Fever of unknown origin revealing testicular nocardiosis: a case report and literature review.

BACKGROUND: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. CASE PRESENTATION: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. CONCLUSIONS: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

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.

Antimicrobial peptide MPX attenuates LPS-induced inflammatory response and blood-testis barrier dysfunction in Sertoli cells.

Orchitis accounts for a high proportion of male animal reproductive disorders. Hence, it is urgent to identify drugs for the prevention and treatment of orchitis. Antimicrobial peptides (AMPs) are currently recognized as one of the most promising alternatives to antibiotics. However, the protective effects of AMPs on lipopolysaccharide (LPS)-induced orchitis have not been reported. In this study, we developed an LPS-induced orchitis model in which primary bovine Sertoli cells were used as model cells. MPX was indicated to effectively reduce the inflammatory response of Sertoli cells. MPX attenuated the gene expression of the proinflammatory cytokines TNF-α, IL-6 and IL-1ß by suppressing the MAPK pathway, especially the phosphorylation of p38 and ERK. MPX also decreased the oxidative stress response caused by LPS and upregulated Occludin and Claudin-1 expression, thereby maintaining the integrity of the blood-testis barrier. Moreover, we found that MPX inhibited apoptosis in Sertoli cells. In a mouse model, we found that MPX significantly inhibited the disruptive effects of LPS, reducing seminiferous epithelium damage, vacuolations, hyperplasia, and apoptosis in spermatogenic cells and rescuing spermatogenesis. In addition, the expression of inflammatory factors such as IL-1ß, IL-18, IL-6 and TNF-α was decreased after MPX treatment in the mouse testes. MPX had no effect on other organs in mice, indicating its safety. This study was undertaken to investigate how MPX regulates the inflammatory response in Sertoli cells and provide a reference for the clinical prevention and treatment of male animal orchitis.

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.

Effects of Rosmarinus officinalis on orchitis following spermatic cord torsion-detorsion in male mice with emphasis on anti- inflammatory and antioxidant properties.

Orchitis as inflammation of testis occurs following traumatic injuries such as testicular torsion leading to high levels of oxidative stress and inflammation. Rosmarinus officinalis is a herb with anti-inflammatory and antioxidant properties. This study assessed therapeutic effects of rosemary following testicular torsion. A total of 36 male mice were categorised; control, torsion, rosemary (100 and 200 mg/kg) and torsion+rosemary groups. Torsion was induced surgically, and rosemary was gavaged. Total antioxidant capacity of extract was approved by Ferric Reducing Ability of Plasma. Malondialdehyde and Griess protocols were hired to assess oxidative stress. Finally, sperm parameters and testosterone levels were analysed. Immunofluorescent (of Tumour Necrosis Factor Alpha), hematoxylin and eosin stainings and expression of inflammatory genes (Interleukin-1α, Interleukin-1ß, Interferon-γ) were also assessed. Data were analysed using SPSS (v. 19), and graphs were drawn by GraphPad Prism (v. 9). Significantly (p < .05), oxidative stress indices and inflammatory genes expression were increased in torsion group, and total antioxidant capacity was increased in rosemary groups. In torsion+rosemary groups, total antioxidant capacity, sperm parameters and testosterone levels were increased, and inflammatory gene expression decreased significantly (p < .05). Rosemary with anti-inflammatory and antioxidant properties accelerates testicular healing in torsion cases, especially in therapeutic dose of 200 mg/kg.

Aspirin Alleviates Particulate Matter Induced Asymptomatic Orchitis of Mice via Suppression of cGAS-STING Signaling.

As an important source of air pollutant, airborne particulate matter (PM) has become a major threat to public health. Orchitis is characterized by acute or chronic testicular inflammation and is a primary cause of male infertility. Although accumulating evidence indicates that PM exposure is associated with increased male infertility rates, the mechanism by which PM is involved is not well understood. Here, we found that short-term PM exposure activated NF-κB signaling in mouse Leydig cells and testes and leading to asymptomatic orchitis. Analyzing the mitochondrial abundance and cGAMP levels in PM exposed mouse Leydig cells, we found that PM exposure induced mitochondrial injury and mtDNA release, leading to inflammation via the cGAS-STING axis. We also found that aspirin-induced acetylation of cGAS inhibited the inflammation in mice after PM exposure, especially in the testes. Moreover, aspirin pretreatment rescued offspring growth in PM-exposed mice. In summary, our study not only provides evidence that PM-induced asymptomatic orchitis in mice may be amenable to aspirin pre-treatment by acetylating cGAS, but also provides a potential explanation for male infertility caused by air pollutants.

