Histopathologic Features Aid in Predicting Risk for Progression of IgA Nephropathy

Background and objectives: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Accurately identifying patients who are at risk for progressive disease is challenging. The extent to which histopathologic features improves prognostication is uncertain.Design, setting, participants, & measurements: We studied a retrospective cohort with biopsy-proven IgAN in Calgary, Canada. Renal biopsies were reviewed by a nephropathologist with histopathologic data abstracted using a standardized form. The primary outcome was the composite of doubling of serum creatinine, ESRD, or death. Spline models defined significant levels of interstitial fibrosis, glomerulosclerosis, hypertension, proteinuria, and creatinine. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models.Results: Data from 146 cases were available for analysis with a median follow-up of 5.8 years. Greater than 25% interstitial fibrosis, >40% glomerular sclerosis, and a systolic BP >150 mmHg were risk thresholds. In univariable analyses, baseline creatinine, proteinuria, systolic BP, glomerular sclerosis, interstitial fibrosis, and crescentic disease were predictors of the primary outcome. In multivariable models adjusted for clinical characteristics, interstitial fibrosis (hazard ratio [HR]2.7; 95% confidence interval [CI] 1.2 to 6.0), glomerular sclerosis (HR 2.6; 95% CI 1.2 to 4.5), and crescents (HR 2.4; 95% CI 1.2 to 5.1) remained independent predictors of the primary outcome and significantly improved model fit compared with clinical characteristics alone.Conclusions: Baseline histopathologic parameters are independent predictors of adverse outcomes in IgAN even after taking into consideration clinical characteristics. Relatively small degrees of interstitial fibrosis confer an increased risk for progressive IgAN.IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Patients with IgAN have a variable clinical course with between 6 and 43% progressing to ESRD over 10 yr (1–5). Given this variability, identifying reliable prognostic factors is important to help stratify clinical monitoring and treatment regimens.Previous studies have identified clinical features including high-grade proteinuria, reduced kidney function, and hypertension at the time of diagnosis as predictors of adverse outcomes (4–7). Studies have identified interstitial fibrosis and glomerular sclerosis as poor prognostic features (8–10). This is not surprising considering that these features are a common final result of damage from glomerulonephritis; however, histopathologic features frequently correlate with serum creatinine, and whether they add prognostic values beyond the measurement of serum creatinine is uncertain. Histopathologic features are commonly categorized on the basis of arbitrary thresholds to denote significant degrees of damage (3,5,11), a factor that may contribute to poor performance in multivariable models of risk prediction in IgAN and result in an underestimation of their ability independently to predict outcomes. We performed a retrospective study using detailed baseline clinical data and quantitative analysis of renal biopsies, including the degree of interstitial fibrosis and glomerulosclerosis, to assess the factors that determine adverse outcomes including chronic kidney disease (CKD) progression and death.     

Prospective study of transitional cell carcinoma in the prostatic urethra and prostate in the cystoprostatectomy specimen. Incidence, characteristics and preoperative detection

OBJECTIVES: To prospectively evaluate the incidence of transitional cell carcinoma (TCC) in the prostatic urethra and prostate in the cystoprostatectomy specimen, investigate characteristics of bladder tumours in relation to the risk of involvement of the prostatic urethra and prostate and examine the sensitivity of preoperative loop biopsies from the prostatic urethra. MATERIAL AND METHODS: Preoperatively, patients were investigated with cold cup biopsies from the bladder and transurethral loop biopsies from the bladder neck to the verumontanum. The prostate and bladder neck were submitted to sagittal whole-mount pathological analysis. RESULTS: The incidence of TCC in the prostatic urethra and prostate in the cystoprostatectomy specimen was 29% (50/175 patients). Age, previous bacillus Calmette-Guérin treatment, carcinoma in situ (Cis) in the cold cup mapping biopsies and tumour grade were not associated with the risk of TCC in the prostatic urethra/prostate. Cis, multifocal Cis (> or = 2 locations) and tumour location in the trigone were significantly more common in cystectomy specimens with TCC in the prostatic urethra and prostate: 21/50 (42%) vs 32/125 (26%), p=0.045; 20/50 (40%) vs 27/125 (22%), p=0.023; and 20/50 (40%) vs 26/125 (21%), p=0.01, respectively. Preoperative resectional biopsies from the prostatic urethra in the 154 patients analysed identified 31/47 (66%) of patients with TCC in the prostatic urethra/prostate, with a specificity of 89%. The detection of stromal-invasive and non-stromal involvement was similar: 66% and 65%, respectively. CONCLUSIONS: The incidence of TCC in the prostatic urethra and prostate was 29% (50/175) in the cystoprostatectomy specimen. Preoperative biopsies from the prostatic urethra identified 66% of patients with such tumour growth. Our findings suggest that preoperative cold cup mapping biopsies of the bladder for detection of Cis add little extra information with regard to the risk of TCC in the prostatic urethra and prostate.     

