Does Left Atrial Size Predict Mortality in Asymptomatic Patients with Severe Aortic Stenosis?

Background: We assessed the hypothesis that diastolic function represented by left atrial size determines the rate of development of symptoms and the risk of all‐cause mortality in asymptomatic patients with severe aortic stenosis (AS). Methods: From a database of 622 asymptomatic patients with isolated severe AS (velocity by Doppler ≥ 4 m/sec) followed for 5.4 ± 4 years, we reviewed the echocardiograms and evaluated Doppler echocardiographic indices of diastolic function. Prediction of symptom development and mortality by left atrial diameter with and without adjusting for clinical and echocardiographic parameters was performed using Cox proportional‐hazards regression analysis. Results: The age was 71 ± 11 years and 317 (62%) patients were males. The aortic valve mean gradient was 46 ± 11 mmHg, and the Doppler‐derived aortic valve area was 0.9 ± 0.2 cm². During follow‐up, symptoms developed in 233 (45%), valve surgery was performed in 290 (57%) and 138 (27%) died. Left atrial enlargement was significantly correlated with symptom development (P < 0.05) but the association diminished after adjusting for aortic valve area and peak velocity (P = 0.2). However, atrial diameter predicted death independent of age and gender (P = 0.007), comorbid conditions (P = 0.03), and AS severity and Doppler parameters of diastolic function (P = 0.002). Conclusion: Diastolic function, represented as left atrial diameter, is related to mortality in asymptomatic patients with severe AS. (ECHOCARDIOGRAPHY 2010;27:105‐109)     

Nocturnal Hydration—An Effective Modality to Reduce Recurrent Abdominal Pain and Recurrent Pancreatitis in Patients with Adult-Onset Cystic Fibrosis

Recurrent abdominal pain and recurrent pancreatitis are common problems associated with some patients with cystic fibrosis (CF). There is no known effective method to prevent recurrent abdominal pain and recurrent pancreatitis in such patients. The objective of this study was to determine whether nocturnal hydration (NH) prevents recurrent abdominal pain and recurrent acute pancreatitis in patients with adult-onset CF. Adult CF patients who were referred to our Pancreatic Diseases Clinic for recurrent abdominal pain and pancreatitis were enrolled in the study. Each patient was encouraged to drink plenty of water during the night and established a 6-month diary (3 months before and 3 months after NH was initiated), recording the frequency and severity of their abdominal pain, the amount of pain medication taken, and the volume of their water intake. We also reviewed the number of doctor's clinic visits, emergency room visits, and hospitalizations for about 1 year before and 1 year after the initiation of the NH. The frequency and the severity of abdominal pain in this group of patients were significantly reduced. The amount of pain medication and the number of emergency room visits and hospitalizations for abdominal pain and acute pancreatitis were reduced. NH is a simple and cost-effective method to prevent recurrent abdominal pain and pancreatitis in patients with adult-onset CF.     

Soluble CD14 Subtype—A New Biomarker in Predicting the Outcome of Critically Ill Septic Patients

Background

We evaluated the role of presepsin (soluble CD14 subtype, sCD14-ST) in predicting the outcome of critically ill septic patients in parallel with procalcitonin and C-reactive protein.

Treatment of Severe Edema in Children with Nephrotic Syndrome with Diuretics Alone — A Prospective Study