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.

Hard bilateral syphilitic testes with vasculitis: a case report and literature review.

BACKGROUND: We report the case of a patient with syphilitic testicular gumma and vasculitis with adrenal failure due to chronic steroid use. CASE PRESENTATION: A 63-year-old male presented with hard right eye swelling and very firm bilateral testes on palpation, which he had for 2 years. Testicular tumor markers were negative; syphilis test was positive. Radiological examination suggested aortitis and bilateral testicular malignancy. The patient received ampicillin for the infection and prednisolone for vasculitis. Left orchidectomy was performed to confirm the presence of testicular tumor; histological examinations revealed granulomatous orchitis. The prednisolone doses were adjusted because of relapses and adverse effects of steroid use. Unfortunately, the patient died in the intensive care unit because of uncontrolled blood pressure and pneumonia. CONCLUSIONS: This is a rare case of syphilis with testicular involvement and vasculitis. This report shows the importance of broadening the differential diagnoses of testicular firmness.

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.

Case Report: A Rare Case of Crimean-Congo Hemorrhagic Fever Associated with Epididymo-Orchitis.

Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease that affects multiple organ systems and is characterized by extensive ecchymosis, internal hemorrhage, and hepatic dysfunction. The reported case fatality rate varies between 8% and 80%. It is frequently transmitted by Hyalomma ticks, which are endemic in the Northeast Anatolia region of Turkey in spring and summer. Our patient presented from an endemic area with fever, malaise, joint pain, and scrotal pain following a tick bite, and real-time PCR analysis of venous blood was positive for CCHF. Based on Doppler ultrasound performed because of the patient's scrotal pain, he was diagnosed as having epididymo-orchitis, which was considered secondary to CCHF after ruling out other etiologies and resolved with scrotal elevation and anti-inflammatory treatment. Being a very rare complication, this report aimed to document this case of CCHF-associated epididymo-orchitis in the literature.

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.

Methane Ameliorates Lipopolysaccharide-Induced Acute Orchitis by Anti-inflammatory, Antioxidative, and Antiapoptotic Effects via Regulation of the PK2/PKR1 Pathway.

OBJECTIVE: The present study is aimed at investigating the anti-inflammatory, antioxidative, and antiapoptotic effects of methane on lipopolysaccharide- (LPS-) induced acute orchitis and its potential mechanisms. METHODS: Adult male rats were intraperitoneally (i.p.) injected with methane-rich saline (MS, 20 mL/kg) following LPS (5 mg/kg, i.p.). The survival rate was assessed every 12 h until 72 h after LPS induction, and surviving rats were sacrificed for further detection. The wet/dry (W/D) ratio was determined, and testicular damage was histologically assessed. Inflammatory cytokines in the testes and serum, including interleukin-1ß (IL-1ß), IL-6, IL-10, and tumor necrosis factor-α (TNF-α), were measured using ELISA and RT-qPCR. Oxidative stress was evaluated by the level of superoxide dismutase (SOD) and malondialdehyde (MDA). Testicular apoptosis was detected via TUNEL staining. The expression of prokineticin 2 (PK2)/prokineticin receptor 1 (PKR1) was also analyzed using RT-qPCR, western blotting, and immunohistochemistry. RESULTS: It was found that methane significantly prolonged rat survival, decreased the W/D ratio, alleviated LPS-induced histological changes, and reduced apoptotic cells in the testes. Additionally, methane suppressed and promoted the production of pro- and anti-inflammatory cytokines, respectively. Furthermore, methane significantly increased SOD levels, decreased MDA levels, and decreased testicular expression of PK2 and PKR1. Therefore, methane exerts therapeutic effects on acute orchitis and might be a new and convenient strategy for the treatment of inflammation-related testicular diseases.

Protective effect of Alpha-Linolenic acid on Lipopolysaccharide-Induced Orchitis in mice.

Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) have anti-inflammatory effects. One specific PUFA, alpha-linolenic acid (ALA), shows both anti-inflammatory and antioxidant properties. In the testes, inflammatory mediators are known to increase when orchitis is induced by bacterial lipopolysaccharide (LPS). This study aimed to determine whether the anti-inflammatory properties of ALA could have a protective effect against LPS-induced orchitis in mice. The mice were divided into untreated control, orchitis and ALA-treated orchitis groups. Orchitis was induced by intraperitoneal injection of LPS. The ALA-treated group was administered ALA by gavage three days before intraperitoneal LPS injection. Cyclooxygenase-2 (COX-2), cytosolic phospholipase A2 (cPLA2), inducible nitric oxide synthase (iNOS) enzymes and nuclear factor kappa-B (NF-κB) in the testes, as well as serum interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α), were analysed using enzyme-linked immunosorbent assay (ELISA) tests. LPS administration increased the expression of several inflammatory mediators, including IL-6, TNF-α and NF-κB, as well as the COX-2, cPLA2 and iNOS enzymes. ALA administration significantly prevented the LPS-induced increases in these inflammatory mediators and enzymes (p < .05). The anti-inflammatory and antioxidant effects of ALA may make it a useful candidate for the treatment of orchitis caused by bacterial LPS.

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.

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.

Acute epididymo-orchitis due to Salmonella Typhi in a young man from Bangladesh.

S. typhi infection rarely involves the genitourinary system. We report the first described case of acute epididymo-orchitis due to S. typhi in a 14-year-old boy from Bangladesh. A high index of suspicion should be maintained when evaluating patients coming from endemic countries also in case of unusual sites of infection.

Atypical testicular pain.

Testicular tuberculosis (TB) is rare, and, because of this, the lack of pathognomonic clinical features and its tendency to mimic other commoner conditions, the diagnosis is frequently delayed or may be missed. In this case, the initial clinical presentation was typical for bacterial epididymo-orchitis in a 38-year-old man. When the patient failed to improve with standard treatment including broadening of antibiotics, the diagnosis was re-considered because some unusual signs suggested testicular malignancy or lymphoma. Further, history-taking and subsequent cross-sectional imaging with CT/MRI identified co-existent pulmonary nodularity, thoracic and abdominal lymphadenopathy and bony changes that, together, raised the suspicion of TB. Mycobacterium tuberculosis was confirmed on DNA-based testing of the hydrocele fluid, although standard acid-fast bacilli culture was negative. This case prompted a review of the literature to explore the optimal steps in the investigation and diagnosis of this rare disease.

Positron emission tomography and reframing vasculitis as a spectrum of disease when investigating a patient with a fever of unknown origin.

A retired businessman presented to the infectious diseases department with a history of ongoing fevers and myalgia and raised inflammatory markers. This continued despite adequate antibiotic treatment of an epididymo-orchitis. Extensive investigations, including bone marrow and liver biopsies and a positron emission tomography, did not reveal a cause but showed reactive change in the bone marrow. Later, he developed a vasculitic rash and vision loss due to non-arteritic anterior ischaemic optic neuropathy. High-dose steroids were immediately initiated. A temporal artery biopsy was performed, which confirmed a healing large vessel vasculitis, possibly giant cell arteritis. He has responded very well to therapy. We must better appreciate the limitations of positron emission tomography in investigating a fever of unknown origin. The case also encourages awareness of autoimmune disorders as the leading category of causative diseases for this in older age groups.

Testicular plasmacytoma misdiagnosed as orchitis.

Testicular plasmacytomas are rare, accounting for only 1.3% of all extramedullary plasmacytomas. The infrequency in which it is encountered, coupled with its non-specific clinical and sonographic presentation, makes its diagnosis a challenge. We present a case of a 70-year-old man with multiple myeloma, which was systemically responding to chemotherapy, who developed testicular swelling, erythema and pain. Ultrasound findings were concerning for infection, although urine and serum testing were unremarkable. The patient did not improve after several rounds of antibiotics prompting further evaluation. The patient underwent radical orchiectomy which revealed testicular plasmacytoma. Fluorescent in situ hybridisation (FISH) of the testicular tissue noted mutations which had not been present in the FISH analysis of bone marrow. Positron emission tomography scan later revealed new retroperitoneal plasmacytomas involving the new clone and his chemotherapy regimen needed to be adjusted for treatment.