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Misplaced central line piercing common carotid removed and stented through a multidisciplinary approach: A video description
No full textCentral venous catheterizations, or central lines, are commonly placed in critical care situations for vasopressor support and resuscitation. However, central line placement still carries a 3% risk of major complications.1 While rare, inadvertent placement of large-bore central venous lines into the carotid arteries can be seen in 0.1% to 0.5% of cases.2 Utilizing a minimally invasive technique, such as a stent graft, to quickly seal the pierced artery after removal should be considered in cases needing vascular repair. We present the case of a 54-year-old female who was admitted to the intensive care unit for management of septic shock. At an outside hospital, her systolic blood pressure was 60 mmHg. She had a subclavian vein central line misplaced-inadvertently piercing the left common carotid, passing through the aortic valve, and terminating in the left ventricle. After a multidisciplinary discussion, the vascular surgery team felt surgery to be too high-risk. The patient was taken to a hybrid interventional suite with neurointerventional radiology and cardiothoracic surgery, where she underwent stenting of the left common carotid with a covered stent graft and simultaneous removal of the misplaced central line under fluoroscopy. The patient had excellent flow through the carotid stents with repeat computed tomography angiography head and neck imaging post-procedure and after three months. This case highlights the importance of considering endovascular management for iatrogenic vascular events in cases where surgical access is challenging or in critical conditions where there are increased risks of complications
Perceptions and attitudes toward sexual norms: key insights from the International Society of Sexual Medicine Young Researchers Committee survey
No full textBackground: Sexuality is a complex aspect of human life, and the perception of sexual normality may vary across genders, religious beliefs, and other aspects.
Aim: To report preliminary findings of a pilot survey on sexual attitudes, behaviors, and individual perception of sexual normality in a contemporary cross-cultural scenario.
Methods: A 48-item survey was developed by the Young Researchers Committee (YRC) on behalf of the International Society for Sexual Medicine (ISSM) to collect data on cross-cultural perceptions and attitudes toward sexual norms. The survey consisted of questions related to sexual attraction, behavior, identity, orientation, and subjective perception of sexual normality. Data were collected via five translated versions across five countries (Italy, United States, Brazil, Spain, and Japan) and analyzed to investigate how cultural norms, personal experiences, and social expectations shape individuals' views on sexual normality.
Outcomes: The primary outcome was to assess gender-based differences in sexual behaviors, satisfaction, religious beliefs' impact, pornography use, and anatomical perceptions.
Results: This pilot study included 3423 respondents [63.5% female, 36.2% male; median (IQR) age 39 (30.00, 50.00) years]. Of all, active sexual life was reported by 83.3% participants, with 58.8% expressing satisfaction with their sex life. Heterosexual orientation was predominant (90%), with significant differences in distribution between genders in terms of sexual orientation (P 16.1 cm: 13.1% vs 6.2%, P 80% of sexual encounters (38.2% vs 66.5%, P < .001).
Clinical implications: Our findings shape the development of sexual education, fostering inclusivity, equity, and sexual health for overall satisfaction.
Strengths and limitations: Possible biases associated with different modalities throughout data collections and with different linguistic and cultural weights given the cross-sectional nature of the pilot survey.
Conclusion: Current preliminary findings from the pilot survey developed by the ISSM YRC start shedding lights on perceptions and attitudes toward sexual norms, and gender differences in sexual behaviors and satisfaction
Clinical decision instruments for predicting mortality in patients with cirrhosis seeking emergency department care
No full textObjective: Clinical decision instruments (CDIs) could be useful to aid risk stratification and disposition of emergency department (ED) patients with cirrhosis. Our primary objective was to derive and internally validate a novel Cirrhosis Risk Instrument for Stratifying Post-Emergency department mortality (CRISPE) for the outcomes of 14- and 30-day post-ED mortality. Secondarily, we externally validated the existing Model for End-Stage Liver Disease (MELD) scores for explicit use in ED patients and prediction of the same outcomes.
Methods: A cohort of 2093 adults with cirrhosis, at 16 sites in a statewide health system, was analyzed for 119 candidate variables available at ED disposition. LASSO with 10-fold cross-validation was used in variable selection for 14-day (CRISPE-14) and 30-day (CRISPE-30) logistic regression models. Area under the receiver operating characteristic curve (AUROC) was calculated for each variant of the CRISPE and MELD scores and compared via Delong's test. Predictions were compared to actual ED disposition for predictive value and reclassification statistics.
Results: Median (interquartile range [IQR]) characteristics of the cohort were age 62 (53-70) years and MELD 3.0 13.0 (8.0-20.0). Mortality was 4.3% and 8.5% at 14 and 30 days, respectively. CRISPE-14 and CRISPE-30 outperformed each MELD variant, achieving AUROC of 0.824 (95% CI: 0.781-0.866) and 0.829 (0.796-0.861), respectively. MELD 3.0 AUROCs were 0.724 (0.667-0.781) and 0.715 (0.672-0.781), respectively. Compared to ED disposition, CRISPE-14, CRISPE-30, and MELD 3.0 significantly improved positive and negative predictive value and net reclassification index at multiple cutoffs. Applying CRISPE-30 (cutoff 4.5) favorably reclassified one net ED disposition for mortality for every 12 patients, while MELD 3.0 net reclassified one disposition per 84 patients.
