Real-World Experience With Tofacitinib Dose De-Escalation in Patients With Moderate and Severe Ulcerative Colitis.

BACKGROUND & AIMS: Tofacitinib is associated with sustained steroid-free remission in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there are limited real-world data to guide decisions on the optimal maintenance regimen. We aimed to evaluate predictors and outcomes of disease activity after tofacitinib dose de-escalation in this population. METHODS: Included were adults with moderate-severe UC treated with tofacitinib between June 2012 and January 2022. The primary outcome was evidence of UC disease activity-related events: hospitalization/surgery, corticosteroid initiation, tofacitinib dose increase, or therapy switch. RESULTS: Among 162 patients, 52% continued 10 mg twice daily while 48% underwent dose de-escalation to 5 mg twice daily. Cumulative incidence rates of UC events at 12 months were similar in patients with and without dose de-escalation (56% vs 58%; P = .81). In univariable Cox regression among patients with dose de-escalation, an induction course with 10 mg twice daily for more than 16 weeks was protective of UC events (hazard ratio [HR], 0.37; 95% CI, 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC events (HR, 6.41; 95% 95% CI, 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and corticosteroid use at dose de-escalation (HR, 6.05; 95% CI, 2.00-18.35). Twenty-nine percent of patients with UC events had their dose re-escalated to 10 mg twice daily, with only 63% able to recapture clinical response at 12 months. CONCLUSIONS: In this real-world cohort, we observed a 56% cumulative incidence of UC events at 12 months in patients with tofacitinib dose de-escalation. Observed factors associated with UC events after dose de-escalation included induction course for fewer than 16 weeks and active endoscopic disease 6 months after initiation.

Racial Disparities in Endoscopy Cancellations During the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic has disrupted healthcare delivery including elective endoscopy. We aimed to determine the prevalence of endoscopy cancellations in the COVID-19 era and identify patient characteristics associated with cancellation due to the pandemic. METHODS: Medical charts were reviewed for adults who cancelled an outpatient endoscopic procedure from 5/2020 to 8/2020. The association of patient characteristics with cancellation of endoscopy due to COVID-19 was assessed using logistic regression. RESULTS: There were 652 endoscopy cancelations with 211 (32%) due to COVID-19, 384 (59%) due to non-COVID reasons, and 57 (9%) undetermined. Among COVID-19 related cancellations, 75 (36%) were COVID-19 testing logistics related, 121 (57%) were COVID-19 fear related, and 15 (7%) were other. On adjusted analysis, the odds of cancellation due to COVID-19 was significantly higher for black patients (OR 2.04, 95% CI 1.07-3.88, p = 0.03), while patients undergoing EGD (OR 0.56, 95% CI 0.31-0.99, p = 0.05) or advanced endoscopy (OR 0.18, 95% CI 0.07-0.49, p = 0.001) had lower odds of cancellation. The odds of cancelling due to COVID-19 testing logistics was significantly higher among black patients (OR 3.12, 95% CI 1.03-9.46, p = 0.05) and patients with Medi-Cal insurance (OR 2.89, 95% CI 1.21-6.89, p = 0.02). CONCLUSION: Black race is associated with an increased risk of COVID-19 related cancellation. Specifically, black patients and those with Medi-Cal are at increased risk of cancellation related to logistics of obtaining pre-endoscopy COVID-19 testing. Racial and socioeconomic disparities in access to endoscopy may be further amplified by the COVID-19 pandemic and warrant further study.

Direct Acting Antivirals Improve HCV Treatment Initiation and Adherence Among Underserved African Americans.

INTRODUCTION AND AIM: Adherence to hepatitis C (HCV) care was suboptimal in the interferon era among underserved African Americans (AA), but adherence data in the era of direct acting antivirals (DAA) is lacking in this population. We aimed to evaluate the impact of DAA on HCV care in underserved AA. MATERIAL AND METHODS: Clinical records of AAs undergoing HCV evaluation attending a safety net health system liver clinic were reviewed from 2006 to 2011 (pre-DAA), and January 1, 2014 to December 31, 2016 (post-DAA). RESULTS: 291 patients were identified (129 pre-DAA, and 162 post-DAA). Median age was 58, 66% were male, 91% had HCV genotype 1, and 70% had fibrosis ≥ stage 2. Post-DAA patients were older (60 vs. 53 years; p < 0.001), had higher rates of insurance (98 vs. 88%; p < 0.001), liver fibrosis ≥ stage 2 (77 vs. 61%; p = 0.048), ≥ 2 medical comorbidities (19 vs. 0.8%; p < 0.001), and median baseline log10 HCV RNA (6.07 vs. 5.81 IU/mL; p < 0.001), but lower median ALT (46 vs. 62 U/L; p < 0.001). Post-DAA, fewer patients were treatment ineligible (5.6 vs. 39%; p < 0.001) and more initiated therapy (71 vs. 8.5%; < 0.001), were adherent to HCV care (82 vs. 38%; p < 0.001), and achieved cure (95.7 vs. 63.6%, p < 0.001). Availability of DAA was independently associated with improved adherence to HCV care (OR 10.3, 95% CI 4.84-22.0). CONCLUSION: Availability of DAA is associated with increased treatment eligibility, initiation, adherence to HCV care, and cure in HCV-infected underserved AAs; highlighting the critical role of access to DAA in this population.

Sofosbuvir-Containing Regimens for Chronic Hepatitis C Are Successful in the Safety-Net Population: A Real-World Experience.

