Evaluating outcomes of mother-infant pairs using dolutegravir for HIV treatment during pregnancy.

OBJECTIVES: Dolutegravir (DTG), a second-generation integrase inhibitor, is an effective treatment for HIV but its safety and efficacy are not well established in pregnancy. Here, we assess maternal and infant outcomes of mother-infant pairs using DTG-containing regimens during pregnancy. METHODS: We performed a retrospective cohort analysis of pregnant women with HIV on DTG from two urban clinics in the United States, 2015-2018. Maternal outcomes included viral suppression (viral load of <20 copies/ml prior to delivery), development of resistance, and tolerability to DTG. Infant outcomes included preterm delivery (birth at <37 weeks), small for gestational age (SGA, weight <10th percentile), infant HIV status at birth, birth defect(s), and Appearance, Pulse, Grimace, Activity, Respiration (APGAR) scores. We performed a trend analysis to assess DTG use over time. RESULTS: A total of 66 women used DTG during pregnancy and the proportion on DTG increased each year: in 2015, 8% (5/60) of women were on DTG, versus 22% (15/67) in 2016, 42% (30/71) in 2017, and 59% (16/27) in 2018 (P < 0.05). Among women who delivered (n = 57), 77.2% were undetectable at delivery. There were no drug resistance and no reported side effects during pregnancy. Infants had a mean APGAR score of 8 (SD 1.5) at 1 min and 9 (SD 0.8) at 5 min; 31.6% were born prematurely and 15.8% were SGA, and 2 infants had a birth defect. No cases of HIV transmission occurred. CONCLUSION: Our findings suggest that DTG can be an effective treatment during pregnancy. Infant outcomes (preterm deliveries and birth defects) need to be investigated in larger studies.

Streptococcus pyogenes and invasive central nervous system infection.

Streptococcus pyogenes is a Gram-positive beta-hemolytic bacteria, also known as group A streptococci, that causes a range of infections. The most common presentation is acute pharyngitis; however, it is also implicated in skin and soft tissue infections, and less commonly bacteremia, osteomyelitis, pneumonia, otitis media and sinusitis. Group A streptococci infections of the central nervous system are exceedingly rare in the antibiotic era. The mechanism of infection is typically contiguous spread from existing infection or via direct inoculation. We present a case of an 81-year-old female with a past medical history of dementia, transient ischemic attacks, type 2 diabetes mellitus, hypertension, descending thoracic aortic aneurysm status post-stent placement in 2008, hepatitis C and hyperlipidemia who initially presented after being found unresponsive at home. Her initial symptoms were primarily of altered mentation and on evaluation was found to be in septic shock with suspicion of meningoencephalitis. Her initial workup included a computed tomography of head which was remarkable for left and right mastoid effusions. A lumbar puncture was performed with cloudy purulent fluid, an elevated white blood cell count, low glucose and elevated protein. The patient was initially started on broad spectrum coverage and soon had 4/4 blood cultures and cerebrospinal fluid cultures growing Streptococcus pyogenes. Empiric vancomycin, ceftriaxone and ampicillin were administered but switched to penicillin G in the setting of elevated total bilirubin and septic shock with multi-organ failure and narrowed to ampicillin-sulbactam based on sensitivities. Unfortunately, the patient deteriorated further due to septic shock and multi-organ failure and later died in the medical intensive care unit.

Effect of heartfulness meditation on burnout, emotional wellness, and telomere length in health care professionals.

Background: Burnout poses significant challenges during training years in residency and later in the career. Meditation is a tool to treat stress-related conditions and promote wellness. Telomere length may be affected by burnout and stress. However, the benefits of meditation have not been fully demonstrated in health care professionals. Objective: We assessed the effects of a 12-week 'Heartfulness Meditation' program on burnout, emotional wellness, and telomere length in residents, faculty members, and nurses at a large community teaching hospital during the 2015-16 academic year. Methods: All subjects completed a baseline Maslach Burnout Inventory (MBI) and Emotional Wellness Assessment (EWA) at the beginning of the study. Meditators received instructions in Heartfulness Meditation. At week 12, subjects completed a follow up MBI and EWA scores. Salivary telomere length was measured at baseline and week 12. Results: Twenty-seven out of a total 155 residents (17.4%) along with eight faculty physicians and 12 nurses participated in the study. Thirty-five enrolled as meditators and 12 as controls. At 12 weeks, the meditators had statistically significant improvement in all measures of burnout and in nearly all attributes of EWA. Controls showed no statistically significant changes in either burnout or emotional wellness scores. Relative telomere length increased with statistical significance in a younger subset of meditators. Conclusion: Our results indicate that meditation offers an accessible and efficient method by which physician and nurse burnout can be ameliorated and wellness can be enhanced. The increased telomere length is an interesting finding but needs to be confirmed with further research. Abbreviations: EWA: Emotional wellness assessment; MBI: Maslach burnout inventory; EE: Emotional exhaustion; DP: Depersonalization; PA: Personal accomplishment; PI: Prinicipal investigator; JT: Jayaram Thimmapuram.

Thymosin beta4 promotes matrix metalloproteinase expression during wound repair.

Immobilized patients, diabetics, and the elderly suffer from impaired wound healing. The 43-amino acid angiogenic peptide thymosin beta4 (Tbeta4) has previously been found to accelerate dermal wound repair in rats, aged mice, and db/db diabetic mice. It also promotes corneal repair in both normal rats and mice. Because proteinases are important in wound repair, we hypothesized that Tbeta4 may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Analysis by RT-PCR of whole excised mouse dermal wounds on days 1, 2, and 3 after wounding showed that Tbeta4 increased several metalloproteinases, including MMP-2 and -9 expression by several-fold over control on day 2 after wounding. We further analyzed the metalloproteinases secreted in response to exogenous Tbeta4 by cells normally present in the wound. Western blot analysis of cultured keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of Tbeta4 showed increases in the levels of MMP-1, -2, and -9 in a cell-specific manner. Tbeta4 also enhanced the secretion of MMP-1 and MMP-9 by activated monocytes. The central actin-binding domain, amino acids 17-23, had all of the activity for metalloproteinase induction. We conclude that part of the wound healing activity of Tbeta4 resides in its ability to increase proteinase activity via its central actin-binding domain. Thus, Tbeta4 may play a pivotal role in extracellular matrix remodeling during wound repair.