Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Bioremoval of copper by filamentous fungi isolated from contaminated soils of Puchuncaví-Ventanas Central Chile.

Pollution represents a high risk to plants, animals, and human beings, causing an imbalance and affecting the environment. Soil is considered a universal sink, containing the highest load of environmental pollution. Puchuncaví-Ventanas sector, decreed as a saturated contamination zone in 1993, is considered one of the most affected areas by industrial pollution and belongs to one of the 5 sacrifice zones of Chile. The localities of Puchuncaví and Ventanas have heavy metal pollution levels that exceed up to 99% of the limits allowed by Canadian standards. The objective of this study was to characterize heavy metal tolerance and removal potential of filamentous fungi isolated from polluted soils for their use in decontamination systems and in situ soil improvement. Six fungal strains were selected based on their tolerance and a high capability to accumulate heavy metals, achieving copper bioaccumulation of 84% (Mortierella sp. strain LG01), 49% (Clonostachys sp. strain CQ23) and 48-77.5% (Trichoderma sp. strain LM01A). Trichoderma sp. strain LM01A was able to remove 41% of copper from contaminated soil under ex situ conditions. Some fungal strains belong to beneficial fungal genera, which are used as bioproducts in agriculture. The results of this study highlighted the use of Trichoderma sp. in soils contaminated, which may be of special interest in agriculture due to the large amounts of copper sulfate still applied as a pesticide in Chile and the world.

First test-day postcalving risk factors for clinical mastitis in southern Chile dairy farms: A retrospective cohort study.

We conducted a retrospective cohort study to evaluate risk factors associated with clinical mastitis in dairy cows in southern Chile between the first milk test after calving to 200 d in milk (DIM). Data from 8,772 cows were collected from June 2017 to November 2019 on 10 dairy farms selected by convenience in southern Chile. Data were analyzed using a multivariable mixed logistic regression using a manual backward selection process with logit link function and farm as a random effect. The dependent variable was clinical mastitis between the first milking sample collected by monthly milk sampling program up to 200 DIM. Days in milk, fat, urea, parity, season, and somatic cell counts were statistically associated with clinical mastitis in the first 200 d in milk. Cows with higher than average milk yield, parity, urea, and somatic cell count were at greater odds of being diagnosed with clinical mastitis compared with their respective referents. In contrast, higher milk fat was associated with lower odds of clinical mastitis. Significant interactions between days in milk with season and parity were observed, where for every 5-d increase in DIM, the odds of clinical mastitis decreased by different proportions depending on the interaction. Identified risk factors for clinical mastitis using first monthly milk sampling data can help dairy farmers in Chile implement herd-level mastitis prevention and control measures.

Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.

Descriptive analysis of endoscopic findings in patients with a family history of colorectal cancer.

BACKGROUND: The presence of a family history implies an increased risk for developing colorectal cancer (CRC), and may require a different screening strategy. The aim of this study was to evaluate lesions found during colonoscopies of patients that had a family history of CRC. MATERIAL AND METHODS: A retrospective study was conducted that included consecutive colonoscopies performed on patients with a family history of CRC at a referral center within the period from April 2000 to January 2012. The colonoscopic findings were analyzed in relation to sex, age, and the presence or absence of symptoms. RESULTS: Data from 3,792 colonoscopies were collected. The mean age of the patients was 53.14 years (SD 12.22), and 57.4% were women. Colonoscopy was normal in 71.7% of the cases, with hyperplastic polyps being detected in 7.1%, and adenomatous polyps in 19.8% (39.4% of them were high risk). There was a 1.5% presence of adenocarcinomas in the subjects. Polyps and CRC were predominant in men (P=.001 and P=.027, respectively) and there was a linear increase with age. Symptomatic patients had a higher CRC detection rate (P<.001), but no differences were observed in relation to polyp diagnosis. CONCLUSIONS: Age and male sex increased the risk for presenting with CRC or adenomas in the group of patients with a family history of CRC, and the presence of symptoms was associated with a greater risk for presenting with CRC.

Malignant gastrointestinal obstruction: endoscopic stenting versus surgical palliation.

BACKGROUND: Malignant gastrointestinal obstruction is a secondary complication of cancers in an advanced state. Treatment has consisted of gastrojejunostomy. However, the endoscopic placement of metallic stents has provided positive results. This study aimed to compare the efficiency of both therapeutic options. METHODS: A total of 41 patients with gastrointestinal obstruction caused by inoperable neoplasm were treated endoscopically with enteral stent (24 patients) or gastrojejunostomy (17 patients). RESULTS: In the endoscopic group (EG) 24 patients (100%) achieved efficient gastric emptying, as compared with 82.3% in the surgical group (SG). The difference was not significant. The average time for initiating oral food tolerance was 2.4 days for the EG and 5 days for the SG (p < 0.001). The average inpatient time was 7.1 days for the EG and 11.5 days for the SG (p < 0.001). Mortality at 30 days was lower in the EG (16.6%) than in the SG (29.4%) (p < 0.05). The survival time was 20 weeks for the EG and 21.6 weeks for the SG. The difference was not significant. The rate of complications was 4% in the (EG) and 17.6% in the (SG), with the difference was not significant. CONCLUSION: Endoscopic treatment of malignant gastrointestinal obstruction provides an adequate palliation of the symptoms. It is less invasive, avoids the morbidity associated with open gastrojejunostomy, and achieves a faster start to oral food and a shorter hospital stay, leading to a higher quality of life.

