Relevance of B-Lines on Lung Ultrasound in Volume Overload and Pulmonary Congestion: Clinical Correlations and Outcomes in Patients on Hemodialysis.

BACKGROUND: Volume overload in patients on hemodialysis (HD) is an independent risk factor for cardiovascular mortality. B-lines detected on lung ultrasound (BLUS) assess extravascular lung water. This raises interest in its utility for assessing volume status and cardiovascular outcomes. METHODS: End-stage renal disease patients on HD at the Island Rehab Center being older than 18 years were screened. Patients achieving their dry weight (DW) had a lung ultrasound in a supine position. Scores were classified as mild (0-14), moderate (15-30), and severe (>30) for pulmonary congestion. Patients with more than 60 were further classified as very severe. Patients were followed for cardiac events and death. RESULTS: 81 patients were recruited. 58 were males, with a mean age of 59.7 years. 44 had New York Heart Association (NYHA) class 1, 24 had class 2, and 13 had class 3. In univariate analysis, NYHA class was associated with B-line classes (<0.001) and diastolic dysfunction (0.002). In multivariate analysis, NYHA grade strongly correlated with B-line classification (0.01) but not with heart function (0.95). 71 subjects were followed for a mean duration of 1.19 years. 9 patients died and 20 had an incident cardiac event. A Kaplan-Meier survival analysis demonstrated an interval decrease in survival times in all-cause mortality and cardiac events with increased BLUS scores (p = 0.0049). Multivariate Cox regression analysis showed the independent predictive value of BLUS class for mortality and cardiac events with a heart rate of 2.98 and 7.98 in severe and very severe classes, respectively, compared to patients in the mild class (p = 0.025 and 0.013). CONCLUSION: At DW, BLUS is an independent risk factor for death and cardiovascular events in patients on HD.

Curcumin potentiates the ability of sunitinib to eliminate the VHL-lacking renal cancer cells 786-O: rapid inhibition of Rb phosphorylation as a preamble to cyclin D1 inhibition.

Curcumin, an important component of the culinary spice turmeric, has been shown to harbor anticancer properties against a wide range of cancer cells with minimal toxicity toward normal cells. Two general tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib are currently used in treating renal cancer. Though the use of these TKIs has significantly improved survival, both elicit distressing side effects, limiting their long-term use. We tested the activity of sunitinib and sorafenib to eliminate 786-O renal cancer cells and the efficacy of curcumin to enhance this process. A four-fold decrease in the IC50 of sunitinib, from 4.5 µM to 1.2 µM, was observed in the presence of 20-µM curcumin. However, curcumin did not potentiate the activity of sorafenib. The sunitinib-curcumin (SunC) combination sharply inhibited hyperphosphorylation of the tumor suppressor protein Rb within 8 hours of SunC treatment. Although the levels of cyclin D1 did not change in 8 hours, its expression was dramatically inhibited after 24 hours of SunC exposure. Since curcumin is known to inhibit the cyclin D1-dependent G1/S-phase kinase CDK4 and the cyclin B-dependent G2/M-phase kinase CDK1 that catalyze phosphorylation-mediated inactivation of Rb, our results indicate that SunC containing a lower dose of sunitinib would be effective in restoring the tumor suppressor activity of Rb, thereby truncating cell cycle and triggering cell death. Our results submit the possibility of using SunC as an effective antitumor formulation to reduce the dose and risk of adverse effects of sunitinib.

Effect of hepatitis C virus infection on erythropoiesis in patients on hemodialysis.

