Outcome of acute epididymo-orchitis: risk factors for testicular loss.

PURPOSE: Acute epididymo-orchitis (AEO) is a common urological condition characterised by pain and swelling of the epididymis which can affect men of any age. The aetiology and to some extent the management of the patient differ between paediatric and young and older adult groups. METHODS: A retrospective analysis was performed at the University Hospital Limerick from 2012 to 2016. Hospital In-Patient Enquiry (HIPE) data were obtained for all patients diagnosed with orchitis, epididymitis, epididymo-orchitis or testicular abscess over this 5-year period. RESULTS: 140 patients were identified, the age range was 0-89, median age 35.6. These were then split into 3 clinical groups, pre-pubertal (Group 1, 0-15-year-olds), sexually active young men (Group 2a, 16-35-year-olds) and men over 35 (Group 2b). Nine patients had an abscess on ultrasound investigation. There was a significant correlation between the presence of an abscess and the need for an orchidectomy (2 patients, P = 0.035). Two patients were reported as having an atrophic testis following AEO and both were in Group 2b. CONCLUSION: Overall, 7/131 (5%) patients had loss or atrophy of a testicle following an episode of AEO. Nineteen patients had further readmissions with AEO (14%).

Research progress on complications of Brucellosis.

Brucellosis is a common zoonotic disease that is widely spread worldwide and poses a major threat to human health. Clinically, it often presents with non-specific symptoms such as fever, excessive sweating, malaise, myalgia, arthralgia, loss of appetite, weight loss, and enlarged liver, spleen and lymph nodes. The disease has a long and recurrent course, often accumulating in multiple systems and organs. Of these, osteoarticular involvement is the most common complication, with a prevalence of approximately 2-77%, usually manifesting as spondylitis, sacroiliac arthritis and peripheral arthritis. Hepatosplenomegaly is seen in about 50% of patients with brucellosis, and gastrointestinal disturbances such as abdominal pain, nausea, and vomiting are common. Although respiratory involvement is less common, pneumonia, pleurisy, pleural effusion, and pulmonary nodules have been reported. Besides, approximately 2-20% of cases involve infections of the male genitourinary system, mainly manifesting as unilateral epididymal-orchitis and orchitis. The most serious complication facing brucellosis is cardiovascular involvement, and although the overall mortality rate of brucellosis is about 1% and the incidence of brucellosis endocarditis is less than 2%, more than 80% of deaths are associated with endocarditis. Furthermore, brucellosis is complicated by hematologic disease, with anemia occurring in approximately 20-53% of children during the acute phase. In addition, the neurological incidence of brucellosis is about 0.5-25%, mainly manifested as meningitis. In this study, we review the multisystem complications of brucellosis with the aim of improving early diagnosis, timely treatment and prevention of long-term complications.

Epididymo-orchitis Presenting as Bilateral Hydrocele in a Young Adult.

We present a case of young patient who presented with a progressive scrotal swelling and low-grade fever. An ultrasound of the scrotum revealed multiple small well-defined hypoechoic lesions in both testes with bulky epididymis and bilateral hydrocele. The final diagnosis was confirmed on cytology. The typical imaging findings may help to reach the diagnosis and to plan the further management in such cases.

Outcomes and affecting factors for ICSI and microTESE treatments in nonobstructive azoospermia patients with different etiologies: A retrospective analysis.

