Bictegravir Use During Pregnancy: A Multi-Center Retrospective Analysis Evaluating HIV Viral Suppression and Perinatal Outcomes.

This study describes the largest cohort to date (n=147) of pregnant patients living with HIV on bictegravir (BIC). BIC in pregnancy was associated with high levels of viral suppression and similar perinatal outcomes to published literature. These findings support consideration for use of BIC in management of HIV during pregnancy.

Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature.

PURPOSE OF REVIEW: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA. RECENT FINDINGS: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple safety and tolerability concerns with older regimens, there are now multiple options of regimens that are highly efficacious and have good safety data in pregnancy. Most pregnant patients who are virally suppressed on a well-tolerated regimen are able to safely continue those medications during pregnancy.

Postoperative outcomes and stimulation responses for sectioned nerve roots during selective dorsal rhizotomy in cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is the most cause of motor dysfunction in children. Selective dorsal rhizotomy (SDR) plays a major role in long term spasticity control. However, limited data exists on the effect of SDR on postoperative spasticity treatment requirements and supraspinal effects, and the stimulation responses of dorsal nerve roots in those with CP. METHODS: The current study included the outcome for 35 individuals undergoing SDR for motor functional outcome, spasticity, baclofen dose changes, botulinum toxin injection frequency, and spasticity related orthopedic procedures. We also report on the stimulation responses in 112 individuals who underwent SDR at our institution. RESULTS: There was a significant difference in gross motor function measures (GMFM)-66 scores at last follow up that remained present when considering only ambulatory children but not with non-ambulatory children. Ashworth scores were significantly decreased for both upper and lower extremities after SDR at all follow up points. There was a significant decrease in Baclofen dose and botulinum toxin injections requirements after SDR, but no significant difference in the need for orthopedic intervention. A total of 5502 dorsal nerve roots were tested showing a decrease in stimulation intensity and increase in grade on the right side and for descending lumbosacral levels. CONCLUSIONS: SDR improves gross motor scores during short term follow up but has additional benefits in decreasing baclofen dosing and botulinum toxin injections requirements after surgery. They stimulation responses of sectioned dorsal nerve roots adds to the limited available data and our understanding of the pathological changes that occur in CP.

Evaluating the Outcomes and Trainee Performance of a Canadian Medical Imaging Clinician Investigator Program.

Purpose: To measure the research productivity of trainees from the University of Toronto's Medical Imaging Clinician Investigator Program (MI-CIP) and comparing it with the research productivity of trainees from MI-non-CIP and General Surgery (GSx) Clinician Investigator Program. Methods: We identified residents who completed an MI-CIP, MI-non-CIP and GSx-CIP from 2006-2016. In each group of trainees, we assessed 3 research productivity outcomes with non-parametric tests before residency and at 7 years post-CIP completion/post-graduation. Research productivity outcomes include the number of total publications, the number of first-author publications, and the publication's average journal impact factor (IF). Results: We identified 11 MI-CIP trainees (male/female: 9 [82%]/2 [18%]), 74 MI-non-CIP trainees (46 [62%]/28 [38%]) and 41 GSx-CIP trainees (23 [56%]/18 [44%]). MI-CIP trainees had statistically significant higher research productivity than MI-non-CIP in all measured outcomes. The median (interquartile range, IQR) number of total publications of MI-CIP vs MI-non-CIP trainees was 5.0 (8.0) vs 1.0 (2.0) before residency and 6.0 (10.0) vs .0 (2.0) at 7 years post-CIP completion/post-graduation. The median (IQR) first-author publications of MI-CIP vs MI-non-CIP trainees was 2.0 (3.0) vs .0 (1.0) before residency and 2.0 (4.0) vs (.0) (1.0) at 7 years post-CIP completion/post-graduation. The median (IQR) average journal IF of MI-CIP vs MI-non-CIP trainees was 3.2 (2.0) vs .3 (2.4) before residency and 3.9 (3.2) vs .0 (2.6) at 7 years post-CIP completion/post-graduation. Between MI-CIP and GSx-CIP trainees, there were no significant differences in research productivity in all measured outcomes. Conclusion: MI-CIP trainees actively conducted research after graduation. These trainees demonstrated early research engagement before residency. The similar research productivity of MI-CIP vs GSx-CIP trainees shows initial success of MI-CIP trainees.