BACKGROUND: Erythropoietin is a hormone that regulates erythropoiesis and is mainly produced by the kidneys. Several animal studies as well as a few case reports and case series have demonstrated that regenerating hepatic tissue can produce more erythropoietin than normal hepatic tissue. The purpose of the study was to examine the difference in hemoglobin and hematocrit levels as well as epoetin dosage in patients on hemodialysis with and without hepatitis C (HCV). METHODS: A retrospective chart review was performed. Seventy-six patients were included in the study (19 with HCV and 57 without HCV) at a ratio of 1:3. Exclusion criteria were a history of gastrointestinal bleeding or blood transfusion over the previous six months, polycystic kidney disease, and pregnancy. Variables examined included gender, age, duration of hemodialysis, hemoglobin, hematocrit, epoetin dose, aspartate transaminase, and ferritin levels over a three-month period. RESULTS: The patients were divided into two groups. The first consisted of patients with HCV on hemodialysis and the second of patients on hemodialysis without HCV. Mean hemoglobin was 12.6 ± 1.2 g/dL for the HCV-positive group and 11.9 ± 1.1 g/dL for the HCV-negative group. The difference was statistically significant (P = 0.03). Mean hematocrit was higher in the HCV-positive group, but was not significantly different at 39.08% ± 4.06% versus 37.43% ± 3.4% in the HCV-negative group (t-test, P = 0.11). Further, the HCV-positive group required less epoetin, but this was not significantly different from that required in the HCV-negative group at 6258 ± 5208 IU versus 7596 ± 7056 IU, respectively (t-test, P = 0.38). CONCLUSION: In our study, patients with HCV infection were found to have higher hemoglobin and hematocrit levels and lower epoetin requirements than those without HCV. Although the findings were not statistically significant, the computed values between these two groups of patients did follow a general trend. Further investigation with more patients, a longer duration of follow-up, and incorporation of additional medical variables is needed to clarify the role of HCV on erythropoiesis in hemodialysis patients.

Association between coronary artery disease diagnosed by coronary angiography and breast arterial calcifications on mammography: meta-analysis of the data.

BACKGROUND: Previous studies evaluating breast arterial calcifications (BAC) as a risk marker for coronary artery disease (CAD) have been limited by sample size and have yielded mixed results. Our objective was to evaluate the association of BAC and CAD. METHODS: Data sources included Medline (1970-2010), the Cochrane Controlled Trials Register electronic database (1970-2010), and CINAHL (1970-2010). The search strategy included the keywords, breast artery calcification, vascular calcification on mammogram, coronary angiography, and meta-analysis. Eligible studies included female patients who had undergone coronary angiography, the gold standard for diagnosing CAD, and had screening mammograms that revealed the presence or absence of BAC. Information on eligibility criteria, baseline characteristics, results, and methodologic quality was extracted by two reviewers. Disagreements were resolved by consensus. RESULTS: A total of 927 patients were enrolled in the five studies. There was a 1.59 (95% confidence interval [CI] 1-21-2.09) increased odds of angiographically defined CAD in patients with BAC seen on mammography. CONCLUSIONS: The presence of BAC on mammography appears to increase the risk of having obstructive CAD on coronary angiography; thus, BAC may not be a benign finding.

Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study).

BACKGROUND: Previous studies have demonstrated the role of inflammation in diabetic nephropathy (DN). Neutrophil to lymphocyte ratio (NLR) rather than other white cell parameters was found to be a useful inflammatory marker to predict adverse outcomes in medical and surgical conditions. Nevertheless, the value of NLR in predicting DN has not been elucidated. METHOD: An observational study included 338 diabetic patients, who were followed at our clinic between 2007 and 2009. We arranged our patients into tertiles according to their 2007 NLR. The primary outcome was continuous decrease of GFR >12 mL/min between 2007 and 2009 with the last GFR <60 mL/min. RESULT: The lowest NLR tertile had fewer patients (2.7%) with primary outcome (i.e., worsening renal function) compared with middle and highest NLR tertiles, which had more patients with primary outcomes (8.7% and 11.5%, respectively) with a significant p-value 0.0164. When other potential confounders were individually analyzed with NLR tertile, the NLR tertiles remained a significant predictor of poor GFR outcome in the presence of other variables (hemoglobin A1C, systolic blood pressure, diastolic blood pressure, age, and congestive heart failure with p-values 0.018, 0.019, 0.017, 0.033, and 0.022, respectively). CONCLUSION: NLR predicted the worsening of the renal function in diabetic patients. Further studies are needed to confirm this result.

