Search Results (16)

Introduction: Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory biomarker (hemogram-derived-ratio) related to ischemic-inflammatory diseases. Its usefulness in the diagnosis of pediatric testicular torsion (TT) has recently been reported, although its prognostic implication has not been evaluated. Our aim is to analyze the role of NLR in the evolution of TT in children, determining its potential for predicting the risk of adverse outcomes such as orchiectomy or testicular atrophy. Methods: We performed a retrospective multicentric case-control study in patients with clinical and ultrasound suspicion of TT, in whom surgical testicular examination was performed between 2016–2022 in seven pediatric hospitals. Patients’ outcomes were analyzed according to the intraoperative and postoperative evolution (orchiectomy/testicular atrophy or not). Demographics and clinical, ultrasound and laboratory features at admission were analyzed. Sensitivity and specificity were determined by the area under the curve (AUC) represented on the receiver operating characteristic (ROC) curves. Results: A total of 455 patients (median age 13.2 years; interquartile range 10.6–14.4 years) were included, in whom 87 orchiectomies (19.1%) were performed and 34 cases of testicular atrophy (7.5%) were observed during follow-up (median follow-up: 10 months). When comparing clinical, ultrasound and laboratory predictors of both events on ROC curves, NLR was the most sensitive and specific parameter for predicting orchiectomy (AUC = 0.834; p < 0.001), as well as testicular atrophy (AUC = 0.849; p < 0.001). Compared with other parameters, the designed cut-off point of NLR = 5.2 had maximum sensitivity and specificity (82.2% and 77.0%, respectively) for predicting orchiectomy or atrophy after testicular torsion. Conclusions: NLR may be considered the best predictor for the risk of orchiectomy or testicular atrophy following torsion in pediatric patients, helping the identification of high-risk cases. It can be useful both for obtaining more accurate preoperative information on patient prognosis and for closer follow-up of high-risk testicular atrophy patients. Full article

Testicular torsion is a common emergency in adolescents, and can lead to severe ischemia reperfusion injury (IRI). LncRNA H19 has been shown to increase during ischemia, but its role in testicular IRI remains unknown. Focusing on this research gap, we utilized H19 biallelic mutant mice and Sertoli cell line (TM4) to construct in vivo and in vitro models of ischemia/reperfusion (I/R) and oxygen–glucose deprivation/reperfusion (OGD/R). Compared to WT I/R mice, H19^−/− I/R mice showed milder tissue disorganization and cell loss, with a more intact blood–testis barrier (BTB). The cell viability decreased, ROS levels and apoptosis-related factors such as Bax/Bcl-2 increased in TM4 cells after OGD/R, whereas these changes were reversed when H19 was knocked down followed by OGD/R (si-H19+OGD/R). In contrast, over-expression of H19 in TM4 cells exacerbates OGD/R-induced cell apoptosis. Through in-depth analysis of KEGG-enriched pathways, the PI3K/AKT pathway was identified as a potential target of H19 modulation. Western blotting confirmed that, in OGD/R cells, elevated H19 levels were accompanied by the excessive AKT phosphorylation and the tight junction marker ZO-1 degradation; and in si-H19+OGD/R cells, the decreased AKT phosphorylation was recovered and the up-regulated ZO-1 expression was weakened simultaneously via using the AKT activator SC79. These results suggest that inhibiting H19 in OGD/R cells might preserve the integrity of the BTB by reversing the excessive phosphorylation of AKT. Moreover, H19 deficiency in si-H19+OGD/R cells alleviated the disturbances in glycolysis, fatty acid biosynthesis, and amino acid metabolism. Our study indicates that H19 might be a potential therapeutic target for clinic testicular I/R treatment. Full article

Inflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia/reperfusion (I/R) injury was investigated in this research. Five groups of six animals each were created: ischemia, Ischemia+Reperfusion (I+R), Ischemia+Reperfusion+Bromelain (I+R+Bro; 10 mg/kg), control (sham), and Bromelain (Bro; 10 mg/kg). An I/R damage resulted from two hours of 720° clockwise twisting of the left testis. Blood samples and epididymal sperm were collected after reperfusion to analyze sperm parameters (recovery, motility, viability, and morphology) and cytokines that promote inflammation (IL-1β, IL-6, and TNF-α). Using Western blotting, testicular tissue was examined for histopathological alterations, antioxidant enzymes (GSH, SOD), lipid peroxidation (MDA), apoptosis, and survival-related proteins (TLR4, Caspase-3, Bcl-2, NRF-2, HO-1, PI3K, mTOR, AKT-1). While raising the activities of GSH and SOD, two antioxidant enzymes, Bro administration dramatically reduced MDA concentrations. The I+R+Bro group had significantly reduced amounts of cytokines that promoted inflammation compared to the I+R group. Bro’s protective properties are also attributed to proteins that are altered by it and participate in the apoptosis and survival of cells. Sperm morphology, motility, and concentration notably improved in the bromelain-treated group, according to spermatological examination. Testicular samples treated with bromelain showed less tissue damage according to histological evaluations than the untreated I+R group. These findings imply that Bro has anti-inflammatory, anti-apoptotic, and antioxidant qualities. It effectively reduces oxidative stress and inflammation by modulating the PI3K/Akt/mTOR and NRF-2/HO-1 pathways, hence minimizing I/R injury. Full article

Oxidative stress triggered by testicular torsion and detorsion in young males could negatively impact future fertility. Using a rat animal model for testicular IRI (tIRI), we aim to study the induction of autophagy (ATG) during testicular ischemia and tIRI and the role of oxidative-stress-induced c-Jun N-terminal Kinase (JNK) as a cytoprotective mechanism. Sixty male Sprague-Dawley rats were divided into five groups: sham, ischemia only, ischemia+SP600125 (a JNK inhibitor), tIRI only, and tIRI+SP600125. The tIRI rats underwent an ischemic injury for 1 h followed by 4 h of reperfusion, while ischemic rats were subjected to 1 h of ischemia only without reperfusion. Testicular-ischemia-induced Beclin 1 and LC3B expression was associated with decreased p62/SQSTM1 expression, increased ATP and alkaline phosphatase (AP) activity, and slightly impaired spermatogenesis. SP600125 treatment improved p62 expression and reduced the levels of Beclin 1 and LC3B but did not affect ATP or AP levels. The tIRI-induced apoptosis lowered the expression of the three ATG proteins and AP activity, activated caspase 3, and caused spermatogenic arrest. SP600125-inhibited JNK during tIRI restored sham levels to all investigated parameters. This study emphasizes the regulatory role of JNK in balancing autophagy and apoptosis during testicular oxidative injuries. Full article

Objectives: Testicular torsion is a time-critical, organ-threatening diagnosis requiring prompt surgical intervention for successful salvage of the organ. In Australia, 28% of individuals live in rural and remote areas and face barriers to health care such as greater distance, lower socioeconomic status, (SES), and limited health infrastructure. We hypothesize that these barriers would delay intervention and access to surgical care, and lead to higher orchidectomy rates. Objectives: A 12-year retrospective audit was conducted at a large rural referral center in Australia, focusing on patients undergoing scrotal exploration for testicular torsion. Primary outcomes were orchidectomy rate, time to operation, and ultrasound (US) and their relationship with patient distance, SES, age, and peripheral hospital attendance. Data on SES for geographic postcodes was obtained from the Australian Government Socio-Economic Indexes for Areas 2016. Statistical analysis was performed using IBM SPSS Statistics software, and a P value < 0.05 was considered significant. Results: The study involved 107 patients, of whom 46% had left-sided pathology. The median age of the patients was 14 years. Median SES was in the 37% to 41% centile range, median distance from travelled was 62 kilometers, and median time to operation from triage was 194 minutes. Of the patients, 34 attended a peripheral hospital. No significant risk factors for orchidectomy were identified. US was used in 65% of cases, with torsion detected in 50% of those cases, and orchidectomy performed in 11 patients. US had a sensitivity of 86.1% and specificity of 52.9%. Conclusion: Despite significant differences in geographical distance, SES, age, and access to health care, patients in rural and remote areas of Australia experienced equivalent outcomes in testicular torsion management. Testicular torsion was safely managed at a central referral center using a peripheral hospital catchment in rural and remote areas of Australia, despite significant time delays due to greater distance or lower SES. Full article

