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Mitochondria contain an independently maintained genome that encodes several proteins required for cellular respiration. Deletions in the mitochondrial genome have been identified that cause several maternally inherited diseases and are associated with certain cancers and neurological disorders. The majority of these deletions in human cells are flanked by short, repetitive sequences, suggesting that these deletions may result from recombination events. Our current understanding of the maintenance and repair of mtDNA is quite limited compared to our understanding of similar events in the nucleus. Many nuclear DNA repair proteins are now known to also localize to mitochondria, but their function and the mechanism of their action remain largely unknown. This study investigated the contribution of the nuclear double-strand break repair (DSBR) proteins Rad51p, Rad52p and Rad59p in mtDNA repair. We have determined that both Rad51p and Rad59p are localized to the matrix of the mitochondria and that Rad51p binds directly to mitochondrial DNA. In addition, a mitochondrially-targeted restriction endonuclease (mtLS-KpnI) was used to produce a unique double-strand break (DSB) in the mitochondrial genome, which allowed direct analysis of DSB repair in vivo in Saccharomyces cerevisiae. We find that loss of these three proteins significantly decreases the rate of spontaneous deletion events and the loss of Rad51p and Rad59p impairs the repair of induced mtDNA DSBs.

Objective We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group. Conclusion We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

We describe a case of new onset movement disorder in a patient with ventricular tachycardia storm supported with peripheral VA ECMO. The differential diagnosis of abnormal movements in a post cardiac arrest patient requiring temporary mechanical circulatory support for cardiogenic shock is explored.

Background: Electroencephalography (EEG) is commonly used after cardiac arrest. Burst suppression with identical bursts (BSIB) has been reported as a perfectly specific predictor of poor outcome but published case series are small. We describe two patients with BSIB who awakened from coma after cardiac arrest. Methods: We identified two out-of-hospital cardiac arrest (OHCA) patients with coma and BSIB. We determined the etiology of arrest, presenting neurological examination, potential confounders to neurological assessment, neurodiagnostics and time to awakening. We reviewed and interpreted EEGs using 2021 American Clinical Neurophysiology Society guidelines. We quantified identicality of bursts by calculating pairwise correlation coefficients between the first 500 ms of each aligned burst. Results: In case one we present a 62-year-old man with OHCA secondary to septic shock. EEG showed burst suppression pattern, with bursts consisted of high amplitude generalized spike waves in lock-step with myoclonus (inter-burst correlation = 0.86). He followed commands 3 days after arrest, when repeat EEG showed a continuous, variable and reactive background without epileptiform activity. Case two was a 49-year-old woman with OHCA secondary to polysubstance overdose. Initial EEG revealed burst suppression with high amplitude generalized polyspike-wave bursts with associated myoclonus. She followed commands on post-arrest day 4, when repeat EEG showed a continuous, variable and reactive background with frequent runs of bifrontal predominant sharply contoured rhythmic delta activity. Conclusion: These cases highlight the perils of prognosticating with a single modality in comatose cardiac arrest patients.

OBJECTIVES:. To measure the frequency of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis among decedents in hospitals of different sizes and teaching statuses. DESIGN:. We performed a multicenter, retrospective cohort study. SETTING:. Four large teaching hospitals, four affiliated small teaching hospitals, and nine affiliated nonteaching hospitals in the United States. PATIENTS:. We included a sample of all adult inpatient decedents between August 2017 and August 2019. MEASUREMENTS AND MAIN RESULTS:. We reviewed inpatient notes and categorized the immediately preceding circumstances as withdrawal of life-sustaining therapy for perceived poor neurologic prognosis, withdrawal of life-sustaining therapy for nonneurologic reasons, limitations or withholding of life support or resuscitation, cardiac death despite full treatment, or brain death. Of 2,100 patients, median age was 71 years (interquartile range, 60–81 yr), median hospital length of stay was 5 days (interquartile range, 2–11 d), and 1,326 (63%) were treated at four large teaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred in 516 patients (25%) and was the sole contributing factor to death in 331 (15%). Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis was common in all hospitals: 30% of deaths at large teaching hospitals, 19% of deaths in small teaching hospitals, and 15% of deaths at nonteaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis happened frequently across all hospital units. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis contributed to one in 12 deaths in patients without a primary neurologic diagnosis. After accounting for patient and hospital characteristics, significant between-hospital variability in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis persisted. CONCLUSIONS:. A quarter of inpatient deaths in this cohort occurred after withdrawal of life-sustaining therapy for perceived poor neurologic prognosis. The rate of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred commonly in all type of hospital settings. We observed significant unexplained variation in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis across participating hospitals.

