Prevention of Complications and Symptomatic Recurrences in Diverticular Disease with Mesalazine: A 12-Month Follow-up

In uncomplicated diverticular disease, treatment is aimed at relieving symptoms. The aim of the present study was to evaluate the efficacy of mesalazine for symptomatic relief of uncomplicated diverticular disease of the colon. Two hundred sixty-eight consecutive eligible outpatients (122 male, 146 female; age, 66.1 years; range, 31–81 years) were enrolled in four treatment schedules in a randomized fashion: Group R1 (66 patients), rifaximin, 200 mg bid; Group R2 (69 patients), rifaximin, 400 mg bid; Group M1 (67 patients), mesalazine, 400 mg bid; and Group M2 (66 patients), mesalazine, 800 mg bid. Treatments were administered for 10 days every month for 12 months. Clinical evaluations were performed at admission and at 3-month intervals for 12 months considering 12 clinical variables (upper and lower abdominal pain/discomfort, tenesmus, diarrhea, abdominal tenderness, fever, bloating, general illness, nausea, emesis, dysuria, bleeding) graded as 0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe. The Global Symptomatic Score (GSS) was calculated using the sum of each symptom score. Two hundred forty-four patients completed the 12- month study; 24 were discontinued (14 treated with rifaximin and 10 treated with mesalazine) either as voluntary dropouts or because they developed side effects and/or complications. Group M2 demonstrated a lower frequency of many symptoms after 6 and 12 months of treatment; the mean GSS was significantly lower in Group M2 after 6 and 12 months of therapy by both intention-to-treat and per-protocol analyses. Patients treated with mesalazine (Groups M1+M2) had a lower GSS than subjects treated with rifaximin (Groups R1+R2) during the 12-month follow-up period. We conclude that cyclic administration of mesalazine is effective for symptomatic relief of uncomplicated diverticular disease of the colon. Some symptoms showed greater improvement with mesalazine, 800 mg bid, than with the other treatment schedules.     

Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study

BACKGROUND/AIM: To evaluate long-term outcomes in decompensated HCV-related cirrhotic patients treated with antiviral therapy. METHODS: Of 129 eligible patients, 66 received peginterferon alfa-2b and ribavirin for 24 weeks, and 63 were controls. Survival and recurrence of liver failure events after therapy were main outcomes. RESULTS: Therapy was tolerated by 27 patients, dose reduced in 26 for toxicity, and discontinued in 13 for intolerance. End-of-therapy and sustained virological response (SVR) rates were 82.6% and 43.5% for HCV 2/3 patients, and 30.2% and 7.0% for HCV 1/4 patients. During therapy, odds ratios for severe infections or deaths due to infection were 2.95 (95% C.I. 0.93-9.3) and 1.97 (95% C.I. 0.40-9.51) in treated patients as compared with controls. During a follow-up of 30 months off-therapy, decompensated events occurred in 52, 33, and 3 of controls, non-responders, and SVR patients. Odds ratios for ascites, encephalopathy, and oesophageal bleeding in treated patients significantly decreased as compared with controls. Annualized incidence of death was 2.34, 1.91, and 0 per 1000 patient-years, respectively, in controls, non-responders, and SVR patients. Survival curves showed early separation of SVR patients from both non-responders and controls at approximately 6 months. CONCLUSIONS: In decompensated cirrhotics, HCV clearance by therapy is life-saving and reduces disease progression.     

S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood

RBCs distribute oxygen to tissues, but, paradoxically, blood transfusion does not always improve oxygen delivery and is associated with ischemic events. We hypothesized that storage of blood would result in loss of NO bioactivity, impairing RBC vasodilation and thus compromising blood flow, and that repleting NO bioactivity would restore RBC function. We report that S-nitrosohemoglobin (SNO-Hb) concentrations declined rapidly after storage of fresh venous blood and that hypoxic vasodilation by banked RBCs correlated strongly with the amounts of SNO-Hb (r(2) = 0.90; P < 0.0005). Renitrosylation of banked blood during storage increased the SNO-Hb content and restored its vasodilatory activity. In addition, canine coronary blood flow was greater during infusion of renitrosylated RBCs than during infusion of S-nitrosothiol-depleted RBCs, and this difference in coronary flow was accentuated by hypoxemia (P < 0.001). Our findings indicate that NO bioactivity is depleted in banked blood, impairing the vasodilatory response to hypoxia, and they suggest that SNO-Hb repletion may improve transfusion efficacy.     

