Protective effect of allicin on ischemia-reperfusion injury caused by testicular torsion-detorsion in rats.

OBJECTIVE: Testicular ischemia-reperfusion induced by testicular torsion-detorsion increases the level of reactive oxygen species, leading to testicular damage. Allicin, one of the most active ingredients in garlic, is a significant exogenous antioxidant. In the research, the efficacy of allicin in treating testicular ischemia-reperfusion injury was assessed. MATERIALS AND METHODS: The study included sixty Sprague-Dawley male rats. Three groups with 20 rats per group were created as follows: control group, testicular ischemia/reperfusion-induced group, and testicular ischemia-reperfusion plus treatment with allicin group. The control group underwent a sham operation of the left testis without other interventions. In the testicular ischemia/reperfusion-induced group, rat left testis was subjected to 720° torsion for two hours and then detorsion. In the allicin-treated group, in addition to testicular ischemia-reperfusion, 50 mg/kg of allicin was injected intraperitoneally, starting immediately following detorsion. Testicular tissue samples were obtained to measure the protein expression of xanthine oxidase, which is a major source of reactive oxygen species formation, malondialdehyde level (a reliable marker of reactive oxygen species), and testicular spermatogenic function. RESULTS: Testicular ischemia-reperfusion significantly increased the expression of xanthine oxidase and malondialdehyde levels in ipsilateral testes while reducing testicular spermatogenic function. The expression of xanthine oxidase and malondialdehyde levels were significantly lower in ipsilateral testes, whereas testicular spermatogenic function in the allicin-treated group was significantly higher compared with those in the testicular ischemia-reperfusion group. CONCLUSIONS: Our findings indicate that allicin administration improves ischemia/reperfusion-induced testicular damage by limiting reactive oxygen species generation via inhibition of xanthine oxidase expression.

The potential prophylactic and therapeutic impacts of niacin on ischemia/reperfusion injury of testis.

INTRODUCTION: The testicular ischemia-reperfusion (I/R) injury is characterized by the excessive aggregation of un-scavenged reactive oxygen species, leading to the heightened levels of oxidative stress. This phenomenon plays a pivotal role in the pathophysiology of testicular torsion damage. OBJECTIVE: The current study aimed to detect the prophylactic and therapeutic effects of niacin on testicular I/R injury. STUDY DESIGN: Twenty-four healthy adult male Sprague Dawley rats were randomly allocated into three groups as follows: (1) sham group, (2) torsion/detorsion (T/D) group, and (3) treatment group which received 200 mg/kg niacin along with testicular T/D. Torsion/detorsion was induced by 2 h of torsion followed by 10 days of reperfusion period. In the treatment group, niacin was injected 30 min before the reperfusion period intraperitoneally and continued for 10 days by oral gavage. RESULTS: T/D was associated with marked decreases in terms of sperm count, viability, and kinematic parameters versus the sham group (P < 0.05), which niacin significantly reverted the kinematic parameters (P < 0.05). I/R injury caused a significant increase in the number of abnormal epididymal sperms compared to the sham group (P < 0.05). Niacin decreased the epididymal sperm abnormality significantly compared to the T/D group (P < 0.05). Tissue abnormalities in T/D group, such as edema, hyperemia, inflammation, and necrosis were completely visible histopathologically, while the histological changes in the niacin-treated group were better than those in the T/D group. Regarding the pathological parametric evaluations, I/R injury significantly reduced the mean testicular biopsy score (MTBS), germinal epithelial cell thickness (GECT), and mean seminiferous tubular diameter (MSTD), and increased the tubular hypoplasia/atrophy (THA) compared to the sham group (P < 0.05), which niacin treatment significantly improved the MTBS and GECT compared to the T/D group (P < 0.05). T/D significantly increased the oxidative stress index (OSI) and lipid peroxidation (MDA) (P < 0.05). Niacin significantly reduced the OSI and MDA levels compared to the T/D group (P < 0.05). DISCUSSION: The current study found that niacin has preventive/therapeutic effects against the elevation of oxidative stress markers and depletion of antioxidants during I/R injury. Following administration of niacin, a reduction in histologic injury was observed in rats. In our study, we showed the antioxidant properties of niacin and its capacity to protect against I/R damage. CONCLUSION: The findings of the present investigation revealed that niacin, as an antioxidant agent, can suppress the oxidative stress induced by testicular I/R injury, and can be used as a supplementary agent in the treatment of those undergoing testicular torsion surgery.

