The Adverse Event Landscape of Stem Cell Transplant: Evidence for aGVHD Driving Early Transplant Associated Toxicities.

Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the "ABA2" randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (aGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of aGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/platelet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major observations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 aGVHD, only aGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 aGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified aGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between aGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant aGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials.gov (#NCT01743131).

A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma.

PURPOSE: Given its heterogeneity and diverse clinical outcomes, precise subclassification of Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. EXPERIMENTAL DESIGN: We recruited 2,626 patients with BCLC-C HCC from multiple centers, comprising training/test (n = 1,693) and validation cohorts (n = 933). The XGBoost model was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-, intermediate-, high-, and very high-risk subgroups based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C). RESULTS: The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-, 12-, and 24-month survival of patients with BCLC-C were 0.800, 0.831, and 0.715, respectively-significantly higher than those of the conventional models, which were consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKI) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab-bevacizumab as the best therapy, particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high- to very high-risk subgroup. CONCLUSIONS: ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.

"Better at home": Mixed methods report of intricacies in pediatric febrile neutropenia management.

INTRODUCTION: Many febrile neutropenia (FN) episodes are low risk (LR) for severe outcomes and can safely receive less aggressive management and early hospital discharge. Validated risk tools are recommended by the Children's Oncology Group to identify LR FN episodes. However, the complex dynamics of early hospital discharge and burdens faced by caregivers associated with the FN episode have been inadequately described. METHODS: An adapted quality-of-life (QoL) survey instrument was administered by a convergent mixed methods design; qualitative and quantitative data from two sources, the medical record and the mixed methods survey instrument, were independently analyzed prior to linkage and integration. Code book was informed by conceptual framework; open coding was used. Mixed methods analysis used joint display of results to determine meta-inferences. RESULTS: Twenty-eight patient-caregiver dyads participated with a response rate of 87%. Of the 27 FN episodes, 51.8% (14/27) were LR and 40.7% (11/27) had an early hospital discharge. The LR and early hospital discharge groups had higher mean QoL scores comparatively. Meta-inferences are reciprocal influencers and expand the complex situation; FN negatively affects the entire family, and the benefits of hospital management were outweighed by risks and worsened symptoms, so an individualized approach to management and care at home was preferred. CONCLUSION: Early discharge of LR FN episodes positively impacts QoL, yet risk-stratified management for FN is intricately complex. Optimal FN management should prioritize the patient's overall health; shared decision-making is recommended and can improve care delivery. These results should be confirmed in a larger, more heterogeneous population.

Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD ('ocGVHD'), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

Timing of treatment for opioid use disorder among birthing people.

BACKGROUND: The number of pregnant women with opioid use disorder (OUD) has increased over time. Although effective treatment options exist, little is known about the extent to which women receive treatment during pregnancy and at what stage of pregnancy care is initiated. METHODS: Using a national private health insurance claims database, we identified women aged 13-49 who gave birth in 2006-2019 and had an OUD or nonfatal opioid overdose (NFOO) diagnosis during the year prior to or at delivery. We then identified women who received their first OUD treatment prior to or during pregnancy. In this cross-sectional study, we investigated how rates and timing of the initial OUD treatment changed over time. Furthermore, we examined factors associated with early initiation of OUD treatment among birthing people. RESULTS: Of the 7057 deliveries from 6747 women with OUD or NFOO, 63.3 % received any OUD treatment. Rates of OUD treatment increased from 42.9 % in 2006 to 69 % in 2019. Of those treated, in 2006, 54.5 % received their first treatment prior to conception and 24.2 % initiated care during the 1st trimester. In 2019, 68.9 % received their first treatment prior to conception, and 15.1 % initiated care during the 1st trimester. The percentage of women who were first treated in the 2nd trimester or later decreased from 21.2 % in 2006 to 16.1 % in 2019. Factors associated with early treatment initiation include being 25 years or older (age 25-34: aOR, 1.51, 95 % CI, 1.28-1.78; age 35-49: aOR, 1.82, 95 % CI, 1.39-2.37), living in urban areas (aOR, 1.28; 95 % CI, 1.05-1.56), having pre-existing behavioral health comorbidities such as anxiety disorders (aOR, 1.8; 95 % CI, 1.40-2.32), mood disorders (aOR, 1.63; 95 % CI, 1.02-2.61), and substance use disorder other than OUD (aOR, 2.56; 95 % CI, 2.03-3.32). CONCLUSION: Overall, rates of OUD treatment increased over time, and more women initiated OUD treatment prior to conception. Despite these improvements, over one-third of pregnant women with OUD/NFOO either received no treatment or did not initiate care until the 3rd trimester in 2019. Future research should examine barriers to OUD treatment initiation among pregnant women.