Conclusions: CDIs may be useful in risk-stratifying ED patients with cirrhosis and aiding disposition decision making. The novel CRISPE CDI showed powerful performance and requires external validation, while the existing MELD 3.0 score has moderate performance and is now externally-validated in an ED population for short-term mortality
Serial amplification of tau filaments using Alzheimer's brain homogenates and C322A or C322S recombinant tau
No full textThe assembly of tau into amyloid filaments is a hallmark of Alzheimer's disease (AD) and other tauopathies. Cryo-EM revealed the existence of disease-specific tau folds, which are challenging to replicate in vitro. We studied three full-length recombinant 0N3R tau forms (the wild-type and the C322A and C322S variants) using an RT-QuIC assay with brain homogenate seeding. C322A tau formed filaments resembling AD paired helical filaments (PHFs) but with a more open C-shaped core. C322S tau yielded structurally distinct filaments with an ordered C-terminal region. Both mutants seeded further aggregation, whereas the wild-type showed poor reproducibility and mainly unfolded aggregates. These results highlight the importance of optimised conditions to produce disease-relevant tau filaments and aid the development of targeted therapies. Impact statement We investigated the seeded assembly of 0N3R tau and its two mutational variants C322A and C322S, using Alzheimer's disease brain homogenates in a real-time quaking-induced conversion (RT-QuIC) assay. The C322A variant formed filaments partially resembling the AD PHF structure, showing the importance of optimised conditions to produce disease-relevant tau filaments
2025 Bank of America Study of Philanthropy: Charitable Giving by Affluent Households
No full textThis study is a continuation of the 2006, 2008, 2010, 2012 Bank of America Study of High Net Worth Philanthropy, the 2014, 2016, and 2018 U.S. Trust® Study of High Net Worth Philanthropy, and the 2021 and 2023 Bank of America Study of Philanthropy: Charitable Giving by Affluent Households research series.Bank of Americ
Accounting for Misclassification of Cause of Death in Weighted Cumulative Incidence Functions for Causal Analyses
No full textMisclassification between causes of death can produce bias in estimated cumulative incidence functions. When estimating causal quantities, such as comparing the cumulative incidence of death due to specific causes under interventions, such bias can lead to suboptimal decision making. Here, a consistent semiparametric estimator of the cumulative incidence function under interventions in settings with misclassification between two event types is presented. The measurement parameters for this estimator can be informed by validation data or expert knowledge. Moreover, a modified bootstrap approach to variance estimation is proposed for confidence interval construction. The proposed estimator was applied to estimate the cumulative incidence of AIDS-related mortality in the Multicenter AIDS Cohort Study under single- vs combination-drug antiretroviral therapy regimens that may be subject to confounding. The proposed estimator is shown to be consistent and performed well in finite samples via a series of simulation experiments
Human Skeletal Remains at US Medical Schools: Provenance, Management, and Barriers to Ethical Stewardship
No full textIUIFollowing calls to action to ethically interact with human skeletal remains (HSR), the Task Force for Legacy Anatomical Collections within the American Association for Anatomy published guidelines on how to ethically manage HSR. Despite calls to action and recommendations, the literature lacks empirical investigation into the provenance of HSR and the current state of HSR management at US medical schools. Therefore, the purpose of this study was to investigate the provenance(s) of HSR at US medical schools, their current management, and barriers to improving management.
To investigate provenance and current management of HSR, a questionnaire was nationally distributed via email to gross anatomy educators and lab managers identified through an internet search. Results were analyzed using descriptive statistics. To investigate the barriers experienced by faculty and staff in improving HSR management, 60-minute focus groups were conducted; data was analyzed using framework thematic analysis. The Theoretical Domains Framework was applied to the inductively interpreted themes.
The results of this work show that provenance for HSR at US medical schools is largely undocumented and that the quality of HSR management varies by operational domain. For example, storage conditions and handling procedures are largely in line with professional recommendations at most medical schools. However, inventories and oversight committees are not active at over half of US medical schools and provenance investigations are not occurring at most US medical schools. Described barriers that hamper improvement of HSR management include ‘Social Influences’ and ‘Environmental Context and Resources’ from a lack of collegial and financial support as well as the management of HSR being a low ‘Goal’ for faculty and staff due to an overload of responsibilities.
This work provides empirical evidence that most HSR at US medical schools are of unknown provenance and shows that there are relatively few aspects of HSR management where US medical schools currently excel. It also demonstrates barriers experienced by faculty and staff in improving the management of HSR and provides potential solutions to those barriers. Lastly, this work serves as a further call to action to show HSR the respect and dignity they deserve
Radical nephroureterectomy vs kidney sparing surgery for upper tract urothelial carcinoma in solitary kidney patients: a multi-institutional analysis of the ROBUUST 2.0 registry
No full textPurpose: Radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) in solitary kidney patients is a rare and underreported scenario. This study aims to compare the outcomes of UTUC solitary kidney patients becoming anephric after RNU to those of patients undergoing kidney-sparing surgery (KSS).
