Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease

Introduction

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity.

Case presentation

We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies.

Conclusion

High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

     

Pericardial mesothelioma presenting as constrictive pericarditis

A 46-year-old woman underwent pericardiocentesis and pericardial window for recurrent pericardial effusion. She presented 17 months later with signs and symptoms consistent with constrictive pericarditis. Cardiac magnetic resonance imaging revealed an infiltrative mass surrounding the pericardium. A transcutaneous core needle biopsy of the pericardium confirmed the diagnosis of pericardial mesothelioma.     

Sodium‐glucose co‐transporter (SGLT) and glucose transporter (GLUT) expression in the kidney of type 2 diabetic subjects

The sodium‐glucose co‐transporters (SGLTs) are responsible for the tubular reabsorption of filtered glucose from the kidney into the bloodstream. The inhibition of SGLT2‐mediated glucose reabsorption is a novel and highly effective strategy to alleviate hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2 inhibitor therapy is diminished due, in part, to a compensatory increase in the maximum reabsorptive capacity (Tm) for glucose in patients with T2DM. We hypothesized that this increase in Tm could be explained by an increase in the tubular expression of SGLT and glucose transporters (GLUT) in these patients. To examine this, we obtained human kidney biopsy specimens from patients with or without T2DM and examined the mRNA expression of SGLTs and GLUTs. The expression of SGLT1 is markedly increased in the kidney of patients with T2DM, and SGLT1 mRNA is highly and significantly correlated with fasting and postprandial plasma glucose and HbA1c. In contrast, our data demonstrate that the levels of SGLT2 and GLUT2 mRNA are downregulated in diabetic patients, but not to a statistically significant level. These important findings are clinically significant and may have implications for the treatment of T2DM using strategies that target SGLT transporters in the kidney.     

Role of MyD88-adaptor-like gene polymorphism rs8177374 in modulation of malaria severity in the Pakistani population

Introduction

The present study was designed to investigate the association between rs8177374 polymorphism and malaria symptoms due to exposure of Plasmodium vivax and Plasmodium falciparum.

Baseline anemia in patients undergoing percutaneous coronary intervention after an acute coronary syndrome—A paradox of high bleeding risk,high ischemic risk,and complex coronary disease

Objectives

To define more clearly the associations between baseline anemia, bleeding/ischemia risk, coronary disease severity, and outcomes by revascularization completeness.

Background

Anemia is associated with adverse outcomes in patients presenting with an acute coronary syndrome (ACS).

Methods and Results

Data was sourced from hospital databases for patients admitted with an ACS to a single center between 2011 and 2014. Using WHO anemia criteria, 468 (26.9%) of 1731 patients were anemic. In anemic patients, the mean CRUSADE score (34.6 ± 16.9 vs 24.6 ± 13.4, P < 0.0001), mean GRACE scores (165.8 ± 44.9 vs 141.6 ± 40.1, P < 0.0001), and percentage of patients with a high/very high CRUSADE score combined with a high GRACE score (69.3 vs 48.3%, P < 0.0001) was much greater than non‐anemic patients. Patients with baseline anemia were more likely to have left main or chronic occlusive disease, and more diseased vessels. The percentage of patients with residual disease (41.2 vs 30.7%, P < 0.0001), the number of residual diseased vessels (0.59 ± 0.83 vs 0.42 ± 0.72, P < 0.0001), and the percentage with a residual CTO (62.4 vs 56.4%, P = 0.036) were all higher than in non‐anemic patients. The duration of anti‐platelet therapy was significantly shorter in anemic patients (7.8 ± 4.3 vs 11.2 ± 2.4 months, P < 0.001). At 12‐months, mortality and stent thrombosis were more likely to occur in anemic patients, with the number of residual vessels associated with adverse survival regardless of anemia status.

Conclusions

Patients with anemia present with high ischemia and bleed risk scores, complex coronary disease, and have adverse outcomes. Incomplete revascularization was associated with worse survival regardless of anemia status.

     

Progression of Ulcerative Dermatitis Lesions in C57BL/6Crl Mice and the Development of a Scoring System for Dermatitis Lesions