Insights on Protective Effect of Platelet Rich Plasma and Tadalafil on Testicular Ischemia/Reperfusion Injury in Rats Exposed to Testicular Torsion/Detorsion.

BACKGROUND/AIMS: Ischemic reperfusion (I-R) injury is greatly influenced by the testicular torsion/detorsion process (TDP). In this instance, the anti-inflammatory properties of plateletrich plasma (PRP) combined with tadalafil (Td) significantly promote tissue healing in the I-R injury model. METHODS: Five groups of rats were created: the control group, the I-R group not receiving any therapy, the I-R group receiving a single dosage of Td (0.25 mg/kg, I.P.), the I-R group receiving a single dose of PRP (80 l, intratesticular), and the I-R group receiving both Td and PRP. Sperm morphology, motility, and histology were assessed. The levels of TNF-, BAX, antioxidant status, and testosterone were measured. Additionally, E-selectin expression was done. RESULTS: PRP reduced oxidative stress, inflammation, and apoptosis while also boosting testosterone levels, which alleviated I-R injury. Otherwise, PRP reduces E-selectin expression, which modifies the pathways that control endothelial function. Td also partially demonstrated its testicular-protective activity at the same time. CONCLUSION: PRP's proven anti-inflammatory, antioxidant, and antiapoptotic potentials make it a natural treatment for testicular harm caused by tadalafil. For the first time, it was demonstrated that PRP therapy restored the functionality of the vascular endothelium, specifically the control of E-selectin expression. Combining Td and PRP therapy may be a promising strategy for improving response to PDE5 inhibitors.

Cut-off time for surgery and prediction of orchiectomy in spermatic cord torsion: a retrospective multicentric study over 15 years.

PURPOSE: Cut-off time to avoid orchiectomy relies on small series of patients. The objective was to determine the cut-off time to avoid orchiectomy in torsion of the spermatic cord in a large cohort. METHODS: We performed a retrospective multicenter study (TORSAFUF cohort) of patients with suspected spermatic cord torsion between 2005 and 2019. All patients aged > 12 years who were suspected of having a torsion of the spermatic cord in 14 University Hospitals in France were included (n = 2986). Patients for whom data on pain duration were not available (n = 923) or for whom the final diagnosis was not torsion of the spermatic cord (n = 807) were excluded. The primary outcome was orchiectomy. The secondary outcomes were testicular survival time and the prediction of orchiectomy with the duration of pain. RESULTS: 1266 patients were included with an orchiectomy rate of 12% (150 patients). The mean age was 21.5 years old in the salvage group and 23.7 years old in the orchiectomy group (p = 0.01), respectively. The median time from the onset of pain to surgery was 5.5 (IQR = 5) hours in the salvage group and 51.1 (IQR = 70) hours in the orchiectomy group (p < 0.0001). The risk of orchiectomy increased after a time cut-off of 6 h 30. A delay of 15 h 30 in pain duration was found to predict orchiectomy (sensitivity: 0.81; specificity: 0.87). CONCLUSIONS: Pain duration can predict the probability of salvaging the testicles and performing orchiectomy. Rapid intervention should be recommended, regardless of the time elapsed from the onset of pain.

Pretreatment with remote ischemic conditioning attenuates testicular damage after testicular ischemia and reperfusion injury in rats.

