Citations

LINKED CONTENTThis article is linked to Idalsoaga et al papers. To view these articles, visithttps://doi.org/10.1111/apt.18193andhttps://doi.org/10.1111/apt.18220

Summary Background Oesophageal disorders and chronic liver disease are common worldwide and significantly impact quality of life. The intricate link between these conditions, including how oesophageal disorders like GERD, Barrett's oesophagus and oesophageal cancer affect and are affected by chronic liver disease, remains poorly understood. Aims To review the relationship between oesophageal disorders and chronic liver disease, evaluating epidemiology, pathophysiology and therapeutic factors. Methods We reviewed the literature on the relationship between oesophageal disorders and chronic liver disease, including cirrhosis, using the PubMed database Results Oesophageal disorders such as gastroesophageal reflux disease, Barrett's oesophagus, oesophageal cancer, oesophageal motor disorders and oesophageal candidiasis are prevalent among individuals with cirrhosis, exacerbating the burden of liver disease. These diseases have a multifaceted symptomatology and pathogenic basis, posing a significant challenge in cirrhotic patients that necessitates careful diagnosis and management. Additionally, therapies frequently used for these diseases, such as proton pump inhibitors, require careful consideration in cirrhotic patients due to potential adverse effects and altered pharmacokinetics. Managing oesophageal disorders in cirrhotic patients requires a cautious approach due to possible interactions with medications and the risk of adverse effects. Furthermore, symptoms associated with these conditions are often exacerbated by common interventions in patients with cirrhosis, such as band ligation for oesophageal varices. Conclusions Oesophageal disorders are common in cirrhosis and increase the disease burden. These conditions require careful management due to complex symptoms and treatment risks. Proton pump inhibitors and other therapies must be used cautiously, as cirrhosis interventions can worsen symptoms.

Abstract Purpose Rapid sequence intubation (RSI) is a common emergency department (ED) procedure with an associated complication of postintubation hypotension (PIH). It has not been clearly established whether the selection and dose of induction agent affect risk of PIH. The objective of this study was to determine the incidence of PIH in patients receiving full-dose compared to reduced-dose induction agent for RSI in the ED. Methods This was a health system–wide, retrospective cohort study comparing incidence of PIH based on the induction medication and dose given for RSI in the ED. Patients were included if they underwent RSI from July 1, 2018, through December 31, 2020, were 18 years of age or older, and received etomidate or ketamine. A reduced dose was defined as a ketamine dose of 1.25 mg/kg or less and an etomidate dose of 0.2 mg/kg or less. Results A total of 909 patients were included in the final analysis, with most receiving etomidate (n = 764; 84%) and a smaller number receiving ketamine (n = 145; 16%). Patients who received ketamine had a higher mean pre-intubation shock index (full dose, 1.08; reduced dose, 1.04) than those who received etomidate (full dose, 0.89; reduced dose, 0.92) (P ≤ 0.001). Reduced doses of induction agent were observed for 107 patients receiving etomidate (14.0%) and 60 patients receiving ketamine (41.4%). Patients who received full-dose ketamine for induction had the highest rate of PIH (n = 31; 36.5%), and the difference was statistically significant compared to patients receiving reduced-dose ketamine (16.7%; P = 0.021) and full-dose etomidate (22.8%; P = 0.010). Conclusion We observed that full-dose ketamine was associated with the highest rate of PIH; however, this group had the poorest baseline hemodynamics, confounding interpretation. Our results do not support broad use of a reduced-dose induction agent.

ABSTRACT Chilaiditi sign is an incidental radiological finding where the intestine is interposed between the diaphragm and liver. Chilaiditi syndrome (CS), characterized by gastrointestinal symptoms and Chilaiditi sign on imaging, is of important clinical significance despite its rarity given associated complications including intestinal obstruction, bowel ischemia, and perforation. While most cases involve the large intestine, we report a rare case of CS with ileal involvement complicated by small bowel obstruction, managed conservatively. Failure to recognize Chilaiditi sign or CS may prompt unnecessary surgical interventions, emphasizing the need for physician awareness to ensure accurate timely diagnosis and appropriate management.

