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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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

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 χ 2 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: None disclosed.

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., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

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., (Copyright © 2024 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Tractable and commercially available esters (and amides) of β-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.

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.

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.

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., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

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., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

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.

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., Competing Interests: Conflict of Interest There are no conflicts to declare.

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., Competing Interests: CD, KL, AJ, JW, JY, DS, MU, KK, SW No competing interests declared, (© 2023, Descovich et al.)

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.

Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied., Methods: Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3-5 conditions. Logistic regression was used to estimate the risk of grade 3-4 conditions in BMT recipients who were alive at the time of this study compared with siblings., Results: The median age at transplantation was 11.3 years (range, 0.4-22.0 years), and the median length of follow-up was 11.7 years (range, 2.0-45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3-4 condition was 53.8% (95% CI, 46.7%-60.3%). The adjusted odds ratio of a grade 3-4 condition was 15.1 in survivors (95% CI, 9.5-24.0) compared with siblings. The risk of a grade 3-5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05) and was higher among females (HR, 1.27; 95% CI, 1.02-1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27-2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09-1.74)., Conclusions: Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3-4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up., (© 2022 American Cancer Society.)

Living in a disadvantaged neighborhood is associated with poor health outcomes. Blood or Marrow Transplant (BMT) survivors remain at risk of chronic health conditions requiring anticipatory management. We hypothesized that among BMT survivors, neighborhood disadvantage was associated with poor self-reported routine health care utilization and health. We leveraged data from BMTSS - a retrospective cohort study examining long-term outcomes among individuals surviving ≥2 y following BMT at three institutions between 1974 and 2014. Participants in this analysis completed the BMTSS survey (sociodemographics; chronic health conditions; time since routine check-up; self-reported health). The Area Deprivation Index (ADI) represented neighborhood disadvantage; this composite indicator of 17 census measures is a percentile rank (0 = least deprived to 100 = most deprived). Multivariable ordered logit regression adjusted for clinical factors and individual-level sociodemographics, modeling associations between ADI, time since routine check-up, and self-reported health. Among 2,857 survivors, median ADI was 24 (interquartile range: 10-46). Adjusting for self-reported individual-level socioeconomic indicators and chronic health conditions, patients in more disadvantaged neighborhoods had higher odds of reporting longer intervals since routine check-up (ORADI&#95;continuous = 1.007, P < .001) and poorer health status (controlling for time since check-up; ORADI&#95;continuous = 1.005, P = .003). Compared with patients living in the least disadvantaged neighborhood (ADI = 1), patients in the most disadvantaged neighborhood (ADI = 100), had twice the odds (ORADI = 1.007^99 = 2.06) of reporting no routine visits and 1.65-times the odds of reporting poor health (ORADI = 1.005^99 = 1.65). In BMT survivors, access to health care and health status are associated with area disadvantage. These findings may inform strategies to address long-term care coordination and retention for vulnerable survivors., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: The financial burden experienced by blood or marrow transplant (BMT) survivors during the COVID-19 pandemic remains unstudied. We evaluated the risk for high out-of-pocket medical costs and associated financial burden experienced by BMT survivors and a sibling comparison group during the COVID-19 pandemic., Methods: This study included 2,370 BMT survivors and 750 siblings who completed the BMT Survivor Study survey during the pandemic. Participants reported employment status, out-of-pocket medical costs, and financial burden. Medical expenses ≥ 10% of the annual household income constituted high out-of-pocket medical costs. Logistic regression identified factors associated with high out-of-pocket medical costs and financial burden., Results: BMT survivors were more likely to incur high out-of-pocket medical costs (11.3% v 3.1%; adjusted odds ratio [aOR], 2.88; 95% CI, 1.84 to 4.50) than the siblings. Survivor characteristics associated with high out-of-pocket medical costs included younger age at study (aOR per&#95;year&#95;younger&#95;age , 1.02; 95% CI, 1.00 to 1.03), lower prepandemic annual household income and/or education (< $50,000 US dollars and/or < college graduate: aOR, 1.96; 95% CI, 1.42 to 2.69; reference: ≥ $50,000 in US dollars and ≥ college graduate), > 1 chronic health condition (aOR, 2.82; 95% CI, 2.00 to 3.98), ≥ 1 hospitalization during the pandemic (aOR, 2.11; 95% CI, 1.53 to 2.89), and being unemployed during the pandemic (aOR, 1.52; 95% CI, 1.06 to 2.17). Among BMT survivors, high out-of-pocket medical costs were significantly associated with problems in paying medical bills (aOR, 10.57; 95% CI, 7.39 to 15.11), deferring medical care (aOR, 4.93; 95% CI, 3.71 to 6.55), taking a smaller dose of medication than prescribed (aOR, 4.99; 95% CI, 3.23 to 7.70), and considering filing for bankruptcy (aOR, 3.80; 95% CI, 2.14 to 6.73)., Conclusion: BMT survivors report high out-of-pocket medical costs, which jeopardizes their health care and may affect health outcomes. Policies aimed at reducing financial burden in BMT survivors, such as expanding access to patient assistance programs, may mitigate the negative health consequences.