BACKGROUND: Vulnerable populations are disproportionately affected by hepatitis C virus (HCV) infection and experience high rates of health disparity. There are no data on real-world experience with highly efficacious direct-acting anti-HCV treatment in this population. AIMS: We aimed to evaluate the real-world experience with sofosbuvir-based regimens among a vulnerable HCV-infected population. METHODS: HCV treatment response was assessed among 204 patients who completed 12-24 weeks of sofosbuvir-based regimens (in combination with pegylated interferon and ribavirin, simeprevir, ledipasvir, or daclatasvir) at the San Francisco safety-net healthcare system liver specialty clinic between January 2014 and December 2015. Virologic response during therapy was assessed at weeks 4 and 8, end of therapy, and 12-week treatment discontinuation (SVR 12). RESULTS: Patient characteristics were median age 58 years, 60 % male, 42 % Caucasian (21 % black, 19 % Hispanic), 72 % had genotype 1 (23 % genotype 2 or 3), and the median baseline log10 HCV viral load was 6.1 IU/ml and alanine transaminase 63 U/l. Cirrhosis was present in 36 % (of whom 40 % were decompensated), and 18 % were HCV treatment-experienced. Overall, SVR 12 was achieved in 97 % (99 % genotype 1, 100 % genotype 2, 84 % genotype 3). Five of six (83 %) patients who relapsed had decompensated cirrhosis, and 67 % were also non-adherent to therapy. On-treatment virologic response did not impact SVR. CONCLUSIONS: High rates of sustained virologic response can be achieved in safety-net HCV-infected patients. Access to DAA-based regimens is critical to addressing HCV-related health disparity in this at-risk population.

Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies.

BACKGROUND: Peripheral arterial disease (PAD) is common but commonly unrecognized. Improved recognition of PAD is needed. We used high-throughput proteomic profiling to find PAD-associated biomarkers. METHODS AND RESULTS: Plasma was collected from PAD patients (ankle brachial index of <0.90; n=45) and subjects with risk factors but without PAD (n=43). Plasma was analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify 1619 protein peaks. The peak intensity of a 12-kDa protein was higher in PAD patients. Western blot analyses and immunoaffinity studies confirmed that this protein was beta2-microglobulin (B2M). In a validation study, B2M was measured by ELISA in plasma in age- and gender-matched PAD (n=20) and non-PAD (n=20) subjects. Finally, we studied a larger cohort of subjects (n=237) referred for coronary angiography but without known PAD. Plasma B2M levels were higher in PAD patients than in non-PAD patients with coronary artery disease. Plasma B2M correlated with ankle brachial index and functional capacity. Independent predictors of PAD were diabetes mellitus, age, and the combination of B2M and C-reactive protein level. CONCLUSIONS: In PAD patients, circulating B2M is elevated and correlates with the severity of disease independent of other risk factors. These findings might provide a needed biomarker for PAD and new insight into its pathophysiology. Further studies in other populations are needed to confirm the utility of measuring B2M in cardiovascular disease risk assessment.

Colonoscopy in Acute Lower Gastrointestinal Bleeding: Diagnosis, Timing, and Bowel Preparation.

Lower gastrointestinal bleeding is bleeding from a colonic source. Rapid colon purge using 4 to 6 L of polyethylene glycol followed by early colonoscopy, within 24 hours of presentation, is recommended to optimize the detection and management of bleeding sources. Although the data are mixed, early colonoscopy seems to be associated with higher detection of bleeding lesions and therapeutic interventions. There is no clear benefit for early colonoscopy in terms of reduced duration of stay, rebleeding, transfusion requirement, or surgery compared with patients undergoing elective colonoscopy. Further studies are needed to determine the effect of early colonoscopy on clinically important outcomes.

Use of Palliative Care Consultation for Patients with End-Stage Liver Disease: Survey of Liver Transplant Service Providers.

BACKGROUND/AIM: Palliative care services (PCS) are recommended to enhance quality of care for hospitalized patients. METHODS: We evaluated the attitudes of liver transplant (LT) providers and perceived barriers to PCS for their patients by conducting a web-based survey of intensive care unit nurses, postgraduate year 1 (PGY1) physician trainees, nurse practitioners, fellows, and attending physicians on the LT service at an academic medical center. RESULTS: The response rate was 44% (88/200). Providers agreed that LT and PCS are not mutually exclusive (86%, n = 76). Respondents reported confusion regarding criteria and timing for referral to PCS. Most suggested that referral is appropriate when death is imminent (78%, n = 69). Many providers felt that patients' depression (66%, n = 58) was poorly managed, although few identified that PCS were consulted for depression (28%, n = 25). Overall, 84% (n = 74) identified attending physicians as the main barrier to involving PCS, and attendings (93%, n = 82) were more likely than PGY1 (67%, n = 59) and nurses (55%, n = 48) to describe PCS as end-of-life care (p = 0.03). Nearly all LT providers agreed that patients welcomed goals of care discussions (83%, n = 73), were grateful for PCS (96%, n = 85), and received higher quality care with PCS (96%, n = 85). CONCLUSION: LT providers overwhelmingly report that PCS benefit patients and are consistent with LT goals even while patients are listed for LT. Barriers to PCS include confusion over referral criteria and describing PCS as end-of-life care by attending physicians. PCS teams may expand access for LT patients by establishing clear criteria for PCS referral and targeting educational interventions about palliative care to attendings.