Predictive value of haematologic parameters in diagnosis of testicular torsion: Evidence from a systematic review and meta-analysis.

To compare the difference of mean platelet volume (MPV), platelet lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), platelet (PLT) and leucocyte between testicular torsion (TT), epididymo-orchitis and healthy controls and further evaluate predictive values of these haematologic parameters in diagnosis and the differential diagnosis of TT. Databases were systematically retrieved, and reference search was also conducted manually. We applied Stata software 12.0 to perform a systematic review and meta-analysis. Ultimately, five case-control studies with 672 participants were recruited for analyses. Pooled analyses indicated that TT patients had lower NLR (WMD = -1.66, 95% CI = -3.25 to -0.06) and PLT (WMD = -27.39, 95% CI = -48.03 to -6.75) compared to epididymo-orchitis patients. In the meantime, TT patients had higher NLR and leucocyte than healthy controls (p < .05). That is to say, when a man develops TT, his NLR and leucocyte will rise up but his NLR will not reach the level of epididymo-orchitis. To sum up, NLR, PLT and leucocyte were vital factors for TT diagnosis. Leucocyte is an useful parameter for diagnosing both TT and epididymo-orchitis, but it cannot be used in differentiating the two diseases. NLR is beneficial parameter for differential diagnosis between TT and epididymo-orchitis. PLT can also be utilised in differential diagnosis among young patients.

Comparison of inflammatory markers between brucella and non-brucella epididymo-orchitis

ABSTRACT Objectives: Brucellosis is a multi-system infectious disease that is associated with inflammation, which causes an increase in acute phase reactants. Hematological inflammatory markers of brucellosis include mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). In this study, we aimed to evaluate the diagnostic value of hematological inflammatory markers in Brucella epididymo-orchitis (BEO), and to investigate the utility of these markers for differential diagnosis from non-Brucella epididymo-orchitis (non-BEO). Materials and Methods: We retrospectively reviewed the records of 22 BEO and 50 non-BEO patients. Hematological parameters were recorded and compared between the two groups. The main diagnostic criteria for BEO were positive clinical findings (i.e., testicular pain, tenderness and scrotal swelling), a positive Rose Bengal test result, standard tube agglutination (STA) titer ≥ 1/160, and/or a positive blood culture. Results: The most decisive factors in discriminating between BEO and non-BEO were NLR, RDW, and MPV, in decreasing order of their strength. Regardless of other factors, NLR values < 2.3 significantly increased the odds of BEO (OR=8.080, 95% CI: 1.929-33.843, p=0.004). After adjusting for other factors, RDW values >14.45% significantly increased the odds of BEO (OR=7.020, 95% CI: 1.749-28.176, p=0.006). Independent of the other factors, patients with MPV < 7.65 fL had a 6.336 times higher risk for BEO (95% CI: 1.393 - 28.822, p=0.017). Conclusion: Hematological inflammatory markers such as NLR, RDW, and MPV can aid in the differential diagnosis of BEO and non-BEO.

Comparison of inflammatory markers between brucella and non-brucella epididymo-orchitis.

OBJECTIVES: Brucellosis is a multi-system infectious disease that is associated with inflammation, which causes an increase in acute phase reactants. Hematological inflammatory markers of brucellosis include mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). In this study, we aimed to evaluate the diagnostic value of hematological inflammatory markers in Brucella epididymo-orchitis (BEO), and to investigate the utility of these markers for differential diagnosis from non-Brucella epididymo-orchitis (non-BEO). MATERIALS AND METHODS: We retrospectively reviewed the records of 22 BEO and 50 non-BEO patients. Hematological parameters were recorded and compared between the two groups. The main diagnostic criteria for BEO were positive clinical findings (i.e., testicular pain, tenderness and scrotal swelling), a positive Rose Bengal test result, standard tube agglutination (STA) titer ≥ 1/160, and/or a positive blood culture. RESULTS: The most decisive factors in discriminating between BEO and non-BEO were NLR, RDW, and MPV, in decreasing order of their strength. Regardless of other factors, NLR values < 2.3 significantly increased the odds of BEO (OR=8.080, 95% CI: 1.929- 33.843, p=0.004). After adjusting for other factors, RDW values >14.45% significantly increased the odds of BEO (OR=7.020, 95% CI: 1.749-28.176, p=0.006). Independent of the other factors, patients with MPV < 7.65 fL had a 6.336 times higher risk for BEO (95% CI: 1.393 - 28.822, p=0.017). CONCLUSION: Hematological inflammatory markers such as NLR, RDW, and MPV can aid in the differential diagnosis of BEO and non-BEO.

