Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease Codes in Patient Records.

PURPOSE: Current approaches to accurately identify immune-related adverse events (irAEs) in large retrospective studies are limited. Large language models (LLMs) offer a potential solution to this challenge, given their high performance in natural language comprehension tasks. Therefore, we investigated the use of an LLM to identify irAEs among hospitalized patients, comparing its performance with manual adjudication and International Classification of Disease (ICD) codes. METHODS: Hospital admissions of patients receiving immune checkpoint inhibitor (ICI) therapy at a single institution from February 5, 2011, to September 5, 2023, were individually reviewed and adjudicated for the presence of irAEs. ICD codes and an LLM with retrieval-augmented generation were applied to detect frequent irAEs (ICI-induced colitis, hepatitis, and pneumonitis) and the most fatal irAE (ICI-myocarditis) from electronic health records. The performance between ICD codes and LLM was compared via sensitivity and specificity with an α = .05, relative to the gold standard of manual adjudication. External validation was performed using a data set of hospital admissions from June 1, 2018, to May 31, 2019, from a second institution. RESULTS: Of the 7,555 admissions for patients on ICI therapy in the initial cohort, 2.0% were adjudicated to be due to ICI-colitis, 1.1% ICI-hepatitis, 0.7% ICI-pneumonitis, and 0.8% ICI-myocarditis. The LLM demonstrated higher sensitivity than ICD codes (94.7% v 68.7%), achieving significance for ICI-hepatitis (P < .001), myocarditis (P < .001), and pneumonitis (P = .003) while yielding similar specificities (93.7% v 92.4%). The LLM spent an average of 9.53 seconds/chart in comparison with an estimated 15 minutes for adjudication. In the validation cohort (N = 1,270), the mean LLM sensitivity and specificity were 98.1% and 95.7%, respectively. CONCLUSION: LLMs are a useful tool for the detection of irAEs, outperforming ICD codes in sensitivity and adjudication in efficiency.

Adaptations to COVID-19 by US abortion clinics: Analysis of Society of Family Planning survey data.

OBJECTIVE: Analyze changes in abortion practices during the early coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: Sites recruited by Society of Family Planning participated in a longitudinal descriptive analysis comprising three surveys between February and October 2020. Average monthly total and medication abortion volume was analyzed by χ2 and linear regression. RESULTS: Total average volume of abortion services did not change among participating sites (p = 0.79). Volume and proportion of medication abortion increased over the study period (p = 0.02, p < 0.01). CONCLUSIONS: The early COVID-19 pandemic marked a shift toward medication abortion. IMPLICATIONS: Our findings are interlaced in a national trend predating the Dobbs ruling, likely accelerated by the COVID-19 pandemic.

Assessing actigraphy performance for daytime sleep detection following stroke: insights from inpatient monitoring in a rehabilitation hospital.

Study Objectives: Stroke can result in or exacerbate various sleep disorders. The presence of behaviors such as daytime sleepiness poststroke can indicate underlying sleep disorders which can significantly impact functional recovery and thus require prompt detection and monitoring for improved care. Actigraphy, a quantitative measurement technology, has been primarily validated for nighttime sleep in healthy adults; however, its validity for daytime sleep monitoring is currently unknown. Therefore this study aims to identify the best-performing actigraphy sensor and algorithm for detecting daytime sleep in poststroke individuals. Methods: Participants wore Actiwatch Spectrum and ActiGraph wGT3X-BT on their less-affected wrist, while trained observers recorded daytime sleep occurrences and activity levels (active, sedentary, and asleep) during non-therapy times. Algorithms, Actiwatch (Autoscore AMRI) and ActiGraph (Cole-Kripke, Sadeh), were compared with on-site observations and assessed using F2 scores, emphasizing sensitivity to detect daytime sleep. Results: Twenty-seven participants from an inpatient stroke rehabilitation unit contributed 173.5 hours of data. The ActiGraph Cole-Kripke algorithm (minute sleep time = 15 minutes, bedtime = 10 minutes, and wake time = 10 minutes) achieved the highest F2 score (0.59). Notably, when participants were in bed, the ActiGraph Cole-Kripke algorithm continued to outperform Sadeh and Actiwatch AMRI, with an F2 score of 0.69. Conclusions: The study demonstrates both Actiwatch and ActiGraph's ability to detect daytime sleep, particularly during bed rest. ActiGraph (Cole-Kripke) algorithm exhibited a more balanced sleep detection profile and higher F2 scores compared to Actiwatch, offering valuable insights for optimizing daytime sleep monitoring with actigraphy in stroke patients.

