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Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

AimsMucinous cystic neoplasms (MCN) are defined by the presence of an ovarian‐type stroma (OTS). Once ovarian stroma has become a requirement for the diagnosis of MCNs, studies using this criterion have disclosed that MCNs are seen almost exclusively (97%) in women. The occurrence of MCNs (with ovarian stroma) in men is exceedingly rare and raises questions about the origin of OTS and the role of hormones in tumourigenesis. This study aims to investigate the clinical and histopathological features of pancreatic or hepatic MCNs in men.Methods and resultsWe examined the MCN cases in men and compared them with age‐matched women. We further investigated MCN in premenopausal and postmenopausal women to explore the impact of hormonal status.The stromal cellularity tended to be lower in men as compared to women; however, limited numbers prevented statistical significance. Clinical presentation, tumour location, body mass index and cyst complexity were similar between men and age‐matched women, similarly in pre‐ and postmenopausal woman groups. All MCN cases, regardless of gender or hormonal status, showed OTS with positivity for oestrogen receptor (ER), androgen receptor (AR) and SF‐1 immunostains. Additionally, the presence of AR and ER‐beta in lining epithelial cells, in addition to the stromal cells, raised the probability for a potential role for local hormonal signalling in the pathogenesis of these tumours.ConclusionsMCNs in men had overlapping histopathologic and immunohistochemical profiles with those in women, regardless of menopausal status.

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute‐on‐chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first‐line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so‐called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug‐induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up‐to‐date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug‐induced, autoimmune‐like hepatitis (DI‐AIH).

Physician categorizations of electronic health record (EHR) data (e.g., depression) into sensitive data categories (e.g., Mental Health) and their perspectives on the adequacy of the categories to classify medical record data were assessed. One thousand data items from patient EHR were classified by 20 physicians (10 psychiatrists paired with ten non-psychiatrist physicians) into data categories via a survey. Cluster-adjusted chi square tests and mixed models were used for analysis. 10 items were selected per each physician pair (100 items in total) for discussion during 20 follow-up interviews. Interviews were thematically analyzed. Survey item categorization yielded 500 (50.0%) agreements, 175 (17.5%) disagreements, 325 (32.5%) partial agreements. Categorization disagreements were associated with physician specialty and implied patient history. Non-psychiatrists selected significantly ( p = .016) more data categories than psychiatrists when classifying data items. The endorsement of Mental Health and Substance Use categories were significantly ( p = .001) related for both provider types. During thematic analysis, Encounter Diagnosis (100%), Problems (95%), Health Concerns (90%), and Medications (85%) were discussed the most when deciding the sensitivity of medical information. Most (90.0%) interview participants suggested adding additional data categories. Study findings may guide the evolution of digital patient-controlled granular data sharing technology and processes.

AbstractInformation about the effects of angiotensin II receptor blocker (ARB) therapy on the hemodynamic and cardiac structure in patients with chronic aortic regurgitation (CAR) and isolated systolic hypertension (ISH) is limited.This study planned to test the hypothesis that l-arginine could further enhance the beneficial effect of an ARB, losartan, and provide a favorable effect on the natural history of CAR and ISH.Sixty patients with CAR and ISH were enrolled in a randomized, double-blind trial comparing hemodynamic and ultrasonic change in two treatment arms: losartan + l-arginine and losartan-only treated groups. Serial echocardiographic and hemodynamic studies were evaluated before and after treatment.Both groups had a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP), left ventricular end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), LV mass index (LVMI), and LV mean wall stress after 6- and 12-month treatment (p <0.01 in all comparisons). Both groups had a significant increase in LV ejection fraction and exercise duration after 6- and 12-month treatment (p < 0.01 in all comparisons). Using multivariate linear regression analysis, only losartan + l-arginine therapy achieved a significantly lower LVESVI (38.89 ± 0.23 mL/m2), LVEDVI (102.3 ± 0.3 mL/m2), LVMI (107.6 ± 0.3 g/m2), SBP (123.5 ± 1.0 mm Hg), and greater exercise duration (7.38 ± 0.02 minutes) than those of the losartan-only treated groups (p <0.01 in all comparisons).These findings suggest that early co-administrative strategy provides a beneficial approach to favorably influence the natural history of CAR.