Specific autoantigens identified by sera obtained from mice that are immunized with testicular germ cells alone.

There are various autoimmunogenic antigens (AIs) in testicular germ cells (TGCs) recognized as foreign by the body's immune system. However, there is little information of TGC-specific AIs being available. The aim of this study is to identify TGC-specific AIs. We have previously established that immunization using viable syngeneic TGC can also induce murine experimental autoimmune orchitis (EAO) without using any adjuvant. This study is to identify TGC-specific AIs by TGC liquid chromatography-tandem mass spectrometry analysis, followed by two-dimensional gel electrophoresis that reacted with serum IgG from EAO mice. In this study, we identified 11 TGC-specific AIs that reacted with serum from EAO mice. Real-time RT-PCR analysis showed that the mRNA expressions of seven TGC-specific AIs were significantly higher in only mature testis compared to other organs. Moreover, the recombinant proteins of identified 10 (except unnamed protein) TGC-specific AIs were created by using human embryonic kidney 293 (HEK293) cells and these antigencities were reconfirmed by Western blot using EAO serum reaction. These results indicated Atp6v1a, Hsc70t, Fbp1 and Dazap1 were candidates for TGC-specific AIs. Identification of these AIs will facilitate new approaches for understanding infertility and cancer pathogenesis and may provide a basis for the development of novel therapies.

[The correlation between testosterone levels and C-reactive protein in acute bacterial epididymo-orchitis]. / Korelacja stezenia testosteronu i bialka C-reaktywnego w ostrym zapaleniu jadra i najadrza.

UNLABELLED: Acute bacterial epididymo-orchitis is common urological condition that usually originates from ascending infection of lower urinary tract. It is characterized by infection of testis combined with spermatogenesis and steroidogenesis impairment. There is also a component of local and systemic inflammation. AIM: The aim of this study was to assess the effect of systemic inflammation associated with acute epididymo-orchitis on testis steroidogenesis. MATERIALS AND METHODS: 30 patients with acute bacterial epididymoorchitis treated in our ward without any oncologic involvement or other systemic inflammatory conditions were considered for the study. Total serum levels of testosterone and C-reactive protein measured within 12 hours of admission. RESULTS: Low total testosterone levels regarding to random laboratory population norms were noticed in 11 patients. Diminished serum total testosterone levels regarding to medium age levels were identified in 24 patients (80%). 29 patients had serum CRP levels elevated what gives average 22x fold. There is a statistically significant negative correlation between serum total testosterone levels and CRP serum levels were found (R - 0.75; p<0.000002 Spearman's correlation). CONCLUSIONS: There is a strong influence of ongoing systemic inflammation caused by bacterial infection on steroidogenesis in testis in acute epididymo-orchitis patients.

Clinical application of neutrophil CD64 quantification for differential diagnosis of acute scrotum.

The management of acute scrotum can be challenging, especially in infants or patients with a neurological or neurodevelopmental disorder in whom presentation, diagnosis and definitive management tends to be delayed. This leads to poor outcomes, such as loss of the affected testis. Here we present two cases of testicular torsion in patients with neurodevelopmental disorders, and a further two cases of epidydimo-orchitis in whom measurement of CD64 expression on neutrophils was helpful for differential diagnosis. These data suggest that the levels of expression of CD64 by neutrophils, known as a marker of infection, could also be useful for differentiating between testicular torsion and infection in acute scrotum.

Elevation of Serum Levels of High-Sensitivity Procalcitonin, C-reactive Protein, and Amyloid A in a Prepubertal Child with Mumps Orchitis.

BACKGROUND: Serum CRP concentrations are significantly elevated at the acute phase in patients with mumps orchitis, but little is known currently about other inflammatory biomarkers. METHODS: We report the measurements of serum inflammatory biomarkers [high-sensitivity procalcitonin (hs-PCT), C-reactive protein (CRP) and amyloid A] in a child with mumps orchitis. RESULTS: The patient's serum levels of CRP, hs-PCT, and amyloid A were highly increased at the acute phase, but returned to normal levels at convalescence. CONCLUSIONS: This case suggests that hs-PCT and amyloid A may not be useful for distinguishing between mumps orchitis accompanied by highly elevated serum concentrations of CRP and systemic bacterial infections.

