Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy.

INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I). MATERIALS AND METHODS: After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7). RESULTS: In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed. CONCLUSION: These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage.     

The effect of appendectomy on the course of ulcerative colitis: a systematic review

Aim Previous studies have shown significantly lower appendectomy rates in ulcerative colitis (UC) patients compared with healthy controls. Evidence indicating that the appendix has an immunomodulatory role in UC has been accumulating. To examine the latest evidence on the effect of appendectomy on the disease course of UC. Method PubMed, The Cochrane Library and EMBASE were searched. Primary end‐points were number of relapses, use of steroids, number of hospital admissions and number of colectomies. Results The search resulted in six observational studies (five case–control studies and one cohort study) totalling 2532 patients. Owing to clinical heterogeneity, no meta‐analysis could be conducted. One study found lower relapse rates in patients appendectomized before the onset of UC [absolute risk reduction (ARR) = 21.5%; 95% CI: 1.71–45.92%]. Another two studies found a reduced requirement for immunosuppression in appendectomized patients (ARR = 20.2%; 95% CI: 9.67–30.46% in the first study and ARR = 21.4%; 95% CI: 10.32–32.97% in the second study). In addition, one study found lower colectomy rates in nonappendectomized patients (ARR = 8.7%; 95% CI: 1.29–18.66%) and two studies found lower colectomy rates in appendectomized patients (ARR = 21.4%; 95% CI: 13.17–28.79% in the first study and ARR = 18.7%; 95% CI: 7.50–29.97% in the second study). Conclusion There are limited and conflicting data available regarding the effect of appendectomy on the disease course of UC. Most studies suggest a beneficial effect and the minority find no, or a negative, effect.     

Increased cancer risk in a large population-based cohort of patients with primary biliary cirrhosis: follow-up for up to 36 years

Background and aims

The natural history of primary biliary cirrhosis (PBC) has so far mainly been studied in tertiary referral centres. The aim of the present investigation was to describe the natural history of PBC in a large population-based cohort in order to identify risk factors for development of malignancies and disease progression.

Methods

Four independent hospital databases were searched in 44 hospitals in a geographically defined area, after which all medical records were evaluated on site. In addition, PBC registries in the three liver transplant centers were checked for missed referrals from the area of interest.

Results

In total, 992 cases fulfilled the inclusion criteria. The median follow-up was 73 months (range 0–434). Mortality was similar to the age- and gender matched population (SMR 1.1; 95 % CI 0.9–1.4). Male gender, smoking, and elevated bilirubin, decreased albumin, and elevated AST at time of diagnosis, were associated with an increased risk for the combined end point PBC-related death or liver transplantation. In total, 133 (13 %) patients developed one or more malignancies (SIR 1.5; 95 % CI 1.1–1.9). There was a ninefold increased risk of developing hepatobiliary malignancies (SIR 9.4; 95 % CI 3.04–21.8), a fivefold increased risk of developing urinary bladder cancer (SIR 5.0; 95 % CI 1.6–11.6), and a 1.8-fold increased risk of developing breast cancer (SIR 1.8; 95 % CI 1.08–2.81).

Conclusion

PBC is associated with an increased risk of hepatobiliary, bladder and breast cancer. Still, survival—under treatment with ursodeoxycholic acid (UDCA)—was comparable to the general population in this population-based study.     

MRI characteristics of proctitis in Crohn’s disease on perianal MRI

Purpose

Multiple features have been described for assessing inflammation in Crohn’s disease (CD) in MR enterography, but have not been validated in perianal magnetic resonance imaging (MRI). Retrospectively, we studied which MRI features are valuable in assessing proctitis.

Materials and methods

CD patients (≥18 years) who underwent colonoscopy (reference standard) and perianal fistula MRI within 8 weeks were included. Seventeen MRI features were blindly scored by three observers and correlated to endoscopy (regression analysis). Reproducibility (multirater kappa, intraclass correlation coefficient) was determined for all three observer pairs. MRI features were considered relevant when significantly correlated to endoscopy for ≥2 observers, and reproducibility was ≥0.40 for ≥2 observer pairs.

Results

Perianal MRI of 58 CD patients were included. Wall thickness, rectal mural fat, creeping fat, and size of mesorectal lymph nodes showed a significant correlation with endoscopy for ≥2 observers (p = 0.000–0.023, p = 0.011–0.172, p = 0.007–0.011 and p = 0.000–0.005, respectively) with a kappa/intraclass correlation coefficient of ≥0.60 for ≥2 observer pairs. Perimural T2 signal and perimural enhancement significantly correlated to endoscopy (all p values ≤0.05) for all three observers and the reproducibility was ≥0.40 for ≥2 observer pairs. Mural T2 signal and degree and pattern of T1 enhancement showed significant correlation to endoscopy for two observers, but with poor to moderate reproducibility.

Conclusion

Wall thickness, mural fat, and mesorectal features (perimural T2 signal, perimural enhancement, creeping fat, and size of mesorectal lymph nodes) had significant correlation to endoscopy and were reproducible in diagnosing proctitis. Some established luminal features in MRE were considered not useful.

     

Increased hepatitis E virus prevalence on Dutch pig farms from 33 to 55% by using appropriate internal quality controls for RT-PCR

Pigs have been suggested to be a potential reservoir for locally acquired human hepatitis E virus (HEV) infections in the Netherlands. To study possible trends in HEV prevalence in the Dutch pig population, 97 pig farms have been screened for the presence of HEV in stools. The prevalence rate of HEV was estimated at 55% (53/97) in 2005, indicating a significant increase as compared to the prevalence rate of 22% (25/115) as was reported in 1999. The current data suggest that this increase is due to the inclusion of appropriate quality assurance controls such as internal amplification controls for RT-PCR. The abundant presence of pigs excreting HEV raises concerns on potential zoonotic transmission of the virus, either by exposure through the environment or by consumption of contaminated pork products. Moreover, one of the detected strains belonged to a European cluster which was not detected in the Netherlands before, suggesting that HEV strains spread through European countries. These data demonstrate the need to include appropriate controls in diagnostic assays, especially in complex matrices such as feces which are known to contain PCR inhibitory substances.     

Formal and informal care for community‐dwelling frail elderly people over time: A comparison of integrated and usual care in the Netherlands

While integration has become a central tenet of community‐based care for frail elderly people, little is known about its impact on formal and informal care and their dynamics over time. The aim of this study was therefore to examine how an integrated care intervention for community‐dwelling frail elderly people affects the amount and type of formal and informal care over 12 months as compared to usual care. A quasi‐experimental design with a control group was used. Data regarding formal and informal care were collected from frail elderly patients (n = 207) and informal caregivers (n = 74) with pre/post‐questionnaires. Within‐ and between‐group comparisons and multiple linear regression analyses were performed. The results showed marginal changes over time in the amount of formal and informal care in both integrated care and usual care. However, different associations between changes in formal and informal care were found in integrated and usual care. Most notably, informal caregivers provided more instrumental assistance over time if formal caregivers provided less personal care (and vice versa) in integrated care but not in usual care. These results suggest that integrated care does not necessarily change the contribution of formal or informal care, but changes the interaction between formal (personal care) and informal (instrumental) activities. Implications and recommendations for research and practice are discussed. Trial registration: Current Controlled Trials ISRNT05748494.