Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial.

BACKGROUND: Right-sided heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Similar to left heart failure, sympathetic overactivation and ß-adrenoreceptor (ßAR) abnormalities are found in PAH. Based on successful therapy of left heart failure with ß-blockade, the safety and benefits of the nonselective ß-blocker/vasodilator carvedilol were evaluated in PAH. METHODS: PAH Treatment with Carvedilol for Heart Failure (PAHTCH) is a single-center, double-blind, randomized, controlled trial. Following 1-week run-in, 30 participants were randomized to 1 of 3 arms for 24 weeks: placebo, low-fixed-dose, or dose-escalating carvedilol. Outcomes included clinical measures and mechanistic biomarkers. RESULTS: Decreases in heart rate and blood pressure with carvedilol were well tolerated; heart rate correlated with carvedilol dose. Carvedilol-treated groups had no decrease in exercise capacity measured by 6-minute walk, but had lower heart rates at peak and after exercise, and faster heart rate recovery. Dose-escalating carvedilol was associated with reduction in right ventricular (RV) glycolytic rate and increase in ßAR levels. There was no evidence of RV functional deterioration; rather, cardiac output was maintained. CONCLUSIONS: Carvedilol is likely safe in PAH over 6 months of therapy and has clinical and mechanistic benefits associated with improved outcomes. The data provide support for longer and larger studies to establish guidelines for use of ß-blockers in PAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT01586156FUNDING. This project was supported by NIH R01HL115008 and R01HL60917 and in part by the National Center for Advancing Translational Sciences, UL1TR000439.

Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. METHODS: This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

Metabolic and Functional Evaluation of the Heart and Lungs in Pulmonary Hypertension by Gated 2-[18F]-Fluoro-2-deoxy-D-glucose Positron Emission Tomography.

Pulmonary hypertension (PH) is associated with a metabolic shift towards glycolysis in both the right ventricle and lung. This results in increased glucose uptake to compensate for the lower energy yield of glycolysis, which creates a potential for 2-[18F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to be a useful tool in the evaluation of participants with PH. We investigated the utility of PET for PH by comparing FDG-PET uptake in the right ventricle and lungs in 30 participants with PH and eight healthy controls and correlating these measurements with echocardiographic (ECHO) measurements and other traditional assessments commonly used in PH. All participants underwent gated FDG-PET scanning in the fasting state, ECHO, six-minute walk test (6MWT), and blood draw for NT-proBNP. Participants also completed the CAMPHOR questionnaire. Right ventricular (RV) end-diastolic and end-systolic volumes, RV ejection fraction, and FDG uptake by PET were significantly different between PH and healthy controls and strongly correlated with plasma NT-proBNP levels and RV ECHO parameters including TAPSE, RV systolic pressure, Tei index, and global peak systolic strain. In addition, lung standardized uptake value (SUV) was also found to be significantly higher in participants with PH than healthy controls. However, lung SUV did not show any significant correlations with NT-proBNP levels, 6MWT, or functional and pressure measurements by ECHO. In this study, we demonstrated the ability to evaluate both lung and right heart metabolism and function in PH by using a single gated FDG-PET scan.

Endoluminal Bariatric Interventions: Where do we stand? Where are we going?

BACKGROUND: Obesity is an epidemic leading to high morbidity, mortality, and therefore health-related costs. Thus, there is a huge need for development of safe and effective treatments. Even though success rates of conservative methods are highly limited, the surgical approaches lead to major complications in as many as 25% of the patients. In this study, we aimed to review the currently available, less-invasive, endoscopic bariatric techniques which provides an option to reduce the risks of the patients and the medical costs. METHODS: A systematic literature review through Pubmed and Medline was performed to find the studies on this topic, and all controlled clinical trials, case reports, and case series were reviewed. RESULTS: Endoluminal bariatric interventions include restrictive, malabsorptive approaches, and other techniques including transpyloric shuttle, botulinum toxin, gastric pacing and vagal nerve stimulation. Restrictive procedures act by limiting the gastric volume and leading to early satiety, while malabsorptive procedures create a malabsorption state. Transpyloric shuttle is a device decreasing the rate of gastric emptying. Botox injection causes a delay in gastric emptying, and vagal nerve stimulation modulates eating behavior. CONCLUSION: Endoluminal bariatric techniques can become the primary choice of therapy in the near future for bariatric care.

Skin cancer in immunosuppressed transplant patients: Vigilance matters.

