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Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system). Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug. In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis. Gilead Sciences.

In this randomized comparison of treatment with tenofovir disoproxil fumarate or adefovir dipivoxil for 48 weeks in patients with chronic hepatitis B, tenofovir was more likely to result in viral suppression. The follow-up period was not long enough to assess the resistance patterns, risks, and benefits of long-term treatment. In this randomized comparison of treatment with tenofovir disoproxil fumarate or adefovir dipivoxil for 48 weeks in patients with chronic hepatitis B, tenofovir was more likely to result in viral suppression. Chronic hepatitis B virus (HBV) infection is a major health problem. 1 – 3 Since most patients with chronic HBV infection require long-term therapy, 4 – 6 there is a need for new drugs with potent antiviral activity and established long-term safety, as well as a proven low rate of HBV antiviral resistance, a high genetic barrier (i.e., requiring more than one amino acid substitution to confer resistance to HBV treatment), or both. The ultimate goal of treatment of chronic HBV infection is to prevent liver complications. This goal is seldom achieved through hepatitis B surface antigen (HBsAg) loss and seroconversion, which are associated . . .

Background Biliary decompression is a key factor in the treatment of postcholecystectomy bile leak. However, the optimal size of the stent introduced by therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is yet to be determined. The aim of the study was to compare the effectiveness of two straight plastic stents with different sizes (10-Fr and 7-Fr) in the treatment of postcholecystectomy bile leak. Methods Between January 2003 and August 2006, 63 patients underwent therapeutic ERCP for postcholecystectomy bile leak. After visualization of the bile duct injury, endoscopic sphincterotomy was performed and the patients were randomized to receive either a 7-Fr (31 subjects, group A) or a 10-Fr (32 subjects, group B) straight plastic stent for four weeks. The success of the endoscopic treatment was determined by the elimination of the symptoms and the removal of the drain without any adverse outcomes. Results The endoscopic intervention was successful in 29 patients of group A (93.54%) and in 31 patients of group B (96.87%). In the remaining two patients of group A, the 7-Fr stent was substituted by a 10-Fr stent after 7 days because the leak remained unaffected, resulting in healing of the leaks. Surgery was required in the remaining one patient of group B. Eight patients developed post-ERCP pancreatitis (5 mild, 2 moderate, 1 severe), which was treated conservatively. Conclusions This trial suggests that the stent size does not affect the outcome of the endoscopic intervention in postcholecystectomy bile leaks due to minor biliary tract injury; however, larger cohorts are required to confirm the optimal stent size in bile leaks due to major bile duct injury.

Background In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. Methods A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. Results WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 ± 30.6, 107.1 ± 29.1 vs. 101.4 ± 29.9 g/m2 and 0.68 ± 0.16, 0.68 ± 0.21 vs. 0.63 ± 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 ± 25.9 vs. 101.4 ± 29.9 g/m2); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 ± 0.15 vs. 0.63 ± 0.15 mm). Conclusions WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

Among patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B, the rates of suppression of hepatitis B virus DNA to below 20,000 copies per milliliter were 43 percent with peginterferon alfa-2a alone, 44 percent with peginterferon alfa-2a plus lamivudine, and 29 percent with lamivudine alone after 48 weeks of treatment and 24 weeks of follow-up; the rates of suppression to below 400 copies per milliliter were 19 percent, 20 percent, and 7 percent, respectively. Peginterferon alfa-2a was more effective than lamivudine for HBeAg-negative chronic hepatitis B. Chronic infection with hepatitis B virus (HBV) is a major global health problem, affecting more than 400 million people worldwide. 1 Chronic hepatitis B is associated with serious complications, including liver failure, cirrhosis, and hepatocellular carcinoma. Hepatitis B e antigen (HBeAg)–negative chronic hepatitis B represents a late phase of the infection that is characterized by progressive liver damage 2 , 3 and viral variants with changes in the precore or core promoter region, 4 , 5 which abolish or suppress the expression of HBeAg. Spontaneous, sustained remissions are rare in HBeAg-negative chronic hepatitis B, 6 which has a poor prognosis. HBeAg-negative chronic hepatitis B occurs throughout . . .

Background/Objectives: The potential side effects of the use of biological agents in the perioperative period are still under investigation. This animal prospective study aimed to evaluate the overall impact of biological factor administration after intestinal surgery. Methods: This study included 80 female Wistar rats sorted into four groups: three groups received one of the biological factors, infliximab, vedolizumab, or ustekinumab; the control group received placebo therapy. After enterotomy and intestinal anastomosis, the bursting pressure (BP) of the anastomosis was compared among the groups on postoperative days (PODs) 3 and 7. Results: On POD3, the control group presented with a significantly higher mean BP (154.6 ± 39.7 mmHg) compared to the infliximab (66.8 ± 10.4 mmHg), vedolizumab (105.4 ± 37.6 mmHg), and ustekinumab (98.8 ± 47.9 mmHg) groups. A post hoc analysis among the three biological agent groups revealed differences only when comparing infliximab and vedolizumab rats with the controls on POD3 (p < 0.001) and with the ustekinumab rats on POD7, having a greater mean BP (282.5 ± 80.1 mmHg, p = 0.031). No differences were observed regarding the event of broken anastomosis among the four groups. Conclusions: This experimental study’s findings highlight the varying detrimental effects of different biological agents on the strength of intestinal anastomosis, with ustekinumab demonstrating superior performance.

COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211, and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe, and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data support the notion that the host’s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708, and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.