Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified?

BACKGROUND AND STUDY AIMS: This study aimed to reassess whether the Forrest classification is still useful for the prediction of rebleeding and mortality in peptic ulcer bleedings and, based on this, whether the classification could be simplified. PATIENTS AND METHODS: Prospective registry data on peptic ulcer bleedings were collected and categorized according to the Forrest classification. The primary outcomes were 30-day rebleeding and all-cause mortality rates. Receiver operating characteristic curves were used to test whether simplification of the Forrest classification into high risk (Forrest Ia), increased risk (Forrest Ib-IIc), and low risk (Forrest III) classes could be an alternative to the original classification. RESULTS: In total, 397 patients were included, with 18 bleedings (4.5%) being classified as Forrest Ia, 73 (18.4%) as Forrest Ib, 86 (21.7%) as Forrest IIa, 32 (8.1%) as Forrest IIb, 59 (14.9%) as Forrest IIc, and 129 (32.5%) as Forrest III. Rebleeding occurred in 74 patients (18.6%). Rebleeding rates were highest in Forrest Ia peptic ulcers (59%). The odds ratios for rebleeding among Forrest Ib-IIc ulcers were similar. In subgroup analysis, predicting rebleeding using the Forrest classification was more reliable for gastric ulcers than for duodenal ulcers. The simplified Forrest classification had similar test characteristics to the original Forrest classification. CONCLUSION: The Forrest classification still has predictive value for rebleeding of peptic ulcers, especially for gastric ulcers; however, it does not predict mortality. Based on these results, a simplified Forrest classification is proposed. However, further studies are needed to validate these findings.

Escherichia coli bacteriuria in female adults is associated with the development of hypertension.

OBJECTIVE: To investigate whether Escherichia coli bacteriuria is associated with the development of hypertension during a long-term follow-up. METHODS: A prospective cohort study was performed among the participants of two population-based studies. Between 1974 and 1986 all women aged 39 to 68 years old, who lived in Utrecht, the Netherlands, were invited to participate in a breast cancer screening program. The participants completed a questionnaire, underwent a medical examination, and collected a morning urine sample that remained stored. From 1993 to 1997 another population-based study was performed. We performed a full cohort analysis for 444 women who participated in both studies. E. coli bacteriuria was diagnosed by a real-time PCR. Hypertension was defined as the use of antihypertensive medication and/or a measured systolic blood pressure of at least 160 mmHg or a diastolic blood pressure of 95 mmHg or higher. The mean follow-up was 11.5+/-1.7 years. RESULTS: Forty women (9%) had E. coli bacteriuria at baseline. Women who had bacteriuria at baseline had a mean blood pressure at study endpoint of 133+/-20 mmHg systolic and 78+/-11 mmHg diastolic, and women without bacteriuria had values of 129+/-20 and 78+/-11 mmHg, respectively (p-values for difference 0.33 and 0.88). Although E. coli bacteriuria was not associated with the blood pressure as a continuous variable, it was associated with the development of hypertension during follow-up (OR 2.8, 95% CI 1.4-5.5). CONCLUSION: E. coli bacteriuria may increase the risk of future hypertension.

Association between Escherichia coli bacteriuria and renal function in women: long-term follow-up.

BACKGROUND: We sought to investigate whether Escherichia coli bacteriuria is associated with a decline in renal function or with the development of end-stage renal failure after long-term follow-up. METHODS: We performed a full cohort analysis for women who participated in 2 population-based studies. The baseline cohort consisted of women who collected morning midstream urine samples that were stored. In the cohort study, the presence of E coli bacteriuria was subsequently determined by real-time polymerase chain reaction. After a mean +/- SD follow-up of 11.5 +/- 1.7 years, blood samples were drawn from 490 women. In the nested case-control study, cases comprised all women who underwent kidney therapy (hemodialysis or renal transplantation) between participation in the baseline cohort study and a mean +/- SD of 13.8 +/- 7.4 years later. RESULTS: The mean +/- SD age at baseline was 45.0 +/- 3.2 years, and 48 women (10%) had E coli bacteriuria. After 11.5 years, the mean +/- SD creatinine clearance (Cockroft-Gault formula) was similar between the 2 groups (87 +/- 21 mL/min [1.5 +/- 0.4 mL/s] and 85 +/- 18 mL/min [1.4 +/- 0.3 mL/s] for women who had and those who did not have bacteriuria, respectively). In the nested case-control study, the prevalence of E coli bacteriuria was 14% among cases and control subjects. The odds ratio corrected for age for the development of end-stage renal failure in the presence of E coli bacteriuria at baseline was 1.1 (95% confidence interval, 0.4-2.8; P = .86). CONCLUSION: Escherichia coli bacteriuria is not associated with a decline in renal function or with the development of end-stage renal failure in a population of generally healthy women during 12 to 14 years of follow-up.