Testicular torsion is a urological emergency. However, surgical detorsion of the torsed spermatic cord can cause testicular reperfusion injury. Although remote ischemic preconditioning (RIPC) has been convincingly shown to protect organs against ischemia/reperfusion (I/R) injury, little is known regarding the effect of RIPC on testicular torsion/detorsion-induced reperfusion injury. Therefore, we aimed to evaluate the effect of RIPC on testes after testicular I/R injury in a rat model in vivo. Male Sprague-Dawley rats were randomly classified into 4 groups: sham-operated (sham), testicular I/R (TI/R), or remote liver (RIPC liver) and limb (RIPC limb) ischemic preconditioning groups. Testis I/R was induced by 3 h of right spermatic cord torsion (720° clockwise), and reperfusion was allowed for 3 hours. In the RIPC group, four cycles of 5 min of ischemia and 5 min of reperfusion were completed 30 min prior to testicular torsion. The ERK1/2 inhibitor U0126 was administered intravenously at the beginning of reperfusion (1 mg/kg). The testes were taken for the oxidative stress evaluations, histology, apoptosis, immunohistochemical and western blotting analysis. Remote liver and limb ischemic preconditioning attenuated ipsilateral and contralateral testicular damage after testicular I/R injury. For example. RIPC reduced testicular swelling and oxidative stress, lessened structural damage, and inhibited the testicular inflammatory response and apoptosis. Furthermore, RIPC treatment enhanced testicular ERK1/2 phosphorylation postI/R. Inhibition of ERK1/2 activity using U0126 eliminated the protection offered by RIPC. Our data demonstrate for the first time that RIPC protects testes against testicular I/R injury via activation of the ERK1/2 signaling pathway.

Factors Determining Testicular Torsion and Consequent Orchiectomy in Pediatric Patients Presenting With Scrotal Pain.

OBJECTIVE: Factors associated with testicular torsion (TT) and consequent orchiectomy in patients presenting to pediatric emergency departments (PEDs) with scrotal pain (SP) are not well described. We report the factors predicting TT and consequent orchiectomy in children with SP. METHODS: The data on patients (aged ≤18 years) who presented with SP to PEDs at 4 branches of the Chang Gung Hospital through 10 years were analyzed. RESULTS: In all, 256 pediatric patients presented with SP. Their mean age was 11.60 ± 4.61 years and 72.7% (n = 186) were aged 10 to 18 years. The pain was left-sided in 54.7% (n = 140) and the interval between SP onset and PED arrival was 22.45 ± 31.27 hours. Overall, 84 (32.8%) patients needed surgery and 72 (28.1%) had TT. Of the patients with TT, 28 (38.9%) patients needed an orchiectomy. After analysis, TT and consequent orchiectomy were associated with a longer interval between SP onset and PED arrival, absent of testicular ultrasonic blood flow, interval between SP onset and surgery of more than 24 hours, and a high degree of TT. None of them experienced recurrent SP symptoms or TT again. CONCLUSIONS: The rate of TT in patients presenting to PEDs with an SP was 28.1%, and 38.9% of the patients with TT needed an orchiectomy. Early diagnosis and intervention helped to prevent subsequent orchiectomy in pediatric patients with TT.

Testicular ischemia secondary to acute epididymitis: A case report.

RATIONALE: Rare side effects of acute epididymitis include testicular infarction and ischemia. Distinguishing them from testicular torsion is challenging, both clinically and radiologically. However, only a few such cases have been reported to date. PATIENT CONCERNS: A 12-year-old child presented with persistent right testicular pain for 3 days. It developed after trauma and was accompanied by gradual swelling and enlargement of the right scrotum, with nausea and vomiting. Scrotal color Doppler ultrasonography demonstrated right epididymitis, right scrotal wall swelling, and right testicular torsion. Routine blood tests revealed leukocyte and neutrophil counts were both above normal. DIAGNOSIS: Scrotal exploration revealed edema and adhesions in all layers of the scrotal wall. The right testicle was pale. The patient was diagnosed with testicular ischemia secondary to acute epididymitis. INTERVENTIONS: The patient underwent simultaneous lower spermatic cord sheath dissection and decompression, testicular sheath reversal, and right testicular fixation. OUTCOMES: Blood flow to the testicles gradually recovered after decompression, as did the color. Postoperatively, the patient's scrotal swelling and pain improved significantly. LESSONS: Despite the rarity of this condition, it is a potentially serious consequence of epididymitis and should be considered when patients experience sudden scrotal pain.

The Role of Manual Detorsion in Pediatric Testicular Torsion During the Global COVID-19 Pandemic: Experience From 2 Centres.