Introduction: Nonobstructive azoospermia (NOA) is a common and severe form of male infertility. Microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI) is an optimal treatment for men with NOA. However, the outcomes and affecting factors of ICSI for NOA patients with different etiologies receiving microTESE treatment are still unclear. Methods: A total of 335 NOA patients undergoing microTESE from January 2017 to December 2021 were included in this retrospective analysis. The patients were divided into five groups (idiopathic, Klinefelter syndrome (KS), Y chromosome microdeletions (YCMDs), cryptorchidism and mumps orchitis) according to the etiologies. The clinical characteristics and outcomes of microTESE and ICSI were collected and comparisons were performed between clinical characteristics of patients who had successful sperm retrieval (SSR) and sperm retrieval failure (SRF). In addition, relationships between clinical characteristics and rates of SSR were explored by Kendall correlation analysis. Results: The overall SSR rate was 40.90%. SSR rate of the idiopathic group (31.22%) was the lowest and was much lower than that of other groups (KS: 48.65%, 28/58; YCMDs: 60.87%; cryptorchidism: 80.95%; mumps orchitis: 75.00%). The overall fertilization rate was 72.26%. No group differences were found among five groups (idiopathic: 73.91%; KS: 71.43%; YCMDs: 64.29%; cryptorchidism: 70.59%; mumps orchitis: 77.78%). The overall clinical pregnancy rate was 66.67%. No group differences were found among five groups (idiopathic: 68.63%; KS: 65.00%; YCMDs: 44.44%; cryptorchidism: 66.67%; mumps orchitis: 85.71%). The overall live birth rate was 66.67%. No group differences were found among five groups (idiopathic: 71.43%; KS: 53.85%; YCMDs: 50.00%; cryptorchidism: 75.00%; mumps orchitis: 66.67%). For SSR patients, the average age was significantly lower in the idiopathic group, while the average testicular volume was significantly greater in the cryptorchidism and mumps orchitis groups. However, no significant differences were found in the level of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) between patients who had SSR and SRF. In addition, negative relationships were found between age and rates of SSR in idiopathic NOA patients while positive relationships were found between testis volume and rates of SSR in patients with cryptorchidism and mumps orchitis. Conclusion: Patients with idiopathic NOA had lowest SSR. In addition, the age in idiopathic NOA patients was a predictor for SSR while testicular volume in NOA patients with cryptorchidism and mumps orchitis was a predictor for SSR. However, the relationships between clinical characteristics and clinical outcomes in NOA patients were preliminary, and further validation needed to be carried out in a larger sample to increase statistical capacity before a definitive conclusion could be drawn.

Testicular necrosis as a complication of severe epididymo-orchitis: a case report.

The symptoms of epididymo-orchitis (EO) are usually mild, but serious complications such as abscess and testicular necrosis can occur. There are a few cases of testicular necrosis secondary to EO to our knowledge. We present a case of a 60-year-old diabetic male patient who presented with left scrotal pain and fever in the last week. The scrotal ultrasonography (US) revealed increased flow of the left testicle in favour of the left EO. After seven days of antibiotic therapy, the patient´s condition worsened and developed into a scrotal abscess. The scrotal US showed scrotal abscess with the absence of left testicular arterial vascularity in favour of testicular necrosis. For that, a left orchiectomy was performed, and a histopathology report confirmed the diagnosis. In conclusion, testicular necrosis secondary to EO is a rare occurrence. When there is a suspicion of EO, medical therapy should be started as soon as possible to avoid significant complications.

Is testicular microlithiasis associated with testicular pathologies in children?

PURPOSE: To analyze the association of testicular pathologies with TM. METHOD: The retrospective study included pediatric patients who underwent scrotal ultrasonography (US) due to complaints, including testicular pain, discomfort, swelling, scrotal redness in our clinic between June 2020 and January 2022. The patients were divided into two groups. Group 1; patients were diagnosed with testicular pathology or presented with testicular pain. Group 2; patients without testicular pathology or complaints. Patients were also classified as having undescended testis, epididymo-orchitis, varicocele and testicular pain without testicular pathology in group 1. Group 1 and subgroups of group 1 were compared with group 2 for the presence of TM. RESULTS: A total of 516 patients were included in the study. Median age at the time of US examination was 24 months (range 1 month-17 years). There was no significant difference between groups 1 and 2, and boys with undescended testis and group 2 with regard to the presence of TM (p = 0.85, p = 0.55, respectively). TM was significantly higher in patients who had undergone orchiopexy and presented with testicular pain compared to group 2 (p = 0. 013, p = 0.03, respectively). TM was not detected in patients with epididymo-orchitis, varicocele. CONCLUSION: We found no association between TM and testicular pathologies. Testicular pain may be a symptom of microlithiasis.

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.