Providers Have a Responsibility to Discuss Options for Infant Feeding With Pregnant People With Human Immunodeficiency Virus in High-Income Countries.

Guidelines in high-income countries generally recommend against breastfeeding for a pregnant person with HIV due to the historical risk of transmission to the infant and generally acceptable, safe, and sustainable access to formula. Maternal antiretroviral therapy and infant prophylaxis have been shown to significantly decrease the risk of transmission during breastfeeding. In addition, formula may not be acceptable to patients for a variety of cultural, social, or personal reasons, and its sustainability is called into question in the setting of the current nationwide formula shortage. Providers caring for pregnant people with HIV have a responsibility to discuss infant feeding with their patients, and help them weigh the risks and benefits within the limits of the current body of evidence. We outline a process, including a written agreement, that can be used to discuss infant feeding with all patients and help them make the best decision for their family.

Breastfeeding Among People With Human Immunodeficiency Virus in North America: A Multisite Study.

BACKGROUND: In North American countries, national guidelines have strongly recommended formula over breastmilk for people with human immunodeficiency virus (HIV) because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is <1% among virally suppressed people. Information regarding breastfeeding experience in high-resource settings is lacking. METHODS: A retrospective multisite study was performed for individuals with HIV who breastfed during 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. RESULTS: Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range, 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available ≥6 weeks after weaning. CONCLUSIONS: This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients with HIV who chose to breastfeed at any 1 location, and the need for further multisite studies to identify best care practices.

Screening for Substance Use Disorders during Pregnancy: A Decision at the Intersection of Racial and Reproductive Justice.

OBJECTIVE: Improve racial equity with routine universal drug screening / Study Design: Commentary on the medicolegal and social history of the United States and the field of obstetrics and gynecology regarding drug screening policy / Results: Critical aspects to inform an equitable drug screening policy include (1) racial bias and stigma related to substance use, (2) the legislative history surrounding substance use during pregnancy, (3) the relationship between substance use and mass incarceration which disproportionately affects persons of color, (4) propensity toward punitive measures for Black mothers with substance use, including termination of parental rights, (5) the role of the medical field in fostering mistrust among our patients / Conclusion: new practices in screening for substance use during pregnancy are needed. KEY POINTS: · Increasing demand for racial justice warrants reframing the issue of urine drug screening.. · The current legal constructs continue to disproportionately impact women of color.. · Routine verbal screening can replace urine drug screening and diminish implicit biases..

Social Drivers of COVID-19 Disease Severity in Pregnant Patients.

OBJECTIVE: While coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had global impact in all populations, certain groups of patients have experienced disproportionate rates of morbidity and mortality. The purpose of this study was to assess the relationship between COVID-19 disease severity, demographic variables, race and ethnicity, and social determinants of health among pregnant patients in a diverse urban population. STUDY DESIGN: A retrospective analysis was performed of all pregnant patients diagnosed with COVID-19 at two urban tertiary care centers in Houston, TX between March and August 2020. Maternal demographic, COVID-19 illness criteria, and delivery characteristics were collected. The Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and COVID-19 Community Vulnerability Index (CCVI) were obtained based on a patients' census tract of residence. Analyses compared persons with asymptomatic, mild, or severe-critical disease at diagnosis. RESULTS: A total of 317 persons tested positive for COVID-19 during this time period. Asymptomatic persons were more likely to be diagnosed at later gestational ages, but there were no other differences in baseline maternal characteristics. Persons with more severe disease had greater social vulnerability specifically for housing and transportation than those with mild disease (mean SVI [standard error]: 0.72 [0.06] vs. 0.58 [0.2], p = 0.03). Total SVI, total CCVI, and other themed SVI and CCVI indices were not significantly different between groups. CONCLUSION: In this cohort of pregnant persons infected with SARS-CoV-2, an association was shown between disease severity and increased vulnerability in living conditions and transportation. Drivers of the pandemic and COVID-19 outcomes are complex and multifactorial, and likely change over time. However, continued efforts to accurately identify and measure social determinants of health in medicine will likely help identify geographic areas and patient populations that are at risk of higher disease burden. This could facilitate preventative and mitigation measures in these areas in future disaster or pandemic situations. KEY POINTS: · SVI and CCVI estimate social determinants of health.. · COVID-19 is associated with housing and transportation vulnerability.. · Social determinants contribute to disease burden in pregnancy..