Methods: Data from patients with a solitary kidney were retrieved from the ROBUUST 2.0 database, a global, multicenter registry containing data on patients who underwent curative surgery for UTUC. Baseline patient demographics, disease characteristics, and surgical features were compared between RNU and KSS. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) in patients undergoing RNU, with 3-year and 5-year cutoffs applied.
Results: Thirty-nine patients (76.5%) underwent RNU, whereas 12 (23.5%) underwent KSS. Despite a comparable preoperative renal function, the distribution of CKD stages differed significantly between the groups (p = 0.019). Despite a similar rate of postoperative complications, patients undergoing RNU experienced a significantly higher median LOS (p < 0.001). Among RNU patients, OS was 83.9%, CSS was 96.9%, RFS was 71.8%, and MFS was 84.4% at the 3-year follow-up. After 5 years post-surgery, OS was 73.4%, CSS was 83.1%, RFS was 59.9%, and MFS was 78.5% in the same cohort.
Conclusions: UTUC solitary kidney patients undergoing RNU or KSS face a substantial perioperative burden. Despite these challenges, our cohort demonstrated favorable oncological outcomes comparable to those reported in the existing literature
What is the impact of the chief resident designation on career direction: a cross-sectional analysis of a US database over 15 years
No full textBackground: It is unclear whether recruitment into academia will keep pace with attrition. Examining the events and opportunities that occur in residency, including the Chief Resident (CR) opportunity, will add to the pre-existing understanding about the proximate step to academic career choice. We evaluated whether there is an association between CR and type of employment the following year. Given that minoritized communities are underrepresented in academics, we evaluated whether the association varies by race-ethnicity.
Methods: We performed a cross-sectional analysis using de-identified individual-level data from the Graduate Medical Education (GME) Track, a national database and tracking system, from 2005 to 2020. The GME Track pulls data from the National GME census and is managed by the Association of American Medical Colleges (AAMC) and the American Medical Association (AMA). Participants were residents in their final year of training. Exposure variable was CR status (y/n). Main outcome was intended employment type the following year (fellowship, academic, other, or private practice [referent]). Multinomial logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals. We assessed, through interaction analyses, how intended employment varied by self-identified race-ethnicity.
Results: Among the study population (N = 450,598), 103,204 (22.9%) were CRs. CRs had increased odds of pursuing academics (1.04, 95% CI 1.01–1.06), but decreased odds of fellowship (0.76, 95% CI 0.75–0.78) or other careers (0.63, 95% CI 0.62–0.65) in comparison to private practice. Interaction analysis was significant (p < 0.0001). CRs who were Asian (1.13, 95% CI 1.07–1.19), Black (1.16, 95% CI 1.05–1.29), or multiracial (1.10, 95%CI 1.01–1.21), but not those who were Hispanic (0.94, 95% CI 0.83–1.08) or White (0.99, 95% CI 0.96–1.03) had increased odds of pursuing academics compared to non-CRs in those same race-ethnic categories.
Conclusions: CR was associated with the odds of initiating academic careers, which varied by race-ethnicity. The CR opportunity can be leveraged to diversify the pipeline into academic medicine
Real-world Observations on Neuroinflammation-related Drug Responses in Alzheimer’s Disease
No full textBackground:
Alcohol use disorder (AUD), epilepsy, hemorrhagic stroke (HS), and traumatic brain injury (TBI) are all linked to neuroinflammation and associated with an increased risk of Alzheimer’s disease (AD). Drug responses in cognitive health remain largely unknown in patients with neuroinflammation-related conditions.
Objective:
To investigate the associations between drug exposure and AD incidence in patients with neuroinflammation-related conditions.
Methods:
We derived covariate matched cohorts for individuals with and without neuroinflammation-related conditions (e.g., AUD, epilepsy, HS and TBI) from a US nationwide insurance claim data. We used covariate-adjusted Cox models to estimate the hazard ratios (HRs) of drug exposure on AD. We identified neuroinflammation-specific drug responses by comparing HRs between individuals with and without neuroinflammation-related conditions.
Results:
We identified 0.4 million matched pairs of individuals with and without neuroinflammation-related conditions. We identified three drugs (levothyroxine [HR =0.89], mirabegron [HR =0.69], and ropinirole [HR =0.81]) had a lower HR and two drugs (levetiracetam [HR =1.19], and quetiapine [HR =1.83]) had a higher HR in individuals with neuroinflammation-related conditions compared to without (false discovery rate <0.05).
Conclusions:
In patients with neuroinflammation-related conditions, we identified drugs associated with lower risks (levothyroxine, mirabegron and ropinirole) and higher risks (levetiracetam and quetiapine) of AD incidence