Advances in pharmacotherapy for primary biliary cirrhosis

Introduction: Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive.

Areas covered: Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids.

Expert opinion: We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.     

A patient-reported outcome measure for patients with pituitary adenoma undergoing transsphenoidal surgery

Pituitary - Pituitary adenomas affect patients’ quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While...     

Predictors of response to a behavioral treatment in patients with chronic gastric motility disorders

Chronic gastric motility disorders have proven intractable to most traditional therapies. Twenty-six patients with chronic nausea and vomiting were treated with a behavioral technique, autonomic training (AT) with directed imagery (verbal instructions), to help facilitate physiological control. After treatment, gastrointestinal symptoms decreased by >30% in 58% of the treated patients. We compared those improved patients to the 43% who did not improve significantly. No significant differences existed in baseline symptoms and autonomic measures between both groups. However, baseline measures of gastric emptying and autonomic function predicted treatment outcome. Patients who improved manifested mild to moderate delay in baseline gastric emptying measures. The percent of liquid gastric emptying at 60 mins and the sympathetic adrenergic measure of percent of change in the foot cutaneous blood flow in response to cold stress test predicted improvement in AT outcome, with clinical diagnostic values of 77% and 71%, respectively. We conclude that AT treatment can be efficacious in some patients with impaired gastric emptying and adrenergic dysfunction. More work is warranted to compare biofeedback therapy with gastric motility patients and controls in population-based studies.     

Rationale, design, and methods for a pivotal randomized clinical trial for the assessment of a cardiac support device in patients with New York health association class III-IV heart failure

BACKGROUND: Heart failure remains a progressive disease with incremental morbidity and mortality despite optimal medical therapy. A growing body of evidence suggests that progressive left ventricular (LV) remodeling is directly related to a deterioration in LV performance and untoward clinical outcomes for heart failure patients. Preclinical and early phase I clinical studies with the CorCap Cardiac Support Device (CSD), a passive cardiac support device that prevents cardiac remodeling, have shown that it is safe and is associated with improvements in LV structure and function, as well as patient symptomatology. METHODS AND RESULTS: The Acorn Pivotal Trial is a pivotal prospective, randomized, evaluation of the CorCap CSD in patients with New York Heart Association class III-IV heart failure. Patients will be enrolled into one of two different strata. Patients who require a mitral valve repair/replacement (MVR) will fall into the "MVR stratum" and will be randomized to either treatment (MVR surgery plus the CSD) or control (MVR surgery alone). Patients who do not have a clinical indication for MVR surgery will fall into the "no-MVR stratum" and will also be randomized to either treatment (CSD implant plus optimal medical therapy) or control (optimal medical therapy alone). A total of 300 patients (150 treatment and 150 control) will be enrolled. The primary endpoint of the trial is the change in clinical status from baseline to the end of the efficacy phase (1 year), as determined by a clinical composite score. Patients will be classified as improved, worsened, or unchanged based upon patient vital status, the occurrence of a major cardiac procedure indicative of heart failure progression, and a change in the assessment of New York Heart Association functional class. CONCLUSIONS: The Acorn Pivotal Trial will formally test the hypothesis that preventing LV remodeling using a passive cardiac support device will favorably impact the untoward natural history of heart failure and thus represents an important departure from all previous medical and device studies that have been reported to date.     

Reversible airway obstruction in rheumatic mitral valve disease

Lung function was studied in 24 patients with advanced mitral stenosis scheduled for mitral valve replacement (MVR), and revealed an obstructive ventilatory pattern [rewording of this sentence OK] . Forty per cent of the patients had a forced expiratory volume in 1 s (FEV₁)<60% of that predicted in the preoperative period. Twenty-five per cent of those operated upon showed a similar pattern up to 110 weeks postoperatively. A blind study of the effect of placebo and β₂ agonist (salbutamol) inhalation was performed preoperatively and 6 months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, flow volume curve and body plethysmographic measurement of airway resistance (Rex) and intrathoracic gas volume (VTG). Patients in the pre and postoperative period showed a significant difference between the placebo and the β₂ agonist responses for FEV₁, FEV₁ as percentage of FVC (FEV₁% FVC), peak expiratory flow rate (PEFR), flow rate of 50% of expiratory vital capacity ([¨max₅₀), Rex and VTG (P<0.001). We conclude that salbutamol inhalation improves obstructive impairment in patients with MVR pre- and postoperatively.     

Diagnostic value of serum human Galactomannan aspergillus antigen and 1,3‐beta‐D‐glucan in immunocompromised patient suspected fungal infection

BackgroundThe prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3‐beta‐D‐glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells.MethodA cross‐sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman''s correlation coefficient, ROC curve analysis and 2 × 2 contingency table.ResultsSerum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut‐off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut‐off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection.ConclusionsThe immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.     

The effect of botulinum toxin A in patients with excessive gingival display with and without zinc supplementation: randomized clinical trial

Clinical Oral Investigations - The objective is to determine the effect of oral zinc supplement intake on the clinical efficacy and sustained effect of BTXA injection, in patients with excessive...     

Arrhythmogenic right ventricular cardiomyopathy: use of a left ventricular assist device as a bridge to transplantation?

The principal characteristic of arrhythmogenic right ventricular cardiomyopathy (ARVC) is the tendency for ventricular arrhythmia and sudden death to occur without overt ventricular dysfunction. Current recommendations for management of patients with ARVC include insertion of an automated implantable cardioverter–defibrillator (AICD) to prevent sudden cardiac death. However, despite the use of AICD and/or anti-arrhythmic drugs some patients suffer recurrent ventricular arrhythmias unresponsive to optimum medical management. We present two cases of ARVC with refractory recurrent ventricular arrhythmias that were successfully managed by left ventricular assist device (LVAD) implantation, as a bridge to transplant (BTT). These two cases are unconventional examples of use of LVAD, given the predominant right ventricular pathology of ARVC and the arrhythmogenic nature of their presentation. The novelty of these cases should be taken in the context of increasing pressure to standardize indications for use of mechanical circulatory support.