AAV1.NT-3 gene therapy for X-linked Charcot-Marie-Tooth neuropathy type 1.

X-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the gene encoding Gap Junction Protein Beta-1 (GJB1)/Connexin32 (Cx32) in Schwann cells. Neurotrophin-3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulating axon regeneration and myelination. Improvements in these parameters have been shown previously in a CMT1 model, TremblerJ mouse, with NT-3 gene transfer therapy. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of 3-month-old Cx32 knockout (KO) mice. Measurable levels of NT-3 were found in the serum at 6-month post gene delivery. The outcome measures included functional, electrophysiological and histological assessments. At 9-months of age, NT-3 treated mice showed no functional decline with normalized compound muscle action potential amplitudes. Myelin thickness and nerve conduction velocity significantly improved compared with untreated cohort. A normalization toward age-matched wildtype histopathological parameters included increased number of Schmidt-Lanterman incisures, and muscle fiber diameter. Collectively, these findings suggest a translational application to CMTX1.

Neurophysiologic intraoperative monitoring (NIOM) in pediatric patients with polyneuropathy.

PURPOSE: Neurophysiologic intraoperative monitoring (NIOM) abnormalities during scoliosis surgery led to a diagnosis of Friedreich's ataxia in this illustrative case. This prompted the retrospective examination of NIOM for pediatric scoliosis surgery in polyneuropathy patients. METHODS: Among patients who underwent scoliosis surgery in 2010-2017, there were six polyneuropathy patients identified. Their clinical history and baseline NIOM data were reviewed. RESULTS: Scoliosis accompanied Charcot-Marie-Tooth disease, Friedreich's ataxia, and ataxia telangiectasia. Some patients with no recorded somatosensory evoked potentials (SEPs) exhibited motor evoked potentials (MEPs); no patients with absent MEPs had SEPs present. NIOM modifications included SEP stimulation rate; type of SEP electrodes used; train parameters for MEP acquisition; and sweep speed. CONCLUSIONS: This sample of NIOM data for previously monitored scoliosis cases in children with polyneuropathy allowed investigation of patterns of findings and troubleshooting attempts to optimize monitoring. Attentiveness to pertinent medical history prepared the NIOM team to change typical recording parameters based on underlying polyneuropathy. A multimodality approach provided useful information as several of these cases would have been unmonitorable with use of SEPs alone. As for the case described, the awareness of NIOM patterns in polyneuropathy may guide evaluations of patients with presumed idiopathic scoliosis who have unrecognized polyneuropathy.

Parental preferences on diagnostic imaging tests for paediatric appendicitis.