Liver transplantation (LT) is a widely-accepted, definitive therapy of irreversible liver diseases including hepatitis C, alcoholic liver disease and metabolic liver disease. After transplantation, patients generally use a variety of immunosuppressive medications for the rest of their lives to prevent rejection of transplanted liver. Mortality after LT is mainly caused by recurrence of alcoholic hepatitis which is mostly seen in the patients who resume heavy drinking. On the other hand, de-novo malignancies after LT are not seldom. Skin cancers make up 13.5% of the de-novo malignancies seen in these patients. Malignancies tend to affect survival earlier in the course with a 53% risk of death at 5 years after diagnosis. We aimed to report a case who underwent LT secondary to alcoholic liver disease and developed squamous cell carcinoma of the skin eighteen years after transplantation. In summary, transplant recipients are recommended to be educated on self examination for skin cancer; health care providers should be further suspicious during routine dermatological examinations of the transplant patients and biopsies of possible lesions for skin cancer is warranted even many years after transplantation.

Air leak syndrome after endoscopic retrograde cholangiopancreatography: a rare and fatal complication.

Endoscopic retrograde cholangiopancreatography (ERCP) is a state of the art diagnostic and therapeutic procedure for various pancreatic and biliary problems. In spite of the well-established safety of the procedure, there is still a risk of complications such as pancreatitis, cholangitis, bleeding and perforation. Air leak syndrome has rarely been reported in association with ERCP and the optimal management of this serious condition can be difficult to establish. Our group successfully managed a case of air leak syndrome following ERCP which was caused by a 3cm Stapfer type I perforation in the posterolateral aspect of the second part of the duodenum and was repaired surgically. Hereby, we describe the presentation and subsequent therapeutic approach.

Endoscopic clips for the closure of acute iatrogenic perforations: Where do we stand?

BACKGROUND AND AIM: Iatrogenic perforation of the gut during endoscopy remains an uncommon but critical complication with significant morbidity and probable mortality than usual surgical treatment. Some authors have adopted a non-surgical closure method in chosen cases and, since 1993, endoclips have been used to close perforation in the stomach. The endoscopic practice of endoclips has been commonly used in the gut for hemostasis. Currently, the use of endoscopic techniques is increasing for the closure of endoscopic submucosal dissection or endoscopic mucosal resection. Endoscopic perforations that improved with endoscopic closure in the literature prior to 2008 have been previously described. In the present article, we present a descriptive review of cases with iatrogenic perforation in the gut treated with endoclips between 2008 and 2014. METHODS: Comprehensive literature screening and a systematic review using PubMed and Medline was done for all reports published between January 2008 and December 2014 using the endoclip technique in the closure of iatrogenic perforations. RESULTS: A total of 47 studies published between 2008 and 2014 using endoclips for the closure of iatrogenic perforations of the gut (nine esophagus, 11 stomach, 15 duodenum, 12 colon and rectum) were found. All studies were explained briefly and summarized in a table. CONCLUSIONS: There is strong evidence to show the efficacy of endoclips in the management of iatrogenic perforations, especially when recognized early. Limitations of endoclipping such as inefficiency against large perforations may be overcome by improving novel techniques in the future.

Lesser celandine (pilewort) induced acute toxic liver injury: The first case report worldwide.

Lesser celandine, also known as Ranunculus ficaria, is a herbaceous perennial plant that commonly utilizes piles and is taken either internally or used externally. The causality assessment of several reports provided evidence for the existence of Greater Celandine hepatotoxicity. However, there hasn't been any case report published thus far, about lesser celandine induced liver injury. Here, we present a case of 36-year-old woman admitted to the hospital with acute hepatitis and jaundice on her sclera with no history of drug abuse or alcohol consumption. However, the patient had a recent history of lesser celandine extract consumption for hemorrhoids, for about 10 d, prior to the admission. Viral hepatitis, autoimmune hepatitis, and drug induced toxic hepatitis were ruled out by further imaging studies and laboratory analysis. Using the Council for International Organizations of Medical Sciences scale, the type of liver injury was assumed as hepatocellular and was scored as 7 which shows probable causality. Immediate discontinuation of lesser celandine extract resulted in rapid decrease of the elevated enzymes. Herbs have been reported to cause liver injury and therefore should be suspected in the case of acute hepatitis with an unknown etiology. This case is important to be the first to explain hepatotoxicity caused by lesser celandine. Physicians should consider lesser celandine as a causative agent for hepatotoxicity.

Impaired right ventricular-pulmonary vascular function in myeloproliferative neoplasms.

