Chronic Thromboembolic Pulmonary Hypertension: Epidemiology, Diagnosis, and Management.

Chronic thromboembolic pulmonary hypertension (CTEPH), classified as World Health Organization (WHO) group 4 pulmonary hypertension (PH), is an interesting and rare pulmonary vascular disorder secondary to mechanical obstruction of the pulmonary vasculature from thromboembolism resulting in PH. The pathophysiology is complex, beginning with mechanical obstruction of the pulmonary arteries, which eventually leads to arteriopathic changes and vascular remodeling in the nonoccluded arteries and in the distal segments of the occluded arteries mediated by thrombus nonresolution, abnormal angiogenesis, endothelial dysfunction, and various local growth factors. Based on available data, CTEPH is a rare disease entity occurring in a small proportion (0.5-3%) of patients after acute pulmonary embolism with an annual incidence ranging anywhere between 1 and 7 cases per million population. It is often underdiagnosed or misdiagnosed as idiopathic pulmonary arterial hypertension due to a lack of clinical suspicion or the under-utilization of radionuclide ventilation/perfusion scan. Although the current standard remains planar ventilation/perfusion scintigraphy as the initial imaging study to screen for CTEPH, and invasive pulmonary angiography with right heart catheterization as confirmatory modalities, they are likely to be replaced by modalities that can provide both anatomic and functional data while minimizing radiation exposure. Surgery is the gold standard treatment and offers better improvements in clinical and hemodynamic parameters compared with medical therapy. The management of CTEPH requires a multidisciplinary team, operability assessment, experienced surgical center, and the consideration of medical PH-directed therapies in patients who have inoperable disease, in addition to supportive therapies. Although, balloon pulmonary angioplasty is gaining interest to improve pulmonary hemodynamics and symptoms in CTEPH patients not amenable to surgery, further investigative randomized studies are needed to validate its use. It is very important for the present-day physician to be familiar with the disease entity and its appropriate evaluation to facilitate early diagnosis and appropriate management.

Congenital and infantile malignant melanoma of the scalp: A systematic review.

Congenital and infantile malignant melanomas are rare and typically carry poor prognosis. The purpose of this article was to review the data on congenital and infantile malignant melanomas of the scalp in order to understand its presentation, diagnosis, management, and outcomes of congenital melanoma of scalp. We searched PubMed, CINAHL and Cochrane databases. Ten cases of congenital and 3 cases of infantile malignant melanoma of scalp were identified. The diagnosis was confirmed by biopsy and histological analysis for confirmation. The prognosis depends on the origin of disease (congenital melanocytic nevus, transplacental metastasis, or de-novo), tumor thickness, the presence of ulceration and/or necrosis, and anatomic site (scalp lesions having poor prognosis). The most commonly used treatment of the reported cases of congenital and infantile melanoma was surgical excision of the primary lesion. Further modes of treatment may be extrapolated from the treatment of childhood and adult melanomas.

Cardiac Resynchronization Therapy for Heart Failure.

Cardiac resynchronization therapy (CRT) has emerged as a valued nonpharmacologic therapy in patients with heart failure, reduced ejection fraction (EF), and ventricular dyssynchrony manifest as left bundle branch block. The mechanisms of benefit include remodeling of the left ventricle leading to decreased dimensions and increased EF, as well as a decrease in the severity of mitral regurgitation. This article reviews the rationale, effects, and indications for CRT, and discusses the patient characteristics that predict response and considerations for nonresponders.

Advances in chemical pharmacotherapy for managing acute decompensated heart failure.

INTRODUCTION: Acute decompensated heart failure (ADHF) contributes largely to the burden of heart failure and is associated with a poorer prognosis. Although numerous clinical trials evaluated the benefit of newer medications for ADHF, most of them were not successful. Areas covered: This review focusses on the updates on recent developments in chemical pharmacotherapy for the management of ADHF. A MEDLINE search for relevant review articles and original investigations on newer drugs for ADHF provided us with necessary literature. Expert opinion: Currently, popular therapies like diuretics, vasodilators, and inotropes offer symptomatic relief but do not provide survival benefit. Although multiple medications targeting novel pathways in ADHF were studied extensively, they failed to show either symptomatic or mortality benefit in available randomized trials. Improving our understanding of the complex pathophysiology of ADHF along with designing studies which include patients who are more representative of the real-world heart failure population, standardizing methods for endpoint assessment, and evaluating the role on novel biomarkers of organ dysfunction is important to improve ADHF research. Enhancing preventive strategies like improving baseline therapy in chronic heart failure patients and developing strategies for early identification of ADHF are important as our quest for innovative ADHF pharmacotherapy continues.

Ambulatory pulmonary artery pressure monitoring in advanced heart failure patients.