Physicians' and parents' ratings of inactive disease are frequently discordant in juvenile idiopathic arthritis

OBJECTIVE: To investigate discrepancies between physicians' and parents' ratings of inactive disease in children with juvenile idiopathic arthritis (JIA) and the determinants of the discrepancy. METHODS: Study data were obtained from the clinical database generated at the study unit. Each patient visit included a standardized assessment of JIA outcome measures. One visit for each patient was selected for analysis. Three definitions of inactive disease were applied to the data: a physician-based definition (physician global assessment = 0); a parent-based definition (parent global assessment = 0); and a formal definition, based on fulfillment of newly developed criteria for inactive disease in JIA. RESULTS: Of 1237 visits made by 537 patients that included both physician and parent global assessments, 265 fulfilled the physician-based definition and/or the parent-based definition of inactive disease. Concordance between physicians and parents in rating the disease as inactive was seen in 40% of the visits, whereas in 60% of visits the 2 assessments were discordant. Parents tended to disagree with physicians in rating the disease as inactive if the child had pain or functional impairment, whereas physicians tended to disagree with parents in the presence of active joint symptoms. Only 2/3 of the 79 visits that fulfilled the formal definition of inactive disease also met the parent-based definition of inactive disease. CONCLUSION: We found frequent discordance between physicians' and parents' ratings of inactive disease in children with JIA, which suggests that the parent's rating of a child's disease activity should be considered for inclusion in the definition of clinical remission for JIA.     

Molecular diagnosis of hypobetalipoproteinemia: an ENID review

Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-30 are not detectable in plasma; they are more frequent in patients with the most severe phenotype. Only a single amino acid substitution (R463W) has been reported as the cause of FHBL. Approximately 50% of FHBL subjects are carriers of pathogenic mutations in APOB gene; therefore, a large proportion of FHBL subjects have no apoB gene mutations or are carriers of rare amino acid substitutions in apoB with unknown effect. In some kindred FHBL is linked to a locus on chromosome 3 (3p21) but the candidate gene is unknown. Recently a FHBL plasma lipid phenotype was observed in carriers of mutations of the PCSK9 gene causing loss of function of the encoded protein, a proprotein convertase which regulates LDL-receptor number in the liver. Inactivation of this enzyme is associated with an increased LDL uptake and hypobetalipoproteinemia. HBL carriers of PCSK9 mutations do not develop fatty liver disease.     

Diverticular disease in the elderly

There are few diseases whose incidence varies as greatly worldwide as that of diverticulosis. Its prevalence is largely age-dependent: the disease is uncommon in those under the age of 40, the prevalence of which is estimated at approximately 5%; this increases to 65% in those > or =65 years of age. Of patients with diverticula, 80-85% remain asymptomatic, while, for unknown reasons, only three-fourths of the remaining 15-20% of patients develop symptomatic diverticular disease. Traditional concepts regarding the causes of colonic diverticula include alterations in colonic wall resistance, disordered colonic motility and dietary fiber deficiency. Currently, inflammation has been proposed to play a role in diverticular disease. Goals of therapy in diverticular disease should include improvement of symptoms and prevention of recurrent attacks in symptomatic, uncomplicated diverticular disease, and prevention of the complications of disease such as diverticulitis. Diverticulitis is the most usual clinical complication of diverticular disease, affecting 10-25% of patients with diverticula. Most patients admitted with acute diverticulitis respond to conservative treatment, but 15-30% require surgery. Predictive factors for severe diverticulitis are sex, obesity, immunodeficiency and old age. Surgery for acute complications of diverticular disease of the sigmoid colon carries significant rates of morbidity and mortality, the latter of which occurs predominantly in cases of severe comorbidity. Postoperative mortality and morbidity are to a large extent driven by patient-related factors.     

How many parkinsonian patients are suitable candidates for deep brain stimulation of subthalamic nucleus? Results of a questionnaire

We used a CAPSIT-based questionnaire to estimate the percentage of parkinsonian patients suitable for subthalamic nucleus (STN) deep brain stimulation (DBS) in a movement disorders clinic. We found that out of 641 consecutive PD patients only 1.6% fulfilled strict STN-DBS criteria. When we applied more flexible criteria, the percentage of eligibility increased to 4.5%. Most patients (60%) were ineligible because they did not satisfy multiple questionnaire items. Items related to disease severity were responsible for the largest number of exclusions. This knowledge will help make decisions on resource allocation in centres wishing to start DBS surgery.