BACKGROUND: Increased bone marrow hemangioblast numbers, alterations in erythroid/myeloid lineages, increased reticulin, and greater circulating bone marrow progenitor cells are present in patients with pulmonary arterial hypertension (PAH). The data suggest that myeloid progenitors contribute to the pathogenesis of PAH, but there are little data on the prevalence of pulmonary vascular disease among the different forms of myeloid diseases. We hypothesized that there would be a higher prevalence of pulmonary vascular disease in myeloproliferative neoplasms that have high circulating progenitor cells, such as myelofibrosis and chronic myelogenous leukemia (CML), compared with those with low circulating progenitors, such as in aplastic anemia. METHODS: Patients with myelofibrosis, CML, and aplastic anemia who underwent echocardiographic evaluation of cardiac function in preparation for bone marrow transplantation at the Cleveland Clinic between 1997 and 2012 were identified and their electronic medical records were queried for demographic data, blood cell counts, and pulmonary function tests. All echocardiograms were uniformly analyzed in a blinded fashion by an advanced sonographer and cardiologist for measures of right and left ventricular function and estimation of pulmonary vascular disease. RESULTS: Gender and race distribution among disease groups was similar. Patients with myelofibrosis (n = 19) and aplastic anemia (n = 30) had increased right ventricle (RV) wall thickness compared with CML (n = 82) patients (aplastic anemia, 0.7 ± 0.1; CML, 0.5 ± 0.1; and myelofibrosis, 0.7 ± 0.1; p = 0.02). Patients with myelofibrosis had higher levels of estimated RV systolic pressure compared with the other groups (aplastic anemia, 29.9 ± 1.5; CML, 26.2 ± 1.1; and myelofibrosis, 36.7 ± 3.7 mm Hg; p < 0.01). CONCLUSIONS: The findings suggest an important role for myeloid progenitors in the maintenance of pulmonary-vascular health, in which abnormal myeloproliferative progenitors are associated with RV pathology.

The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in inactive hepatitis B carriers.

AIM: Neutrophil-lymphocyte ratio (NLR) has been used as a simple, affordable, and easily accessible marker to predict prognosis in a variety of inflammatory and neoplastic diseases. However, there are few studies investigating their role in patients with hepatitis B. The aim of this study was to investigate the relationship between NLR and liver fibrosis in patients who were being followed as inactive hepatitis B carriers. MATERIALS AND METHODS: The study included 78 patients who were followed for 1 year as inactive hepatitis B carriers. Liver biopsy was performed and the fibrosis scores of the histological activity index were assessed according to the Metavir scoring system. The patients were divided into two groups on the basis of the fibrosis scores: those with a score below 2 and those with a score above 2. In both groups, demographic data such as sex, age, and BMI were similar. The NLR of patients was calculated from blood samples taken at the same time as the biopsy. RESULTS: Histopathologic analysis of 78 patients showed that 41 (53%) had fibrosis grade 0-1 and 37 (47%) patients had fibrosis grade greater than 2. According to the biopsy results, there were no cirrhotic patients. NLR was found to be statistically significantly lower in the group with fibrosis grade of at least 2 (1.51±0.61 vs. 1.79±0.64, P=0.043). Other biochemical and hematological data were found to be similar in both groups. No correlation was found between laboratory values and NLR. In addition, there was no correlation between NLR with histologic activity. Spearman correlation analysis showed a negative correlation between the fibrosis score and NLR (r=-0.279, P=0.013). CONCLUSION: In inactive hepatitis B carriers, the histological activity index and NLR were found to be correlated negatively. NLR can be used as a predictor of fibrosis in combination with other noninvasive markers.

Impact of inflammatory markers on the prognosis of patients with operable breast cancer.

PURPOSE: To investigate the effect of inflammatory markers on the prognosis of patients with operable breast cancer. METHODS: This study was conducted on breast cancer patients followed up between December 2009 and December 2012 at the Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Medical School. A total of 704 patients with stages I to III disease whose inflammatory markers were assessed at the time of diagnosis were included the study. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, ferritin, ß2 microglobulin (ß2-M), and lactate dehydrogenase (LDH) levels were evaluated as inflammatory markers. RESULTS: The median age at diagnosis was 50 years (range 25-92). Of the patients 42.8% were premenopausal and 48.2 % postmenopausal. Invasive ductal carcinoma was the most common histology (76.5 %). Serum ferritin, LDH, ß2-M, ESR, and CRP were higher than the normal values in 1.0, 4.3, 9.5, 32.4 and 36.4 % of the patients, respectively. Serum albumin levels were lower than the normal values in 1.7 % of the patients. The median patient follow-up period was 22 months (range 3-227). During follow-up, metastatic disease developed in 31 patients (4.4%) and 11 patients (1.56%) died due to disease progression. Two-year overall survival (OS) and disease free survival (DFS) rates were not statistically different among patients with normal and abnormal values with respect to albumin, ferritin, LDH, ß2-M, CRP, and ESR. CONCLUSION: Our study is the first study to investigate the effect of inflammatory markers on the prognosis of operable breast cancer patients. We showed that inflammatory markers such as ESR, CRP, ferritin, ß2-M, albumin and LDH have no effect on prognosis.