Consequences of the 2019 Public Charge Rule Announcement and Publication on Prenatal WIC Participation Among Immigrant Families: Evidence of Spillover Effects.

This study analyzed the effects of the announcement and publication of the 2019 Public Charge Rule on participation of the special supplemental nutrition program for women, infants, and children (WIC) among pregnant immigrants. A difference-in-differences approach was used to analyze the changes in prenatal WIC participation before and after the 2019 Public Charge Rule announcement and publication among immigrants relative to US natives. We identified 17,623,683 live singletons born in a hospital from 2015 to 2019. Compared to US natives, the odds of prenatal WIC participation among immigrants were 11.4% lower after the 2019 Public Charge Rule announcement, and 19% lower after the final rule was published. The results of this study suggest that pregnant immigrants may decide not to participate in the WIC program due to the fear of jeopardizing their immigration status after the announcement and publication of the 2019 Public Charge Rule.

Joint Display of Integrated Data Collection for Mixed Methods Research: An Illustration From a Pediatric Oncology Quality Improvement Study.

PURPOSE: Researchers often struggle to integrate quantitative and qualitative data. Joint displays of data collected using mixed methods provide a framework for supporting integration, yet the literature lacks methodologic articles illustrating in detail the iterative nature of constructing such displays. We demonstrate the process for creating a joint display for integrating the collection of data obtained by qualitative and quantitative methods. METHODS: Within a convergent mixed methods cohort study, the Early Discharge of Febrile Neutropenic Children with Cancer Study, we constructed a joint display to inform integrated collection of 2 forms of data (quantitative and qualitative) from 2 sources (a patient-caregiver mixed methods survey and a manual abstraction of medical records). RESULTS: In a first step, we used a data sources table to align related quantitative and qualitative data. The resulting table consisted of 2 side-by-side columns based on the mixed survey data. After several additional iterative steps, we constructed a final 6-column joint display. This final display delineated the separate data sources, linked constructs to the quantitative and qualitative variables within each source, and integrated the constructs across the separate data sources. CONCLUSIONS: Challenges of integration, though not unique to prospective mixed methods cohort studies, stem from the sheer volume of qualitative and quantitative information and the need to logically organize the data in preparation for integrated data analysis. Tailoring joint displays to specific studies is challenging, but mixed methods researchers who embrace the methodologic malleability can produce effective joint displays to illustrate the mixed data collection linkages and create a preliminary structure ultimately for organizing mixed data findings.

The Association of the Publication of a Proposed Public Charge Rule with Preterm Births among Uninsured Foreign-Born Latinx Birthing People in the United States.

Following the inauguration, the Trump administration authorized a series of anti-immigrant policies, including modifications to the public charge regulation. This study analyzed the effect of the publication of a proposed public charge rule in 2018 on the risk of preterm birth between uninsured and privately insured Latinx birthing people in the United States by using natality files from the National Center for Health Statistics. In total, 1,375,580 Latinx birthing people reported private insurance as their primary source of delivery from 2014 to 2019, while 317,056 Latinx birthing people reported self-pay as their primary source of delivery during the same period. After the publication of the proposed public charge rule in 2018, the odds of preterm birth among uninsured foreign-born Latinx birthing people increased by 6.2% compared with privately insured foreign-born Latinx birthing people (OR: 1.062; 95% CI: 1.016, 1.110). On the other hand, the odds of preterm births among uninsured US-born Latinx birthing people did not significantly increase after the publication of the proposed rule compared with privately insured US-born Latinx birthing people. These findings suggest the publication of the public charge rule proposed in 2018 may be associated with adverse birth outcomes among uninsured foreign-born Latinx birthing people in the United States.

Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events.

In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes. We tested the association between the trough after dose 1 (Ctrough_1) and grade (GR) 2 or 4 aGVHD (GR2-4 aGVHD) through day +100. An optimal Ctrough_1 threshold was identified via recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a 2-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 µg/mL. However, a higher Ctrough_1 (≥39 µg/mL, attained in ∼60% of patients on ABA2) was associated with a favorable GR2-4 aGVHD risk (hazard ratio, 0.35; 95% confidence interval, 0.19-0.65; P < .001), with a Ctrough_1 <39 µg/mL associated with GR2-4 aGVHD risk indistinguishable from placebo (P = .37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, and cytomegalovirus or Epstein-Barr virus viremia. These data demonstrate that a higher abatacept Ctrough_1 (≥39 µg/mL) was associated with a favorable GR2-4 aGVHD risk, without any observed exposure-toxicity relationships. This trial was registered at www.clinicaltrials.gov as #NCT01743131.

Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation.

BACKGROUNDCurrently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differences between practices across institutions. Herein, we aimed to define risk groups for SOS occurrence using 3 proteins: L-ficolin, hyaluronic acid (HA), and stimulation 2 (ST2). METHODSBetween 2017 and 2021, we prospectively accrued 80 pediatric patients across 4 US centers. Biomarkers were tested by ELISA blind to patient groupings and associated with SOS incidence on day 35 after HCT, and overall survival (OS) on day 100 after HCT. Cutpoints were identified using retrospective cohorts and applied to the prospective cohort.RESULTSCombination of the 3 biomarkers measured on day 3 after HCT in the prospective cohort provided 80% (95% CI 55%-100%) sensitivity and 73% (95% CI 62%-83%) specificity for risk of SOS occurrence. Patients with low L-ficolin were 9 times (95% CI 3-32) more likely to develop SOS, while patients with high HA and ST2 were 6.5 (95% CI 1.9-22.0) and 5.5 (95% CI 2.3-13.1) times more likely to develop SOS. These 3 markers also predicted worse day 100 OS - L-ficolin: HR, 10.0 (95% CI 2.2-45.1), P = 0.0002; HA: HR, 4.1 (95% CI 1.0-16.4), P = 0.031; and ST2: HR, 3.9 (95% CI 0.9-16.4), P = 0.04.CONCLUSIONL-ficolin, HA, and ST2 levels measured as early as 3 days after HCT improved risk stratification for SOS occurrence and OS and may guide risk-adapted preemptive therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT03132337.FUNDINGNIH.

Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology (PROFILE): Updated Report 2012-2020.

BACKGROUND: In January of 2011, the U.S. Food and Drug Administration released a safety communication regarding the potential association between breast implants and anaplastic large-cell lymphoma (ALCL). In 2012, the American Society of Plastic Surgeons, The Plastic Surgery Foundation, and the Food and Drug Administration signed a cooperative research and development agreement to develop the Patient Registry and Outcomes for Breast Implants and Anaplastic Large-Cell Lymphoma Etiology and Epidemiology (PROFILE) patient registry. METHOD: This is an updated report of registry findings. From August of 2012 to August of 2020, 330 unique, suspected, or confirmed cases of breast implant-associated (BIA) ALCL in the United States were reported to PROFILE, including 144 cases newly reported since the 2018 publication. RESULTS: Median time from implantation of any device to BIA-ALCL diagnosis was 11 years (range, 2 to 44 years). At the time of presentation, 91% of cases had local symptoms and 9% had concurrent systemic symptoms. The most common local symptom was seroma, seen in 79% of patients. All patients had a history of a textured device; there were no patients who had a confirmed smooth-only device history. Approximately 11% of the reported cases were diagnosed with stage 1A disease (tumor-node-metastasis staging classification). CONCLUSIONS: The PROFILE registry continues to be an essential tool in unifying the collection of granular-level data pertaining to BIA-ALCL. These data emphasize the critical importance of detailed tracking of BIA-ALCL cases, and will contribute significantly to our understanding of the relationship between breast implants and ALCL.

Tethered platelet capture provides a mechanism for restricting circulating platelet activation to the wound site.

Background: Puncture wounding is a longstanding challenge to human health for which understanding is limited, in part, by a lack of detailed morphological data on how the circulating platelet capture to the vessel matrix leads to sustained, self-limiting platelet accumulation. Objectives: The objective of this study was to produce a paradigm for self-limiting thrombus growth in a mouse jugular vein model. Methods: Data mining of advanced electron microscopy images was performed from authors' laboratories. Results: Wide-area transmission electron mcrographs revealed initial platelet capture to the exposed adventitia resulted in localized patches of degranulated, procoagulant-like platelets. Platelet activation to a procoagulant state was sensitive to dabigatran, a direct-acting PAR receptor inhibitor, but not to cangrelor, a P2Y12 receptor inhibitor. Subsequent thrombus growth was sensitive to both cangrelor and dabigatran and sustained by the capture of discoid platelet strings first to collagen-anchored platelets and later to loosely adherent peripheral platelets. Spatial examination indicated that staged platelet activation resulted in a discoid platelet tethering zone that was pushed progressively outward as platelets converted from one activation state to another. As thrombus growth slowed, discoid platelet recruitment became rare and loosely adherent intravascular platelets failed to convert to tightly adherent platelets. Conclusions: In summary, the data support a model that we term Capture and Activate, in which the initial high platelet activation is directly linked to the exposed adventitia, all subsequent tethering of discoid platelets is to loosely adherent platelets that convert to tightly adherent platelets, and self-limiting, intravascular platelet activation over time is the result of decreased signaling intensity.

