Citations

AbstractElevated blood levels of C‐reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC‐specific mortality. Our study included 16 142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium. We identified 618 common single nucleotide polymorphisms (SNPs) associated with CRP levels from the NHGRI‐EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between SNPs and CRC‐specific mortality adjusting for age, sex, genotyping platform/study and principal components. We investigated their interactions with sex and lifestyle factors using likelihood ratio tests. Of 5472 (33.9%) deaths accrued over up to 10 years of follow‐up, 3547 (64.8%) were due to CRC. No variants were associated with CRC‐specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC‐specific mortality (corrected Pinteraction = .0004); women had higher CRC‐specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04‐1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82‐0.94). There was no evidence of interactions between CRP‐associated SNPs and alcohol, obesity or smoking. Our study observed a significant interaction between sex and a CRP‐associated variant in relation to CRC‐specific mortality. Future replication of this association and functional annotation of the variant are needed.

INTRODUCTION: The optimal instrument for assessing histologic disease activity in patients with eosinophilic esophagitis (EoE) is unclear. We assessed the responsiveness of the EoE Histologic Scoring System (EoE-HSS) when compared with that of the peak eosinophil count (PEC). METHODS: Histopathology slides were obtained from patients with EoE at baseline and after 8 weeks of treatment with swallowed topical budesonide or elimination diet. Two blinded gastrointestinal pathologists scored biopsies on the EoE-HSS, PEC, and 100-mm visual analog scale (VAS) of overall histologic severity. Change was defined as an improvement by ≥0.5 SD in baseline VAS. Responsiveness was quantified using the standardized effect size (SES) and the probability that the index distinguishes a patient with improvement from a patient without improvement, which is the area under the receiver operating characteristic curve (AUC). Longitudinal validity was assessed using Pearson correlations between changes in EoE-HSS and both PEC and VAS. RESULTS: The EoE-HSS grade (SES 2.18 [95% confidence interval, CI: 1.46–2.88]; AUC 0.73 [95% CI: 0.57–0.84]) and stage (SES 2.07 [95% CI: 1.37–2.77]; AUC 0.73 [95% CI: 0.58–0.84]) were highly responsive, similar to PEC (SES 1.44 [95% CI: 0.80–2.07]; AUC 0.73 [95% CI: 0.58–0.84]). The EoE-HSS grade and stage were more highly correlated with changes in VAS (grade 0.92 [95% CI: 0.86–0.95]; stage 0.89 [95% CI: 0.81–0.94]) than with changes in PEC (grade 0.74 [95% CI: 0.58–0.85]; stage 0.66 [95% CI: 0.47–0.80]). DISCUSSION: The EoE-HSS is highly responsive, performs similarly to PEC, and is better correlated with changes in overall histologic activity in patients with EoE.

AbstractBackgroundHypertrophic cardiomyopathy (HCM) presents with a hypertrophied left ventricle (LV). It is often associated with LV outflow tract obstruction (LVOTO) and a risk for sudden death. This study aimed to describe outcomes of patients with HCM who underwent liver transplant (LT).MethodsA retrospective review was conducted for patients diagnosed with HCM undergoing LT. Patient characteristics, preoperative echocardiography results, HCM risk of sudden cardiac death prediction model score, and 5‐year mortality were examined. A univariable Cox proportional hazards model was used to evaluate the association between risk factors and 5‐year mortality. All tests were two‐sided with the alpha level set at .05.ResultsTwenty‐nine patients were included in the analysis. Six patients (21%) had a perioperative cardiopulmonary complication. The 5‐year survival rate was 61% (95% CI, 45–82). The analyzed risk factors showed that 5‐year post‐LT survival was significantly predicted by maximal LV outflow tract gradient at rest > 60 mmHg (hazard ratio, 1.04 [95% CI, 1.01‐1.06]).ConclusionsPreoperative LV outflow tract resting gradient > 60 mmHg was associated with 5‐year post‐LT mortality. The results suggest the severity of LVOTO identified by echocardiography is a prognostic tool for patients with HCM after LT.

Abstract Background Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. Methods We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. Results A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. Conclusions Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

Histology is used to confirm the diagnosis of inflammatory bowel disease, exclude superimposed infections, and to evaluate for dysplasia. Histology has rarely been used to measure disease activity and guide therapy despite evidence that histologic measurements have value in predicting important clinical outcomes. More recently, there have been numerous studies supporting a role for histologic disease activity measurements in predicting a variety of outcomes including relapse, hospitalizations, steroid use, and dysplasia. The histologic assessment was superior to endoscopic measurements in many of these studies. This review will summarize the recent literature regarding histologic disease activity measurements in ulcerative colitis and Crohn disease. A detailed description of histologic scoring systems will also be provided to provide pathologists with the necessary tools to accurately measure disease activity.

Hemophagocytic lymphohistiocytosis (HLH) syndrome is a hyperinflammatory state that leads to life-threatening, disproportionate activation of the immune system and may be confused for and concomitantly exist with sepsis. However, its treatment differs from sepsis, requiring early initiation of immunosuppressive treatment. While HLH syndrome is more commonly diagnosed in children, internists and other primary care providers must be familiar with the diagnosis and treatment of adult patients with HLH in the hospital and outpatient setting. In this article, we review the essentials that an internist and other primary care providers managing adult HLH patients should know.

Background Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC). Methods A CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score. Results Three CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts. Conclusions This study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.