[Effects of glutamine on antioxidants systems and hepatic detoxification in rats: influence of formulation]. / Influencia de la formulación de la glutamina en sus efectos sobre los sistemas antioxidantes y de destoxificación hepática en la rata.

GOALS: The goal of this study is to assess the effect that supplementing parenteral diets with L-glutamine or with L-alanyl-L-glutamine has on the balance of oxidants/antioxidants in the liver and on detoxification systems mediated by P-450 cytochrome in rats. MATERIAL AND METHODS: Central catheters were inserted in the animals (n = 60) and they were randomly assigned to one of the following groups: a control group (C) with oral feeding and I.V. infusion of saline solution, a total parenteral nutrition group without glutamine (TPN without GLN), a parenteral nutrition group with glutamine supplement (TPN GLN), and a total parenteral nutrition group with a supplement of alanine-glutamine dipeptide (20 g/L) (TPN ALA-GLN). The parenteral nutrition provided was all isocaloric and isonitrogenated, and the infusions were administered at a speed of 2 ml/h over 5 days. RESULTS: In the animals of the group without GLN, the liver concentration of glutathione was reduced while the levels of thiobarbituric acid reaction products (TBARS) increased. Supplementing with either glutamine or alanine-glutamine normalized the levels of glutathione but the TBARS levels only fell in the group with the dipeptide. This effect was parallel to the partial recovery of the antioxidant enzyme activities analyzed. The liver concentrations of P-450 cytochrome, P-450 cytochrome dependent mono-oxygenases and the clearance of antipyrine were not modified by the supplements of glutamine or alanine-glutamine. CONCLUSIONS: Our data suggest a greater protection by alanine-glutamine supplements against the injury produced by free radicals during TPN and the absence of any effect with either glutamine or alanine-glutamine supplements on the oxidative metabolism of the liver.

[Dilatation of the papilla of Vater in the treatment of choledocholithiasis in selected patients]. / Dilatación de la papila de Vater en el tratamiento de la coledocolitiasis en pacientes seleccionados.

OBJECTIVE: To prospectively analyze the results obtained with papillary balloon dilatation (PBD) in the treatment of common bile duct stones in patients at risk of complications if endoscopic sphincterotomy (ES) were performed. PATIENTS AND METHOD: Thirty-three patients were included between January 2001 and June 2003 (mean age 76.2 years). The criteria for PBD were: choledocholithiasis < or =10 mm in patients with peripapillary diverticula, hemostatic alterations, Billroth-II, and preservation of Oddi's sphincter. In 79% of the patients sedation was performed by an anesthetist. PBD was performed with a balloon catheter dilator with a diameter of 8 or 10 mm for 2 minutes. The efficacy and duration of the procedure as well as complications at 30 days and patient satisfaction were evaluated. RESULTS: Stone extraction was achieved in all patients (100%). The mean duration of the procedure was 26 minutes. Two patients (6%) presented mild pancreatitis. Serum amylase was elevated in 16 patients (48%): > or =3 times (post-PBD hyperamylasemia) in 11 (33%). The procedure caused no discomfort in 25/26 (96%) of the patients sedated by an anesthetist vs 2/5 patients (49%) who underwent endoscopic sedation. CONCLUSIONS: PBD is an effective and simple therapeutic option in the treatment of small common bile duct stones (< or =10 mm) and in patients at high risk. The duration of endoscopic retrograde cholangiopancreatography is not prolonged. Complications are infrequent (6%) and mild. Post-PBD hyperamylasemia is frequent and generally without clinical importance. Sedation by an anesthetist improves patient satisfaction.

Palliative treatment of malignant obstruction of gastric outlet using an endoscopically placed enteral Wallstent.

