Predictors of Respiratory Failure Development in a Multicenter Cohort of Inpatients With Cirrhosis.

INTRODUCTION: Hospitalized patients with cirrhosis can develop respiratory failure (RF), which is associated with a poor prognosis, but predisposing factors are unclear. METHODS: We prospectively enrolled a multicenter North American cirrhosis inpatient cohort and collected admission and in-hospital data (grading per European Association for the Study of Liver-Chronic Liver Failure scoring system, acute kidney injury [AKI], infections [admission/nosocomial], and albumin use) in an era when terlipressin was not available in North America. Multivariable regression to predict RF was performed using only admission day and in-hospital events occurring before RF. RESULTS: A total of 511 patients from 14 sites (median age 57 years, admission model for end-stage liver disease [MELD]-Na 23) were enrolled: RF developed in 15%; AKI occurred in 24%; and 11% developed nosocomial infections (NI). At admission, patients who developed RF had higher MELD-Na, gastrointestinal (GI) bleeding/AKI-related admission, and prior infections/ascites. During hospitalization, RF developers had higher NI (especially respiratory), albumin use, and other organ failures. RF was higher in patients receiving albumin (83% vs 59%, P < 0.0001) with increasing doses (269.5 ± 210.5 vs 208.6 ± 186.1 g, P = 0.01) regardless of indication. Admission for AKI, GI bleeding, and high MELD-Na predicted RF. Using all variables, NI (odds ratio [OR] = 4.02, P = 0.0004), GI bleeding (OR = 3.1, P = 0.002), albumin use (OR = 2.93, P = 0.01), AKI (OR = 3.26, P = 0.008), and circulatory failure (OR = 3.73, P = 0.002) were associated with RF risk. DISCUSSION: In a multicenter inpatient cirrhosis study of patients not exposed to terlipressin, 15% of patients developed RF. RF risk was highest in those admitted with AKI, those who had GI bleeding on admission, and those who developed NI and other organ failures or received albumin during their hospital course. Careful volume monitoring and preventing nosocomial respiratory infections and renal or circulatory failures could reduce this risk.

In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection.

IMPORTANCE: Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. AIM: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT. METHODS: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT. RESULTS: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition. CONCLUSION: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms.

The Impact of the COVID-19 Pandemic on IBD Care in Alberta: Patient and Provider Perspectives.

Objective: The COVID-19 pandemic necessitated changes in the delivery of ambulatory care for patients with inflammatory bowel disease (IBD), including transitioning many visits to virtual formats and delaying non-urgent assessments. We aimed to evaluate the impact of the COVID-19 pandemic on IBD patient care from health care providers' (HCP) and patients' perspectives. Methods: We administered a 42-question HCP survey and a 44-question patient survey, which evaluated HCP and patient experience and satisfaction with care delivery and delays in access to IBD care during the first wave of the COVID-19 pandemic. Results: Surveys were completed by 19.2% (24/125) HCPs and 25.8% (408/1581) patients. Overall, 82.7% of patients with IBD maintained their care without disruption. The majority of patients were satisfied with a transition to virtual care. All HCPs were willing to use virtual care in the future; however, 60% (14/24) of HCPs reported that virtual care was not equivalent to in-person visits. Patients reported concerns around access to health resources, the uncertainty of IBD-specific care, and fear and stress due to employment uncertainty and safety. Providers also reported concerns about patient safety, patient education, adequate remuneration and challenges with providing care for new patients on virtual platforms. Conclusion: While some delays in health care delivery occurred during the first wave of the pandemic, both patients and HCPs were satisfied with a transition to new models of care delivery. These models may remain in place post-pandemic and allow for flexibility in care delivery that is acceptable to both patients and HCPs.

Isolated Hepatic Chronic Ductopenic Rejection Requiring Liver Retransplant in the Absence of Kidney Graft Rejection After Combined Liver-Kidney Transplant: A Case Report.

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss.

International Classification of Diseases Codes are Useful in Identifying Cirrhosis in Administrative Databases.

BACKGROUND: Health administrative databases are essential to define patient populations, make socioeconomic predictions, and facilitate medical research and healthcare planning. The accuracy of this data is dependent on valid codes/coding algorithms. AIMS: The aim of this study was to systematically identify and summarize the validity of International Classification of Diseases (ICD) codes for identifying patients with cirrhosis in administrative data. METHODS: Electronic databases, MEDLINE (via Ovid), EMBASE (via Ovid), the Web of Science, and CINAHL (via EBSCOhost), were searched for validation studies which compared ICD codes related to cirrhosis to a clinical reference standard, and reported statistical measures of performance. RESULTS: Fourteen studies were included in the review. There was a large variation in the algorithms used to validate ICD codes to diagnose cirrhosis. Despite the variation, the positive predictive value (PPV) was greater than 84% and the specificity was greater than 75% in the majority of the studies. The negative predictive value (NPV) was lower, but still was associated with values greater than 70% in the majority of studies. Sensitivity data varied significantly with values ranging from 0.27 to 99%. CONCLUSIONS: Evaluated ICD codes for cirrhosis, including codes for chronic liver disease, cirrhosis-specific codes, and cirrhosis-related complications, have demonstrated variable sensitivity and reasonable specificity for the identification of cirrhosis. Additional research is needed to maximize the identification of persons with cirrhosis to avoid underestimating the burden of disease.

