Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65–97) vs. 65 (51–75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.     

Hypercalcemia After Cosmetic Oil Injections: Unraveling Etiology,Pathogenesis, and Severity

Intramuscular injections of paraffin oil can cause foreign body granuloma formation and hypercalcemia. Macrophages with the ability to produce high levels of 1,25(OH)₂D₃ may induce the mineral disturbance, but no major series of patients have been published to date. Here, medical history, physical evaluation, biochemical, and urinary analysis for calcium homeostasis were obtained from 88 males, who 6 years previously had injected paraffin or synthol oil into skeletal muscle. Moreover, granuloma tissue from three men was cultured for 48 hours ex vivo to determine 1,25(OH)₂D₃ production supported by qPCR and immunohistochemistry of vitamin D metabolism and immune cell populations after treatment with 14 different drugs. The 88 men were stratified into men with hypercalcemia (34%), whereas normocalcemic men were separated into men with either normal (42%) or suppressed parathyroid hormone (PTH) (24%). All men had high calcium excretion, and nephrolithiasis was found in 48% of hypercalcemic men, 22% of normocalcemic men with normal PTH, and 47% of normocalcemic men with suppressed PTH. Risk factors for developing hypercalcemia were oil volume injected, injection of heated oil, high serum interleukin-2 receptor levels, and high urine calcium. High 1,25(OH)₂D₃/25OHD ratio, calcium excretion, and low PTH was associated with nephrolithiasis. The vitamin D activating enzyme CYP27B1 was markedly expressed in granuloma tissue, and 1,25(OH)₂D₃ was released in concentrations corresponding to 40% to 50% of the production by human kidney specimens. Dexamethasone, ketoconazole, and ciclosporin significantly suppressed granulomatous production of 1,25(OH)₂D₃. In conclusion, this study shows that injection of large oil volumes alters calcium homeostasis and increases the risk of nephrolithiasis. Hypercalciuria is an early sign of disease, and high granulomatous 1,25(OH)₂D₃ production is part of the cause. Prospective clinical trials are needed to determine if ciclosporin, ketoconazole, or other drugs can be used as prednisolone-sparing treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).     

In Vitro Impact of Pro-Senescent Endothelial Microvesicles on Isolated Pancreatic Rat Islets Function

BackgroundIschemia-driven islet isolation procedure is one of the limiting causes of pancreatic islet transplantation. Ischemia-reperfusion process is associated with endothelium dysfunction and the release of pro-senescent microvesicles. We investigated whether pro-senescent endothelial microvesicles prompt islet senescence and dysfunction in vitro.Material and methodsPancreatic islets were isolated from male young rats. Replicative endothelial senescence was induced by serial passaging of primary porcine coronary artery endothelial cells, and microvesicles were isolated either from young passage 1 (P1) or senescent passage 3 (P3) endothelial cells. Islet viability was assessed by fluorescence microscopy, apoptosis by flow cytometry, and Western blot. Function was assessed by insulin secretion and islet senescence markers p53, p21, and p16 by Western blot. Microvesicles were stained by the PKH26 lipid fluorescent probe and their islet integration assessed by microscopy and flow cytometry.ResultsRegardless of the passage, half microvesicles were integrated in target islets after 24 hours incubation. Insulin secretion significantly decreased after treatment by senescent microvesicles (P3: 1.7 ± 0.2 vs untreated islet: 2.7 ± 0.2, P < .05) without altering the islet viability (89.47% ± 1.69 vs 93.15% ± 0.97) and with no significant apoptosis. Senescent microvesicles significantly doubled the expression of p53, p21, and p16 (P < .05), whereas young microvesicles had no significant effect.ConclusionPro-senescent endothelial microvesicles specifically accelerate the senescence of islets and alter their function. These data suggest that islet isolation contributes to endothelial driven islet senescence.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Salivary Content Might be Associated With Skeletal Status in Postmenopausal Women: SilesiaOsteoActive Study Results

Aim: The aim of the study was to investigate whether salivary mineral content may be associated with bone status in women after menopause. Material and methods: The study group consisted of 125 postmenopausal women aged 64.3 ± 6.9 yr, derived from the epidemiological SilesiaOsteoActive Study. All participants underwent hip and spine bone densitometry using dual energy X-ray absorptiometry, dental examination, and saliva content analysis. Data for salivary pH, copper, calcium, phosphorus, and zinc concentrations were evaluated. Results: Mean femoral neck bone mineral density (BMD) was 0.739 ± 0.118 g/cm², total hip BMD 0.891 ± 0.14 g/cm², and spine BMD 0.868 ± 0.14 g/cm². Salivary pH was significantly lower in women with spinal osteoporosis defined as T-score below ?2.5, compared to individuals with normal BMD (pH: 6.65 ± 0.67 vs 6.96 ± 0.58, p < 0.05). There was a significant though weak inverse correlation between Ca concentration in saliva and femoral neck BMD (r = ?0.23, p < 0.05). Conclusions: High salivary calcium content and low salivary pH may be indicative of low hip and decreased spine BMD, respectively. These associations may reflect demineralization process (calcium redistribution) influencing bone, and a negative effect of acidity on mineral tissues, although causal pathway remains not clear.     

Long-term rates of bladder dysfunction after decompression in patients with cauda equina syndrome

BACKGROUND CONTEXTCauda equina syndrome (CES) occurs due to compression of the lumbar and sacral nerve roots and is considered a surgical emergency. Although the condition is relatively rare, the associated morbidity can be devastating to patients. While substantial research has been conducted on the timing of treatment, the literature regarding long-term rates of bladder dysfunction in CES patients is scarce.PURPOSEThe aim of this study was to identify long-term rates of bladder dysfunction in CES patients and to compare those rates to non-CES patients who underwent similar spinal decompression.STUDY DESIGN/SETTINGRetrospective database study.PATIENT SAMPLEThe CES cohort was comprised of 2,362 patients who underwent decompression surgery following CES diagnosis with a 5-year follow-up. These patients were matched to 9,448 non-CES control patients who underwent spinal decompression without a diagnosis of CES.OUTCOME MEASURESDiagnosis of bladder dysfunction, surgical procedure to address bladder dysfunctionMETHODSUsing the national insurance claims database, PearlDiver, CES patients who underwent decompression surgery were identified and 1:4 matched to non-CES patients who underwent similar spinal decompression surgery. The 1-year, 3-year, and 5-year rates of progression to a bladder dysfunction diagnosis and surgical intervention to manage bladder dysfunction were recorded. The CES and non-CES groups were compared with univariate testing, and an analysis of risk factors for bladder dysfunction was performed with multivariate logistic regression analysis.RESULTSA total of 2,362 CES patients who underwent decompression surgery were identified and matched to 9,448 non-CES control patients. After 5 years, CES patients had a 10%–12% increased absolute risk of continued bladder dysfunction and a 0.7%–0.9% increased absolute risk of undergoing a surgical procedure for bladder dysfunction, as compared to matched non-CES patients. Multivariate analysis controlling for age, sex, obesity, tobacco use, and diabetes, identified CES as independently associated with increased 5-year risk for bladder dysfunction diagnosis (odds ratio [OR]: 1.72; 95% confidence interaval [CI] 1.56–1.89; p<.001) and procedure (OR: 1.40; 95% CI 1.07–1.81; p=.012).CONCLUSIONSUnderstanding the long-term risk for bladder dysfunction in CES patients is important for the future care and counseling of patients. Compared to non-CES patients who underwent similar spinal decompression, CES patients were observed to have a significantly higher long-term likelihood for both bladder dysfunction diagnosis and urologic surgical procedure.