Abstract Background Image-based renal morphometry scoring systems are used to predict the potential difficulty of partial nephrectomy (PN), but they are centered entirely on tumor-specific factors ...and neglect other patient-specific factors that may complicate the technical aspects of PN. Adherent perinephric fat (APF) is one such factor known to make PN difficult. Objective To develop an accurate image-based nephrometry scoring system to predict the presence of APF encountered during robot-assisted partial nephrectomy (RAPN). Design, setting, and participants We prospectively analyzed 100 consecutive RAPNs performed by one surgeon and defined APF as the need for subcapsular renal dissection to isolate the renal tumor for RAPN. Outcome measurements and statistical analysis The scoring algorithm to predict the presence of APF was developed with a multivariable logistic regression model using a forward selection approach with a focus on improvement in the area under the receiver operating characteristic curve. Results and limitations Thirty patients (30%; 95% confidence interval, 21–40) had APF. Single-variable analysis noted an increased likelihood of APF in male patients ( p < 0.001), higher body mass index ( p = 0.003), greater posterior perinephric fat thickness ( p < 0.001), greater lateral perinephric fat thickness ( p < 0.001), and those with perirenal fat stranding ( p < 0.001). Two of these variables, posterior perinephric fat thickness and stranding, were most highly predictive of APF in multivariable analysis and were therefore used to create a risk score, termed Mayo Adhesive Probability (MAP) and ranging from 0 to 5, to predict the presence of APF. We observed APF in 6% of patients with a MAP score of 0, 16% with a score of 1, 31% with a score of 2, 73% with a score of 3–4, and 100% of patients with a score of 5. Conclusions MAP score accurately predicts the presence of APF in patients undergoing RAPN. Prospective validation of the MAP score is required. Patient summary The Mayo Adhesive Probability score that we we developed is an accurate system that predicts whether or not adherent perinephric, or “sticky,” fat is present around the kidney that would make partial nephrectomy difficult.
Mosaic aneuploidy and uniparental disomy (UPD) arise from mitotic or meiotic events. There are differences between these mechanisms in terms of (i) impact on embryonic development; (ii) co-occurrence ...of mosaic trisomy and UPD and (iii) potential recurrence risks. We used a genome-wide single nucleotide polymorphism (SNP) array to study patients with chromosome aneuploidy mosaicism, UPD and one individual with XX/XY chimerism to gain insight into the developmental mechanism and timing of these events. Sixteen cases of mosaic aneuploidy originated mitotically, and these included four rare trisomies and all of the monosomies, consistent with the influence of selective factors. Five trisomies arose meiotically, and three of the five had UPD in the disomic cells, confirming increased risk for UPD in the case of meiotic non-disjunction. Evidence for the meiotic origin of aneuploidy and UPD was seen in the patterns of recombination visible during analysis with 1–3 crossovers per chromosome. The mechanisms of formation of the UPD included trisomy rescue, with and without concomitant trisomy, monosomy rescue, and mitotic formation of a mosaic segmental UPD. UPD was also identified in an XX/XY chimeric individual, with one cell line having complete maternal UPD consistent with a parthenogenetic origin. Utilization of SNP arrays allows simultaneous evaluation of genomic alterations and insights into aneuploidy and UPD mechanisms. Differentiation of mitotic and meiotic origins for aneuploidy and UPD supports existence of selective factors against full trisomy of some chromosomes in the early embryo and provides data for estimation of recurrence and disease mechanisms.
Additive manufacturing (3D printing) is a technology with near-unlimited potential for the chemical educator. However, its adoption into higher education has been limited by the dual requirements of ...expertise in 3D printing and 3D computer-aided design (CAD). Thus, its reported utilization in the chemistry curriculum has been within the creation of 3D models for the macroscopic visualization of molecular models and processes. With the commercialization of inexpensive 3D printers, we seek to provide a series of optical mounts and tools for use in chemical research or education by designing systems which may be mounted on a breadboard and used to construct chemical instrumentation. These designs include mounts for cylindrical lenses or mirrors with 0.5, 1, and 2 in. diameters, 0.5 in. diffraction gratings, an adjustable optical slit, cuvette holders, stepper motor (NEMA 17) adapters, and a modular, 3D printed breadboard. All designs were created using Solidworks CAD, and have been provided in Supporting Information and uploaded to https://github.com/EdavisAPU/Education-Optics in both Solidworks native format (*.SLDPRT) and a standard file exchange format for 3D objects (*.STL) format for use, modification, or collaboration. All files are released under the MIT Open-Source license (modified for Design). In comparison with commercially available products, the prototypes presented herein provide significant cost-savings, with many designs 1–2 orders of magnitude cheaper than commercial equivalents. In addition, these designs have been utilized in an upper division instrumental analysis course as students designed and constructed a visible spectrophotometer using these optical devices. Data from the resultant instrument is presented and compared with a commercially available spectrophotometer.
Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers ...of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.
In humans, touching the skin is known to activate, among others, the contralateral primary somatosensory cortex on the postcentral gyrus together with the bilateral parietal operculum (i.e. the ...anatomical site of the secondary somatosensory cortex). But which brain regions beyond the postcentral gyrus specifically contribute to the perception of touch remains speculative. In this study we collected structural magnetic resonance imaging scans and neurological examination reports of patients with brain injuries or stroke in the left or right hemisphere, but not in the postcentral gyrus as the entry site of cortical somatosensory processing. Using voxel-based lesion-symptom mapping, we compared patients with impaired touch perception (i.e. hypoaesthesia) to patients without such touch impairments. Patients with hypoaesthesia as compared to control patients differed in one single brain cluster comprising the contralateral parietal operculum together with the anterior and posterior insular cortex, the putamen, as well as subcortical white matter connections reaching ventrally towards prefrontal structures. This finding confirms previous speculations on the 'ventral pathway of somatosensory perception' and causally links these brain structures to the perception of touch.
Immune checkpoint inhibitors (ICI) are revolutionizing care for cancer patients. The list of malignancies for which the Food and Drug Administration is granting approval is rapidly increasing. ...Furthermore, there is a concomitant increase in clinical trials incorporating ICI. However, the safety of ICI in patients undergoing surgery remains unclear. Herein, we assessed the safety of ICI in the perioperative setting at a single center. We conducted a retrospective review of patients who underwent planned surgery while receiving ICI in the perioperative setting from 2012 to 2016. We collected 30-day postoperative morbidity and mortality utilizing the Clavien-Dindo classification system. We identified 17 patients who received perioperative ICI in 22 operations. Patients were diagnosed with melanoma (
= 14), renal cell carcinoma (
= 2), and urothelial carcinoma (
= 1). Therapies included pembrolizumab (
= 10), ipilimumab (
= 5), atezolizumab (
= 5), and ipilimumab/nivolumab (
= 2). Procedures included cutaneous/subcutaneous resection (
= 6), lymph node resection (
= 5), small bowel resection (
= 5), abdominal wall resection (
= 3), other abdominal surgery (
= 3), orthopedic surgery (
= 1), hepatic resection (
= 1), and neurosurgery (
= 2). There were no Grade III-IV Clavien-Dindo complications. There was one death secondary to ventricular fibrillation in the setting of coronary artery disease. ICI appear safe in the perioperative setting, involving multiple different types of surgery, and likely do not need to be stopped in the perioperative setting. Further studies are warranted to confirm these findings.
Objective
To validate a new baseline estimated glomerular filtration rate (NB‐GFR) formula in a cohort of robotic‐assisted partial nephrectomies (RAPN).
Methods
NB‐GFR = 35 + preoperative GFR (× ...0.65) – 18 (if radical nephrectomy) – age (× 0.25) + 3 (if tumor size >7 cm) – 2 (if diabetes). NB‐GFR was calculated in 464 consecutive RAPN from a single surgeon cohort. 143 patients were excluded secondary to insufficient eGFR follow up. We analyzed NB‐GFR accuracy utilizing the last observed eGFR 3–12 months post RAPN. Categorical variables were summarized with the frequency and percentage of patients. Numerical variables were summarized with the median, 25th percentile, and 75th percentile.
Results
The mean difference between observed and predicted NB‐GFR was 4.6 ml/min/1.73m2 (95% CI −6.9 to 16.1 ml/min/1.73m2). There was a pattern of higher observed NB‐GFRs being underestimated by the NB‐GFR equation while lower observed NB‐GFRs were overestimated by the NB‐GFR equation. The NB‐GFR formula had a high level of accuracy with 98.8% of predicted NB‐GFRs falling within 30% of the observed NB‐GFR (95% CI 86.8% to 99.5%). The median and interquartile range of the difference between observed and predicted NB‐GFR was 3.9 ml/min/1.73m2 (IQR 0.7 to 8.2 ml/min/1.73m2). The sensitivity, specificity, positive predictive value, and negative predictive value for the ability of predicted NB‐GFR to identify those with an observed NB‐GFR <60 ml/min/1.73m2 after RAPN was 98%, 92%, 88%, and 99%, respectively.
Conclusion
The NB‐GFR equation developed with partial and radical nephrectomy cohorts is accurate in predicting post‐operative eGFR 3–12 months following RAPN.
