Joshua T. Hanson

Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection

Because ex vivo rapamycin generates murine Th2 cells that prevent Graft-versus-host disease more potently than control Th2 cells, we hypothesized that rapamycin would generate Th2/Tc2 cells (Th2/Tc2.R cells) that abrogate fully MHC-disparate hemopoietic stem cell rejection more effectively than control Th2/Tc2 cells. In a B6-into-BALB/c graft rejection model, donor Th2/Tc2.R cells were indeed enriched in their capacity to prevent rejection; importantly, highly purified CD4+ Th2.R cells were also highly efficacious for preventing rejection. Rapamycin-generated Th2/Tc2 cells were less likely to die after adoptive transfer, accumulated in vivo at advanced proliferative cycles, and were present in 10-fold higher numbers than control Th2/Tc2 cells. Th2.R cells had a multifaceted, apoptosis-resistant phenotype, including: 1) reduced apoptosis after staurosporine addition, serum starvation, or CD3/CD28 costimulation; 2) reduced activation of caspases 3 and 9; and 3) increased anti-apoptotic Bcl-xL expression and reduced proapoptotic Bim and Bid expression. Using host-versus-graft reactivity as an immune correlate of graft rejection, we found that the in vivo efficacy of Th2/Tc2.R cells 1) did not require Th2/Tc2.R cell expression of IL-4, IL-10, perforin, or Fas ligand; 2) could not be reversed by IL-2, IL-7, or IL-15 posttransplant therapy; and 3) was intact after therapy with Th2.R cells relatively devoid of Foxp3 expression. We conclude that ex vivo rapamycin generates Th2 cells that are resistant to apoptosis, persist in vivo, and effectively prevent rejection by a mechanism that may be distinct from previously described graft-facilitating T cells.

Brush cytology in the diagnosis of upper gastrointestinal malignancy

In a review of 196 cases of malignant neoplasms of the esophagus and stomach, endoscopically guided brush cytology at the initial examination appreciably improved diagnostic accuracy of esophageal lesions. However, cytology may have been superfluous when routinely applied to the evaluation of lesions intrinsic to the stomach. In these cases, when biopsy is negative while radiography or endoscopic appearance is that of mailgnancy, then brush cytology is recommended as an adjunct to repeated endoscopy.

High priority for hepatitis C screening in safety net hospitals: Results from a prospective cohort of 4582 hospitalized baby boomers

Low‐income populations are disproportionately affected by hepatitis C virus (HCV) infection. Thus, implementing baby boomer screening (born 1945‐1965) for HCV may be a high priority for safety net hospitals. We report the prevalence and predictors of HCV infection and advanced fibrosis or cirrhosis based on the Fibrosis‐4 score plus imaging for a baby boomer cohort admitted to a safety net hospital over a 21‐month interval with >9 months of follow‐up. Anti‐HCV antibody testing was performed for 4582, or 90%, of all never‐screened patients, of whom 312 (6.7%) tested positive. Adjusted odds ratios of testing anti‐HCV‐positive were 2.66 for men versus women (P < 0.001), 1.25 for uninsured versus insured (P = 0.06), 0.70 for Hispanics versus non‐Hispanic whites (P = 0.005), and 0.93 per year of age (P < 0.001). Among 287 patients tested for HCV RNA (91% of all anti‐HCV‐positive cases), 175 (61%) were viremic (3.8% overall prevalence in cohort), which was 5% less likely per year of age (P < 0.03). Noninvasive staging of 148 (84.6%) chronic HCV patients identified advanced fibrosis or cirrhosis in 50 (33.8%), with higher adjusted odds ratios of 3.21 for Hispanics versus non‐Hispanic whites/Asians (P = 0.02) and 1.18 per year of age (P = 0.001). Other factors associated with significantly higher adjusted odds ratios of advanced fibrosis or cirrhosis were alcohol abuse/dependence, obesity, and being uninsured. Conclusion: In this low‐income, hospitalized cohort, 4% of 4582 screened baby boomers were diagnosed with chronic HCV, nearly twice the rate in the community; one‐third had noninvasive testing that indicated advanced fibrosis or cirrhosis, which was significantly more likely for Hispanics, those of older age, those with obesity, those with alcohol abuse/dependence, and those who lacked insurance. (Hepatology 2015;62:1388–1395)

Implementing hospital-based baby boomer hepatitis c virus screening and linkage to care: Strategies, results, and costs

BACKGROUND/OBJECTIVE The US Preventive Services Task Force recommends 1-time hepatitis C virus (HCV) screening of all baby boomers (born 1945-1965). However, little is known about optimal ways to implement HCV screening, counseling, and linkage to care. We developed strategies following approaches used for HIV to implement baby boomer HCV screening in a hospital setting and report results as well as costs. DESIGN/PATIENTS Prospective cohort of 6140 baby boomers admitted to a safety-net hospital in South Texas from December 1, 2012 to January 31, 2014 and followed to December 10, 2014. PROCEDURES/MEASUREMENTS The HCV screening program included clinician/staff education, electronic medical record algorithm for eligibility and order entry, opt-out consent, anti-HCV antibody test with reflex HCV RNA, personalized inpatient counseling, and outpatient case management. Outcomes were anti-HCV antibody-positive and HCV RNA-positive results. RESULTS Of 3168 eligible patients, 240 (7.6%) were anti-HCV positive, which was more likely (P < 0.05) for younger age, men, and uninsured. Of 214 (89.2%) patients tested for HCV RNA, 134 (4.2% of all screened) were positive (chronic HCV). Among patients with chronic HCV, 129 (96.3%) were counseled, 108 (80.6%) received follow-up primary care, and 52 (38.8%) received hepatology care. Five patients initiated anti-HCV therapy. Total costs for start-up and implementation for 14 months were

High priority for hepatitis C screening in safety net hospitals

286,482. CONCLUSIONS This inpatient HCV screening program diagnosed chronic HCV infection in 4.2% of tested patients and linked >80% to follow-up care. Yet access to therapy is challenging for largely uninsured populations, and most programmatic costs of the program are not currently covered.