Background: Blood or marrow transplantation (BMT) is increasingly offered to older individuals with hematologic malignancies. The high prevalence of chronic health conditions in such individuals necessitates use of multiple medications. Beers Criteria represent a list of potentially inappropriate medications (PIMs) shown to increase the risk of health problems in the elderly. We sought to determine the prevalence and predictors of PIM use in older BMT survivors and identify associations with health problems., Methods: Study participants were drawn from the BMT Survivor Study, a cohort study of patients transplanted at three US transplant centers between 1974 and 2014 and surviving ≥2 years. For this report, the survivors were aged ≥65 years. Siblings served as a comparison group. Participants self-reported sociodemographics, chronic health conditions, and medication use. Logistic regression analyses identified predictors of PIM use and associations with health problems., Results: Overall, PIM use was comparable between BMT survivors (49.4%) and siblings (49.3%) (odds ratio [OR] = 0.9; 95% CI, 0.7-1.2); however, BMT survivors were more likely to use >1 PIM (17.4% vs. 12.4%; OR = 1.5; 95% CI, 1.01-2.4) and central nervous system-related PIMs (8.3% vs. 4.3%; OR = 2.18; 95% CI, 1.17-4.09). Predictors of PIM use included presence of severe/life-threatening chronic health conditions (OR = 1.5; 95% CI, 1.1-2.0), and chronic graft versus host disease (OR = 1.7; 95% CI, 1.1-2.7). Survivors taking >1 PIM reported more issues with vertigo (OR = 2.3; 95% CI, 1.1-4.7), balance (OR = 2.6; 95% CI, 1.7-4.1), faintness/dizziness (OR = 2.8; 95% CI, 1.8-4.6), and personal care (OR = 4.5; 95% CI, 1.4-14.8)., Conclusions: This study shows the health problems associated with PIM use and identifies vulnerable populations at higher risk for PIM use, providing evidence for caution in using PIMs in high-risk populations., (© 2022 American Cancer Society.)

Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols with methylallene (1,2-butadiene) or 1,3-butadiene to form products of anti-crotylation with good to excellent levels of diastereo- and enantioselectivity. Distinct from other methods, direct crotylation of primary alcohols in the presence of unprotected secondary alcohols is possible, enabling generation of spirastrellolide B (C9-C15) and leucascandrolide A (C9-C15) substructures in significantly fewer steps than previously possible., (© 2022 Wiley-VCH GmbH.)

Purpose: Obesity is prevalent among economically disadvantaged and racially underrepresented populations. It has been suggested that socioeconomic factors, race, and lifestyle habits are important factors associated with weight loss and comorbidity remission after bariatric surgery. This study analyzes outcomes of bariatric surgery at a private hospital (PH) versus an affiliated safety-net hospital (SNH)., Methods: Retrospective review of laparoscopic sleeve gastrectomies (LSG) performed by the same surgeons at a PH and SNH in a large metropolitan setting. Demographics, socioeconomic status, insurance status, weight metrics, and perioperative outcomes were compared. A postoperative telephone survey was conducted to study dietary and lifestyle differences between cohorts., Results: Of the 243 LSG performed, 141 (58%) occurred at PH versus 102 (42%) at SNH. Most patients at SNH were Hispanic, lower socioeconomic status, and had government-sponsored insurance. Based off the results from the postoperative telephone survey, there were no significant differences in dietary and lifestyle habits between both cohorts. Postoperative weight loss outcomes were similar across cohorts. The two groups had similar percent excess weight loss (EWL) at all time points up to 36 months and similar rates of failure to achieve 50% EWL at 12 months. However, patients at PH had greater resolution of diabetes and hypertension after surgery., Conclusion: Our study demonstrates outcomes after bariatric surgery are similar at a PH and its affiliated SNH. Despite differences in race and socioeconomic factors between the two cohorts, perioperative outcomes, short-term postoperative weight loss, and weight loss failure rates were equivalent between SNH and PH patients., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The ratio of hernia size to fascial defect size, termed the hernia-to-neck ratio (HNR), has been proposed as a novel predictive factor for umbilical hernia complications. HNR ≥ 2.5 has been suggested to warrant surgery due to association with bowel strangulation, incarceration, and necrosis. The aim of this study was to evaluate the association between HNR and emergent ventral hernia repair at our institution., Methods: A retrospective cohort study was performed of consecutive patients with ventral hernias evaluated at a large safety-net hospital from 2017 to 2019. Patients who required emergent ventral hernia repair were compared to patients who did not require repair at latest follow-up. HNR was calculated using a previously described method: maximal hernia sac size and maximal fascial defect size (termed "hernia neck size") were measured in the sagittal plane on CT scan. Data are described as mean ± standard deviation and median (interquartile range)., Results: A total of 166 patients were included: 84 (51%) required emergent hernia repair and 82 (49%) did not undergo repair. Median follow-up was 19 (8-27) months. Patient groups were similar except the emergent repair group had more males (50% vs. 34%, p = 0.03), umbilical hernias (93% vs. 56%, p < 0.01), recurrent hernias (31% vs. 15%, p < 0.01), and lower mean BMI (34.3 ± 9.9 vs. 39.1 ± 6.5, p < 0.01). Hernia sac size did not differ between groups (5.8 [3.8-8.4] cm vs. 6.1 [3.5-11.8] cm, p = 0.45). Hernia neck size was significantly smaller in the emergent repair group (1.5 [2.3-3.5] cm vs. 3.4 [1.8-6.2] cm, p < 0.01). Hernia-to-neck ratio was significantly higher in the emergent repair group (2.4 [1.8-3.1] vs. 1.7 [1.1-2.9], p < 0.01)., Conclusion: This study demonstrated an association between higher HNR and increased risk of emergent ventral hernia repair. Future studies will evaluate the use of HNR to risk-stratify patients with ventral hernias in a safety-net hospital., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Blood or marrow transplantation (BMT) is an integral part of consolidation and/or salvage therapy for patients with acute myeloid leukemia (AML). With the growing population of AML survivors, there is a need to understand the quality of their survival., Materials and Methods: This multisite study included 1,369 2-year survivors who underwent BMT for AML between 1974 and 2014 at age ≥ 21 years and 1,310 siblings. Using Common Terminology Criteria for Adverse Events, severe/life-threatening and fatal chronic health conditions were identified. Multivariable regression analysis was used to compare the risk of severe/life-threatening conditions and health status between survivors and siblings, and to identify risk factors for health conditions among BMT survivors., Results: The prevalence of severe/life-threatening conditions was 54.9% in BMT survivors compared with 28.5% in siblings ( P < .001), yielding 3.8-fold higher odds of severe/life-threatening conditions (95% CI, 3.1 to 4.7) among the BMT survivors. The most prevalent conditions included subsequent neoplasms, diabetes, cataracts, venous thromboembolism, and joint replacement. Survivors were more likely to report poor general health (odds ratio [OR], 3.8; 95% CI, 2.8 to 5.1), activity limitation (OR, 3.7; 95% CI, 3.0 to 4.5), and functional impairment (OR, 2.9; 95% CI, 2.3 to 3.6). Among BMT recipients, the 20-year cumulative incidence of severe/life-threatening/fatal conditions was 68%. History of chronic graft-versus-host disease was associated with a higher risk of pulmonary disease (hazard ratio [HR], 3.1; 95% CI, 1.0 to 9.3), cataract (HR, 2.6; 95% CI, 1.4 to 3.8), and venous thromboembolism (HR, 2.3; 95% CI, 1.3 to 4.7). Relapse-related mortality (RRM) plateaued at 30%, whereas non-RRM increased to 50% at 30 years., Conclusion: The burden of severe/life-threatening conditions is substantially higher in BMT recipients when compared with an unaffected comparison group, contributing to an increasing incidence of non-RRM over time. Chronic graft-versus-host disease was an important risk factor for severe/life-threatening/fatal conditions among BMT recipients, informing the need for close monitoring to anticipate and manage morbidity.

