Generalizable pipeline for constructing HIV risk prediction models across electronic health record systems.

OBJECTIVE: The HIV epidemic remains a significant public health issue in the United States. HIV risk prediction models could be beneficial for reducing HIV transmission by helping clinicians identify patients at high risk for infection and refer them for testing. This would facilitate initiation on treatment for those unaware of their status and pre-exposure prophylaxis for those uninfected but at high risk. Existing HIV risk prediction algorithms rely on manual construction of features and are limited in their application across diverse electronic health record systems. Furthermore, the accuracy of these models in predicting HIV in females has thus far been limited. MATERIALS AND METHODS: We devised a pipeline for automatic construction of prediction models based on automatic feature engineering to predict HIV risk and tested our pipeline on a local electronic health records system and a national claims data. We also compared the performance of general models to female-specific models. RESULTS: Our models obtain similarly good performance on both health record datasets despite difference in represented populations and data availability (AUC = 0.87). Furthermore, our general models obtain good performance on females but are also improved by constructing female-specific models (AUC between 0.81 and 0.86 across datasets). DISCUSSION AND CONCLUSIONS: We demonstrated that flexible construction of prediction models performs well on HIV risk prediction across diverse health records systems and perform as well in predicting HIV risk in females, making deployment of such models into existing health care systems tangible.

Epidemiology of Cancer-Associated Venous Thromboembolism in Patients With Solid and Hematologic Neoplasms in the Veterans Affairs Health Care System.

Importance: Identifying changes in epidemiologic patterns of the incidence and risk of cancer-associated thrombosis (CAT), particularly with evolving cancer-directed therapy, is essential for risk stratification. Objective: To assess the incidence of CAT over time and to determine pertinent patient-specific, cancer-specific, and treatment-specific factors associated with its risk. Design, Setting, and Participants: This longitudinal, retrospective cohort study was conducted from 2006 to 2021. Duration of follow-up was from the date of diagnosis until first venous thromboembolism (VTE) event, death, loss of follow-up (defined as a 90-day gap without clinical encounters), or administrative censoring on April 1, 2022. The study took place within the US Department of Veterans Affairs national health care system. Patients with newly diagnosed invasive solid tumors and hematologic neoplasms were included in the study. Data were analyzed from December 2022 to February 2023. Exposure: Newly diagnosed invasive solid tumors and hematologic neoplasms. Main Outcomes: Incidence of VTE was assessed using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification and natural language processing confirmed outcomes. Cumulative incidence competing risk functions were used to estimate incidence of CAT. Multivariable Cox regression models were built to assess the association of baseline variables with CAT. Pertinent patient variables included demographics, region, rurality, area deprivation index, National Cancer Institute comorbidity index, cancer type, staging, first-line systemic treatment within 3 months (time-varying covariate), and other factors that could be associated with the risk of VTE. Results: A total of 434 203 patients (420 244 men [96.8%]; median [IQR] age, 67 [62-74] years; 7414 Asian or Pacific Islander patients [1.7%]; 20 193 Hispanic patients [4.7%]; 89 371 non-Hispanic Black patients [20.6%]; 313 157 non-Hispanic White patients [72.1%]) met the inclusion criteria. Overall incidence of CAT at 12 months was 4.5%, with yearly trends ranging stably from 4.2% to 4.7%. The risk of VTE was associated with cancer type and stage. In addition to confirming well-known risk distribution among patients with solid tumors, a higher risk of VTE was observed among patients with aggressive lymphoid neoplasms compared with patients with indolent lymphoid or myeloid hematologic neoplasms. Compared with no treatment, patients receiving first-line chemotherapy (hazard ratio [HR], 1.44; 95% CI, 1.40-1.49) and immune checkpoint inhibitors (HR, 1.49; 95% CI, 1.22-1.82) had a higher adjusted relative risk than patients receiving targeted therapy (HR, 1.21; 95% CI, 1.13-1.30) or endocrine therapy (HR, 1.20; 95% CI, 1.12-1.28). Finally, adjusted VTE risk was significantly higher among Non-Hispanic Black patients (HR, 1.23; 95% CI, 1.19-1.27) and significantly lower in Asian or Pacific Islander patients (HR, 0.84; 95% CI, 0.76-0.93) compared with Non-Hispanic White patients. Conclusions and Relevance: In this cohort study of patients with cancer, a high incidence of VTE was observed, with yearly trends that remained stable over the 16-year study period. Both novel and known factors associated with the risk of CAT were identified, providing valuable and applicable insights in this current treatment landscape.

Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy.