Abstract Background Precision medicine, sometimes referred to as personalized medicine, is rapidly changing the possibilities for how people will engage health care in the near future. As technology to support precision medicine exponentially develops, there is an urgent need to proactively improve our understanding of precision medicine and pose important research questions (RQs) related to its inclusion in the education and training of future emergency physicians. Methods A seven‐step process was employed to develop a research agenda exploring the intersection of precision and emergency medicine education/training. A literature search of articles about precision medicine was conducted first, which informed the creation of future four scenarios in which trainees and practicing physicians regularly discuss and incorporate precision medicine tools into their discussions and work. Based on these futurist narratives, potential education RQs were generated by an expert panel. A total of 59 initial questions were subsequently categorized and refined to a priority list through a nominal group voting method. The top/priority questions were presented at the 2023 SAEM Consensus Conference on Precision Medicine, Austin, Texas, for further input. Results Eight high‐value education RQs were developed, reflecting a holistic view of the challenges and opportunities for precision medicine education in the knowledge, skills, and attitudes relevant to emergency medicine. These questions contend with topics such as most effective pedagogical methods; intended resulting outcomes and behaviors; the generational differences between practicing emergency physicians, educators, and future trainees; and the desires and expectations of patients. Conclusions Emergency medicine and emergency physicians must be prepared to understand precision medicine and incorporate this information into their “toolbox” of thinking, problem solving, and communication with patients and colleagues. This research agenda on how best to educate future emergency physicians in the use of personalized data to provide optimal health care is the focus of this article.

There is a paucity of human in vitro models available to study the effects of alcohol in hepatocellular carcinoma (HCC). HCC cell lines are often deficient in either alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1). VL‐17a is currently the most widely studied model available. VL‐17a is derived from a HepG2 cell line engineered to overexpress mouse ADH and human CYP2E1. LH86 is a novel HCC cell line previously developed in our laboratory. Here we compare the LH86 cell line with the current model to identify a novel tool to study the effects of alcohol in HCC. The aim of this study is to evaluate the LH86 cell line as a novel human in vitro model to study the effects of alcohol in HCC. The cell lines were cultured with alcohol and gene expression and epigenomic changes were identified. The LH86 cell line was observed to have unique functional properties indicating that it is a potential novel tool to study the effects of alcohol in HCC. Support or Funding Information R01 AA19976 TO KR AND CL

ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P < .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

We previously demonstrated that increased expression of the SERPINA5 gene is associated with hippocampal vulnerability in Alzheimer’s disease (AD) brains. SERPINA5 was further demonstrated to be a novel tau-binding partner that colocalizes within neurofibrillary tangles. Our goal was to determine whether genetic variants in the SERPINA5 gene contributed to clinicopathologic phenotypes in AD. To screen for SERPINA5 variants, we sequenced 103 autopsy-confirmed young-onset AD cases with a positive family history of cognitive decline. To further assess the frequency of a rare missense variant, SERPINA5 p.E228Q, we screened an additional 1114 neuropathologically diagnosed AD cases. To provide neuropathologic context in AD, we immunohistochemically evaluated SERPINA5 and tau in a SERPINA5 p.E228Q variant carrier and a matched noncarrier. In the initial SERPINA5 screen, we observed 1 individual with a rare missense variant (rs140138746) that resulted in an amino acid change (p.E228Q). In our AD validation cohort, we identified an additional 5 carriers of this variant, resulting in an allelic frequency of 0.0021. There was no significant difference between SERPINA5 p.E228Q carriers and noncarriers in terms of demographic or clinicopathologic characteristics. Although not significant, on average SERPINA5 p.E228Q carriers were 5 years younger at age of disease onset than noncarriers (median: 66 [60–73] vs 71 [63–77] years, P = .351). In addition, SERPINA5 p.E228Q carriers exhibited a longer disease duration than noncarriers that approached significance (median: 12 [10–15]) vs 9 [6–12] years, P = .079). More severe neuronal loss was observed in the locus coeruleus, hippocampus, and amygdala of the SERPINA5 p.E228Q carrier compared to noncarrier, although no significant difference in SERPINA5-immunopositive lesions was observed. Throughout the AD brain in either carrier or noncarrier, areas with early pretangle pathology or burnt-out ghost tangle accumulation did not reveal SERPINA5-immunopositive neurons. Mature tangles and newly formed ghost tangles appeared to correspond well with SERPINA5-immunopositive tangle-bearing neurons. SERPINA5 gene expression was previously associated with disease phenotype; however, our findings suggest that SERPINA5 genetic variants may not be a contributing factor to clinicopathologic differences in AD. SERPINA5-immunopositive neurons appear to undergo a pathologic process that corresponded with specific levels of tangle maturity.