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In utero gene editing (IUGE) is a potential treatment for inherited diseases that cause pathology before or soon after birth. Preexisting immunity to adeno-associated virus (AAV) vectors and Cas9 endonuclease may limit postnatal gene editing. The tolerogenic fetal immune system minimizes a fetal immune barrier to IUGE. However, the ability of maternal immunity to limit fetal gene editing remains a question. We investigated whether preexisting maternal immunity to AAV or Cas9 impairs IUGE. Using a combination of fluorescent reporter mice and a murine model of a metabolic liver disease, we demonstrated that maternal anti-AAV IgG antibodies were efficiently transferred from dam to fetus and impaired IUGE in a maternal titer-dependent fashion. By contrast, maternal cellular immunity was inefficiently transferred to the fetus, and neither maternal cellular nor humoral immunity to Cas9 impaired IUGE. Using human umbilical cord and maternal blood samples collected from mid- to late-gestation pregnancies, we demonstrated that maternal-fetal transmission of anti-AAV IgG was inefficient in midgestation compared with term, suggesting that the maternal immune barrier to clinical IUGE would be less relevant at midgestation. These findings support immunologic advantages for IUGE and inform maternal preprocedural testing protocols and exclusion criteria for future clinical trials., Introduction In utero gene editing (IUGE) is a potential treatment for inherited diseases that takes advantage of normal fetal developmental properties to institute the therapy before the onset of pathology. [...]

This project examines risk and protective factors for preterm birth (PTB) among Black women in Oakland, California. Women with singleton births in 2011-2017 (n = 6199) were included. Risk and protective factors for PTB and independent risk groups were identified using logistic regression and recursive partitioning. Having less than 3 prenatal care visits was associated with highest PTB risk. Hypertension (preexisting, gestational), previous PTB, and unknown Women, Infant, Children (WIC) program participation were associated with a two-fold increased risk for PTB. Maternal birth outside of the USA and participation in WIC were protective. Broad differences in rates, risks, and protective factors for PTB were observed.

Preliminary evidence suggests that the experience of the novel coronavirus is not shared equally across geographic areas. Findings in the United States suggest that the burden of COVID-19 morbidity and mortality may be hardest felt in disadvantaged and racially segregated places. Deprived neighborhoods are disproportionately populated by people of color, the same populations that are becoming sicker and dying more often from COVID-19. This commentary examines how structurally vulnerable neighborhoods contribute to racial/ethnic inequities in SARS-COV-2 exposure and COVID-19 morbidity and mortality and considers opportunities to intervene through place-based initiatives and the implementation of a Health in All Policies strategy.

Acute encephalopathy is a common presenting symptom in the emergency room and complicates many hospital and intensive care unit admissions. The evaluation of patients with encephalopathy poses several challenges: limited history and examination due to the patient's mental status, broad differential diagnosis of systemic and neurologic etiologies, low yield of neurodiagnostic testing due to the high base rate of systemic causes, and the importance of identifying less common neurologic causes of encephalopathy that can be life-threatening if not identified and treated. This article discusses the differential diagnosis of acute encephalopathy, presents an approach to the history and examination in a patient with encephalopathy, reviews the literature on the yield of neurodiagnostic testing in this population, and provides a diagnostic framework for the evaluation of patients with altered mental status. [ABSTRACT FROM AUTHOR]

Case-based diagnostic reasoning conferences, like morning reports, allow undergraduate medical trainees to practice diagnostic reasoning alongside senior clinicians. However, trainees have reported discomfort doing so. Peer-assisted learning offers an alternative approach. We describe the design, implementation, and evaluation of a virtual, student-only diagnostic reasoning conference that leverages peer-assisted learning. Student virtual morning report's (VMR) design was informed by social and cognitive congruence and experience-based learning. We evaluated participant experiences using a survey focused on participant perceptions of Student VMR's value, their methods for participation, and their preferences for Student VMR compared with VMR with more senior clinicians. 110 participants (28.9%) completed the survey. 90 participants (81.2%) reported that Student VMR was educational. Compared to VMR, participants reported being more likely to participate in Student VMR by turning on their video (50.0%), presenting a case (43.6%), verbally participating (44.5%), or participating in the chat (70.0%). Strengths included a safe learning environment to practice DR and the opportunity to engage with an international learning community. When asked whether they preferred Student VMR or non-Student VMR, most respondents (64.5%, 71/110) identified that they did not have a preference between the two. A student-focused DR conference may offer a valuable complement to, but not a replacement of, apprenticeship-based DR case conferences. [ABSTRACT FROM AUTHOR]