OBJECTIVE: To evaluate the role of emergency manual detorsion as first line management for testicular torsion in the context of the COVID-19 pandemic. METHODS: This retrospective observational study includes 90 pediatric patients ≤14 years old with diagnosis of testicular torsion made at 2 tertiary centers between October 2020 and June 2022. Variables examined included age, presentation delay, surgical wait time, number of attempts at manual testicular detorsion, and manual testicular detorsion success. All patients finally underwent surgery, including contralateral testicular fixation. Outcomes included predictors of successful manual detorsion, testicular findings at surgery, and operation time. RESULTS: Mean (SD) age at diagnosis was 11.51 (2.64) years. Mean presentation delay was 11.76 (13.79) hours. Detorsion was attempted in 72 (80%) patients, resulting successful in 58 (80.5%). Surgical wait time after successful manual detorsion was 22.85 (16.94) hours. On multivariable analysis, successful manual detorsion was associated with a presentation delay<6 hours (odds ratios [OR] 0.154, 95% confidence intervals (CI) 0.036-0.655, P = 0.01) and absence of scrotal edema (OR 0.171, 95% CI 0.038-0.769, P = 0.02). Vice versa, a heterogeneous echo-texture (OR 0.57, 95% CI 0.007-0.461, P = 0.007) and absent blood flow on Doppler ultrasound scan (OR 0.256, 95% CI 0.067-0.971, P = 0.045) were significantly associated with the likelihood of manual detorsion failure. CONCLUSION: In our experience, manual detorsion provided safe and effective emergency treatment for pediatric testicular torsion, especially in absence of edema and when presentation delay is <6 hours. This maneuver should be more widely attempted immediately after diagnosis as temporizing rescue.

Remote limb ischemic postconditioning attenuates myocardial dysfunction induced by testicular torsion/detorsion in rats.

Torsion of the spermatic cord is a urological emergency that must be treated immediately with surgery, yet detorsion of the testis can cause testicular tissue damage because of ischemia-reperfusion (I/R) injury. I/R injury is a complex pathophysiological process that may affect the functions of distant organs. Here, we examined whether testicular torsion/detorsion (TT) causes myocardial dysfunction. We next investigated the potential beneficial effect and underlying mechanisms of remote ischemic postconditioning (RIPost) on cardiac function after testicular torsion/detorsion. Male Sprague-Dawley rats were assigned to three different sets of experimental groups. Testicular I/R was induced by rotating the right testis to 1080° clockwise for 3 h followed by 3 h of detorsion. RIPost was induced at the onset of testicular detorsion by four cycles of 5-min bilateral femoral artery occlusion with 5-min reperfusion. Cardiac function was determined postdetorsion, and the cardioprotective effect of RIPost was examined. Testicular torsion/detorsion-treated rats had reduced serum testosterone levels, impaired systemic hemodynamics, elevated systemic inflammatory responses, and increased serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), α-hydroxybutyrate dehydrogenase (α-HBDH), and cardiac troponin I (cTnI). However, RIPost attenuated remote heart dysfunction induced by testicular torsion/detorsion. Furthermore, RIPost enhanced the phosphorylation of ventricular signal transducer and activator of transcription (STAT)-3, which is a key component of the survivor activating factor enhancement (SAFE) signaling pathways. Inhibition of STAT-3 with Ag490 abolished the RIPost-induced cardioprotection and STAT-3 phosphorylation. Testicular torsion followed by detorsion may cause impaired cardiac function in rats. RIPost effectively attenuates this remote cardiac dysfunction. RIPost-induced protective effects may be mediated by the STAT-3 signaling pathway.

Protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse spermatogenesis and sperm chromatin condensation following unilateral testicular torsion.