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer Institute comorbidity index. Weighted Cox regressions with robust standard error were used to assess the hazard ratio (HR) and 95% confidence interval (CI). We found that among comparable advanced cancers, first-line ICI (n = 1823) and first-line chemo (n = 6345) had similar rates of VTE (8.49% for ICI and 8.36% for chemo at 6 months). The weighted HR was 1.06 (95% CI 0.88-1.26) for ICI versus chemo. In a subgroup analysis restricted to lung cancers, first-line ICI/chemo (n = 828), ICI monotherapy (n = 428), and chemo monotherapy (n = 4371) had similar rates of VTE (9.60% for ICI/chemo, 10.04% for ICI, and 8.91% for chemo at 6 months). The weighted HR was 1.05 (95% CI 0.77-1.42) for ICI versus chemo, and 1.08 (95% CI 0.83-1.42) for ICI/chemo versus chemo. In conclusion, ICI as a systemic therapy has a similarly elevated risk as cytotoxic chemo for VTE occurrence in cancer patients. This finding can inform future prospective studies exploring thromboprophylaxis strategies.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Interobserver Variability and Challenges in Intraoperative Frozen Section Evaluation of Pancreatic Margins in Pancreatectomy Specimens.

OBJECTIVE: Frozen-section evaluation of the pancreatic margin is challenging. We aimed to determine interobserver variability among gastrointestinal pathologists for the assessment of frozen sections of pancreatic margins with marked chronic pancreatitis and to determine the challenging histological features in discrepant cases. METHODS: We identified 45 patients who underwent pancreas resection for pancreatic ductal adenocarcinoma and showed marked chronic pancreatitis at pancreatic margin. Deidentified first levels of frozen-sections of the pancreatic margins from all cases were independently reviewed by 5 experienced gastrointestinal pathologists for the presence of carcinoma and/or high-grade dysplasia. RESULTS: Interobserver agreement among pathologists was calculated as kappa coefficients ([Formula: see text]). A consensus diagnosis for discordant cases was obtained after group review and discussion. Interobserver agreement for adenocarcinoma diagnosis was 87%, and there was "substantial agreement" (Fleiss [Formula: see text]=0.78, P<0.01) and "almost perfect agreement" (Brennan-Prediger [Formula: see text]=0.86, P<0.01). Using the final diagnosis based on frozen and permanent sections as the gold standard and the concordant read of at least 3 of 5 pathologists for comparison, the diagnosis of adenocarcinoma was made in frozen-sections of pancreas margins, with accuracy 98%, sensitivity 83%, specificity 100%, negative predictive value 97%, positive predictive value 100%, false negative rate 9%, and false positive rate 0%. CONCLUSIONS: We showed excellent interobserver agreement among gastrointestinal pathologists for diagnosis of adenocarcinoma on frozen sections of pancreatic margins with marked chronic pancreatitis. Missed adenocarcinoma at the margin was mainly caused by freezing or cautery artifacts or by overlooking a tiny focus of perineural invasion in a background of marked chronic pancreatitis. The evaluation of deeper levels led to perfect agreement.

Prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and biliary injury in liver biopsies from patients with non-alcoholic steatohepatitis.

The significance of portal tract histological changes in non-alcoholic fatty liver disease (NAFLD) remains unclear. In 2019, CymaBay Therapeutics halted clinical trials of seladelpar (a PPARδ agonist) because initial end-of-treatment liver biopsies of patients with non-alcoholic steatohepatitis (NASH) showed concerning features of portal inflammation with plasma cells, interface hepatitis and focal bile duct abnormalities. Adjudication concluded that these findings were present in the initial, as well as the subsequent biopsies. Thus, this study's aim was to determine the prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and features of bile duct damage in liver biopsies of adult patients with NAFLD. The pathology database was searched for cases of NAFLD, including steatosis alone and NASH, from January 2016 to October 2020. Liver biopsies were selected from age and sex matched adult patients with diagnoses of steatosis alone (n=10), NASH fibrosis stage 1 (n=10), stage 2 (n=10), stage 3 (n=10), and stage 4 (n=10). There were 24 males and 26 females with a mean age of 48 years (range 20-79). Exclusion criteria included age <18 years, daily alcohol intake >14 drinks per week, elevation of alkaline phosphatase level, comorbid chronic liver disease, or liver biopsy performed as part of a clinical trial for NASH. Control liver biopsies were selected from age and sex matched persons without significant steatosis and normal liver biochemical tests (n=10). Histological parameters were evaluated in 10 portal tracts or 10 septal areas in each liver biopsy. Portal inflammation and interface hepatitis were graded on a scale of 0-4. Portal plasma cells and bile duct damage were scored from 0-3. Ductular proliferation was assessed by CK7 immunostain and graded from 0-4. NASH biopsies with advanced fibrosis (stage 3 and 4) showed portal inflammatory infiltrates (score 2-3) with readily identifiable plasma cells (score 2), and mild to moderate interface hepatitis (score 2-3). All cases and controls showed focal, mild cholangiocyte changes, characterised by cytoplasmic vacuolation, segmental loss of nuclei, nuclear disarray and apoptosis. NASH patients with advanced fibrosis had frequent and diffuse cholangiocyte changes, along with focal lymphocytic cholangitis and moderate to marked ductular reaction (score 3-4). Histopathological features of advanced NASH frequently include increased portal inflammation with plasma cells, interface hepatitis, cholangiocyte injury and prominent ductular reaction.

