Summary Background COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. Aims To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. Methods We conducted a retrospective, case–control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. Results A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). Conclusion Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality.
Background Approximately 19% of people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progress to severe or critical stages of the coronavirus disease 2019 (COVID-19) with a mortality rate exceeding 50%. We aimed to examine the characteristics, mortality rates, intubation rate, and length of stay (LOS) of patients hospitalized with COVID-19 disease with high oxygen requirements (critically ill). Methods We conducted a retrospective analysis in a single center in Brooklyn, New York. Adult hospitalized patients with confirmed COVID-19 disease and high oxygen requirements were included. We performed multivariate logistic regression analyses for statistically significant variables to reduce any confounding. Results A total of 398 patients were identified between March 19th and April 25th, 2020 who met the inclusion criteria, of which 247 (62.1%) required intubation. The overall mortality rate in our study was 57.3% (n = 228). The mean hospital LOS was 19.1 ± 17.4 days. Patients who survived to hospital discharge had a longer mean LOS compared to those who died during hospitalization (25.4 ± 22.03 days versus10.7 ± 1.74 days). In the multivariate analysis, increased age, intubation and increased lactate dehydrogenase (LDH) were each independently associated with increased odds of mortality. Diarrhea was associated with decreased mortality (OR 0.4; CI 0.16, 0.99). Obesity and use of vasopressors were each independently associated with increased intubation. Conclusions In patients with COVID-19 disease and high oxygen requirements, advanced age, intubation, and higher LDH levels were associated with increased mortality, while diarrhea was associated with decreased mortality. Gender, diabetes, and hypertension did not have any association with mortality or length of hospital stay.
Cantú syndrome (CS), caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8 ) and accessory (SUR2, ABCC9 ) ATP-sensitive potassium (K ATP ) channel subunit genes, is frequently accompanied by gastrointestinal (GI) dysmotility, and we describe 1 CS patient who required an implanted intestinal irrigation system for successful stooling. We used gene-modified mice to assess the underlying K ATP channel subunits in gut smooth muscle and to model the consequences of altered K ATP channels in CS gut. We show that Kir6.1/SUR2 subunits underlie smooth muscle K ATP channels throughout the small intestine and colon. Knockin mice, carrying human KCNJ8 and ABCC9 CS mutations in the endogenous loci, exhibited reduced intrinsic contractility throughout the intestine, resulting in death when weaned onto solid food in the most severely affected animals. Death was avoided by weaning onto a liquid gel diet, implicating intestinal insufficiency and bowel impaction as the underlying cause, and GI transit was normalized by treatment with the K ATP inhibitor glibenclamide. We thus define the molecular basis of intestinal K ATP channel activity, the mechanism by which overactivity results in GI insufficiency, and a viable approach to therapy.
Background Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population is limited. Aim To delineate the adverse factors associated with outcomes of COVID- 19 patients ≥75 years of age. Design Retrospective cohort study. Methods Patients were classified into mild/moderate, severe/very severe, and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. Results 355 patients aged ≥75 years hospitalized with COVID-19 between March 19th and April 25th, 2020 were included. Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease : 17.4%, severe/very severe disease : 71.3%, critical disease: 94.9%, p < 0.001). Increased age, dementia, and severe/very severe and critical disease groups were each significantly associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR : 0.12, 95% CI : 0.02-0.60, p < 0.05)]. None of the cardiovascular comorbidities were significantly associated with mortality. Conclusion Age and dementia are associated with increased odds for mortality in patients ≥75 years of age hospitalized with COVID-19. Those who require intubation have the greatest odds for mortality. Diarrhea as a presenting symptom was associated with lower odds for mortality.
Takotsubo cardiomyopathy (TC) or stress cardiomyopathy with the presence of transient apical ballooning of the left ventricle in the absence of obstructive coronary artery disease. The recurrence of TC is extremely rare, with an annual recurrence risk of 1.5% and approximately 5% recurrence risk after six years. We present a case of a patient with a history of TC who presented with chest pain and ST-segment elevation in her electrocardiogram and was found to have normal coronaries and diagnosed with recurrent TC.
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