Sodium zirconium cyclosilicate and metabolic acidosis: Potential mechanisms and clinical consequences.

Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH4+) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H+. This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study.

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.

Dor Torácica na sala de emergência / Chest Pain in the Emergency Departments

A dor torácica é reponsável por um grande volume de atendimento em serviços de emergência, sendo sua apresentação clínica muitas vezes inespecífica, gerando dúvida no médico assistente, podendo resultar em diagnósticos errôneos, manejo clínico inadequado e ônus desnecessário. As uidades de dor torácica facilitam o diagnóstico diferencial discernindo pacientes graves, que necessitam de intervenções precoces, daqueles que podem receber alta hospitalar com posterior acompanhamento ambulatorial. O uso de uma estratégia diagnóstica sistematizada permit um melhor manuseio dos pacientes com dor torácica, com conseuqnete melhora no prognóstico dos pacientes tratados, além da redução dos custos decorrentes e admissões e exames desnecessários...