Multiple Myeloma as the Underlying Cause of Thrombotic Microangiopathy Leading to Acute Kidney Injury: Revisiting a Very Rare Entity.

Thrombotic microangiopathy (TMA) describes a pathological process of microvascular thrombosis, consumptive thrombocytopenia, and microangiopathic hemolytic anemia, leading to end-organ ischemia and infarction, affecting particularly the kidney and brain. TMA is a pathological feature of a number of clinical disorders including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and atypical hemolytic uremic syndrome. Rare but important, TMA may also occur in malignancy, connective tissue disease, malignant hypertension, and renal transplantation (rejection or drug toxicity). We present a very rare case where the patient developed acute kidney injury from TMA but found to have multiple myeloma as the possible underlying etiology.

Reversal agents of non-vitamin K dependent anticoagulants: a rapid review of the changing horizon.

The newer non-vitamin K dependent anticoagulants (NOACs) have provided a new tool in the armamentarium of physicians treating nonvalvular atrial fibrillation and thromboembolism. Slowly, but steadily, there has been an increased preference of NOACs over vitamin K antagonists. However, the major limiting factor and the concern that precluded their use was lack of reversal in emergent situations. With the advent of reversal agents such as idarucizumab, andexanet alfa and PER977, this gap is also being filled. This will further increase the spectrum of usage of NOACs. In this review we present the detailed information on the completed trials on the reversal agents, the ongoinng trials, and their site of action. The reversal agent idarucizumab is FDA approved and readily available. The others are in clinical trials and are soon expected to be available in clinical practice.

Neutropenia in Congenital and Adult Babesiosis.

OBJECTIVES: Anemia and thrombocytopenia are expected hematologic abnormalities in patients with acute babesiosis, whereas neutropenia (defined as an absolute neutrophil count of ≤1,800 neutrophils/µL for adults and <1,200 neutrophils/µL for infants) is not usually considered a feature of this infection. We studied the frequency with which neutropenia occurs in congenital and adult cases of babesiosis. METHODS: The frequency of neutropenia in cases of congenital babesiosis was determined based on a literature review and on the findings in an unreported case. The frequency of neutropenia in adult patients was assessed based on a review of the medical records of 51 patients who were diagnosed with babesiosis between 2010 and 2013 at two medical centers in the Northeastern United States. RESULTS: Four (80%; 95% confidence interval [CI], 36%-98%) of five infants with congenital babesiosis whose neutrophil count was reported were neutropenic. Among 51 adult cases with babesiosis, 11 (22%; 95% CI, 12%-35%) were neutropenic on clinical presentation, and seven others developed neutropenia over the next 1 to 21 days. Thus, a total of 18 (35%; 95% CI, 24%-49%) of the adult patients with babesiosis had neutropenia. CONCLUSIONS: Neutropenia appears to be a common finding in infants with congenital babesiosis and is also observed not infrequently in adults with this infection.

Warfarin use and prevalence of coronary artery calcification assessed by multislice computed tomography.

Warfarin inhibits the synthesis and function of matrix Gla protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification. We had earlier reported the association of warfarin use with valvular calcification in patients with nonvalvular atrial fibrillation. The aim of our present study was to investigate the association of warfarin use with the presence and severity of coronary artery calcification. A total of 233 patients underwent computed tomography scan (CT) at our institution for the assessment of coronary artery calcium score (CACS). Of 233 patients, the mean age was 63 years, 28 patients (12%) were treated with warfarin, and 205 patients (88%) were not on warfarin. Based on their total CACS, the patients were subsequently stratified into 59 with no coronary calcium (CACS = 0), 63 with low CACS (1-100), 49 with moderate CACS (101-400), 33 with severe CACS (410-1000), and 29 with very severe CACS (>1000). The χ test and Student t-test were used for the comparison of categorical and continuous variables, respectively, between warfarin users and nonusers. Using the variables age, gender, race, smoking, hypertension, diabetes, dyslipidemia, glomerular filtration rate, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins, stepwise logistic regression analysis did not show any association of coronary calcification with use of warfarin. In our study, warfarin use was not associated with a higher prevalence or severity of CACS assessed by coronary computed tomography.

Statins and venous thromboembolic disease prophylaxis.