Testicular torsion is considered a urological disorder that requires immediate detorsion surgery. Ischemia/reperfusion (I/R) injury after testicular torsion detorsion causes of drastic impairment of spermatogenesis and infertility. Cell-free-based approaches seem to be a promising strategy to prevent I/R injury, they have more stable biological properties, and they contain paracrine factors of mesenchymal stem cells. The purpose of this study was to evaluate the protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse sperm chromatin condensation and spermatogenesis improvement after I/R injury. hAMSCs were isolated and characterized by RT- PCR and flow cytometry, preparation of hAMSCs secreted factors was performed. Forty male mice were randomly divided into 4 groups: sham-operated, torsion detorsion, torsion detorsion+ intratesticular injection of DMEM/F-12, and torsion detorsion+ intratesticular injection of hAMSCs secreted factors. After one cycle of spermatogenesis, the mean number of germ cells, Sertoli, Leydig, myoid as well as tubular parameters, Johnson score, and spermatogenesis indexes were evaluated by H& E and PAS stainings. Sperm chromatin condensation and relative expression of c-kit and prm 1 genes were assessed by aniline blue staining and real-time PCR, respectively. The mean number of spermatogenic cells, Leydig, myoid, Sertoli, spermatogenesis parameters, Johnson score, as well as germinal epithelial height and diameters of seminiferous tubules decreased significantly after I/R injury. The thickness of basement membrane and percentage of sperm with excessive histone significantly increased, while the relative expression of c-kit and prm 1 significantly decreased in torsion detorsion group (p 0.001). hAMSCs secreted factors remarkably restored normal sperm chromatin condensation, spermatogenesis parameters and histomorphometric organization of seminiferous tubules via intratesticular injection (p 0.001). Thus, hAMSCs secreted factors may potentially salvage torsion-detorsion-induced infertility.

Testicular torsion in vivo models: Mechanisms and treatments.

BACKGROUND: Testicular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter-rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side-effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss. OBJECTIVES: To discuss testicular torsion surgery-based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion. MATERIALS AND METHODS: We reviewed all original research and epidemiological papers related to testicular torsion condition. RESULTS: Testicular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion-induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti-inflammatory agents, or vasodilating agents in order to decrease these effects. DISCUSSION AND CONCLUSION: To the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion-induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.

Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Testicular and scrotal abnormalities in pediatric and adult patients.

Testicular and scrotal abnormalities can occur in children, adolescents, and adults. The lesions, often accompanied by pain and swelling/enlargement of the scrotum, can cause anxiety in patients and their parents. Regardless of age, proper diagnosis is based on adequate anamnesis and physical examination. Color Doppler ultrasound is the first-line test in the differential process of testicular and scrotal diseases. Testicular and scrotal lesions require differentiation for benign and malignant processes as well as therapeutic management, including urgent surgical intervention. The aim of this paper is to present the most common causes of testicular and scrotal abnormalities in pediatric and adult patients and to outline the symptoms and diagnostic and therapeutic management.

Baicalein Alleviates Testicular Ischemia-Reperfusion Injury in a Rat Model of Testicular Torsion-Detorsion.

Testicular torsion/detorsion-induced ischemia/reperfusion injury is partly due to the overgeneration of reactive oxygen species. Baicalein, a main bioactive constituent derived from the dried root of Scutellaria baicalensis Georgi, possesses powerful antioxidative and anti-inflammatory properties. Therefore, we designed the research to explore the possible protective effect of baicalein against testicular ischemia-reperfusion injury. Sprague-Dawley rats were randomized into 4 groups, including control, testicular ischemia-reperfusion, testicular ischemia-reperfusion+vehicle injection, and testicular ischemia-reperfusion+baicalein therapy groups. The control group received surgical exposure of the left testis without torsion-detorsion. In the testicular ischemia-reperfusion group, the left testis underwent 720° counterclockwise torsion for two hours and then was allowed detorsion. Rats in the testicular ischemia-reperfusion+vehicle injection group received intraperitoneal injection of the vehicle at detorsion. In the baicalein-treated group, the intraperitoneal administration of baicalein dissolved in the vehicle was performed at detorsion. At four hours or three months following testicular detorsion, testicular tissues were removed to detect the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) which can recruit neutrophils into the testis, myeloperoxidase activity (an index of neutrophil infiltration in the testis), protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in neutrophils which can catalyze reactive oxygen species production, malondialdehyde concentration (a common marker of reactive oxygen species), and spermatogenesis. Both testicular ischemia-reperfusion and testicular ischemia-reperfusion+vehicle injection significantly increased the TNF-α and IL-1ß levels, myeloperoxidase activity, NADPH oxidase protein expression, and malondialdehyde concentration, while decreased spermatogenesis in ipsilateral testes. In contrast, baicalein administration remarkably reduced TNF-α and IL-1ß levels, myeloperoxidase activity, NADPH oxidase protein expression, and malondialdehyde concentration and also elevated spermatogenesis in ipsilateral testes. The results of our experiment demonstrate that baicalein alleviates testicular ischemia-reperfusion injury by inhibiting TNF-α and IL-1ß secretion, neutrophil infiltration in the testis, and NADPH oxidase protein expression in neutrophils to reduce reactive oxygen species production.

