testicular torsion

睾丸扭转
  • 文章类型: Journal Article
    背景:将患有睾丸扭转的儿科患者从社区医院转移到儿科中心可能是紧急手术干预的时间和资源密集型步骤。
    目的:我们试图描述本州患者转移的趋势,并比较主要在儿科中心转移和治疗的患者的临床结局和卫生系统成本。
    方法:这项回顾性队列研究比较了2018年至2023年直接到儿科中心就诊的1-18岁患者与因急性睾丸扭转而转移的患者。排除标准包括年龄<1岁,非紧急手术,从诊所入院。患者年龄,BMI,坦纳舞台,ASA类,保险范围,和演示时间是协变量。通过双侧Studentt检验比较了从症状发作到最初ED表现到手术的组特征和时间。临床结果(睾丸切除术,睾丸萎缩)通过Fisher精确测试进行比较。转移医院的成本是根据我们机构的成本估算的,从运输机构和儿科中心之间的合同价格推断医疗运输费用,以比较总的护理费用.
    结果:共133例(37例原发性,96次转让)符合纳入标准。在研究期间,转账增加(67%-75%)。在年龄上没有显著差异,坦纳舞台,ASA得分,BMI,或小组之间的演示时间。中值传输距离为12英里(IQR7-22),时间为1小时(IQR1-2)。超过一半的病例(53%)是由于医院关于未成年人手术治疗的政策而转移的,和25%是由于缺乏泌尿外科保险。转移组从初始ED部位到OR的时间几乎翻了一番(中位数4.5vs2.5h,p=0.02)。尽管原发性睾丸切除术的发生率较高(43vs22%,p=0.01),按症状持续时间分层后,这一差异并不显著.转移患者的平均护理费用估计是原发性患者的两倍($15,082vs$6898)。
    结论:近年来,我们州的小儿患者因睾丸扭转的转移有所增加。医院政策和当地泌尿外科覆盖率是患者转移的主要驱动因素,这几乎使手术干预时间增加了一倍,护理费用增加了一倍以上。临床结果由延迟报告驱动。
    结论:将睾丸扭转患儿转移到手术干预的时间几乎增加了一倍,护理费用也增加了一倍以上。限制性医院政策和农村医院泌尿外科覆盖率的差距为提高这些儿童的护理质量和效率提供了机会。
    BACKGROUND: The transfer of pediatric patients with testicular torsion from community hospitals to pediatric centers can be a time and resource-intensive step toward emergent surgical intervention.
    OBJECTIVE: We sought to describe trends of patient transfer in our state and compare clinical outcomes and health system costs between patients transferred and treated primarily at a pediatric center.
    METHODS: This retrospective cohort study compared patients aged 1-18 years who presented directly to a pediatric center to those transferred for acute testicular torsion from 2018 to 2023. Exclusion criteria included age <1 year, non-urgent surgery, and admission from clinic. Patient age, BMI, Tanner stage, ASA class, insurance coverage, and presentation time were covariates. Group characteristics and times from symptom onset to initial ED presentation to surgery were compared via two-sided Student\'s t-tests. Clinical outcomes (orchiectomy, testicular atrophy) were compared via Fisher\'s exact tests. Costs from transferring hospitals were estimated from costs at our institution, and medical transport costs were extrapolated from contract prices between transport agencies and the pediatric center to compare total episode-of-care cost.
    RESULTS: A total of 133 cases (37 primaries, 96 transfers) met inclusion criteria. Transfers increased over the study period (67%-75%). There were no significant differences in age, Tanner stage, ASA score, BMI, or time of day of presentation between groups. Median transfer distance was 12 miles (IQR 7-22) and time was 1 h (IQR 1-2). More than half of cases (53%) were transferred due to hospital policy regarding surgical treatment of minors, and 25% due to lack of urology coverage. Time from initial ED site to OR was nearly doubled for the transfer group (median 4.5 vs 2.5 h, p = 0.02). Despite a higher rate of orchiectomy in the primary group (43 vs 22%, p = 0.01), this difference was not significant after stratification by symptom duration. The estimated average cost of care for patients transferred was twice that of primary patients ($15,082 vs $6898).
