The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers ...associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA–treated external controls.
Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis.
During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10–0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12–0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03–1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09–1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21–0.85) including hepatic decompensation.
Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.
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Patients with primary biliary cholangitis treated with obeticholic acid in the POISE study had fewer deaths and liver transplants vs comparable patients in the Global PBC and UK-PBC disease registries.
Postanal pilonidal sinus is a skin condition in the midline of the natal cleft. A primary pit forms in the midline, caused by a hair follicle that has become infected, into which loose hairs enter to ...create a track or abscess.
This article explains how a pilonidal sinus develops and presents, and details methods of treatment in the primary care setting and specialist management options.
The devastation of recurrence with further pain, embarrassment, and time off work or school (in some cases for months or years), plus the prospect of more surgery is still common for patients with postanal pilonidal sinus. This can be avoided with the correct management. Surgery now has methods that produce early healing, low recurrence rates and acceptable cosmetic results.
Parenteral nutrition and the absence of luminal feeding result in impaired intestinal growth and differentiation of enterocytes. Glucagon-like peptide 2 (GLP-2) and epidermal growth factor (EGF) have ...each been shown to have trophic effects on the intestine, and thus have the potential to benefit patients fed parenterally, such as those with intestinal failure from short bowel syndrome. We report studies aimed to determine whether there may be synergistic effects of these 2 peptides.
Rats were established on parenteral nutrition (PN) and infused for 6 days with GLP-2 (20 microg/d), EGF (20 microg/d), or GLP-2 + EGF (20 microg/d of each). These groups were compared with untreated PN-fed and orally-fed controls. Tissue was obtained from small intestine and colon to determine growth, proliferation, and representative gene expression.
Small intestinal weight was increased by 75%, 43%, and 116% in the GLP-2, EGF, and GLP-2 + EGF groups, respectively, compared with PN controls (all p < .001). Cell proliferation increased with GLP-2, EGF, and GLP-2 + EGF in proximal small intestine by factors of 2.3, 1.7, and 3.4 respectively (p < .001). A synergistic effect on villous and crypt area was observed in the proximal small intestine when GLP-2 and EGF were combined (p < .05). GLP-2 had no effect in the colon, unlike EGF. Further studies showed GLP-2 + EGF significantly increased expression in distal small intestine of transcripts for the bile acid transport protein IBABP (p < .05) and showed a significant correlation between the expression of IBABP and the transcription factor HNF-4.
Both GLP-2 and EGF upregulate growth of the small intestine, and this is augmented when GLP-2 and EGF are combined. These findings may lead to improved treatment of patients receiving PN.
Microscopic colitis: the tip of the iceberg? Kitchen, Paul A; Levi, A Jonathen; Domizio, Paula ...
European journal of gastroenterology & hepatology,
2002-November, Letnik:
14, Številka:
11
Journal Article
Recenzirano
The aims were to determine whether a wide variation exists between hospitals in the diagnosis of microscopic colitis and to assimilate clinical data.
Retrospective study of 90 patients with ...microscopic colitis aged between 16 and 92 years from 11 hospitals in south-east England.
A questionnaire was designed to collect relevant data from all patients in whom a new diagnosis of microscopic colitis had been made at the source hospital between January 1990 and December 1996. The inclusion criteria were presentation with watery diarrhoea, a normal endoscopy and a histological report of microscopic colitis. Histology slides were then requested and reviewed. Clinical data were analysed with reference to the confirmed diagnosis.
The number of patients diagnosed at each hospital ranged between zero and 30, with a median of six. Sixty-eight patients had histological slides reviewed. The numbers of patients with a final reviewed diagnosis of collagenous colitis, lymphocytic colitis and microscopic colitis, type undesignated, were 37, 18 and seven respectively. In thirty-one patients (34%) there was a recent history of the use of non-steroidal anti-inflammatory drugs.
These data confirm that there is wide hospital variation in the diagnosis of microscopic colitis. Furthermore, the small group with the undesignated type may be associated with the use of non-steroidal anti-inflammatory drugs.
Background: In situ disease surrounding invasive tumours is an important consideration in the management of patients with early breast cancer. This study of screen‐detected breast cancers assessed ...the influence of in situ disease including an extensive in situ component (defined as ductal carcinoma in situ involving more than 25% of the area within the invasive tumour) on surgical management, local recurrence and survival of a group of patients.