Surgical gastrojejunostomy is the standard treatment for malignant gastric outlet obstruction, although it is associated with significant morbidity and mortality. The aim of this study was to evaluate the efficacy and feasibility of a newly designed expandable metal stent (Wallstent Enteral) to treat malignant gastric outlet obstruction. Six patients (five women, one man; mean age 76 years) underwent stenting. Stents 20-22 mm in diameter and 60-90 mm in length were deployed through a duodenoscope channel under endoscopic and fluoroscopic control, without previous stricture dilation. In all six cases the stent was adequately positioned and food intake was possible in the next 24 h. The mean time for hospital discharge was 2.5 days (1-5 days), without complications related to the procedure. Five patients died in the follow-up from progression of their cancer and one remains alive; none had recurrent obstruction. The median survival time was 9 weeks (95% CI: 3-15 weeks). In conclusion, endoscopic self-expandable stent (Wallstent Enteral) placement is safe and effective palliation for malignant gastric outlet obstruction and appears to be a therapeutic alternative to surgical gastrojejunostomy.

Impairment of metabolic function in chronic hepatitis C is related to factors associated with resistance to therapy.

OBJECTIVE: Liver disease causes a loss of hepatic function, and remission is associated with improved functional hepatic mass. The object of the present study was to investigate whether liver metabolic function assessed by antipyrine clearance is related to other disease characteristics influencing response to therapy in chronic hepatitis C. METHODS: Patients (n = 96) received three different treatment regimens: one group received interferon alfa-2b for 48 wk; in a second group with maintained positive hepatitis C virus (HCV) RNA after 12 wk, interferon was combined for 36 wk with oral ribavirin; and patients who were relapsers or nonresponders to a previous therapy with interferon alone received interferon alfa-2b plus ribavirin for 48 wk. RESULTS: Twenty-five patients (26%) showed sustained normalization of ALT levels and negative HCV RNA 6 months after therapy. The response was more likely to be sustained in patients with a genotype other than 1 (52.0% vs 15.5% in patients with genotype 1, p < 0.001), and the percentage of sustained responders was higher among patients who demonstrated negativity of HCV RNA at the end of 4 wk of treatment (64% vs 13% without negativity, p < 0.001). Sustained response was associated with significantly lower baseline serum ferritin (-46%, p < 0.01) and duration of infection (-33%, p < 0.01). Baseline antipyrine clearance was higher in sustained responders than in nonresponders (+19%, p < 0.05) and lower in genotype 1 patients than in those with a genotype other than 1 (-24%, p < 0.05). Antipyrine clearance increased by 12% at the end of the 48-wk course of treatment among sustained responders (+34% vs nonresponders, p < 0.001) and still remained elevated at the end of the follow-up (+35% vs nonresponders, p < 0.001). CONCLUSION: In summary, the present study shows that liver oxidative metabolism is related to antiviral response rates and suggests that much of the effect is explained by viral genotype.

C282Y and H63D mutations of the haemochromatosis gene in patients with iron overload.

OBJECTIVE: To determine the relevance of C282Y and H63D mutations of HEF gene in patients with iron overload. PATIENTS AND METHODS: Patients with iron overload referred to our Liver Unit were included in the study. The association of mutations to different diagnosis and their impact on the severity of the hepatopathy were explored. Sensitivity, specificity and positive and negative predictive values of mutations for the diagnosis of haemochromatosis were determined. RESULTS: The study included 78 patients with iron overload. The control group included 21 patients of similar age and sex ratio without iron overload nor hepatopathy. Twenty three patients had haemochromatosis, 22 alcoholic liver disease and 33 other diseases unrelated to iron metabolism. Seventy three per cent of patients with haemochromatosis were homozygous for the C282Y mutation. All the C282Y homozygous subjects had also haemochromatosis. Fifty three per cent of patients with alcoholic hepatopathy had some kind of mutation. This has been also observed in 70% of patients with iron-unrelated diseases. Such percentage was significantly greater than in the control group (24% with H63D mutation). C282Y homozygosity in patients with iron overload had a sensitivity of 73.9%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 89.6%. CONCLUSIONS: In our population, as in all the Western countries, haemochromatosis is mainly associated to homozygous C282Y mutation. The high frequency of mutations in patients with iron overload and without haemochromatosis suggests the involvement of such mutations in iron overload.

Antipyrine clearance and metabolite formation in primary biliary cirrhosis.

The disposition of antipyrine is altered and may be a prognostic factor in the presence of various types of hepatic dysfunction. The object of the present study was to investigate whether antipyrine clearance and metabolite formation are useful to detect altered metabolic function in primary biliary cirrhosis. Saliva clearance of antipyrine and the formation clearance of antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) were investigated in a group of 34 women with biopsy-proven PBC (mean age 60 years; range 39-87 years) and in 15 healthy control women (mean age 62 years; range 46-78 years). Parameters of antipyrine clearance of patients in stage I and II were similar to those observed in healthy subjects. When compared to patients in stage I, patients in advanced stages showed a reduction in antipyrine clearance (-29% and -44% in stages III and IV, respectively) and increases in antipyrine half-life (+24% and +75% in stages III and IV, respectively). The reduction in antipyrine clearance was due to a reduction in the formation of all three antipyrine metabolites, with the formation clearance of both HMA and NORA decreasing to a slightly greater extent than that of OHA. Antipyrine clearance correlated significantly with serum bilirubin (P < 0.017) and the Mayo risk score (P < 0.001). Logistic regression analysis indicated that antipyrine clearance was an independent predictor of the histological stage of the disease (P < 0.001). Antipyrine clearance and metabolite formation is a sensitive parameter for assessing hepatic metabolic function in primary biliary cirrhosis.

