Summary
Background
Crohn's disease recurs in the majority of patients after intestinal resection.
Aim
To compare the relative efficacy of thiopurines and anti‐TNF therapy in patients at high risk of ...disease recurrence.
Methods
As part of a larger study comparing post‐operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine‐intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.
Results
A total of 101 patients 50% male; median (IQR) age 36 (25–46) years were included. There were no differences in disease history between thiopurine‐ and adalimumab‐treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2–i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab‐treated patients intention‐to‐treat (ITT); P = 0.028 or 24 of 62 (39%) vs. 3 of 24 (13%) respectively per‐protocol analysis (PPA); P = 0.020. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).
Conclusions
In Crohn's disease patients at high risk of post‐operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
Summary
Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study ...demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss.
Introduction
This prospective study investigated bone health in women following premenopausal oophorectomy.
Methods
Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up.
Results
Mean age was 42.4 ± 2.6 years (
n
= 30) for the surgery group and 40.2 ± 6.3 years for controls (
n
= 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (
k
bend
) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all
p
< 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and
k
bend
(14.8%) were observed at 24 months (all
p
< 0.01). HT prevented losses in
k
bend
, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (
p
= 0.01).
Conclusion
This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.
Introduction:
Patients with Crohn’s disease have poorer health-related quality of life HRQoL than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve ...drug-induced or surgically induced remission, the effects of surgery overall have not been well characterised.
Methods:
In a randomised trial, patients undergoing intestinal resection of all macroscopically diseased bowel were treated with postoperative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. C-reactive protein CRP, Crohn’s Disease Activity Index CDAI, and faecal calprotectin FC were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed with a general SF36 and disease-specific IBDQ questionnaires at the same time points.
Results:
A total of 174 patients were included. HRQoL was poor preoperatively but improved significantly p < 0.001 at 6 months postoperatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared with males and non-smokers, respectively. Persistent endoscopic remission, intensification of drug treatment at 6 months, and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes different from those when these factors were not present. There was a significant inverse correlation between CDAI, but not endoscopic recurrence, CRP, or FC on HRQoL.
Conclusion:
Intestinal resection of all macroscopic Crohn’s disease in patients treated with postoperative prophylactic drug therapy is associated with significant and sustained improvement in HRQoL irrespective of type of drug treatment or endoscopic recurrence. HRQoL is lower in female patients and smokers. A higher CDAI, but not direct measures of active disease or type of drug therapy, is associated with a lower HRQoL.
Summary
Clostridium septicum is the causative agent of spontaneous gas gangrene or atraumatic myonecrosis, a sudden and frequently fatal infection that is increasingly associated with malignancy of ...the colon. Little is known about the disease process although the focus of virulence studies has been the α‐toxin, a pore‐forming cytolysin that is encoded by the csa gene and secreted as an inactive protoxin. Until now a lack of techniques for the genetic manipulation of C. septicum has hindered the use of molecular approaches to understand pathogenesis. By introducing plasmids by conjugation from Escherichia coli, we have developed methods for the genetic manipulation of C. septicum and constructed a chromosomal csa mutant by allelic exchange. Virulence testing of an isogenic series of strains consisting of the wild type, the csa mutant, and a csa mutant complemented with the wild‐type csa gene revealed that the development of fulminant myonecrosis in mice was dependent on the ability to produce a functional haemolytic α‐toxin. Furthermore, the inhibition of leukocyte influx into the lesion, which is very typical of clostridial myonecrosis, was also dependent on the ability to produce α‐toxin. This study represents the first definitive identification of a virulence factor in this organism and opens the way for further studies that will delineate the role of other putative virulence factors in this significant pathogen.
Summary
In this study, we detected multiple var gene transcripts within single,
mature trophozoite‐infected red blood cells (iRBCs) bound to chondroitin sulphate
A (CSA). Several of the var detected ...had previously been demonstrated to encode
Plasmodium falciparum erythrocyte membrane protein‐1 (PfEMP‐1) variants with
domains that mediated iRBC adhesion to receptors other than CSA. Parasites expressing
the CSA‐adherent phenotype transcribed far more of one var than of all others,
but this gene was different from the two other var previously purported to
encode adhesion to CSA. Previous work suggesting that only single var are transcribed by mature trophozoites needs re‐examination in the light of these data from single, infected cells.
Twelve strains of Escherichia coli previously reported to cause diarrhea in rabbits were examined for properties associated with virulence. Ten strains met the criteria for classification as ...enteropathogenic E. coli in that they were diarrheagenic strains that evoked attaching-effacing lesions in the small intestine and did not produce detectable enterotoxins or cytotoxins. These bacteria exhibited a variety of patterns when investigated for adherence to HEp-2 epithelial cells. Although several strains displayed localized and/or diffuse adherence to epithelial cells, they did not hybridize with DNA probes that recognize the genes responsible for these phenotypes in diarrheagenic E. coli from humans. The bacteria also varied in their ability to bind to erythrocytes and intestinal brush borders from various animal species. Six strains adhered to rabbit brush borders; two of these also adhered to brush borders from other animals. Two strains that did not adhere to rabbit brush borders adhered to those from guinea pigs or sheep. Only one of the strains investigated carried AF/R1 fimbriae, which are believed to govern the host specificity of this category of diarrheagenic E. coli. This strain was E. coli RDEC-1, which remains the only E. coli strain to date that is known to carry fimbriae of this type. The results indicate that although diarrheagenic E. coli strains from rabbits may have common properties associated with the ability to produce attaching-effacing lesions, they differ from each other and from enteropathogenic E. coli of humans in terms of some of the adhesins that mediate binding to eukaryotic cells
The ability to cause attaching and effacing (AE) lesions in intestinal epithelial cells is an essential virulence trait of enteropathogenic E. coli (EPEC) that requires several chromosomal genes ...acting in concert with one another. In this study, we show that the ability to cause AE lesions can be transferred by conjugal mating from a high frequency recombinant (Hfr) derivative of a rabbit EPEC strain, E. coli RDEC-1, to a strain of E. coli K-12. Although the recipient acquired a considerable amount of donor DNA during the transfer process, it expressed the AE phenotype only weakly. The findings suggest that AE is a multigene phenomenon, the genes for which may not reside on a single region of the bacterial chromosome.
The ability to cause attaching and effacing (AE) lesions in intestinal epithelial cells is an essential virulence trait of enteropathogenic E. coli (EPEC) that requires several chromosomal genes ...acting in concert with one another. In this study, we show that the ability to cause AE lesions can be transferred by conjugal mating from a high frequency recombinant (Hfr) derivative of a rabbit EPEC strain, E. coli RDEC-1, to a strain of E. coli K-12. Although the recipient acquired a considerable amount of donor DNA during the transfer process, it expressed the AE phenotype phenotype only weakly. The findings suggest the AE is a multigene phenomenon, the genes for which may not reside on a single region of the bacterial chromosome.
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