Introduction The Hiatt Residency in Global Health Equity program at Brigham and Women's Hospital partnered with Loyola University Medical Center and the Stritch School of Medicine to build and share an innovative global health dinner curriculum (GHDC) based on the methodologies of transformative learning theory. This educational approach encourages trainees to critically analyze their frame of reference and has the potential to create practitioners equipped to advance health equity. Methods The GHDC explored broad global health (GH) topics through facilitated discussions with faculty and an experienced guest discussant over dinner. Medical students and internal medicine residents attended sessions based on their availability and interest. Participants completed surveys before and after every dinner. Comprehensive post-curriculum surveys were collected after participants had been involved for at least 1 year. Results In 2017–2018, 98% of the 37 participants preferred the dinner-style learning session to a didactic-style lecture (97% of the 37 participants in 2018–2019). Eighty-five percent (2017–2018) agreed or strongly agreed that dinners provided them with new knowledge on a GH topic (92% in 2018–2019). Seventy-two percent (2017–2018) agreed that the dinner introduced them to a new potential mentor in GH (66% in 2018–2019). Discussion The GHDC has been particularly successful in introducing participants to unfamiliar areas of medicine and new mentors. A second strength is its accessibility to medical students and residents. Its dependence on local resources allows versatility and customization; however, this trait also makes it difficult to prepackage the curriculum for interested institutions.

Abstract Background HIV remains a significant public health dilemma in West and Central Africa. HIV-related morbidity and mortality are unjustly high, yet little is known about the spectrum of complicating comorbidities in HIV-positive patients who are admitted to hospitals in these regions. Methods This study involved a retrospective chart review to determine the common comorbidities and mortality rate of HIV-infected patients admitted over a six month period to the internal medicine service at the Komfo Anokye Teaching Hospital (KATH), a tertiary care center in Ghana. Patients admitted with a known or new HIV diagnosis from January to July 2016 were included. Data were collected regarding the number of new versus known cases admitted, the most common presenting complaints, final admitting diagnoses, and causes of mortality in these patients. Results During the six-month study period, 250 HIV-positive patients were admitted to KATH, and 245 of these individuals had valid survival time recorded. Of these patients, 145/245 (59.2%) were female. Median age of patients included in the study was 42 years old (IQR 35–51). The mortality rate for HIV patients admitted to the hospital was 35.5% (87 patients). One hundred and forty-five (59.4%) patients had a known history of HIV documented in their patient charts, while the remaining patients were newly diagnosed with HIV during their inpatient stay. Pulmonary tuberculosis predominated among diagnostic findings, with 40.4% of HIV-infected patients diagnosed with the condition while admitted. Patients presenting with neurological symptoms on admission were 2.14 (95% CI: 1.27–3.61) times more likely to die than those without neurological symptoms (p = .004). Conclusions Over 40% of HIV-positive patients admitted to KATH were newly diagnosed with HIV at admission. While pulmonary tuberculosis was the most common co-morbidity, patients presenting with neurological symptoms were at higher risk of death. This study suggests that enhanced outpatient screening is needed for early diagnosis and prompt HAART initiation, as well as increased access to diagnostic modalities and treatment for HIV-positive patients with neurological symptoms.