ß-Hydroxy Esters as Malonic Semialdehyde Proelectrophiles in Enantioselective Butadiene-Mediated Crotylation: Total Synthesis of Octalactins A and B.

Tractable and commercially available esters (and amides) of ß-hydroxypropionic acid serve as malonic semialdehyde proelectrophiles in enantioselective ruthenium-catalyzed hydrogen autotransfer crotylations mediated by butadiene. Through iterative asymmetric butadiene-mediated crotylations of ethyl 3-hydroxypropanoate, total syntheses of the polyketide natural products octalactin A and B were achieved in fewer steps than previously possible.

Contraceptive Attitudes and Beliefs of Women With Sickle Cell Disease: A Qualitative Study.

OBJECTIVES: We aimed to qualitatively explore factors influencing contraceptive use in women living with sickle cell disease (SCD). STUDY DESIGN: We conducted a semi-structured qualitative study using data from interviews with reproductive-aged women with SCD. The Theory of Planned Behavior, which describes an individual's attitudes, subjective norms, and perceived behavioral control as drivers of a health behavior, served as a framework for data collection and thematic analysis. RESULTS: We analyzed interviews from 20 participants. Attitudes toward contraception showed skepticism regarding hormonal contraception and concern about adverse effects of contraception related to SCD. The role of subjective norms in contraceptive choice depended on whether participants possessed trusted sources of information, such as health care providers, family, and friends, or whether they relied on themselves alone in their contraceptive decision-making. The influence of health care providers was complicated by inconsistent and sometimes conflicting counseling. Finally, with regard to participants' perceived control in their contraceptive choices, some were motivated to alleviate menstrual pain or prevent SCD-related pregnancy risks, but many reported feeling disempowered in contraceptive decision-making settings because of ways that healthcare providers exerted pressure or responded to participants' demographic characteristics. CONCLUSIONS: Women living with SCD are influenced by many factors similar to those documented for other populations when making decisions about contraception. However, SCD amplifies both the importance and risks of contraception and may also complicate individuals' autonomy and contraceptive access. Hematology and reproductive health providers should recognize the risk of coercion, maximize patients' reproductive agency, and coordinate reproductive health counseling for patients with SCD.

The Great Debate: Robotic vs Traditional Surgical Approach in the Acute Care Setting.

Robotic surgery was first introduced in the 1980s as a system to aid patients in the battlefield. Since then, robotic surgery has become an important minimally invasive tool and plays an important role in elective surgery among various surgical specialties. However, the role for robotic surgery in the emergent setting is not well established or studied. Robotic surgery has been shown to be advantageous to both patients and operating surgeons. Though limited, studies have found robotic surgery in the acute setting to be safe for patients. These studies found robotic surgery to have improved perioperative outcomes when compared to an open or laparoscopic approach. Additionally, the robotic platform is thought to be an effective tool to prevent conversion to open procedures in emergent settings. Although some studies demonstrate advantages to robotic acute surgery, others have shown increased complications with robotic acute surgery or no distinct advantage when comparing robotic to laparoscopic surgery. Additionally, some of the published papers supporting the use of robotic surgery in the emergent setting may have a degree of bias favoring the robotic platform. Robotic surgery is a mainstay in minimally invasive elective surgery and gaining popularity among patients and surgeons. There are pros and cons to the adaptation of the robotic platform in the acute care setting. Additional large population studies are indicated to determine the true role of the robotic platform in the emergent setting.

Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

BACKGROUND: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. METHODS: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. RESULTS: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. CONCLUSIONS: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.

Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a "mature diet" high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a "pre-packaged" dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet-microbiota and microbiota-outcome associations may mediate this relationship.