The Implementation of the Tennessee Fetal Assault Law and Its Association With Out-of-State Births Among Residents of Tennessee.

INTRODUCTION: This study analyzed the association between the implementation of the Tennessee Fetal Assault Law (TFAL), which allowed prosecutors to incarcerate people who used substances during pregnancy, and out-of-state births among residents of Tennessee. METHODS: The main data source is vital records on singleton births in hospitals to people aged 15-44 years during the period January 2010 to June 2016. We include data from 33 states and the District of Columbia where birth certificate data are comparable over this time period. The statistical significance of the difference in outcomes observed before and after TFAL implementation was tested using a difference-in-differences analysis between Tennessee and the comparison group. RESULTS: After TFAL implementation, the odds of having an out-of-state birth increased by 13% for residents of Tennessee (odds ratio, 1.13; 95% confidence interval, 1.09-1.16) relative to residents of the comparison states. When we adopted different thresholds for travel distances to the birth hospital, the odds of residents of Tennessee having an out-of-state birth more than 75 miles away increased by 17% (odds ratio, 1.17; 95% confidence interval, 1.13-1.21) after TFAL implementation. CONCLUSION: The results of this study suggest that the implementation of a policy allowing incarceration of people who use substances during pregnancy is associated with an increase in out-of-state births, potentially putting pregnant people and their infants at greater risk.

Self-paced polling increases medical student engagement in recorded lectures and improves examination performance.

Engaging preclinical medical students in the curriculum is challenging. To address this challenge, the investigators developed and implemented self-paced polling with recorded lectures, in which students answered audience response questions at their own pace. In 2021, we retrospectively assigned second-year medical students (N = 165) as Active or Inactive based on their answered polling questions. We subdivided the Active group into two groups, a Live group who predominantly responded to polling in live classes and a Self-paced group who predominantly used polling with recorded lectures. Outcomes were academic performance on customized National Board of Medical Examiners (NBME) examinations and engagement. Compared with the Inactive group, the Self-paced group performed better on the customized NBME examination after extensive self-paced polling. Students answered a significantly larger proportion of questions correctly in self-paced polling compared with live polling. Students who used self-paced polling reported a positive experience and indicated they had emotional, behavioral, or cognitive engagement with the curriculum. This study introduces self-paced polling with recorded lectures, which medical educators can potentially use to enhance student engagement and academic performance.NEW & NOTEWORTHY More medical students utilize recorded lectures than live lectures. Self-paced polling questions allow students to participate while watching recorded lectures. Second-year medical students performed significantly better on examination after actively using the self-paced polling compared with inactive students. They also reported emotional, behavioral, and cognitive engagement with the course material while using the self-paced polling.

The IFNγ-PDL1 Pathway Enhances CD8T-DCT Interaction to Promote Hypertension.

BACKGROUND: Renal T cells contribute importantly to hypertension, but the underlying mechanism is incompletely understood. We reported that CD8Ts directly stimulate distal convoluted tubule cells (DCTs) to increase NCC (sodium chloride co-transporter) expression and salt reabsorption. However, the mechanistic basis of this pathogenic pathway that promotes hypertension remains to be elucidated. METHODS: We used mouse models of DOCA+salt (DOCA) treatment and adoptive transfer of CD8+ T cells (CD8T) from hypertensive animals to normotensive animals in in vivo studies. Co-culture of mouse DCTs and CD8Ts was used as in vitro model to test the effect of CD8T activation in promoting NCC-mediated sodium retention and to identify critical molecular players contributing to the CD8T-DCT interaction. Interferon (IFNγ)-KO mice and mice receiving renal tubule-specific knockdown of PDL1 were used to verify in vitro findings. Blood pressure was continuously monitored via radio-biotelemetry, and kidney samples were saved at experimental end points for analysis. RESULTS: We identified critical molecular players and demonstrated their roles in augmenting the CD8T-DCT interaction leading to salt-sensitive hypertension. We found that activated CD8Ts exhibit enhanced interaction with DCTs via IFN-γ-induced upregulation of MHC-I and PDL1 in DCTs, thereby stimulating higher expression of NCC in DCTs to cause excessive salt retention and progressive elevation of blood pressure. Eliminating IFN-γ or renal tubule-specific knockdown of PDL1 prevented T cell homing into the kidney, thereby attenuating hypertension in 2 different mouse models. CONCLUSIONS: Our results identified the role of activated CD8Ts in contributing to increased sodium retention in DCTS through the IFNγ-PDL1 pathway. These findings provide a new mechanism for T cell involvement in the pathogenesis of hypertension and reveal novel therapeutic targets.