Background and objective: Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone.Design, setting, participants, & measurements: Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) <1%. VC patients received IV albumin and furosemide. VE patients received IV furosemide and oral spironolactone. On the basis of phase 1 observations, FeNa <0.2% identified VC in 20 phase 2 patients.Results: All phase 1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff of 0.2%; it was noted that VC patients had higher BUN, BUN/creatinine ratio, urine osmolality, and lower FeNa and urine sodium compared with VE patients. Similar results were observed in phase 2. VC patients had significantly higher renin, aldosterone, and antidiuretic hormone levels. In phase 2, 11 VE patients received diuretics alone and 9 VC patients received albumin and furosemide. There was no difference in hospital stay and weight loss in VC and VE groups after treatment.Conclusions: FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone in VE patients is safe and effective.Idiopathic nephrotic syndrome (NS) is a common renal disease in children. Children with severe edema are usually hospitalized and treated with intravenous (IV) albumin and diuretics. In contrast to adults, children are often more severely hypoalbuminemic and edematous, necessitating hospitalization and IV albumin administration. Albumin is routinely used in children because of (1) low serum oncotic pressure due to hypoalbuminemia, (2) reports of diuretic resistance and decreased efficacy in NS (1–4), (3) increased diuresis when diuretics are given after IV albumin (1,5,6), and (4) a reluctance to treat patients with diuretics only because of concerns about dehydration and increased risk of thromboembolic complications.The routine use of albumin for severe edema (7) in children with NS is based on two mutually exclusive hypotheses proposed for the pathogenesis of edema (8–11). According to the underfill hypothesis, severe hypoalbuminemia decreases intravascular oncotic pressure, leading to circulatory volume depletion and subsequent sodium/water retention (8–11). The overfill mechanism proposes a primary renal defect in sodium excretion leading to sodium/water retention and thereby hypervolemia and edema (8–11). The underfill hypothesis is believed to be more common (7,12). Also, clinically it is not possible to differentiate severely edematous NS patients with intravascular volume expansion (VE) from those with intravascular contraction (VC) (7,12). Hence, the pediatric practitioners are reluctant to only treat the former group of patients with diuretics. The objective of this study was to evaluate the use of diuretics alone for the treatment of severe edema in a subset of children with NS, identified as VE.     

Quality of Life in Patients with Cirrhosis—Measurement and Clinical Impact

Purpose of the Review

As understanding of liver disease progression to cirrhosis has expanded, there has also been an acceleration in clinical trials and treatment options for the different underlying causes of cirrhosis to include chronic viral hepatitis, alcoholic and non-alcoholic fatty liver disease. It is imperative that healthcare practitioners fully appreciate the impact of liver disease and treatment from the patients’ and society perspective.

Recent Findings

An important aspect of patient-reported outcomes (PROs) is assessment of health-related quality of life (HRQL) completed using generic or disease-specific instruments. In the past decades, substantial evidence has been complied that demonstrates development of cirrhosis which has a significant negative impact on a patients’ HRQL while effective treatment leads to significant gains in HRQL especially for patients with decompensated cirrhosis.

Summary

Clinicians and clinical investigators must understand the importance of PROs for inclusion in clinical trials to fully assess the impact of cirrhosis on patients and the society.

     

Association Between Polymorphism of Tumor Necrosis Factor-α Promoter and Response to Lamivudine Treatment in Patients with Chronic Hepatitis B

Background  

TNF-α promoter polymorphism is known to play an important role in the immunopathogenesis of infection of hepatitis B virus.     

Combined Chelation Therapy with Deferoxamine and Deferiprone in β-Thalassemia Major: Compliance and Opinions of Young Thalassemic Patients

Treatment of β-thalassemia major (β-TM) includes regular blood transfusions and iron chelation with subcutaneous injection of deferoxamine (DFO). During the last decade, a new chelation agent, deferiprone (L1), was introduced. The purpose of our study was to determine the level of awareness/education regarding chelation therapy, the degree of compliance to this therapy and their views of L1 in patients with β-TM. A relevant questionnaire was administered to 36 patients (12–26 years old) who were on combination chelation therapy with both DFO and L1. The majority of patients was well aware/educated about chelation therapy (76.6%), was compliant with this therapy (74.4%) and had a positive view towards oral chelation (86.0%). In conclusion, most patients with β-TM who were on combination chelation therapy with DFO and L1 were satisfied with this treatment and this results in high compliance rates.     

Non-association of IL-12 +1188 and IFN-�� +874 Polymorphisms with Cytokines Serum Level in Occult HBV Infected Patients

Background/Aim:

Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI.

Materials and Methods:

In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg^-/anti-HBc⁺ samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA.

Results:

Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg^-/anti-HBc⁺ and HBV-DNA was detected in 57/352 (16.1%) of HBsAg^-/anti-HBc⁺ samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines.

Conclusion:

According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.     