Clinicopathologic correlations of superficial esophageal adenocarcinoma in endoscopic submucosal dissection specimens.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists' experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett's esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions. METHODS: We retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking. RESULTS: Two patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 µm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up. CONCLUSIONS: Our results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

A Phenotyping Algorithm to Identify People With HIV in Electronic Health Record Data (HIV-Phen): Development and Evaluation Study.

BACKGROUND: Identification of people with HIV from electronic health record (EHR) data is an essential first step in the study of important HIV outcomes, such as risk assessment. This task has been historically performed via manual chart review, but the increased availability of large clinical data sets has led to the emergence of phenotyping algorithms to automate this process. Existing algorithms for identifying people with HIV rely on a combination of International Classification of Disease codes and laboratory tests or closely mimic clinical testing guidelines for HIV diagnosis. However, we found that existing algorithms in the literature missed a significant proportion of people with HIV in our data. OBJECTIVE: The aim of this study is to develop and evaluate HIV-Phen, an updated criteria-based HIV phenotyping algorithm. METHODS: We developed an algorithm using HIV-specific laboratory tests and medications and compared it with previously published algorithms in national and local data sets to identify cohorts of people with HIV. Cohort demographics were compared with those reported in the national and local surveillance data. Chart reviews were performed on a subsample of patients from the local database to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the algorithm. RESULTS: Our new algorithm identified substantially more people with HIV in both national (up to an 85.75% increase) and local (up to an 83.20% increase) EHR databases than the previously published algorithms. The demographic characteristics of people with HIV identified using our algorithm were similar to those reported in national and local HIV surveillance data. Our algorithm demonstrated improved sensitivity over existing algorithms (98% vs 56%-92%) while maintaining a similar overall accuracy (96% vs 80%-96%). CONCLUSIONS: We developed and evaluated an updated criteria-based phenotyping algorithm for identifying people with HIV in EHR data that demonstrates improved sensitivity over existing algorithms.

Real World Long-term Assessment of The Efficacy of Tocilizumab in Patients with COVID-19: Results From A Large De-identified Multicenter Electronic Health Record Dataset in the United States.

BACKGROUND: Studies have shown conflicting results on the efficacy of tocilizumab (TCZ) for patients with COVID-19, with many confounders of clinical status and limited duration of the observation. Here, we evaluate the real-world long-term efficacy of TCZ in COVID-19 patients. METHODS: We conducted a retrospective study of hospitalized adult patients with COVID-19 using a large US-based multicenter COVID-19 database (Cerner Real-World Data; updated in September, 2020). The TCZ group was defined as patients who received at least one dose of the drug. Matching weight (MW) and a propensity score weighting method were used to balance confounding factors. RESULTS: A total of 20,399 patients were identified. 1,510 and 18,899 were in the TCZ and control groups, respectively. After MW adjustment, no statistically significant differences in all-cause mortality were found for the TCZ vs. control group (Hazard Ratio [HR]:0.76, p=0.06). Survival curves suggested a better trend in short-term observation, driven from a subgroup of patients requiring oxygen masks, BIPAP or CPAP. CONCLUSION: We observed a temporal (early) benefit of TCZ, especially in patients on non-invasive high-flow supplemental oxygen. However, the benefit effects faded with longer observation. The long-term benefits and risks of TCZ should be carefully evaluated with follow-up studies.

