Faculty Bibliography

INTRODUCTION/BACKGROUND:Neighborhood deprivation is associated with shorter survival, cognitive impairment and neurodegeneration in aging and Alzheimer's disease. However, the association of neighborhood deprivation with disease progression in behavioral-variant frontotemporal degeneration (bvFTD) is unknown. METHODS:We examined associations between tertiles of neighborhood deprivation, using the Area Deprivation Index (ADI), and survival in 311 individuals clinically diagnosed with bvFTD from the Penn FTD Center. In a subset (n=161) with complete baseline data across measures of global cognition, executive function, and language, we examined the association of ADI with longitudinal change. RESULTS:Compared to adults living in the least deprived neighborhoods, those living in the most deprived neighborhoods showed shorter survival after symptom onset and faster decline in global cognition, executive and language functions, independent of genetic risk. DISCUSSION/CONCLUSIONS:Living in more deprived neighborhoods was associated with an accelerated disease course in bvFTD, highlighting an important socioeconomic disparity in disease prognosis.

INTRODUCTION/BACKGROUND:Neighborhood deprivation is associated with shorter survival, cognitive impairment, and neurodegeneration in aging and Alzheimer's disease. However, the association of neighborhood deprivation with disease progression in behavioral-variant frontotemporal degeneration (bvFTD) is unknown. METHODS:= 161) with complete baseline data across measures of global cognition, executive function, and language, we examined the association of ADI with longitudinal change. RESULTS:Compared to adults living in the least deprived neighborhoods, those living in the most deprived neighborhoods showed shorter survival after symptom onset and faster decline in global cognition, executive and language functions, independent of genetic risk. DISCUSSION/CONCLUSIONS:Living in more deprived neighborhoods was associated with an accelerated disease course in bvFTD, highlighting an important socioeconomic disparity in disease prognosis. CLINICAL TRIAL REGISTRATION INFORMATION/BACKGROUND:N/A.

Patients with myotonic disorders are at risk for severe generalized muscle contraction, referred to as a "myotonic crisis." For those patients with nondystrophic myotonia (NDM), the most common trigger of a myotonic crisis is exposure to succinylcholine. In this case, a 10-year-old female patient with NDM secondary to an SCN4A pathogenic variant developed a severe myotonic crisis in the setting of an upper respiratory infection and asthma flare treated with a beta-adrenergic agonist (ß-agonist). She presented with generalized rigidity and features of hypermetabolism resembling an anesthetic-related malignant hyperthermia. Management necessitated multidisciplinary collaboration, a complex intubation strategy, and an extended course in the pediatric intensive care unit. We suspected that this crisis was precipitated in part by continuous ß-agonist use during her initial asthma management. Treatments targeting sequential steps of the myocyte activation cascade tempered the contractile apparatus leading to clinical improvement in rigidity.

OBJECTIVES/OBJECTIVE:To systematically review and meta-analyze the recurrent rate of iodinated contrast medium (ICM)-associated adverse drug reactions (ADRs) and the preventive effect of using alternative ICM lacking a common carbamoyl side chain. MATERIALS AND METHODS/METHODS:A systematic literature search was conducted in the MEDLINE and EMBASE databases to identify studies that investigated the recurrence rate of ICM-associated ADRs or hypersensitivity reactions (HSRs). Studies that included patients who subsequently underwent contrast-enhanced computed tomography scans after their index reactions were included, while studies with overlapping cohorts were excluded. The first search was conducted on November 10, 2023. The pooled recurrence rate of ICM-associated ADR was determined using the DerSimonian-Laird random-effects model. Subgroup analyses were also conducted based on the substitution of ICM, with particular consideration given to the N-(2,3-dihydroxypropyl) carbamoyl side chain. RESULTS:A total of ten original articles were included in the analysis, collectively spanning from June 2001 to March 2021. The pooled recurrence rate of ICM-associated ADR was not significantly different from that of ICM-associated HSR (16.6% [95% CI, 7.8-31.9%] vs. 15.5% [95% CI, 10.8-21.8%], p = 0.87). In the subgroup analyses, the pooled odds ratio for ICM-associated recurrent ADR when using a different ICM compared with using the same ICM was 0.31 (95% CI, 0.21-0.45), which means a 69% reduction. Moreover, the pooled odds ratio for ICM-associated recurrent ADR when substituting ICMs with different side chains compared with substituting with common side chains was 0.65 (95% CI, 0.52-0.82), which means an additional 35% reduction. CONCLUSION/CONCLUSIONS:Substituting with an alternative ICM led to a 69% reduction in recurrent ADRs, with an additional 35% reduction observed when using ICM lacking a common carbamoyl side chain. KEY POINTS/CONCLUSIONS:Question No standardized guidelines exist for replacing previously used iodinated contrast medium (ICM) to prevent recurrent adverse reactions. Findings Using alternative contrast medium with a different carbamoyl side chain prevents adverse drug reactions effectively. Clinical relevance This study advocates using alternative ICM without a common carbamoyl side chain to prevent recurrent adverse drug reactions in patients with a history of such events.