Heart failure (HF) is an emerging epidemic associate with significant morbidity, mortality, and health care expenditure. Although there were major advances in pharmacologic and device based therapies for the management of HF, mortality of this condition remains high. Accurate monitoring of HF patients for exacerbations is very important to reduce recurrent hospitalizations and its associated complications. With the failure of clinical signs, tele-monitoring, and laboratory bio-markers to function as early markers of HF exacerbations, more sophisticated techniques were sought to accurately predict the circulatory status in HF patients in order to execute timely pharmacological intervention to reduce frequent hospitalizations. CardioMEMSTM (St. Jude Medical, Inc., Saint Paul, Minnesota) is an implantable, wireless pulmonary arterial pressure (PAP) monitoring system which transmits the patient's continuous PAPs to the treating health care provider in the ambulatory setting. PAP-guided medical therapy modification has been shown to significantly reduce HF-related hospitalization and overall mortality. In advanced stages of HF, wireless access to hemodynamic information correlated with earlier left ventricular assist device implantation and shorter time to heart transplantation.

The association between socioeconomic status and the symptoms at diagnosis of celiac disease: a retrospective cohort study.

BACKGROUND: There are little data on patient factors that impact diagnosis rates of celiac disease. This study aims to evaluate the association between patient socioeconomic status and the symptoms at diagnosis of celiac disease. METHODS: A total of 872 patients with biopsy-proven celiac disease were categorized based on the presence or absence of (1) diarrhea and (2) any gastrointestinal symptoms at diagnosis. Univariate and multivariate analyses were used to assess the association between socioeconomic status and symptoms. RESULTS: Patients without diarrhea at presentation had a higher mean per capita income (US$34,469 versus US$32,237, p = 0.02), and patients without any gastrointestinal symptoms had a higher mean per capita income (US$36,738 versus US$31,758, p < 0.01) compared with patients having such symptoms. On multivariable analysis adjusting for sex, age, autoimmune or psychiatric comorbidities, and income, per capita income remained a significant predictor of diagnosis without gastrointestinal symptoms (odds ratio: 1.71, 95% confidence interval: 1.17-2.50, p < 0.01), and it showed a trend towards significance in diagnosis without diarrhea (odds ratio: 1.40, 95% confidence interval: 0.98-2.02, p = 0.06). CONCLUSIONS: Patients with nonclassical symptoms of celiac disease are less likely to be diagnosed if they are of lower socioeconomic status. Celiac disease may be under-recognized in this population due to socioeconomic factors that possibly include lower rates of health-seeking behavior and access to healthcare.

Update on pulmonary arterial hypertension pharmacotherapy.

Pulmonary artery hypertension (PAH) refers to several subgroups of disease in which the mean pulmonary artery pressure (mPAP) is elevated to more than 25 mm Hg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR) > 3 Wood units as confirmed by right heart catheterization. The prevalence and geographic distribution of PAH vary depending on the type and etiology of the disease. Despite enormous efforts in the research and development of therapeutic agents in the last twenty years, the disease remains relatively incurable and the overall prognosis remains guarded. Median survival for an untreated patient is 2.8 years. In the last three decades, there have been dramatic advances in understanding the molecular mechanisms and signaling pathways involved in the disease, resulting in emerging new treatment strategies. In the following pages, we will review currently approved treatments for PAH, as well as a new generation of investigational drugs.

Use of Extracorporeal Membrane Oxygenation in Refractory Cardiogenic Shock.

Cardiogenic shock is a condition marked by low cardiac output and end-organ hypoperfusion frequently requiring hemodynamic support, and it carries a high mortality. Extracorporeal membrane oxygenation (ECMO) is an effective tool in providing mechanical circulatory support in patients with cardiogenic shock refractory to conventional medical therapies. ECMO can be an essential bridge to recovery, ventricular assist device implantation or transplant. A multidisciplinary team approach is needed in managing such patients and intensive monitoring is required to avoid complications from ECMO. Nevertheless, randomized clinic trials are warranted to prove a survival benefit.

Socioeconomic Risk Factors for Celiac Disease Burden and Symptoms.

BACKGROUND & AIMS: Celiac disease (CD) affects approximately 1% of the population and negatively affects aspects of life including physical and social function. The relationship between socioeconomic (SE) factors, symptom severity, and perceived burden of living with CD is not well understood. The objective of this study was to assess the relationships between income, symptoms, and perceived burden of CD. METHODS: In this survey study conducted at a tertiary care center, 773 patients 18 years of age or more with biopsy confirmed CD were eligible to participate. Patients completed a survey with information on SE data, the validated Celiac Symptom Index (CSI), and visual analog scales (VAS) assessing overall health, CD-related health, difficulty in following a gluten-free diet (GFD), and importance of following a GFD. RESULTS: Three hundred forty one patients completed the survey. Higher income predicted better overall health, better CD related health, and fewer symptoms. In the logistic regression model, low income was associated with greater CD symptoms (odds ratio=6.04, P=0.002). Other factors associated with greater symptoms were younger age, poor overall health state, and more physician visits. Factors associated with increased burden of CD included hospitalizations, more symptoms, poor overall health state, and burden of following a GFD. CONCLUSIONS: Patients with lower incomes have worse CD-related health and greater symptoms. Those with low income had 6 times the odds of greater symptoms compared with those with high income. Our data suggest that income is associated with perceived overall health, CD-related health, and CD symptoms.

Use of Inotropic Agents in Treatment of Systolic Heart Failure.