Retention in Care and Viral Load Improvement After Discharge Among Hospitalized Out-of-Care People With HIV Infection: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Understanding factors influencing retention in care (RIC) and viral load improvement (VLI) in people with HIV (PWH) who are out of care and hospitalized will assist in intervention development for this vulnerable population. METHODS: The study was a post hoc analysis of prospectively collected data. Hospitalized participants were enrolled if they were newly diagnosed with HIV during the hospitalization or out of HIV care. Participants completed surveys at baseline and 6 months postenrollment and laboratory studies of viral load (VL). Outcomes were RIC (2 completed visits, 1 within 30 days of discharge) and VLI (VL <400 or at least a 1-log10 decrease) 6 months after discharge. Univariate and multivariate regression analyses were conducted examining the contributions of predisposing, enabling, and need factors to outcomes. RESULTS: The study cohort included 417 participants enrolled between 2010 and 2013. The population was 73% male, 67% non-Hispanic black, 19% Hispanic, and 70% uninsured. Sixty-five percent had a baseline CD4 <200 cells/mm3, 79% had a VL >400 copies/mL or missing, and the population was generally poor with low educational attainment. After discharge from the hospital, 60% did not meet the definition for RIC, and 49% did not have VLI. Modifiable factors associated with the outcomes include drug use (including marijuana alone and other drugs), life instability (eg, housing, employment, and life chaos), and using avoidance coping strategies in coping with HIV. CONCLUSIONS: Hospitalized out-of-care PWH in the United States are at high risk of poor re-engagement in care after discharge. Interventions for this population should focus on improving socioeconomic stability and coping with HIV and reducing drug use.

Retrospective analysis of long-term outcome 10 years after liver transplantation for Wilson disease: experience over three decades.

We evaluated long-term outcomes for patients with Wilson disease (WD) after liver transplantation (LT) and searched for risk factors for poor survival. Retrospective analysis of UNOS/OPTN data identified 156 pediatric and 515 adult cases of LT for WD between 1987 and 2016. Comparison cases were 10 442 pediatric and 104 874 adult non-WD transplant recipients. Survival was calculated using Kaplan-Meier analysis. Recipient, donor, and surgical variables were compared by Cox regression. Survival rates 3, 5, and 10 years after LT for adult WD patients (87.5%, 85.4%, and 80.5%, respectively) were significantly higher than those for non-WD patients (P < 0.001); survival rates for pediatric WD patients (90.5%, 89.7%, and 86.5%, respectively) did not differ significantly from non-WD patients. Graft survival in adult and pediatric patients followed similar trends. Regression analysis identified older age, female gender, and use of life support at the time of transplant as risk factors for decreased survival for adults with WD, and younger age, male gender, obesity, and high serum creatinine at the time of transplant as risk factors for poor survival in pediatric recipients with WD. Presentation with fulminant liver failure was not associated with survival in WD patients. No donor characteristic predicted poor survival. Long-term patient and graft survival after LT is excellent for both adult and pediatric WD patients.

The Association of Unmet Needs With Subsequent Retention in Care and HIV Suppression Among Hospitalized Patients With HIV Who Are Out of Care.

BACKGROUND: Unmet needs among hospitalized patients with HIV may prevent engagement in HIV care leading to worse clinical outcomes. Our aim was to examine the role of unmet subsistence needs (eg, housing, transportation, and food) and medical needs (eg, mental health and substance abuse treatment) as barriers for retention in HIV care and viral load (VL) suppression. METHODS: We used data from the Mentor Approach for Promoting Patients' Self-Care intervention study, the enrolled hospitalized HIV patients at a large publicly funded hospital between 2010 and 2013, who were out-of-care. We examined the effect of unmet needs on retention in HIV care (attended HIV appointments within 0-30 days and 30-180 days) and VL suppression, 6 months after discharge. RESULTS: Four hundred seventeen participants were enrolled, 78% reported having ≥1 unmet need at baseline, most commonly dental care (55%), financial (43%), or housing needs (34%). Participants with unmet needs at baseline, compared to those with no needs, were more likely to be African American, have an existing HIV diagnosis and be insured. An unmet need for transportation was associated with lower odds of retention in care [odds ratio (OR): 0.5; 95% confidence interval (CI): 0.34 to 0.94, P = 0.03], even after adjusting for other factors. Compared to participants with no need, those who reported ≥3 unmet subsistence needs were less likely to demonstrate VL improvement (OR: 0.51; 95% CI: 0.28 to 0.92; P = 0.03) and to be retained in care (OR: 0.52; 95% CI: 0.28 to 0.95; P = 0.03). CONCLUSION: Broader access to programs that can assist in meeting subsistence needs among hospitalized patients could have significant individual and public health benefits.

Participants' perspectives on improving retention in HIV care after hospitalization: A post-study qualitative investigation of the MAPPS study.

