Background: Elevated histone deacetylase (HDAC) isoenzyme levels have been described in patients with carcinomas and leukemias. HDAC inhibitors (HDACi) have shown promise in the treatment of carcinomas and are currently under intense research. To make better use of HDACi in treating chronic lymphocytic leukemia (CLL), HDAC isoenzyme levels were studied. Methods: Quantitative reverse transcriptase polymerase chain reaction for HDAC isoenzyme was measured in 32 patients with CLL and compared with 17 normal volunteer controls. ZAP-70, CD38 and CD44 were also assayed and correlated to HDAC isoenzyme levels. Results: The results showed: (1) HDAC isoenzyme levels in CLL were significantly increased in class I including HDAC1 and HDAC3, in class II including HADC6, HDAC7, HDAC9 and HDAC10, and in class III including SIRT1 and SIRT6; (2) higher expression of HDAC isoenzyme levels was found in ZAP-70+ compared to ZAP-70– patients, and CD44 expression levels were correlated with HDAC isoenzyme expression levels in the majority of HDAC classes. Conclusions: These results suggest: (1) in CLL, elevated HDAC isoenzyme activity is not restricted to one class, and therefore, HDACi therapy may need to be directed to more than one specific class of HDAC; (2) higher HDAC expression activity may indicate a poor prognosis and more advanced disease stage (through indirect evidence), since higher values were found in patients with ZAP-70+ and higher CD44 expression levels.
Cancers of the small bowel are relatively rare and account for approximately 1–2% of all gastrointestinal neoplasms. The most common histologic subtype – adenocarcinoma – constitutes 40% of all cases. These cancers generally present with vague abdominal discomfort and are often diagnosed at a late stage and carry a poor prognosis. The treatment of choice of early-stage small bowel adenocarcinoma is surgical resection. No standard treatment protocol has been defined for unresectable or metastatic disease. Here, we report a case of a 56-year-old woman who presented with unexplained iron deficiency anemia. Extensive initial studies with serial CT scans of the abdomen, esophagogastroduodenoscopy, small bowel capsule endoscopy and colonoscopy were noncontributory. She was later found to have a metastatic small bowel adenocarcinoma and treated with palliative chemotherapy. She achieved a modest response to the treatment. Interestingly, in our case, the sole presentation was unexplained iron deficiency anemia. Physician’s awareness regarding the possibility of small bowel cancer especially in the setting of iron deficiency and its workup has been emphasized. This enhances the chance of early detection and hence better survival.
Background: Anemia (defined by the World Health Organization as a hemoglobin level of less than 13 mg/dl in men and less than 12 mg/dl in women) is common in diabetic patients, particularly in those with reduced renal function. Most studies attribute anemia in diabetic patients to kidney function impairment. There are no controlled systematic studies of the prevalence and predictors of anemia in patients with diabetes in the absence of overt nephropathy. Objective: This retrospective cohort study was designed to measure the prevalence of anemia in diabetic patients with normal kidney function (estimated glomerular filtration rate (EGFR) greater than 90 ml/min/1.73 m2 and negative micro albuminuria) and compare it to a control group of non-diabetic patients. The study was designed to investigate diabetes as an independent risk for causing anemia. Methods: We undertook a retrospective review of medical records of 400 patients (older than 18 years old) visiting the outpatient clinic in our institution between January and June 2015. 200 patients with diabetes (glycosylated hemoglobin (HgA1C) greater than 7) were compared to 200 non-diabetic patients (HgA1C level below 5.6), to identify the prevalence of anemia, with and without kidney disease and any other associated factors. Results:The prevalence of anemia in all diabetic patients was 22% vs. 9% in non-diabetic group (OR: 2.69, 95% CI; 1.49 to 4.86, P = 0.001). Out of the 22% (n = 44) anemic patients, 18 patients had anemia with normal kidney function, out of those; 5 had iron deficiency anemia and one had autoimmune disease, while the remaining 12 patients (6%) did not have any obvious cause of anemia other than diabetes vs. 2 patients (1%) in non-diabetic patients who we did not find any explanation for the their anemia (OR: 6.6, 95% CI; 1.45 to 30, P < 0.015). Conclusion: Most studies have highlighted an association between anemia and nephropathy in diabetic patients. This retrospective cohort study suggests a high incidence of anemia with unidentified pathology in the diabetic population. The mechanism of this anemia is not well understood, although direct glucose toxicity to erythrocyte precursors in the bone marrow or oxidative stress to mature erythrocytes are both possibilities. Prospective study of hemoglobin levels in patients with diabetes may help elucidate the precise mechanism of anemia in this group. Disclosures No relevant conflicts of interest to declare.
We describe a rare case of adult T-cell leukemia characterized by an expansion of CD4+ CD8+ double-positive lymphocytes associated with human T-lymphotropic virus type 1 (HTLV-1) and a complex karyotype in a 43-year-old Caribbean male who was initially admitted to our hospital with significant lethargy, visual disturbances, dysphagia, right facial palsy and numbness in both feet for 3 days. He was found to have severe hypercalcemia (15.6 mg/dl). Peripheral blood smear showed multilobulated clover-shaped nuclei. Bone marrow and CSF flow cytometries revealed abnormal monoclonal expansion of T cells positive for CD4, CD5, CD8 and CD25 but negative for CD7, CD20, CD56, CD68 and terminal deoxynucleotidyl transferase. The polymerase chain reaction analysis showed a distinct band of the T-cell receptor γ gene, revealing T-cell clonal integration of the proviral DNA of HTLV-1, thus confirming the diagnosis of acute adult T-cell leukemia/lymphoma. Cytogenetic study revealed a male karyotype with monosomy 12, unbalanced translocation 5q and 13q and additional material on 5q, 7q, 14q and 17q. The patient underwent prednisone (EPOCH) chemotherapy followed by autologous transplantation with BEAM regimen. Although patients with a rare mixed CD4+ CD8+ immunophenotype usually present with an aggressive clinical course and have a poor prognosis, our patient was able to survive for 2.5 years.
Multiple myeloma (MM), a plasma cell neoplasm, has a typical presenting pattern consisting of bone pain, renal failure, anemia, and/or hypercalcemia. Even though MM is a cancer that impairs the immune system, rarely is a systemic infection the first sign of disease. In this case report, our patient presented with altered mental status due to meningitis and was later diagnosed with MM. Furthermore, we display a case of a rare but emerging and serious fungus, Candida auris, that the patient developed during his inpatient stay. This is the first such record of C. auris in an MM patient.
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