Ulcerative dermatitis (UD) is a common, spontaneous condition in mice with a C57BL/6 background. Although initial lesions may be mild, UD is a progressive disease that often results in ulcerations or debilitating fibrotic contractures. In addition, lesions typically are unresponsive to treatment. Euthanasia is often warranted in severe cases, thereby affecting study outcomes through the loss of research subjects. Because the clinical assessment of UD can be subjective, a quantitative scoring method and documentation of the likely time-frame of progression may be helpful in predicting when animals that develop dermatitis should be removed from a study. Such a system may also be helpful in quantitatively assessing success of various treatment strategies and be valuable to clinical laboratory animal veterinarians. In this 1.5-y, prospective cohort study, we followed 200 mice to monitor the development and course of UD. Mice were examined every 2 wk. A clinical sign (alopecia, pruritus, or peripheral lymphadenopathy) was not identified that predicted development of UD lesions in the subsequent 2-wk period. Once UD developed, pruritus, the character of the lesion (single or multiple crust, coalescing crust, erosion, or ulceration), and the size of the lesion were the only parameters that changed (increased) over the course of the disease. Pruritus was a factor in the rapid progression of UD lesions. We used these findings to develop a quantitative scoring system for the severity of UD. This enhanced understanding of the progression of UD and the quantitative scoring system will enhance the monitoring of UD.Abbreviation: UD, ulcerative dermatitis; S number, scratching number; COL, character of lesionsUlcerative dermatitis (UD) is an idiopathic, spontaneous, debilitating syndrome of laboratory mice that is typically a disease of aged^1,19,43,46 C57BL/6 mice or genetically engineered mice on a C57BL/6 background.^1,19,43,44 Some reports discuss a similar condition in young, weanling mice that presents initially as alopecia.^24,42,44,45 Prevalence rates of UD between 4.1% to 21% have been reported.^1,6,19 Although no etiology has been identified, environmental factors,^{6,19,41,42,44} diet,^{5,29,41,42,46} season,^19,41,43,44 age at weaning,⁴² alopecia,^24,42,44,45 sex,^19,39,41,43 immune complex vasculitis,¹ follicular dysplasia,⁴⁴ lesion location,²⁰ and deficiencies in vitamin A metabolism⁴⁴ have all been implicated as predisposing factors for disease development. In addition, oronasal pain and chronic inflammation may lead to self-mutilation as a result of, initiating an “itch” response.¹⁰ UD is diagnosed by ruling out other causes of dermatitis in laboratory mice, such as fur mites,⁹ infections, fight wounds,¹⁷ strain phenotype,^15,35,40,49 and experimentally induced dermatitis.^4,50 Other diagnostic criteria are based on professional judgment and may include strain (C57BL/6 background),^1,19,44 lesion location (head and dorsal thorax),^1,19,43,44 intense pruritus,^1,19,44 peripheral lymphadenopathy,^6,19,39 and failure to respond to treatment.¹⁹ The rapid progression of UD lesions results in significant morbidity in laboratory mice.^6,19,44 Typically, the lesions progress to large, irregularly shaped, confluent ulcerations on the dorsal cervical and thoracic region.^1,19,39,44 As the lesions heal, contracted scar tissue forms, which can impair species-typical behaviors and mobility.^39,41,43,44 The presence of large dermal ulcerations or debilitating contractures affect animal welfare and typically necessitate euthanasia of affected mice. Although reports on the later stages of UD have been consistent,^{1,19,39,41,43,44} information on the initiation and progression of UD lesions is conflicting. Pruritus,^1,19,44 pain,¹⁰ and genetic predisposition^1,19,43,44 have been implicated as initiators of the disease. Alopecia, pruritus, erythema, and single or multiple(s) crust have all been reported as early signs of the disease.^{1,19,39,42-44} However, the majority of this information has been collected retrospectively, at timed necropsies, or based on anecdotal reports.Scoring systems are useful tools to evaluate clinical diseases in laboratory animals. For example, scoring systems have been published for tumors,^14,28 body condition,^14,28,47 and neurologic phenotype¹³ in mice to aid in assessment of clinical disease severity. Even though the progressive and severe nature of UD typically warrants eventual euthanasia, determining the severity of disease has typically been based on professional judgment,^1,39 subjective scoring,^{12,15,19,40,43,48,49} or postmortem histology.^40,44 A quantitative scoring system for UD in live mice has not been described and could greatly aid laboratory animal veterinarians and researchers in determining the severity of the disease and response to treatment.The purpose of the current study is to investigate clinical parameters that reflect the progression of UD to facilitate management and veterinary care of mice with UD. We followed 200 mice from 3 wk of age until the development of UD to determine the initial signs and progression of UD lesions. We hypothesized that mice will first develop signs of pruritus prior to any clinical lesion. From there, we predicted that clinical lesions will progress stepwise though the following stages of severity, with or without alopecia: (1) excoriations; (2) a single, small punctuate crust; (3) multiple, small punctuate crusts; (4) coalescing crust; (5) erosion; and (6) ulceration. In addition, we hypothesized that a quantitative, validated, and reliable UD scoring system can be created that is based on physical examination parameters that do, in fact, predict development and progression of UD. Having a more thorough understanding of the initiation and progression of ulcerative lesions likely will enhance our ability to predict the outcome for a given mouse and develop earlier end-points for that mouse. Furthermore, use of this scoring system will enable accurate monitoring of UD lesions.     

Influence of Bentonite on Mechanical and Durability Properties of High-Calcium Fly Ash Geopolymer Concrete with Natural and Recycled Aggregates

In this study, bentonite (a naturally occurring pozzolana) was incorporated as a partial replacement (up to 20%) for high-calcium fly ash (HCFA)-based geopolymeric natural aggregate concrete (GNAC) and geopolymeric recycled aggregate concrete (GRAC). The mechanical (compressive strength and splitting tensile strength), durability (chloride migration coefficient, water absorption, and acid attack resistance), and rheological properties (slump test, fresh density, and workability) were investigated. The results revealed that incorporation of bentonite (10 wt % with ordinary Portland cement) showed appreciable improvement in the strength and durability of both the GNAC and GRAC, though its effect is more significant for GRAC than the GNAC.     

Nonalcoholic Fatty Liver Disease after Liver Transplant

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the world. The rising prevalence of nonalcoholic steatohepatitis (NASH) has led to a 170% increase in NASH cirrhosis as the listing indication for liver transplantation from 2004 to 2013. As of 2018, NASH has overtaken hepatitis C as an indication for liver transplantation in the USA. After liver transplantation, the allograft often develops recurrent NAFLD among patients with known NASH cirrhosis. In addition to recurrent disease, de novo NAFLD has been reported in patients with other indications for liver transplantation. In this review, we will discuss the risk factors associated with recurrent and de novo NAFLD, natural course of the disease, and management strategies after liver transplantation.