Small Esophageal Varices in Patients with Cirrhosis—Should We Treat Them?

Purpose of Review

The natural history and classification systems of small varices (≤?5 mm in diameter) in cirrhotic patients with portal hypertension are summarized. Studies that assessed the course of and therapeutic intervention for small varices are discussed.

Recent Findings

Current non-invasive methods show suboptimal sensitivity to detect small varices in patients with cirrhosis. Next to etiological therapy, hepatic venous pressure gradient (HVPG)-guided non-selective betablocker or carvedilol treatment has shown to impact on natural history of small varices.

Summary

The main therapeutic focus in cirrhotic patients with small varices is the cure of the underlying etiology. The optimal management of small varices should include measurement of HVPG. A pharmacological decrease in HVPG by non-selective betablocker therapy of ≥?10% reduces the risk of progression to large varices, first variceal bleeding, and hepatic decompensation. If HVPG is not available, we would recommend carvedilol 12.5 mg q.d. for treatment of small varices in compensated patients without severe ascites. Only if small esophageal varices (EV) are not treated or in hemodynamic non-responders, follow-up endoscopies should be performed in 1–2 years of intervals considering the activity of liver disease or if hepatic decompensation occurs.

     

Microvolt T-Wave Alternans in End-Stage Renal Disease Patients—Associations with Uremic Cardiomyopathy

Summary

Background and objectives

Premature cardiovascular (CV) events, especially sudden cardiac death, are common in ESRD patients and associated with uremic cardiomyopathy. Identification of high-risk patients is difficult. Microvolt T-wave alternans (MTWA) is a noninvasive method of detecting variability in electrocardiogram (ECG) T-wave morphology and is a promising technique for identifying patients at high risk of ventricular tachyarrhythmias. MTWA results of ESRD and hypertensive left ventricular hypertrophy (LVH) patients were assessed to determine the prevalence of abnormal results and associations with uremic cardiomyopathy.

Design, setting, participants, & measurements

In this single-center observational study, 200 ESRD and 30 LVH patients underwent assessment including CV history, ECG, cardiac magnetic resonance imaging, and an MTWA exercise test. MTWA results were classified as “negative” or “abnormal” on the basis of previously published reports.

Results

An abnormal MTWA result was more common in ESRD compared with LVH patients (57.5% versus 26.7%, respectively; P = 0.002). In ESRD patients, MTWA was significantly associated with uremic cardiomyopathy, clinical history of atherosclerosis (coronary, cerebral, peripheral) and diabetes mellitus, older age, and hemodialysis therapy. Independent associations with an abnormal MTWA result were older age, macrovascular disease, increased left ventricle (LV) mass, and LV dilation.

Conclusions

Features of uremic cardiomyopathy are associated with an abnormal MTWA result.     

Certolizumab Pegol Compared to Natalizumab in Patients with Moderate to Severe Crohn’s Disease: Results of a Decision Analysis

Introduction  

A significant proportion of patients with Crohn’s disease (CD) lose response to antibodies directed against tumor necrosis factor α (TNF). Prior TNF-antagonist failure is associated with lower rates of response to subsequent TNF-antagonist therapy. In patients failing two anti-TNF agents, a choice exists between using a third-anti-TNF therapy or natalizumab (NAT), an α-4 integrin inhibitor. A cost-effectiveness analysis comparing these competing strategies has not been performed.     

Right Ventricular Failure—A Continuing Problem in Patients with Left Ventricular Assist Device Support

The discrepancy between the limited availability of donor hearts and the ever-increasing number of patients with heart failure has led to the increasing use of left ventricular assist devices (LVAD) as a bridge to transplant. One of the main complications inherent following institution of LVAD therapy is right ventricular (RV) failure, manifested by the need for inotropic and/or nitric oxide support >14 days after LVAD implant and/or the need for right-sided mechanical circulatory support. RV failure is a major contributor of significant morbidity and mortality after LVAD placement. The complex pathophysiology of RV failure, which could potentially be related to RV myocardial dysfunction, interventricular dependence, and RV afterload, has led to inconsistencies in predicting risk factors for RV dysfunction. Several strategies have evolved over the years of experience with mechanical circulatory support that have aimed to avoid as well as reduce the incidence of RV failure. It is imperative that patients who definitely need biventricular support are identified. Despite the numerous risk factors identified in many studies as well as the development of risk factor profile scores, this continues to be a challenging problem. However, the lower incidence of RV failure following LVAD in the current era is encouraging, suggesting a favorable relationship between RV unloading and function, and continuous-flow physiology.     

