Improved Treatment Outcomes With Bedaquiline When Substituted for Second-line Injectable Agents in Multidrug-resistant Tuberculosis: A Retrospective Cohort Study.

BACKGROUND: Bedaquiline is used as a substitute for second-line injectable (SLI) intolerance in the treatment of multidrug-resistant (MDR) tuberculosis, but the efficacy and safety of this strategy is unknown. METHODS: In this retrospective cohort study adults receiving bedaquiline substitution for MDR tuberculosis therapy, plus a matched control group who did not receive bedaquiline, were identified from the electronic tuberculosis register in the Western Cape Province, South Africa. The primary outcome measure was the proportion of patients with death, loss to follow-up, or failure to achieve sustained culture conversion at 12 months of treatment. RESULTS: Data from 162 patients who received bedaquiline substitution and 168 controls were analyzed; 70.6% were infected with human immunodeficiency virus. Unfavorable outcomes occurred in 35 of 146 (23.9%) patients in the bedaquiline group versus 51 of 141 (36.2%) in the control group (relative risk, 0.66; 95% confidence interval, .46 -.95). The number of patients with culture reversion was lower in those receiving bedaquiline (1 patient; 0.8%) than in controls (12 patients; 10.3%; P = .001). Delayed initiation of bedaquiline was independently associated with failure to achieve sustained culture conversion (adjusted odds ratio for every 30-day delay, 1.5; 95% confidence interval, 1.1-1.9). Mortality rates were similar at 12 months (11 deaths in each group; P = .97). CONCLUSIONS: Substituting bedaquiline for SLIs in MDR tuberculosis treatment resulted in improved outcomes at 12 months compared with patients who continued taking SLIs, supporting the use of bedaquiline for MDR tuberculosis treatment in programmatic settings.

Mitral valve chord rupture in a pregnant patient with uncontrolled hyperthyroidism.

Summary: Graves' disease can have multiple cardiac manifestations. A rare complication is that of severe mitral regurgitation secondary to mitral valve chordae rupture, due to both compromise of valve integrity by deposition of glycosaminoglycans and the hemodynamic stresses of thyrotoxicosis. Pregnancy, with its related hemodynamic changes, is another setting in which mitral valve chordae rupture has occasionally been documented. We present a unique case of a 36-year-old female with uncontrolled Graves' disease who presented during pregnancy at 13 weeks gestation with atrial flutter and features of congestive heart failure. Echocardiogram found severe mitral regurgitation secondary to a ruptured mitral chord. She was treated conservatively with diuresis and ultimately delivered her baby without complication at 28 weeks when she had preterm premature rupture of membranes. She is currently on methimazole and propranolol and pending definitive management of her Graves' disease. This represents not only a rare cardiac complication in a patient with Graves' disease but also is the first in the literature, to our knowledge, which describes this complication in a pregnant patient with Graves' disease. Learning points: Thyroid disease can have multiple effects on the heart through hemodynamic and structural changes and can result in heart failure, arrhythmias, valvular disease, and pulmonary hypertension. Graves' disease can cause glycosaminoglycan deposition in valvular tissue resulting in fragile leaflets that can rupture with little stress. Pregnancy and thyrotoxicosis have similar hemodynamic consequences with increased cardiac output and reduced systemic vascular resistance. Be vigilant in those with hyperthyroidism with a new murmur or features of acute heart failure, as a ruptured valve chord can result in increased morbidity and mortality if not recognized and addressed quickly.

Impact of achieving euthyroidism on pulmonary artery systolic pressures in hyperthyroidism-associated pulmonary hypertension - a systematic review.

In this systematic review, we seek to clarify the impact of treatment of hyperthyroidism on pulmonary hypertension in patients with both these conditions. We included 39 of 709 articles retrieved, that studied patients with hyperthyroidism and pulmonary hypertension (PH). From these, those with a documented pre-treatment Pulmonary Artery Systolic Pressure (PASP) > 35 mmHg and complete follow up were analyzed, yielding 3 case series and 22 case reports with a total of 81 cases. A significant improvement in PASP was noted with achieving euthyroidism in the 3 case series. The case reports showed a significant reduction in mean PASP from 60.5 ± 13.2 mmHg to 37.5 ± 10.1 mmHg (p < 0.001) in patients with Grave's disease with achieving euthyroidism. No deaths were reported during the follow up period. Achievement of a euthyroid state in patients with hyperthyroidism is associated with statistically significant reductions in PASP.

The relationship between diabetes and clinical outcomes in COVID-19: a single-center retrospective analysis.

AIMS: Coronavirus disease 19 (COVID-19) has become a pandemic. Diabetic patients tend to have poorer outcomes and more severe disease (Kumar et al. in Diabetes Metab Syndr 14(4):535-545, 2020. https://doi.org/10.1016/j.dsx.2020.04.044 ). However, the vast majority of studies are representative of Asian and Caucasian population and fewer represent an African-American population. METHODS: In this single-center, retrospective observational study, we included all adult patients (> 18 years old) admitted to Einstein Medical Center, Philadelphia, with a diagnosis of COVID-19. Patients were classified according to having a known diagnosis of diabetes mellitus. Demographic and clinical data, comorbidities, outcomes and laboratory findings were obtained. RESULTS: Our sample included a total of 355 patients. 70% were African-American, and 47% had diabetes. Patients with diabetes had higher peak inflammatory markers like CRP 184 (111-258) versus 142 (65-229) p = 0.012 and peak LDH 560 (384-758) versus 499 (324-655) p = 0.017. The need for RRT/HD was significantly higher in patients with diabetes (21% vs 11% p = 0.013) as well as the need for vasopressors (28% vs 18% p = 0.023). Only age was found to be an independent predictor of mortality. We found no significant differences in inpatient mortality p = 0.856, need for RRT/HD p = 0.429, need for intubation p = 1.000 and need for vasopressors p = 0.471 in African-Americans with diabetes when compared to non-African-Americans. CONCLUSIONS: Our study demonstrates that patients with COVID-19 and diabetes tend to have more severe disease and poorer clinical outcomes. African-American patients with diabetes did not differ in outcomes or disease severity when compared to non-African-American patients.