[Toxic hepatitis caused by nimesulide, presentation of a new case and review of the literature]. / Hepatitis tóxica por nimesulida, presentación de un nuevo caso y revisión de la bibliografía.

Nimesulide is a potent non-steroidal anti-inflammatory drug. It is a new, selective cyclooxygenase-2 inhibitor with few adverse effects on the gastrointestinal system. We present a case of hepatotoxicity in which other possible causes of liver damage were excluded. A biochemical pattern of cholestasis was predominant. Evolution was favorable after the drug was stopped and enzymatic alterations progressively returned to normal. The cases reported to date are reviewed. The precise mechanism by which nimesulide produces liver damage is not known but it is probably caused by an idiosyncratic reaction. Because of the severity of the hepatitis described in some cases, treatment should be stopped when liver dysfunction is detected and the patients should be closely monitored.

Sensitivity of breasts reconstructed with the autologous latissimus dorsi flap.

The purpose of this study was to measure, both objectively and subjectively, the sensitivity of breasts reconstructed with the autologous latissimus dorsi flap and to compare these results with those of other reconstruction techniques, especially the transverse rectus abdominis myocutaneous flap. The study population included 50 patients with autologous latissimus dorsi flap breast reconstruction; these patients had an average age of 51 years and an average follow-up of 27 months. Patients answered a seven-item questionnaire that attempted to define the sensitivity of the reconstructed and opposite breasts. This sensitivity was then measured objectively using standard techniques for heat, cold, and tactile sensations. After statistical analysis, these results were compared with those published for other reconstruction techniques. Overall results were comparable or superior to those published for other techniques for autologous breast reconstruction. A total of 56 percent of patients had fine or very fine sensitivity, but 70 percent deemed this sensitivity to be less than that of the opposite breast. A total of 94 percent of patients perceived the reconstructed breast as integral to their body image. The superior medial part of the breast had the greatest sensitivity, both objectively and subjectively. Autologous latissimus dorsi breast reconstruction, a good technique with excellent aesthetic results, affords satisfactory sensitivity. This is yet another advantage of the technique.

[Tolerance, reliability and efficiency of inflatable breast implants after breast reconstruction. Retrospective study of 101 consecutive cases]. / Tolérance, fiabilité et efficacité des prothèses mammaires gonflables en reconstruction mammaire. Etude rétrospective de 101 cas consécutifs.

A long-term retrospective study of breast reconstruction with inflatable implants is presented. One hundred and one patients were studied, with a median follow-up of 44 months. Prosthetic implants used were round McGhan implants, model 168. Median volume was 215 mL. Twenty-two patients had contralateral symmetrisation, an average of five months after implant. The advantages of this sort of reconstruction are ease, speed and homogenously good results. Drawbacks include the appearance of prosthetic leaks (7%), waves and folds (13%), stage III and IV capsular contractures (26%), asymmetry and incorrect placement of the implant (25%). Breast reconstruction with implants alone gives good results for specific indications: immediate reconstructions, bilateral reconstructions, no history of radiotherapy, and good quality chest wall tissues.

[Helical CT compared to ERCP in obstructive biliary pathology]. / TC helicoidal frente a CPRE en la patología biliar obstructiva.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the examination of choice in the diagnosis of biliary tract pathology although newer, less invasive techniques with high diagnostic sensitivity should be evaluated. The aim of this study was to evaluate the diagnostic efficacy of helical computed tomography (CT) in bile duct obstruction, particularly in choledocholithiasis. PATIENTS AND METHODS: Forty-four patients with suspected bile duct obstruction were prospectively evaluated. Helical TC was carried out 12 hours before ERCP and patients were grouped according to risk of choledocholithiasis. RESULTS: Choledocholithiasis was found in 20 patients (45.4%). Helical TC identified this pathology in 17 and correctly ruled it out in 18 of 24 patients (S: 85%, E: 75%, positive predictive value 74%, negative predictive value 85.7%. Of the patients with choledocholithiasis, bile duct dilatation was found in 18. Helical TC correctly diagnosed this pathology in 16 of the 18 patients (88.8%). Helical TC correctly diagnosed one of two patients (50%) with choledocholithiasis and normal bile ducts. CONCLUSIONS: Helical TC is effective in the diagnosis of choledocholithiasis but is not sufficiently accurate to be used in the screening of this entity.