Introduction: Although mortality rates after esophagectomy have decreased over the last 30 years, anastomotic leaks still commonly persist and portend significant morbidity. Previous studies have analyzed patient and perio-perative risk factors for leaks, yet data describing the association of leaks and an open or minimally invasive approach are lacking. The purpose of this study was to evaluate the impact of operative approach on leak rates and subsequent management of the leaks., Methods: We queried the Procedure-Targeted National Surgical Quality Improvement Program Database for patients undergoing esophagectomy for cancer in the years from 2016 to 2019. Patient demographics, disease-related information, peri-operative data, and short-term outcomes were reviewed. Multivariable, stepwise logistic regression analysis was performed to investigate factors associated with post-operative anastomotic leaks., Results: Of the 2696 patients who underwent esophagectomy for cancer, anastomotic leaks occurred in 374 (14%). Based on approach, 13% of open, 14% of laparoscopic, and 18% of robotic cases were complicated by leak ( P = .123). Multivariable analysis identified the following significant risk factors for leak: diabetes (OR 1.32, P = .047), hypertension (OR 1.32, P = .022), and longer operative time (OR 1.61, P < .001). The percentage of leaks requiring endoscopic or operative intervention was 75% for open, 79% for laparoscopic, and 54% for robotic cases ( P = .004)., Conclusions: Anastomotic leaks after esophagectomy for cancer occur frequently regardless of surgical approach. Furthermore, these leaks are managed differently after an open, laparoscopic, or robotic approach. Robotic esophagectomies complicated by anastomotic leak required less invasive management.

