Refractory Ulcerative Colitis With Associated Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis Syndrome Successfully Treated With Tofacitinib.

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare inflammatory condition associated with inflammatory bowel disease. Limited data exist on standardized management. We report a case of refractory SAPHO syndrome and ulcerative colitis (UC) treated successfully with tofacitinib. A 54-year-old man with UC presented with an intractable headache. A diagnosis of SAPHO syndrome was made based on the finding of sterile osteitis in the skull base and persistent severe UC. Symptoms, imaging, and endoscopy revealed persistent UC and osteitis despite multiple therapies. Tofacitinib was initiated and clinical remission was achieved. Tofacitinib is an effective treatment of refractory inflammatory bowel disease and SAPHO syndrome.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

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.

TNF-α inhibition in the setting of undiagnosed HIV infection: a call for enhanced screening guidelines.

BACKGROUND: Despite the risks of immunosuppression, recommendations regarding screening for HIV infection prior to initiation of biologic therapies targeting common rheumatologic disorders, including inflammatory bowel disease (IBD) and inflammatory arthritides, are limited. Few cases of patients started on biologics while living with undiagnosed HIV infection have been reported. METHODS: We report three cases of patients initiated on biologics in the absence of recent or concurrent HIV screening who developed refractory disease or unanticipated complications and were later found to have undiagnosed chronic HIV infection. RESULTS: In Case 1, a 53-year-old MSM with negative HIV testing 2 years prior presented with presumed rheumatoid arthritis. He did not respond to methotrexate, so adalimumab was started. HIV testing to evaluate persistent symptoms was positive 9 months later; CD4+ T-cell count was 800 cells/µl. Antiretroviral therapy (ART) resulted in resolution of symptoms, which were attributed to HIV-associated arthropathy. In Case 2, a 55-year-old woman with injection drug use in remission and no prior HIV testing presented with hidradenitis suppurativa. She started infliximab and methotrexate therapy with good response. After she developed weight loss and lymphopenia, an HIV test was positive; CD4+ T-cell count was 334 cells/µl. Biologic hidradenitis suppurativa therapy was discontinued, with subsequent poor hidradenitis suppurativa control. In Case 3, a 32-year-old MSM with no prior HIV testing presented with presumed IBD; infliximab and steroids were started. Symptoms progressed despite IBD-directed therapy, and he was diagnosed with extensive Kaposi sarcoma with visceral and cutaneous involvement, likely exacerbated by immunosuppression. HIV testing was positive; CD4+ T-cell count was 250 cells/µl. Kaposi sarcoma initially worsened due to ART-associated immune reconstitution inflammatory syndrome. He is now improving with systemic chemotherapy and ART. HIV-associated Kaposi sarcoma is presumed to be the underlying diagnosis. CONCLUSION: All three patients had elevated risk for HIV infection, and two had final diagnoses attributed to chronic HIV infection, not warranting therapeutic immunosuppression. Screening for HIV infection prior to initiation of biologic therapy should be incorporated into clinical practice guidelines.

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.

AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis. METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing. RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance. CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.

Safety of dual biological therapy in Crohn's disease: a case series of vedolizumab in combination with other biologics.

Uncertainty exists regarding safety and efficacy of dual biological therapy (DBT) in inflammatory bowel disease. We present four cases of DBT in Crohn's disease. Three patients had refractory disease non-responsive to biological monotherapy or combination therapy with immunomodulators. One patient had concomitant ankylosing spondylitis. DBT was implemented by combining vedolizumab with an anti tumour necrosis antibody or with ustekinumab. DBT was well-tolerated, though two patients did experience self-limited infections. The efficacy of DBT remains unproven but it appears promising as three of the four patients achieved clinical remission. Our case series contributes insight into the safety of DBT that incorporates vedolizumab for future efficacy studies.

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.

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.

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.

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.