Evaluating the accuracy of functional biomarkers for detecting histological changes in chronic allograft nephropathy

The most common cause of late kidney transplant failure is chronic allograft nephropathy (CAN). Much research has focused on identifying biomarkers (or correlates) that would predict subsequent CAN and allow timely intervention. Functional biomarkers such as serum creatinine and estimated glomerular filtration rate (eGFR) have been widely adopted, even though they have not been rigorously evaluated as surrogate markers. This study evaluated serum creatinine and eGFR for predicting the early histopathological changes seen in transplant protocol biopsies (TPB). We prospectively followed 289 kidney transplant patients in the Southern Alberta Transplant Program who had TPB at 6-12 months post-transplant. Tissue samples (n = 280) were independently examined by renal pathologists. The ability of serum creatinine or eGFR to predict the threshold level for abnormal histopathology was evaluated by calculating the area under the receiver operator characteristic curve. Serum creatinine and eGFR had poor predictive value (most confidence intervals included 0.5, indicating no predictive ability) for ten individual histological measurements (Banff 97 scores), and the Chronic Allograft Damage Index. We conclude that serum creatinine and eGFR have a limited clinical role in predicting the early histopathological changes that precede CAN and should not be used for this purpose.     

Suggestibility and compliance among alleged false confessors and resisters in criminal trials

This paper describes a study which compares the interrogative suggestibility and compliance scores of 20 alleged false confessors and 20 subjects who had persistently denied their involvement in the crime they were charged with in spite of forensic evidence against them (labelled 'resisters'). The two groups were 'matched' for age, sex, intelligence, memory recall capacity, and the seriousness of the offence. It was hypothesized that the resisters would score significantly lower on tests of suggestibility and compliance than the alleged false confessors. The findings were confirmed at a high level of significance. A separate analysis of 14 resisters and 72 alleged false confessors, where IQ and memory were used as covariates rather than 'matching' the two groups on the relevant variables, gave almost identical results. The clinical implications of the findings are discussed.     

Illicit drug use among Icelandic prisoners prior to their imprisonment

This study investigates illicit drug use among new admissions to Icelandic prisons over a 21-month period. Of all new admissions, 344 (96%) agreed to participate in the study. They were asked questions about their previous use of illicit drugs and this was related to the nature of their current offence. Cannabis and amphetamines were the most commonly used illicit drugs, with 62% and 50% of the subjects admitting to having used these substances at some time in their life. The corresponding figures for having consumed these illicit drugs during the previous six months were 31% and 28%, respectively. Only 11 subjects (3%) reported having used opiates. Seventy-three subjects (23%) reported intravenous drug use. Women prisoners (43%) more commonly reported injecting drugs than men (21%) prisoners. Significant differences were found between offence categories, with persons convicted of drug and property offences most commonly having used illicit drugs. Copyright © 1996 Whurr Publishers Ltd.     

Results of Attempted Cardiopulmonary Resuscitation of Patients Dying Suddenly outside the Hospital in Reykjavik and the Surrounding Area, 1976–1979

ABSTRACT. Cardiopulmonary resuscitation (CPR) was attempted in 222 cases of sudden death at the City Hospital, Reykjavik, during 1976–79. Of the 68 patients (31%) successfully resuscitated, 47 died in the hospital and 21 (9%) were discharged, 17 in good mental and physical condition. The mean combined response and transport time was 12.1 min and the ambulance mean time of response 7.3 min. The first ECG revealed considerable prognostic indications. Of the 90 patients who had ventricular fibrillation on admission, 42 (47%) were successfully resuscitated and 18 (20%) were subsequently discharged. Among 114 patients with asystole, resuscitation was successful in 23 (20%) and two (2%) were discharged. Immediate first aid in situ had a definite prognostic influence. These results compare favourably with those obtained elsewhere where the organization of first aid and emergency transport is similar. They do not, however, match the results achieved by fully specialized resuscitation teams trained to operate outside the hospital. Results of CPR of patients with cardiac arrest out of hospital in Reykjavik show increasing improvement over the years. This may be partly explained by a considerable public debate on this issue in 1978 and subsequent streamlining of activities.