Objective IgG4‐related disease (IgG4‐ RD ) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4‐ RD . Methods An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology ( ACR ) and the European League Against Rheumatism ( EULAR ). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included. Results A 3‐step classification process was developed. First, it must be demonstrated that a potential IgG4‐ RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4‐ RD . Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4‐ RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval [95% CI ] 97.2–99.8%) and a sensitivity of 85.5% (95% CI 81.9–88.5%). In the second, the specificity was 97.8% (95% CI 93.7–99.2%) and the sensitivity was 82.0% (95% CI 77.0–86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. Conclusion ACR / EULAR classification criteria for IgG4‐ RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.

Background: Patients with pulmonary hypertension (PH) experience distressing symptoms that can undermine quality of life (QoL) and treatment adherence. Complementary health approaches are known to help manage symptoms of chronic conditions and may have therapeutic benefits in PH. Objective: To explore the impact of Urban Zen Integrative Therapy (UZIT) on PH-related symptoms. Design: A within-subjects, pre-/post-intervention, repeated-measures design. Subjects/Setting: Community-dwelling adults with PH received weekly UZIT sessions in an outpatient setting. Measurements: Participants ( n = 14) rated symptoms before and after each session and before and after the six-week UZIT program. Mixed-effects modeling with repeated measures was used to estimate differences in mean symptom scores before and after individual sessions. Cohen's d effect sizes were used to evaluate the impact of the UZIT program on symptoms. Results: Mean scores for pain ( F (1, 105) = 19.99, p < 0.001), anxiety ( F (1, 96) = 24.64, p < 0.001), fatigue ( F (1, 120) = 15.68, p < 0.001), and dyspnea ( F (1, 68) = 16.69, p < 0.001) were significantly reduced after UZIT sessions. Effects were moderate to large for symptom severity ( d = 0.59–1.32) and moderate for symptom burden ( d = 0.56) and fatigue ( d = 0.62), and small for QoL ( d = 0.33) after the six-week UZIT program. Conclusions: Individualized UZIT sessions were associated with reductions in symptom severity for pain, anxiety, fatigue, and dyspnea. The six-week UZIT program was associated with improvements in symptom burden, activity limitation, and QoL. ClinicalTrial.gov no.: NCT03194438

Interplay between cell polarity module Scribble‐Lethal Giant Larvae‐Discs Large 1 (DLG1) and Yes‐associated protein (YAP) appears critical in tumor metastasis. We identified zinc finger protein 191 (ZNF191) as a metastasis suppressor acting through DLG‐YAP crosstalk in hepatocellular carcinoma (HCC). Overexpression of ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted cell migration in vitro and metastasis in vivo through triggering YAP signaling. Chromatin immunoprecipitation‐sequencing revealed that ZNF191 specifically bound to the promoter of DLG1, a cell polarity maintainer and a negative regulator of YAP. The binding sequence of ZNF191 at the DLG1 promoter is a seven‐repeat of TCAT motif. Double‐knockdown experiments inferred that DLG1 was not only the mediator of the function of ZNF191 to suppress migration but also a link between ZNF191 and YAP signaling. Decreased expression of ZNF191 in human metastatic HCC specimens correlated positively with DLG1 levels but inversely with YAP activation. Our findings illustrate a YAP‐targeting, antimetastasis function of ZNF191, thereby representing a possible prognostic marker and a potential target for metastasis therapy. Conclusion: ZNF191 directly binds to the DLG1 promoter at a typical TCAT repeating motif and activates the expression of DLG1; through up‐regulating DLG1, ZNF191 inhibits cell migration and YAP activation in HCC cells and eventually inhibits metastasis. (Hepatology 2016;64:1148‐1162)

Objective Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.