Objective: To understand patient attitudes and preferences when faced with the uncertainty of pregnancy of unknown location (PUL)., Design: Qualitative, interview-based study., Setting: University Hosptial., Patients: Patients aged >18 years sampled from the emergency department and a subspecialty fertility practice of a university hospital system., Interventions: Six to 8 weeks after resolution of a PUL, with an ultimate clinical outcome of either an intrauterine pregnancy, spontaneous abortion, or ectopic pregnancy. Participants underwent either surgical, medical, or expectant management., Main Outcome Measures: Thematic analysis of the virtual, semistructured interviews (45-60 minutes in length) conducted with participants to identify commonly expressed priorities was performed., Results: Interviews were completed from October 2020 to March 2021 until thematic saturation was achieved (n = 15). Resolution diagnoses included intrauterine pregnancy (26.7%, n = 4), ectopic pregnancy (40.0%, (n = 6), and spontaneous abortion (33.3%, n = 5). Moreover, 66.7% (n = 10) of the patients presented to the emergency department, whereas 33.3% (n = 5) presented to a subspecialty fertility clinic. All had desired pregnancies. Thematic analyses revealed 4 related priorities around PUL management: health of pregnancy ; health of self ; future fertility ; and diagnostic prediction and diagnostic certainty. The relative balance of these priorities was dynamic and evolved throughout the course of management with different outcomes. A second set of themes related to logistical preferences included mental health support , clarity of treatment and next steps , and continuity of care. Interrater reliability was validated with a pooled κ of >0.8. Limitations include that all participants had desired pregnancies, and the experiences of those who experienced different pregnancy outcomes may have been affected by recall bias., Conclusions: These data demonstrate novel themes around related priorities in patients with desired pregnancies diagnosed with a PUL previously underappreciated by clinicians. The balance of these priorities evolved throughout management with increasing information and clarity. Continually reevaluating relevant patient priorities and preferences is essential to the comprehensive management of PUL., (© 2022 Published by Elsevier Inc. on behalf of American Society for Reproductive Medicine.)

Purpose: We determined trends in life expectancy and cause-specific late mortality after autologous blood or marrow transplantation (BMT) performed over a 30-year period, using the BMT Survivor Study., Methods: We constructed a cohort of 4,702 individuals with hematologic neoplasms who lived ≥ 2 years after autologous BMT performed between 1981 and 2014 at three transplant centers. The end of follow-up was April 19, 2021. The primary exposure variable was autologous BMT performed in four eras: 1981-1999; 2000-2005; 2006-2010; and 2011-2014. Vital status and cause of death were obtained from National Death Index Plus program and Accurinct databases., Results: The median age at BMT was 53 years (range, 0-78 years), 58.7% were male, 67.8% were non-Hispanic White, and 28.3% had undergone transplantation between 2011 and 2014. Autologous BMT recipients experienced a 7-year reduction in life expectancy. The adjusted hazard of 5-year all-cause mortality declined over the four eras (reference: 1981-1999; hazard ratio [HR] 2000-2005 = 0.77; 95% CI, 0.62 to 0.94; HR 2006-2010 = 0.64; 95% CI, 0.51 to 0.79; HR 2011-2014 = 0.56; 95% CI, 0.45 to 0.71; P trend < .001), as did years of life lost (5.0 years to 1.6 years). The reduction in all-cause mortality was most pronounced among those transplanted for Hodgkin lymphoma or plasma cell dyscrasias, but was not observed among those transplanted for non-Hodgkin lymphoma or those conditioned with total-body irradiation. We also observed a decline in late deaths because of infection ( P trend < .0001; primarily for BMTs before 2006) and subsequent neoplasms ( P trend = .03; confined to decline in therapy-related myeloid neoplasm-related mortality) but not because of cardiovascular or renal disease., Conclusion: Late mortality among autologous BMT recipients has declined over a 30-year period. However, ongoing efforts are needed to mitigate development of infections, subsequent neoplasms, and cardiovascular and renal disease to further reduce late mortality., Competing Interests: Smita BhatiaThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript. Wendy LandierResearch Funding: Merck Sharp & Dohme (Inst) Stephen J. FormanStock and Other Ownership Interests: MustangBio, Lixte BiotechnologyConsulting or Advisory Role: Alimera Sciences, Lixte Biotechnology, MustangBioResearch Funding: MustangBioPatents, Royalties, Other Intellectual Property: MustangBio Daniel J. WeisdorfConsulting or Advisory Role: Incyte, Fate TherapeuticsResearch Funding: Incyte Mukta AroraConsulting or Advisory Role: Fate TherapeuticsResearch Funding: Syndax (Inst), Kadmon (Inst), Pharmacyclics (Inst)No other potential conflicts of interest were reported.

