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ObjectiveTo determine patient outcomes across a range of pelvic fracture urethral injury (PFUI) severity. PFUI is a devastating consequence of a pelvic fracture. No study has stratified PFUI outcomes based on severity of the urethral distraction injury.MethodsAdult male patients with blunt-trauma-related PFUI were followed prospectively for a minimum of six months at 27 US medical centers from 2015-2020. Patients underwent retrograde cystourethroscopy and retrograde urethrography to determine injury severity and were categorized into three groups: (1) major urethral distraction, (2) minor urethral distraction, and (3) partial urethral injury. Major distraction vs minor distraction was determined by the ability to pass a cystoscope retrograde into the bladder. Simple statistics summarized differences between groups. Multi-variable analyses determined odds ratios for obstruction and urethroplasty controlling for urethral injury type, age, and Injury Severity Score.ResultsThere were 99 patients included, 72(72%) patients had major, 13(13%) had minor, and 14(14%) had partial urethral injuries. The rate of urethral obstruction differed in patients with major (95.8%), minor (84.6%), and partial injuries (50%) (P < 0.001). Urethroplasty was performed in 90% of major, 66.7% of minor, and 35.7% of partial injuries (P < 0.001).ConclusionIn PFUI, a spectrum of severity exists that influences outcomes. While major and minor distraction injuries are associated with a higher risk of developing urethral obstruction and need for urethroplasty, up to 50% of partial PFUI will result in obstruction, and as such need to be closely followed.

Today's reproductive endocrinology and infertility providers have many tools at their disposal when it comes to achieving pregnancy. In the setting of highly efficacious assisted reproductive technology, it is natural to assume that male factor infertility can be overcome by acquiring sperm and then bypassing the male evaluation. In this review, we go through guideline statements and a stepwise male factor infertility evaluation to propose that a thorough male evaluation remains important to optimize pregnancy and live birth. The foundation of this parallel evaluation is referral to a reproductive urologist for the optimization of the male partner, for advanced diagnostics and interventions, and for the detection of other underlying male pathology. We also discuss what future developments might have an impact on the workup of the infertile male.

PURPOSE: The aim of this investigation was to design a perfusion-based decellularization protocol to provide whole human uterine bio-scaffolds with preserved structural and componential characteristics and to investigate the in vivo properties of the decellularized tissues. METHODS: Eight human uteri, donated by brain-dead patients, were decellularized by perfusion of sodium dodecyl sulfate (SDS) through the uterine arteries using a peristaltic pump. The bio-scaffolds were evaluated and compared with native human uterus regarding histological, immunohistochemical, structural, and bio-mechanical properties, in addition to CT angiographies to examine the preservation of the vascular networks. Subsequently, we obtained acellular patches and implanted them on uterine defects of female Wistar rats to investigate the bio-compatibility and regenerative potential of the bio-scaffolds. Finally, we performed immunostaining to investigate the potential role of circulating stem cells in recellularization of the implanted bio-scaffolds. RESULTS: The outcomes of this investigation confirmed the efficacy of the proposed protocol to provide whole human uterine scaffolds with characteristics and extra-cellular matrix components similar to the native human uterus. Subsequent in vivo studies demonstrated the bio-compatibility and the regenerative potential of the scaffolds and suggested a signaling pathway as an underlying mechanism for the regenerative process. CONCLUSIONS: To the best of our knowledge, this investigation provides the first efficient perfusion-based decellularization protocol for the human uterus to obtain whole-organ scaffolds. The outcomes of this investigation could be employed in future human uterus tissue engineering studies which could ultimately result in the development of novel treatments for female infertile patients.