Statins have dramatically improved the treatment of hyperlipidemia and cardiovascular disease through its inhibition of hydroxymethylglutaryl-coenzyme A reductase. Although its main effect has long been known, much is yet to be understood about the wide and varied pleiotropic properties of statins. Some studies have demonstrated that statins contain antiplatelet, antithrombotic, antiinflammatory, cardioprotective, and neuroprotective properties independent of their ability to lower plasma low-density lipoprotein cholesterol. More recently, statins have been used in novel ways in the treatment of Alzheimer disease, sepsis, pneumonia, and bacteremia. In 2000, it was first suggested that statins could decrease the incidence of venous thromboembolisms (VTEs). A recent publication showed that not only do statins lower the incidence of deep vein thrombosis and pulmonary embolism, but they do so in a dose-dependent manner. Although there is certainly strong evidence demonstrating that statins do indeed lower VTEs, the mechanism is not understood. Possible hypotheses include their antiinflammatory and antithrombotic properties. With only one randomized clinical trial available, further studies must be conducted before routinely recommending statins for prophylaxis of VTEs.

Vascular and heart diseases in the incumbent presidents and vice presidents of the United States of america: a medical-historical perspective.

Vascular diseases have been the major cause of death and disability in presidents and vice presidents of the United States. Untreated hypertension and cigarette smoking have contributed greatly to this increased morbidity and mortality risk, which has impacted on historical events, especially in the 20th century. In this article, the medical histories of those incumbent Presidents and Vice Presidents who suffered from coronary artery and cerebrovascular diseases will be reviewed. A discussion of how atrial fibrillation has affected the Presidents is also included.

The effects of biofilm on the transport of stabilized zerovalent iron nanoparticles in saturated porous media.

The transport of stabilized zerovalent iron nanoparticles (nZVI) has recently been the topic of extensive research due to its proven potential as an in situ remediation tool. However, these studies have ignored the effects of biofilms-complex aggregations of bacterial cells and excreted extracellular polymeric substances present in nearly all aquatic systems-on the transport of these particles. This study examines the effects of Pseudomonas aeruginosa (PAO1) biofilm, at a cell concentration similar to that reported for saturated aquifers, on the transport of commercially available, poly (acrylic acid) stabilized nZVI (pnZVI) in 14 cm long columns packed with saturated glass beads at salt concentrations of 1 and 25 mM NaCl. Compared to retention on uncoated columns, in the presence of biofilm the retention of pnZVI increased at higher ionic strength, while ionic strength played no role in retention of these nanoparticles in the absence of biofilm. The Tufenkji-Elimelech correlation equation predicts lower retention of pnZVI on biofilm coated columns compared to uncoated columns due to a lower Hamaker constant, and DLVO energy considerations predict the most favorable attachment to uncoated porous media at higher ionic strength. A steric (polymer-mediated) model that considers the combined influence of steric effects of polymers and DLVO interactions is shown to adequately describe particle retention in columns.

Hepatocellular carcinoma in non-cirrhotic liver without evidence of iron overload in a patient with primary hemochromatosis. Review.

BACKGROUND: We report a case of a 70-year-old male with hepatocellular carcinoma (HCC) with a history of hemochromatosis but with no evidence of cirrhosis or iron overload and with a history of exposure to atomic bomb radiation. It is very rare to see hepatocellular carcinoma in the absence of evidence of liver injury. METHODS: We did an extensive review of current English medical literature through Pubmed from 1980 to 2009 and found 14 case reports of patient with hepatocellular cancer in absence of cirrhosis. The details of these cases were reanalyzed as reported and documented for review. RESULTS: There are 14 previous case reports of HCC developing in hemochromatosis in absence of cirrhosis but ten of them had evidence of iron overload in the non-tumorous livers. Our case is the fifth case of Hepatocellular cancer in hemochromatosis in absence of cirrhosis and iron overload. CONCLUSION: Hepatocellular carcinoma is a very rare in absence of cirrhosis but patient with other risk factors like hemochromatosis, viral infections, radiation, and toxin exposure should be monitored closely for any sign and symptoms suggestive of malignancy.

Investigational antiplatelet drugs for the treatment and prevention of coronary artery disease.