    CONCLUSIONS: Transfer of pediatric patients in our state for testicular torsion has increased in recent years. Hospital policies and local urology coverage are primary drivers of patient transfer which nearly doubled time to surgical intervention and more than doubled cost of care. Clinical outcomes were driven by delayed presentation.
    CONCLUSIONS: Transfer of pediatric patients for testicular torsion nearly doubles time to surgical intervention and more than doubles cost of care. Restrictive hospital policies and gaps in rural hospital urology coverage present opportunities to improve the quality and efficiency of care for these children.
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  • 文章类型: Journal Article
    睾丸扭转带有诱发急性阴囊窘迫和睾丸萎缩的危险后果的不祥前景,需要立即手术干预以恢复重要的睾丸灌注,尽管再灌注具有矛盾的有害影响。虽然没有药物在这种紧急情况下获得批准,抗氧化剂成为有希望的候选者。这项研究旨在说明依普罗沙坦的影响,AT1R拮抗剂,大鼠睾丸扭转。将Wistar白化病大鼠精心分为五组,(n=6):假手术组,依普罗沙坦组,睾丸扭转-扭转(T/D)组,和两组T/D用两种口服剂量的依普沙坦(30或60mg/kg)治疗。血清睾酮,进行精子分析和组织病理学检查以评估精子发生。评估氧化应激标志物。Bax,使用ELISA或qRT-PCR估计BCL-2,SIRT1,Nrf2,HO-1以及裂解的caspase-3睾丸含量。作为自噬标志物,研究了SQSTM-1/p62、Beclin-1、mTOR和AMPK。我们的研究结果强调,依普罗沙坦有效改善血清睾酮水平,睾丸重量,和精子数量/活力/活力,同时减轻T/D引起的组织学不规则和精子异常睾丸功能的恢复是由细胞保护性SIRT1/Nrf2/HO-1轴的激活所支撑的。减少了睾丸氧化应激,通过降低MDA含量和增加GSH含量来表示。在细胞凋亡方面,依普罗沙坦通过降低裂解的caspase-3含量有效地对抗凋亡过程,抑制Bax和刺激Bcl-2基因表达。同时,它通过增加Beclin-1表达重新激活受损的自噬,降低SQSTM-1/p62的表达并调节AMPK和mTOR蛋白的磷酸化。依普罗沙坦有望治疗睾丸扭转引起的睾丸功能障碍,通过激活SIRT1/Nrf2/HO-1以及Beclin-1/AMPK/mTOR途径的促自噬和抗凋亡作用。
    Testicular torsion carries the ominous prospect of inducing acute scrotal distress and the perilous consequence of testicular atrophy, necessitating immediate surgical intervention to reinstate vital testicular perfusion, notwithstanding the paradoxical detrimental impact of reperfusion. Although no drugs have secured approval for this urgent circumstance, antioxidants emerge as promising candidates. This study aspires to illustrate the influence of eprosartan, an AT1R antagonist, on testicular torsion in rats. Wistar albino rats were meticulously separated into five groups, (n = 6): sham group, eprosartan group, testicular torsion-detorsion (T/D) group, and two groups of T/D treated with two oral doses of eprosartan (30 or 60 mg/kg). Serum testosterone, sperm analysis and histopathological examination were done to evaluate spermatogenesis. Oxidative stress markers were assessed. Bax, BCL-2, SIRT1, Nrf2, HO-1 besides cleaved caspase-3 testicular contents were estimated using ELISA or qRT-PCR. As autophagy markers, SQSTM-1/p62, Beclin-1, mTOR and AMPK were investigated. Our findings highlight that eprosartan effectively improved serum testosterone levels, testicular weight, and sperm count/motility/viability, while mitigating histological irregularities and sperm abnormalities induced by T/D. This recovery in testicular function was underpinned by the activation of the cytoprotective SIRT1/Nrf2/HO-1 axis, which curtailed testicular oxidative stress, indicated by lowering the MDA content and increasing GSH content. In terms of apoptosis, eprosartan effectively countered apoptotic processes by decreasing cleaved caspase-3 content, suppressing Bax and stimulating Bcl-2 gene expression. Simultaneously, it reactivated impaired autophagy by increasing Beclin-1 expression, decreasing the expression of SQSTM-1/p62 and modulate the phosphorylation of AMPK and mTOR proteins. Eprosartan hold promise for managing testicular dysfunction arising from testicular torsion exerting antioxidant, pro-autophagic and anti-apoptotic effect via the activation of SIRT1/Nrf2/HO-1 as well as Beclin-1/AMPK/mTOR pathways.
