Testicular Torsion in Jiaodong Peninsula: A 14-Year Multicenter Retrospective Study.

BACKGROUND: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. METHODS: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher's exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson's correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. RESULTS: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson's r = -0.228, 95% confidence interval (CI): -0.366 to -0.079, p = 0.003). Logistic regression analysis revealed that the independent risk factor for testicular torsion was TD on admission day (odds ratio, 1.82; 95% CI, 1.28-2.59; p < 0.001). CONCLUSIONS: To some extent, external temperature can affect the body surface temperature of patients and then induce testicular torsion. We concluded that testicular torsion easily occurs in the season in which the temperature drops and the TD is high.

Testicular Torsion in Jiaodong Peninsula: A 14-Year Multicenter Retrospective Study

Background: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. Methods: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher’s exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson’s correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. Results: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson’s r = −0.228, 95% confidence interval (CI): −0.366 to −0.079, p = 0.003) (AU)

Impact of seasonal variations on incidence and laterality of testicular torsion.

Nowadays, there is confusing evidence in the literature regarding the association between seasonal variations and events of testicular torsion (TT). We attempted to assess the correlation between seasonal variations, including season, ambient temperatures, and humidity levels to onset and laterality of testicular torsion. We conducted a retrospective review of patients diagnosed with testicular torsion and confirmed surgically between January 2009 and December 2019, at Hillel Yaffe Medical Center. Weather data was collected from meteorological observation stations near the hospital. TT incidents were stratified into five temperature categories (< 15 °C, 15-20 °C, 20-25 °C, 25-30 °C, > 30 °C) and into two categories of humidity (≤ 50%, > 50%). Potential associations between TT and seasonal variations were investigated. Of 235 patients diagnosed with TT, 156 (66%) were children and adolescents and 79 (34%) were adults. In both groups, rate of TT incidents increased in winter and fall months. Significant correlation between TT and temperatures below 15 °C was observed in both groups; OR 3.3 [95% IC 1.54-7.07], p = 0.002 in children and adolescents and 3.77 [1.79-7.94], p < 0.001) in adults. The correlation between TT and humidity was non-significant in both groups. Among children and adolescents left-sided TT was observed in most of the cases, with strong correlation to lower temperatures; OR 3.15 [1.34-7.40], p = 0.008. Higher rates of acute TT were observed in patients admitted to the emergency department (ED) during the cold seasons in Israel. Significant association was observed between left-side TT and temperatures below 15 °C in the children and adolescents' group. Our findings suggest that there might be a predilection for TT occurrence in cold weather, particularly left-side laterality among children and adolescents.

Testicular torsion-detorsion causes dysfunction of mitochondrial oxidative phosphorylation.

BACKGROUND: Semen quality impairment is a serious consequence of testicular torsion-detorsion. Adequate germ-cell mitochondrial oxidative phosphorylation plays a crucial role in male fertility. Changes in cellular oxidative phosphorylation in testicular tissues after testicular torsion-detorsion remain unclear. OBJECTIVES: This study investigated whether testicular torsion-detorsion induces alternations of mitochondrial oxidative phosphorylation in testicular tissues. MATERIALS AND METHODS: BALB/c male mice were divided into a Sham group and a testicular torsion-detorsion group. At the end of the procedure, the mice were euthanized, and their bilateral testicles were removed. Mitochondria morphology was evaluated through transmission electron microscopy. The cellular respiratory functions of germ cells were evaluated using a Seahorse analyzer assay. The proteome profiles in testicular tissues were analyzed using liquid chromatography-tandem mass spectrometry. The differences in the expression levels of each component in the oxidative phosphorylation were revealed using Ingenuity Pathways Analysis. RESULTS: Inner mitochondrial membrane disruption was found in ipsilateral twisted testicular mitochondria in the torsion-detorsion group but not in contralateral untwisted testes. The cellular respiratory function in germ cells was significantly decreased after testicular torsion-detorsion in ipsilateral twisted testes but not in contralateral untwisted testes. Liquid chromatography-tandem mass spectrometry analysis of ipsilateral twisted testicular tissue revealed that mitochondrial proteins were differentially expressed after testicular torsion-detorsion. Testicular torsion-detorsion induced downregulation of oxidative phosphorylation and revealed alternations of specific proteins in the oxidative phosphorylation complexes. DISCUSSION AND CONCLUSION: Testicular torsion-detorsion produced mitochondria injury and dysregulation of mitochondrial oxidative phosphorylation in ipsilateral twisted testes. Different protein expressions were identified in the mitochondrial oxidative phosphorylation complexes with testicular torsion-detorsion; new therapeutic targets may be identified to restore the oxidative phosphorylation function of germ cells.

Henoch-Schönlein Purpura With Scrotal Involvement: A Case Report and Literature Review.

Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels, leading to arthritis, abdominal pain, and renal involvement. However, scrotal involvement is a rare complication of HSP and scrotal pain. Swelling is the most frequent clinical presentation and can be easily confused with testicular torsion. If not treated in time, the scrotal inflammation will result in irreversible testicular necrosis. We report a 6-year-old male with HSP and scrotal involvement, characterized by swelling and pain on the left side of the scrotum, rashes on both lower extremities, and epididymitis. He was treated with conservative care, corticosteroids, and antibiotic therapy. We were able to avoid surgical intervention. On the 10 days of treatment, he recovered sufficiently well and was discharged. We have reviewed the literature related to HSP with scrotal involvement, identified 21 cases, and revealed that steroid therapy and/or antibiotics are the first-line of therapy in children with scrotal involvement. Vasculitis in the scrotum may predispose to testicular torsion, which is a complication that should not be overlooked. Clinicians should be aware of the atypical types of HSP. Timely diagnosis and appropriate treatment are essential for achieving the best results.

Cryptorchid testicular torsion in children: characteristics and treatment outcomes.

This study aimed to review and compare the characteristics and treatment outcomes of cryptorchid testicular torsion in pre- and postpubertal children. We reviewed the clinical data of 22 patients with testicular torsion complicated by cryptorchidism who were treated between January 2010 and December 2019. Patients were categorized into prepubertal (1 month to 9 years; n = 12) and postpubertal groups (10-16 years; n = 10). The age at presentation, clinical presentations, physical examination, and operation outcomes were assessed. The common clinical presentations in both groups were inguinal pain and a tender inguinal mass. Patients in the prepubertal group were significantly more likely to present with restlessness (33.3%) than those in the postpubertal group (0%; P = 0.044). After detorsion, testicular blood flow recovered during surgery in 25.0% of the prepubertal and 80.0% of the postpubertal patients (P = 0.010). Orchiectomy was required in 50.0% of the prepubertal and 20.0% of the postpubertal patients (P = 0.145). Of the 22 patients with follow-up data, the rates of testicular salvage were significantly different, at 16.7% in the prepubertal patients and 60.0% in the postpubertal patients (P = 0.035). Cryptorchid testicular torsion has various manifestations. Although an empty hemiscrotum and a painful groin mass were common in both groups, restlessness was more prevalent in the prepubertal patients during early testicular torsion onset than that in the postpubertal patients. Notably, the testicular salvage rate was significantly lower in the prepubertal patients than that in the postpubertal patients.

Torsión de testículo: aspectos medicolegales a recordar. Conceptos y matices / Testicular torsion: Legal aspects to keep in mind. Concepts and tricks

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Structural and functional significance of scrotal ligament: a comparative histological study.

Gubernaculum testes is the most important parameter in testicular migration. At the end of migration, it is described as scrotal ligament, which has implications in testicular torsion. The present study aims to examine the structure of scrotal ligament and compare it with gubernaculum. Sixteen adult cadaveric testicular specimens and fourteen fetal testicular specimens of different age groups were examined after getting ethical clearance from the institute ethics committee and consent from the parents. Meticulous dissection was done. The length, site of proximal, and distal attachment of scrotal ligament and gubernaculum were noted and histologically evaluated. A separate scrotal ligament could not be delineated in any adult specimens. It merged with testicular coverings. Histological examination showed the presence of patchy areas of dense collagen fibres of variable density amidst loose areolar connective tissue. In contrast, fetal specimens showed the presence of a definitive gubernaculum testes and revealed the presence of mesenchymal tissue, collagen, elastic fibres, and myocytes which varied according to gestational age of fetuses. Structure of scrotal ligament and gubernaculum testes is highly variable. Description of scrotal ligament as a firm attachment from lower pole of testes to scrotum is controversial, questioning its role as protective factor in testicular torsion.

Testicular Torsion From Bell-clapper Deformity.

A 12-year-old otherwise healthy boy presents to a local emergency room with sudden onset, sharp, continuous left testicular pain for 9 hours, associated with nausea and vomiting. Exam and ultrasound is consistent with testicular torsion. During scrotal exploration, a bell-clapper deformity of the left testicle is appreciated, with a normal gubernacular attachment of the right testicle. Bell-clapper deformity is a congenital failure of the posterior attachment of the gubernaculum to the testis, which increases testicular mobility within the tunica vaginalis and predisposes individuals to testicular torsion.

Perinatal testicular torsion.

Testicular torsion (TT) occurs when the testis rotates around the axis of the spermatic cord attachments and prevents blood flow to the testis, resulting in tissue ischemia. If this occurs in the first month of life it is referred to as "perinatal TT" (PTT) or "neonatal TT" (NTT). PTT has an incidence of 6.1 per 100,000 live births. Some of these cases occur prenatally. It can be missed on the initial newborn examination, as it can be asymptomatic. Hence, the true incidence is much higher since it is underdiagnosed. The types of TT include extravaginal, intravaginal, and mesorchial. Most cases of PTT are extravaginal. The diagnosis can generally be made on physical examination. Ultrasonography (US) can help exclude other rare diagnoses as long as surgical intervention is not delayed. There has been some debate regarding the timing of surgery. Although the torsed testicle may not be salvageable, the likelihood of asymptomatic bilateral TT has to be borne in mind and contralateral orchiopexy done at the time of exploration would prevent an asynchronous torsion. Nonoperative maneuvers to detorse in PTT are not recommended. The evaluation, diagnostic approach, and management of this relatively rare condition are described.

Pediatric Trauma-Induced Testicular Torsion: A Surgical Emergency.

OBJECTIVE: To evaluate the features of testicular torsion (TT) resulting from minor groin trauma and to raise the awareness of trauma-induced testicular torsion (TITT). METHODS: This is a retrospective chart review of patients presenting with TT resulting from minor genital trauma that was performed from January 2010 to December 2018 at a single tertiary care institution. The demographic, clinical, and perioperative characteristics, as well as data on follow-up and complications, were analyzed. RESULTS: Of the 155 patients treated for TT, 15 were included in this study. The average age of the patients was 10.3 years (range: 3.2-13.3 years). All patients experienced a direct scrotal trauma and subsequently presented with an ipsilateral scrotal or testicular pain secondary to the twisted testicle. Six patients were misdiagnosed as having scrotal inflammation or hematoma, and all were initially treated at local hospitals. The mean duration of symptoms before hospitalization was 138 h (range: 5-504 h). The mean degree of torsion was 390° (range: 180-720°). The testicular salvation rate, at 33%, was poor. No serious postoperative complications or recurrences of TT was observed. CONCLUSIONS: TITT is a rare entity and still has delayed diagnosis. This may subsequently lead to a low testicular salvation rate. Emergency surgeons, especially in local hospitals, should be aware of the possibility of TT following testicular trauma in pediatric patients. Improving the parents' awareness regarding TT is also important.

Cold weather increases the risk of scrotal torsion events: results of an ecological study of acute scrotal pain in Scotland over 25 years.

The role of ambient temperature in the aetiology of acute scrotal pain (ASP) remains uncertain. The most common causes of ASP are torsion of the testis (TT) or its appendages (TA) and epidymo-orchitis (EO). We undertook an ecological study of ASP in Scotland to determine whether a seasonal variation could be observed. Episode reports for TT, TA and EO in Scotland over 25 years were collated monthly. Statistical analyses were performed to determine whether changes in ambient temperature during the year could explain variations in monthly frequency. 7882 episodes of TT and TA (Group A), and 25,973 episodes of EO (Group B) were reported. There was significant variance in the frequency of Group A (p < 0.0001) and B (p = 0.0031) episodes by month, higher frequency of Group A episodes in the colder half of the year (p < 0.0001), and an inverse correlation between the frequency of Group A episodes and ambient temperature (Spearman r = - 0.8757, 95% CI - 0.9661 to - 0.5941, p = 0.0004). Ambient temperature is likely to be playing a role in the aetiology of TT and TA in Scotland but not EO. Further study is warranted to explain underlying mechanisms.

Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREMτ Expression.

Testicular torsion/detorsion-induced damage is considered as a typical ischemia-reperfusion injury attributed to excessive reactive oxygen species (ROS) production. ROS may regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The cAMP-responsive element modulator-τ (CREMτ) gene expression in the testis is essential for normal germ cell differentiation. The present study was aimed at investigating the effect of sesamol, a powerful antioxidant, on testicular ischemia-reperfusion injury and related mechanisms in an experimental testicular torsion-detorsion rat model. The type of our study was a randomized controlled trial. Sixty rats were randomly divided into the following 3 groups: (1) sham-operated control group (n = 20), (2) testicular ischemia-reperfusion group (n = 20), and (3) testicular ischemia-reperfusion+sesamol-treated group (n = 20). Testicular ischemia-reperfusion was induced by left testicular torsion (720° rotation in a counterclockwise direction) for 2 hours, followed by detorsion. Orchiectomy was performed at 4 hours or 3 months after detorsion. The testis was obtained for the analysis of the following parameters, including malondialdehyde level (a sensitive indicator of ROS), CREMτ expression, and spermatogenesis. In the testicular ischemia-reperfusion group, the malondialdehyde level was significantly increased with a concomitant significant decrease in CREMτ expression and spermatogenesis in ipsilateral testis. These results suggest that overproduction of ROS after testicular ischemia-reperfusion may downregulate CREMτ expression, which causes spermatogenic injury. Sesamol treatment resulted in a significant reduction in the malondialdehyde level and significant increase in CREMτ expression and spermatogenesis in ipsilateral testis. These data support the above suggestion. Our study shows that sesamol can attenuate testicular ischemia-reperfusion injury through scavenging ROS and upregulating CREMτ expression.

Acute Scrotum Secondary to Torsion of a Tunica Vaginalis Cyst.

This is a case of an 8-year-old boy with a chief complaint of left-lower-quadrate abdominal pain for 3 days. Examination revealed swollen left hemi-scrotum and scrotal ultrasound showed a para-testicular cystic mass, which was later proven to be a torsion of a benign scrotal tunica cyst during emergent scrotal exploration. Torsion of the tunica vaginalis cyst is a rare cause of acute scrotum, and we present this case to share our experience of diagnosis and management of this peculiar disease.

Comparison of Intraperitoneal and Intratesticular GYY4137 Therapy for the Treatment of Testicular Ischemia Reperfusion Injury in Rats.

The efficacy of intraperitoneal GYY4137 therapy and intratesticular GYY4137 therapy in an experimental rat model was investigated. Four groups were set up as the sham-operation group, torsion/detorsion (T/D) group, T/D plus intraperitoneal GYY4137 (G-IP) group, and T/D plus intratesticular GYY4137 (G-IT) group. In order to establish a testicular T/D model, the left testis was operated and the rotation reached 720° clockwise which lasted 1 h before reperfusion. The G-IP group accepted 100 µmol/kg of GYY4137 intraperitoneally 30 min after testicular rotation, while the G-IT group was treated with the same dose by intratesticular injection. Six h after detorsion, the testis was collected and subsequently assessed. The T/D group showed significant changes in histology and an enhancement in the level of oxidative stress and apoptosis compared to the sham-operation group. The expression of Caspase-3 and Bax turned out to be strengthened by T/ D and relatively decreased with GYY4137 treatment in both the G-IP and G-IT groups. Moreover, the Bcl-2 expression was inhibited in the T/D group, and promoted by GYY4137 in the G-IP and G-IT groups. GYY4137, moderating these observed changes, displayed a more protective effect with G-IT therapy than G-IP therapy.This study indicated that the efficacy of intratesticular therapy with GYY4137 is better than that of intraperitoneal therapy, which may provide a more valuable approach for testicular torsion therapy.

[PUBERTAL TESTICULAR TORSION OF POLYORCHIDISM DIAGNOSED IN INFANCY: A CASE REPORT].

Left polyorchidism was found in a 2-month-old boy with a left scrotal mass. As he was asymptomatic and all testes were in the scrotum, he was conservatively followed up. At 17 years of age, he presented with left acute scrotum due to testicular torsion of the left supernumerary testis. Counterclockwise 720-degree rotation of the left supernumerary testis was noted during emergency surgery, and orchidopexy of the 3 testes (2 left testes and 1 right testis) was performed. Biopsy of the left supernumerary testis demonstrated spermatogenesis and no malignancy. One and a half years after surgery, all testes were viable without atrophy.Polyorchidism is a rare condition and there is no consensus on the management of asymptomatic cases detected early in life. The position of the supernumerary testis (intrascrotal or extrascrotal) is important when deciding the management strategy because of the risk of malignancy. If conservative management is selected initially, elective surgery, such as prophylactic orchiectomy or orchidopexy, may be needed because of the risk of malignancy and torsion.

Acute scrotum and testicular torsion in children: a retrospective study in a single institution.

INTRODUCTION: Testicular torsion (TT), as per the reported incidences in children and preadolescents, is an emergency medical condition that requires prompt surgical treatment. In cases of TT, early and accurate diagnosis of acute scrotum (AS) is important to preserve testicular fertility. In this study, the authors aimed to determine the incidence, clinical examination, etiology, clinical predictors, and treatment of patients with AS and TT. MATERIAL AND METHODS: The authors retrospectively reviewed all children (age, ≤15 years) with AS who visited their hospital between January 2012 and June 2019. Data on age and diagnosis, clinical findings, mode of treatment, and blood examination results were collected. RESULTS: The authors examined 165 children aged between 0 days and 15 years (mean age, 9.4 years). Final diagnosis identified 72 patients with torsion of the appendix testis, 44 patients with epididymitis, and 38 patients with TT. Testes were salvaged in 23 of the 38 patients with TT (60.5%). Statistically significant variables revealed that the risk factors of TT were age (older than 12 years), white blood cell (WBC) count (>12,000 cells/mm3), and laterality (left side). The level of C-reactive protein (CRP), duration of symptoms, and degree of torsion were significantly higher in the non-salvageable testis group than in the salvageable testis group. Furthermore, the significant predictive factor for non-salvageable testis was the level of CRP >1.0 mg/dl. CONCLUSION: The study results indicates that age, WBC count, and laterality are key factors to distinguish TT from AS. Salvageability largely depended on the duration of symptoms and the degree of TT. The salvage rate of the testis can be improved by educating pediatricians, parents, patients, and medical staff about the early diagnosis and treatment of torsion.

The split sign: The MRI equivalent of the bell clapper deformity.

METHODS:: The cases of eight patients who underwent MRI and surgery for acute scrotum between January 2010 and January 2017 were evaluated. We recorded whether hyperintense fluid on T2 weighted images existed between the posterior aspect of the epididymis and the scrotal wall ("split sign") and investigated if it correlated with BCD in surgical findings. RESULTS:: In one patient without hydrocele, readers were unable to evaluate the anatomy of the tunica vaginalis. Among seven patients with hydrocele, five had the split sign and all were surgically confirmed as BCD. In two patients with hydrocele but no split sign, one had normal scrotal anatomy and the other had a BCD with a necrotic testis adherent to the scrotal wall. CONCLUSION:: The split sign on MRI corresponded well to the lack of fixation of the epididymis to the scrotal wall and detected BCD with high sensitivity (5/6). ADVANCES IN KNOWLEDGE:: A hyperintense area on T2 weighted image between the posterior aspect of the epididymis and scrotal wall ("split sign") is a useful MRI finding for diagnosing BCD.

Testicular Torsion Postorchiopexy: A Case of Twisted Hammock.

We herein report an unusual case of testicular torsion a decade after orchiopexy. An occurrence of postorchiopexy testicular torsion is an exceedingly rare event, infrequently reported in literature. Previously placed anchoring sutures in the inferior pole resulted in a "hammock" testicular torsion, resulting in twisting of cord with involvement of the sutures themselves.

Controversies in the management of neonatal testicular torsion: A meta-analysis.

OBJECTIVE: This meta-analysis seeks to discern the optimal management strategy in neonatal testicular torsion (NTT). METHODS: Reviewed all English-language articles published between 2005 and 2015 in Medline/Pubmed that had a defined diagnosis of NTT within the first thirty days of life, and discussed specific surgical and nonsurgical management. Exclusion criteria were non-English literature, case reports, case studies, and failure to clearly describe the management of NTT. Data from 9 studies were analyzed, individually and together as pooled data, using a random effect model with a random intercept to estimate the pooled proportions of interest. Results are presented with 95% confidence interval. All analyses were done in SAS 9.4®. RESULTS: 9 publications met criteria for this analysis with a total of 196 patients. Bilateral testicular torsions (n = 14) were less common as compared to right/left testicular torsion (n = 85/97). Asynchronous NTTs (n = 9) were more common than synchronous NTTs (n = 2). There was a higher incidence of NTT in neonates delivered by vaginal delivery (n = 110) as compared to those delivered by c-section (n = 25). Extravaginal torsion (n = 54) is far more common than intravaginal torsion (n = 2). Full-term neonates (n = 122) have a higher incidence of NTT as compared to preterm neonates (n = 9). A total of 15 testicles were salvaged. Of the salvaged testicles 2 were documented as prenatal, 10 postnatal and 3 were undocumented. A strategy of bilateral exploration allows for salvage of about 7% of ipsilateral testicles and prevent asynchronous torsion in about 4% of neonates. CONCLUSIONS: Based on our population, between 8-12% of patients would benefit from bilateral exploration at the time of diagnosis. We recommend urgent bilateral exploration with orchiopexy of the contralateral testicle in order to avert anorchia. TYPE OF STUDY: Systematic review. LEVEL OF EVIDENCE: Level 5 meta-synthesis (Evidence from systematic reviews of qualitative and descriptive studies).