Citations

Objective: We evaluated whether single-layer renorrhaphy (SLR) without collecting system (CS) closure is sufficient following robot-assisted partial nephrectomy (RAPN). Patients and Methods: One hundred fifty consecutive patients underwent RAPN by a single surgeon and were prospectively labeled with regard to CS entry during surgery. Patients with CS entry were subdivided into two groups: those with classical renorrhaphy (CR) (i.e., two-layer repair) and those with SLR (i.e., without CS repair). Perioperative variables and outcomes were compared between CR and SLR groups. Results: Ninety patients had CS entry during RAPN. Of these 90 patients, 64 had CR, and 26 had SLR, with mean ages of 62 and 59 years ( p = 0.22), tumor sizes of 3.4 and 3.3 cm ( p = 0.61), Mayo Adhesive Probability scores of 1.8 and 1.8 ( p = 0.95), and radius, exophytic/endophytic, nearness to CS, and laterality scores of 8.5 and 8.0 ( p = 0.16), respectively. Mean warm ischemia times (WITs) were 19.6 and 17.3 minutes ( p = 0.04), hospital stays of 3.0 and 2.8 days ( p = 0.62), and drain times of 2.9 and 2.7 days ( p = 0.65), for the CR and SLR groups, respectively. Using the Clavien-Dindo classification, there were a total of six grade III or higher complications, with no difference between the CR and SLR subgroups ( p = 1.0). Renal function using creatinine or glomerular filtration rate as surrogates showed no difference between groups preoperatively or up until 2 years postoperatively. Conclusions: Omitting CS repair during RAPN with SLR decreases WIT without altering complications, hospital stay, or drain time. Long-term renal function was not associated with CS repair.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Objective: The current gold standard treatment for peripheral nerve gaps remains the use of nerve autografts. Decellularized nerve allografts provide a potential ideal alternative, avoiding important disadvantages of the autograft such as donor site morbidity and the limited supply without the need for immunosuppressive therapy. In the ideal decellularized nerve allograft, all cellular debris is removed while maintaining the nerves’ ultrastructure. For the optimization of processing techniques for nerve allografts, it is essential to compare the effect of different processing techniques on a histological level. Although several studies describe some form of (subjective) histological scoring system, evaluation techniques are not uniform and nothing has been validated yet. A validated method that is simple and could easily be adopted by other groups would allow for a more standardized comparison of nerve decellularization techniques. Therefore, the aim of this study was to describe and validate an easy, fast, and inexpensive method to compare different nerve decellularization strategies on a histological level. Materials and Methods: Fifty rat sciatic nerve and 70 human nerve segments (35 sensory and 35 motor) were used for this study. Nerve segments were processed using 5 different processing techniques and compared with unprocessed nerve segments (control). Three different stainings were used to visualize general morphology and different components of the nerve tissue. Toluidine blue was used for visualization of myelin sheaths, hematoxylin-eosin (H&E) for general morphology, and laminin y-l for visualization of the basal lamina. All slides were scored by 4 independent observers who were blinded for the different processing techniques used. Each slide was given a score from 1 to 5 where 5 resembles a “perfect” structure similar to the native nerve and 1 resembles severe structural damage or absence of the component. To validate this scoring system, the agreement between the observers was calculated using the intraclass correlation coefficient (ICC). Results: The 4 different observers similarly scored the processed nerve segments. Significant differences between the processing groups could be identified. We found a good correlation between the different observers for the Toluidine Blue (ICC = .73, 95% confidence interval [CI], 0.66-0.79), H&E (ICC = .72, 95% CI, 0.64-0.78), and Laminin staining (ICC = .74, 95% CI, 0.67-0.80). Conclusion: This study demonstrates the validity of the scoring system to evaluate nerve tissue after different processing protocols. A good correlation was found for the scoring of the structural integrity (Toluidine Blue, H&E, and Laminin). This method is suitable to compare different processing techniques in vitro on the route to engineering the ideal nerve allograft. Use of this method by other groups will make it possible to compare results of different nerve processing studies. Using valid outcome measurements is essential when striving to create new innovative options for nerve reconstruction.

Objective/Hypothesis: Processed nerve allografts provide a promising alternative to nerve autografts with the advantages of a readily available unlimited supply, no donor site morbidity, and without the need for immunosuppression. The nerve allografts currently available for clinical use do not provide satisfactory results. The processing technique was optimized to reduce the allografts immunogenicity and cellular debris while maintaining the ultrastructural properties. The aim of this study was to evaluate the functional recovery after reconstruction of a long nerve gap using the optimized nerve allograft in a rabbit model. To study the influence of storage techniques on functional recovery, processed nerve allografts were either cold or frozen stored. The nerve allografts were challenged to the gold standard, the nerve autograft. Materials and Methods: Nerve allografts were decellularized using our optimized protocol and stored at either 4°C or −80°C. In 36 New Zealand White rabbits, a 3-cm peroneal nerve gap was repaired with either a cold or frozen stored processed nerve allograft or a nerve autograft (control). Nerve recovery was longitudinally evaluated with ultrasound measurements performed prior to surgery and at 10, 16, and 24 weeks follow-up. Functional motor recovery was determined 24 weeks postoperatively using electrophysiology (compound muscle action potentials [CMAP]), isometric tetanic force (ITF), wet muscle weight (MW), and histomorphometry. Results: The longitudinal ultrasound measurements showed that the cold stored nerve allograft provides faster and earlier regeneration than the frozen stored nerve allograft. At 24 weeks, the cold stored allograft showed equal results compared with the autograft based on ultrasound measurements. Ultrasound furthermore showed significantly impaired recovery in the frozen stored allograft group compared with both the cold stored allograft and autograft ( P < .05). The functional outcome measurements, MV and ITF, both showed that the cold stored allograft proved to have a similar result compared with the autograft ( P > .05 for both MW and ITF, respectively). The frozen stored allograft, however, had a significantly inferior result to the autograft ( P < .05 for both MW and ITF). The CMAP and histomorphometry results showed no significant differences between all 3 groups. Conclusions: Nerve reconstruction with the cold stored optimized nerve allograft results in successful recovery of a long motor nerve defect in a rabbit model, statistically equivalent to the gold standard nerve autograft. Freeze storage of the processed allograft impairs the functional outcome.

Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.