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  • 文章类型: Journal Article
    睾丸扭转(TT)是一种罕见但紧急的疾病;它导致严重的疼痛和肿胀,必须立即诊断和治疗,预期期为6-8小时。这是到达急诊科的重要预后因素。提高对TT的认识对于确保早期诊断和及时治疗至关重要,可以防止不可逆的损害和生育能力的丧失。
    我们的研究旨在测量意识,知识,沙特阿拉伯普通人群对睾丸扭转(TT)的态度。
    这是一项对居住在沙特阿拉伯的普通人群进行的横断面研究。使用在线调查在人群中分发了一份自我管理的问卷。问卷包括社会人口统计特征(即,年龄,性别,区域,等。),评估睾丸扭转知识的问卷,和调查问卷来评估患病率,管理,以及对睾丸扭转的态度。
    在473名参与者中,56%是男性,61%的人年龄在18至30岁之间。不幸的是,我们四分之一的人口对睾丸扭转有很好的了解。关于睾丸扭转评分的总体平均知识低于平均水平(8分中的3分)。与知识增加相关的因素包括年龄较小,男性,生活在中部地区,在医疗领域工作,听说了睾丸扭转,有睾丸扭转的个人或家族史。
    总而言之,一般人群缺乏睾丸扭转知识。应该进行进一步的研究和社会运动,以鼓励普通人群的理解并提高他们的知识水平。
    UNASSIGNED: Testicular torsion (TT) is a rare but urgent condition; it leads to severe pain and swelling that must be diagnosed and treated immediately, where there is an expectant period of 6-8 h. It is an important prognostic factor in the arrival time to the emergency department. Raising awareness about TT is essential to ensure early diagnosis and timely treatment, which can prevent irreversible damage and loss of fertility.
    UNASSIGNED: Our study aimed to measure the awareness, knowledge, and attitude toward testicular torsion (TT) among the general population in Saudi Arabia.
    UNASSIGNED: This is a cross-sectional study conducted among the general population living in Saudi Arabia. A self-administered questionnaire was distributed among the population using an online survey. The questionnaire includes socio-demographic characteristics (i.e., age, gender, region, etc.), a questionnaire to assess the knowledge of testicular torsion, and questionnaires to assess the prevalence, management, and attitude toward testicular torsion.
    UNASSIGNED: Of the 473 participants, 56% were males, and 61% were aged between 18 to 30 years old. Unfortunately, One quarter of our population has a good knowledge level about testicular torsion. The overall mean knowledge about Testicular Torsion score was below average (3 out of 8 points). Factors associated with increased knowledge include younger age, male gender, living in the Central Region, working in the medical field, having heard of testicular torsion, and having a personal or family history of testicular torsion.
    UNASSIGNED: In conclusion, there was a lack of testicular torsion knowledge among the general population. Further studies and social campaigns should be done to encourage the general population\'s understanding and increase their knowledge level.
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  • 文章类型: Journal Article
    研究乙酰水杨酸(ASA)和超声弹性成像对睾丸扭转的影响。
    这里,形成6个相等组的大鼠(n:48):对照组,假手术组,扭转/扭转(T/D)-1h组,T/D-1h+ASA组,T/D-8h组,T/D-8h+ASA组。通过顺时针旋转左睾丸720°来产生睾丸扭转。扭转前30分钟,腹膜内注射100mg/kg的ASA。弹性成像在8和24小时进行。睾丸切除术后,收集标本进行组织病理学评估。
    当比较从8小时施加的弹性成像获得的左睾丸体积(LV)参数时,在以下组对之间观察到显着差异:假手术和T/D-8h组,T/D-1h和T/D-8h组,和T/D-1h+ASA和T/D-8h组(分别为p=0.004,p=0.023和p=0.026)。各组的平均LVS(速度)(刚度评估)在8小时相似。当比较24小时的LV参数时,T/D-1h和T/D-8h组之间以及T/D-8h和T/D-8h+ASA组之间存在显著差异(分别为p=0.008和p=0.004).对于24小时的LVS平均值,对照组和假手术组之间存在显著差异,假手术组和T/D-1h组,假手术组和T/D-8h组,和假手术组和T/D-8h+ASA组(分别为p=0.009,p=0.021,p=0.027和p=0.009)。组织病理学评估显示,与T/D-1h组相比,T/D-1hASA组的形态学等级降低,平均睾丸损伤评分增加。T/D-8h+ASA组的形态学分级高于T/D-8h组,而他们的平均睾丸损伤评分相似。
    ASA治疗睾丸扭转无效。弹性成像可以作为诊断睾丸扭转的多普勒超声检查的补充方法,并可以指导外科医生的手术方法。
    UNASSIGNED: To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
    UNASSIGNED: Herein, 6 equal groups of rats were formed (n: 48): control group, sham group, torsion/detorsion (T/D)-1 h group, T/D-1 h + ASA group, T/D-8 h group, and T/D-8 h + ASA group. Testicular torsion was created by rotating the left testis 720° clockwise. At 30 min before torsion, 100 mg/kg of ASA was injected intraperitoneally. Elastography was performed at 8 and 24 h. After orchiectomy, specimens were collected for histopathological evaluation.