We examine the impact of conditioning intensity (low intensity: nonmyeloablative/reduced intensity vs high intensity: myeloablative) and total body irradiation (TBI) on the probability of live birth after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 1607 transplant survivors between 1974 and 2014 at age ≤45 years, with survival ≥2 years post-BMT and age at study ≥18 years. Closest-age, same-sex biologic siblings (n = 172) were 1:1 matched with 172 survivors. Survivors and siblings self-reported information on sociodemographic, chronic health conditions, and pregnancies. Within survivor analysis: the association between the primary exposure variable (no TBI/low-intensity conditioning; 200 to 800 cGy TBI/low-intensity conditioning; no TBI/high-intensity conditioning; >800 cGy TBI/high-intensity conditioning) and the odds of no post-BMT live birth were examined using multivariable logistic regression, adjusting for clinical and demographic variables. Median age at BMT was 31 years (IQR, 0 to 45), and median length of follow-up was 14.3 years (IQR, 2.4 to 41.4); 39.3% were autologous BMT recipients, and 46.6% were female. Overall, 120 (8.7%) survivors reported post-BMT live births. Receipt of >800 cGy TBI/high-intensity conditioning (odds ratio [OR], 3.7; 95% CI, 1.9-7.0; ref: no TBI/low-intensity conditioning) was associated with higher odds of reporting no live birth post-BMT. In contrast, 200 to 800 cGy TBI/low-intensity conditioning (OR, 1.3; 95% CI, 0.5-3.3), and no TBI/high-intensity conditioning (OR, 0.9; 95% CI, 0.5-1.7) were at similar risk of reporting post-BMT live birth as no TBI/low-intensity conditioning. Comparison with biologic siblings: Using conditional logistic regression, we found that BMT survivors were more likely to report no live birth (OR, 2.0; 95% CI, 1.2-3.3) compared with siblings. These findings could inform conditioning intensity options for patients wishing to preserve fertility post-BMT., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Epithelial cell-cell junctions remodel in response to mechanical stimuli to maintain barrier function. Previously, we found that local leaks in tight junctions (TJs) are rapidly repaired by local, transient RhoA activation, termed "Rho flares," but how Rho flares are regulated is unknown. Here, we discovered that intracellular calcium flashes and junction elongation are early events in the Rho flare pathway. Both laser-induced and naturally occurring TJ breaks lead to local calcium flashes at the site of leaks. Additionally, junction elongation induced by optogenetics increases Rho flare frequency, suggesting that Rho flares are mechanically triggered. Depletion of intracellular calcium or inhibition of mechanosensitive calcium channels (MSCs) reduces the amplitude of calcium flashes and diminishes the sustained activation of Rho flares. MSC-dependent calcium influx is necessary to maintain global barrier function by regulating reinforcement of local TJ proteins via junction contraction. In all, we uncovered a novel role for MSC-dependent calcium flashes in TJ remodeling, allowing epithelial cells to repair local leaks induced by mechanical stimuli., (© 2022 Varadarajan et al.)

Background: In a pregnancy of unknown location, an intrauterine fluid collection may represent either the early gestational sac of an intrauterine pregnancy, or as reported in previous literature, the pseudogestational sac of an ectopic pregnancy. Various sonographic features have been used to distinguish these 2 entities, but the clinical relevance of the pseudogestational sac remains unclear., Objective: To establish the incidence and relative rate of intrauterine fluid collection among ectopic and intrauterine pregnancies and to determine if the size of the collection differs between ectopic and intrauterine pregnancies STUDY DESIGN: We performed a retrospective cohort study of women with pregnancies of unknown location and pelvic or abdominal pain or bleeding. We calculated the incidences of intrauterine fluid collections among ectopic and intrauterine pregnancies, including both ongoing pregnancies and spontaneous abortions, given that that our focus was location and not viability. We calculated the relative risk of ectopic pregnancy if an intrauterine fluid collection was present, adjusting for age and vaginal bleeding. We compared the incidences of ectopic and intrauterine pregnancies among those with and without intrauterine fluid collections. Among those with collections, we compared the mean sac diameter between ectopic and intrauterine pregnancies in continuous and categorical fashions., Results: We evaluated 1236 women presenting with a pregnancy of unknown location. The rates of ectopic and intrauterine pregnancies (including spontaneous abortions) were 13.1% and 63.9%, respectively, with the remainder lost to follow-up. On ultrasound, 452 women (36.6%) had an intrauterine fluid collection. Eight of 162 ectopic pregnancies (4.9%) had a collection, compared with 363 of 789 intrauterine pregnancies (46.0%) (P=.01). Of the ectopics with a fluid collection, 5 had an adnexal mass. The presence of intrauterine fluid collection decreased the risk of ectopic pregnancy (adjusted relative risk, 0.09; 95% confidence interval, 0.05-0.19) after adjusting for age and the presence of bleeding. Among those with an intrauterine fluid collection, the rate of ectopic pregnancy was 2.2%, and the rate of intrauterine pregnancy was 97.8%; among those without a collection, the rate of ectopic pregnancy was 26.7%, and the rate of intrauterine pregnancy was 73.3%. The mean sac diameter did not differ between ectopic and intrauterine pregnancies, whether analyzed continuously or categorically., Conclusion: In the presence of an intrauterine fluid collection, the rate of ectopic pregnancy is very low. The size of the intrauterine fluid collection in a woman with a pregnancy of unknown location cannot be used to distinguish between a gestational sac and a pseudogestational sac. Pseudogestational sacs are uncommon and of little clinical consequence. In assessing pregnancies of unknown location, clinicians should incorporate the entire clinical picture, including other sonographic findings, to avoid incorrect or delayed diagnoses., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ruxolitinib is a Janus kinase (JAK) inhibitor that is FDA-approved for the treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease. Its use in treating various dermatologic diseases has been a topic of growing interest due to its favorable safety profile and targeted inhibition of several cytokines that perpetuate inflammatory skin conditions. The PubMed/MEDLINE and ClinicalTrials.gov databases were searched for literature on off-label uses of ruxolitinib in dermatology and ongoing trials studying its safety and efficacy. There is randomized controlled trial (RCT) evidence for the successful use of ruxolitinib in treating alopecia, atopic dermatitis, and psoriasis, with ongoing RCTs for its use in vitiligo. Smaller studies have confirmed the success of ruxolitinib in treating conditions such as dermatomyositis and hypereosinophilic syndrome, among others. No serious adverse effects were reported with the use of ruxolitinib in dermatology, but further research is needed to determine its efficacy, delivery route, and optimal dosing for treating dermatologic conditions.