Combined Thrombophilic Risk Factors and Essential Thrombocythemia in Patient with Recurrent Venous Thromboembolic Episodes—Thirty-Three-Year Follow-Up

We present the case of a 64 year-old female patient, with a clearly positive family history of venous thromboembolism (VTE), multiple VTE episodes (massive pulmonary embolism, ovarian venous plexus thrombosis, deep venous thrombosis with submassive pulmonary embolism and second deep venous thrombosis) and myocardial infarction.Laboratory tests revealed the resistance to the activated protein C, elevated FVIII and PAI-1. The patient was found to be a heterozygous carrier of FV Leiden, MTHFR C677T and PAI-1 4G/5G mutations. She was diagnosed with essential thrombocythemia at the age of 60.The thirty-three-year follow-up of our patient and detection of recurrent thrombotic episodes in the light of multiple coagulation defects with proved acquired risk factors, contributes to the risk stratification in the group of patients with very high risk. In case of our patient, we stress inadequacy of widely-accepted standard prevention measures. In our opinion, patients with very high risk require additional mechanic and specific medicament methods of VTE prevention.     

JIKEI HEART Study—A Morbi-Mortality and Remodeling Study with Valsartan in Japanese Patients with Hypertension and Cardiovascular Disease

BACKGROUND: Several recent clinical trials have demonstrated that angiotensin II receptor blockers (ARBs) have cardiovascular as well as renal protective effects. Asian patients including Japanese were under-represented in these trials, however, and no large-scale clinical trials of ARBs have yet been performed in Japan. It is therefore important to verify that the results of these studies are also valid for Japanese patients. The JIKEI HEART Study has been designed to investigate whether concomitant treatment with valsartan, an angiotensin II receptor blocker, in addition to conventional treatment, will improve the prognosis of Japanese patients with cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure). METHOD AND EVALUATION OF RESULTS: Around 3,000 patients with hypertension, ischemic heart disease and/or congestive heart failure will be randomized to receive either additional treatment with valsartan (80 mg/day) or conventional therapy. The follow-up period will be three years. The primary endpoint will be the onset of any cardiovascular event. Secondary endpoints will include death from any cause, changes in left ventricular size and function, renal function, changes in neuro-hormonal levels and quality-of-life assessments. Sub-studies will explore the effect in patients with diabetes mellitus, hyperlipidemia and the effects of combination of drugs. CONCLUSION: Improved prognosis would confirm the role of angiotensin II receptor blockers in the treatment of the cardiovascular disease in Japanese patients.     

The Effect of Oral Administration of Silymarin on Serum Levels of Tumor Necrosis Factor-α and Interleukin-1ß in Patients with Rheumatoid Arthritis

Background: Rheumatoid Arthritis (RA) is a systemic chronic autoimmune disease. Several inflammatory agents play key roles in RA pathogenesis, among which tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) are of great importance. Silymarin is a potent anti-oxidant extracted from Silybummarianum L. seeds. Objective: To study the effect of silymarin on serum levels of TNF-α and IL-1β in patients with RA. Methods: Patients with stable RA received 140 mg of silymarin, 3 times a day, for 3 months. Serum samples were collected before and after the treatment. Both TNF-α and IL-1β serum levels were measured by ELISA. Results: 42 patients (14.3% male, and 85.7% female, with a mean age of 47.59±12.8 years old) completed the treatment course. There was no significant difference in the overall mean concentration of either TNF-α (p=0.14) or IL-1β (p=0.27) in all 42 patients after the treatment with silymarin. Conclusion: The addition of silymarin to the treatment regimen of patients with stable RA has no significant effect on the serum levels of TNF-α and IL-1β, however, this study needs further evaluation with a larger sample size.