IL-6 and IFNγ are elevated in severe mumps cases: a study of 960 mumps patients in China.

INTRODUCTION: Mumps is a common infectious disease. Epidemics of mumps are reported globally every year and represent a threat to public health, especially in China and other developing countries. METHODOLOGY: Clinical and laboratory findings of 960 mumps patients admitted to Beijing You'an Hospital, China, between January 2010 and December 2012 were collected and analyzed. Patients with isolated complication were selected and grouped as aseptic meningitis/encephalitis (AME) patients (n = 156) and Orchitis patients (n = 72). One hundred and fifty patients without complication were grouped as control. Levels of T cell subtypes and 8 serum cytokines were also tested. RESULTS: Majority of mumps patients were male (76.3%) and younger than 17 years old (76.2%). AME was complicated in 41.6% of mumps cases, and orchitis was in 21.3% (64.7% were left-sided). Unvacinated patients had more chance to have AME or orchitis (p = 0.034 and 0.027). The rates of AME and orchitis in mumps patients rapidly increased during the last three years. No laboratory findings were associated with AME or orchitis (all p > 0.05). Serum IL-10 level was elevated in almost all patients. IL-6 and IFNγ levels were correlated with AME (p = 0.025 and p = 0.018). Their levels peaked at day one after admission, and started to decline thereafter. CONCLUSIONS: This study suggests that the incidence of serious complications has become more common in recent years, moreover IL-6 and IFNγ may possibly be used as early serum markers for identifying patients with risk of developing complications in mumps.

Effect of P/E-selectin blockage on antisperm antibody development and histopathological alterations in experimental orchitis.

AIM: This study aimed to evaluate the effect of P/E-selectin blockage on antisperm antibody (ASA) development and histopathological alterations in experimental orchitis. MATERIALS AND METHODS: Thirty-six Wistar albino-type male rats weighing 100-150 g were included in the study. Rats were allocated into six groups (n = 6) including control (CG), sham (SG), orchitis (OG), antimicrobial treatment (AG), P/E-selectin blockage (PESG), and both antimicrobial and P/E-selectin treatment (TG) groups. In CG, serum samples were taken from the tail vein prior to the procedure and followed by extraction of both testes. In SG, 1 ml of saline solution was injected in testicular parenchyma. OG was obtained by injecting 0.1 ml 106 cfu/ml Escherichia coli (0:6 strain) and 1 ml saline solution into the right testes. AG received ciprofloxacin (50 mg/kg/day) twice a day through gastrogavage 24 hours after generating orchitis. In PESG, P/E-selectin antibody (100 µg) was administered intravenously via the tail vein 24 hours after the induction of orchitis. Finally, both ciprofloxacin and P/E-selectin antibody were administered in TG 24 hours after the induction of orchitis for 14 days. At the end of treatment, 1 ml of serum sample was obtained to evaluate the ASA, P-selectin and E-selectin levels. In order to evaluate spermatogenesis (Johnsen score) and testicular injury (Cosentino score), both testes were extracted at the end of the 14th day. RESULTS: In orchitis-induced groups (OG, ATG, PSEG, TG), ASA levels were significantly increased at the 14th day when compared to SG (p < 0.05). In TG, ASA levels were decreased when compared to AG. However, similar alteration in ASA levels was not detected in PSEG (p > 0.05). In OG and AG, P-selectin levels were decreased at the 14th day when compared to levels observed on 0 day (p < 0.05). E-selectin levels on 0 day showed that each group had higher levels of E-selectin when compared to CG (p > 0.05). There was no significant difference regarding E-selectin when compared to CG (p > 0.05). No significant differences regarding E-selectin levels were detected on the 0th and 14th days between AG and CG (p > 0.05). When the Cosentino and Johnsen scores were compared among groups, TG and PSEG has decreased scores of Cosentino than OG on the right testicle (p < 0.05). In contrast, an increased Johnsen score was detected in TG and PSEG when compared to OG (p < 0/05). No significant difference was detected for both Cosentino and Johnsen scores on the left testicle (p > 0.05). There was no difference with regard to the right and left testicular injury in TG. In P/E-blocked groups, decreased histopathological alterations were observed in the contralateral testis. CONCLUSION: P/E-selectin blockage may reduce ASA production after orchitis when combined with antimicrobial treatment. P/E-selectin blockage not only has a protective effect on blood-testis barrier but also decreases the histopathological alterations in both the affected and contralateral testis. Histopathological parameters of spermatogenesis may also be prevented by P/E-selectin blockage in experimental orchitis.