    UNASSIGNED: When comparing the left testicular volume (LV) parameters obtained from the elastography applied at 8 h, significant differences were observed between the following group pairs: the sham and T/D-8 h groups, T/D-1 h and T/D-8 h groups, and T/D-1 h + ASA and T/D-8 h groups (p = 0.004, p = 0.023, and p = 0.026, respectively). The mean LVS (velocity) (stiffness assessment) of the groups was similar at 8 h. When comparing the LV parameters at 24 h, significant differences were found between the T/D-1 h and T/D-8 h groups and between the T/D-8 h and T/D-8 h + ASA groups (p = 0.008 and p = 0.004, respectively). For the LVS mean values at 24 h, significant differences were found between the control and sham groups, sham and T/D-1 h groups, sham and T/D-8 h groups, and sham and T/D-8 h + ASA groups (p = 0.009, p = 0.021, p = 0.027, and p = 0.009, respectively).Histopathological evaluation showed a decrease in the morphological grades and an increase in the mean testicular injury scores in the T/D-1 h + ASA group compared to the T/D-1 h group. The T/D-8 h + ASA group had a higher morphological grade than the T/D-8 h group, whereas their mean testicular injury scores were similar.
    UNASSIGNED: ASA treatment for testicular torsion was shown to be ineffective. Elastography can be a complementary method to Doppler ultrasonography in the diagnosis of testicular torsion and can guide surgeons in their approach to surgery.
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  • 文章类型: Journal Article
    本研究的目的是研究骨髓间充质干细胞(BM-MSCs)对大鼠实验性睾丸扭转的愈合作用。
    创建由10只Wistar白化病大鼠组成的三组。在第一组中,我们对左睾丸进行了探查,并将其重新定位在阴囊中,而没有尝试对其进行任何修饰.在第二组中,左睾丸扭转了3小时,然后被扭转并重新定位。在第三组中,除了扭转和扭曲,BM-MSC被网状地施用。在第七天处死大鼠,通过组织病理学和生化分析研究睾丸的愈合状况。通过免疫荧光显微镜研究BM-MSC的参与。采用SPSS15.0进行统计学分析。P值<0.05被认为对于所有变量具有统计学意义。
    免疫荧光显微镜显示,在第III组中,BM-MSCs位于睾丸间质细胞周围。在光学显微镜下,组III的平均Johnsen评分显著高于组II(p=0.035).与II组相比,III组的白介素10(IL-10)水平显着高于II组(p=0.003)。而I组(对照组)的丙二醛(MDA)值低于其他组(p=0.037),超氧化物歧化酶(SOD)值相似(p=0.158)。尽管在MDA方面,II组和III组之间没有统计学上的显着差异,在第三组中更低。尽管III组的组织SOD水平高于II组,差异无统计学意义。
    该研究表明,睾丸扭转后,BM-MSC显着纠正了Johnsen评分并增加了抗炎细胞因子水平。BM-MSCs可用于睾丸扭转作为支持疗法,以最大程度地减少组织损伤。
    UNASSIGNED: The aim of this study was to investigate the healing effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on experimental testicular torsion in rats.