Sonographic findings of COVID-19 related acute scrotal infection and associations with clinical-laboratory data.

BACKGROUND: During the Coronavirus Disease 2019 (COVID-19) pandemic, patients present to hospitals with a wide range of symptoms. Some of these symptoms include acute orchitis and epididymitis. The goal of this research is to see if COVID-19 infection and scrotal infection are associated. MATERIALS AND METHODS: Patients with a COVID-19 (+) who agreed to a scrotal ultrasound (US) examination were studied prospectively in a tertiary care center between October 2021 and February 2022. The severity of the disease was used to divide patients into groups. Patients diagnosed with acute scrotal infection based on scrotal ultrasonography findings were compared in these groups, as were their age, comorbidities, and laboratory data. RESULTS: The median age of the 213 participants was 61.7 ± 8.3. During the ultrasonographic examination of the patients, 15 (7%), 8 (3.7%), 17 (7.9%), and 40 (18.7%) were diagnosed with acute orchitis, acute epididymitis, acute epididymo-orchitis, and scrotal infection, respectively. Acute scrotal infection was far more common in patients with a higher clinical severity of the disease. The patients' comorbidities were also assessed, and it was discovered that they were statistically more common in the same group. CONCLUSIONS: Even if there are no clinical symptoms, ultrasonography can help detect acute scrotal infection in COVID-19 patients. Furthermore, in groups with higher clinical severity, this association is more likely to be seen. It is critical to understand this in order to avoid complications.

Testicular infarction and spontaneous scrotal rupture secondary to acute epididymo-orchitis.

Epididymo-orchitis is a common cause of acute unilateral testicular pain. Both infectious or non-infectious causes have been proposed and, rarely, testicular abscess formation and even infarction can occur as a severe complication. We present here a case of acute epididymo-orchitis leading to testicular abscess formation, infarction and spontaneous rupture through the scrotal wall despite appropriate antibiotic treatments. Orchidectomy and partial scrotectomy were performed during surgical exploration for management of the non-viable testis and associated scrotal sinus. Clinical vigilance is important to prevent this complication by close clinical follow up with ultrasonography and even early surgical decompression to prevent testicular loss.

Testicular Atrophy and Epididymitis-Orchitis Associated with Infectious Bronchitis Virus in Broiler Breeder Roosters.

Infectious bronchitis is a respiratory disease of chickens caused by a gammacoronavirus named infectious bronchitis virus (IBV). In addition to affecting the respiratory tract, IBV may also induce urogenital infections, leading to nephropathogenic disease, false layer syndrome in laying hens, and epididymal lithiasis and epididymitis in males. Here, we report a case of decreased reproductive efficiency due to male infertility in 33- to 38-wk-old broiler breeders. At necropsy, the males presented with urates deposited on the skin around the vent and testicular asymmetry due to marked unilateral atrophy. Histopathology revealed lymphocytic epididymitis, epididymal lithiasis, and orchitis. IBV antigen was detected within collecting and efferent ducts of epididymides by immunohistochemistry. IBV strain DMV/1639 was detected by reverse transcription-quantitative PCR in pools of testes, oviducts, tracheas, cecal tonsils, and kidneys from a 37-wk-old affected flock. This report shows evidence of the role of IBV in male chicken infertility and highlights the importance of performing molecular surveillance of IBV to monitor vaccine strains and to detect emerging variants that can potentially hinder production.

