The role of interferon-α in the treatment of idiopathic myelofibrosis

 Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow, varying degrees of extramedullary hematopoiesis, splenomegaly, anemia, and a leukoerythroblastic peripheral blood smear. Bone marrow fibrosis develops as a secondary phenomenon and is caused by increased intramedullary activity of mitogens such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and calmodulin. Because of the variable clinical course of IMF, attempts have been made to define prognostic parameters that can be helpful in detecting patients with a shortened life expectancy. The most important adverse prognostic parameters that have been reported are hemoglobin concentration, age, leukocyte count, number of thrombocytes, and cytogenetic abnormalities. However, no standardized prognostic score for IMF has yet been established. Therapeutic strategies in IMF remain predominantly supportive. The most common are blood transfusions, androgens, and cytoreductive agents such as hydroxyurea. Bone marrow transplantation is increasingly being taken into consideration, but it still has to be regarded as an experimental approach. Interferon-α (IFN-α) has shown promising results in early hyperproliferative stages of IMF but has no or only very little effect in more advanced stages of the disease. Whether IFN-α is able to postpone marrow fibrosis if administered in early disease stages remains to be determined in future clinical trials. Received: February 26, 1999 / Accepted: June 22, 1999     

Etanercept in the treatment of patients with primary Sjögren's syndrome: a pilot study

OBJECTIVE: This pilot study evaluated the effect of anti-tumor necrosis factor-a antiinflammatory treatment with etanercept (Enbrel(R)) on sicca, systemic, and histological signs in patients with primary Sj?gren's syndrome (SS). METHODS: Fifteen patients with well defined primary SS were treated with 25 mg etanercept subcutaneously twice per week during 12 weeks, with followup visits at Weeks 18 and 24. Evaluation measures included a Multidimensional Fatigue Inventory (MFI) questionnaire, serological monitoring, salivary flow tests, Schirmer test, rose bengal cornea staining, and tear film breakup time. A sublabial minor salivary gland biopsy was performed at baseline and at Week 12 and lymphocytic focus score and percentage IgA-containing plasma cells (IgA%) were assessed. RESULTS: No increase of salivary or lachrymal gland function was observed in any participant. In 4 patients a decrease of fatigue complaints was noted, which was also reflected by decreased scores in the MFI questionnaire. Reduced erythrocyte sedimentation rate was observed in 3 of 4 patients with reduced fatigue. No significant change of lymphocyte focus score or IgA% was observed. A repeated treatment up to 26 weeks showed the same results. CONCLUSION: A 12-week or prolonged treatment of etanercept 25 mg twice weekly did not appear to reduce sicca symptoms and signs in SS. However, etanercept treatment may be beneficial in a small subgroup of SS patients with severe fatigue. Etanercept 25 mg twice weekly did not affect minor salivary gland biopsy results.     

The patient’s perioperative perspective during the treatment of obstructive sleep apnea: a pilot study

Purpose

This study aims to determine patients’ pre-operative and post-operative experiences relating to surgical treatment for obstructive sleep apnea (OSA), while understanding how patients’ perceptions influence their outcome and satisfaction.

Methods

This is a phenomenological qualitative study using a semi-structured interview to evaluate patients who failed continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea and underwent airway surgery. Meaningful codes from the interviews were organized into overarching themes of patient experiences. The same surgeon in a tertiary care otolaryngology practice treated all patients. All patients underwent a modified or traditional uvulopalatopharyngoplasty (UPPP) between 2009 and 2013. Patients were diagnosed with OSA by polysomnogram and had failed CPAP use. Patients were interviewed regarding their experience with OSA, CPAP, and surgery. Thematic saturation was reached after 17 patients.

Results

Six themes exemplify patient’s experience of OSA and treatment: (1) OSA impacted patients personally and professionally, (2) CPAP discomfort limited its therapeutic use, (3) patients had personal motivations for undergoing surgery, (4) patient knowledge influenced their perceptions, (5) post-operative challenges exceeded patient expectations, and (6) post-operative outcomes reflected positive effect on patients.

Conclusions

Patients’ experiences prior to surgery can largely influence their perceived outcome and satisfaction. Post-operative sleep studies may not capture the full outcome of the patients’ response to surgery. This study suggests that the patient’s subjective reported outcomes should be used in conjunction with objective post-operative sleep studies.

     

Diagnostic accuracy of T-cell interferon-γ release assays in tuberculous pleurisy: a meta-analysis

Background and objective: The diagnosis of tuberculous pleurisy by analysis of pleural fluid using standard diagnostic tools is difficult. Recently, T‐cell interferon‐γ release assays (IGRA) have been introduced for the diagnosis of tuberculous pleurisy. The aim of the present meta‐analysis was to establish the overall diagnostic accuracy of IGRA on both pleural fluid and peripheral blood, for diagnosing tuberculous pleurisy. Methods: A systematic review was performed of English language publications. Sensitivity, specificity and other measures of the accuracy of IGRA for the diagnosis tuberculous pleurisy using both pleural fluid and blood were pooled using a random‐effects model or a fixed‐effects model. Receiver operating characteristic curves were used to summarize overall test performance. Results: Seven out of eight studies met the inclusion criteria. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and diagnostic odds ratio were, for pleural fluid: 0.75, 0.82, 3.49, 0.24, 0.85, 0.70 and 19.04, respectively; and for blood: 0.80, 0.72, 2.86, 0.28, 0.78, 0.74 and 11.06, respectively. Conclusions: As almost 20% of non‐tuberculosis patients would be erroneously treated for tuberculosis and 25% of patients with tuberculous pleurisy would be missed, pleural fluid IGRA are not useful for the clinical diagnosis of tuberculous pleurisy.     

Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report

The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-α (rIFNα) in "early" PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFNα-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFNα-2a 45 or 90 μg weekly. International Working Group for Myelofibrosis Research and Treatment criteria for prognosis and response were used. Eleven patients were women and 6 were men. Their median age at diagnosis was 57 years. Eleven patients were low risk and 6 were intermediate-1 risk. Two achieved complete remission, 7 partial, 1 clinical improvement, 4 stable disease, and 3 had progressive disease. Thus, more than 80% derived clinical benefit or stability. Improvement in marrow morphology occurred in 4. Toxicity was acceptable. These results, with documented marrow reversion because of interferon treatment, warrant expanded evaluation.     

Alterations in the mucosa-associated bacterial composition in Crohn’s disease: a pilot study

Introduction

Changes in the intestinal bacterial composition seem to play a major role in the pathogenesis and in the clinical course of inflammatory bowel diseases (IBD), which consist of Crohn’s disease (CD), and ulcerative colitis (UC). Mutations in the NOD2 gene are the most important genetic risk factors for the development of CD. In this study, the association between mucosal biopsies and the mucosa-associated bacterial composition from CD and UC patients regarding their genetic risk factors (mutations in the NOD2 gene), their endoscopic activity, and their medical therapy (TNF-α blocking therapy) was examined.

Material and methods

Seventy biopsies from routine colonoscopies from 33 IBD patients (26 CD and 7 UC) were obtained. Disease activity and clinical characteristics were assessed. Seven different bacterial strains (Bacteroides fragilis, Escherichia coli, Prevotella melaninogenica, Clostridium coccoides, Clostridium difficile, Bifidobacterium bifidum, and Faecalibacterium prausnitzii) were quantified using real-time PCR. NOD2 genotyping from patients with CD was performed.

Results

Five of the 24 patients were positive for at least one mutation in the NOD2 gene. The bacterial composition was different in CD compared to UC, in macroscopic healthy compared to macroscopic inflamed biopsies, in NOD2 mutated compared to NOD2 wildtype patients, and in patients receiving TNF-α blocking therapy compared to patients without this treatment.

Conclusion

This study further characterizes the mucosa-associated bacteria in IBD patients. Different clinical situations lead to an altered mucosa-associated bacterial composition. The analyzed bacteria could be promising targets for cost-effective surveillance or therapies in IBD patients.

     

The clinical utility of tuberculin skin test and interferon-γ release assay in the diagnosis of active tuberculosis among young adults: a prospective observational study

Background

The roles of the tuberculin skin test (TST) and QuantiFERON^®-TB Gold In-Tube assay (QFT-IT) in the diagnosis of active tuberculosis (TB) are not clear in young adults. We evaluated the diagnostic accuracy of the TST and QFT-IT in smear-negative TB among young adults with no underlying disease.

Methods

We prospectively enrolled 166 young participants 20-29 years of age with suspected active TB in a military hospital of South Korea. The TST and QFT-IT were performed for all participants.

Results

Of the 143 patients included in the analysis, active TB was diagnosed in 100 (69.9%). There were 141 male patients, none of whom had immunosuppressive disease. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TST were 94% (95% CI, 87-98%), 88% (95% CI, 74-96%), 95% (95% CI, 88-98%), and 86% (95% CI, 72-94%), respectively. The sensitivity, specificity, PPV, and NPV of the QFT-IT were 93% (95% CI, 86-97%), 95% (95% CI, 81-99%), 98% (95% CI, 92-99%), and 84% (95% CI, 69-93%), respectively. No significant differences were found between the TST and QFT-IT in any statistic.

Conclusions

Both the TST and QFT-IT showed high sensitivity and specificity in differentiating active TB from other diseases. The diagnostic accuracy of these two tests did not differ significantly when applied to this clinical population of young, immunocompetent adults in whom neonatal BCG vaccination was common, there was no history of previous TB and in whom suspicion of TB was high.

Trial registration

ClinicalTrials.gov: NCT00982969

     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Long-term antifibrotic action of interferon-γ treatment in patients with chronic hepatitis B virus infection

BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C virus.However,in many liver diseases the cause is either unknown or untreatable.The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma(IFN-γ)treatment in patients chronically infected with hepatitis B virus. METHODS:A total of 42 patients,30 treated with IFN-γand 12 controls,were enrolled from an original clinical trial(Clin Gastroenter...     

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome – a pilot study

Abstract

Objective. Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. Material and methods. Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. Results. One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22–45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). Conclusions. There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.