Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers.

HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch.

Sutureless hernioplasty with light-weight mesh and fibrin glue versus Lichtenstein procedure: a comparison of outcomes focusing on chronic postoperative pain.

PURPOSE: Groin hernia is one of the most common disease requiring surgical intervention (8-10% of the male population). Nowadays, the application of prosthetic materials (mesh) is the technique most widely used in hernia repair. Although they are simple and rapid to perform, and lower the risk of recurrence, these techniques may lead to complications. The aim of the present study is to assess the incidence and degree of chronic pain, as well as the impairment in daily life, in two procedures: (1) the "Lichtenstein technique" with polypropylene mesh fixed with non-absorbable suture, and (2) the "sutureless" technique carried out by using a partially absorbable mesh (light-weight mesh) fastened with fibrin glue. METHODS: This was a study conducted over a period of 3 years from July 2006 to July 2009. A total of 148 consecutive male patients suffering from groin hernia were divided randomly into two groups: (1) Group A: patients operated with "sutureless" technique with partially absorbable mesh and plug fastened with 1 ml haemostatic sealant; (2) Group B: patients operated with Lichtenstein technique using non-absorbable mesh and plug anchored with polypropylene suture. Follow-up took place after 7 days, and 1, 6 and 12 months and consisted of examining and questioning patients about chronic pain as well as the amount of time required to return to their normal daily activities. RESULTS: No major complications or mortality were observed in either group. In group A there was a faster return to work and daily life activities. Six patients (7.8%) in group B suffered from chronic pain, whereas no patient in group A demonstrated this feature. CONCLUSIONS: Our experience shows that the combined use of light-weight mesh and fibrin glue gives significantly better results in terms of postoperative pain and return to daily life.

Oesophageal achalasia in elderly people: results of the laparoscopic Heller-Dor myotomy.

AIMS: To assess the outcome of laparoscopic Heller-Dor myotomy for oesophageal achalasia in two groups of patients identified by age (under and over 70 years) using functional and clinical instruments. BACKGROUND: Current therapies for achalasia can't restore normal motility but can palliate dysphagia. Many other symptoms may persist difficult to quantify and to compare. In order to understand if age is a factor that influences the therapeutic outcome we tested the reliability of a specific QoL instrument for comparing outcomes of surgery for achalasia. METHODS: Functional examinations and the Gastrointestinal Quality of Life Index (GIQLI) were used before and after laparoscopic Heller-Dor myotomy. RESULTS: Starting in January 1996, 28 consecutive patients of 32 diagnosed (instrumental evidences) achalasia were operated on laparoscopically for various clinical stages of achalasia. In 78% of patients dysphagia disappeared, the incidence of gastro-oesophageal reflux was of 11%. The patients completed a GIQLI questionnaire preoperatively and after a minimum postoperative follow-up of 1 year. Median preoperative GIQLI score was 78(range 38-109) out of a theoretical maximum score of 144. At a median follow-up of 35 months (range 18-72), the score had significantly improved to 115 (range 71-140). All the items assessing gastrointestinal symptoms and physical, social, and emotional function were significantly improved. There is no difference between the two groups identified. CONCLUSIONS: The laparoscopic Heller-Dor myotomy is an effective palliation for acalasia, the medium-term outcome is not affected by the age of the patients. The GIQLI is a reliable instrument to compare the impact of achalasia symptoms on health-related QoL.

Long-acting nitrates in portal hypertension: to be or not to be?

The major complication of portal hypertension is represented by gastrointestinal haemorrhage from ruptured oesophageal varices. Gold standard prophylaxis with non selective beta-blockers is able to decrease the risk of bleeding or rebleeding only in a fraction of patients, thus additional forms of treatment are under investigation. Long-acting nitrates have been considered the best candidates to improve the pharmacological response. The rationale for the use of nitrates in portal hypertension is primarily based on the fact that they lead to a decrease in the hepatic venous pressure gradient and on the knowledge that deficient intrahepatic nitric oxide release could be one of the mechanisms involved in the development of increased portal resistance in early cirrhosis. Ten randomised controlled trials have, so far, investigated the clinical usefulness of long-acting nitrates in portal hypertension. Five of them explored the field of primary prophylaxis and the others, the use of nitrates in the prevention of rebleeding. The results of these randomised controlled trials are partially contradictory as far as concerns prevention of bleeding or rebleeding, survival and treatment-related complications. A common finding emerging from most of these studies suggests that the potential for a beneficial or detrimental effect of nitrates depends on the stage of liver disease and the extension of portal collaterals. Thus, in the early stage of cirrhosis, it would be desirable to target nitrates to the liver microvasculature, while, in a later stage, nitrates could be deleterious by aggravating the hyperdynamic syndrome through the expansion of the vascular bed. Whether or not nitrates may have a role in the primary and/or secondary prophylaxis of bleeding needs to be addressed in further long-term studies.

Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats.

The aim of this study was to investigate the influence of different strategies of blood volume restitution in the outcome of portal hypertension-related bleeding in anesthetized cirrhotic rats. Gastrointestinal hemorrhage was induced by sectioning a first order branch of the ileocolic vein in 38 cirrhotic rats (common bile duct ligation and occlusion). The subsequent hypovolemic shock was treated with no transfusion (n = 17), moderate transfusion (50% of expected blood loss, 5 mL, n = 11), and total transfusion (100% of expected blood loss, 10 mL, n = 10). At the end of the blood transfusion period (minute 15), mean arterial pressure (MAP) partially recovered in rats receiving moderate transfusion or no transfusion but decreased in the 10-mL transfusion group ( downward arrow 12 +/- 43%, P < .05 vs. no transfusion and 5 mL transfusion). After transfusion, groups given no or 5 mL transfusion remained hemodynamically stable. However, rats receiving 10 mL transfusion continued to deteriorate with persistent bleeding and progressive fall in MAP ( downward arrow 65 +/- 12%; P < .05 vs. no transfusion and 5 mL transfusion). Collected blood loss was significantly greater in the 10-mL group (20.0 +/- 1.5 g) than in groups given 5 mL (15.9 +/- 2.8 g; P < .05) or no transfusion (13.2 +/- 2.1 g; P < .05 vs. 10 mL and 5 mL transfusion). Survival in the no transfusion group was 47%. Rats given 5-mL transfusion had 64% survival. The worst survival was observed in the 10-mL transfusion group (0% survival; P < .05). We concluded that a transfusion policy aimed at completely replacing blood loss worsens the magnitude of bleeding and mortality from portal hypertensive-related bleeding in cirrhotic rats. On the contrary, moderate blood transfusion allowed hemodynamic stabilization and increased survival.

Modification of cardiac function in cirrhotic patients with and without ascites.

OBJECTIVES: Abnormalities in cardiac function have been reported in liver cirrhosis, suggesting a latent cardiomyopathy in these patients. In this study we investigated cardiac function in cirrhotic patients and in controls. METHODS: A total of 20 cirrhotic patients without previous or ongoing ascites, 20 cirrhotic patients with moderate-to-severe ascites, and 10 healthy controls were studied by two-dimensional Doppler echocardiography. Cardiac dimensions and left and right ventricular function were evaluated. The left ventricular geometric pattern was calculated according to Ganau's criteria. Diastolic function was evaluated by the peak filling velocity of E wave and A wave, E/A ratio, and deceleration time of E wave. The pulmonary systolic arterial pressure was also estimated in patients with tricuspid insufficiency. RESULTS: Right and left atrium and right ventricle diameters were significantly enlarged in cirrhotic patients versus controls. E/A ratio was decreased (p < 0.05) in patients with ascites (0.9 +/- 0.2) versus those without ascites (1.3 +/- 0.4) and controls (1.3 +/- 1). The estimated pulmonary systolic arterial pressure was slightly elevated in patients with ascites (35 +/- 5 mm Hg, six patients) versus those with no ascites (28 +/- 5, 10 patients) and controls (27 +/- 8, 6 controls, analysis of variance, p < 0.05). The pattern of left ventricular geometry was normal in the majority of patients. Nitrite and nitrate levels were increased in cirrhotics irrespective of the presence of ascites. CONCLUSIONS: Liver cirrhosis is associated with enlarged right cardiac chambers. Diastolic dysfunction and mild pulmonary hypertension are evident in cirrhotic patients with ascites. These changes do not depend on variations in the left ventricular geometry.

Influence of the surgical treatment on local recurrence of rectal cancer: a prospective study (1980-1992).