Efficacy of Hemospray (TC-325) in the Treatment of Gastrointestinal Bleeding: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Hemospray (TC-325) is now approved for use in gastrointestinal bleeding. Data regarding their use pattern, efficacy, complications, and impact on clinical outcomes is limited. METHODS: Electronic search from relevant databases was conducted up to January 2019. Etiologies, therapy characteristics, hemostasis rates, rebleed rates, additional procedures, complications and mortality rates were extracted and pooled. RESULTS: Twenty-seven articles were included for analysis (n=1916). Pooled hemostasis was 94.5%. Pooled rebleed rate within 3 days was 9.9%, and within 30 days 17.6%. Pooled repeat Hemospray use was 13.6%. Radiology guided embolization was required with rate of 3.3% and surgery at rate of 4.7%. Rate of adverse events directly attributable to Hemospray was 0.7%. 30-day mortality was 11.8%. Comparison of conventional endoscopic therapy to Hemospray augmented therapy demonstrated that Hemospray therapy had increased immediate hemostasis [odds ratio (OR) 4.40]. There was no difference in rate of rebleeding at 8 days (OR 0.52) or overall mortality at 30 days (OR 0.53). Benign nonvariceal bleeds, malignant bleeds, and postprocedural bleeds had similar rates of hemostasis but rebleed rate at 30 days was less for postprocedural bleeding. CONCLUSIONS: The addition of Hemospray to conventional therapy appears to increase immediate hemostasis but does not decrease rebleeding or mortality. As such, the use of Hemospray will likely be limited to clinical situations requiring urgent, but temporary, hemostasis to bridge to more definitive therapy.

Hepatic steatosis as measured by the computed attenuation parameter predicts fibrosis in long-term methotrexate use.

INTRODUCTION: To determine predictors of hepatic steatosis by the computed attenuation parameter (CAP) and fibrosis via transient elastography (TE) in persons on methotrexate (MTX) therapy with rheumatologic and dermatologic diseases. METHODS: A single-centred retrospective cohort study was performed. Patients on >6 months of MTX for a rheumatologic or dermatologic disease who had undergone TE from January 2015 to September 2019 were included. Multivariate analysis was performed to determine predictors of steatosis and fibrosis. RESULTS: A total of 172 patients on methotrexate were included. Psoriasis was the most frequent diagnosis (n = 55), followed by rheumatoid arthritis (n = 45) and psoriatic arthritis (n = 34). Steatosis (CAP ≥245 dB/m) was present in 69.8% of patients. Multivariate regression analysis revealed that diabetes mellitus (OR 10.47, 95% CI 1.42-75.35), hypertension (OR 5.15, 95% CI 1.75-15.38), and BMI ≥30 kg/m2 (OR 16.47, 95% CI 5.56-45.56) were predictors of steatosis (CAP ≥245 dB/m). Predictors of moderate to severe fibrosis (Metavir ≥F2 = TE ≥8.0 kPa) by multivariate regression analysis included moderate to severe steatosis (CAP ≥270 dB/m) (OR 8.36, 95% CI 1.88-37.14), diabetes mellitus (OR 2.85, 95% CI 1.09-7.48), hypertension (OR 5.4, 95% CI 2.23-13.00), dyslipidemia (OR 3.71, 95% CI 1.50-9.18), and moderate alcohol use (OR 3.06, 95% CI 1.2-7.49). CONCLUSIONS: In patients on MTX for rheumatologic and dermatologic diseases, hepatic steatosis as measured by CAP was common and moderate to severe steatosis predicted moderate to severe fibrosis.

A transcriptional toolbox for exploring peripheral neuroimmune interactions.

ABSTRACT: Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies, and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type-specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3 1/2 months after the initial injury. This raises the question of whether the commonly used categorisation of pain into "inflammatory" and "neuropathic" is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq data sets on neurons, macrophages, and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data mining of peripheral neuroimmune interactions. http://rna-seq-browser.herokuapp.com/.

Public awareness of acetaminophen and risks of drug induced liver injury: Results of a large outpatient clinic survey.

Acetaminophen is one of the most commonly consumed analgesics world wide. Generally perceived as a safe medication, it is the most common cause of acute liver failure in the United States with inadvertent hepatotoxicity in half of all cases. We therefore conducted a survey on the public perceptions of acetaminophen in patients attending the outpatient clinic in Vancouver, Canada. Among 928 patients who were asked, 765 completed the survey questionnaire. The majority of respondents were female (59%), Caucasian (61%), and educated beyond the secondary school level (81%). 23% reported using acetaminophen at least once a week. A significant minority were unaware of the potential liver toxicity of acetaminophen (24%), and knowledge of hepatotoxicity did not vary with education status. In terms of the medicinal composition of acetaminophen products, over half of the respondents (58%) did not know that extra strength preparations of acetaminophen contained the same drug but in a different dose. This knowledge was more prevalent among those with higher level of education (49% in graduate school educated respondents), but was still low overall. The knowledge that alcohol use with acetaminophen was more harmful was low (43%), but improved with level of education (P for trend 0.03). Among respondents who consumed alcohol regularly, 21% were consuming over 1.5 grams of acetaminophen at a time. These patients had similar harm perception to liver as patients who consumed lower doses of acetaminophen. Overall, in a large, well-educated cohort of patients, knowledge about the adverse effects of acetaminophen, the additional risks with alcohol and composition of various retailed products was suboptimal. We speculate that consumer ignorance is a significant reason why acetaminophen is a leading cause of acute liver failure.