Effect of atorvastatin versus placebo on efficacy in patients with diffuse large B-cell lymphoma receiving R-CHOP.

STOP-CA was a multicenter, double-blind, randomized, placebo-controlled trial comparing atorvastatin to placebo in treatment-naïve lymphoma patients receiving anthracycline-based chemotherapy. We performed a preplanned subgroup to analyze the impact of atorvastatin on efficacy in patients with diffuse large B-cell lymphoma (DLBCL). Patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard doses for six 21-day cycles and were randomly assigned to receive atorvastatin 40 mg daily (n = 55) or placebo (n = 47) for 12 months. The complete response (CR) rate was numerically higher in the atorvastatin arm (95% [52/55] vs. 85% [40/47], p = .18), but this was not statistically significant. Adverse event rates were similar between the atorvastatin and placebo arms. In summary, atorvastatin did not result in a statistically significant improvement in the CR rate or progression-free survival, but both were numerically improved in the atorvastatin arm. These data warrant further investigation into the potential therapeutic role of atorvastatin added to anthracycline-based chemotherapies.

Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults-a BMTSS report.

We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3-4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3-5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0-40.0) and median follow-up was 9.8 years (2.0-32.1). Survivors were at a 3-fold higher adjusted odds for grade 3-4 conditions (95% CI = 2.3-4.1) vs. comparison subjects. Factors associated with grade 3-5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27-4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13-2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34-0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.

Disruption of trauma research: an analysis of the top cited versus disruptive trauma research publications.

Introduction: The analysis of surgical research using bibliometric measures has become increasingly prevalent. Absolute citation counts (CC) or indices are commonly used markers of research quality but may not adequately capture the most impactful research. A novel scoring system, the disruptive score (DS) has been found to identity academic work that either changes paradigms (disruptive (DIS) work) or entrenches ideas (developmental (DEV) work). We sought to analyze the most DIS and DEV versus most cited research in civilian trauma. Methods: The top papers by DS and by CC from trauma and surgery journals were identified via a professional literature search. The identified publications were then linked to the National Institutes of Health iCite tool to quantify total CC and related metrics. The top 100 DIS and DEV publications by DS were analyzed based on the area of focus, citation, and perceived clinical impact, and compared with the top 100 papers by CC. Results: 32 293 articles published between 1954 and 2014 were identified. The most common publication location of selected articles was published in Journal of Trauma (31%). Retrospective reviews (73%) were common in DIS (73%) and top CC (67%) papers, while DEV papers were frequently case reports (49%). Only 1 publication was identified in the top 100 DIS and top 100 CC lists. There was no significant correlation between CC and DS among the top 100 DIS papers (r=0.02; p=0.85), and only a weak correlation between CC and DS score (r=0.21; p<0.05) among the top 100 DEV papers. Conclusion: The disruption score identifies a unique subset of trauma academia. The most DIS trauma literature is highly distinct and has little overlap with top trauma publications identified by standard CC metrics, with no significant correlation between the CC and DS. Level of evidence: Level IV.

Carbonyl Allylation and Crotylation: Historical Perspective, Relevance to Polyketide Synthesis, and Evolution of Enantioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer Processes.

The evolution of methods for carbonyl allylation and crotylation of alcohol proelectrophiles culminating in the design of iodide-bound ruthenium-JOSIPHOS catalysts is prefaced by a brief historical perspective on asymmetric carbonyl allylation and its relevance to polyketide construction. Using gaseous allene or butadiene as precursors to allyl- or crotylruthenium nucleophiles, respectively, new capabilities for carbonyl allylation and crotylation have been unlocked, including stereo- and site-selective methods for the allylation and crotylation of 1,3-diols and related polyols.

AGS3 antagonizes LGN to balance oriented cell divisions and cell fate choices in mammalian epidermis.

