Bioengineered kidneys: new sights on a distant horizon

The need for renal replacement therapy is currently rising at an annually increasing rate. Current treatment options for patients with end-stage kidney disease include dialysis or organ transplantation. Yet, even though transplant survival has increased due to refined immunosuppressive therapy, morbidity remains high because of organ shortage. Here we discuss a recent publication that describes the transplantation of a bioengineered biocompatible kidney from a decellularized organ scaffold, thus possibly providing a solution to both transplant organ shortage and morbidity associated with long-term immunosuppression.     

Levator ani defect scores and pelvic organ prolapse: is there a threshold effect?

Introduction and hypothesis

The goal of this study was to use a well-described system of quantifying levator ani defect (LAD) severity using magnetic resonance imaging (MRI) to examine the relationship between defect severity and the presence or absence of prolapse.

Methods

This is a secondary analysis of two case–control studies comparing 284 cases (with prolapse) to 219 controls (normal support) defined by using Pelvic Organ Prolapse Quantification (POP-Q) exams. LAD were assessed on MRI, with scores from 0 (no defects) to 6 (complete, bilateral defects). The number of cases and controls at each score were compared. Logistic regression and receiver operating characteristic (ROC) analyses were used to quantify relationships between LAD and prolapse.

Results

The proportion of cases exceeds the overall prolapse rate in this study at LAD scores ≥3, with higher rates of prolapse at higher LAD scores (p?p?Conclusions There are three clusters of prolapse risk: low (0–2), moderate (3–5), and high (6). Although LAD have a dose-response-like effect for prolapse, other factors are clearly involved.     

Severe hypoglycemia incidence and predisposing factors in 85 pregnancies of type I diabetic women.

OBJECTIVE--To evaluate the incidence and predisposing factors of severe hypoglycemia (SH) in pregnant women with insulin-dependent (type I) diabetes mellitus. RESEARCH DESIGN AND METHODS--SH (impairment of consciousness due to hypoglycemia subsequently treated with glucagon or i.v. glucose) was recorded in all pregnant type I diabetic women (n = 77) who attended our pregnancy clinic during 85 pregnancies from 1986 to 1990. RESULTS--Ninety-four SHs were reported during 35 pregnancies. Of 94 SHs, 84% occurred before the 20th gestational wk (median 12th wk) and 77% during sleep. In the group with SH, there was no permanent maternal sequelae, and there was a favorable fetal outcome (no perinatal death and no congenital malformation). Mean HbA1c values were not different between the group with and without SH for the first half (6.4 +/- 1.1 vs. 6.3 +/- 0.9%) and 2nd half (5.4 +/- 0.6 vs. 5.5 +/- 0.7%) of pregnancy. The percentage of women with SH before pregnancy (51 vs. 28%, P less than 0.05) and the incidence of SH patients before pregnancy (0.49 vs. 0.08 SH/patient/yr) was different between the group with and without SH. CONCLUSIONS--SH is frequent during pregnancies of type I diabetic women with near normoglycemia. The risk for SH is particularly pronounced during the first half of pregnancy and in women with a history of SH.     

Effectiveness of antihyperlipidemic drug management in clinical practice

Although randomized clinical trials have convincingly shown the efficacy of antihyperlipidemic drugs, both discontinuation of antihyperlipidemic drugs and failure to achieve goal lipid levels would be expected to attenuate the effect of these drugs on reducing the rates of hospitalization for coronary events. This study compares the rates of hospitalization and low-density lipoprotein cholesterol (LDL-C) levels during and after discontinuation of antihyperlipidemic drug therapy. A retrospective cohort study was conducted among 2369 patients at 2 health maintenance organizations (HMOs) during the period 1988 to 1994. Rates of coronary heart disease (CHD)-related hospitalization and non-CHD-related hospitalization and the LDL-C levels between 14 and 180 days after the initiation or discontinuation of drug therapy were compared for periods of antihyperlipidemic drug use and nonuse. The rate ratio for CHD hospitalization during periods of antihyperlipidemic drug use compared with periods of nonuse was 1.02 (95% CI, 0.74 to 1.40), excluding the first 6 months after initiation or discontinuation and controlling for patient sex, age, history of CHD, hypertension, diabetes, and HMO site. By contrast, the adjusted rate ratio was 0.70 (95% CI, 0.61 to 0.80) for non-CHD hospitalization. The percentage of patients with a history of CHD who achieved LDL-C levels <130 mg/dL was 27% < or =6 months after initiation of antihyperlipidemic drug therapy compared with 18% during gaps in drug therapy (P = 0.04). This study failed to demonstrate the effectiveness of lipid-lowering therapy in reducing CHD hospitalizations in community settings, apparently because most recipients either discontinued therapy or failed to achieve the desired LDL-C reduction while receiving therapy. These results indicate the need for interventions to improve patient compliance and management of lipid disorders.     

Determination of molecules regulating gene delivery using adenoviral vectors in ovarian carcinomas

Gene therapeutic approaches currently favor adenoviral vectors over alternatively available vector systems. Ovarian cancer represents an attractive model for an intraperitoneal adenovirus-based gene therapy, which is now under intensive clinical investigation. Adenovirus-mediated gene transfer depends on adequate virus uptake and thus on the presence of sufficient amounts of high-affinity coxsackie-adenovirus receptor (CAR) and alphavbeta3- and alphavbeta5 integrins on target cells. This fact has been ignored in most ongoing clinical trials. This investigation, therefore, determined expression of CAR by immunohistochemistry in 37 ovarian carcinomas and compared it with that of alphavbeta3 and alphavbeta5 integrins. In all samples, except one undifferentiated carcinoma, CAR was immunohistochemically demonstrable. Grade 1 tumors exhibited stronger CAR immunostaining as compared with higher-grade cancers (P < 0.03). Integrins alphavbeta3 and alphavbeta5 were detectable in 62% and 65% of carcinomas, respectively, and staining for both classes correlated positively (P < 0.005). Cancers classified as undifferentiated completely lacked alphavbeta3 expression. Furthermore, in undifferentiated and grade 3 carcinomas the three molecules studied exhibited marked distributional heterogeneity with regard to focal positivity and negativity within the same tumor. Either the absence of CAR, alphavbeta3 and alphavbeta5 or the pronounced heterogeneity in their expression might seriously compromise the efficiency of adenovirus-based gene therapy in ovarian cancer.     

The Influence of Screening on Outcomes of Clinically Locally Advanced Rectal Cancer

Background

Screening for colorectal cancer has resulted in declining incidence rates of both colon and rectal cancer and it may influence stage at presentation and improve survival. The aim of this study was to assess the impact of screening on patients diagnosed with locally advanced rectal cancer.

Methods

A retrospective analysis of a consecutive series of patients who underwent neoadjuvant therapy and had an R0-resection for clinical AJCC stage II or stage III disease. All patients received surgery at a single center between 2004 and 2015. Patients diagnosed through screening were compared to patients diagnosed through symptomatic presentation.

Results

Three hundred nine patients were included, of whom 43 (13.9%) were diagnosed through screening. Screened patients had more often a white ethnicity, while there were no other differences in baseline characteristics or median household income. Screened patients had a lower rate of disease recurrence in addition to a longer disease free survival and overall survival.

Conclusions

Patients with locally advanced rectal cancer diagnosed through screening demonstrated more favorable short and long-term outcomes than patients diagnosed through symptoms. Findings of this study reinforce the need for screening programs in addition to the need for research regarding optimization of screening adherence.