Asymptomatic bacteriuria in women with diabetes mellitus: effect on renal function after 6 years of follow-up.

BACKGROUND: The long-term consequences of asymptomatic bacteriuria (ASB) on renal function in women with diabetes mellitus (DM) are unknown. METHODS: A prospective study was performed among women with type 1 or type 2 DM. Women with ASB (diagnosis based on findings from 1 urine culture specimen) were compared with women without ASB for differences in renal function development and incidence of hypertension. RESULTS: A total of 644 women were included in the study (296 with type 1 DM and 348 with type 2 DM; mean [SD] age, 51 [15] years) and followed up for a mean (SD) duration of 6.1 (1.9) years. The prevalence of ASB was 17%. In women with DM and ASB, the creatinine clearance decreased from 87 mL/min (1.45 mL/s) at baseline to 76 mL/min (1.27 mL/s) at study end point; in women with DM without ASB the creatinine clearance decreased from 97 to 88 mL/min (from 1.62 to 1.47 mL/s). In the multivariate analyses, adjusted for age, length of follow-up, duration of DM, and microalbuminuria at baseline, no association was found between ASB and the relative or the absolute decrease in creatinine clearance; the same results were shown also when women with DM type 1 and women with DM type 2 were analyzed separately. Women with ASB developed hypertension more often than women without ASB (54% vs 37%; P = .045), but there was no significant association in the multivariate analysis (odds ratio, 1.5; 95% confidence interval, 0.7-3.6). CONCLUSION: Women with DM (type 1 or type 2) with ASB do not have an increased risk for a faster decline in renal function or the development of hypertension after 6 years of follow-up.

Fimch antiserum inhibits the adherence of Escherichia coli to cells collected by voided urine specimens of diabetic women.

PURPOSE: With the increasing problem of resistance in pathogenic microorganisms the development of nonantimicrobial therapies is important. Diabetes mellitus (DM) is associated with an increased incidence of urinary tract infections. The majority of Escherichia coli strains, which is the most prevalent uropathogen, have type 1 fimbriae that bind to uroplakin in the bladder, as mediated by the adhesin FimH. A vaccine is being developed based on FimH adhesion. MATERIALS AND METHODS: The sequence of FimH adhesion of 29 E. coli strains isolated from women with DM was determined. For adherence experiments we used E. coli isolated from women with DM and a T24 bladder cell line as well as the 2 well-defined type 1 fimbriated E. coli strains Ctrl 39 and NU14, and uroepithelial cells from women with DM. RESULTS: The fimH sequence of E. coli strains isolated from women with DM was highly homologous to the known fimH sequence of E. coli from patients without DM. Adherence assays in a T24 bladder cell line showed that adherence of these E. coli strains from women with DM could be inhibited by pre-incubation with antiserum raised against the chaperone-adhesin complex FimC-FimH. AntiFimCH antiserum also inhibited the adherence of the 2 well-defined E. coli strains expressing type 1 fimbriae, NU14 and Ctrl 39, but not of the FimH mutant strain NU14 H-, to uroepithelial cells from women with DM. CONCLUSIONS: These findings suggest that a vaccine based on FimH adhesin of type 1 fimbriated E. coli is a potential method of preventing urinary tract infection in women with DM.

History taking and leukocyturia predict the presence of asymptomatic bacteriuria in women with diabetes mellitus.

OBJECTIVE: To investigate the accuracy of history taking to diagnose asymptomatic bacteriuria (ASB) in diabetic women, and the added value of leukocyturia. METHODS: Data were obtained from a multicenter study including 465 women with diabetes. Many patient characteristics were considered as potential diagnostic determinants. A urinary leukocyte count and a urine culture (the criterion standard) were performed. Logistic regression analyses were performed and areas under the receiver operating characteristic curves (AUC) were calculated. RESULTS: For women with type 1 diabetes (n = 236; ASB 11%), duration of diabetes and glycosylated hemoglobin (GHb) were powerful predictors of ASB. The AUC of the model including these two variables was 0.66 (95% confidence interval (CI) 0.53-0.78). After addition of leukocyturia, the AUC increased considerably to 0.78 (95% CI 0.68-0.88; p = 0.018). For women with type 2 diabetes (n = 229; ASB 19%), age and the number of symptomatic urinary tract infections (UTIs) in the previous year were the strongest predictors of ASB. The AUC of the model including these variables was 0.70 (95% CI 0.61-0.80). After addition of leukocyturia, the AUC increased to 0.79 (95% CI 0.71-0.86; p = 0.023). CONCLUSION: In diabetic women, ASB can be diagnosed using two easily obtainable variables (duration of diabetes and GHb for women with type 1 diabetes, and age and the number of UTIs in the previous year for women with type 2 diabetes) in combination with a urinary leukocyte count. This results in a model with sufficient accuracy (AUC > 0.75).

Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus.

Urinary tract infections (UTIs) are more common and tend to have a more complicated course in patients with diabetes mellitus (DM). The mechanisms, which potentially contribute to the increased prevalence of both asymptomatic and symptomatic bacteriuriai in these patients are defects in the local urinary cytokine secretions and an increased adherence of the microorganisms to the uroepithelial cells. The need for treatment of asymptomatic bacteriuria remains controversial. No evidence is available on the optimal treatment of acute cystitis and pyelonephritis in patients with DM. Because of the frequent (asymptomatic) upper tract involvement and the possible serious complications, many experts recommend a 7-14-day oral antimicrobial regimen for bacterial cystitis in these patients, with an antimicrobial agent that achieves high levels both in the urine and in urinary tract tissues. Current data suggest that shorter regimens will lead to failure also in uncomplicated UTI in women. The recommended treatment of acute pyelonephritis does not differ from that in nondiabetic patients. Clinical trials specifically dealing with the treatment of UTIs in diabetic patients, comparing the optimal duration and choice of antimicrobial agent, are needed. Besides that, new approaches to preventive strategies must prove their value in this specific patient group.

Management of bacterial urinary tract infections in adult patients with diabetes mellitus.

Urinary tract infections (UTIs) are more common and tend to have a more complicated course in patients with diabetes mellitus than in the general population. The mechanisms that potentially contribute to the increased prevalence of both asymptomatic and symptomatic bacteriuria in these patients are defects in the local urinary cytokine secretions and an increased adherence of the microorganisms to the uroepithelial cells. The need for treatment of asymptomatic bacteriuria remains controversial. No evidence is available on the optimal treatment of acute cystitis and pyelonephritis in patients with diabetes. Because of the frequent (asymptomatic) upper tract involvement and the possible serious complications, many experts recommend a 7- to 14-day oral antibacterial regimen for bacterial cystitis in these patients, with an antibacterial agent that achieves high concentrations both in the urine and in urinary tract tissues. The recommended treatment of acute pyelonephritis does not differ from that in patients without diabetes. Clinical trials specifically dealing with the treatment of UTIs in patients with diabetes, comparing the optimal duration and choice of antibacterial agent, are needed. In addition, new approaches to preventive strategies must prove their value in this specific patient group.

Pathogenesis of bacteriuria in women with diabetes mellitus.

Women with diabetes mellitus (DM) have asymptomatic bacteriuria (ASB) and symptomatic urinary tract infections (UTIs) more often than women without DM. The increased prevalence of bacteriuria in diabetic patients can be the result of differences in the host responses between diabetic and nondiabetic patients, or a difference in the infecting bacterium itself. We have shown that the increased prevalence of ASB in diabetic women is not the result of a difference in bacteria, because the same number of virulence factors was found in the infecting Escherichia coli (most common causative microorganism of ASB) in our diabetic women with ASB, as listed in the literature for nondiabetic patients with ASB. We found that bacterial growth in vitro was increased after the addition of different glucose concentrations, as found in urine of poorly controlled patients. However, we could not confirm that glucosuria was a risk factor for ASB in vivo. In addition, we demonstrated that women with both DM and ASB have lower urinary cytokine and leukocyte concentrations than women without DM but with ASB. Finally, we found that E. coli expressing type 1 fimbriae (the virulence factor that plays an important role in the pathogenesis of UTIs) adhere better to uroepithelial cells of women with DM compared with the cells of women without DM.

Adherence of type 1-fimbriated Escherichia coli to uroepithelial cells: more in diabetic women than in control subjects.

OBJECTIVE: Women with diabetes have bacteriuria more often than women without diabetes. Because Escherichia coli adhere better to vaginal cells of nondiabetic patients with recurrent urinary tract infections (UTIs) than to those obtained from healthy control subjects, it was hypothesized that E. coli adhere more to the uroepithelial cells of diabetic women, either because of substances excreted in the urine (e.g., albumin, glucose, and Tamm Horsfall protein) or because of a difference in the uroepithelial cells. RESEARCH DESIGN AND METHODS: A T24 bladder cell line and uroepithelial cells of 25 diabetic women and 19 control subjects were incubated with three different E. coli strains. RESULTS: The mean numbers of type 1-fimbriated E. coli that adhered to diabetic and control cells were 12.9 and 6.1 (P = 0.001), respectively, whereas those of P-fimbriated E. coli were 8.8 and 8.1 (P = 0.8), and those of nonfimbriated E. coli were 2.7 and 3.4 (P = 0.4). The addition of various substances did not influence the adherence of E. coli to a T24 bladder cell line. CONCLUSIONS: Type 1-fimbriated E. coli adhere more to diabetic than to control uroepithelial cells.