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.

Multimodal ultrasound diagnosis of epididymo-orchitis with secondary testicular infarction: A case report.

We report a case of a 48-year-old man with testicular infarction caused by epididymo-orchitis (EO). Multimodal ultrasound showed extensive necrosis of the testis, and the patient underwent right orchiectomy. Postoperative pathology confirmed extensive necrosis of the testis. After 3 months of follow-up, the examination of scrotal ultrasound showed that the left testis and epididymis had no obvious abnormality.

Association between left-sided varicocele and epididymo-orchitis with sonographic findings.

OBJECTIVE: The aim of this study was to investigate the relationship between left-sided varicocele and epididymitis or epididymo-orchitis. MATERIALS AND METHODS: The study included 72 patients with left side epididymitis (EP) or epididymo-orchitis (EPO) (Group 1) and a control group of 72 patients without EP or EPO (Group 2). Those with right EP-EPO were excluded due to possible other underlying retroperitoneal pathologies causing varicocele. Groups were evaluated for presence of left side varicocele, varicocele grade and pampiniform plexus vein diameter. RESULTS: The average age was 38 ± 8.4 years (range, 18-50 years) in Group 1, and 36 ± 9.1 years (range, 16-47 years) in Group 2. Varicocele was significantly more common in patients with EP or EPO (p < 0.001). The rate of varicocele was 66.7% (48/72) in Group 1, and 22.3% (16/72) in Group 2. The median grade of varicocele was 2 in Group 1, and 0 in Group 2. Pampiniform plexus vein diameters were found to be significantly larger in patients with EP or EPO compare to patients without EP and EPO. The median vein diameter was 3.3 mm with the 25th and 75th percentiles at 2.7 and 3.8 mm, and was 1.9 mm with the 25th and 75th percentiles at 1.7 and 2.3 mm, respectively (p < 0.001). CONCLUSIONS: Left-sided varicocele was significantly more common in patients with EP or EPO and it is an important cause for the development of EP/EPO because of chronic venous stasis.

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.

Fibrinonecrotic enteritis and orchitis associated with Salmonella enterica subsp houtenae infection in a short-tailed boa (Boa constrictor amarali).

Salmonella enterica subsp houtenae has been recovered from a wide variety of species, including reptiles, and has been linked to important clinical manifestations in snakes and lizards. We describe a case of concomitant fibrinonecrotic enteritis and orchitis associated with S. enterica subsp houtenae infection in a short-tailed boa (Boa constrictor amarali). At necropsy, the mucosa of the large intestine was covered by a focally extensive fibrinonecrotic exudate (diphtheritic pseudomembrane). The left testicle was enlarged, firm and diffusely expanded by a thick fibrinous yellow exudate. Polymerase chain reaction and conclusive antigenic testing indicated that the bacteria isolated from the lesions were S. enterica subsp houtenae, and the virulence genes InvA, slyA, stn and spvC were identified. This report reinforces that, although S. enterica subsp houtenae has been isolated from asymptomatic reptiles, it has the potential to cause life-threatening disease in snakes.

Iron regulatory proteins 1 and 2 have opposing roles in regulating inflammation in bacterial orchitis.

Acute bacterial orchitis (AO) is a prevalent cause of intrascrotal inflammation, often resulting in sub- or infertility. A frequent cause eliciting AO is uropathogenic Escherichia coli (UPEC), a gram negative pathovar, characterized by the expression of various iron acquisition systems to survive in a low-iron environment. On the host side, iron is tightly regulated by iron regulatory proteins 1 and 2 (IRP1 and -2) and these factors are reported to play a role in testicular and immune cell function; however, their precise role remains unclear. Here, we showed in a mouse model of UPEC-induced orchitis that the absence of IRP1 results in less testicular damage and a reduced immune response. Compared with infected wild-type (WT) mice, testes of UPEC-infected Irp1-/- mice showed impaired ERK signaling. Conversely, IRP2 deletion led to a stronger inflammatory response. Notably, differences in immune cell infiltrations were observed among the different genotypes. In contrast with WT and Irp2-/- mice, no increase in monocytes and neutrophils was detected in testes of Irp1-/- mice upon UPEC infection. Interestingly, in Irp1-/- UPEC-infected testes, we observed an increase in a subpopulation of macrophages (F4/80+CD206+) associated with antiinflammatory and wound-healing activities compared with WT. These findings suggest that IRP1 deletion may protect against UPEC-induced inflammation by modulating ERK signaling and dampening the immune response.

Ultrasound diagnosis of Mondor's disease involving the superficial scrotal veins: Unveiling a rare mimicker of acute scrotal emergencies.

