Appalanaidu Sasapu

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.

Acquired Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab

Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition who presented with left-sided weakness and seizure-like activity preceded by headache and easy bruising. She did not achieve optimal response to plasma exchange, corticosteroids, rituximab, and vincristine. We initiated treatment with eculizumab, following which she had durable remission that continued for 30 months after discontinuation of the drug. We later found that our patient has homozygous deletion in two closely related genes, complement factor H–related 1 and complement factor H–related 3.

A 16-Year-Old African American Girl With Necrotizing Lymphadenitis:

A 16-year-old African American woman presented to an outside hospital with a 3-week history of fatigue, intermittent fevers, nausea, and vomiting and swelling on the right side of the neck a week prior to presentation. She was treated with intravenous fluids and antibiotics but continued to have fever up to 101.7°F, and the swelling in the neck had enlarged. Review of systems was significant for decreased appetite, a 6-lb weight loss, night sweats, and headaches. She denied any rash, oral ulcers, visual changes, chest pain, dyspnea, dysurea, or diarrhea. Her past medical history and family history were noncontributory except for a distant relative in her father’s family having lupus. On physical exam, the vital signs were significant for temperature of 101.4°F, blood pressure of 131/86, and heart rate of 96. A swollen (3 × 4 cm), tender right anterior cervical lymph node, in addition to several smaller lymph nodes, were seen in the same region. Her joints showed no signs of swelling or arthritis. Laboratory analysis revealed leukopenia with a white blood cell count of 3.5 × 10/μL (3.7-11.7), a hemoglobin level of 8.3 g/dL (10.2-14.0), a hematocrit of 25% (31%-42%), and platelets count of 124 × 10/μL (135-450). Her creatinine level was 1.3 mg/dL (0.1-1.4); serum lactate dehydrogenase (LDH) 267 mg/dL, and uric acid 5.7 mg/dL. Erythrocyte sedimentation rate and C-reactive protein were elevated at 135 mm/h and 13 mg/dL, respectively. Urine analysis showed 15 to 19 red blood cells/hpf, and 1+ protein. Blood and urine cultures were negative. Epstein-Barr virus and cytomegalovirus titers were normal. HIV and hepatitis panel were negative. Purified protein derivative (PPD) skin test was negative. The chest radiograph and CT scan of the abdomen were normal. Ophthalmological consult showed no intraocular inflammatory changes. Because malignancy was still a strong possibility, an excisional biopsy of the right cervical lymph node was done, which showed necrotizing lymphadenitis with stellate microabscesses harboring prominent neutrophilic infiltrates surrounded by fibrin and an ill-defined histiocytic rim, outside of which were lymphocytes (Figure 1). Lymph node acid fast bacillus (AFB) stain, bacterial cultures, and fungal cultures were negative. Based on the biopsy results, atypical Kikuchi-Fujimoto’s disease (KFD) alone versus KFD associated with an underlying autoimmune disease was suspected. Further testing showed positive antinuclear antibodies (ANA) with a titer of 1:2560, positive antibodies to ds-DNA, Smith, RNP, and SSA antibodies. The SSB, SCL-70, and Jo-1 antibodies were negative. Serum was high, at IgG 2460 mg/dL; C3 and C4 levels were low, at 17.9 and 3.3 mg/dL, respectively. ACE levels were normal. Renal biopsy was performed to evaluate the hematuria and showed class IV-S—namely, diffuse segmental proliferative lupus nephritis. Based on the clinical features and laboratory findings, our patient fulfilled 4 of the 11 necessary American College of Rheumatology criteria for the diagnosis of systemic lupus erythematosus (SLE). She was treated with intravenous steroids, hydroxychloroquine, and mycophenolate mofetil. Her fevers resolved within a day, and the cervical lymphadenitis resolved over a 2-week duration. After 7 weeks of treatment, her ds-DNA antibodies were negative, and erythrocyte sedimentation rate and C-reactive protein dropped to normal levels (13 mm/h and <0.3 mg/dL, respectively). The patient continued to follow up with our pediatric rheumatology and nephrology services.

Primary central nervous system high-grade B-cell lymphoma, with rearrangements of MYC and BCL6

Abstract This article has been retracted.

Imatinib-Associated Tumor Lysis Syndrome in a Patient With Myeloid Neoplasm With Eosinophilia and PDGFRA Rearrangement: A Case Report and Review of the Literature

The term hypereosinophilic syndrome (HES) is defined as a persistent elevation of the eosinophil count ≥ 1,500/mm3 in the peripheral blood for at least 6 months, with evidence of end-organ damage.1 Etiologies for some forms of HES have been described, and the 2016 revision to the WHO classification of myeloid neoplasms and acute leukemia separates neoplasms associated with hypereosinophilia into two distinct groups. The first group falls under the category of myeloproliferative neoplasms, and it is named chronic eosinophilic leukemia, not otherwise specified. It is characterized by an eosinophil count ≥ 1,500/mm3, with evidence of clonality in the eosinophil lineage, or an increase in myeloblasts, but < 20%, in peripheral blood or bone marrow. In the absence of clonality or increased blasts, the diagnosis of idiopathic HES is made. By definition, there should be no Philadelphia chromosome or a rearrangement involving PDGFRA/B and FGFR12. The second group falls under the category of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2.3 The most common molecular abnormality is rearrangement of PDGFRA, and it predicts a favorable response to imatinib; however, the incidence of FIP1L1-PDGFRA rearrangement in patients with hypereosinophilia is only 10% to 20%.4,5 Given the historically poor prognosis of chronic eosinophilic leukemias and the exquisite sensitivity to imatinib in patients with rearranged PDGFRA/B, consensus has emerged that these individuals be treated even in the absence of organ dysfunction.6 Several case reports and small case series of patients with chronic eosinophilic leukemia with PDGFRA/B rearrangement have described the efficacy of imatinib at a dose of 100 to 400 mg per day to produce durable complete hematologic responses.7-11

