Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients.METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 μg/wk) or PegIFN alpha 2b (1 or 1.5 μg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk.RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001).CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.     

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: A retrospective multicentre study

BackgroundAcoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis.AimTo evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography.MethodsA multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients.ResultsThe best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels > 5× the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively.Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5× the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively.For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5× the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa.ConclusionLiver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.     

The role of Dietary Approaches to Stop Hypertension (DASH) diet food groups in blood pressure in type 2 diabetes

The role of each Dietary Approaches to Stop Hypertension (DASH) diet component in blood pressure (BP) of patients with diabetes is still uncertain. The aim of the present study was to evaluate possible associations of the recommended food groups of the DASH diet eating plan with BP values in patients with type 2 diabetes. In the present cross-sectional study, 225 patients with type 2 diabetes (age 61·1 (SD 10·4) years; diabetes duration 13·1 (SD 9·1) years; males 48·4 %; BMI 28·5 (SD 4·3) kg/m(2); HbA1c 7·1 (SD 1·3) %; systolic BP 136·7 (SD 20·0) mmHg; diastolic BP 78·4 (SD 11·8) mmHg) without dietary counselling during the previous 6 months had their dietary intake assessed by 3 d weighed-diet records. Patients were divided into two groups according to BP tertiles: LOW BP (first tertile) and HIGH BP (second plus third tertiles). Multivariate logistic regression models demonstrated that the daily intake of 80 g of fruits per 4184 kJ (1000 kcal) (OR 0·781; 95 % CI 0·617, 0·987; P = 0·039) or 50 g of vegetables per 4184 kJ (1000 kcal) (OR 0·781; 95 % CI 0·618, 0·988; P = 0·040) reduced the chance of the presence of HIGH mean BP (MBP ≥ 92 mmHg) by 22 % each, adjusted for possible confounders. In conclusion, fruit and vegetables were the food groups of the DASH diet associated with reduced BP values in patients with type 2 diabetes, and their consumption might play a protective role against increased BP values.     

Multiple Intestinal Atresia With Combined Immune Deficiency Related to TTC7A Defect Is a Multiorgan Pathology: Study of a French-Canadian-Based Cohort

Hereditary multiple intestinal atresia (HMIA) is a rare cause of intestinal obstruction in humans associated with a profound combined immune deficiency. Deleterious mutations of the tetratricopeptide repeat domain–7A (TTC7A) gene lead to HMIA, although the mechanism(s) causing the disease in TTC7A deficiency has (have) not yet been clearly identified.To evaluate the consequences of TTC7A deficiency, we studied the morphology of several organs from HMIA patients at different developmental stages, as well as the expression of the TTC7A protein. We performed histological and immunohistochemical analyses on biopsies and autopsies of 6 patients and 1 fetus with HMIA. Moreover, we characterized for the first time the expression of the TTC7A protein by immunostaining it in several organs from control (including fetal samples), infants, and 1 fetus with HMIA.Besides the gastrointestinal tract, HMIA disease was associated with morphological alterations in multiple organs: thymus, lung, spleen, and liver. Moreover, we demonstrated that normal TTC7A protein was expressed in the cytoplasm of epithelial cells of the intestine, thymus, and pancreas. Surprisingly, altered TTC7A protein was highly expressed in tissues from patients, mainly in the epithelial cells.We have established that HMIA associated with a TTC7A defect is characterized by multiorgan impairments. Overall, this report suggests that TTC7A protein is critical for the proper development, preservation, and/or function of thymic and gastrointestinal epithelium.     

Three cases of familial hairy cell leukemia

In a 10-year interval, a total of 12 cases of familial hairy cell leukemia have been published. They were noted in first degree relatives, mostly in men. In some instances, when the HLA type was performed, a specific HLA type was found in the studied family, but a different haplotype was seen in other families. It appeared that familial cases of hairy cell leukemia were not associated with a “specific HLA antigen” and other factor(s) such as environmental, or some kind of occupational exposure, were suggested to play a role in the familial occurrence of hairy cell leukemia. We add three more familial hairy cell leukemia cases which are different from other published cases, showing a female predominance. The HLA typing revealed interesting findings. The HLA type shared by case 1 and 3 was A2, A30/31(19), B27, Bw4, Bw6. From these, HLA A2, Bw4, and Bw6 were previously reported (Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH: Cancer 65:319–321, 1990). Case 2, shared with the other two the antigen Bw6. Its specific HLA type was A3 and B7, the type previously reported in a family (Begley CG, Tait B, Crapper RM, Briggs RG, Brodie GN, Mackay IR: Leuk Res 11:1027–1028, 1987). Based on these observations, we may conclude that a “specific HLA type,” A2, Bw4, Bw6 and A3, B7 might have a role in the genetic predisposition for hairy cell leukemia. © 1993 Wiley-Liss, Inc.     