We describe a rare case of Mondor disease of the superficial scrotal veins, which can clinically mimic acute testicular pathologies such as testicular torsion or epididymo-orchitis, and highlight the value of grayscale/Doppler ultrasound examination in distinguishing these entities, which have different management implications.

Brucella infection in rough-toothed dolphin (Steno bredanensis) with severe orchitis stranded on the Pacific coast of Japan.

In the western North Pacific, prominent granulomatous testes have been detected in many Brucella-infected common minke whales (Balaenoptera acutorostrata), but there have been no reports in toothed cetaceans. We found severe orchitis with granulomatous lesions in a rough-toothed dolphin (Steno bredanensis) stranded on the Pacific coast of Japan in 2011. Histopathological examination revealed leukocyte infiltration of the lesions. DNA from the lesion was analyzed by PCR and it showed molecular biological similarities with those of Brucella-infected common minke whales and Brucella ceti of sequence-type 27 (ST27). These results suggest that the type of Brucella ceti that infected the dolphin was ST27, which may have caused severe orchitis. This study adds to our understanding of Brucella infections in marine mammals.

Gasdermin D in macrophages drives orchitis by regulating inflammation and antigen presentation processes.

Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using antibiotics and broad-spectrum anti-inflammatory drugs are ineffective against non-bacterial orchitis and induce side effects. This highlights the need to explore the pathogenesis of orchitis and develop alternative therapeutic strategies. In this study, we demonstrated that Gasdermin D (GSDMD) was activated in the testes during uropathogenic Escherichia coli (UPEC)-induced acute orchitis, and that GSDMD in macrophages induced inflammation and affected spermatogenesis during acute and chronic orchitis. In testicular macrophages, GSDMD promoted inflammation and antigen presentation, thereby enhancing the T-cell response after orchitis. Furthermore, the pharmacological inhibition of GSDMD alleviated the symptoms of UPEC-induced acute orchitis. Collectively, these findings provide the first demonstration of GSDMD's role in driving orchitis and suggest that GSDMD may be a potential therapeutic target for treating orchitis.

Granulomatous orchitis: A case report of misdiagnosis and review of the literature.

Granulomatous orchitis is a relatively rare clinical testicular lesion. The imaging manifestations and clinical symptoms are similar to those of testicular tumors. In order to improve the understanding of this disease, this article reports the ultrasonographic manifestations of a case of granulomatous orchitis and reviews the relevant literature with.

Paediatric acute epididymo-orchitis temporally related to SARS-CoV-2 infection: A case series and review of the literature.

INTRODUCTION: Acute epididymo-orchitis (AEO) is becoming an increasingly common differential diagnosis in children with acute scrotal pain. It has been noted in adult men that SARS-CoV-2 has a propensity for involving the testis and epididymis, affecting sperm and testosterone production. Our literature search revealed only one case report of COVID-19 presenting with epididymo-orchitis in a child. We present three more children who presented with AEO, all recovering from PCR-confirmed SARS-CoV-2 infection. This article reviews the post-inflammatory aetiology of paediatric epididymo-orchitis, and the propensity SARS-CoV-2 has for the testis. PATIENTS AND METHODS: Two pre-pubertal ten-year-old patients presented to the emergency department with a 48-h history of gradual onset unilateral scrotal pain and increasing erythema of the ipsilateral scrotal skin. One fifteen-year-old boy was referred for ongoing symptoms four days following a diagnosis of AEO made by his General Practitioner. On further questioning, all three had PCR-confirmed COVID infection two weeks prior to the onset of their scrotal symptoms and had just ended their isolation period. A literature search was then performed using the keywords SARS-CoV-2, testes and paediatric acute epididymo-orchitis. DISCUSSION: The SARS-Cov-2 virus has a propensity for affecting the testis and epididymis. This puts patients at increased risk of acute epididymo-orchitis during COVID infections. The inflammation induced by the virus appears to affect the cells responsible for testosterone production and sperm quality. However, there is no evidence that viral transmission can happen via semen. CONCLUSION: SARS-Cov-2 infection can lead to acute epididymo-orchitis. Knowledge of this is clinically significant, firstly to avoid unnecessary surgical intervention due to a mistaken diagnosis of testicular torsion and secondly, due to the potential of the virus to affect sperm quality and testosterone production.

Salidroside Ameliorates Furan-Induced Testicular Inflammation in Relation to the Gut-Testis Axis and Intestinal Apoptosis.