Primary CNS high-grade B-cell lymphoma, with rearrangements of MYC and BCL6 : a case report

Fig. 1. Brain biopsy showing characteristic findings. (A) ×100 magnification; (B) ×400 magnification. Small foci of necrosis and frequent mitosis noted. (C-I) ×400 magnification. IHC stains on tumor cells were positive for CD20 (C), BCL2 (G), BCL6 (F), and MYC (I). The Ki-67 index was >95% (H). Tumor cells were negative for CD3 (D) and CD10 (E). leukemia/lymphoma with lymphopenia in a Korean. J Korean Med Sci 2000;15:233-9. 14. Ryu JH, Park JS, Hong SI, Son SJ, Suh CI. A case adult T-cell leukemia/lymphoma. Korean J Dermatol 2002;40:295-9. 15. Jung JY, Lee JH, Lee KH. A case of adult T-cell leukemia/ lymphoma. Korean J Dermatol 2007;45:58-62.

Cytomegalovirus appendicitis after hematopoietic stem cell transplantation

We present the case of a young man with acute lymphoblastic leukemia who developed cytomegalovirus (CMV) appendicitis after receiving alemtuzumab for acute refractory graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation (HSCT). CMV appendicitis is a rare complication; and we are reporting the first case to our knowledge of CMV appendicitis following HSCT. Our case highlights the importance of recognition of CMV viral reactivation following the use of alemtuzumab. Using a preemptive strategy of checking CMV PCR, with initiation of early effective treatment on detection of CMV replication, may be appropriate following use of alemtuzumab in hematologic malignancies in patients after HSCT.

Complement Regulatory Genetic Mutations in the Setting of Autoimmune Thrombotic Thrombocytopenic Purpura: A Case Series

Objective To explore the benefits of adding eculizumab for the treatment of refractory autoimmune thrombotic thrombocytopenic purpura (iTTP) with complement dysregulation. Patients and Methods From January 1, 2014, through July 1, 2017, we identified patients with iTTP defined by ADAMTS13 (disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels less than 5% and the presence of ADAMTS13 inhibitor. Patients who progressed after receiving standard of care management for iTTP were subjected to a comprehensive evaluation to look for evidence of complement activation. Herein, we share our single-institute experience regarding the clinical course and treatment algorithm for 3 patients with refractory iTTP. Results All the patients had clinical deterioration despite treatment with plasma exchange, corticosteroids, rituximab, and vincristine, which prompted us to look for evidence of complement activation and associated genetic mutations. Complement-related genetic aberrations were present in all 3 patients, who had had different degrees of complement activation. The first 2 patients did not benefit from eculizumab when treatment was started before complete clearance of inhibitors to ADAMTS13. However, they had durable remissions when eculizumab was introduced after clearance of ADAMTS13 inhibitors. The third patient started eculizumab therapy after inhibitor levels were undetectable. Conclusion We found eculizumab therapy to be effective in all 3 patients. However, its efficacy was prominent only after clearance of antibodies against ADAMTS13 via therapeutic plasma exchange.

Addressing Opioid-Associated Constipation Using Quality Oncology Practice Initiative Scores and Plan-Do-Study-Act Cycles

Using the Quality Oncology Practice Initiative, an affiliate program of ASCO, we outlined opioid-associated constipation (OAC) as a subject in need of quality improvement (QI) in our fellowship program at the University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System. We initiated a fellow-led QI project to advance the quality of patient care and provide a valuable avenue for QI training of young physicians. Fellows organized meetings with all stakeholders, addressed the scope of the problem, and devised strategies for OAC management. Monthly meetings were organized using Plan-Do-Study-Act principles. Mandatory check boxes were inserted into our electronic medical record templates to remind all physicians to identify patients on opioid medications and assess and address OAC. Final chart audit and patient satisfaction surveys were performed 6 months after project initiation. Assessment of OAC improved from 52% at baseline to 92% ( P < .003). This improvement corresponded with high patient satisfaction scores, with 90% of surveyed patients reporting adequate management of their constipation. In this QI initiative, we showed that participation in ASCOs Quality Oncology Practice Initiative helps identify areas in need of QI, and such fellow-led QI projects can serve as models for QI training of young physicians.

Etiologies and posttreatment conditions of thyrotoxic patients in Sylhet division, Bangladesh: A clinical series

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a B-cell lymphocytic neoplasm with indolent clinical course. If identified early, observation is opted. Many variables lead to the initiation of treatment. Authors describe a 62-year-old male presenting with shortness of breath and found to have white cell count of 1360 × 109/L and subsequently was diagnosed with CLL/SLL. The patient received leukapheresis along with tumor lysis treatment and systemic chemotherapy with fludarabine, cyclophosphamide, and rituximab regimen. His course was complicated with deep venous thrombosis, extensive cutaneous, and sinus mucosa involvement by CLL/SLL. The patient clinically improved and on follow-up clinic visits documented normalization of his white cell counts. The case report brings up a rare presentation of CLL/SLL with such an extreme high white cell count, leukostasis symptoms and extramedullary involvement of disease and encourages providers to be vigilant of rare presentation of CLL/SLL.