Increasing utilization of the TWIST score in workup of patients with acute scrotal pain: Role in diagnosis and risk stratification.

INTRODUCTION: The TWIST score is a 5-component physical examination score used to aid in diagnosis of testicular torsion (TT) and could lessen need for radiologic testing in certain clinical scenarios. OBJECTIVE: TWIST use was not previously widespread at our institution. The primary objective of this quality improvement study was to achieve 100% compliance in TWIST utilization among urology and ED residents and to assess for score concordance between ED and urology assessments. Secondary goals were correlation of TWIST components with need for orchiectomy. METHODS: ED staff were educated about the TWIST score and asked to complete assessment for patients presenting with acute scrotal pain. Simultaneously, an electronic medical record-based dot phrase was introduced for urology trainees to complete an independent TWIST evaluation. Spearman correlation was performed to assess association between ED and Urology TWIST scores. Multivariable logistic regression was performed to assess association of TWIST score components and need for orchiectomy. RESULTS: 103 patients presented to the ED from 3/2018-11/2020 with a complaint of acute scrotal pain; 47 were diagnosed with torsion. As compared to our retrospective cohort, the documentation rate of complete TWIST score components on exam rose from 9% to 98% (P < 0.001) on ED evaluation and 16%-66% on urology evaluation (P < 0.001). Rates of repeat ultrasound for patient's transferred between facilities was similar (58% vs. 63%; p = 0.66) as was median time to OR (160 min vs. 145 min; p = 0.5). Using TWIST cutoff of >5 yielded a specificity of 94.5% for diagnosis of torsion, with corresponding strong correlation between ED and urology scores (rho = 0.71). A firm testicle was noted on urology evaluation in 100% of orchiectomy patients (vs. 61% of salvage patients) with persistent association after controlling for duration of symptoms (OR 28.1; P = 0.016). DISCUSSION: Through two-pronged quality improvement efforts, we significantly improved utilization of the TWIST score by ED and urology staff for workup of patients with acute testicular pain. We confirmed the high sensitivity and specificity of the TWIST score and demonstrated inter-rater reliability between ED and urology assessments. On prospective analysis, testicular firmness on exam was predictive of need for orchiectomy. CONCLUSION: The TWIST score is an accurate diagnostic tool for both ED and urology providers in workup of children with acute scrotal pain, with a normal score essentially ruling out the condition. Future work should aim at minimizing unnecessary testing in patients demonstrated to be at high risk for torsion.

The evaluation of citral effects on experimental unilateral testicular ischemia/reperfusion injury.

This investigation aimed to evaluate the defensive impacts of citral on ischemia/reperfusion (I/R) injury induced by testicular torsion/detorsion (T/D) in rats in an experimental model. The grouping of subjects was as follows: (1) sham, (2) T/D, (3) and (4) T/D plus citral 150 and 300 mg/kg, respectively, and (5) intact (citral 300 mg/kg). T/D was performed by testicular 720° turning for 2 h and then detorsion for 24 h. Blood serum was obtained to assess testosterone and oxidative stress markers, epididymal sperms were collected for sperm staining and sperm analysis, and testicular tissues were examined for histopathology. T/D damage was associated with a remarkable decline in sperm total count, viability, and some velocity parameters in comparison to the sham group (p < 0.05), which could be reversed significantly by citral (p < 0.05). Histopathologically, T/D damage caused severe oedema, haemorrhage, inflammation, and seminiferous tubules disruption, while citral improved significantly the mean seminiferous tubular diameter, Cosentino's score, and Johnsen's score (p < 0.05). I/R injury was associated with significant increased malondialdehyde and oxidative stress index, and also significant reduced total antioxidant capacity and testosterone versus the sham group (p < 0.05), which all were prevented significantly by citral administration (p < 0.05). The outcomes greatly proved that testicular I/R injury could be significantly prevented by citral.

