Altitude as a risk factor for the development of hypospadias. Geographical cluster distribution analysis in South America

Q2307.e1-307.e5Objective Hypospadias is the most common congenital anomaly affecting the genitals. It has been established as a multifactorial disease with increasing prevalence. Many risk factors have been identified such as prematurity, birth weight, mother's age, and exposure to endocrine disruptors. In recent decades multiple authors using surveillance systems have described an increase in prevalence of hypospadias, but most of the published literature comes from developed countries in Europe and North America and few of the published studies have involved cluster analysis. Few large-scale studies have been performed addressing the effect of altitude and other geographical aspects on the development of hypospadias. Acknowledging this limitation, we present novel results of a multinational spatial scan statistical analysis over a 30-year period in South America and an altitude analysis of hypospadias distribution on a continent level. Method A retrospective review was performed of the Latin American collaborative study of congenital malformations (ECLAMC). A total of 4,020,384 newborns was surveyed between 1982 and December 2011 in all participating centers. We selected all patients with hypospadias. All degrees of clinical severity were included in the analysis. Each participating center was geographically identified with its coordinates and altitude above sea level. A spatial scan statistical analysis was performed using Kulldorf's methodology and a prevalence trend analysis over time in centers below and above 2000 m. Results During the study period we found 159 hospitals in six different countries (Colombia, Bolivia, Brazil, Argentina, Chile, and Uruguay) with 4,537 cases of hypospadias and a global prevalence rate of 11.3/10,000 newborns. Trend analysis showed that centers below 2000 m had an increasing trend with an average of 10/10,000 newborns as opposed to those centers above 2000 m that showed a reducing trend with an average prevalence of 7.8 (p = 0.1246). We identified clusters with significant increases of prevalence in five centers along the coast at an average altitude of 219.8 m above sea level (p > 0.0000). Reduction in prevalence was found in clusters located in two centers on the Andes mountains. Altitude of 2,000 m was associated with hypospadias (Figure), with an OR 0.59 (0.5–0.69). There are ethnic arguments to support our results supported by protective polymorphism distribution in high lands. Conclusion Altitude above 2,000 m is suggested to have a protective effect for hypospadias. Specific clusters have been identified with increased risk for hypospadias. Environmental risk factors in these areas need to be further studied given the association seen between altitude and the distribution of more severe cases

Prevalence, Risk Factors, and Clinical Relevance of Fluoroquinolone-Resistant Organisms in Rectal Cultures: Should We Target Antibiotic Prophylaxis Prior to Prostate Biopsy?

The rise of infectious complications after prostate biopsy has been linked to the growing resistance of enterobacteria to fluoroquinolone (FQ) antibiotics. In this review, we investigated the potential benefit of targeted antibiotic prophylaxis based on rectal cultures prior to prostate biopsy. An electronic search for all related literature published in English was performed from April until June 2015 using the MEDLINE and EMBASE databases. Data were obtained regarding the true prevalence of FQresistant bacteria in the rectum of patients, the identification of those patients at risk of harbouring FQ-resistant bacteria, the risk of infectious complications after transrectal prostate biopsy in patients with FQ-resistant bacteria, and the effect of targeted prophylaxis. Although there is limited evidence that a targeted approach might be beneficial, we conclude that current studies on the use of rectal cultures in the prebiopsy setting have too many limitations and confounding variables to definitely accept this approach in clinical practice. Whether this methodology is useful in a certain region will greatly depend on local fluoroquinolone-resistance rates

Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts

The increased usage of marginal grafts has triggered interest in perfused kidney preservation to minimize graft injury. We used a donation after circulatory death (DCD) porcine kidney autotransplantation model to compare 3 of the most frequently used ex vivo kidney perfusion techniques: nonoxygenated hypothermic machine perfusion (non-oxHMP), oxygenated hypothermic machine perfusion (oxHMP), and normothermic ex vivo kidney perfusion (NEVKP). Methods: Following 30 min of warm ischemia, grafts were retrieved and preserved with either 16 h of non-oxHMP, oxHMP, or NEVKP (n = 5 per group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed for 8 d. Kidney function and injury markers were compared between groups. Results: NEVKP demonstrated a significant reduction in preservation injury compared with either cold preservation method. Grafts preserved by NEVKP showed superior function with lower peak serum creatinine (NEVKP versus non-oxHMP versus oxHMP: 3.66 ± 1.33 mg/dL, 8.82 ± 3.17 mg/dL, and 9.02 ± 5.5 mg/dL) and more rapid recovery. The NEVKP group demonstrated significantly increased creatinine clearance on postoperative day 3 compared with the cold perfused groups. Tubular injury scores on postoperative day 8 were similar in all groups. Conclusions: Addition of oxygen during HMP did not reduce preservation injury of DCD kidney grafts. Grafts preserved with prolonged NEVKP demonstrated superior initial graft function compared with grafts preserved with non-oxHMP or oxHMP in a model of pig DCD kidney transplantation

Laminin expression in colorectal carcinomas varying in degree of differentiation

We are studying the ability of colorectal carcinomas, which vary in degree of differentiation, to assemble a basement membrane and the relationship between differences in this ability and perturbations in laminin expression. For these studies, we are using human colorectal carcinoma cells grown both in vitro and in nude mice as well as tumors obtained at surgery. Immunoperoxidase staining of human tumors indicates that laminin is present in a defined basement membrane in moderately to well-differentiated tumors. This staining pattern is absent in poorly differentiated tumors. In these tumors, staining is discontinuous and sometimes observed intracellularly. The laminin synthesized by in vitro cells was immunoprecipitated and analyzed by acrylamide electrophoresis. Neither poorly nor well-differentiated carcinoma cells exhibit marked differences in the rate of synthesis of laminin. Differences are present in the rate at which newly synthesized laminin is secreted. These differences may result from alterations in posttranslational processing. Such alterations may contribute, along with other factors, to the inability of poorly differentiated tumors to make a basement membrane

Heterotopic Renal Autotransplantation in a Porcine Model : A Step-by-Step Protocol

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication

Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction

Intrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm-derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2(+) cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm-derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction

Utilization of postpenile surgery illustrated healing atlas : a comparative study

Q3Q1151-154Objective: To determine the effect of the postpenile surgery illustrated healing atlas on caregivers' anxiety levels pre- and postoperatively, the frequency of family's postoperative communication with the urology care team, and the number of unplanned emergency room (ER) return for wound checks. Methods: A prospective cohort enrolled children who underwent penile surgeries (distal hypospadias repair and phalloplasty) with no concomitant procedures from December 2016 to June 2017. A 6-item short-form Spielberger State-Trait Anxiety Inventory (STAI) was used to determine baseline and postoperative anxiety levels of the caregivers. Two groups were created: caregivers who did not view the illustrated atlas vs caregivers who were shown the atlas. Baseline characteristics and demographics were compared, along with caregiver's pre- to postoperative anxiety level difference, frequency of postoperative communication, and number of unplanned ER return for wound checks. Results: Fifty-four patients were enrolled with 27 families in each group. Baseline characteristics and demographics were comparable with no significant differences. The assessment of the pre- to postoperative anxiety levels in both groups showed no significant differences (median difference -5 [interquartile range -8 to -5] vs -5 [interquartile range -8 to -4], P = .94). Although no differences were noted for ER-return rates between the groups (18% vs 11.1%, P = .704), significantly less postoperative calls and e-mails were noted among families who received or viewed the postpenile surgery illustrated healing atlas (51.9% vs 11.1%, P = .003). Conclusion: The utilization of a postpenile surgery illustrated healing atlas as part of the postoperative support provided to families was able to decrease postoperative calls and e-mails