MANAGEMENT OF VARICEAL HEMORRHAGE: CURRENT CONCEPTS

Introduction

The treatment of portal hypertension is complex and the the best strategy depends on the underlying disease (cirrhosis vs. schistosomiasis), patient''s clinical condition and time on it is performed (during an acute episode of variceal bleeding or electively, as pre-primary, primary or secondary prophylaxis). With the advent of new pharmacological options and technical development of endoscopy and interventional radiology treatment of portal hypertension has changed in recent decades.

Aim

To review the strategies employed in elective and emergency treatment of variceal bleeding in cirrhotic and schistosomotic patients.

Methods

Survey of publications in PubMed, Embase, Lilacs, SciELO and Cochrane databases through June 2013, using the headings: portal hypertension, esophageal and gastric varices, variceal bleeding, liver cirrhosis, schistosomiasis mansoni, surgical treatment, pharmacological treatment, secondary prophylaxis, primary prophylaxis, pre-primary prophylaxis.

Conclusion

Pre-primary prophylaxis doesn''t have specific treatment strategies; the best recommendation is treatment of the underlying disease. Primary prophylaxis should be performed in cirrhotic patients with beta-blockers or endoscopic variceal ligation. There is controversy regarding the effectiveness of primary prophylaxis in patients with schistosomiasis; when indicated, it is done with beta-blockers or endoscopic therapy in high-risk varices. Treatment of acute variceal bleeding is systematized in the literature, combination of vasoconstrictor drugs and endoscopic therapy, provided significant decline in mortality over the last decades. TIPS and surgical treatment are options as rescue therapy. Secondary prophylaxis plays a fundamental role in the reduction of recurrent bleeding, the best option in cirrhotic patients is the combination of pharmacological therapy with beta-blockers and endoscopic band ligation. TIPS or surgical treatment, are options for controlling rebleeding on failure of secondary prophylaxis. Despite the increasing evidence of the effectiveness of pharmacological and endoscopic treatment in schistosomotic patients, surgical therapy still plays an important role in secondary prophylaxis.     

A Meta‐Analysis of the Association of Fracture Risk and Body Mass Index in Women

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m²) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m², the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m² was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.     

Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis.

The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.     

Hemoglobinopathies in the Christmas Island population

Christmas Island is a remote Australian territory 2,400 km north of Perth. Health care is administered from Perth. The population is predominantly Chinese, with some Malay, Indian and European. As hemoglobinopathies are known to be common amongst these ethnic groups, a study was performed to determine their prevalence and significance in the Christmas Island population. Three-hundred and sixty-four individuals (adults and children) were tested. All subjects were assessed by full blood count, alpha-globin multiplex polymerase chain reaction (PCR) and PCR testing for Hb Constant Spring [alpha142, Term-->Gln, TAA-->CAA (alpha2)]. Microcytic patients (MCV <80 fL) were further investigated by high performance liquid chromatography (HPLC) and serum ferritin was determined. Where present, beta-thalassemia (thal) mutations were characterised by PCR. Thirty-four subjects (9.3%) were microcytic and of these five were iron deficient. The remainder were heterozygous for a hemoglobinopathy, giving a 9.1% incidence of hemoglobinopathies in Christmas Islanders. alpha-Thalassemia was identified in 23 subjects, seven of whom were heterozygous for alpha(-3.7); the remaining 16 were heterozygous for the - -SEA deletion. One case of heterozygous deltabeta-thal and one case of heterozygous Hb E [beta26(B8)Glu-->Lys] was detected. Of the eight subjects heterozygous for beta-thal, at least five mutations are represented, indicating a diverse and heterogeneous origin for this population.     

Effect of hysterectomy on anorectal and urethrovesical physiology.

To investigate whether vaginal or total abdominal hysterectomy is associated with changes in anorectal and urethrovesical physiology, 26 women were studied before operation and six weeks and six months afterwards. The results showed a postoperative increase in both rectal and vesical sensitivity (p less than 0.01). Similar results were observed irrespective of the type of hysterectomy. No significant changes in rectal or bladder compliance were noted, and anal pressure and urethral pressure and length were unchanged after surgery. Whole gut transit was not affected by hysterectomy. Urinary symptoms occurred de novo in 6/26 women and gastrointestinal symptoms in 2/26 women. These results show that significant changes in rectal and vesical sensitivity occur after hysterectomy for benign disease. These persist for at least six months postoperatively but are not always associated with development of urinary or gastrointestinal symptoms.     

Back to the Future with Phenotypic Screening

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Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men

Purpose

To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data.

Methods

Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences.

Results

Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high.

Conclusions

Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.     

Circulating angiogenic and inflammatory cytokine responses to acute aerobic exercise in trained and sedentary young men

Purpose

Endurance exercise training can ameliorate many cardiovascular and metabolic disorders and attenuate responses to inflammatory stimuli. The purpose of this study was to determine whether the angiogenic and pro-inflammatory cytokine response to acute endurance exercise differs between endurance-trained and sedentary young men.

Methods

Ten endurance-trained and ten sedentary healthy young men performed 30 min of treadmill running at 75 % VO_2max with blood sampling before and after exercise. Plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble VEGF receptor-1 (sFlt-1) were measured by multiplex ELISA.

Results

Acute exercise increased IL-6 by 165 % (P < 0.05), IL-8 by 32 % (P < 0.05), PlGF by ~16 % (P < 0.05), sFlt-1 by 36 % (P < 0.001), and tended to increase bFGF by ~25 % (P = 0.06) in main effects analyses. TNF-α and VEGF did not change significantly with exercise in either group. Contrary to our hypothesis, there were no significant differences in TNF-α, IL-6, VEGF, bFGF, PlGF, or sFlt-1 between groups before or after acute exercise; however, there was a tendency for IL-8 concentrations to be higher in endurance-trained subjects compared to sedentary subjects (P = 0.06).

Conclusions

These results indicate that 30 min of treadmill running at 75 % VO_2max produces a systemic angiogenic and inflammatory reaction, but endurance exercise training does not appear to significantly alter these responses in healthy young men.