Antiplatelet therapy for the prevention and treatment of coronary artery disease (CAD) has undergone dramatic changes and improvements. Aspirin remains the first-line antiplatelet drug for clinical use. Newer platelet inhibitors such as the thienopyridine agents, ticlopidine and clopidogrel, have also been shown to be effective in treating CAD. There have been ongoing efforts to evaluate newer antiplatelet drugs, with the potential to improve clinical efficacy and safety. Some of the more promising antiplatelet agents include new adenosine diphosphate receptor antagonists such as prasugrel, cangrelor, and ticagrelor (AZD6140). In addition, a new thromboxane receptor antagonist, NCX-4016, a newly discovered protease-activated receptor antagonist that targets thrombin-induced platelet aggregation, and anti-von Willebrand factor aptamers show tremendous promise in refining antiplatelet therapy by targeting different receptors and molecules.

Elastography in the management of liver disease.

Normal liver tissue is soft and pliable. With inflammation, however, many of the cells die and are replaced by collagenous fibrils and the tissue gets stiffer. The progress is often slow-extending over decades in many cases. When liver stiffness increases by a factor of about five, the condition is called cirrhosis, a disease with serious medical implications. After the onset of cirrhosis, the probability of developing hepatic cancer increases at the rate of about 5% per year. Precise, noninvasive measurement of liver stiffness, a simple application of elastography, promises to be a safe, inexpensive method to monitor the progress of liver patients, improve outcome, save many lives and much suffering and reduce the cost of medical care.

Variability of response to clopidogrel: possible mechanisms and clinical implications.

Clopidogrel has been shown to inhibit adenosine diphosphate-induced platelet aggregation and has been demonstrated to be effective in reducing the risk of arterial thrombotic events in several large clinical studies. However, the clinical benefit could be attenuated by the variability of response to the antiplatelet effects of clopidogrel in as many as 30% of patients. Multiple mechanisms likely contribute to clopidogrel variability of response, including inappropriate dosing or underdosing of clopidogrel, drug-drug interactions, and genetic polymorphisms. The best laboratory procedure to screen for possible clopidogrel variability of response remains to be determined.

Aspirin resistance: mechanisms and clinical implications.

Acetylsalicylic acid (aspirin) has been shown to irreversibly interfere with platelet function, an effect that is associated with a reduction in morbid and mortal arterial thrombotic events in multiple clinical studies. This clinical benefit appears to be attenuated by resistance to the antiplatelet effects of aspirin in up to 35% of patients. The mechanisms for aspirin resistance are multifactorial and include noncompliance with aspirin therapy, diabetes mellitus, cell-cell and drug-drug interactions, genetic polymorphisms, and coronary artery disease. It has not been determined what the best laboratory procedure is to screen for aspirin resistance. Those individuals at high risk for aspirin resistance might best be treated with an additional oral antiplatelet drug (eg, clopidogrel) to achieve maximal protection against arterial thrombotic events.

Evaluation of temozolomide in patients with myelodysplastic syndrome.

In our previous phase I study of temozolomide in patients with acute leukemia, temozolomide was well tolerated and demonstrated significant anti-leukemic activity. The maximum tolerated dose was 200 mg/m2/d for 7 days, repeated approximately every 5-6 weeks. In the current study, we evaluated the same dose of temozolomide in patients with myelodysplastic syndrome. Fourteen patients received 19 courses of temozolomide. The median age was 71 years. In this study, treatment was poorly tolerated with patients requiring admission in 9 of 19 courses. Toxicity included worsening cytopenias, neutropenic fever, and exacerbation of cardiac disease, the latter due to worsening anemia. An unusual finding was the development of leukocytoclastic vasculitis in 4 patients. There were no formal responses to therapy. The current schedule of temozolomide is not efficacious in patients with myelodysplastic syndrome.

Anemia and hypocholesterolemia.

The authors reviewed the available data on the relationship between hypocholesterolemia and anemia with various etiologies. The data were collected from sources identified by a MEDLINE search of English-language literature published between 1966 and 2001 and bibliographies of relevant articles. The study selection included primary research articles, metaanalyses, and abstracts concerning the relation between hypocholesterolemia and anemia. Textbooks, meeting proceedings, and reference lists were also searched. Despite differences in study design, a relation was found between hematocrit and serum cholesterol levels and between hemoglobin and cholesterol levels. Further studies are required to determine the exact etiology and clinical significance of these findings.