Medication-specific variations in morphological patterns of injury in immune check-point inhibitor-associated colitis.

AIMS: A varied spectrum of histopathological changes has been associated with immune checkpoint inhibitor (ICI) colitis. This study was performed to evaluate the prevalence of different histopathological patterns of injury in patients with ICI colitis and their association with specific immune check-point inhibitors. METHODS AND RESULTS: Biopsies from patients with clinically and histologically confirmed ICI colitis were reviewed blindly to determine the predominant pattern of injury and to quantitate discrete histological parameters using the Geboes score. Paneth cell metaplasia, intraepithelial lymphocytes, abnormal subepithelial collagen and degree of crypt epithelial apoptosis was also recorded. A total of 86 patients with ICI colitis (ipilimumab, n = 14; ipilimumab + nivolumab, n = 29; nivolumab, n = 20 and pembrolizumab, n = 23) were included. The patterns of injury identified included diffuse active colitis (n = 22), chronic active colitis (n = 22), lymphocytic colitis (LC, n = 16), collagenous colitis (CC, n = 14), graft-versus-host disease-like colitis (n = 7) and mixed colitis (n = 5). Patients on ipilimumab were more likely to have a diffuse active colitis pattern without features of chronicity (P < 0.01) and less likely to have LC (P < 0.05) compared to other ICIs. LC and CC were more common in patients on nivolumab and pembrolizumab relative to other groups (P < 0.05). Chronic active colitis was most frequent in nivolumab patients (P < 0.05), and these patients had received more ICI doses and had been on ICI treatment longer compared to other treatment groups. CONCLUSIONS: ICI colitis should be considered in the differential diagnosis of all the common inflammatory patterns of colitis and shows medication specific differences in patterns of injury.

Tetralogy of Fallot With Absent Left Pulmonary Artery in a Patient Who Passed Critical Congenital Heart Disease Screening.

The literature on tetralogy of Fallot (TOF) is abundant. It is a fairly common cyanotic congenital heart disease. It results from the anterior malalignment of the conal septum resulting in the aberrant formation of the ventricular septum leading to a defect. This presents a very important clinical significance because the prognosis usually depends on the clinical evaluation and initiation of timely therapy. We present a two-week-old baby with normal birth history and an uncomplicated newborn nursery course. He also passed the Critical Congenital Heart Disease screen at 24 hours of life. The routine examination by the pediatrician led to further investigations and treatments, highlighting the importance of good history-taking and clinical examination skills.

Association of particles of lipoprotein subclasses with arterial stiffness in a high-risk working population: the Baptist Employee Healthy Heart Study (BEHHS).

BACKGROUND: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) morbidity and mortality. A risk factor-independent association of arterial stiffness with traditional lipids has been described extensively, but it is still unclear whether an independent relationship exists between arterial stiffness and particles of lipoprotein subclasses. METHODS: The Baptist Employee Healthy Heart Study (BEHHS) is a lifestyle intervention study examining the effects of web-based programs on reducing CVD risk in high-risk persons. Participants had their brachial arterial augmentation index (AI, a measure arterial stiffness) assessed using the EndoPAT 2000 device. Cardio IQ™ ion mobility lipoprotein fractionation was utilized for measurement of particles of lipoprotein subclasses. RESULTS: The population consisted of 182 participants, (74% women, 49% Hispanic) with a mean age of 52 ± 9 years. There was a significant trend association between quartiles of AI and total cholesterol, HDL-c, large LDL-p, small IDL-p, large IDL-p, and all subclasses of HDL particles (total HDL-p, small HDL-p, and large HDL-p). In logistic regression analysis, only HDL-c, total LDL-p, large LDL-p, small IDL-p, large IDL-p, total HDL-p, small HDL-p, and large HDL-p demonstrated significant independent association with AI. CONCLUSION: Several lipoprotein subclasses demonstrate independent significant associations with arterial stiffness. A safe and relatively inexpensive blood test may be useful in identifying subclinical atherosclerosis process in a relatively young high CVD risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01912209. Registered July 31, 2013.

Association Between Coronary Artery Disease and MicroRNA: Literature Review and Clinical Perspective.

BACKGROUND: Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. METHODS: A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online,(PUBMED/EMBASE/MEDLINE) search were conducted for relevant information. Search was limited to the articles published in English language and conducted on humans, January 2000 onwards. We excluded studies of heart surgery, coronary artery bypass grafting (CABG), angioplasty and heart transplant. Eighteen studies met the inclusion criteria. RESULTS: Seven out of 18 studies were multivariate, i.e. adjusted for age, gender, body mass index (BMI), smoking, hypertension, diabetes, and blood lipid profiles, while the remaining twelve studies were univariate analysis. Different sources of miRNAs were used, i.e. plasma/serum, microparticles, whole blood, platelets, blood mononuclear intimal and endothelial progenitor cells were investigated. Fourteen out of 18 studies showed up-regulation of different miRNA in CAD patients and in vulnerable plaque disease. Four out of 18 studies showed both the up-regulation and down-regulation of miRNA in the population, while only three studies showed down-regulation of miRNA. Various sources and types of miRNA were used in each study. CONCLUSION: This review gives an extensive overview of up-regulation and down-regulation of miRNA in CAD and non-CAD patients. The pattern of miRNA regulation with respect to CAD/non-CAD study subjects varies across individual studies and different parameters, which could be the possible reason for this aberrancy. We suggest further trials be conducted in future for highlighting the role of miRNA in CAD, which may improve both the diagnostic and therapeutic approaches to stratifying CAD burden in the general population.