Faculty Bibliography

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.

Kenya is experiencing a clade Ib mpox outbreak, with 28 confirmed cases reported by the Ministry of Health from July to December 2024. Polymerase chain reaction testing was performed for varicella zoster virus (VZV). Testing was also part of the differential diagnosis for mpox, and a subset of cases was genetically sequenced. Of 277 specimens tested for mpox, 170 (61%) tested positive for VZV, including instances of coinfection with both viruses in four cases. Genome analysis was used to identify clade 5 human alphaherpesvirus 3 in eight of the genetically sequenced cases. Expanding laboratory capacity during this outbreak enhanced disease intelligence by confirming another etiology of rash among patients who tested negative for mpox, underscoring the need for a broad differential diagnosis when diseases present with overlapping clinical signs and symptoms.

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.

OBJECTIVE:To evaluate the incidence and risk factors of acute adverse drug reactions (ADRs) to nonionic low-osmolar iodinated contrast media (LOCM) in a pediatric population. MATERIALS AND METHODS/METHODS:This single-center retrospective study included consecutive data on nonionic LOCM injections in pediatric patients (≤18 years) between January 1, 2016, and June 30, 2023. The per-examination incidences of acute ADRs (physiologic and allergic-like reactions) were assessed along with their severities. Multivariable Poisson regression analysis with generalized estimating equations was used to explore the risk factors associated with the occurrence of each ADR type. RESULTS:= 0.28). Moderate reactions occurred in three cases that were re-exposed to the same LOCM, whereas all four reactions with different LOCM were mild. CONCLUSION/CONCLUSIONS:Acute allergic-like and physiologic reactions to nonionic LOCM occurred in 0.89% and 0.55% of cases, respectively. Older age and a history of prior reactions were significant risk factors. Particular care is warranted during contrast-enhanced CT in these high-risk groups.

BACKGROUND:Geographical factors can affect infectious disease transmission, including SARS-CoV-2, a virus that is spread through respiratory secretions. Prioritization of surveillance and response activities during a pandemic can be informed by a pathogen's geographical transmission patterns. We assessed the relationship between geographical factors and SARS-CoV-2 prevalence in Zambia. METHODS:We did a cross-sectional study of SARS-CoV-2 prevalence in six districts in July 2020, which was during the upslope of the first wave in Zambia. In each district, 16 Standard Enumeration Areas (SEAs) were randomly selected and 20 households from each SEA were sampled. The SEA PCR prevalence was calculated as the number of persons testing PCR positive for SARS-CoV-2 in the SEA times the individual sampling weight for the SEA divided by the SEA population. We analysed SEA geographical data for population density, socioeconomic status (SES) (with lower scores indicating reduced vulnerability), literacy, access to water, and sanitation, and hygiene (WASH) factors. Gaussian conditional autoregressive (CAR) models and Generalised estimating equations (GEE) were used to measure adjusted prevalence Ratios (aPRs) and 95% confidence intervals (CIs) for SARS-CoV-2 prevalence with geographical factors, after adjusting for clustering by district, in R. RESULTS:Overall, the median SARS-CoV-2 prevalence in the 96 SEAs was 41.7 (Interquartile range (IQR), 0.0-96.2) infections per 1000 persons. In the multivariable CAR analysis, increasing SES vulnerability was associated with lower SARS-CoV-2 prevalence (aPR) = 0.85, 95% CI: 0.78-0.94). Conversely, urban SEAs and poor access to WASH were associated with a higher SARS-CoV-2 prevalence (aPR = 1.73, 95% CI: 1.46-2.03, No soap: aPR = 1.47, 95% CI: 1.05-2.05, households without piped water: aPR = 1.32, 95% CI: 1.05-1.65, 30 min to fetch water: aPR = 23.39, 95% CI: 8.89-61.52). Findings were similar in the multivariable GEE analysis. CONCLUSIONS:SARS-CoV-2 prevalence was higher in wealthier, urban EAs, with poor access to WASH. As this study was conducted early in the first wave could have impacted our findings. Additional analyses from subsequent waves could confirm if these findings persist. During the beginning of a COVID-19 wave in Zambia, surveillance and response activities should be focused on urban population centres and improving access to WASH.

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.

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.

PURPOSE/OBJECTIVE:To evaluate the impact of image quality on the diagnostic performance of biparametric MRI (bpMRI) for detecting clinically significant prostate cancer (csPCa). PATIENTS AND METHODS/METHODS:This retrospective study included patients who underwent bpMRI at outside imaging facilities and were referred to our tertiary centre between January 2020 and November 2021. The image quality of bpMRI was assessed by two radiologists in consensus using Prostate Imaging Quality Score version 2 (PI-QUAL v2). Technical parameters of T2WI and DWI were extracted, and their associations with imaging quality criteria were evaluated. Sensitivity, specificity, and positive and negative predictive values for detecting csPCa were compared according to PI-QUAL v2 scores. RESULTS:Among 112 men who underwent bpMRI at 69 different imaging facilities, 47 (42.0 %) MRIs were considered not applicable for PI-QUAL v2 scoring. Of the remaining MRIs, 30 (26.8 %), 17 (15.2 %), and and 18 (16.1 %) were assigned PI-QUAL v2 scores of 1, 2, and 3, respectively. MRIs with PI-QUAL v2 scores ≤ 1 demonstrated significantly lower sensitivity (74.3 %) than those with scores of 2 or 3 (100.0 %; P = 0.045). In-plane resolution on T2WI and the number of b values on DWI were significantly associated with image quality assessment (P = 0.037 and 0.028). CONCLUSIONS:The diagnostic accuracy of bpMRI for detecting csPCa is influenced by image quality, as assessed by the PI-QUAL v2 scoring system. Adequate in-plane resolution on T2WI and the use of at least three b values on DWI should be emphasised to achieve optimal image quality and diagnostic performance.