The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.). Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

Patient perception of treatment burden is high in celiac disease compared with other common conditions.

OBJECTIVES: The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of CD, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares with other medical treatments, and there are limited data on the socioeconomic factors influencing treatment adherence. In this study, we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence. METHODS: Survey was mailed to participants with CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome, inflammatory bowel disease, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, and end-stage renal disease (ESRD) on dialysis. Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific health status, and overall health status. RESULTS: We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education, and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment. CONCLUSIONS: Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for CD argues for the need for safe adjuvant treatment, as well as interventions designed to lower the perceived burden of the GFD.

Clinical utility of celiac disease-associated HLA testing.

BACKGROUND: Negative predictive value (NPV) of celiac disease (CD)-related human leukocyte antigens (HLA) DQ2 and DQ8 approaches 100 % in individual patients. However, studies evaluating its exclusionary utility in patient groups are lacking. AIM: We aim to assess the performance of HLA testing when applied to patient groups with varying characteristics and propose evidence-based recommendations for its clinical use. METHODS: Demographic and clinical information was recorded in patients undergoing HLA testing. Using predetermined criteria, patients were classified as CD, non-CD, or indeterminate. Diagnostic yield of HLA testing was defined as the percentage of patients in whom CD could be excluded based on negative HLA test. RESULTS: Two hundred and fifty-six patients underwent testing for CD-related HLA DQ2 and DQ8. 102 (100 non-CD, 2 CD) patients tested HLA negative for a 98 % NPV and 39 % diagnostic yield. Diagnostic yield was highest (60 %) in patients with intraepithelial lymphocytosis plus normal IgA tissue transglutaminase antibody (IgA-tTG) and lowest in patients with positive IgA-tTG plus villous atrophy (0 %). CD was diagnosed in two HLA-negative patients, who carried half of DQ2.5 trans genotype. CONCLUSIONS: Diagnostic yield of CD-related HLA testing varies widely depending on clinical indication. HLA testing is a practical and valuable test for most patients in whom initial evaluation for CD is inconclusive. A negative HLA result usually obviates the need for further celiac testing including endoscopy and gluten challenge. Rarely, in patients reported as HLA negative, half of HLA DQ2.5 (cis or trans) is sufficient for development of CD.

Open conformation tissue transglutaminase testing for celiac dietary assessment.

OBJECTIVES: Anti tissue-transglutaminase antibody is the mainstay of celiac disease serologic testing. Whilst it has high sensitivity in patients on an unrestricted diet, sensitivity is poor for evaluation of gluten free diet adherence. AIM: To assess the utility of a novel assay measuring Immunoglobulin-A antibodies to catalytically active open conformation tissue-transglutaminase in assessment of ongoing gluten exposure in celiac disease patients on an alleged gluten free diet. METHODS: Through prospective assessment, 147 patients with celiac disease were divided into good and poor adherence. Open and closed (conventional) tissue-transglutaminase titres were measured using standard enzyme linked immunosorbent assay. 50 patients with inflammatory bowel disease served as disease controls. RESULTS: Overall 128 patients had been on gluten free diet for more than six months and 19 were found to be poorly adherent on dietary review. Within this group 13 (68.4%) and 10 (52.6%) patients respectively were positive for the open conformation and conventional assay (p=0.51). Two and one control patients tested positive for closed and open assays respectively. CONCLUSIONS: Compared to native assays open conformation tissue-transglutaminase may have higher sensitivity in the poor gluten free diet adherence group and higher specificity in the control population. Larger population studies are warranted to assess whether the open conformation tissue-transglutaminase assay may be superior to the conventional assay.

The incidence and clinical spectrum of refractory celiac disease in a north american referral center.

OBJECTIVES: Refractory celiac disease (RCD) is one of the most serious causes of persistent symptoms in patients with celiac disease (CD). Published reports suggest that approximately half of patients in Europe are RCD type II, which carries a poor prognosis with a 5-year survival rate of ~50% compared with ~90% for RCD type I. However, disease patterns may be different in North America. The aim of this study was to explore the clinical spectrum of RCD in a North American population. METHODS: Medical records of patients with biopsy-proven CD presenting to our institution were reviewed for a diagnosis of RCD. Demographic data, clinical characteristics, and mortality were evaluated and compared with our general CD population. RESULTS: In all, 34 out of 844 (4.0%) CD patients had RCD. The cumulative incidence of RCD for patients diagnosed with CD at our center was 1.5%. Unintentional weight loss at diagnosis of RCD was found in 76.5% (n=26) compared with 16.7% (n=141) at diagnosis of CD (P<0.0001) and diarrhea at diagnosis of RCD was found in 79.4% (n=27) compared with 40.5% (342) at diagnosis of CD (P<0.0001). Five patients (14.7%) were diagnosed with RCD type II and of these, two died of enteropathy-associated lymphoma within 24 months of diagnosis of CD (observed mortality rate 5.9%). CONCLUSIONS: Although RCD is a serious condition with significant morbidity; the observed mortality rates are low in our population. This study suggests that RCD may be less severe in North American vs. European populations.