Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial.

Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524 ). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by ≥1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l-1 (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well tolerated and without imbalance in serious or severe AEs between arms. Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600 mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.

Somatostatin compared with cimetidine in the treatment of bleeding peptic ulcer without visible vessel.

In a randomized double-blind trial 100 patients with severe bleeding peptic ulcers were treated with an intravenous (i.v.) infusion of cimetidine or somatostatin. Only those patients in whom endoscopy performed within 6 h of admission showed non-arterial bleeding or signs of recent haemorrhage without a visible vessel entered the trial. The two treatment groups were well matched for age, sex, presence of underlying disease, prior ingestion of ulcerogenic drugs, tobacco habits, type of bleeding, haematocrit at admission, presence of hypovolaemic shock, source of bleeding and endoscopic findings. Four patients in each group were excluded after randomization. Further haemorrhage occurred in eight (17.3%) patients in the somatostatin group and in 10 (21.7%) in the cimetidine group, but the difference was not statistically significant. The number of surgical procedures, blood transfusion requirement, duration of hospitalization and mortality rates were similar in the two treatment groups. These results suggest that somatostatin does not improve the results obtained with cimetidine in patients with bleeding peptic ulcer, in whom the endoscopy discloses non-arterial bleeding or signs of recent haemorrhage without a visible vessel.

[Genital infection and infertility]. / Infección genital y esterilidad.

BACKGROUND: Genital infection is the most important cause of infertility worldwide, affecting not only Fallopian tubes but all anatomic urogenital sites, both male and female. METHODS: We present a randomized,prospective and normalized study about sexually transmitted diseases(STD). We include 487 patients, 376 of whom were infertile and the remaining 111 were not and act as control group. RESULTS: 47.3% of infertile patients showed at least one infection: 10.7% had Chlamydia trachomatis infection, whereas only 0.3% had gonococal infection. We found none syphilis. 12.9% of the patients showed yeast belonging to genus Candida, 5% bacterial vaginosis, 3.8% Escherichia coli and 0.3% Klebsiella pneumoniae. The percentage of isolation of Ureaplasma urealyticum and Mycoplasma hominis were 23.5% and 4.8%, respectively. We detected antibodies against Hepatitis B (any serological marker) in 7.8% of the cases. Chlamydial infection and the presence of U. urealyticum were related with infertility (X 12=6,070, p<0.005 and X12=8,782, p<0.005,respectively). CONCLUSIONS: We think these results conclude that is necessary to perform routine tests to screen for C. trachomatis, N. gonorrhoeae, and for infections caused by micoplasma as well, among infertile patients. These patients must be considered of being at risk of acquiring STD, since the percentage of these diseases is higher than the percentage we found among the control group. It is important to insist on prevention and early diagnosis and treatment as a main goal to decrease the number of tubal occlusion and infertile couples.

[Treatment of Helicobacter pylori infection in patients with duodenal ulcer: a cost-benefit study]. / Tratamiento de la infección por Helicobacter pylori en pacientes con úlcera duodenal: estudio de costo-beneficio.

BACKGROUND: Epidemiological differences suggest that treatments for H. pylori eradication should be locally validated. AIM: To perform a cost benefit study of different treatment options for H. pylori infection. PATIENTS AND METHODS: One hundred and sixty-seven patients with active duodenal ulcer and H. pylori infection who completed a 2-week treatment with one of the following regimens were included: famotidine plus amoxycillin plus metronidazole (FAM), omeprazole plus amoxycillin plus tinidazole (OAT) or lansoprazole plus clarithromycin plus amoxycillin in 3 (LAC1) or 2 (LAC2) daily doses. We compared efficacy, adverse effects and cost. RESULTS: Eradication rate was 74.6, 72.9, 96.4 y 91.7% for FAM, OAT, LAC1 and LAC2 respectively (p < 0.05). Direct cost ranged from US$ 50 for FAM to US$ 220 for LAC1. A decision analysis was carried out in a model including direct and indirect costs and considering retreatment with antibiotics after the first treatment failure and one-year treatment with H2-blockers in case of a second failure. FAM was selected as the most cost-effective option, with an estimated cost of about US$ 300 +/- 148 per patient. However, cost associated to LAC2 was very similar (US$ 320 +/- 58) and the lower standard deviation suggests less variation. Sensitivity analyses, considering reasonable fluctuation in parameters such as eradication rate, cost and follow-up period suggest that a regimen containing a proton pump inhibitor, clarithromycin and amoxycillin may be the most cost-effective treatment. CONCLUSIONS: These results should be confirmed in other settings, specially in ordinary clinical practice, far from clinical research.