Introduction Approximately 15% of couples in the reproductive age are struggling with infertility which, in nearly half of them, is caused by male factors. Material and methods The present study comprised of two groups of sixteen C57BL/6 mice; each mouse received either an intraperitoneal injection of 30 mg/kg of an alkylating agent or the same amount of distilled water. Testes were harvested 30 days following the injection. Morphometric analysis of hematoxylin and eosin (H&E) stained slides including mean tubular area, diameter and intratubular particles were performed. Spermatogenesis rate was assessed by spermatogonial markers including promyelocytic leukemia zinc finger protein (PLZF) and neurogenin-3 (NGN3). Moreover, the expression rate of Wilms Tumor-1 (WT-1), A-Kinase Anchoring Protein 4 (AKAP4) and adenosine deaminase domain containing 1 (ADAD1) genes were evaluated via real-time polymerase chain reaction (RT-PCR). Results The body weight gradually increased in both groups after a period of 30 days, however, the increase was significantly (p-value = 0.023) lower in the chemically treated group. All the morphometric parameters were considerably decreased in the azoospermic mice. Also, promyelocytic leukemia zinc finger protein and neurogenin-3 expression dramatically declined (p-value

Previous studies indicated that the treatment of male hypogonadism can be beneficial for intraoperative and postsurgical outcomes. In this study, we aimed to determine the impact of male hypogonadism on urologic surgeries. We provided an overview of the key studies in the field with the focus on the outcomes of urologic surgeries in hypogonadal men with/without testosterone replacement therapy (TRT).We performed a literature review in PubMed and Google Scholar databases for the most relevant articles pertaining to the outlined topics without placing any limitations on publication years or study designs. We included full-text English articles published in peer reviewed journals between January 1970 and March 2022.Androgen deficiency is a common finding after major urologic surgeries. Although guidelines recommend against TRT in men with prostate carcinoma, recent investigations showed no association between TRT and disease progression and recurrence. Indeed, recent evidence suggested that low androgen levels could be related to high grade prostate carcinoma and increased risk of upgrading from low to high grade disease. Investigations on the application of TRT in benign prostatic hyperplasia (BPH) patients also revealed contrasting results. While some studies suggested higher rates of prostate-related events in men who received TRT, others showed that TRT could alleviate urinary symptoms in hypogonadal men with BPH. Decreased testosterone level is commonly seen in bladder cancer patients. The treatment of perioperative androgen deficiency can reduce postoperative morbidities and lower the risk of recurrence in these patients. Low testosterone levels are observed in approximately half of the men who undergo artificial urinary sphincter (AUS) placement and can increase the risk of complications.The role of testosterone treatment in patients with urologic diseases such as prostate carcinoma and BPH is controversial. Further investigations are needed to determine the impact of hypogonadism and TRT on the outcomes of urologic surgeries in patients with androgen deficiency.

To evaluate and compare the efficacy of urinary carbohydrate antigen 19-9 (CA19-9), neutrophil gelatinase–associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) biomarkers as predictive factors to determine the surgery requirement in patients with ureteropelvic junction obstruction. We obtained urine samples from 161 patients at diagnosis and evaluated their levels of the three biomarkers. The patients were under observation for 2 years; subsequently, they were divided into two groups based on their requirement of pyeloplasty. We determined the correlation between the urinary concentration of the biomarkers and surgical interventions, as well as the kidney function deterioration and sonography outcomes. The non-surgery group included 60 male and 22 female patients with mean age of 21 months. The surgery group comprised 58 boys and 21 girls with mean age of 26.9 months with no significant difference of age and gender between the two groups. The outcomes were indicative of higher efficacy of CA19-9 level with a sensitivity and specificity of 84.2% and 73.2% at the cutoff point of 59.09 U/ml. Also, a significant negative correlation was detected between the kidney function and the concentrations of CA19-9 and NGAL. Our evaluations demonstrate the higher efficacy of CA19-9 to predict the requirement of surgical intervention in comparison with the other biomarkers, as well as a significant correlation between kidney function deterioration and urinary CA19-9 and NGAL. The outcomes of this investigation could pave the way for more extensive clinical application of these urinary biomarkers, besides future research determining the association between markers and kidney fibrosis.