OBJECTIVES: To determine parental preferences for diagnostic imaging tests (DITs) for paediatric appendicitis, to rank the attributes impacting the DIT selection and to identify DIT attributes that would cause parents to switch their DIT. METHODS: Parents of children who had an abdominal ultrasound (US) for right lower quadrant pain were interviewed. Two DITs were compared at a time, parents were asked to indicate their preferred test and to rank its attributes according to the impact each attribute had on their selection. The strength of their preference for the chosen DIT was measured by systematically adjusting attributes of the chosen DIT until the parent changed their choice. RESULTS: Fifty parents were interviewed. For US versus CT, more parents preferred US (68%, P=0.02) with higher importance ranks for cancer risk (P<0.0001), test accuracy (P=0.04), pain during test (P=0.3), and scan length (P<0.0001); and lower ranks for sedation (P=0.02), intravenous (IV) (P<0.02), and oral contrast (P=0.06). For US versus MRI, parents preferred MRI (78%, P<0.0001) with higher importance ranks for accuracy (P=0.2), pain during test (P=0.06), and scan length (P=0.06); and lower for noise (P<0.0001), claustrophobia (P<0.0001), use of IV contrast (P=0.06), and sedation (P=0.2). CONCLUSION: US and MRI were the DIT preferred by parents for the investigation of acute paediatric appendicitis.

Recurrent central nervous system white matter changes in charcot-Marie-tooth type X disease.

INTRODUCTION: X-linked Charcot-Marie-Tooth (CMT1X) disease is caused by mutations in the GJB1 gene. We describe a young man who presented with recurrent central nervous symptoms and transient white matter changes in the setting of a novel mutation in the GJB1 gene. METHODS: Evaluation included clinical examination, neuroimaging, electrophysiological, and molecular genetic studies. RESULTS: Clinical examination on 2 admissions 5 years apart demonstrated hemiparesis with findings of underlying peripheral neuropathy. Electrophysiologic studies revealed a sensorimotor polyneuropathy. MRI studies from both admissions revealed white matter changes, with improvement on an intervening study. Mutation analysis showed a novel mutation (c.98T>A; p.Ile33Asn) in the GJB1 gene. CONCLUSIONS: Mutations in GJB1 can result in recurrent central nervous system symptoms with transient white matter signal changes on MRI. In patients presenting with hemiparesis, the presence of signs of a peripheral neuropathy may facilitate identification of CMT1X, and is likely to affect clinical management.

A multistep genomic screen identifies new genes required for repair of DNA double-strand breaks in Saccharomyces cerevisiae.

BACKGROUND: Efficient mechanisms for rejoining of DNA double-strand breaks (DSBs) are vital because misrepair of such lesions leads to mutation, aneuploidy and loss of cell viability. DSB repair is mediated by proteins acting in two major pathways, called homologous recombination and nonhomologous end-joining. Repair efficiency is also modulated by other processes such as sister chromatid cohesion, nucleosome remodeling and DNA damage checkpoints. The total number of genes influencing DSB repair efficiency is unknown. RESULTS: To identify new yeast genes affecting DSB repair, genes linked to gamma radiation resistance in previous genome-wide surveys were tested for their impact on repair of site-specific DSBs generated by in vivo expression of EcoRI endonuclease. Eight members of the RAD52 group of DNA repair genes (RAD50, RAD51, RAD52, RAD54, RAD55, RAD57, MRE11 and XRS2) and 73 additional genes were found to be required for efficient repair of EcoRI-induced DSBs in screens utilizing both MATa and MATα deletion strain libraries. Most mutants were also sensitive to the clastogenic chemicals MMS and bleomycin. Several of the non-RAD52 group genes have previously been linked to DNA repair and over half of the genes affect nuclear processes. Many proteins encoded by the protective genes have previously been shown to associate physically with each other and with known DNA repair proteins in high-throughput proteomics studies. A majority of the proteins (64%) share sequence similarity with human proteins, suggesting that they serve similar functions. CONCLUSIONS: We have used a genetic screening approach to detect new genes required for efficient repair of DSBs in Saccharomyces cerevisiae. The findings have spotlighted new genes that are critical for maintenance of genome integrity and are therefore of greatest concern for their potential impact when the corresponding gene orthologs and homologs are inactivated or polymorphic in human cells.