Methods: A total of 595 cases of invasive breast cancer detected at St Vincent’s BreastScreen were retrospectively reviewed to determine presence and extent of in situ disease, the surgical procedure and adequacy of excision. Outcome was examined in a cohort of 126 cases.
Results: A total of 438 (74%) patients had in situ foci in or around the invasive tumour and 107 (18%) were defined as extensive in situ component (EIC)‐positive. The initial procedure was mastectomy in 20% of the cases and breast‐conserving surgery in 80% including 18% who underwent further surgery. Re‐excision (P = 0.02) or mastectomy (P = 0.01) was more often required in patients with EIC. After definitive local excision, margins were close or involved with invasive disease in 3% but the patients with EIC were more likely to have margins close or involved with in situ disease (16 vs 2%; P = 0.001). There were seven deaths and one local invasive recurrence in the follow‐up group and none of the deaths were in patients who were EIC‐positive.
Conclusions: EIC predicts for a higher rate of re‐excision and/or mastectomy. For patients with EIC, there is an acceptably low risk of local recurrence if margins are clear.
We sought the extent to which arm morbidity could be reduced by using sentinel-lymph-node-based management in women with clinically node-negative early breast cancer. One thousand eighty-eight women ...were randomly allocated to sentinel-lymph-node biopsy followed by axillary clearance if the sentinel node was positive or not detected (SNBM) or routine axillary clearance (RAC, sentinel-lymph-node biopsy followed immediately by axillary clearance). Sentinel nodes were located using blue dye, alone or with technetium-labeled antimony sulfide colloid. The primary endpoint was increase in arm volume from baseline to the average of measurements at 6 and 12 months. Secondary endpoints were the proportions of women with at least 15% increase in arm volume or early axillary morbidity, and average scores for arm symptoms, dysfunctions, and disabilities assessed at 6 and 12 months by patients with the SNAC Study-Specific Scales and other quality-of-life instruments. Sensitivity, false-negative rates, and negative predictive values for sentinel-lymph-node biopsy were estimated in the RAC group. The average increase in arm volume was 2.8% in the SNBM group and 4.2% in the RAC group (
P
= 0.002). Patients in the SNBM group gave lower ratings for arm swelling (
P
< 0.001), symptoms (
P
< 0.001), and dysfunctions (
P
= 0.02), but not disabilities (
P
= 0.5). Sentinel nodes were found in 95% of the SNBM group (29% positive) and 93% of the RAC group (25% positive). SNB had sensitivity 94.5%, false-negative rate 5.5%, and negative predictive value 98%. SNBM was successfully undertaken in a wide range of surgical centers and caused significantly less morbidity than RAC.
Background: In the present paper we describe the presentation and management of ductal carcinoma in situ (DCIS) of the breast in women in Australia in 1995. This representative, national data set ...provides a historical comparator for studies examining DCIS management that follow.
Methods: Surgeons identified by population‐based cancer registries as having treated a new diagnosis of DCIS between 1 April and 30 September 1995 completed a questionnaire on the presentation and management of each case.
Results: Two hundred and five surgeons supplied treatment details on 418 DCIS tumours in 415 women. Half of all tumours were detected at BreastScreen clinics and a further 25% were detected at other mammography centres. Twenty‐six percent of tumours were palpable at presentation, 33% were multifocal and 55% were high grade (including comedocarcinoma). Breast conserving therapy (BCT) rather than mastectomy was utilized in 260 (62%) of cases. Tumours that were of low grade, small in size and not multifocal were more likely to be treated by BCT. Surgeons seeing six or more DCIS cases in the 6‐month period were more likely to utilize BCT. Of the conservatively treated cases, 22% were referred for a radiation oncology consultation. The most common reasons for treating DCIS with mastectomy were that the tumour was too extensive or multifocal (63%), it extended to margins of the specimen (42%), or patient concerns about recurrence (34%).
Conclusions: In 1995 the majority of DCIS was treated with breast conserving surgery alone. Surgeons treating more DCIS cases were more likely to perform conservative surgery than surgeons treating only one DCIS case in the study period.