Evaluating the effects of betaine on testicular ischemia/reperfusion injury induced by torsion/detorsion in the rat.

In this research, the effects of betaine on testicular ischemia-reperfusion were evaluated. Forty rats were randomly divided into 4 groups of sham, torsion/detorsion (TD), torsion/detorsion with two different dosage of betaine 200 mg/kg, and 300 mg/kg, respectively. At the end of the experiment, the testosterone concentration, sperm motility, concentration and vitality, oxidative stress biomarkers including Malondialdehyde (MDA), Glutathione peroxidase (GPx), Catalase (CAT), and total antioxidant capacity (TAC) were assessed. Moreover, histopathological parameters including seminiferous tubules diameter (STD), seminiferous epithelium thickness (SET), spermatogonia nuclei diameter (SpND), Sertoli cell nuclei diameter (StND) and miotic index were evaluated. The testosterone concentration altered during torsion/detorsion and betaine could increase slightly the testosterone concentration after 15 days. Sperm motility and vitality significantly increased in the betaine treated groups compared to the TD group on days 3 and 15. Among oxidative stress biomarkers, only CAT on day 3 and GPx on day 15 were significantly higher in the betaine groups compared to the TD group. Among histopathological parameters an increase in the STD and SET in betaine-200 and betaine-300 groups were observed on 15th day of post-surgery, compared to the TD group. These findings indicate that betaine can ameliorate testicular damages triggered by torsion/detorsion.

LOCAL-IGF-1 and GH application IMPROVES germ cell histology, spermatogenesis and fertility after experimental testicular torsion and detorsion.

OBJECTIVE: To evaluate the impact of insulin like growth factor-1(IGF-1) and growth hormone (GH) on testis histology, spermatogenesis, and fertility in prepubertal rats exposed to 6 h of testicular torsion (TT) and detorsion. MATERIAL-METHOD: Forty-eight male Wistar-albino rats weighing 30-70g and at 3-week age were allocated into six groups involving eight rats in each group as follows: Group 1:Sham, Group 2:Control, Group 3:Gelatin, Group 4:Local-IGF-1, 5: Local-GH, Group 6: Systemic-GH. Right testis was only exposed and sutured in the sham group, and right testes were rotated clockwise, 720°, fixed, and 6 h later, detorsion on the testis was done in groups 2-6. Unloaded gelatin, 5 µg local-IGF-1 loaded, and 2IU rhGH loaded gelatin were sutured to the right testis after detorsion in groups 3-5. In Group 6, 0.3IU/100gr/d rhGH was given for seven days via subcuticular route after detorsion. Each of the rats cohabited with two female rats five weeks later. Afterward, both right and left testes were removed. Mean diameter of seminiferous tubules (STD), mean biopsy score count of the testis (TBSC), mean percentage of haploid cells (HCP) were assessed, and fertility parameters were evaluated. RESULTS: STD and TBSC of the ipsilateral testes were significantly reduced in control and gelatin groups when compared to sham, local-IGF-1, and local-GH groups. STD and TBSC of the ipsilateral testes of the systemic-GH group were decreased compared to the sham group. HCP of the ipsilateral testes of control, gelatin, and systemic-GH groups were significantly lower than the sham, local-IGF-1, and local-GH groups. STD, TBSC, and HCP of the contralateral testes were significantly reduced in control and gelatin groups when compared separately to sham, local-IGF-1, systemic- GH, and local-GH groups. The difference between groups regarding potency, fertility, fecundity indexes, and mean fetus numbers were not significant. CONCLUSION: Even though there was significant and permanent histologic germ cell damage and reduced HCP in both ipsilateral and contralateral testes, experimental 6 h TT and detorsion in prepubertal rats did not have a negative impact on future fertility. Local-IGF-1and rhGH treatment improved germ cell histology and spermatogenesis in both ipsilateral and contralateral testes of prepubertal rats, subjected to 6 h of TT and detorsion.