Survival after blood or marrow transplantation (BMT) for inborn errors of metabolism (IEM) is excellent; however, the burden of morbidity in long-term survivors of BMT for IEM remains understudied. This study examined the risk of chronic health conditions (CHC) in ≥2-year survivors of allogeneic BMT for IEM performed between 1974 and 2014 using the BMT Survivor Study. In this retrospective cohort study, participants (or their parents; n = 154) reported demographic data and CHCs (graded using Common Terminology Criteria for Adverse Events version 5), and transplantation characteristics were obtained from institutional databases. Unaffected siblings (n = 494) served as a comparison group. Logistic regression was used to estimated the odds of severe/life-threatening CHCs compared with siblings. Cox proportional hazards regression was used to estimate factors associated with severe/life-threatening/fatal CHCs in survivors of BMT for IEM. Survivors of allogeneic BMT for IEM (leukodystrophies, 43.5%; mucopolysaccharidoses, 41.0%) were at 12.5-fold higher odds of severe/life-threatening CHCs (95% confidence interval [CI], 5.4 to 28.9) compared with their siblings. The mean 10-year post-BMT cumulative incidence of grade 3-5 CHCs was 47.5 ± 4.0%. Reduced-intensity conditioning (RIC) was associated with a 2.7-fold higher risk (95% CI, 1.2 to 6.2; P = .02) of any grade 3-5 CHC, a 6.7-fold higher risk of grade 3-5 cardiopulmonary conditions (95% CI, 1.3 to 35.4), and a 3.0-fold higher risk of severe hearing/vision deficits (95% CI, 1.4 to 6.6). Older (age >26 years) BMT survivors were significantly less likely to graduate from college (odds ratio [OR], 0.3; 95% CI, 0.1 to 0.7) or marry (OR, 0.01; 95% CI, 0.004 to 0.07) compared with their siblings. Survivors of BMT for IEM carry a significant burden of morbidities, which affects their ability to attain adult milestones. Efforts to reduce chronic health conditions in this population are needed., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Treatment of benign renal masses may often be unnecessary and can lead to significant morbidity, mortality, and health care costs. However, individual burdens such as decisional regret and financial costs associated with treatment are not well understood., Methods: Members of a support group who have been diagnosed with benign renal tumors were surveyed to evaluate demographic and clinical characteristics as well as decisional regret, using the modified Decision Regret Scale (DRS), and financial toxicity, using the Comprehensive Score for Financial Toxicity (COST). Predictors of decisional regret (DRS score >25) and financial toxicity were explored using logistic and linear regression analyses, respectively., Results: Of 70 respondents with complete data, 49 (70%) received definitive treatment while 21 (30%) elected surveillance. Decisional regret was expressed by 34/70 (49%) of patients and was associated with increasing age, smaller tumor size, and use of surveillance vs active treatment in univariable analysis. Patients reported significant financial toxicity from the diagnosis of a benign renal mass with a median COST score of 24, similar to a historical cohort of patients with stage IV solid organ cancers undergoing chemotherapy. Qualitative analysis of patient responses identified a lack of discussion by the provider of the likelihood of benign disease, postoperative complications, and financial burden as common themes in their experiences., Conclusions: High levels of decisional regret and financial toxicity were found among individuals with benign renal lesions regardless of treatment approach. Improved counseling and diagnostic tools may limit the psychological and financial burdens from these benign entities.

Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal in vitro models have struggled to recapitulate tau phenomena observed in vivo . Here, we aimed to define the minimal requirements to achieve endogenous tau aggregation in functional neurons utilizing human induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical neurons seeded with AD brain-derived competent tau species or recombinant tau fibrils displayed increases in insoluble, endogenous tau aggregates. Importantly, MAPT- wild type and MAPT- mutant hiPSC-neurons exhibited unique propensities for aggregation dependent on the seed strain rather than the repeat domain identity, suggesting that successful templating of the recipient tau may be driven by the unique conformation of the seed. The in vitro model presented here represents the first successful demonstration of combining human neurons, endogenous tau expression, and AD brain-derived competent tau species, offering a more physiologically relevant platform to study tau pathobiology., Competing Interests: J.D.M., C.N.P., N.V., P.R., T.K., K.Y., E.K., and X.L. are employees of AbbVie. A.D.W., J.T., K.T., and T.R.J. were employees of AbbVie at the time of the study. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication., (© 2021 The Authors.)

Importance: The past 4 decades have seen substantial changes in allogeneic blood or marrow transplantation (BMT) practice, with the overarching goal of expanding the eligible patient pool while optimizing disease-free survival., Objective: To determine trends in life expectancy and cause-specific late mortality after allogeneic BMT performed over a 40-year period., Design, Setting, and Participants: A retrospective cohort study of 4741 individuals who lived 2 or more years after allogeneic BMT performed between January 1, 1974, and December 31, 2014, was conducted at City of Hope, University of Minnesota, or University of Alabama at Birmingham. The end of follow-up was March 23, 2020., Exposures: Allogeneic BMT performed in 3 eras: 1974-1989, 1990-2004, and 2005-2014., Main Outcomes and Measures: All-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Information regarding vital status and cause of death was obtained from the National Death Index Plus and Accurint databases., Results: Of the 4741 individuals included in the study, 2735 (57.7%) were male; median age at BMT was 33 years (range, 0-75 years). The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% (95% CI, 11.0%-13.4%) at 30 years from BMT. In contrast, the incidence of nonrecurrence-related mortality continued to increase and was 22.3% (95% CI, 20.4%-24.3%) at 30 years. Leading causes of nonrecurrence-related mortality included infection (30-year cumulative incidence, 10.7%; standardized mortality ratio [SMR], 52.0), subsequent malignant neoplasms (30-year cumulative incidence, 7.0%; SMR, 4.8), cardiovascular disease (30-year cumulative incidence, 4.6%; SMR, 4.1), and pulmonary disease (30-year cumulative incidence, 2.7%; SMR, 13.9). Compared with the general population, the relative mortality remained higher at 30 or more years after BMT (SMR, 5.4; 95% CI, 4.0-7.1). The cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost). Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio (HR) of all-cause mortality declined over the 3 eras (1990-2004: HR, 0.67; 95% CI, 0.53-0.85; 2005-2014: HR, 0.52; 95% CI, 0.39-0.69; P < .001 for trend), as did years of life lost (1974-1989: 9.9 years [reference]; 1990-2004: 6.5 years; and 2005-2014: 4.2 years). The reduction in late mortality was most pronounced among individuals who underwent transplantation at ages younger than 18 years (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; reference: 1974-1989; P < .001 for trend) and those who received bone marrow (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR, 0.45; 95% CI, 0.29-0.69; reference: 1974-1989; P < .001 for trend)., Conclusions and Relevance: This cohort study noted that late mortality among recipients of allogeneic BMT has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general US population. Furthermore, the reduction in risk of late mortality appeared to be confined to those who underwent transplantation at a younger age or those who received bone marrow. Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population.

Allogeneic blood or marrow transplant (BMT) recipients are at risk for venous thromboembolism (VTE) because of high-intensity therapeutic exposures, comorbidities, and a proinflammatory state due to chronic graft-versus-host disease (GVHD). The long-term risk of VTE in allogeneic BMT survivors remains unstudied. Participants were drawn from the Blood or Marrow Transplant Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived ≥2 years after BMT. We analyzed the risk of VTE in 1554 2-year survivors of allogeneic BMT compared with 907 siblings. Using backward variable selection guided by minimizing Akaike information criterion, we created a prediction model for risk of late-occurring VTE. Allogeneic BMT survivors had a 7.3-fold higher risk of VTE compared with siblings (95% CI, 4.69-11.46; P < .0001). After a median follow-up of 11 years, conditional on surviving the first 2 years after BMT, the cumulative incidence of late-occurring VTE was 2.4% at 5 years, 4.9% at 10 years, and 7.1% at 20 years after BMT. The final model for VTE risk at 2 years post-BMT included History of stroke, chronic GVHD, Hypertension, Sex (male vs female) and Stem cell source (peripheral blood stem cells vs other) ("HiGHS2") (corrected C-statistics: 0.73; 95% CI = 0.67-0.79). This model was able to classify patients at high and low VTE risk (10-year cumulative incidence, 9.3% vs 2.4% respectively; P < .0001). The BMTSS HiGHS2 risk model when applied at 2 years post-BMT can be used to inform targeted prevention strategies for patients at high risk for late-occurring VTE., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Therapeutic practices for multiple myeloma (MM) have evolved, such that novel-agent-based therapy and autologous peripheral blood stem cell transplantation (aPBSCT) is the current standard. Whether cause-specific mortality has changed with time remains unclear. We examined late cause-specific mortality among patients with MM receiving aPBSCT from 1989 to 2014. We conducted a prospective cohort study using participants enrolled in the enrolled in the Blood or Marrow Transplant Survivor Study. We created 3 eras to reflect changing MM therapy: <2000 (pre-thalidomide); 2000-2005 (thalidomide); 2006-2014 (lenalidomide). We used Kaplan-Meier techniques and Cox regression for examining all-cause mortality, and subdistribution hazards models for cause-specific mortality. In total, 1906 patients were followed up for a median of 9.2 years. Conditional on surviving 2 years, the 10-year overall survival was 45%. The 10-year cumulative incidence of myeloma- and non-myeloma-related mortality was 33% and 13%, respectively. Multivariable analysis showed declining MM-specific mortality (subdistribution hazard ratio [SHR] 2000-2005  = 0.80, 95% confidence interval [CI], 0.60-1.07; SHR 2006-2014  = 0.46, 95% CI, 0.34-0.62; referent group: <2000), infection-related mortality (SHR 2000-2005  = 0.50, 95% CI, 0.29-0.85; SHR 2006-2014  = 0.35, 95%CI 0.21-0.60; referent group: <2000) and cardiovascular disease-related mortality (SHR 2000-2005  = 0.45, 95% CI 0.20-0.99; SHR 2006-2014  = 0.41, 95% CI 0.18-0.93; referent group: <2000). Although primary disease remains the major cause of late mortality, we observed a significant temporal decline in myeloma-, infection-, and cardiac-related late mortality over the past 25 years., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The first examples of rhodium-catalyzed carbonyl addition via hydrogen autotransfer are described, as illustrated in tandem butadiene-mediated carbonyl addition-redox isomerizations that directly convert primary alcohols to isobutyl ketones. Related reductive coupling-redox isomerizations of aldehyde reactants mediated by sodium formate also are reported. A double-labeling crossover experiment reveals that the rhodium alkoxide obtained upon carbonyl addition enacts redox isomerization without dissociation of rhodium at any intervening stage.