BACKGROUND AND OBJECTIVES: The incidence of locoregional recurrences (LR) following radical surgery of rectal cancer varies from 5% to 30% according to the literature. The purpose of this prospective study was to compare the outcome of the Abdomino-Perineal Excision (APE) vs. the Anterior Resection (AR) in a consecutive series of 188 patients who underwent surgery for cure from 1980 to the end of 1992 (81 APE and 107 AR), followed for 5 years, evaluating their influence on the incidence of the recurrences. METHODS: The patients were enrolled at random in the two surgical groups, provided that a radical excision of the tumour, with only two limits: the level of the lesion from the anal verge and the presence of a severe incontinence instrumentally proven. TNM, Dukes staging, grading, and tumour location were statistically evaluated. Further primary suture vs. packing of the perineal wound in APE and handsewn vs. stapled anastomosis in AR were compared in relation with the incidence of LR. RESULTS: The overall local recurrence rate was 19.2% (32/167), in details 19.7% for APE and 18.5% for AR. Similar recurrence rates were observed following both procedures, matching the patients according to the Dukes stage and different details of techniques. A slight statistically significant difference was found as far as the tumour location is concerned in the group treated with anterior resection (p = <0.05) because of the higher recurrence observed in AR performed for tumours of the lower third of the rectum in comparison with the more proximal level. CONCLUSIONS: The AA conclude that the choice of the right surgical procedure in the rectal carcinoma depends on the characteristics of the tumour and the conditions of the patients, provided that the oncologic indications were respected, because recurrence and survival rate are independent from the surgical approaches.

A new highly effective short-term therapy schedule for Helicobacter pylori eradication.

BACKGROUND: Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%). AIM: To evaluate the efficacy of a new short-term treatment sequence on H. pylori eradication. METHODS: A total of 52 patients with H. pylori infection and either non-ulcer dyspepsia (34 patients) or peptic ulcer (18 patients) were enrolled to receive a 10-day therapy: omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, followed by omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Bacterial eradication was assessed by endoscopy (peptic ulcer patients) or 13C urea breath test (non-ulcer dyspepsia patients) 4-6 weeks after therapy had ended. RESULTS: All patients completed the study. H. pylori eradication was achieved in all but one patient, with an eradication rate of 98% (95% CI: 94.3-100) with intention-to-treat analysis. Patient compliance was good (consumption of prescribed drugs > 95%) for all but one patient, who took the triple therapy regimen for 4 days instead of 5 days. No major side-effects were reported but three (6%) patients complained of mild side-effects. CONCLUSIONS: The use of this 'five plus five' therapy schedule as an initial treatment for H. pylori deserves further investigation.

Clotting activation after transjugular intrahepatic portosystemic stent shunt.

BACKGROUND AND AIM: Aim of the study was to investigate the behaviour of clotting system in peripheral circulation of cirrhotic patients undergoing transjugular intrahepatic portosystemic stent shunt (TIPS). METHODS: Clotting variables and endotoxemia were measured 48 h and 30 days after TIPS in patients randomised to receive heparin or not. RESULTS: Forty-eight hours after TIPS, a significant increase of prothrombin fragment F1+2 was observed; such increase was less evident in patients given heparin. Similar findings were observed for endotoxemia, which, however, was not affected by heparin treatment. Thirty days after TIPS procedure prothrombin fragment F1+2 and endotoxemia returned to baseline values independently of the treatment given. CONCLUSION: This study shows that TIPS is associated with an increase of clotting activation which might contribute to acute thrombosis observed after this procedure.

Cost analysis for the prevention of variceal rebleeding: a comparison between transjugular intrahepatic portosystemic shunt and endoscopic sclerotherapy in a selected group of Italian cirrhotic patients.

The aim of the present study was to compare the cumulative cost of the first 18-month period in a selected group of Italian cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic sclerotherapy (ES) to prevent variceal rebleeding. Thirty-eight patients enrolled in a controlled trial were considered (18 TIPS and 20 sclerotherapy). The number of days spent in the hospital for the initial treatment and during the follow-up period were defined as the costs of hospitalization. ES sessions, TIPS procedures, angioplasty or addition of a second stent to maintain the shunt patency, were defined as the costs of therapeutic procedures. The two groups were comparable for age, sex, and Child-Pugh score. During the observation period 4 patients died in the TIPS group, and 2 died and 1 was transplanted in the sclerotherapy group. The rebleeding rate was significantly higher in the sclerotherapy group. Despite this, the number of days spent in the hospital was similar in the two groups. This was because of a higher number of hospital admissions for the treatment of hepatic encephalopathy and shunt insufficiency in the TIPS group. The therapeutic procedures were more expensive for TIPS. Consequently, the cumulative cost was higher for patients treated with TIPS than for those treated with sclerotherapy. The extra cost was because of the initial higher cost of the procedure and the difference was still maintained at the end of the 18-month follow-up. When the cumulative costs were expressed per month free of rebleeding, the disadvantage of TIPS disappeared. In conclusion, a program of prevention of variceal rebleeding with TIPS, despite the longer interval free of rebleeding, is not a cost-saving strategy in comparison with sclerotherapy.

