Rahul Ravilla

Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.

Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors.

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related. Sarcoidosis-like syndrome/lymphadenopathy represents a challenging adverse event to the oncologist as it can be mistaken for progressive disease. Hence, awareness of such adverse event and obtaining a biopsy of the enlarged lymph nodes will confirm the diagnosis and avoid the unnecessary change of current therapies for those with stage IV disease or adding new ones for those with stage III disease. We report three cases of immunotherapy-related sarcoidosis-like syndrome/lymphadenopathy; two cases occurred during adjuvant ipilimumab for stage III surgically resected melanoma and one case during pemprolizumab for stage IV metastatic melanoma.

Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature

Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are published. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab-induced progressive necrotic myelopathy.

Do checkpoint inhibitors rely on gut microbiota to fight cancer

The field of gut microbiota is of growing interest, especially in the recent discoveries of its interaction with host immune responses, which when disrupted, can further alter immunity. It also plays a role in cancer development, its microenvironment and response to anticancer therapeutics. Several recently published experimental studies had explored the efficacy of modifying microbiota to enhance the response of checkpoint inhibitors, suggesting its beneficial function in cancer management and potential to be targeted as a therapeutic agent to enhance efficacy of checkpoint inhibitors. Here we review available evidence, mechanisms and hypotheses of its use to enhance cancer response.

Commentary: ATP: The crucial component of secretory vesicles: Accelerated ATP/insulin exocytosis and prediabetes

Department of Endocrinology and Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA, GIM Foundation, Little Rock, AR, USA, Department of Internal Medicine and Hospital Medicine, Christus Trinity Mother Frances Hospital, Tyler, TX, USA, Department of Policy, University of Arkansas for Little Rock, Little Rock, AR, USA, 5 Tutwiler Clinic, Tutwiler, MS, USA, Department of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA, 8 St. Vincent Infirmary (Catholic Health Initiative), Little Rock, AR, USA, 9 The Wright Center, Scranton, PA, USA

Spectrum of Cerebrovascular Disease in Patients with Multiple Myeloma Undergoing Chemotherapy—Results of a Case Control Study

[This corrects the article DOI: 10.1371/journal.pone.0166627.].

A Case of Anaplastic Large Cell Lymphoma Presenting in Leukemic Phase

Anaplastic lymphoma kinase (ALK) with positive Anaplastic Large Cell Lymphoma (ALCL) is has a distinct entity among the peripheral T-cell lymphomas. With a 5-year survival rate of 70%, it carries one of the best prognoses among peripheral T cell lymphomas. In rare instances, ALK positive ALCL presents in leukemic phase and it has a very poor prognosis with negligible number of cases reporting a survival rate of beyond one year. Following Case study as a research technique, the researchers tried to discuss about a patient affected by ALK positive ALCL in leukemic phase, associated with t (2;5)(p23;q35). The patient reported the clinic with a three week history of breathlessness, fever, diarrhoea, and axillary lymphadenopathy. His condition deteriorated in spite of rapid initiation of chemotherapy, and he succumbed to the high tumor burden. The study concludes that early diagnosis and institution of treatment is important in this regard. As this is a rare medical condition, with negligible alternative solutions, the present study underlines the need for further research in this area, emphasizing the need for newer therapies. It particularly stresses the need to examine the association of EBV and ALCL, with a specific reference to ALK-negative ALCL.

Myxoid mesenchymal neoplasm presenting as massive arm and chest wall oedema with pleural effusion.

Myxoid mesenchymal tumours are a heterogeneous group of neoplasms characterised histologically by their abundant mucoid and myxoid extracellular matrix (ECM). Encompassing a broad spectrum of clinical behaviour ranging from benign to malignant, there are more than 60 reactive and neoplastic entities currently classified under its domain. Its varied clinical and histopathologic features continue to pose a diagnostic challenge to clinicians and pathologists. Here, we describe a rare case of myxoid mesenchymal tumour presenting as oedema of the upper extremity with pleural metastasis and partial response to chemotherapy, which to the best of our knowledge has not yet been described in the literature.

Heparin-induced Thrombocytopenia in Patients Receiving Plasma Exchange

Heparin-induced thrombocytopenia is a rare complication of heparin use. Based on pathogenesis, it is classified into 2 types. Type 1 thrombocytopenia is a transient decrease in platelet count, which improves spontaneously, even with continuation of heparin. Heparin-induced thrombocytopenia Type 2, which is more severe, is caused by the formation of an antibody to the heparin-platelet factor 4 complex. The binding of the antibody to the complex results in platelet activation and widespread thrombosis by platelet consumption. Heparin-induced thrombocytopenia is a clinical diagnosis. A 4T score (Timing, degree of Thrombocytopenia, Thrombosis, other causes of Thrombocytopenia) is used to assess the likelihood of heparin-induced thrombocytopenia. It is treated by the discontinuation of heparin and the initiation of a nonheparin anticoagulant. We describe 2 cases of heparin-induced thrombocytopenia that arose in patients receiving heparin while on treatment with plasma exchange for other indications. Patient 1 was a 33-year-old man admitted to our hospital with newly diagnosed acute inflammatory demyelinating polyradiculopathy. Starting on day 3 of admission, he underwent 5 sessions of plasmapheresis, on alternating days. Thrombocytopenia was noticed on day 11. A 4T score of 5 was calculated, and subcutaneous heparin, which was being used for deep vein thrombosis prophylaxis, was discontinued. Heparin antibody assay was positive, with >50% inhibition and level >0.4 optical density units. The patient was started on bivalirudin. Platelets recovered to normal range (150-450 10/L) by day 19 (Figure).