Few interventions have been shown to improve retention in HIV care. We recently completed a randomized, controlled trial of a peer mentoring intervention, which failed to increase retention in care or HIV suppression. We sought to gain insight into this negative result and elicit suggestions for future interventions. We conducted semi-structured one-on-one interviews with a sub-sample of participants and all available interventionists after completion of the primary study. Interviews were coded by two researchers and thematically analyzed. Participants in the intervention arm (N = 16) reported good rapport with and benefit from peer mentoring and found the mentors helpful in facilitating the transition from hospital to out-patient clinic. Control arm participants (N = 9) reported similar emotional and social support benefits from the health educators. In both arms, ongoing challenges including completing paperwork, securing transportation, and rescheduling missed appointments were cited, along with internalized stigma and lack of will to seek care, despite the mentors' best efforts. Suggested improvements to the intervention included: more frequent contact with interventionists; additional support for mental health problems; and targeting overall health rather than a more selective focus on HIV. Mentors and health educators agreed with the participant-reported barriers and added that some participants were too sick to meaningfully participate in the intervention, while others appeared unwilling to engage with the interventionists in a meaningful way. Mentoring was highly acceptable and felt to be impactful, however it was not sufficient to overcome structural barriers or stigma and low motivation in some participants. The attention control intervention may have had an unintended positive impact. Future interventions should focus on broad aspects of health and well-being.

Feasibility of identifying out of care HIV-positive patients in a hospital setting and enrolling them in a retention intervention.

BACKGROUND: The hospital setting provides an opportunity to re-engage people living with HIV (PLWH) in HIV care. We developed and implemented a protocol to identify PLWH in a hospital setting. The aim of the current study was to report on our strategy to recruit hospitalized HIV patients into an intervention study, and to report on lessons learned for future studies. METHODS: Our protocol was developed based on experience of our research staff in recruiting HIV patients as well as clinical input from providers and administrators on delivering care in hospitalized settings. We identified hospitalized PLWH between 2010 and 2013 who were potentially eligible for an intervention study. Patients were identified by review of electronic medical records and clinician referral, followed by in-person screening to confirm eligibility. We examined factors related to identifying and enrolling hospitalized patients, and documented lessons learned. RESULTS: Key strategies included systematic medical record review followed by in-person screening, collaboration with staff, and flexibility in recruitment logistics. We identified 1801 PLWH hospitalized during the 3-year study period. Eighty-four percent (n = 1514) met the met the inclusion criteria based on medical record review. Of these, 48% (n = 733) were ineligible. Among eligible patients, 59% (n = 460) were enrolled. Only 3% (n = 23) of eligible patients declined; 84% (n = 321) were not enrolled because they were discharged before enrollment. Lessons learned included (1) needing to identify patients and deliver the intervention before hospital discharge, (2) limiting the complexity of the intervention, and (3) having research staff available on weekends and after hours. CONCLUSIONS: Targeted recruitment of hospitalized populations is a feasible and productive approach for finding and engaging PLWH who are newly diagnosed or out of routine care.

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S. METHODS: We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features. RESULTS: A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC. CONCLUSIONS: Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.

Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. METHODS: We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients' full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, the metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, and HCV), as well a HCC surveillance and outcomes, among HCC patients. RESULTS: NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%-12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%-68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%-80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%-3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared with patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P < .05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared with patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than patients with HCV-related HCC (77.5%; P < .01). However, the 1-year survival rate did not differ among patients with HCC related to different risk factors. CONCLUSIONS: NAFLD is the third most common risk factor for HCC in the VA population. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC received less HCC surveillance and treatment, a similar proportion survive for 1 year, compared with patients with alcohol-related or HCV-related HCC.

Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the integrator complex.

We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus-centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown. We also identified ASUN as a functional component of Integrator (INT), a multisubunit complex required for 3'-end processing of small nuclear RNAs. We now provide evidence that ASUN acts in the nucleus in concert with other INT components to mediate recruitment of dynein to the NE. Knockdown of other individual INT subunits in HeLa cells recapitulates the loss of perinuclear dynein in ASUN-small interfering RNA cells. Forced localization of ASUN to the cytoplasm via mutation of its nuclear localization sequence blocks its capacity to restore perinuclear dynein in both cultured human cells lacking ASUN and Drosophila asun spermatocytes. In addition, the levels of several INT subunits are reduced at G2/M when dynein is recruited to the NE, suggesting that INT does not directly mediate this step. Taken together, our data support a model in which a nuclear INT complex promotes recruitment of cytoplasmic dynein to the NE, possibly via a mechanism involving RNA processing.