The new education frontier: clinical teaching at night.

Low‐income populations are disproportionately affected by hepatitis C virus (HCV) infection. Thus, implementing baby boomer screening (born 1945‐1965) for HCV may be a high priority for safety net hospitals. We report the prevalence and predictors of HCV infection and advanced fibrosis or cirrhosis based on the Fibrosis‐4 score plus imaging for a baby boomer cohort admitted to a safety net hospital over a 21‐month interval with >9 months of follow‐up. Anti‐HCV antibody testing was performed for 4582, or 90%, of all never‐screened patients, of whom 312 (6.7%) tested positive. Adjusted odds ratios of testing anti‐HCV‐positive were 2.66 for men versus women (P < 0.001), 1.25 for uninsured versus insured (P = 0.06), 0.70 for Hispanics versus non‐Hispanic whites (P = 0.005), and 0.93 per year of age (P < 0.001). Among 287 patients tested for HCV RNA (91% of all anti‐HCV‐positive cases), 175 (61%) were viremic (3.8% overall prevalence in cohort), which was 5% less likely per year of age (P < 0.03). Noninvasive staging of 148 (84.6%) chronic HCV patients identified advanced fibrosis or cirrhosis in 50 (33.8%), with higher adjusted odds ratios of 3.21 for Hispanics versus non‐Hispanic whites/Asians (P = 0.02) and 1.18 per year of age (P = 0.001). Other factors associated with significantly higher adjusted odds ratios of advanced fibrosis or cirrhosis were alcohol abuse/dependence, obesity, and being uninsured. Conclusion: In this low‐income, hospitalized cohort, 4% of 4582 screened baby boomers were diagnosed with chronic HCV, nearly twice the rate in the community; one‐third had noninvasive testing that indicated advanced fibrosis or cirrhosis, which was significantly more likely for Hispanics, those of older age, those with obesity, those with alcohol abuse/dependence, and those who lacked insurance. (Hepatology 2015;62:1388–1395)

Hospital-Based Hepatitis C Screening of Baby Boomers in a Majority Hispanic South Texas Cohort: Successes and Barriers to Implementation

Regulations that restrict resident work hours and call for increased resident supervision have increased attending physician presence in the hospital during the nighttime. The resulting increased interactions between attendings and trainees provide an important opportunity and obligation to enhance the quality of learning that takes place in the hospital between 6 PM and 8 AM. Nighttime education should be transformed in a way that maintains clinical productivity for both attending and resident physicians, integrates high-quality teaching and curricula, and achieves a balance between patient safety and resident autonomy. Direct observation of trainees, instruction in communication, and modeling of cost-efficient medical practice may be more feasible during the night than during daytime hours. To realize the potential of this educational opportunity, training programs should develop skilled nighttime educators and establish metrics to define success.

Response Selectivity for Species-Specific Calls in the Inferior Colliculus of Mexican Free-Tailed Bats is Generated by Inhibition

Objective. To comply with the 2012 CDC recommendations for hepatitis C virus (HCV) screening, we implemented a new HCV screening program for patients born between 1945 and 1965 at a South Texas safety-net hospital. Methods. Patients with no HCV diagnosis or prior HCV test received an automated order for HCV antibody (anti-HCV) tests combined with reflex HCV ribonucleic acid (RNA) polymerase chain reaction. An inpatient counselor educated anti-HCV-positive patients. A bilingual patient navigator assisted newly diagnosed chronic HCV patients with linkage to primary and specialty care. We examined results for Hispanic vs. non-Hispanic patients in the first 10 months of project implementation in 2013–2014. Results. Of 2,327 patients screened for HCV, the 192 (8%) patients who tested anti-HCV positive were younger than those who tested negative (56 vs. 58 years, respectively, p<0.001) and more likely to be male (p<0.001). Of the 167 anti-HCV-positive patients tested for HCV RNA, 108 (65%) were HCV RNA positive (5% of cohort). Barriers to care for HCV RNA-positive patients included a lack of health insurance, current substance abuse, incarceration, and homelessness. Hispanic HCV RNA-positive patients were more likely than non-Hispanic HCV RNA-positive patients to be substance abusers or incarcerated. Of all HCV RNA-positive patients, 103 patients (95%) received counseling, 94 patients (87%) were linked to primary care, 47 patients (44%) were linked to specialty care, and eight patients (7%) started treatment. Conclusion. The prevalence of anti-HCV-positive and chronically HCV-infected patients was higher than many Hispanic or non-Hispanic white cohorts. Most Hispanic patients newly diagnosed with chronic HCV had barriers to care for HCV infection that must be overcome if HCV screening is to reduce morbidity and mortality in this population.