, 95%CI 1.01 - 1.15; p = 0.045) were independent risk factors for postintubation hypotension. Hospital mortality was similar in patients with postintubation hypotension and patients without postintubation hypotension (92.5% versus 85.2%; p = 0.29). CONCLUSION: The incidence of postintubation hypotension was 37.5% in critically ill COVID-19 patients. A shock index ≥ 0.90 and albumin levels < 2.92g/dL were independently associated with postintubation hypotension. Furthermore, a shock index ≥ 0.90 may be a practical tool to predict the increased risk of postintubation hypotension in bedside scenarios before endotracheal intubation. In this study, postintubation hypotension was not associated with increased hospital mortality in COVID-19 patients.

OBJETIVO: Avaliar a incidência de fatores de risco para hipotensão pósintubação em pacientes críticos com COVID-19. METÓDOS: Foi realizado um estudo retrospectivo com 141 pacientes com COVID-19 que foram intubados na unidade de terapia intensiva. Hipotensão pós-intubação foi definida como a necessidade de qualquer dose de vasopressor a qualquer momento em até 60 minutos após a intubação. Pacientes com parada cardiorrespiratória relacionada à intubação e hipotensão antes da intubação foram excluídos do estudo. RESULTADOS: Dos 141 pacientes incluídos, 53 pacientes (37,5%) e 43,6% dos pacientes (n = 17) eram do sexo feminino. A idade mediana do grupo com hipotensão pós-intubação foi de 75 anos (amplitude interquartil: 67,0 - 84,0). Na análise multivariada, índice de choque ≥ 0,90 (RC = 7,76; IC95% 3,14 - 19,21; p < 0,001), níveis de albumina < 2,92g/dL (RC = 3,65; IC95% 1,49 - 8,96; p = 0,005) e níveis de procalcitonina (RC = 1,07, IC95% 1,01 - 1,15; p = 0,045) foram fatores de risco independentes para hipotensão pós-intubação. A mortalidade hospitalar foi semelhante em pacientes com hipotensão pós-intubação e pacientes sem hipotensão pós-intubação (92,5% versus 85,2%; p = 0,29). CONCLUSÃO: A incidência de hipotensão pós-intubação foi de 37,5% em pacientes críticos com COVID-19. Um índice de choque ≥ 0,90 e níveis de albumina < 2,92g/ dL foram independentemente associados à hipotensão pós-intubação. Além disso, índice de choque ≥ 0,90 pode ser uma ferramenta do leito antes da intubação endotraqueal. Neste estudo, a hipotensão pós-intubação não esteve associada ao aumento da mortalidade hospitalar em pacientes com COVID-19.

Fatal cases of hemorrhagic fever with renal syndrome in Udmurtia, Russia, 2010 to 2019.

Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical and histopathological features of fatal HFRS in the Udmurt Republic (Udmurtia), located in the European part of Russia. This retrospective observational study included all fatal cases of HFRS that occurred in Udmurtia from January 2010 through December 2019. The most relevant clinical and autopsy data of these cases were recorded through a review of the patients' medical records and autopsy reports. During 2010-2019, Udmurtia had 41 fatal cases of HFRS of a total of 10,312 confirmed cases (case-fatality rate of 0.4%). Twenty-seven patients died in hypotensive and oliguric phases of HFRS due to refractory septic shock and acute respiratory distress syndrome. Fourteen patients died in the polyuric phase of the disease from complications of acute kidney injury or because of hospital-acquired bacterial infections. Multiorgan involvement was noted in all autopsies with variable degrees of generalized venous congestion, interstitial edema, capillary wall thickening, perivascular deposition of plasma proteins, microthrombosis formation, and perivascular hemorrhage. The more prominent histopathological features were seen in kidneys, lungs, and hypophysis.