Reporte de caso- Atrofia testicular y epididimitis-orquitis asociadas con el virus de la bronquitis infecciosa en gallos reproductores pesados. La bronquitis infecciosa es una enfermedad respiratoria del pollo causada por un gammacoronavirus llamado virus de la bronquitis infecciosa (con las siglas en inglés IBV). Además de afectar el tracto respiratorio, el IBV también puede inducir infecciones urogenitales, lo que conduce a enfermedad nefropatogénica, síndrome de la falsa ponedora en gallinas de postura y litiasis epididimaria y epididimitis en machos. En este reporte se describe un caso de disminución de la eficiencia reproductiva debido a la infertilidad de machos en reproductores pesados de 33 a 38 semanas de edad. En la necropsia, los machos presentaron depósitos de uratos sobre la piel alrededor de la cloaca y asimetría testicular por atrofia unilateral marcada. La histopatología reveló epididimitis linfocítica, litiasis epididimaria y orquitis. Antígenos del virus de la bronquitis infecciosa se detectaron dentro de los conductos colectores y eferentes de los epidídimos mediante inmunohistoquímica. La cepa del virus de la bronquitis DMV/1639 se detectó mediante transcripción reversa y PCR cuantitativa en muestras agrupadas de testículos, oviductos, tráqueas, tonsilas cecales y riñones de una parvada afectada de 37 semanas de edad. Este reporte muestra evidencia del papel del virus de la bronquitis infecciosa en la infertilidad de los pollos machos y destaca la importancia de realizar una vigilancia molecular de este virus para monitorear las cepas vacunales y detectar variantes emergentes que potencialmente pueden dificultar la producción.

Urological Impact of Epididymo-orchitis in Patients with Anorectal Malformation: An ARM-Net Consortium Study.

INTRODUCTION: To investigate the current experience of the ARM-Net Consortium in the management of epididymo-orchitis (EO) in patients with anorectal malformations (ARMs), and to identify specific risk factors and the need for urological care involvement. MATERIALS AND METHODS: We retrospectively collected data of EO in patients with ARM between 2015 and 2019. Data on urological aspects, ARM type, surgical approach, associated anomalies, diagnosis, and treatment of EO were collected and analyzed. RESULTS: Twenty-nine patients were reported by 12 centers. Twenty-six patients with EO (90%) had ARM with a rectourinary fistula. Median age at first EO was 2 years (range: 15 days-27 years). Twenty patients (69%) experienced multiple EO, and 60% of recurrences were ipsilateral. Associated urological anomalies included vesicoureteral reflux (48%), urethral anomalies (41%), neurogenic bladder (41%), and ectopic vas (10%). A positive urine culture during EO was present in 69%. EO was treated with antibiotics (90%), limiting surgical exploration to 14%. Prevention of recurrences included surgery (bulking agents 15%, vasectomy 15%, and orchiectomy 5%) and antibiotic prophylaxis (20%). CONCLUSION: Urologists may encounter patients with EO in ARM patients, frequently with positive urine culture. An appropriate urologic work-up for most ARM patients is necessary to identify and treat underlying risk factors. A practical scheme for the work-up is suggested for a close collaboration between pediatric surgeons and urologists.

Bone Status in a Mouse Model of Experimental Autoimmune-Orchitis.

Investigations in male patients with fertility disorders revealed a greater risk of osteoporosis. The rodent model of experimental autoimmune-orchitis (EAO) was established to analyze the underlying mechanisms of male infertility and causes of reduced testosterone concentration. Hence, we investigated the impact of testicular dysfunction in EAO on bone status. Male mice were immunized with testicular homogenate in adjuvant to induce EAO (n = 5). Age-matched mice were treated with adjuvant alone (adjuvant, n = 6) or remained untreated (control, n = 7). Fifty days after the first immunization specimens were harvested. Real-time reverse transcription-PCR indicated decreased bone metabolism by alkaline phosphatase and Cathepsin K as well as remodeling of cell-contacts by Connexin-43. Micro computed tomography demonstrated a loss of bone mass and mineralization. These findings were supported by histomorphometric results. Additionally, biomechanical properties of femora in a three-point bending test were significantly altered. In summary, the present study illustrates the induction of osteoporosis in the investigated mouse model. However, results suggest that the major effects on bone status were mainly caused by the complete Freund's adjuvant rather than the autoimmune-orchitis itself. Therefore, the benefit of the EAO model to transfer laboratory findings regarding bone metabolism in context with orchitis into a clinical application is limited.

Mumps Orchitis: Clinical Aspects and Mechanisms.