Ongoing prothrombotic state in the portal circulation of cirrhotic patients.

Portal thrombosis may complicate the clinical course of cirrhosis, but the pathophysiologic mechanism is unclear. Aim of the study was to evaluate the behavior of clotting system and endotoxemia in portal vein and in peripheral circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt (TIPS). Portal blood showed higher values of F1 + 2 [Median (range): 2.5 (1.1-5.3) vs. 1.1 (0.6-2.1) nM, p < 0.01], D-dimer [765 (184-1713) vs. 192 (64-813) ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p < 0.01] than peripheral circulation. In the portal vein, all but one sample had F1 + 2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper limit of control values). Fibrinogen was lower in the portal circulation compared to peripheral circulation but the difference was not significant [85 (58-195) vs. 134 (75-244) mg/dl, p > 0.05]. Endotoxemia was directly correlated with F1 + 2 (Rho = 0.92 p < 0.006) and D-dimer (Rho = 0.93, p < 0.005). This study shows that an ongoing prothrombotic state is present in the portal circulation of cirrhotic patients and may play a pivotal role in the thrombotic episodes occurring in this clinical setting.

Whole body and regional body composition analysis by dual-energy X-ray absorptiometry in cirrhotic patients.

OBJECTIVES: To compare whole body and regional (arms, legs and trunk) fat mass, fat-free mineral-free mass bone mineral content and bone mineral density, measured by DXA, in cirrhotic patients and age, sex and BMI matched healthy volunteers. DESIGN: Cross-sectional study. SETTING: Two medical research institutions. SUBJECTS: Twenty-two non ascitic cirrhotic patients and 16 age, sex and BMI matched healthy volunteers. INTERVENTIONS: The Lunar DPX whole-body X-ray densitometer with Lunar software version 3.6z (Lunar Radiation Corp., Madison WI, USA) was used. Regional analysis was performed on the arms, legs, trunk and head. RESULTS: Compared to controls, cirrhotic patients showed a significant reduction in percentage body fat. When differentiated by gender, however, the reduction in percentage body fat was evident in female cirrhotics only, particularly in the trunk. In male cirrhotic patients fat-free mineral-free mass was reduced in absolute terms in the whole body and the limbs. For both genders and in each body segment bone mineral content and density were reduced in cirrhotics compared to controls. In cirrhotic patients bone mineral density was significantly correlated to both fat-free, mineral-free mass (r = 0.85; P < 0.001) and to the Physical Activity Index (r = 0.52; P < 0.01). CONCLUSIONS: Two different patterns of soft tissue loss may be found in cirrhotic patients: in women lean tissue is maintained while fat stores are reduced, as in early starvation; in men lean tissue is reduced, as seen under conditions of stress. Moreover, factors influencing lean body mass, such as nutritional depletion and physical inactivity, may contribute to the reduction of bone density frequently observed in cirrhotic patients.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors.

Forty-seven consecutive patients were prospectively evaluated to study the incidence of hepatic encephalopathy as well as modifications in the PSE index after TIPS. Various clinical, laboratory, and angiographic parameters were also recorded to identify risk factors for the development of post-TIPS hepatic encephalopathy (HE). Mean follow-up was 17 +/- 7 months. During follow-up, six patients died and one underwent transplantation. All other patients were followed for at least a year. Fifteen patients (32%) experienced 20 acute episodes of precipitated HE (hospitalization was necessary in 10 instances), and five patients (11%) presented a continuous alteration in mental status with frequent spontaneous exacerbation during follow-up. Both precipitated and spontaneous HE occurred more frequently during the first three months of follow-up. Moreover the PSE index was significantly worse than basal values one month after TIPS, thereafter returning to near basal values. HE was successfully treated in all patients but one who required a reduction in the stent/shunt diameter. Increasing age (>65 years) and low portacaval gradient (<10 mm Hg) were predictors of HE after TIPS. A gradual dilation of the stent/shunt should be performed to obtain a portacaval gradient >10 mm Hg to avoid an unacceptable rate of HE after TIPS.