Severe oxalosis with systemic manifestations.

UNLABELLED: Ethylene glycol toxicity can have various clinical presentations with different organ system involvements. These presentations are independent of the level of toxicity. We describe a 31 years old male who presented with ethylene glycol toxicity manifesting as anuric renal failure who subsequently developed neurological sequela of its toxicity. Ethylene glycol is known to be metabolized to various metabolites and is ultimately converted to oxalate which results in crystal deposition the renal parenchyma causing renal failure. Oxalate deposition can occur in various organs including the nervous system as seen in our patient. The majority of patients do not recover from severe oxalosis despite the supportive care of hemodialysis in removing the parent compounds. Despite severe oxalosis, our patient was fortunate enough to be left with minimal neurological sequelae, and eventually was able to cease hemodialysis treatments. KEYWORDS: Ethylene glycol; Oxalate; Oxalosis; Glyoxylic acid.

Male human papillomavirus infection post-kidney transplant: an overlooked disease.

While immunosuppressive regimens improve the overall survival of renal transplant recipients, they also contribute to the long-term complications of post-transplant malignancies. Chronic immune suppression in renal transplant recipients (RTR) increases the risk of viral-associated cancers. In male RTR, human papillomavirus (HPV) is implicated in the development of penile, anal, oropharyngeal, and non-melanoma skin carcinomas. Despite the significance of this virus in RTR, there is an overall deficiency in the understanding of the natural history of HPV infection in male RTR. In the next 20 years, it is believed that cancers will be the leading cause of death in kidney transplant recipients. HPV-associated carcinomas are of particular interest since they are sexually transmitted and in theory may be preventable diseases. This commentary highlights some of the progress made in understanding how HPV is transmitted amongst couples in the general population. It also summarizes the current knowledge of HPV infection in male RTR and describes the deficiencies in published medical literature.

Dietary intake in hemodialysis patients does not reflect a heart healthy diet.

OBJECTIVE: Cardiovascular disease is highly prevalent and has a major effect on morbidity and mortality in patients undergoing maintenance hemodialysis (MHD). Dietary factors that may contribute to cardiovascular disease have not been well studied in this population. We hypothesize that dietary intake in this population does not meet the guidelines for cardiovascular risk reduction. DESIGN: A cross-sectional study was completed using the validated "Block Dialysis 1 Food Frequency Questionnaire" to assess dietary intake of MHD patients. SETTING AND PATIENTS: A total of 70 patients undergoing MHD at our outpatient dialysis center completed the questionnaire under the supervision of a trained dietitian. The population consisted of 38 men and 32 women. MAIN OUTCOME MEASURE: Dietary intake was the main outcome measure, with a focus on calories, soluble fiber, saturated fatty acid (SFA), unsaturated fatty acid intake (UFA), and protein. RESULTS: The mean fiber intake was 10.77 (±5.87) g/day, and only 2 of 71 (2.9%) were in compliance with the recommended daily intake of >25 g/day. As percentage of total calories, of the 70 patients, 5 (7.1%) had a fat intake of <30%, 22 (31.4%) had SFA intake of <10%, 64 (91.4%) had a UFA of ≤30%, 22 (31.4%) had a protein-based diet of ≥15%, and 66 (94.3%) had a carbohydrate diet of <60%. CONCLUSIONS: Most patients did not meet the dietary guidelines for reducing the risk of cardiovascular disease. Substituting UFA or soluble fiber for SFA improves low density lipoprotein (LDL) cholesterol levels without negative effects on other lipid parameters.

Fasting hyperglycemia upon hospital admission is associated with higher pneumonia complication rates among the elderly.

