IMPORTANCE Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias.OBJECTIVE To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTSThis was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURESChange in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [−15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI,). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCEIn this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

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Objective To explore a possible link between authors' financial conflicts of interest and their position on the association of rosiglitazone with increased risk of myocardial infarction in patients with diabetes.

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[reaction: see text] An efficient method for the site-specific generation of 2-deoxyribonolactone oxidative DNA damage lesions from a "photocaged" nucleoside analogue was developed. A nucleoside phosphoramidite bearing a C-1' nitrobenzyl cyanohydrin was prepared and incorporated into DNA oligonucleotides using automated DNA synthesis. The caged analogue, which was stable in aqueous solution, was converted to the 2-deoxyribonolactone lesion by UV irradiation. DNA containing the caged analogue and the deoxyribonolactone site were characterized by electrospray mass spectrometry (ES-MS).

Long noncoding RNAs (lncRNA) are emerging as key players in cancer as parts of poorly understood molecular mechanisms. Here, we investigated lncRNAs that play a role in hepatocellular carcinoma (HCC) and identified NIHCOLE, a novel lncRNA induced in HCC with oncogenic potential and a role in the ligation efficiency of DNA double-stranded breaks (DSB). NIHCOLE expression was associated with poor prognosis and survival of HCC patients. Depletion of NIHCOLE from HCC cells led to impaired proliferation and increased apoptosis. NIHCOLE deficiency led to accumulation of DNA damage due to a specific decrease in the activity of the nonhomologous end-joining (NHEJ) pathway of DSB repair. DNA damage induction in NIHCOLE-depleted cells further decreased HCC cell growth. NIHCOLE was associated with DSB markers and recruited several molecules of the Ku70/Ku80 heterodimer. Further, NIHCOLE putative structural domains supported stable multimeric complexes formed by several NHEJ factors including Ku70/80, APLF, XRCC4, and DNA ligase IV. NHEJ reconstitution assays showed that NIHCOLE promoted the ligation efficiency of blunt-ended DSBs. Collectively, these data show that NIHCOLE serves as a scaffold and facilitator of NHEJ machinery and confers an advantage to HCC cells, which could be exploited as a targetable vulnerability. Significance: This study characterizes the role of lncRNA NIHCOLE in DNA repair and cellular fitness in HCC, thus implicating it as a therapeutic target. See related commentary by Barcena-Varela and Lujambio, p. 4899

OBJECTIVE:To measure the effect of duty periods no longer than 16 hours on patient care and resident education. PATIENTS AND METHODS:As part of our Educational Innovations Project, we piloted a novel resident schedule for an inpatient service that eliminated shifts longer than 16 hours without increased staffing or decreased patient admissions on 2 gastroenterology services from August 29 to November 27, 2009. Patient care variables were obtained through medical record review. Resident well-being and educational variables were collected by weekly surveys, end of rotation evaluations, and an electronic card-swipe system. RESULTS:Patient care metrics, including 30-day mortality, 30-day readmission rate, and length of stay, were unchanged for the 196 patient care episodes in the 5-week intervention month compared with the 274 episodes in the 8 weeks of control months. However, residents felt less prepared to manage cross-cover of patients (P=.006). There was a nonsignificant trend toward decreased perception of quality of education and balance of personal and professional life during the intervention month. Residents reported working fewer weekly hours overall during the intervention (64.3 vs 68.9 hours; P=.40), but they had significantly more episodes with fewer than 10 hours off between shifts (24 vs 2 episodes; P=.004).CONCLUSION: Inpatient hospital services can be staffed with residents working shifts less than 16 hours without additional residents. However, cross-cover of care, quality of education, and time off between shifts may be adversely affected.