Leydig cell hypoplasia is a rare autosomal recessive condition caused by mutations in luteinizing hormone/chorionic gonadotropin receptor (LHCGR) genes in which 46, XY patients demonstrate a wide spectrum of disorders/differences of sex development (DSD) phenotypes ranging from normal female external genitalia in severe subtypes to micropenis or hypospadias in patients with less severe presentations. Although most patients with LHCGR defects are diagnosed at puberty, here we describe the prenatal diagnosis of 46, XY DSD due to two likely pathogenic variants in LHCGR, one of which has never been reported.

Thyroid cancer is one of the most common endocrine malignancies, with increasing incidence all over the world. In spite of good prognosis for differentiated thyroid carcinoma, for an unknown reason, about 5-10% of the patients, the cancer will show aggressive behavior, develop metastasis, and be refractory to treatment strategies like radioactive iodine. Regarding the genetic information, each thyroid cancer patient can be considered as an individual unique one, with unique genetic information. Contrary to standard chemotherapy drugs, target therapy components aim at one or more definite molecular pathway on cancer cells, so their selection is underlying patient's genetic information. Nowadays, several mutations and rearrangements including BRAF, VEGF receptors, RET, and RET/PTC, KDR, KIT, PDGFRA, CD274, and JAK2 are taken into account for the therapeutic components like larotrectinib (TRK inhibitor), vemurafenib, sunitinib, sorafenib, selumetinib, and axitinib. With the new concept of personalized treatment of thyroid cancer diagnoses, planning treatment, finding out how well treatment will work, and estimating a prognosis has changed for the better over the last decade.

Background Various investigations have reported that the internal mammary artery (IMA) is an efficient and functional choice of conduit for vascular graft surgeries, especially for coronary artery bypass grafts; however, the quest to find an ideal vascular substitute remains. We hypothesized that acellular IMA could be an appropriate graft for small-diameter vascular bypasses that could be used in various surgeries including coronary artery bypass grafting. Methods We decellularized human IMAs and performed histologic evaluations and scanning electron microscopy to confirm the decellularization process and the preservation of the extracellular matrix. Subsequently, we grafted the scaffolds into the superficial femoral arteries of 8 New Zealand rabbits with an end-to-end anastomosis. Computed tomography angiograms were provided at 3, 12, and 36 months postoperatively. Subsequently, the animals were killed, and biopsies were taken for histologic and immunohistochemical assessments. Results Evaluation of the acellular tissue confirmed the efficacy of the decellularization protocol and the preservation of the extracellular matrix. All 8 animals survived the entire follow-up period. Doppler ultrasonography and computed tomography angiographies verified the conduit's patency. Histologic assessments depicted the recellularization of all 3 layers of the scaffold. Smooth muscle cells were detected in tunica media. Immunohistochemical assessments confirmed these findings. Conclusions In conclusion, we demonstrated that acellular human IMA could be used as an efficient small-diameter vascular substitute with high patency. These findings could pave the path for future investigations on the clinical application of acellular IMA as a novel vascular graft for small-diameter bypass surgeries.

Aim: The aim of this study was to evaluate the efficacy of tissue-engineered amniotic membrane (AM) in the treatment of myocardial infarction lesions. Materials & methods: 20 rats were subjected to coronary arterial ligation in order to induce myocardial infarction injury. Decellularized human AMs were seeded with 2 × 105 adipose-derived mesenchymal stem cells and were implanted in the infarcted hearts. Results & conclusion: Histological and immunohistochemical evaluations indicated the regeneration of cardiomyocytes and reduction of inflammation and fibrosis in the patch-implanted group compared with a control group, 14 days after the surgery. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay was suggestive for apoptosis reduction in the patch-implanted specimens. This study suggested that human AM can be developed into a novel treatment for treating postmyocardial infarction.