The primary aim of this study is to evaluate heterogeneity in the current management of testicular torsion (TT). A secondary aim is to investigate incidences of recurrent torsion and the methods used for primary fixation. An online multiple-choice questionnaire comprising 10 questions was distributed to paediatric surgeons and urologists. There were a total of 99 questionnaires distributed to representatives from 39 paediatric surgery and urology departments in Poland. The majority of participants agreed on fixation of the torsed testicle (98%). Use of sutures was reported by 95% of surgeons: absorbable by 48%, non-absorbable by 42%, and 4% using both. There was no consensus on the number of sutures. The contralateral testicle was always fixed by 69%, with 28% fixing it only in case of necrosis and amputation of the torsed testicle, and the remaining 2% never fixing the contralateral side. In case of negative scrotal exploration, 18% of surgeons would still fix the testis. The recurrence of torsion after prior fixation was identified by eight of the participants. The most commonly reported primarily used technique was absorbable sutures. There is a general consensus on the fixation of torsed testicles; however, other aspects remain controversial. Based on the survey and the literature review, the use of non-absorbable sutures rather than absorbable sutures would be advisable. Full article

Oxidative stress, inflammation and germ cell death are the main characteristics of testicular ischemia reperfusion injury (tIRI), which is considered as the underlying mechanism for testicular torsion and detorsion. The study aimed to examine the effect of tIRI-activated NADPH oxidase (NOX) on the expression of the NLRP3 inflammasome pathway components. Three groups of male Sprague–Dawley rats (n = 12 each) were studied: sham, unilateral tIRI only and tIRI treated with apocynin, a NOX-specific inhibitor. The tIRI rat model was subjected to 1 h of ischemia followed by 4 h of reperfusion. H&E staining, real time PCR, biochemical assays, and Western blot were utilized to evaluate spermatogenic damage, gene expression, oxidative stress markers, and NLRP3 pathway components, respectively. As a result of tIRI, decreased total antioxidant capacity and suppressed activities of superoxide dismutase and catalase were associated with spermatogenic arrest. The components of the NLRP3 inflammasome pathway (TXNIP, NLRP3, ASC, caspase-1, GSDMD, MMP-9) were upregulated transcriptionally and post-transcriptionally during tIRI. In parallel, tissue inflammation was demonstrated by a marked increase in the concentrations of myeloperoxidase, IL-1β, and IL-18. Apocynin treatment prevented testicular oxidative stress and inflammation. Thus, NOX inhibition by apocynin prevented ROS accumulation, proinflammatory cytokine overexpression and NLRP3 inflammasome activation during tIRI. Full article

Cryptorchidism is heritable in cats, and due to the pathological risk of testicular torsion, and the development of testicular neoplasia, cryptorchidectomy is the treatment of choice. For the intra-abdominal testes, a laparotomic approach is generally recommended; however, laparoscopic cryptorchidectomy in cats has been documented in a few clinical case reports. The aim of the study was to report the short-term clinical outcomes for 19 cryptorchid cats with intra-abdominal testes that underwent cryptorchidectomy with laparoscopic techniques. Medical records of client-owned sexually intact male cats that underwent laparoscopic cryptorchidectomy in different veterinary hospitals or ambulatory surgical services were reviewed. The procedure was performed in 19 cats. The average time (mean ± standard deviation, SD) for all procedures was 23 ± 6 min (range 15–35 min). The time for laparoscopic removal of a single abdominal testis was 22 ± 6 min, with 30 min for the bilateral abdominal testes. The time until hospital discharge varied depending on the surgeon’s criteria, with a mean of 6 h (range 3–24 hrs). None of the cases analyzed showed any surgical complications. The results of this study suggest that laparoscopic cryptorchidectomy is an appropriate surgical procedure to treat cryptorchid cats with intra-abdominal testes, all with benefits of minimal invasion surgery. Full article