Predictive clinical factors of visible vessel in bleeding peptic ulcer.

The endoscopic finding of a visible vessel in the base of a bleeding gastrointestinal lesion is a well-known indicator of the possibility of recurrent hemorrhage. We carried out a multivariate analysis of 277 patients with gastrointestinal hemorrhage, but no chronic liver disease, of the clinical history and parameters in relation to hemorrhage, in order to select patients at risk for this endoscopic picture. A clinical history of associated disease, the absence of ulcerogenic drug intake, presentation of bleeding in the form of hematemesis and active hemorrhage on admission had predictive value for visible vessel, The incidence of visible vessel was significantly greater in anastomotic stoma ulcers than in gastric and duodenal sulcers. On the basis of the clinical parameters mentioned, patients with a high probability of having a bleeding lesion with a visible vessel can be selected for priority endoscopy.

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country.

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8%+/-3% in yr 1, 11%+/-4% in yr 2, and 13%+/-4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

Determinants of the geographic variation of invasive cervical cancer in Costa Rica.

The incidence of cervical cancer in Costa Rica is about twice as high in the coastal regions as in the interior. To study these regional variations, we used data from a 1986-1987 case-control study of 192 Costa Rican women with invasive cervical cancer and 372 controls. Risk factors identified included the following: The study participant's (1) number of sexual partners, (2) age at first sexual intercourse, (3) number of live births, (4) presence of type 16/18 human papillomavirus (HPV) DNA, (5) venereal disease (VD) history, (6) Pap smear history, and (7) socioeconomic status. The adjusted relative risks (RR) and 95% confidence intervals (CI) for each of these risk factors were as follows: (1) > or = 4 vs. 1 sexual partner: RR = 2.0, 95% CI = 1.1-3.5; (2) age of initiation < or = 15 vs. > or = 18 years: RR = 1.5, 95% CI = 0.9-2.5; (3) > or = 6 vs. < or = 1 live birth: RR = 1.7, 95% CI = 0.7-3.9; (4) HPV 16/18 DNA in cervix: RR = 2.8, 95% CI = 1.9-4.2; (5) VD history: RR = 2.2, 95% CI = 1.2-4.0; (6) no Pap smear: RR = 2.4, 95% CI = 1.5-3.8; and (7) low socioeconomic status: RR = 2.0, 95% CI = 1.2-3.2. The population-attributable risks related to HPV detection, four or more sexual partners, six or more live births, no prior Pap smear, and low socioeconomic status were 39%, 38%, 29%, 23%, and 22%, respectively. Several of the sexual and reproductive risk factors were relatively more prevalent in the high-risk region, but Pap screening and detection of HPV were equally prevalent in the high-risk and low-risk regions. Though differences in screening quality (laboratory and follow-up) may have been involved, we conclude that the observed regional differences reflect behavioral more than screening differences. This suggests that screening programs should be more aggressive in the high-risk area, given the more frequent occurrence of the disease there. Failure to detect a higher prevalence of HPV in the high-risk region could reflect weaknesses in the in situ hybridization test employed. Alternatively, cofactors may have to be present in order for HPV to exert its role in cervical carcinogenesis.

[Gallbladder polyps. 2d Consensus Workshop of the Chilean Hepatology Association]. / Pólipos vesiculares. Segundo taller de consenso de la asociatión chilena de hepatología.

During a workshop, hepatologists analyzed and gave recommendations about gallbladder polyps. They arrived to the following agreements: gallbladder polyps of less than 10 mm should be followed with ultrasonography at 3, 6 and 12 months if there is no enlargement. If there is enlargement, a cholecystectomy should be performed. Polyps larger than 10 mm should be subjected to cholecystectomy.

Complicaciones de la cirugía de la catarata con implante de LIO de cámara posterior / Complications of cataract surgery with posterior chamber IOL implant

Se hace una revisión retrospectiva de las complicaciones intraoperatorias y postoperatorias inmediatas y tardías de la cirugía extracapsular con implante de lentes de cámara posterior. Un total de 306 ojos son estudiados por un período de 12 a 26 meses. Se analizan las probables causas de las complicaciones y su influencia en el resultado visual de estos pacientes, de los cuales un 4,4% tuvo visiones peores de 20/40 como consecuencia de la cirugía