Objectives Based on the recent advancements in cell therapy techniques, we aimed to evaluate the efficacy of transurethral injection of autologous adipose-derived stem cells, muscle-derived stem cells, and co-cultured cells for the rehabilitation of stress urinary incontinence rat models. We hypothesized that the utilization of co-cultured stem cells could result in enhanced therapeutic outcomes attributed to their more comprehensive environment of paracrine factors and cytokines. Methods We performed bilateral pudendal nerve transection surgeries to simulate urinary incontinence in 25 female Wistar rats and employed urodynamic evaluations to confirm the injury. We autologously isolated and cultured adipose-derived mesenchymal stem cells, muscle-derived stem cells, and a mixed culture of the two types, which we subsequently injected into the urethral lumen of the damaged animals. Three weeks after the injection, urodynamic assays, histological staining, and immunohistochemical evaluations were performed to determine the efficacy of the implanted cell cultures in sphincter function improvements or structural modifications. Results Histological evaluations suggested a regenerative process in the muscular layer of the external sphincter 3 weeks after the injection. Also, immunohistochemical analysis revealed a thickened periurethral striated muscle layer in the co-cultured group. Postinjection urodynamic analysis indicated that the urethral pressure profile significantly increased in the co-cultured group compared with other groups. Conclusions The outcomes of this investigation indicated that the application of co-cultured adipose-derived and muscle-derived stem cells could be associated with higher therapeutic value in stress urinary incontinence patients compared with singular-cell treatments.

The aim of this study was to investigate the rat small intestine mesentery and colon as natural bio-reactors for rat colon-derived scaffolds. We decellularized eight whole rat colons by a perfusion-based protocol using 0.1% sodium dodecyl sulfate for 24 hr. The provided bio-scaffolds were examined by histological staining, scanning electron microscopy, and collagen and sulfated glycosaminoglycan quantification. Subsequently, we implanted 4 cm segments of the provided bio-scaffolds into two groups of animal models comprising tissue grafting into the mesenteric tissue (n: 10) and end-to-end anastomosis (n: 10) to the colon of host rats. Following 9 months of follow-up, we harvested the grafts and performed histological and immunohistochemical studies as well as real-time PCR evaluation for telomerase activity of the samples. Histological staining, scanning electron microscopy and protein content evaluation of the acellular tissues confirmed the complete removal of the cellular components and preservation of the extracellular matrix. Histopathological assessment of the implanted scaffolds was suggestive of a regenerative process in both groups. Moreover, immunohistochemical analysis of the samples confirmed the presence of smooth muscle cells, endothelial progenitor cells, and neural elements in both groups of grafted scaffolds. Our data confirmed the recellularization of the acellular colon grafts in both groups after 9 months of follow up. Also, the implanted tissues demonstrated different characteristics based on their implantation location. The outcomes of this investigation illustrate the capability of acellular tissues for in vivo application and regeneration.

Myocardial infarction (MI) is a major cause of mortality and morbidity in industrialized societies. Myocardial tissue engineering is an alternative and promising approach for substituting injured myocardium through development and seeding of appropriate scaffolds. In this study, we investigated the efficacy of using an acellular pericardium to deliver autologous mesenchymal stem cells (MSCs) to the infarcted site for regeneration of the myocardium. MI was induced in two groups of rats; G1 or MI group, and G2 or patch-implanted group. In G2 group, rats had undergone transplantation of a pericardial patch which was previously seeded with adipose tissue derived MSCs. To evaluate the efficacy of the pericardial patches, biopsies were taken one month after transplantation. In order to evaluate the extent of regeneration, inflammation and fibrosis, histopathological investigations including hematoxylin and eosin (HE), Sirius Red and trichrome staining were performed. In addition, immunohistochemical investigations by Desmin as well as CD68, CD45 and CD34 antibodies were performed. Furthermore, Tunnel assay was performed to detect the extent of apoptosis. HE assessments of biopsies from the patch-implanted group confirmed presence of pre-seeded pericardium containing MSCs along with neo-vessels. Immunohistochemical assessments demonstrated higher number of CD34 positive cells and Desmin-positive cells in the patch implanted group (p 0.05); these findings are suggestive of cardiomyocyte regeneration in G2 rats. This study demonstrates the advantages of application of natural acellular scaffolds as cell delivery devices and it emphasizes neovascularization following this approach. However, further investigations are required to analyze long-term cardiac function in recipients. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2670-2678, 2018.