Furan is a heat-induced food contaminant, and it causes damage to visceral organs, including the testis. To determine the mechanism of the damage to the testis, a mouse model treated with furan (8 mg/kg bw/day) and salidroside (SAL, 10/20/40 mg/kg bw/day) was established, and levels of testicular functional markers and changes of morphology were investigated in furan-induced mice treated with SAL. The change in related proteins and genes suggested that SAL restored the furan-mediated leaky tight junction and triggered the TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome together with inflammation. To find out the gut-testis axis, microbiota PICRUSt analysis and correlation analysis were conducted to investigate the core microbiota and metabolites. The endoplasmic reticulum stress (ERS)-related key protein levels and the result of transmission electron microscopy suggested that SAL inhibited the furan-induced intestinal ERS. The result of TUNEL and levels of apoptosis-related proteins suggested that furan-induced intestinal apoptosis was alleviated by SAL. Collectively, SAL inhibited furan-induced ERS-mediated intestinal apoptosis through modulation of intestinal flora and metabolites, thus strengthening the gut barrier. It inhibited LPS from entering the circulatory system and suppressed the testicular TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome, which alleviated testicular inflammation.

Testicular involvement of Brucellosis: A 10-year, multicentre study.

INTRODUCTION: The genito-urinary system is one of the most common areas of involvement in brucellosis. To present the epidemiological, clinical, and laboratory characteristics of patients with testicular involvement associated with brucellosis, together with the diagnostic and therapeutic approaches. METHODOLOGY: Patients followed up for brucellosis-related testicular involvement between January 2012 and November 2022 were included in the study. Brucellosis is defined as the production of Brucella spp. in cultures, or clinical symptoms together with the serum standard tube agglutination test titer of ≥ 1/160. Inflammation in scrotal Doppler ultrasonography was based on testicular involvement. RESULTS: A retrospective evaluation was made of the data of 194 patients with brucellosis-related testicular involvement. The rate of determination of testicular involvement in brucellosis was 2.57%. The most affected patients were determined in the 16-30 years age range. On presentation, brucellosis was in the acute stage in 83.7% of patients. The most common symptoms on presentation were swelling and/or pain in the testes (86.6%). In the patients where a spermiogram could be performed, oligospermia was determined in 41.7%, and aspermia in 8.3%. When the testicular involvement of brucellosis was evaluated, epididymo-orchitis was present at the rate of 55.7%, epididymitis at 27.3%, and testis abscess at 5.1%. CONCLUSIONS: Although epididymo-orchitis was the most frequently determined form of involvement in this study, there was also seen to be a significant number of patients presenting with epididymitis. Male patients presented with the clinical status of brucellosis should be questioned about swelling and pain in the testes to avoid overlooking testicular involvement.

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)

Human Tularemia Epididymo-Orchitis Caused by Francisella tularensis Subspecies holartica, Austria.

A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors.

Indicaciones e histología de 489 orquiectomías analizadas según la edad del paciente / Indications and histology of 489 orchiectomies analyzed by patient age

Objetivo Evaluar indicaciones e histología de nuestra serie de orquiectomías, analizando los resultados dependiendo de la edad del paciente. Métodos Estudio de las orquiectomías realizadas en nuestro centro entre 2005 y 2020 a pacientes mayores de 18 años. Evaluamos: datos demográficos, indicaciones, histología y efectividad del diagnóstico ecográfico según 3 grupos de edad. Resultados Se realizaron 489 orquiectomías, 364 (74%) en los pacientes entre 18-50 años (grupo A), 59 (12%) entre los pacientes de 51-70 años (grupo B) y 66 (13,4%) en mayores de 70 años (grupo C). En el grupo A, 284 (78%) orquiectomías fueron indicadas por sospecha tumoral, 261/284 (91,9%) fueron neoplasias malignas, 253 (89%) germinales. La ecografía testicular tuvo un valor predictivo positivo (VPP) para tumor testicular maligno del 90%. En el grupo B, 34 (57%) orquiectomías fueron indicadas por sospecha tumoral y 25/34 (73,5%) presentaron neoplasias malignas. La ecografía tuvo un VPP para malignidad del 68%. En el grupo C, la orquiepididimitis fue la causa más frecuente de orquiectomía con 30 casos (45,5%). Entre las 20 orquiectomías por sospecha de tumor (30,3%), se encontró malignidad en 6. La ecografía tuvo un VPP para malignidad del 31%. Conclusión En menores de 70 años la indicación principal de orquiectomía fue la sospecha tumoral y en mayores, la orquiepididimitis. Los tumores germinales fueron la histología más frecuente en los menores de 70 años; en los mayores la malignidad fue infrecuente. Con la edad, disminuyó el VPP de la ecografía testicular para neoplasia maligna. En los mayores de 50 años se debería mejorar el proceso diagnóstico antes de indicar orquiectomía por sospecha tumoral (AU)