    UNASSIGNED: Three groups consisting of 10 Wistar albino rats were created. In Group I, the left testicle was explored and relocated in the scrotum without any attempt to modify it. In Group II, the left testicle underwent torsion for three h and then was detorsed and relocated. In Group III, in addition to torsion and detorsion, BM-MSCs were administered intratesticularly. The rats were sacrificed on the seventh day, and the healing status of the testicles was investigated with histopathological and biochemical analyses. BM-MSC involvement was investigated by immunofluorescence microscopy. Statistical analysis was performed using SPSS 15.0. A p-value < 0.05 was considered statistically significant for all variables.
    UNASSIGNED: Immunofluorescence microscopy showed that BM-MSCs were located around the Leydig cells in Group III. Under light microscopy, the mean Johnsen Score of Group III was significantly higher than that of Group II (p = 0.035). The interleukin-10 (IL-10) level was significantly higher in Group III compared to Group II (p = 0.003). While the malondialdehyde (MDA) values in Group I (the control group) were lower than in the other groups (p = 0.037), the superoxide dismutase (SOD) values were similar (p = 0.158). Although there was no statistically significant difference between Group II and Group III in terms of MDA, it was lower in Group III. Although the tissue SOD levels were higher in Group III than in Group II, the difference was not statistically significant.
    UNASSIGNED: This study has demonstrated that BM-MSCs significantly corrected the Johnsen Score and increased anti-inflammatory cytokine levels after testicular torsion. BM-MSCs can be used in testicular torsion as supportive therapy to minimize tissue damage.
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  • 文章类型: Journal Article
    OBJECTIVE: The current study aimed to explore the potential protective effect of Passiflora Incarnata L., (PI) in treating IR injury after testicular torsion in rats.
    METHODS: This research investigated the impact of PI on IR damage in male Wistar albino rats. Animals were divided to three groups: group 1 (sham), group 2 (IR), and group 3 (IR+PI).
    RESULTS: The malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels did not significantly differ across the groups (p = 0.830, p = 0.153 and p=0.140, respectively). However, Group 3 demonstrated a superior total antioxidant status (TAS) value compared to Group 2 (p = 0.020). Concurrently, Group 3 presented a significantly diminished mean total oxidant status (TOS) relative to Group 2 (p = 0.009). Furthermore, Group 3 showed a markedly improved Johnsen score relative to Group 2 (p < 0.01). IR caused cell degeneration, apoptosis, and fibrosis in testicular tissues. PI treatment, however, mitigated these effects, preserved seminiferous tubule integrity and promoted regular spermatogenesis. Furthermore, it reduced expression of tumor necrosis factor-alpha (TNF-α), Bax, and Annexin V, signifying diminished inflammation and apoptosis, thereby supporting cell survival (p < 0.01, p < 0.01, p < 0.01, respectively).
    CONCLUSIONS: This study revealed that PI significantly reduces oxidative stress and testicular damage, potentially benefiting therapies for IR injuries.
    OBJECTIVE: Explorar el posible efecto protector de Passiflora incarnata L. (PI) en el tratamiento de la lesión por isquemia-reperfusión (IR) después de una torsión testicular en ratas.
    UNASSIGNED: Se estudió el impacto de Passiflora incarnata en el daño por IR en ratas Wistar albinas machos. Los animales se dividieron tres grupos: 1 (simulado), 2 (IR) y 3 (IR+PI).
    RESULTS: Los niveles de malondialdehyde (MDA), myeloperoxidase (MPO) y glutathione (GSH) no difirieron significativamente entre los grupos (p = 0.830, p = 0.153 y p = 0.140, respectivamente). Sin embargo, el grupo 3 tuvo un valor de estado antioxidante total (TAS) superior en comparación con el grupo 2 (p = 0.020). Al mismo tiempo, el grupo 3 presentó un estado oxidante total (TOS) medio significativamente disminuido en comparación con el grupo 2 (p = 0.009). El grupo 3 mostró una mejora notable en la puntuación de Johnsen en comparación con el grupo 2 (p < 0.01). La IR causó degeneración celular, apoptosis y fibrosis en los tejidos testiculares. El tratamiento con PI mitigó estos efectos, preservó la integridad de los túbulos seminíferos y promovió la espermatogénesis regular. Además, redujo la expresión de factor de necrosis tumoral alfa, Bax y anexina V, lo que significa una disminución de la inflamación y de la apoptosis, respaldando así la supervivencia celular (p < 0.01, p < 0.01 y p < 0.01, respectivamente).