PURPOSE: The main purpose of this investigation was to determine an efficient whole-organ decellularization protocol of a human-sized uterus and evaluate the in vivo properties of the bioscaffold. METHODS: Twenty-four ovine uteri were included in this investigation and were decellularized by three different protocols (n 6). We performed histopathological and immunohistochemical evaluations, 4,6-diamidino-2-phenylindole (DAPI) staining, DNA quantification, MTT assay, scanning electron microscopy, biomechanical studies, and CT angiography to characterize the scaffolds. The optimized protocol was determined, and patches were grafted into the uterine horns of eight female Wistar rats. The grafts were extracted after 10 days; the opposite horns were harvested to be evaluated as controls. RESULTS: Protocol III (perfusion with 0.25% and 0.5% SDS solution and preservation in 10% formalin) was determined as the optimized method with efficient removal of the cellular components while preserving the extracellular matrix. Also, the bioscaffolds demonstrated native-like biomechanical, structural, and vascular properties. Histological and immunohistochemical evaluations of the harvested grafts confirmed the biocompatibility and recellularization potential of bioscaffolds. Also, the grafts demonstrated higher positive reaction for CD31 and Ki67 markers compared with the control samples which indicated eminent angiogenesis properties and proliferative capacity of the implanted tissues. CONCLUSIONS: This investigation introduces an optimized protocol for whole-organ decellularization of the human-sized uterus with native-like characteristics and a prominent potential for regeneration and angiogenesis which could be employed in in vitro and in vivo studies. To the best of our knowledge, this is the first study to report biomechanical properties and angiographic evaluations of a large animal uterine scaffold.

Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplantation is an acceptable treatment for native organ failure. However, it is associated with several problems due to a number of reasons, such as the lack of appropriate donors and immunosuppression. In our present study, a novel model is presented for in vivo recellularization of acellular pancreas by implanting between the host pancreas and the adjacent omental flap. In this study, the pancreases were harvested and cannulated via the common bile duct and then, the scaffolds were acellularized by a detergent-based protocol. After that, the abdomens of 35 rats were opened and the spleen was extracted with the adjacent omentum, and placed outside the abdomen. The acellularized scaffold was stretched over the host pancreas and the omentum was wrapped around it to make a sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked with Prolene 4-0 on four sides. All samples were biopsied at 14, 30, 60, 90, and 120 days post-transplantation. The result showed marked recellularization of acellularized pancreas with visible neovascularization and neoβ-cells with minimal inflammatory response. This study provides a new approach to produces a normal-like pancreas by allograft transplantation for pancreas tissue engineering. We observed that in vivo transplantation of acellularized pancreas can promote recellularization, proliferation, and differentiation by blood circulation. These findings support that in vivo studies can contribute to finding faster solutions for the treatment of diabetes.

The aim of this study was to determine an efficient whole-organ decellularisation protocol of a human-sized testis by perfusion through the testicular arteries. In the first step of this study, we determined the most efficient detergent agent, whereas the second phase delineated the optimal time required for the decellularisation process. Initially sheep testes were decellularised by one of three different detergent agents: sodium dodecyl sulphate (SDS), Triton X-100 and trypsin-ethylenediamine tetraacetic acid (EDTA) solutions, each perfused for 6h. In the second phase, the selected detergent agent was applied for different time periods. A total number of 20 organs were processed during this investigation. The efficacy of the decellularisation process and the preservation of the extracellular matrix components and structure were evaluated by histopathological examinations, 4′,6′-diamidino-2-phenylindole (DAPI) staining, DNA quantification, hydroxyproline measurement, magnetic resonance imaging and scanning electron microscopy. Organ perfusion with 1% SDS solution for 6 to 8h demonstrated the most desirable outcomes regarding decellularisation and extracellular matrix preservation. The 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was used to determine the toxicity of the scaffold and its potential for further application in tissue-engineering investigations. This investigation introduces an efficient method to produce a three-dimensional testicular bio-scaffold resembling the properties of the native organ that could be employed in tissue-engineering studies.