Objective To evaluate the indications and histology of our series of orchiectomies, analysing the results by patient's age. Methods We included the orchiectomies realized in our hospital between 2005 and 2020 in patients older than 18 years. We estimated demographic data, indications, histology and effectiveness of testicular ultrasound by three groups of age. Results We included 489 orchiectomies, which 364 (74%) belonged to group A (patients between 18-50 years), 59 (12%) to group B (50-70 years) and 66 (14%) to group C (older than 70 years). In group A, 284 (78%) orchiectomies were indicated due to malignancy suspect. In 91.9% cases (261) malign neoplasm was confirmed at final histology and 253 (89%) were germinal cells. Testicular ultrasound had a positive predictive value (PPV) of 90% in this group. In group B, 34 (57%) orchiectomies were indicated because of malignancy suspect. At final histologic analysis, 25/34 (73.5%) confirmed malign neoplasm. Ultrasound had a PPV of 68%. In group C, orchiepididymitis was the main cause of testicular removal with 30 cases (45,5%). From the 20 cases (30.3%) with suspicion of malignancy, only 6 had confirmed malign histology. Testicular ultrasound PPV for malignancy was 31%. Conclusion In patients younger than 70 years the main orchiectomy's indication was suspect of malignancy and in older than 70, testicular inflammation. The germinal neoplasm was the predominant histology in younger than 70 years. In older than that, malignancy was infrequent. The positive predictive value of testicular ultrasound for malignancy decreased with patient's age. In patients older than 50 years proper image diagnosis to assess malignancy should be considered before orchiectomy is done (AU)

NR2C2 of macrophages promotes inflammation via NF-κB in LPS-induced orchitis in mice.

In brief: Bacterial infection can induce testicular inflammation and damage male fertility. This paper reveals the role of nuclear receptor subfamily 2 group C member 2 (NR2C2) in macrophage cells in orchitis caused by bacterial endotoxin lipopolysaccharide (LPS) infection. Abstract: Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of NR2C2 in testicular inflammatory injury induced by infection with the bacterial endotoxin LPS. We found that NR2C2 was highly expressed in the testes and the expression of NR2C2 was upregulated in testicular macrophages in the LPS-induced mouse orchitis model in vivo. In primary testicular macrophages and RAW264.7 cells in vitro, RNA interference with the Nr2c2 gene downregulated the expression of inflammatory factors such as IL-1ß and IL-6. In addition, the knockdown of NR2C2 in macrophages alleviated the inhibitory effect of the inflammatory supernatant secreted by the macrophages on the proliferation of spermatogonia GC-1 SPG cells. Mechanistically, NR2C2 activated NF-κB signaling by binding with DR elements in the promotor of the Nfκb gene and promoted the development of inflammation. These data are the first to confirm that during LPS-induced bacterial infection, NR2C2 plays a proinflammatory role by activating IL-1ß and IL-6 via the NF-κB pathway in macrophages, consequently inhibiting the proliferation of spermatogonia and damaging the quality of sperm. Our findings reveal the important role of NR2C2 in testicular inflammatory injury induced via LPS and provide a new potential target and a molecular basis for the treatment of male infertility caused by bacterial infection.

Acute orchitis deciphered: Coxsackievirus B strains are the main etiology and their presence in semen is associated with acute inflammation and risk of persistent oligozoospermia.

Although various viruses are considered to be the clinical cause for acute orchitis, it is completely unclear to what extent and which viruses are etiologically involved in acute orchitis and what the clinic and course of these patients are like. Therefore, a prospective study was set up to decipher acute isolated orchitis. Between July 2007 and February 2023, a total of 26 patients with isolated orchitis were recruited and compared with 530 patients with acute epididymitis. We were able to show for isolated orchitis, that (1) orchitis is usually of viral origin (20/26, 77%) and enteroviruses with coxsackievirus B strains (16/26, 62%) are predominant, (2) virus isolates could be received from semen indicating the presence of replication-competent virus particles, (3) a polymerase chain reaction (PCR) for enteroviruses should be conducted using semen provided at the onset of disease, because the virus is not detectable in serum/urine, (4) there is a circannual occurrence with the maximum in summer, (5) orchitis is associated with a characteristic inflammatory cytokine panel in the semen and systemic inflammation, (6) orchitis is usually rapidly self-limiting, and (7) about 30% of patients (6/20) suffer ongoing oligozoospermia. These seven emerging aspects are likely to fundamentally change thinking and clinical practice regarding acute isolated orchitis.