    CONCLUSIONS: Este estudio reveló que PI reduce significativamente el estrés oxidativo y el daño testicular, beneficiando potencialmente las terapias para lesiones por IR.
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  • 文章类型: Case Reports
    背景:老年人的睾丸扭转很少发生,通常通过手术治疗。
    方法:我们介绍了首例报道的70岁男性患者中成功的手动矫正病例,导致临床和放射学改善。
    在本病例报告中,我们讨论了在不需要手术的情况下,仅手动偏转在老年人中的作用。
    结论:对我们的患者进行24小时的治疗后观察,确保了出院前的稳定性。
    BACKGROUND: Testicular torsions in elderly individuals are rare occurrences that are often managed surgically.
    METHODS: We present the first reported case of a successful manual detorsion in a 70-year-old male patient, resulting in clinical and radiological improvement.
    UNASSIGNED: In this case report we discuss the role of manual detorsion alone in elderly without the need for surgery.
    CONCLUSIONS: Observation of our patient for 24 h post-detorsion ensured stability before discharge.
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  • 文章类型: Journal Article
    背景:隐睾和睾丸扭转(TT)是临床实践中相对常见的疾病;但是,关于密码火炬TT的稀疏信息在当前文献中可用。
    方法:我们回顾性回顾了临床特征,治疗方式,以及接受急性隐睾TT治疗的儿科患者的长期结局。
    结果:我们发现8例单侧急性隐睾TT患者,在所有TT病例中患病率为8.9%(8/90)。6例患者左睾丸受累。手术时患者的中位年龄为65个月(四分位距(IQR)4-136个月)。症状的中位持续时间为16小时(IQR9-25小时),而中位治疗时间为60分钟(IQR59-63分钟)。最常见的症状是疼痛(腹部和腹股沟)和腹股沟肿块,同侧半球没有明显的睾丸。术前彩色多普勒超声检查显示,有7/8的患者受影响的睾丸中睾丸血流缺失或减少。不同程度的睾丸扭转(中位数540°,最小360°,术中发现max1260°)。在4/8的患者中发现了导致睾丸切除术的坏死睾丸。中位随访期为42.6个月(IQR12.5-71.2个月),只显示一名睾丸萎缩患者.最终睾丸抢救率为35%。
    结论:需要提高护理人员和初级保健医生对急性隐睾TT的认识,以提高他们的及时诊断和治疗。必须对外生殖器和腹股沟区域进行身体检查,以毫不拖延地进行适当的诊断和治疗。
    BACKGROUND: Cryptorchidism and testicular torsion (TT) are relatively common conditions in clinical practice; however, sparse information about cryptorchid TT is available in the current literature.
    METHODS: We retrospectively reviewed the clinical characteristics, treatment modalities, and long-term outcomes of pediatric patients treated for acute cryptorchid TT.
    RESULTS: We found eight patients with unilateral acute cryptorchid TT with a prevalence of 8.9% (8/90) among all TT cases. The left testis was affected in six patients. The median age of patients at the time of the surgery was 65 months (interquartile range (IQR) 4-136 months). The median duration of symptoms was 16 h (IQR 9-25 h), while the median time to treatment was 60 min (IQR 59-63 min). The most common symptoms were pain (abdominal and inguinal) and inguinal mass with no palpable testis in the ipsilateral hemiscrotum. Preoperative color Doppler ultrasonography revealed absent or decreased testicular blood flow in the affected testes in 7/8 of patients. Various degrees of testicular torsion (median 540°, min 360°, max 1260°) were found during surgery. A necrotic testis that led to orchidectomy was found in 4/8 of patients. The median follow-up period was 42.6 months (IQR 12.5-71.2 months), revealing only one patient with testicular atrophy. The final testicular salvage rate was 35%.
    CONCLUSIONS: Greater awareness among caregivers and primary care physicians about acute cryptorchid TT is required to improve their timely diagnosis and treatment. A physical examination of the external genitalia and inguinal regions should be mandatory to attain a proper diagnosis and treatment without delay.
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