Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: three case reports and review of the literature

Concurrent hemolysis in patients with vitamin B12 deficiency is a well-recognized phenomenon and has been attributed to intramedullary destruction of erythrocytes (ineffective erythropoiesis). Recent studies revealed that homocysteine increased the risk of hemolysis in vitamin B12 deficiency in vitro and there is a high frequency (30%) of vitamin B12 deficiency in asymptomatic patients with homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutation, a known cause of hyperhomocysteinemia. Here we report three patients with MTHFR mutations and vitamin B12 deficiency presenting with hemolytic anemia and severely elevated homocysteine levels. Patients demonstrated complete resolution of hemolysis with simultaneous normalization of serum homocysteine levels after vitamin B12 treatments. We reviewed pertinent literature, and hypothesized that hemolytic anemia may be more prevalent in patients who have a coexisting MTHFR gene mutation and vitamin B12 deficiency possibly related to severely elevated homocysteine levels. The hemolysis in these cases occurred predominantly in peripheral blood likely due to the combined effects of structurally defective erythrocytes and homocysteine-induced endothelial damage with microangiopathy

Pharmacotherapy and the risk for community-acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>Some forms of pharmacotherapy are shown to increase the risk of community-acquired pneumonia (CAP). The purpose of this study is to investigate whether pharmacotherapy with proton pump inhibitors (PPI), inhaled corticosteroids, and atypical antipsychotics was associated with the increased risk for CAP in hospitalized older adults with the adjustment of known risk factors (such as smoking status and serum albumin levels).</p> <p>Methods</p> <p>A retrospective case-control study of adults aged 65 years or older at a rural community hospital during 2004 and 2006 was conducted. Cases (N = 194) were those with radiographic evidence of pneumonia on admission. The controls were patients without the discharge diagnosis of pneumonia or acute exacerbation of chronic obstructive pulmonary disease (COPD) (N = 952). Patients with gastric tube feeding, ventilator support, requiring hemodialysis, metastatic diseases or active lung cancers were excluded.</p> <p>Results</p> <p>Multiple logistic regression analysis revealed that the current use of inhaled corticosteroids (adjusted odds ratio [AOR] = 2.89, 95% confidence interval [CI] = 1.56-5.35) and atypical antipsychotics (AOR = 2.26, 95% CI = 1.23-4.15) was an independent risk factor for CAP after adjusting for confounders, including age, serum albumin levels, sex, smoking status, a history of congestive heart failure, coronary artery disease, and COPD, the current use of PPI, β2 agonist and anticholinergic bronchodilators, antibiotic(s), iron supplement, narcotics, and non-steroidal anti-inflammatory drugs. The crude OR and the AOR of PPI use for CAP was 1.41 [95% CI = 1.03 - 1.93] and 1.18 [95% CI = 0.80 - 1.74] after adjusting for the above confounders, respectively. Lower serum albumin levels independently increased the risk of CAP 1.89- fold by decreasing a gram per deciliter (AOR = 2.89, 95% CI = 2.01 - 4.16).</p> <p>Conclusion</p> <p>Our study reaffirmed that the use of inhaled corticosteroids and atypical antipsychotics was both associated with an increased risk for CAP in hospitalized older adults of a rural community. No association was found between current PPI use and the risk for CAP in this patient population of our study.</p

Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML)

Despite the availability of an increasing number of targeted therapeutics and wider use of allogeneic hematopoietic stem cell transplantation, many patients with acute myeloid leukemia (AML) ultimately succumb to this disease. Given their remarkable efficacy in B-acute lymphoblastic leukemia and other CD19-expressing B cell malignancies, there is hope adoptive cellular transfer, particularly chimeric antigen receptor (CAR)-modified immune effector cell (IEC) therapies, may afford a novel, potent immune-based approach for the treatment of AML that complements or replaces existing ones and improves cure rates. However, it is unclear how best to translate the success of these therapies from B cell malignancies, where use of highly potent immunotherapies is facilitated by identified target antigens with near ubiquitous expression on malignant cells and non-fatal consequences from &ldquo;on-target, off-tumor cell&rdquo; toxicities. Herein, we review the current status of CAR-modified IEC therapies for AML, with considerations regarding suitable, relatively leukemia-restricted target antigens, expected toxicities, and interactions of the engineered cells with a profoundly immunosuppressive tumor microenvironment that restricts their therapeutic efficacy. With these challenges in mind, we will discuss possible strategies to improve the cells&rsquo; potency as well as their therapeutic window for optimal clinical use in AML