Depression in Female Adolescents with Heavy Menstrual Bleeding.

OBJECTIVE: To assess the degree to which heavy menstrual bleeding is associated with depression, independent of hormonal contraception. STUDY DESIGN: We performed a retrospective cohort study of 1168 female adolescents 9-18 years old presenting to general pediatricians for heavy menstrual bleeding or well visits. Depression was the primary outcome and defined as a diagnosis in the health record. Univariable and multivariable regression models were fit to the data to identify factors associated with depression diagnosis. RESULTS: In total, 581 adolescents with heavy menstrual bleeding and 587 without heavy menstrual bleeding were included. Depression diagnoses occurred with greater frequency in youth with heavy menstrual bleeding compared with those without heavy menstrual bleeding (50.9% vs 24.2% P < .001; risk ratio 1.67, 95% CI 1.39-2.01) but did not significantly differ between those taking vs not taking hormonal contraception (risk ratio 0.99; 95% CI 0.84-1.17). Most patients with depression and heavy menstrual bleeding developed depression following or concurrent with heavy menstrual bleeding (261/296, 88%). Of these, 199 of 261 (76%) were treated with hormonal contraception, but the majority (168/199; 84%) were diagnosed with depression before initiation. CONCLUSIONS: Heavy menstrual bleeding is associated with depression diagnosis in female adolescents. The use of hormonal contraception was not associated with depression diagnosis in multivariable analysis, covarying heavy menstrual bleeding, age, body mass index, anxiety, sexual activity, and substance use. As hormonal contraception is often used to treat heavy menstrual bleeding, heavy menstrual bleeding may be partially driving previous reports of increased depression risk in those taking hormonal contraception.

Optimal timing of portal vein embolization (PVE) after preoperative biliary drainage for hilar cholangiocarcinoma.

BACKGROUND: Preoperative biliary drainage (PBD) followed by portal vein embolization (PVE) has increased the chance of resection for hilar cholangiocarcinoma (CCC). We aim to identify the optimal timing of PVE after PBD in patients undergoing hepatectomy for hilar CCC. METHODS: We retrospectively reviewed 64 patients who underwent hepatectomy after PBD and PVE for hilar CCC. The patients were classified into 3 groups: Group 1 (PBD-PVE interval ≤7 days), Group2 (8-14 days) and Group 3 (>14 days). The primary end points were 90 days mortality and grade B/C posthepatectomy liver failure (PHLF). RESULTS: There was no significant difference in primary end points between three groups. A marginally significant difference was found in the incidence of Clavien-Dindo grade ≥3 complications and wound infection (57.1% vs 38.1% vs 72.4%, p = 0.053 and 21.4% vs 38.1% vs 55.2%, p = 0.099). In multivariable analysis, Bismuth type IIIb or IV was independent risk factors for grade B/C PHLF (HR: 4.782, 95% CI 1.365-16.759, p = 0.014). CONCLUSIONS: Considering that the PBD-PVE interval did not affect PHLF, and the surgical complications increased as the interval increases, PVE as early as possible after PBD would be beneficial.

Interactive retrieval practice in renal physiology improves performance on customized National Board of Medical Examiners examination of medical students.

Retrieval practice improves long-term retention. Use of interactive retrieval practice in large group, in-person and online live classes, in combination with outside resources, is unreported for medical physiology classes. The primary study purpose was to compare student cohorts' performance with or without retrieval practice in renal physiology classes, relative to the national average on customized national examinations in renal physiology, nonphysiology, and all questions. The secondary purpose was to examine the students' educational experience. For the primary purpose, we used a nonequivalent group, posttest-only design. For the secondary purpose, we used cross-sectional and qualitative designs. We analyzed examination results of 684 students in four academic years. For renal physiology questions, students performed significantly better in years with retrieval practice compared with years without it (P < 0.001). There was no change in nonphysiology scores over the four years. Performance in all questions, too, significantly improved (P < 0.001). A large majority (86%) of students indicated retrieval practice helped them learn renal physiology. Student ratings of quality in online classes, which featured interactive retrieval practice, were higher than that of in-person classes (P < 0.001). Qualitative analysis revealed students found interactive retrieval practice, scaffolding, outside resources, and the instructor's teaching style helpful. Educators in medical physiology classes can use our findings to implement interactive retrieval practice.