Colorectal Cancer, Age, and Obesity-Related Comorbidities: A Large Database Study.

BACKGROUND AND AIMS: The association between obesity and colorectal cancer (CRC) is well established in older individuals, but evidence is limited in the younger population. The study aims to analyze the relationship of obesity and its related comorbidities in early-onset CRC (E-CRC) and compare it to late-onset CRC (L-CRC). METHODS: A retrospective, cross-sectional study was performed on average-risk individuals ≥ 20 years who were active patients in the commercial database, IBM Watson Health Explorys in the last 5 years. Individuals with CRC were compared to those without CRC across different age groups (20-39, 40-49, and 50-74 years). Individuals with CRC diagnosed < 50 years (E-CRC) were compared to those with CRC between 50 and 74 years (L-CRC). Variables included sex, smoking, obese BMI, diabetes mellitus type 2 (DM2), hypertension (HTN), and hyperlipidemia (HLD). Since Explorys aggregates population-level, de-identified data, approval from institutional review board was not required. RESULTS: Among 37,483,140 individuals, 162,150 cases of sporadic CRC were identified. Compared to the general population, obesity and HLD were independent risk factors for CRC across all age groups; DM2, HTN, and smoking were independent risk factors for CRC in men of all age groups and women with L-CRC. Compared to L-CRC, individuals with E-CRC had lower percentages of obesity-related comorbidities. CONCLUSION: In E-CRC, obesity, DM2, HTN, HLD, and smoking are independent risk factors for CRC among men; obesity and HLD are independent risk factors for CRC in women. These subgroups may benefit from a personalized screening approach to detect early-onset CRC.

High Burden of Obesity and Low Rates of Weight Loss Pharmacotherapy in Inflammatory Bowel Disease: 10-Year Trend.

Background: The prevalence of obesity and inflammatory bowel disease (IBD) has increased in the last decade. There is a paucity of data on the recent trend of obesity and the utilization of anti-obesity pharmacotherapy in IBD. We aimed to use a population-level database to analyze their trends. Methods: A retrospective analysis of population-level data from 2010 to 2019 was performed among individuals ≥18 years of age using a commercial database, IBM Explorys. The prevalence and trends of obesity, diabetes mellitus type 2 (DM2), essential hypertension, dyslipidemia and/or hyperlipidemia, sleep apnea, and anti-obesity pharmacotherapy were studied. Univariate analysis using chi-square test and trend analysis using the Cochrane Armitage test were performed. Results: Among 39 717 520 adults, 37.3% of IBD patients have a diagnosis of obesity (Crohn's disease 36.9% vs ulcerative colitis 38.5%, P < .0001). The proportion of IBD adults with obesity and metabolic comorbidities increased from 2010 to 2019: obesity (19.7%-30.1%), DM2 (8.3%-12.5%), hypertension (25.1%-33.9%), hyperlipidemia (22.1%-32.2%), and sleep apnea (4.1%-10.8%). All comparisons were statistically significant (P < .0001). Only 2.8% of eligible adults with obesity were prescribed anti-obesity pharmacotherapy in the last 10 years, with trends increasing from 1.4% to 3.6%, 2010-2019. Conclusions: With obesity being a harbinger for metabolic syndrome, the increase in obesity in IBD patients was accompanied by a concomitant increase in the diseases associated with obesity in the past decade. However, this alarming rise in obesity was accompanied by a disproportionately small increase in anti-obesity pharmacotherapy similar to general population.

DRESS syndrome in the setting of oxacillin therapy-a call for better patient preparedness: a case report.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms syndrome is a rare but severe and potentially life-threatening hypersensitivity reaction, with significant morbidity and mortality. The clinical presentation of drug reaction with eosinophilia and systemic symptoms may include extensive skin rash, fever, lymphadenopathy, internal organ involvement, eosinophilia, and atypical lymphocytosis, most commonly due to drug-induced reaction. Our case is a rare occurrence of drug reaction with eosinophilia and systemic symptoms syndrome in the setting of oxacillin therapy. CASE PRESENTATION: A 55-year-old Caucasian male presented to the emergency department on account of acute onset, 2-day history of generalized pruritic rash with associated fever, occurring 3 weeks after commencing therapy with intravenous oxacillin for methicillin-sensitive Staphylococcus aureus bacteremia. He had no known drug allergies. Two days prior to hospitalization, he had a telehealth visit with the infectious diseases specialist on account of his rash, and was recommended to use oral diphenhydramine. However, with the onset of fever and persistence of his rash, he was advised to discontinue the oxacillin and present to the emergency department. On examination, he was febrile at 101.2 °F and had a generalized blanchable maculopapular and morbilliform rash involving the face, trunk, upper and lower extremities, but sparing the palms, soles, and oral mucosa. He had palpable nontender lymph nodes in the cervical and inguinal regions bilaterally. Laboratory studies revealed atypical lymphocytosis, eosinophilia, neutrophilia, and elevated serum transaminases. He was started on intravenous diphenhydramine and admitted to the in-patient medical service. On the second day of hospitalization, his fever resolved. However, his rash was persistent and generalized, as well as elevated transaminases and an abnormal cell count on the second day of hospitalization. To complete his 6-week course of antibiotics for methicillin-sensitive Staphylococcus aureus bacteremia, he was switched to an alternative therapy with cefazolin, and he was scheduled for weekly follow-up assessments following hospital discharge. CONCLUSIONS: Healthcare providers should increasingly be aware of the significant morbidity and mortality attributable to drug reaction with eosinophilia and systemic symptoms syndrome and the potential medications which may incite such life-threatening reactions. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and prompt institution of management strategies can promote improved clinical outcomes. Enhanced patient-provider communication strategies should be implemented to better prepare patients for the likelihood of such drug reactions, with the goal of improving patient-centered care and adherence with treatment strategies.

Genetic, immune and vasoactive factors in the vascular dysfunction associated with hypertension in pregnancy.

INTRODUCTION: Preeclampsia (PE) is a major complication of pregnancy that could lead to maternal and fetal morbidity and mortality. The pathophysiological mechanisms of PE are not completely understood, but recent research has begun to unravel some of the potential mechanisms. AREAS COVERED: Genetic polymorphisms and altered maternal immune response may cause impaired remodeling of the spiral arteries; a potential early defect in PE. Inadequate invasion of cytotrophoblasts into the decidua leads to reduced uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia. Placental ischemia causes the release of biologically active factors such as anti-angiogenic factors, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and angiotensin II receptor autoantibodies. These vasoactive factors could cause systemic vascular endotheliosis and consequent increase in vascular resistance and blood pressure, glomerular endotheliosis causing proteinuria, cerebrovascular endotheliosis causing cerebral edema, seizures and visual disturbances, and hepatic endotheliosis, which may contribute to the manifestations of HELLP syndrome. PE-associated vascular endotheliosis causes a decrease in vasodilator mediators such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor, an increase in vasoconstrictors such as endothelin-1, angiotensin II and thromboxane A2, and enhanced mechanisms of vascular smooth muscle contraction such as intracellular Ca(2+), protein kinase C and Rho-kinase. Changes in matrix metalloproteinase activity and extracellular matrix cause vascular remodeling and further vasoconstriction. EXPERT OPINION: Some of the genetic, immune and vasoactive factors involved in vascular endotheliosis could be used as biomarkers for early detection, and as potential targets for prevention and treatment of PE.

The mind and liver test: a new approach to the diagnosis of minimal hepatic encephalopathy in resource-poor settings.

Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible.