Evaluating ChatGPT ability to answer urinary tract Infection-Related questions.

INTRODUCTION: For the first time, the accuracy and proficiency of ChatGPT answers on urogenital tract infection (UTIs) were evaluated. METHODS: The study aimed to create two lists of questions: frequently asked questions (FAQs, public-based inquiries) on relevant topics, and questions based on guideline information (guideline-based inquiries). ChatGPT responses to FAQs and scientific questions were scored by two urologists and an infectious disease specialist. Quality and reliability of all ChatGPT answers were checked using the Global Quality Score (GQS). The reproducibility of ChatGPT answers was analyzed by asking each question twice. RESULTS: All in all, 96.2 % of FAQs (75/78 inquiries) related to UTIs were correctly and adequately answered by ChatGPT, and scored GQS 5. None of the ChatGPT answers were classified as GQS 2 and GQS 1. Moreover, FAQs about cystitis, urethritis, and epididymo-orchitis were answered by ChatGPT with 100 % accuracy (GQS 5). ChatGPT answers for EAU urological infections guidelines showed that 61 (89.7 %), 5 (7.4 %), and 2 (2.9 %) ChatGPT responses were scored GQS 5, GQS 4, and GQS 3, respectively. None of the ChatGPT responses for EAU urological infections guidelines were categorized as GQS 2 and GQS 1. Comparison of mean GQS values of ChatGPT answers for FAQs and EAU urological guideline questions showed that ChatGPT was similarly able to respond to both question groups (p = 0.168). The ChatGPT response reproducibility rate was highest for the FAQ subgroups of cystitis, urethritis, and epididymo-orchitis (100 % for each subgroup). CONCLUSION: The present study showed that ChatGPT gave accurate and satisfactory answers for both public-based inquiries, and EAU urological infection guideline-based questions. Reproducibility of ChatGPT answers exceeded 90% for both FAQs and scientific questions.

Acute cytomegalovirus proctitis and epididymitis acquired via sexual transmission in an immunocompetent patient: a case report.

BACKGROUND: We present a case report of an immunocompetent host with presumed sexually transmitted cytomegalovirus proctitis and epididymitis, where there currently is a sparsity of published data. CASE PRESENTATION: A 21-year-old previously healthy Caucasian individual was admitted for severe rectal and testicular pain in the setting of proctitis and epididymitis. Serology and rectal pathology confirmed acute primary cytomegalovirus infection. CONCLUSIONS: This report details his diagnostic workup and highlights cytomegalovirus as a rare cause of sexually transmitted disease among immunocompetent persons.

Escroto agudo en el lactante / Acute scrotum in infants

El escroto agudo consiste en un cuadro clínico de dolor testicular asociado a signos inflamatorios locales, excepcional en neonatos y lactantes. Presentamos un caso de un lactante de 2 meses con tumefacción y eritema escrotal derecho de 48 horas de evolución y pico febril en Urgencias. A la exploración, teste doloroso a la palpación, con reflejo cremastérico presente. En la ecografía testicular se objetiva orquiepididimitis derecha. La analítica muestra leucocitosis, neutrofilia y mínima elevación de reactantes de fase aguda. En el urocultivo se aísla Escherichia coli. Recibe antibioterapia durante 2 semanas con buena evolución. La orquiepididimitis es la inflamación aguda del testículo y epidídimo, patología muy infrecuente en neonatos y lactantes. La diseminación hematógena es la causa más frecuente en este grupo de edad, siendo el germen más frecuente el E. coli. Por tanto, en neonatos y lactantes con orquiepididimitis, considerando el riesgo de bacteriemia asociada, resulta fundamental optimizar el diagnóstico, incluyendo un estudio completo de sepsis junto con la ecografía Doppler y el inicio precoz de la antibioterapia empírica (AU)

Acute scrotum consists of testicular pain associated with local inflammatory signs and is very unsual in neonates and infants.We present a case of a 2-month-old infant with right scrotal swelling and erythema of 48 hours' evolution. Peak fever in the emergency department. On examination, the teste was painful on palpation, with cremasteric reflex present. Testicular ultrasound showed right orchiepididymitis with associated hydrocele. Laboratory tests show leukocytosis, neutrophilia and minimal elevation of acute phase reactants. Urine culture isolated Escherichia coli. He received antibiotherapy for 2 weeks with good evolution.Orchiepididymitis is an acute inflammation of the testicle and epididymis, and it is a very rare pathology in neonates and infants. Haematogenous dissemination is the most frequent cause in this age group, with E. coli being the most frequently isolated germ. Therefore, in neonates and infants with orchiepididymitis, considering the risk of associated bacteraemia, it is essential to optimize the diagnosis by including a complete sepsis study together with Doppler ultrasound and the early initiation of empirical antibiotherapy. (AU)

[Action mechanisms of Xiaoluowan (II) in the treatment of epididymitis: A network pharmacology-based study].

OBJECTIVE: To explore the potential action mechanisms of Xiaoluowan (II) (XLW-II) in the treatment of epididymitis through a network pharmacology approach. METHODS: We searched various databases for relevant targets associated with epididymitis and XLW-II and obtained the common targets of epididymitis and XLW-II on the Venny platform. We acquired the protein-protein interactions (PPI) using the STRING data and had them visualized with the Cytoscape software. After topological analysis, we retrieved the key targets, followed by gene ontology (GO) and KEGG pathway enrichment analyses using the DAVID database. RESULTS: A total of 2 38 drug targets, 2 150 disease targets and 85 common targets were identified. The core targets for the treatment of epididymitis with XLW-II identified by PPI network analysis included TNF, IL6, IL1B, MMP9, AKT1, PTGS2 and TP53. GO function analysis revealed the involvement of the common targets in such biological processes as response to hypoxia, regulation of apoptotic processes, inflammatory response, and positive regulation of the MAPK cascade. KEGG pathway analysis suggested that the signaling pathways such as the cancer pathway, PI3K-Akt pathway, protein glycosylation pathway in cancer, Ras pathway and chemokine pathway might be related to the action mechanisms of XLW-II in the treatment of epididymitis. CONCLUSION: The potential targets and signaling pathways of Xiaoluowan (II) in the treatment of epididymitis were identified on the basis of network pharmacology, which has provided a novel insight into its action mechanisms and offered a new direction for further relevant studies.

[Mechanism of Xiaoluanwan(II) in treating mouse epididymitis through the regulation of NLRP3 inflammasome].

OBJECTIVE: This study aimed to investigate the mechanism of Xiaoluanwan(II) in treating lipopolysaccharide(LPS)-induced epididymitis and its impact on the NLRP3 inflammasome. METHODS: The murine epididymitis model was established through local injection of LPS. The study included a control group (n=5), a model group (n=5), a model group treated with Xiaoluanwan(II) (Ⅱ) (n=5), and a saline group treated with Xiaoluanwan(II) (n=5). After 14 consecutive days of oral administration of Xiaoluanwan(II) or physiological saline, pathological changes in the epididymal tissues, expression levels of NLRP3 inflammasome and Caspase-1, as well as associated protein levels were examined. RESULTS: Compared to the model group, Xiaoluanwan(II) significantly alleviated inflammatory cell infiltration and lesions, as evidenced by a reduction in the protein expression levels of NLRP3, Caspase-1, Cleaved-Caspase-1, IL-1ß, IL-18, GSDMD, and p-p38 MAPK (P<0.05 or P<0.01), thereby mitigating the inflammatory response. CONCLUSION: Xiaoluanwan(II) alleviates epididymal inflammation and ameliorates mouse epididymal epithelial injury by modulating the NLRP3-mediated cell pyroptosis pathway.

[Clinical observation of Xiaoluowan (II) in treating epididymitis].

OBJECTIVE: To observe the clinical efficacy of Xiaoluowan (II) on epididymitis. METHODS: 61 patients with epididymitis were divided into two groups, acute group (23 cases) and non-acute group (38 cases) . Both groups of patients were treated with Xiaoluowan (II) 6g twice a day orally, while acute group patients were given antibiotics intravenously. The treatment period is 4 weeks. The acute group evaluates the therapeutic efficacy comprehensively based on changes in clinical symptoms and signs, while recording changes in visual pain score (VAS). Chronic epididymitis symptom index (CESI) was used to evaluate the clinical symptoms before and after treatment in the non-acute group, and the curative efficacy was evaluated. RESULTS: After treatment, the VAS scores in the acute group decreased from 7.08 ± 1.09 to 2.10 ± 1.37 (P<0.05). Total efficiency is 82.60% . In the non-acute group, the scores of pain before and after treatment were 7.08 ± 1.09 and 2.10 ± 1.37, the scores of quality of life were 7.28 ± 1.14 and 1.87 ± 1.56, the total scores were 14.37 ± 1.78 and 3.97±2.73, respectively. The difference was significant(P<0.05). Total efficiency is 84.21% . CONCLUSION: Xiaoluowan (II) is an effective method to treat epididymitis and an effective supplement to modern medicine.

Sodium-glucose cotransporter 2 inhibitor-associated severe epididymo-orchitis.

A man in his late 50s, with uncontrolled type 2 diabetes mellitus (T2DM) and morbid obesity, presented to the hospital with complicated epididymo-orchitis. The onset of symptoms (scrotal pain, erythema and swelling) occurred after the use of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, for 2 months. His baseline antidiabetic medications were insulin, glipizide and metformin. Initially, he had failed treatment of epididymo-orchitis with oral levofloxacin for 3 weeks, followed by 2 weeks of doxycycline therapy. At the presentation to the hospital, an ultrasound of the scrotum revealed scrotal and right testicular abscess. The patient underwent right inguinal orchiectomy. Postoperatively, pus culture was positive for Enterococcus faecalis and Candida glabrata, and hence, he was treated with oral antibiotics including high-dose antifungal medications. Adequate wound care and regular follow-up demonstrated resolution of infection. This case highlights the risk of severe urogenital infection associated with the use of SGLT2 inhibitors in the setting of uncontrolled T2DM.

Advances in the antibiotic management of epididymitis.

INTRODUCTION: Acute epididymitis is commonly encountered and typically presents acutely within a wide clinical spectrum. Most cases of acute epididymitis are caused by bacterial infection, most often by sexually transmitted organisms and urinary pathogens. Current treatment regimens remain empirical, although recent advances using modern diagnostic techniques support a change in the management paradigm. AREAS COVERED: The choice of the initial antibiotic regimen is empirical and based on the most likely causative pathogen, whether sexually transmitted, enteric, or other. Adherence of clinical practice remains short of available guidance, which may be improved by thorough clinical and microbiologic assessment, supported by a knowledge of the commonly associated pathogenic organisms, and the appropriate choice of tests required for their identification. The use of advanced microbiology techniques and studies of current practice provide new insights that have challenged traditional management paradigms. The authors discuss these points and provide their expert perspectives on its treatment and future developments. EXPERT OPINION: Relatively sparse direct trial data exists on antimicrobial treatments for acute epididymitis. Much of the presently available guidance is derived from previous guidance recommendations, knowledge of antimicrobial activities of specific agents, and treatment outcomes in uncomplicated infections. Identification of specific pathogens and prescribing accuracy is dependent on the extent to which cases are investigated and is therefore variable.

Surgical management of tuberculous epididymo-orchitis: a retrospective study of 81 cases with long-term follow-up.

BACKGROUND: Nowadays, most studies of tuberculous epididymo-orchitis (TBEO) are case reports or small sample cohort series. Our study is aimed to present the largest series of TBEO with our management experiences and long-term follow-up outcomes. METHODS: Patients diagnosed with TBEO after surgical procedures at Department of Urology, West China Hospital from 2008 to 2019 were included. All clinical features, auxiliary examination results, treatment and histopathological findings were extracted if available. RESULTS: Eighty-one patients (mean age 50.77 ± 16.1 years) were included. Scrotal swelling (N = 47, 58.0%) and pain (N = 29, 35.8%) were the most common presenting complaint. Pyuria and microscopic hematuria were observed in twenty-two (27.2%) and eight patients (9.9%), respectively. Urine acid fast bacilli cultures were available in 16 patients and all were negative. The mean duration between the onset of symptoms and the definite diagnosis was 6.42 ± 7.0 months. TBEO was considered in 30 (37.0%), tumors in 28 (34.6%) and nonspecific bacterial epididymo-orchitis in 23 (28.4%) patients. All patients received triple therapy of chemotherapy-surgery-pharmacotherapy and definite diagnosis was confirmed through histopathology of surgical specimens. Fifty-five patients were followed up regularly (mean follow-up 82.35 ± 36.6 months). One patient (1.2%) died from liver cirrhosis and no recurrence was observed. Postoperative complications included erectile dysfunction in 4 patients (4.9%), premature ejaculation in 5 patients (6.2%) and sterility in 7 patients (8.6%). CONCLUSIONS: We recommend patients with advanced TBEO to receive triple therapy of chemotherapy-surgery-pharmacotherapy. Physicians should pay more attention to patients' sexual function and fertility during follow up after treatment completed.

[Global Testicular Infarction during Treatment for Epididymitis].

We report a case of global testicular infarction associated with epididymitis. A 26-year-old man with a history of clean intermittent self-catheterization since he was 1 year old presented to our hospital with left scrotal pain and swelling. He was diagnosed with epididymitis and was prescribed levofloxacin. On the next day, he returned with worsened symptoms of left scrotal pain, swelling, and fever. He was admitted because of his severe symptoms and high C-reactive protein level in the blood test. Antimicrobial therapy with intravenous flomoxef and analgesic treatment with pentazocine and loxoprofen were started but the symptoms did not improve. The color-Doppler ultrasound repeated on the 1st, 4th, and 5th day of admission showed left epididymal hypervascularity but it did not indicate testicular hypovascularity in any examinations. On the 6th day of admission, a contrast-magnetic resonance imaging (MRI) scan revealed no contrast enhancement in the left testis and high orchiectomy was performed. On pathological examination, abscess of the entire epididymis and generalized necrosis of the testes were observed. Inflammatory cell infiltration and thrombus formation were observed in almost all veins of the testis and spermatic cord, and the diagnosis of global testicular infarction associated with epididymitis was made. Global testicular infarction has been reported as a rare complication of epididymitis and should be considered in the case of atypical course of epididymitis.

United Kingdom British association for sexual health and HIV national guideline for the management of epididymo-orchitis, 2020.

The British Association for Sexual Health and HIV (BASHH) UK guideline for the management of epididymo-orchitis has been updated in 2020. It offers advice on diagnostic tests, treatment and health promotion principles in the effective management of epididymo-orchitis. Empirical treatment should be started in patients with objective swelling and tenderness on testicular examination. First-line empirical treatment for sexually acquired epididymo-orchitis has changed to ceftriaxone 1g intramuscularly and doxycycline. Higher dose of ceftriaxone in line with the BASHH 2018 gonorrhoea guideline ensures effective treatment of strains with reduced susceptibility. Ofloxacin or doxycycline is recommended in patients with epididymo-orchitis probably due to non-gonococcal organisms (e.g. negative microscopy for gram-negative intracellular diplococci or no risk factors for gonorrhoea identified). Where Mycoplasma genitalium is tested and identified, treatment should include an appropriate antibiotic (e.g. moxifloxacin). If enteric pathogens are a likely cause (e.g. older patient, not sexually active, recent instrumentation, men who practice insertive anal intercourse, men with known abnormalities of the urinary tract or a positive urine dipstick for leucocytes and nitrites), ofloxacin and levofloxacin are recommended. A clinical care pathway has been produced to simplify the management of epididymo-orchitis. A patient information leaflet has been developed.

Evaluating the Necessity of Antibiotics in the Treatment of Acute Epididymitis in Pediatric Patients: A Literature Review of Retrospective Studies and Data Analysis.

OBJECTIVES: This literature review and data analysis aims to evaluate the percentage of pediatric patients with acute epididymitis found to have bacterial etiology and the percentage of patients in these studies that were treated with antibiotic therapy versus conservative therapy. METHODS: A search of EBSCO through January 13, 2016, using the key words epididymitis or epididymo-orchitis and child, children, or pediatric, identified 542 potential studies.Twenty-seven retrospective studies met the inclusion criteria, containing patients aged 21 years or younger with acute epididymitis or epididymoorchitis. The number and age of patients, urine cultures and urinalysis results, number of patients treated with antibiotics, and incidence were extracted. RESULTS: A total of 1496 patients with acute epididymitis were identified. A urinalysis was obtained for 1124 patients, and 190 (16.9%) were positive. Aurine culturewas obtained for 670 patients, and 100 (14.9%) were positive. Fourteen studies addressed antibiotic administration wherein 652 patients were with acute epididymitis and 554 (85%) received antibiotics.Of 502 patients with urinalysis results, urine culture results, and antibiotic treatment rates, 54 (10.8%) were positive for a bacterial source. Antibiotics were administered to 410 (81.7%) of these 502 patients. CONCLUSIONS: Practitioners should consider only prescribing antibiotics to patients with acute epididymitis if there is an abnormal urinalysis or urine culture.

Epididymitis and its aetiologies in a central London sexual health clinic.

Epididymitis is a common cause of scrotal pain presentation in sexual health clinics; however, it is unclear what fraction is attributable to transmissible infections. We, therefore, reviewed the aetiologies causing epididymitis. A retrospective data analysis of all cases of epididymitis diagnosed from January 2018 to December 2018 in three sexual health clinics was conducted, collecting demographics, results, management and symptom resolution at two weeks follow up. A total of 127 cases of epididymitis (mean age 32 years, heterosexual 97, MSM 30) were included. Among them 14 cases (11%) were caused by sexual transmitted infections (<35 years n = 9; >35 years n = 5): seven cases of chlamydia, six gonorrhoea, one syphilis and one trichomonas vaginalis. There were three cases of urinary tract infection diagnosed. All cases were treated with antibiotics recommended by the British Association for Sexual Health and HIV (BASHH). At two weeks follow up post-treatment 10 (7%) were symptomatic; 91% did not attend for follow up. Sexually transmitted infections were associated with acute epididymitis in 11% of this study cohort.

Acute epididymo-orchitis from brucellosis melitensis in Australia.

Brucellosis epididymo-orchitis (BEO) is extremely rare in non-endemic areas such as Australia. While epididymo-orchitis is relatively common in adolescent men, when presented with a significant travel history, consideration should be given to rare causes such as this. Here, we present a case of BEO in a young 18-year-old man who recently migrated from Greece, with symptoms of acute scrotal pain, swelling and persistent fever. Brucella melitensis was isolated in the blood culture and confirmed with PCR. We suspect transmission was related to ingestion of unpasteurised goat dairy products. He made a full recovery after 7 days of intravenous gentamicin and 6 weeks of oral doxycycline. BEO should be considered in those who present with acute scrotal pain and fever after a recent history of travel to or from a brucellosis- endemic area.

Clinical pharmacokinetics of oral azithromycin in epididymal tissue.

OBJECTIVES: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. RESULTS: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 µg/mL at 2.42 h in serum and 1.96 µg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 µg/mL in serum and 0.795 µg/g in epididymal tissue. CONCLUSIONS: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

Dexamethasone improves therapeutic outcomes in a preclinical bacterial epididymitis mouse model.

STUDY QUESTION: Can dexamethasone improve infertility-related cauda epididymidal tissue damage caused by bacterial epididymitis? SUMMARY ANSWER: Dexamethasone in addition to anti-microbial treatment effectively reduces long-term deleterious epididymal tissue damage by dampening the host's adaptive immune response. WHAT IS KNOWN ALREADY: Despite effective anti-microbial treatment, ~40% of patients with epididymitis experience subsequent sub- or infertility. An epididymitis mouse model has shown that the host immune response is mainly responsible for the magnitude of epididymal tissue damage that is fundamentally causative of the subsequent fertility issues. STUDY DESIGN, SIZE, DURATION: Bacterial epididymitis was induced in male mice by using uropathogenic Escherichia coli (UPEC). From Day 3 after infection onwards, mice were treated with daily doses of levofloxacin (20 mg/kg, total n = 12 mice), dexamethasone (0.5 mg/kg, total n = 9) or both in combination (total n = 11) for seven consecutive days. Control animals were left untreated, i.e. given no interventional treatment following UPEC infection (total n = 11). Half of the animals from each group were killed either at 10 or 31 days post-infection. PARTICIPANTS/MATERIALS, SETTING, METHODS: A mouse model of induced bacterial epididymitis was applied to adult male C57BL/6J mice. At the respective endpoints (10 or 31 days post-infection), epididymides were collected. Effectiveness of antibiotic treatment was assessed by plating of epididymal homogenates onto lysogeny broth agar plates. Overall tissue morphology and the degree and nature of tissue damage were assessed histologically. Quantitative RT-PCR was used to assess local cytokine transcript levels. Blood was drawn and serum analysed for systemic IgG and IgM levels by ELISA. In addition, correlation analyses of clinical data and serum-analyses of IgG and IgM levels in patients with epididymitis were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The addition of dexamethasone to the standard anti-microbial treatment did not further worsen epididymal tissue integrity. In fact, an obviously dampened immune response and reduced tissue reaction/damage was observed at both 10 and 31 days post-infection following combined treatment. More specifically, epididymal duct continuity was preserved, enabling sperm transit. In contrast, in untreated or antibiotic-treated animals, damage of the epididymal duct and duct constrictions were observed, associated with a lack of cauda spermatozoa. In line with the bacteriostatic/bactericidal effect of levofloxacin (alone as well as in combination), local cytokine transcript levels were significantly and similarly reduced in animals treated with levofloxacin alone (P < 0.01) or in combination with dexamethasone (P < 0.05) compared to UPEC-infected untreated animals. Interestingly, the addition of dexamethasone to the anti-microbial treatment induced a unique dampening effect on adaptive immunity, since systemic IgG and IgM levels as well as the pan-T cell marker CD3 were reduced at both 10 and 31 days post-infection. LIMITATIONS, REASONS FOR CAUTION: Breeding studies to address the fertility-protecting effect of the combined treatment were not possible in the experimental animals because the vas deferens was ligated (model specific). WIDER IMPLICATIONS OF THE FINDINGS: Whereas innate immunity is necessary and involved in acute bacterial clearance, adaptive immunity seems to be responsible for long-term, subclinical immunological activities that may negatively affect the pathogenesis of bacterial epididymitis even after effective bacterial eradication. These effects can be reduced in mice by the additional treatment with dexamethasone. This immunological characteristic of bacterial epididymitis shows similarities to the Jarisch-Herxheimer reaction known from other types of bacterial infection. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Deutsche Forschungsgemeinschaft, Monash University and the Medical Faculty of Justus-Liebig University to the International Research Training Group on 'Molecular pathogenesis of male reproductive disorders' (GRK 1871). R.W., K.L.L. and M.P.H. were supported by grants from the National Health and Medical Research Council of Australia (ID1079646, ID1081987, ID1020269 and ID1063843) and by the Victorian Government's Operational Infrastructure Support Program. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: No clinical trial involved.

Traditional Chinese medicine on treating epididymitis: A systematic review and meta-analysis protocol.

BACKGROUND: Epididymitis is a common disease in nonspecific infections of the male reproductive system according to the clinical incidence of acute epididymitis and chronic epididymitis. Many clinical trials have proven that Chinese medicine has a significant effect in the treatment of epididymitis. In this systematic review, we aim to evaluate the effectiveness and safety of traditional Chinese medicine (TCM) for epididymitis. METHODS: We will search for PubMed, Cochrane Library, AMED, Embase, WorldSciNet, Nature, Science online, China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of epididymitis. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of TCM for treating epididymitis. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.Registration number: PROSPERO CRD42019130569.

Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy.

BACKGROUND: Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life-threatening immune-related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies. CASE PRESENTATION: We describe herein a patient with metastatic melanoma who developed epididymo-orchitis followed by encephalitis while receiving pembrolizumab. The patient developed testicular pain and fever after his third dose of pembrolizumab; ultrasound evaluation demonstrated bilateral epididymo-orchitis. He then developed headaches, fever, and altered mental status over the next week and was admitted to the hospital. Lumbar puncture revealed inflammatory changes consistent with meningoencephalitis; he did not improve with broad-spectrum antibiotics, and an extensive workup for infectious etiologies, including cerebrospinal fluid testing using a clinical metagenomic next-generation sequencing assay, was negative. He received high-dose steroids for suspected autoimmune encephalitis, and both his orchitis and meningoencephalitis improved rapidly after one dose. He fully recovered after a 5-week taper of oral steroids. DISCUSSION: Here, we report a case of epididymo-orchitis complicating immune checkpoint inhibitor therapy. This patient subsequently developed severe encephalitis but rapidly improved with steroids. Clinicians should be aware of rare complications of these agents. KEY POINTS: Epididymo-orchitis is a rare and potentially life-threatening complication of anti-programmed death protein 1 (anti-PD-1) therapy.For patients on anti-PD-1 therapy who develop either epididymo-orchitis or epididymitis without clear infectious cause, immune-related adverse events should be considered in the differential diagnosis.If severe, epididymo-orchitis related to anti-PD-1 therapy may be treated with high-dose corticosteroids.