The causative agent of mumps is a single-stranded, non-segmented, negative sense RNA virus belonging to the Paramyxoviridae family. Besides the classic symptom of painfully swollen parotid salivary glands (parotitis) in mumps virus (MuV)-infected men, orchitis is the most common form of extra-salivary gland inflammation. Mumps orchitis frequently occurs in young adult men, and leads to pain and swelling of the testis. The administration of MuV vaccines in children has been proven highly effective in reducing the incidence of mumps. However, a recent global outbreak of mumps and the high rate of orchitis have recently been considered as threats to male fertility. The pathogenesis of mumps orchitis remains largely unclear due to lack of systematic clinical data analysis and animal models studies. The alarming increase in the incidence of mumps orchitis and the high risk of the male fertility have thus become a major health concern. Recent studies have revealed the mechanisms by which MuV-host cells interact and MuV infection induces inflammatory responses in testicular cells. In this mini-review, we highlight advances in our knowledge of the clinical aspects and possible mechanisms of mumps orchitis.

Is there any association of COVID-19 with testicular pain and epididymo-orchitis?

AIMS: This study aims to analyse the novel Coronavirus disease- (COVID-19) related testicular pain in hospitalised patients because of COVID-19 and to review as an aetiological factor for epididymitis, orchitis or both. METHODS: A total of 91 patients were included in the study. A questionnaire was formed for the questioning of testicular pain or epididymo-orchitis in patients with COVID-19. Demographics and past medical history was also recorded. Patients' neutrophil and lymphocyte counts, neutrophil-lymphocyte ratios (NLR), C-reactive protein (CRP) levels and D-dimer values were recorded. Patients with COVID-19 were divided into two groups according to absence or presence of testicular pain or epididymo-orchitis as group 1 and group 2. All results were compared for both groups. RESULTS: The median age of patients was similar in both groups. Testicular pain was occurred in 10.98% of the patients. Clinical presentation of epididymo-orchitis was diagnosed in only one patient. No statistically significant difference was reported in terms of patients' age, levels of CRP and D-Dimer or NLR and results of questionnaire form queries between the two groups (P > .05). CONCLUSION: Testicular pain was observed more frequently in hospitalised COVID-19 cases. While no inflammation marker which is related to predict of testicular pain or epididymo-orchitis was found in patients with COVID-19.

Assessment of Age and Duration of Symptoms on Outcomes of Emergency Scrotal Exploration for Acute Scrotal Pain.

OBJECTIVE: To study the effects of age and duration of symptoms on the outcomes of scrotal explorations for acute scrotal pain at our institution. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Bradford Teaching Hospital NHS Trust, from January 2006 to December 2017. METHODOLOGY: Retrospective data was collected from electronic case records of the patients who required scrotal exploration for suspected torsion of the testis. Group difference between continuous variables (age and duration of symptoms) were assessed by Kruskal Wallis and independent samples Mann-Whitney U-tests. The Fisher Exact and Chisquare tests were used to analyse relationships between categorical data. RESULTS: In total, 502 patients required scrotal exploration. The median age (years) and duration of symptoms (hours) were 16.4 years (1.3 - 77) and 4 hours (1 - 336), respectively. Torsion of the testis was found in 231 (46%), torsion of the testicular appendix in 126 (25%), epididymal inflammation in 46 (9.2%), and no cause identified in 99 (19.7%). Immediate orchidectomy for non-viable testis performed in 34 (14.7% of TT group and 6.8% of the overall cohort). Duration of symptoms was significantly associated with risk of orchidectomy in torsion patients 4 vs. 27 hours (p <0.0001). Overall 47 (9.3%) patients presented after 12 hours, 22 (46.8%) had TT. There were 13 (2.6%) patients older than 40 years and 8 (61.5%) of these had torsion. CONCLUSION: The most commonest diagnosis for patients presenting with acute scrotal pain was torsion of the testis followed by torsion of appendix testis. Testicular salvage was inversely related to the duration of symptoms. Patient's age did not predict the need for orchidectomy. This data supports the practice of urgent scrotal exploration for acute scrotal pain with a clinical suspicion of torsion regardless of age and duration of symptoms.

More Than Just Torsion: An Unusual Case of Testicular Pain.