BACKGROUND:Randomized control trials (RCTs) are an essential pillar of scientific knowledge and medical practice, and their integrity has important implications for reliable systemic reviews and meta-analyses. However, the number of article retractions due to falsified data and scientific misconduct has increased in recent years. In response, the scientific community has pursued the creation of quality criteria that can be utilized to promote trustworthiness. METHODS:After a quality criteria checklist was created by a team of experts, retracted and nonretracted studies were evaluated for adherence to assess the checklist's usefulness and identify potential pitfalls. Retracted studies published in obstetric literature and retracted between 1994-2024 were identified using the online Retraction Watch Database. A previously created database of non-retracted obstetric RCTs published between 2018-2020 was used for the control group. RESULTS:A total of 173 studies were identified, 136 non-retracted and 37 retracted. Overall, 13 of 17 (76.5 %) criteria were statistically different between retracted and non-retracted articles. A cutoff of ≤ 11 total quality criteria granted 94.9 % (95 % CI, 89.7 - 97.9) sensitivity and 78.4 % (95 % CI, 61.8 - 90.2) specificity in distinguishing non-retracted from retracted studies. CONCLUSIONS:Retracted studies were significantly less likely to adhere to the 17-quality criteria checklist compared to non-retracted studies, providing useful insight to peer-reviewed scientific journals about what to evaluate for in an RCT manuscript prior to publication. The authors recommend that journal editors play close attention to criteria related to research ethics, data falsification, and risk of bias.

OBJECTIVES/OBJECTIVE:Inequities in race, ethnicity and socioeconomic status have been well documented in postpartum hemorrhage (PPH) and hemorrhage-associated morbidity. However, little is known about the impact of language barriers on maternal outcomes in PPH. Our study aim was to investigate language-based inequities in maternal outcomes among gravidas with PPH. METHODS:This is a retrospective cohort of patients with PPH who delivered at an urban academic institution between January 2020 and December 2022. Maternal language is categorized as English primary language (EPL) or non-English primary language (NEPL). PPH is defined as a quantitative blood loss (QBL) greater than 1000 mL within 24 h of delivery. QBL is a calculated measurement of peripartum and postpartum blood loss. Primary outcome is transfusion of packed red blood cells (pRBC). Secondary outcomes include transfusion of 4 + units of pRBC, disseminated intravascular coagulation (DIC) and admission to intensive care unit (ICU). Multivariable logistic regression was used to estimate the association of primary language with maternal outcomes. RESULTS:1723 patients with PPH were included: 1314 (76.3%) with EPL and 409 (23.7%) with NEPL. English-speaking and non-English speaking patients had similar QBL rates (1530.2 ± 634.2 vs 1496.0 ± 668.1, p = 0.3). However, transfusion rates were lower in those with NEPL, when compared to EPL (28.2% vs 22.9%, p = 0.039). After adjusting for age, race/ethnicity, nulliparity, body mass index, pre-eclampsia and pre-delivery anemia, gravidas with NEPL were less likely to be transfused compared with EPL (aOR 0.7, 95% CI 1.012-1.806, p = 0.04). Rates of DIC, ICU admission and transfusion of 4 + units of pRBC were similar between groups. CONCLUSIONS FOR PRACTICE: Despite a similar postpartum blood loss, patients with NEPL had lower rates of blood transfusion in PPH compared to patients with EPL. Further research is needed in health literacy and language proficiency that may impede access to transfusion in patients with PPH.

Primary age-related tauopathy (PART) and Alzheimer's disease (AD) share hippocampal phospho-tau (p-tau) pathology but differ in ß-amyloid burden and degree of p-tau severity and spread. Thus, PART provides a human model to understand the mechanisms of age and amyloid-independent modifiers of p-tau. Given the dynamics of DNA methylation over the lifespan, we (1) performed an epigenome-wide association study of PART that nominated 13 loci associated with p-tau; (2) developed two novel epigenetic clocks predictive of p-tau in age-, and ß-amyloid-independent manners: "TauSeverity" relates hippocampal p-tau severity in PART and AD and synaptic transmission genes; "TauSpread" relates to p-tau spread to frontal cortex of AD and neuroinflammatory genes; and (3) a machine learning classifier that identifies low- and high resilience individuals with overlapping neuropathological features but distinct epigenetic, transcriptomic, and clinical features. We conclude that the epigenome contributes to the severity and spread of p-tau pathology, guided by distinct pathways with cognitive consequences.

OBJECTIVES/OBJECTIVE:To assess the predictive value of magnetic resonance imaging for vesicovaginal fistula development in cervical cancer patients with bladder invasion treated with definitive chemoradiotherapy. METHODS:A retrospective review was conducted of the medical records of 43 cervical cancer patients with bladder invasion between 1999 and 2015. Bladder invasion was confirmed through magnetic resonance imaging (scores ≥3) or cystoscopic findings, with or without biopsy. Treatment included weekly cisplatin plus pelvic external beam radiotherapy, with extended-field radiotherapy. After external beam radiotherapy, patients received intracavitary brachytherapy or an external beam boost. Vesicovaginal fistula was diagnosed based on reported symptoms and relevant imaging tests during follow-up. RESULTS:The median follow-up period was 67.4 months. The 5-year disease-free and overall survival rates were 66.4 %, and 71.8 %, respectively. Vesicovaginal fistula developed in five patients (12.8 %), with three cases occurring within 1 year post-treatment and two others at 16.7 and 64.5 months, respectively. In multivariate analysis, the height of bladder wall involvement on magnetic resonance imaging was the only significant predictor of vesicovaginal fistula (p = 0.041). Specifically, Vesicovaginal fistula occurred in 25 % of cases when bladder wall involvement was ≥20.3 mm, in 50 % of cases at ≥31.1 mm, and in 75 % of cases at ≥41 mm. CONCLUSIONS:The height of bladder wall involvement on magnetic resonance imaging is a significant predictor of vesicovaginal fistula formation in cervical cancer patients with bladder invasion. This finding can aid clinicians in better predicting this complication, improving patient counseling and management strategies.