Risk factors associated with lower defecation frequency in hospitalized older adults: a case control study

BACKGROUND: Constipation is highly prevalent in older adults and may be associated with greater frequency of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We investigated the prevalence of lower defecation frequency (DF) and risk factors (including AECOPD) associated with lower DF among hospitalized elderly patients. METHODS: We conducted a retrospective case-control study in a community hospital of Southeast Ohio. Adults aged 65 years or older admitted during 2004 and 2006 were reviewed (N = 1288). Patients were excluded (N = 212) if their length of stay was less than 3 days, discharge diagnosis of Clostridium difficile-associated diarrhea, death or ventilator- dependent respiratory failure during hospitalization. Lower DF was defined as either an average DF of 0.33 or less per day or no defecation in the first three days of hospitalization; cases (N = 406) and controls (N = 670) were included for the final analysis. RESULTS: Approximately 38% had lower DF in this patient population. Fecal soiling/smearing of at least two episodes was documented in 7% of the patients. With the adjustment of confounders, AECOPD (adjusted odds ratio [AOR] =1.47, 95% confidence interval [CI] =1.01-2.13) and muscle relaxant use (AOR =2.94; 95% CI =1.29-6.69) were significantly associated with lower DF. Supplementation of potassium and antibiotic use prior to hospitalization was associated with lower risk of lower DF. CONCLUSIONS: Approximately 38% of hospitalized older adults had lower DF. AECOPD and use of muscle relaxant were significantly associated with lower DF; while supplementation of potassium and antibiotic use were protective for lower DF risk after adjusting for other variables.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Acute Systemic Viral Infection Masquerading as an Infiltrating Lymphoma in an Elderly Patient: A Case Report and Review of the Literature

Primary Epstein-Barr virus (EBV) infection occurs mainly in adolescents and young adults, with more than 90% of adults having serological evidence of past infection. Primary infection in those over the age of 40 is associated with an atypical and often more severe presentation that can lead to more extensive and invasive, and often unnecessary, diagnostic testing. The incidence of severe EBV-related illness in older adults has been observed to be increasing in industrialized nations. The characteristic presentation of infectious mononucleosis (IM) syndrome in elderly patients (age > 65) is not clearly defined in the literature. Here, we describe a case of primary EBV infection in an 80-year-old female and review the literature regarding primary seroconversion in elderly patients

Impact of region of diagnosis, ethnicity, age, and gender on survival in acute myeloid leukemia (AML)

Aim: Acute myeloid leukemia (AML) is an aggressive hematopoietic clonal disorder characterized by the increased blasts and poor survival outcome, which is mainly driven by cytogenetic and molecular abnormalities. Here, we investigated the prognostic impact of other demographic parameters on the survival outcomes in AML patients. Method: We reviewed the Surveillance, Epidemiology, and End Result (SEER) database to collect demographic information, including age, diagnosis, gender, race, and geographic region in patients with non-acute promyelocytic leukemia AML, between 2004-2008. The primary end-point of our study was 3-year overall survival (OS), which was estimated by the Kaplan-Meier method and Cox regression model. Results: A total of 13,282 patients were included in our analyses. Increasing age (HR 1.2, p < .0001), male gender (HR 1.05, p = .01), and geographic region of Midwest (HR 1.07, p=.002) were associated with inferior 3-year OS in univariate analysis, and these parameters remained independent prognostic factors in multivariate analyses. Conclusions: AML is a heterogeneous myeloid neoplasm with patient outcomes largely dictated by the cytogenetics and somatic mutations. In our study, additional demographic factors, including advanced age, male gender, and geographic region of AML diagnosis were associated with OS outcome in non-APL AML patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]