Gastroesophageal reflux disease (GERD) is steadily increasing in incidence and now affects 18% to 28% of the population in the United States. A thorough understanding of the pathophysiology underlying this disease is necessary to improve the current standard of care. Most GERD pathophysiology models focus on the lower esophageal sphincter (LES) as the key element which prevents esophageal reflux. More recent research has highlighted the crural diaphragm (CD) as an additional critical component of the GERD barrier. We now know that the CD actively relaxes when the distal esophagus is distended and contracts when the stomach is distended. Crural myotomy in animal models increases esophageal acid exposure, highlighting the CD's vital role. There are also multiple physiological studies in patients with symptomatic hiatal hernia that demonstrate CD dysfunction is associated with GERD. Finally, computer models integrating physiological data predict that the CD and the LES each contribute roughly 50% to the GERD barrier. This more robust understanding has implications for future procedural management of GERD. Specifically, effective GERD management mandates repair of the CD and reinforcement of the LES. Given the high rate of hiatal hernia recurrences, it seems that novel antireflux procedures should target this essential component of the GERD barrier. Future research should focus on methods to maintain crural integrity, decrease hiatal hernia recurrence, and improve long-term competency of the GERD barrier., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ustekinumab (STELARA), a human monoclonal antibody directed against IL-12 and IL-23, is FDA-approved to treat psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Increasing recognition of paradoxical skin reactions induced by older biologic therapies used for inflammatory bowel diseases (IBD), such as, adalimumab and infliximab, has led to the investigation of ustekinumab for the treatment of the cutaneous and gastrointestinal manifestations of IBD. In addition, ustekinumab may show efficacy in treating paradoxical cutaneous reactions to tumor necrosis factor-alpha (TNF-α) inhibitors. A search of the Medline/PubMed database, with additional citations obtained from the references section of relevant articles, yielded 22 articles that were included in this review. Ustekinumab is a safe and effective option for treating the cutaneous manifestations of IBD, such as, metastatic Crohn's disease and pyoderma gangrenosum. It is also an effective treatment for TNF-α inhibitor-induced paradoxical skin reactions, such as, psoriasis that do not remit spontaneously or with conventional treatment. Additional studies should focus on the optimal dosing of ustekinumab for dermatologic conditions beyond psoriasis., (© 2021 Wiley Periodicals LLC.)

Food insecurity correlates with poor physical and mental health in older individuals, but has not been studied in a laboratory animal model. This explorative study developed a laboratory mouse model for analyzing the impact of food insecurity on food consumption, stress coping mechanisms, exploratory behavior, and memory. 18-month-old CD-1 female mice were assigned to either the food insecurity exposure condition (31 mice, 8 cages) or the control condition (34 mice, 8 cages) by cage. Over four weeks, the mice that were exposed to food insecurity received varied, unpredictable portions of their baseline food consumption (50%, 75%, 125%, 150% of baseline) for four days, followed by ad libitum access for three days, to approximate the inconsistent access to food observed in households experiencing food insecurity. Behavioral tasks were conducted before and after food insecurity exposure. Mice in the food insecurity exposure condition ate less compared to control mice during food insecurity (two-way ANOVA: group x time interaction: F7,93 = 10.95, P < 0.01) but ate more when given access to high fat food (two-way ANOVA, group x time interaction: F1,14 = 11.14, P < 0.01). Mice exposed to food insecurity increased active escaping behaviors in the forced swim test (repeated measures two-way ANOVA, group x time interaction: F1,63 = 5.40, P = 0.023). Exploratory behaviors were unaffected by food insecurity. Mice exposed to food insecurity showed a reduction in memory (repeated measures two-way ANOVA, group x time interaction: F1,61 = 4.81, P = 0.037). These results suggest that exposure to food insecurity is associated with differences in food consumption patterns, active coping mechanisms, and memory. The behavioral changes associated with food insecurity may inform research on food insecurity's impact on health in elderly humans., Competing Interests: The authors have declared that no competing interests exist.

Ovarian cancer, in particularly high-grade serous ovarian cancer (HGSOC) and ovarian carcinosarcoma (OCS), are highly aggressive and deadly female cancers with limited treatment options. These tumors are generally unresponsive to immune check-point inhibitor (ICI) therapy and are referred to as immunologically "cold" tumors. Cell-based therapy, in particular, adoptive T-cell therapy, is an alternative immunotherapy option that has shown great potential, especially chimeric antigen receptor T cell (CAR-T) therapy in the treatment of hematologic malignancies. However, the efficacy of CAR-T therapy in solid tumors has been modest. This review explores the potential of another cell-based therapy, T-cell receptor therapy (TCR-T) as an alternate treatment option for immunological "cold" OC and OCS tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Dand, Doig, Papenfuss, Scott, Ho and Ooi.)