BACKGROUND: Hyperglycemia is an independent predictor of adverse outcomes during hospitalization. In patients who have pneumonia, significant hyperglycemia is associated with poor outcomes. This study evaluates the interaction of the degree of hyperglycemia and complication rates stratified by age in non-critically ill patients admitted to the hospital for care of community-acquired pneumonia. METHODS: Retrospective review of patient records coded for pneumonia. Analysis included 501 non-critically ill patients admitted to a tertiary care hospital in New York City. Data were stratified by diabetes status, age (less than 65 and 65 and over), and fasting blood glucose (FBG) within the first 24 hours of hospitalization. Among patients with no history of diabetes, FBG was stratified as "normal" [FBG /=126 mg/dl (7 mmol/l)]. The diabetic group included known diabetics regardless of FBG. The Pneumonia Severity Index (PSI) was calculated for all patients. Complications rates, hospital length of stay and mortality were compared among the groups. RESULTS: In patients age 65 and older, complication rates were 16.7% in normoglycemics, 27.5% in the "mild-hyperglycemia" group, 28.6% in the "severe hyperglycemia" group, and 25.5% in those with known diabetes. The mild and severe-hyperglycemics had similar complication rates (p = 0.94). Compared to the normal group, mild and severe groups had higher rates of complications, p = 0.05 and p = 0.03, respectively. PSI tended to be higher in those over the age of 65. PSI was not significantly different when the normal, mild, severe, and known diabetes groups were compared. PSI did not predict complications for new hyperglycemia (normals' mean score 87, mild 84.7, severe 93.9, diabetics 100). Hospital mortality did not differ among groups. Length of stay was longer (p = 0.05) among mild-hyperglycemics (days = 8.4 s.e. 14.3) vs. normals (days = 6.2 s.e.6.5). CONCLUSION: This study shows that FBS between 101-125 mg/dl (5.7-6.9 mmol/l) on hospital admission increases pneumonia complication rates among the elderly with no previous diagnosis of diabetes.

Breast cancer screening in women with chronic kidney disease: the unrecognized effects of metastatic soft-tissue calcification.

Patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) are known to develop metastatic soft-tissue calcification, secondary to hyperparathyroidism, in tissues including the breast. Such calcifications in women could pose a problem for interpretation of mammograms, since they are thought to mimic malignant lesions and interfere with differentiation of benign from malignant disease. Investigation of this issue is important to provide high-quality, accurate breast care to women with CKD or ESRD, but little evidence is so far available. In a systematic review of the literature on the types and patterns of breast calcifications, we found only three studies that examined metastatic soft-tissue calcifications of the breast. The studies did, however, confirm that women with CKD or ESRD have a higher frequency of breast calcification than women with normal kidney function. The two older studies reported that these breast calcifications are not associated with malignancy, but the later study reported a raised rate of suspicious breast calcification among women with ESRD receiving hemodialysis, leading to an increased biopsy referral rate. In this Review we discuss the strengths and limitations of the available data and whether mammography is recommended in women with CKD or ESRD.

Increased breast calcifications in women with ESRD on dialysis: implications for breast cancer screening.

BACKGROUND: Different appearances of breast calcification on mammography can differentiate benign from malignant disease. An increased incidence of breast calcifications in dialysis patients is established, but data for morphological characteristics in renal patients, incidence of benign and malignant calcifications, and clinical consequences are limited. In this study, we compare mammograms and the workup of abnormal calcifications of women on hemodialysis with that of women with normal renal function. METHODS: This is a retrospective case-control study; 45 women on hemodialysis had their screening mammograms reviewed. A control group of 86 age-matched women with normal renal function was randomly obtained for comparison. Mammograms were examined and the recommended workup was traced. Breast calcification morphological characteristics, incidence of benign versus malignant calcifications, callback rate, and biopsy recommendation rates were compared to determine whether breast calcifications in renal patients led to excessive workups. RESULTS: Overall, breast calcifications in the renal group were statistically significantly increased compared with controls, mostly because of several benign-appearing morphological characteristics. No statistically significant difference was present between the 2 groups with respect to callback rates. However, incidences of malignancy-associated calcification and hence biopsy recommendation rate were slightly greater for the renal group. CONCLUSION: Renal patients have an increase in breast calcification, mostly caused by several benign calcifications. The callback rate is no greater than that in the general population. However, there is a slightly greater incidence of malignancy-associated calcifications; hence, once called back, they have a greater probability of being recommended for biopsy.