Citations

Abstract Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65–1.04)] but not BRAF-wildtype tumors [1.09 (0.97–1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case–control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. Significance: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity of B-cell lymphoma. Cell-of-origin (COO) classification of DLBCL is required in routine practice by the World Health Organization classification for biological and therapeutic insights. Genetic subtypes uncovered recently are based on distinct genetic alterations in DLBCL, which are different from the COO subtypes defined by gene expression signatures of normal B cells retained in DLBCL. We hypothesize that classifiers incorporating both genome-wide gene-expression and pathogenetic variables can improve the therapeutic significance of DLBCL classification. To develop such refined classifiers, we performed targeted RNA sequencing (RNA-Seq) with a commercially available next-generation sequencing (NGS) platform in a large cohort of 418 DLBCLs. Genetic and transcriptional data obtained by RNA-Seq in a single run were explored by state-of-the-art artificial intelligence (AI) to develop a NGS-COO classifier for COO assignment and NGS survival models for clinical outcome prediction. The NGS-COO model built through applying AI in the training set was robust, showing high concordance with COO classification by either Affymetrix GeneChip microarray or the NanoString Lymph2Cx assay in 2 validation sets. Although the NGS-COO model was not trained for clinical outcome, the activated B-cell–like compared with the germinal-center B-cell–like subtype had significantly poorer survival. The NGS survival models stratified 30% high-risk patients in the validation set with poor survival as in the training set. These results demonstrate that targeted RNA-Seq coupled with AI deep learning techniques provides reproducible, efficient, and affordable assays for clinical application. The clinical grade assays and NGS models integrating both genetic and transcriptional factors developed in this study may eventually support precision medicine in DLBCL.

Abstract Objectives Autoimmune hepatitis (AIH) is a form of severe hepatitis that can recur after orthotopic liver transplant (OLT). Presentation of AIH in patients with OLT who do not have a history of AIH is called de novo AIH (DNAIH). We evaluated the clinicopathologic characteristics of AIH and DNAIH. Methods Clinicopathologic and outcome measures of 11 patients with recurrent AIH (RAIH) and 22 with DNAIH identified between 2000 and 2017 were compared. Results Both cohorts showed female predominance. The mean clinical follow-up was 13 and 7.8 years in the in the RAIH and DNAIH groups, respectively (P = .1). Moderate portal inflammation was more common in patients with RAIH (64% vs 27%, P = .043). A trend was observed for more cases of DNAIH showing severe inflammation (36% vs 9%, P = .09) and submassive necrosis compared with RAIH (23% vs 0%, P = .086). A trend for more advanced fibrosis was also noted in the RAIH group (27% vs 5%, P = .059). Three patients with RAIH lost their grafts because of RAIH. Five-year disease-specific graft survival (GS) (P = .012) and overall GS (P = .015) were worse in patients with RAIH. Complement component 4d immunohistochemistry was positive in 2 patients with RAIH and 3 with DNAIH but showed no correlation with GS or other parameters. Conclusions RAIH seems to have a more aggressive clinical course than DNAIH and warrants closer clinical follow-up and aggressive treatment.

AbstractObjectiveDescribe hospital readmission for status epilepticus (SE) in the United States, and study potential risk factors for readmission.MethodsThis is a retrospective observational study using the Healthcare Cost and Utilization Project's 2016 Nationwide Readmissions Database. We studied patients of all ages admitted to the hospital due to SE.ResultsWe included 32 327 patients admitted for SE in 2016. 8.4% of these patients were readmitted for SE at least one more time within 2016 (cross‐sectional analysis). The incidence rate was 18 readmissions for SE per 1000 patient‐months. Among the survivors of the index admission for SE who had at least 6 months of follow‐up within this database (16 043 patients), the cumulative probability of having a readmission for SE at 1, 3, and 6 months from the index admission was approximately 3.5%, 7.5%, and 11%, respectively (time‐to‐event analysis). Patients with refractory epilepsy were more likely to have a readmission for SE compared to patients without refractory epilepsy (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.23‐1.82, adjusted P =.0006), and pediatric patients were more likely to have a readmission for SE compared to adult patients (HR 1.53, 95% CI 1.26‐1.87, adjusted P = .0003) during 6‐month follow‐up.SignificanceHospital readmissions for SE in the United States are frequent. Independent factors associated with readmission in this database were refractory epilepsy and pediatric age.

Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor (CAR) T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

AbstractObjectivesSpinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS.MethodsPatients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy.ResultsBetween 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P < 0.001).ConclusionsOur study suggests that socioeconomic disparities may exist in the utilization of SCS among hospitalized patients with CRPS I and FBSS the United States. However, confirming these data from other administrative databases, in the outpatient setting, may shed more insight.

Objective To summarize the current literature on non‐steroidal anti‐inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID‐19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. Background The use of non‐steroidal anti‐inflammatory drugs and corticosteroids in patients during the COVID‐19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID‐19 pandemic. Methods A detailed search of the scientific and popular literature was performed. Results There is limited literature pertaining to the safety of non‐steroidal anti‐inflammatory drugs and corticosteroids during the COVID‐19 pandemic. To date, there are no clear scientific data that preclude the use of non‐steroidal anti‐inflammatory drugs in the general population who may acquire COVID‐19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. Conclusion Scientific information regarding the COVID‐19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non‐steroidal anti‐inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID‐19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.