Background: This study investigates endocrine and exocrine testicular function, oxidative stress (OS) in semen, and erectile function in patients who underwent surgery for suspected testicular torsion (TT). Methods: We evaluated 49 patients over a mean follow-up of 101 months: n = 25 patients treated with surgical exploration, n = 20 patients treated with detorsion, and n = 4 treated with orchiectomy. We performed semen analysis including Male infertility Oxidative System (MyOxSIS) analysis, physical examination, and evaluation of endocrine and erectile function. Results: OS, erectile function and spermiogram categories did not differ significantly between the groups. The interval from the onset of symptoms to surgery differed significantly between groups (p < 0.001). Preservation of the testes was associated with a higher round cell count (p = 0.002) and follicle stimulating hormone (FSH, p = 0.003). OS showed a significant positive correlation with the spermiogram category (0.337; p = 0.022). A negative correlation was observed between OS and age (p = 0.033), sperm concentration (p < 0.001) and total sperm count (p = 0.006). Conclusions: Endocrine, exocrine and erectile function are not significantly affected by TT in the long term. Orchiectomy results in elevated FSH and a lower round cell count compared to preservation of the testis. Full article

The external genitalia are notoriously implicated in every fifth male with Henoch–Schönlein syndrome. Nonetheless, the underlying conditions are poorly categorized. To characterize the involvement of the external male genitalia in this vasculitis, we performed a systematic review of the literature. For the final analysis, we selected 85 reports published between 1972 and 2022, which reported on 114 Henoch–Schönlein cases (≤ 18 years, N = 104) with a penile (N = 18), a scrotal (N = 77), or both a penile and a scrotal (N = 19) involvement. The genital involvement mostly appeared concurrently with or after the cutaneous features of Henoch–Schönlein syndrome, while it preceded the presentation of Henoch–Schönlein syndrome in 10 cases. Patients with penile involvement (N = 37) presented with swelling (N = 26), erythema (N = 23), and purpuric rash (N = 15). Most patients were otherwise asymptomatic except for transient micturition disorders (N = 2) or priapism (N = 2). Patients with scrotal involvement (N = 96) presented with pain (N = 85), swelling (N = 79), erythema (N = 42), or scrotal purpura (N = 22). The following scrotal structures were often involved: scrotal skin (N = 83), epididymis (N = 49), and testes (N = 39). An ischemic testicular damage was noted in nine patients (four with torsion and five without). The scrotal skin involvement was mostly bilateral, while that of the epididymis and testis were mostly (p < 0.0001) unilateral (with a significant predilection for the left side). In conclusion, this analysis allows for better categorization of the involvement of external male genitalia in Henoch–Schönlein vasculitis. Scrotal involvement can result from skin inflammation, epididymitis, orchitis, or testicular ischemia. Full article

Testicular torsion potentially leads to acute scrotum and testicle loss, and requires prompt surgical intervention to restore testicular blood flow, despite the paradoxical negative effect of reperfusion. While no drug is yet approved for this condition, antioxidants are promising candidates. This study aimed to determine astaxanthin’s (ASX), a potent antioxidant, effect on rat testicular torsion−detorsion injury. Thirty-two prepubertal male Fischer rats were divided into four groups. Group 1 underwent sham surgery. In group 2, the right testis was twisted at 720° for 90 min. After 90 min of reperfusion, the testis was removed. ASX was administered intraperitoneally at the time of detorsion (group 3) and 45 min after detorsion (group 4). Quantification of caspase-3 positive cells and oxidative stress markers detection were determined immunohistochemically, while the malondialdehyde (MDA) value, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined by colorimetric assays. The number of apoptotic caspase-3 positive cells and the MDA value were lower in group 4 compared to group 2. A significant increase in the SOD and GPx activity was observed in group 4 compared to groups 2 and 3. We conclude that ASX has a favorable effect on testicular ischemia-reperfusion injury in rats. Full article