Stability of cosmetic formulations containing esters of vitamins E and A: chemical and physical aspects

Cosmetic stability prediction relies on quantitative chemical determinations of active components after certain times and in different temperatures. However, physical stability, an important parameter in skin care products is not considered in these conditions. This study proposes the determination of cosmetic stability chemical and physical parameters validated by (HPLC) chromatography and rheological measurements, respectively, using a gel-cream containing retinyl palmitate and tocopheryl acetate as a model system. The predicted shelf life addresses both the physical and chemical aspects of the system. Results emphasize the importance of studying both parameters by showing the relation of components degradation and physical stability. Moreover, they contribute to an improved understanding of physical and chemical stability aspects of cosmetic formulations, mainly if they contain Vitamins A and E derivatives.     

Retinophotography--screening method in diabetic retinopathy

The paper presents the modern screening method for diabetic retinopathy-the retino-photography. We present our experience on this issue, regarding the patients with diabetic retinopathy screened in Diabetic Eye Department, Ophthalmology Clinic Craiova, between October 2002-June 2005.     

Myocardial infarction and patent coronary arteries--an uneventful association?

BACKGROUND: Although many studies addressed the issue of the occurrence of acute myocardial infarction (MI) in patients with angiographically patent coronary arteries, controversies exist concerning the pathophysiology and clinical outcome in this syndrome. AIM: To evaluate the clinical course of patients with MI and patent coronary arteries as well as to assess the post-infarction short-term prognosis. METHODS: A retrospective analysis of patients with acute MI admitted to our institution over a period of 8 years (1995-2002) was performed. The study group consisted of 62 patients with MI and angiographically patent coronary arteries, examined within the first 30 days after the infarction, and the age and gender-matched control group of 62 patients with acute MI and significant coronary artery stenoses. RESULTS: Cardiovascular risk factors found in the study group versus the control group were: smoking 47 (66.1%) vs 54 (87.1%) patients (NS); dyslipidemia 18 (29.0%) vs 44 (74.2%) patients (p<0.005), and family history of coronary artery disease 16 (25.8%) vs 37 (61.3%) patients (p<0.05). The post-infarction complications were: ischaemic recurrences in 25 (40.3%) vs 46 (74.2%) patients (p<0.05); heart failure in 11 (17.7%) vs 26 (41.9%) patients (p<0.05); mechanical events in 12 (19.4%) vs 16 (25.8%) patients (NS); arrhythmias in 18 (29.0%) vs 12 (19.4%) patients (NS); peripheral thromboembolic complications in 5 (8.1%) vs 2 (3.2%) patients (NS), respectively. CONCLUSIONS: In the population with MI and patent coronary arteries, smoking was the only well represented risk factor. Although there was a significantly lower incidence of ischaemic events and heart failure after MI in patients with patent rather than stenotic coronary arteries, the mechanical, arrhythmic and thromboembolic complications occurred with the same frequency.     

Cellular immunophenotypes in human embryonic, fetal and adult heart

The cellular immunoprofile of cardiac dysfunctions and lesions of ischemic etiology are insufficiently studied to date, especially regarding the contribution of non-cardiomyocytic structures. Aiming to explore this immunoprofile, we used immunohistochemistry applied on embryonic, fetal and adult normal or ischemic myocardium. We observed a decrease of smooth muscle alpha-actin expression in fetal vs. embryonic cardiomyocytes, its absence in normal adult myocardium and its intense expression in the fibrotic scars of ischemic myocardium. DDR2 and vimentin, which are present in the interstitial cells and cardiomyocytes of the embryo, fetus and normal adult heart, are absent in the fibrotic scar tissue and cicatricial infarction, the latter expressing smooth muscle alpha-actin and CD34. This suggested that myofibroblasts and not local fibroblasts that participate in ischemic remodeling. An EGFR-positive vascular network was better represented in the ischemic heart than in the adult normal one, a fact possibly related to EGFR implication in cardiac ischemic pre- and post-conditioning. Therefore, cardiomyocytes and non-cardiomyocytic cells have an undulating immunoprofile according to the intrauterine life stage or age after birth, and a variable contribution in cardiac lesions, mostly in ischemic ones.     

Purinergic transmission in the rostral but not caudal medullary raphe contributes to the hypercapnia-induced ventilatory response in unanesthetized rats

Chronic obstructive pulmonary disease is associated with altered cortical excitability. The relevance of this to the need for non-invasive ventilation is not known. We assessed the diaphragm response to transcranial magnetic stimulation in terms of motor threshold and latency as well as assessing intracortical excitability using paired stimulation in eight long-term users and six non-users of home ventilation with COPD. Overall, intracortical facilitation was strongly correlated with inspiratory muscle strength (r2 0.72, p<0.001) whereas intracortical inhibition was correlated with PaCO2 (r2 0.51, p=0.01). The two groups did not differ in motor evoked potential or latency, nor in the excitability of intracortical inhibitory or facilitatory circuits assessed using paired stimulation. The acute effect of isocapnic non-invasive ventilation was studied in six established ventilator users. Diaphragm motor evoked potential fell but there was no effect on intracortical facilitation or inhibition, implying an effect of neuromechanical feedback at brainstem or spinal level.