Diagnostic reasoning relies on cognitive heuristics to recognise patterns of symptoms and signs in order to arrive at a diagnosis. These rules of thumb allow us to rapidly diagnose common conditions that present in typical ways. However, they may lead us astray when common conditions present atypically or when a patient has a rare condition or multiple conditions causing their constellation of symptoms, signs, and test results, rather than having a single diagnosis to explain them all. This article describes strategies to help counteract diagnostic pitfalls, to expand diagnostic possibilities and to make diagnostic progress with complex, multielement cases. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Cardiovascular risk factors and history of cardiovascular disease are associated with greater morbidity and mortality in patients hospitalized with COVID-19. Limited English proficiency (LEP) has also been associated with worse outcomes in this setting, including requiring intensive care unit (ICU) level of care and in-hospital death. Whether non-- English-language preference (NELP) modifies the association between cardiovascular risk factors or disease and outcomes in patients hospitalized with COVID-19 is unknown. STUDY DESIGN: Retrospective cohort study of adult patients admitted to a large New England health system between March 1 and December 31, 2020, who tested positive for COVID-19. NELP was defined as having a preferred language that was not English noted in the electronic health record. METHODS: Cardiovascular risk factors, history of cardiovascular disease, and NELP were related to the primary composite clinical outcome--death or ICU admission--using multivariable binary logistic regression adjusted for demographic and clinical characteristics. Interaction terms for NELP and model covariates were evaluated. RESULTS: Of 3582 patients hospitalized with COVID-19, 1024 (28.6%) had NELP; 812 (79.3%) of the patients with NELP received interpreter services. Death or ICU admission occurred in 794 (22.2%) of the hospitalized patients. NELP was not significantly associated with the primary composite outcome in unadjusted or adjusted analyses. In the adjusted analyses, only male gender, coronary artery disease, pulmonary circulatory disease, and liver disease significantly predicted the primary outcome. NELP did not modify the effect of these associations. CONCLUSIONS: NELP was not significantly associated with odds of death or ICU admission, nor did it modify the association between cardiovascular risk factors or history of cardiovascular disease and this composite outcome. Because most patients with NELP received interpreter services, these findings may support the role of such services in ensuring equitable outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have demonstrated an increased risk of severe maternal morbidity (SMM) for people living in rural versus urban counties. Studies have not considered rurality at the more nuanced subcounty census‐tract level. This study assessed the relationship between census‐tract‐level rurality and SMM for birthing people in California. Methods: We used linked vital statistics and hospital discharge records for births between 1997 and 2018 in California. SMM was defined by at least 1 of 21 potentially fatal conditions and lifesaving procedures. Rural‐Urban Commuting Area codes were used to characterize census tract rurality dichotomously (2‐category) and at 4 levels (4‐category). Covariates included sociocultural‐demographic, pregnancy‐related, and neighborhood‐level factors. We ran a series of mixed‐effects logistic regression models with tract‐level clustering, reporting risk ratios and 95% confidence intervals (CIs). We used the STROBE reporting guidelines. Findings: Of 10,091,415 births, 1.1% had SMM. Overall, 94.3% of participants resided in urban/metropolitan and 5.7% in rural tracts (3.9% micropolitan, 0.9% small town, 0.8% rural). In 2‐category models, the risk of SMM was 10% higher for birthing people in rural versus urban tracts (95% CI: 6%, 13%). In 4‐category models, the risk of SMM was 16% higher in micropolitan versus metropolitan tracts (95% CI: 12%, 21%). Conclusion: The observed rurality and SMM relationship was driven by living in a micropolitan versus metropolitan tract. Increased risk may result from resource access inequities within suburban areas. Our findings demonstrate the importance of considering rurality at a subcounty level to understand locality‐related inequities in the risk of SMM. [ABSTRACT FROM AUTHOR]