Testicular torsion is a pathology that occurs in young males generally before the age of 25. Despite surgery representing the only effective approach, there is still a need to identify a marker that can predict whether a preserved testicle will be functional. In addition, no therapeutic approach is currently considered in the post-operative phase. Through an approach based on the in vitro culture of a tissue strictly linked to the testicle, the gubernaculum, we defined the healthy state of the organ and the possible responsiveness to a therapy used in the andrology field, chorionic gonadotropin (hCG). Firstly, we optimized a protocol to obtain viable cells starting from a small piece of gubernacular tissue harvested during surgery with the aim to amplify cells in vitro. Intriguingly, only for a patient whose testicle had been removed during surgery due to an excessive necrotic area, gubernacular cells were not able to grow in culture. These data support the possibility of exploiting the gubernaculum to evaluate the healthy state of the testicle. Then, as we demonstrate that gubernacular cells express a luteinizing hormone receptor, to which hCG is specific, we analyzed the cellular response to hCG treatment on in vitro cultured cells derived from patients affected by testicular torsion. Our study opens the way for the possibility of evaluating testicle wellbeing after derotation through in vitro culture of a small piece of gubernaculum together with predicting the response to the treatment with hCG, which can have a positive effect on cell proliferation and vascularization. Full article

Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein. Full article

Background and Objectives: It is of great importance to obtain information about the severity of ischemic damage and duration of testicular torsion for an effective treatment strategy. Nucleolar-organizing regions (NORs) are sites of the ribosomal genes composed of ribosomal DNA and proteins. Post-silver staining NORs are termed “AgNOR”. Since AgNORs clearly reveals the self-renewal potential of cells damaged in ischemic events, we performed the current study. Materials and Methods: The study was carried out in four groups as control, sham, early, and late T/D. In the surgical groups, testes were corrected after a 4-h ischemia period. Testicular tissue samples were taken on the third day after detorsion in group 1, 2, 3, and on the tenth day after detorsion in group 4. TUNEL and silver stainings were applied to all samples. Results: The differences were significant among the groups for both mean AgNOR number and total AgNOR area/total nuclear area (TAA/TNA). Moreover, the differences between control and early torsion-detorsion (T/D), between control and late T/D, between sham and early T/D, between sham and late T/D, and between early T/D and late were statistically significant for AgNOR amount. Furthermore, statistically significant differences among the groups for an average number of apoptotic cells per tubule and the percentage of apoptotic tubule values were detected. Discussion: The apoptotic index gives the ratio of cells that are damaged and will die in a programmed way and cells that remain intact, rather than show the viability of the returning testicle. However, by measuring cells that regenerate with AgNOR, we can show not only those that survive but also cells that can repair themselves. Conclusion: AgNOR proteins are usable for the early observation of ischemic injury levels. The amount of AgNOR protein can enlighten us about the extent of testicular damage after T/D treatment. It may also help the physician in the development of effective treatment strategies for cases. Full article

Testicular torsion is a surgical emergency. Early diagnosis and surgical treatment are vital in order to preserve the affected gonad. Current surgical teaching emphasizes sudden, severe, persistent, unilateral scrotal pain as a cardinal symptom of testicular torsion. We present the case of unilateral testicular torsion in a 14-year-old patient who presented with the absence of severe pain. Despite a delayed presentation to the emergency department, the gonad could be salvaged successfully. Literature on the topic of testicular torsion presenting with minimal pain is limited. Nevertheless, pediatric surgeons might be faced with cases similar to the one we describe. Underestimating this phenomenon might lead to a delay of treatment. In such cases, ultrasound can be a beneficial addition in the diagnosis and accelerate definitive operative treatment. The presented case clearly demonstrates that, although we do not include testicular torsion without severe pain in our surgical teaching algorithms, we might encounter it in our clinical practice. Full article