Alcohol consumption has been associated inversely with renal cell carcinoma (RCC) risk; however, no study has examined effect modification by germline variation in alcohol‐metabolizing genes. We ...investigated whether the association between alcohol intake and RCC risk is modulated by germline variants in alcohol dehydrogenase genes in a large case–control study. Data from 652 RCC cases and 1,366 non‐cancer controls were analyzed. Alcohol intake was assessed using a standardized risk factor questionnaire. Three previously genotyped polymorphisms in ADH6 and ADH7 with the TaqMan assay were examined. Odds ratios (ORs) and 95% confidence interval (CI) were calculated using logistic regression, adjusting for covariates. Compared to non‐drinkers, ever consumption of alcohol was associated with lower RCC risk (OR = 0.52, 95% CI = 0.42–0.65). Analysis with cubic spline regression curve showed a “J‐shaped” relationship between alcohol drinks/day and RCC risk, such that there was no added benefit against RCC for consumption of more than two drinks/day. We observed effect modification by variation in rs1154454 (ADH7) (pinteraction = 0.007); a per unit increase in alcohol drink/day was associated with 35% lower RCC risk among non‐minor allele carriers, a 27% lower risk among those who carry one copy of the minor allele, but no association was observed among those with two copies of the minor allele. These findings indicate that alcohol consumption is associated with lower RCC risk. Consuming more than two drinks a day does not confer additional protection against RCC. The association between alcohol intake and RCC risk appears to be modulated by inter‐individual germline variation in alcohol‐metabolizing genes.
What's new?
Drinking alcohol can reduce kidney cancer risk, but is that true for everyone? These authors looked at alcohol consumption, renal cell carcinoma risk and variants in alcohol metabolizing genes ADH6 and ADH7. They pinpointed a variant of the ADH7 gene that might activate alcohol's benefits: people with two copies of the common allele could reduce their RCC risk with alcohol consumption; those with one copy experienced a smaller benefit. For those lacking the allele, drinking alcohol did not lower RCC risk. The authors also showed that alcohol's protection comes in moderation. Up to two drinks daily lowered RCC risk; beyond that, they saw no additional benefit.
Objective
To validate the Martini nomogram predicting the decline in estimated glomerular filtration rate after robotic‐assisted partial nephrectomy.
Methods
Estimated glomerular filtration rate of ...406 patients from a single surgeon series was calculated before robotic‐assisted partial nephrectomy and at postoperative intervals. To determine the risk group, we calculated the total score and corresponding risk of significant estimated glomerular filtration rate reduction at 15 months using the Martini nomogram. The primary outcome was a reduction in estimated glomerular filtration rate of ≥25% from preoperative levels between 1 and 12 months after surgery.
Results
The median length of follow up for this study was 12 months (interquartile range 6–12 months). Overall, 134 (33%) patients were in the low‐, 143 (35%) in the intermediate‐, 119 (29%) in the high‐ and 10 (2%) in the very high‐risk groups. The Kaplan–Meier estimates for the probability of significant estimated glomerular filtration rate reduction by 12 months after robotic‐assisted partial nephrectomy was 12.9% in the low‐risk group, 24.0% in the intermediate‐risk group, 49.7% in the high‐risk group and 40.0% in the very high‐risk group. Harrell’s C‐index for discriminating between those with and without a significant reduction in estimated glomerular filtration rate 1–12 months after robotic‐assisted partial nephrectomy was 0.73 (95% confidence interval 0.68–0.78).
Conclusions
The risk groups proposed by the Martini nomogram are accurate in predicting those at higher risk for a >25% decline in postoperative estimated glomerular filtration rate after robotic‐assisted partial nephrectomy at 12 months.
Urolithiasis is a common disease with a reported prevalence between 4% and 20% in developed countries. Determination of urinary calculi composition is a key factor in preoperative evaluation, ...treatment, and stone recurrence prevention. Prior to the introduction of dual-energy computed tomography (DECT), available methods for determining urinary stone composition were only available after stone extraction, and thereby unable to aid in optimized stone management prior to intervention. DECT utilizes the attenuation difference produced by two different x-ray energy spectra to quantify urinary calculi composition as uric acid or non-uric acid (with likely further classification in the future) while still providing the information attained with a conventional CT. Knowledge of DECT imaging pitfalls and stone mimics is important, as the added benefit of dual-energy analysis is the determination of stone composition, which in turn affects all aspects of stone management. This review briefly describes DECT principles, scanner types and acquisition protocols for the evaluation of urinary calculi as they relate to imaging pitfalls (inconsistent characterization of small stones, small dual-energy field of view, and mischaracterization from surrounding material) and stone mimics (drainage devices) that may adversely impact clinical decisions. We utilize our clinical experience from scanning over 1200 patients with this new imaging technique to present clinically relevant examples of imaging pitfalls and possible mechanisms for resolution.
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