Oriented cell divisions balance self-renewal and differentiation in stratified epithelia such as the skin epidermis. During peak epidermal stratification, the distribution of division angles among basal keratinocyte progenitors is bimodal, with planar and perpendicular divisions driving symmetric and asymmetric daughter cell fates, respectively. An apically restricted, evolutionarily conserved spindle orientation complex that includes the scaffolding protein LGN/Pins/Gpsm2 plays a central role in promoting perpendicular divisions and stratification, but why only a subset of cell polarize LGN is not known. Here, we demonstrate that the LGN paralog, AGS3/Gpsm1, is a novel negative regulator of LGN and inhibits perpendicular divisions. Static and ex vivo live imaging reveal that AGS3 overexpression displaces LGN from the apical cortex and increases planar orientations, while AGS3 loss prolongs cortical LGN localization and leads to a perpendicular orientation bias. Genetic epistasis experiments in double mutants confirm that AGS3 operates through LGN. Finally, clonal lineage tracing shows that LGN and AGS3 promote asymmetric and symmetric fates, respectively, while also influencing differentiation through delamination. Collectively, these studies shed new light on how spindle orientation influences epidermal stratification.

What can coronial cases tell us about the quality of emergency healthcare for prisoners in Australia?

OBJECTIVE: This research aimed to examine the legal and regulatory obligations of authorities and healthcare professionals in the provision of prison emergency health services and to identify problems in the provision of emergency care to prisoners by using case examples from coronial findings. METHODS: Review of legal and regulatory obligations and a search of coronial cases for deaths related to the provision of emergency healthcare in prisons in the past 10 years in Victoria, New South Wales and Queensland. RESULTS: The case review identified several themes - issues with prison authority policies and procedures that delay access to timely healthcare or compromise the quality of care, operational and logistical factors, clinical issues and stigmatic issues including prison staff attitudes to prisoners requesting urgent healthcare assistance. CONCLUSION: Coronial findings and royal commissions have repeatedly identified deficiencies in the emergency healthcare provided to prisoners in Australia. These deficiencies are operational, clinical and stigmatic and not limited to a single prison or jurisdiction. Applying a health quality of care framework focussed on prevention and chronic health management, appropriate assessment and escalation when urgent medical assistance is requested, and a structured audit framework could avoid future preventable deaths in prisons.

Risk of COVID-19 infection in long-term survivors of blood or marrow transplantation: a BMTSS report.

There is limited information regarding COVID-19 in long-term blood or marrow transplant (BMT) survivors. We leveraged the BMT Survivor Study (BMTSS) to address this gap. BMTSS included patients who underwent BMT at 1 of 3 sites in the United States between 1974 and 2014 and survived ≥2 years after BMT. A sibling cohort serves as a non-BMT comparison group. Participants (2430 BMT survivors; 780 non-BMT participants) completed the BMTSS survey between October 2020 and November 2021 about COVID-19 testing, risk mitigation behaviors, morbidity, and health care use. Median age at BMT was 46 years (range, 0-78 years) and median follow-up since BMT was 14 years (6-46 years); 76% were non-Hispanic White, 54% had received allogeneic BMT. The risk of COVID-19 infection was comparable for BMT survivors vs non-BMT participants (15-month cumulative incidence, 6.5% vs 8.1%; adjusted odd ratio [aOR] = 0.93; 95% confidence interval [CI], 0.65-1.33; P = .68). Among survivors, being unemployed (aOR 1.90; 95% CI, 1.12-3.23; P = .02; reference: retired) increased the odds of infection; always wearing a mask in public was protective (aOR = 0.49; 95% CI, 0.31-0.77; P = .002; reference: not always masking). When compared with COVID-positive non-BMT participants, COVID-positive BMT survivors had higher odds of hospitalization (aOR = 2.23; 95% CI, 0.99-5.05; P = .05); however, the odds of emergency department visits were comparable (aOR = 1.60; 95% CI = 0.71-3.58; P = .25). COVID-19 infection status did not increase the odds of hospitalization among BMT survivors (aOR = 1.32; 95% CI = 0.89-1.95; P = .17) but did increase the odds of emergency department visits (aOR = 2.63; 95% CI, 1.74-3.98; P <.0001). These findings inform health care providers about the management of care for long-term BMT survivors during the ongoing pandemic.

Malignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant.