Testicular pain has a wide differential and the nonspecific presentation should be triaged rapidly for urgent diagnosis and treatment. Scrotal pyoceles are uncommon collections of purulent fluid between the visceral and parietal tunica vaginalis, usually secondary to acute epididymo-orchitis, intra-abdominal infection, or trauma. Epididymitis and epididymo-orchitis are generally secondary to sexually transmitted infections or urinary tract pathogens. Epidymo-orchitis can compromise the testicular blood supply, leading to a microinfarction and rupture through the tunica albuginea; inflammatory and infectious material then translocate into the tunica vaginalis leading to the formation of a pyocele. Ultrasonography is the preferred method of diagnostic imaging, which can show a classic "falling snow" sign, loculations, or gas. The treatment for a scrotal pyocele is pain control, fluid resuscitation, broad-spectrum antibiotics, and early urology/general surgery consultation. In such cases, Fournier gangrene (FG) should be clinically ruled out and the presence of signs of Fournier gangrene should be met with an urgent surgical consult.

[Acute prostatitis associated with noncancerous prostate at the Lubumbashi University Clinics: epidemioclinical and therapeutic features]. / Prostatites aiguës sur prostate non tumorale aux cliniques universitaires de Lubumbashi: aspects épidémio-clinique et thérapeutique.

INTRODUCTION: acute prostatitis is a common urological condition. The purpose of this study was to analyze the epidemioclinical features and therapy of acute prostatitis associated with noncancerous prostate at the Lubumbashi University Clinics. METHODS: we conducted a descriptive cross-sectional and retrospective study of a series of 25 patients with documented acute prostatitis and treated at the Lubumbashi University Clinics over a period of four years, from 2015 to 2018. All patients with prostate cancer were excluded from our study. Data were collected via a survey form based on different study parameters divided into 3 categories, namely epidemiological data including age, study period, residence, clinical data with subjective signs, objective signs, general status, findings on rectal examination as well as paramedical data divided into laboratory and imaging tests. RESULTS: acute prostatitis associated with noncancerous prostate accounted for 1.27% of all surgical diseases and 7.66% in urology. The most affected age group was 19-37 years (64% of cases), mean age was 33.16±2.4 years. Seventeen patients (68%) were followed up in outpatient clinics and 8 (32%) in hospital. Clinically, fever above 38.5°C was found in 15 patients (60%), dysuria in 11 patients (44%), acute urinary retention in 3 patients (12%), burning during urination in 8 patients (32%), pain syndrome in 21 patients (84%), tender prostate on rectal examination in 18 patients (72%). Ultrasound was the only examination performed in 16 patients (64%). Biologically, assessment of inflammation was performed almost systematically in all patients (100%) including complete blood count (CBC), sedimentation rate (SR), C reactive protein (CRP) levels; blood culture was performed in 4 patients (16%), three of whom had positive blood culture. All patients underwent cytobacteriological examination of the urine or prostatic secretions collected by prostate massage. Urine culture was sterile in 6 patients (24%) and positive in 19 patients (76%). Escherichia coli was the most common germ in 16 out of a total of 19 patients (84.21%). All patients received rectal anti-inflammatory drugs. Fluoroquinolones were the most used antibiotics in 18 patients (64%), twelve of whom received antibiotics as monotherapy. Six out of 25 (24%) cases were associated with orchiepididymitis. The lenght of treatment ranged from 2 to 4 weeks, with either sterilization in secretions or urine or disappearance of leukocyturia as the criteria for treatment discontinuation. Thus, out of 19 patients with positive culture on admission, 14 underwent a second culture (73.68%) at 2 weeks of treatment, three of whom (12%) still had positive test and had to undergo a third culture 4 weeks after they had started treatment. Patient's course was good in 22 cases (88%) with complete clinical and biological remission; three patients (12%) persisted in symptoms which became chronic; no patients had prostatic abscess. CONCLUSION: acute prostatitis associated with noncancerous prostate is a really worrying urological, nosologic condition whose management must be rigorous, especially in people at risk, namely those with intense sexual behaviour. Endorectal ultrasound and prostate massage should be integrated into patient care at the Lubumbashi University Clinics.