Importance: Survivors of blood or marrow transplant (BMT) are at increased risk of subsequent malignant neoplasms (SMNs). Cancers of the gastrointestinal (GI) system are of special interest because their clinical behavior is often aggressive, necessitating early detection by increasing awareness of high-risk populations. Objective: To describe the risk of SMNs in the GI tract after BMT. Design, Setting, and Participants: A cohort study of 6710 individuals who lived at least 2 years after BMT performed between January 1, 1974, and December 31, 2014, at City of Hope, University of Minnesota, or University of Alabama at Birmingham. End of follow-up was March 23, 2020. Data analysis was performed between September 1, 2022, and September 30, 2022. Exposures: Demographic and clinical factors; therapeutic exposures before or as part of BMT. Main Outcomes and Measures: Development of SMNs in the GI tract after BMT. Participants self-reported SMNs in the GI tract; these were confirmed with pathology reports, medical records, or both. For deceased patients, death records were used. Standardized incidence ratios determined excess risk of SMNs in the GI tract compared with that of the general population. Fine-Gray proportional subdistribution hazard models assessed the association between risk factors and SMNs in the GI tract. Results: The cohort of 6710 individuals included 3444 (51.3%) autologous and 3266 (48.7%) allogeneic BMT recipients. A total of 3917 individuals (58.4%) were male, and the median age at BMT was 46 years (range, 0-78 years). After 62 479 person-years of follow-up, 148 patients developed SMNs in the GI tract. The standardized incidence ratios for developing specific SMNs ranged from 2.1 for colorectal cancer (95% CI, 1.6-2.8; P < .001) to 7.8 for esophageal cancer (95% CI, 5.0-11.6; P < .001). Exposure to cytarabine for conditioning (subdistribution hazard ratio [SHR], 3.1; 95% CI, 1.5-6.6) was associated with subsequent colorectal cancer. Compared with autologous BMT recipients, allogeneic BMT recipients with chronic graft-vs-host disease were at increased risk for esophageal cancer (SHR, 9.9; 95% CI, 3.2-30.5). Conditioning with etoposide (SHR, 2.0; 95% CI, 1.1-3.5) and pre-BMT anthracycline exposure (SHR, 5.4; 95% CI, 1.3-23.4) were associated with an increased risk of liver cancer compared with no exposure to the respective agents. Conclusions and Relevance: The findings of this cohort study are relevant for oncologists and nononcologists who care for the growing number of survivors of transplant. Awareness of subgroups of survivors of BMT at high risk for specific types of SMNs in the GI tract may influence recommendations regarding modifiable risk factors, as well as individualized screening.

Lower Rates of Unplanned Conversion to Open in Robotic Approach to Esophagectomy for Cancer.

BACKGROUND: Minimally invasive approaches to esophagectomy have gained popularity worldwide; however, unplanned conversion to an open approach is not uncommon. This study sought to investigate risk factors associated with converting to an open approach and to evaluate outcomes following conversion. METHODS: Patients undergoing minimally invasive esophagectomy (MIE) for cancer were identified using the 2016-2019 Procedure Targeted NSQIP Database. Multivariable, stepwise logistic regression analysis was performed to investigate factors associated with unplanned conversion to open esophagectomy. Propensity-matched comparison of robotic (RAMIE) to traditional MIE was performed. RESULTS: A total of 1347 patients were included; 140 patients (10%) underwent conversion to open. Morbid obesity, diabetes, hypertension, American Society of Anesthesiologists class, and squamous cell carcinoma were associated with a higher likelihood of conversion. A robotic approach was associated with a lower likelihood of conversion to open (OR .57, 95% CI 0.32-.99). On multivariable analysis, squamous cell carcinoma pathology was the only variable independently associated with higher odds of conversion (OR 2.66, 95% CI 1.02-6.98). Propensity-matched comparison of RAMIE vs MIE showed no significant difference in conversion rate (6.5% vs 9.1%, P = .298), morbidity, or mortality. DISCUSSION: A robotic approach to esophagectomy was associated with a lower likelihood of unplanned conversion to open, and patients who were converted to open experienced worse outcomes. Future studies should aim to determine why a robotic esophagectomy approach may lead to fewer open conversions as it may be an underappreciated benefit of this newest operative approach.