Is procalcitonin valuable in the differential diagnosis of testicular torsion and epididymo-orchitis.

OBJECTIVE: To evaluate the efficacy of procalcitonin (PCT) in the differential diagnosis of testicular torsion and epididymo-orchitis. METHODS: This experimental study was performed in the research laboratory of Dicle University, School of Medicine, Diyarbakir, Turkey between March and June 2008. The study included 24 male rats randomized equally in 3 groups: sham, epididymo-orchitis, and torsion groups. Blood samples were obtained from all rats at the beginning of the study. After torsion and infection occurred in the testes, new blood samples were obtained for PCT measurement. Then, all the right testes of the rats were excised for histopathological evaluation. The Wilcoxon signed test was used for statistical evaluation. RESULTS: Pre- and post PCT levels were statically compared, and PCT levels were significantly higher in the epididymo-orchitis group. CONCLUSION: Procalcitonin could be an easy, fast, and safe marker for use in the differential diagnosis of testicular torsion and epididymo-orchitis.

Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis.

Testicular inflammation with compromised fertility can occur despite the fact that the testis is considered an immunoprivileged organ. Testicular macrophages have been described as cells with an immunosuppressor profile, thus contributing to the immunoprivilege of the testis. Experimental autoimmune orchitis (EAO) is a model of organ-specific autoimmunity and testicular inflammation. EAO is characterized by an interstitial inflammatory mononuclear cell infiltration, damage of the seminiferous tubules and germ cell apoptosis. Here we studied the phenotype and functions of testicular macrophages during the development of EAO. By stereological analysis, we detected an increased number of resident (ED2+) and non-resident (ED1+) macrophages in the testicular interstitium of rats with orchitis. We showed that this increase was mainly due to monocyte recruitment. The in vivo administration of liposomes containing clodronate in rats undergoing EAO led to a reduction in the number of testicular macrophages, which correlated with a decreased incidence and severity of the testicular damage and suggests a pathogenic role of macrophages in EAO. By immunohistochemistry and flow cytometry we detected an increased number of testicular macrophages expressing MHC class II, CD80 and CD86 costimulatory molecules in rats with orchitis. Also, testicular macrophages from rats with EAO showed a higher production of IFNgamma (ELISA). We conclude that testicular macrophages participate in EAO development, and the ED1+ macrophage subset is the main pathogenic subpopulation. They stimulate the immune response through the production of pro-inflammatory cytokines and antigen presentation and thus activation of T cells in the target organ.

Recurrent epididymo-orchitis in an 8-year-old child with Kostmann syndrome (severe congenital neutropenia).

Underlying congenital genito-urinary tract anomalies are the most common cause of recurrent epididymo-orchitis in prepubertal boys. An 8-year-old boy was admitted with recurrent pulmonary and skin infections, was diagnosed as Kostmann syndrome and developed epididymo-orchitis. This appears to be the first case of Kostmann syndrome associated with epididymo-orchitis.

Elevated serum C-reactive protein in mumps orchitis.

A case of mumps orchitis with a high concentration of C-reactive protein (CRP) prompted us to evaluate the inflammatory response in mumps complications. We compared the CRP titers in mumps patients with orchitis and meningitis. The serum CRP titers were significantly higher in the patients with orchitis than in those with meningitis.

Autoimmune testicular vasculitis.

A 38-year-old man presented for evaluation of new-onset left testicular pain with swelling. Testicular ultrasound revealed multiple intraparenchymal hypoechoic areas in the inferior portion of the left testicle. The patient was treated with a radical inguinal orchiectomy. Pathologic evaluation revealed intratesticular vasculitis, with involvement of medium-sized arteries. This appears to be a rare case of isolated testicular vasculitis, in the absence of any systemic symptoms.

Correlation between inhibin secretion and damage of seminiferous tubules in a model of experimental autoimmune orchitis.

The aim of the present study was to evaluate inhibin secretion in rats with autoimmune orchitis. As we have previously described, experimental autoimmune orchitis (EAO) induced in rats by active immunization with testis homogenate and adjuvants is characterized by an interstitial mononuclear cell infiltrate and sloughing of the germinal epithelium. At 120 days after the first immunization 60% of the rats exhibited a severe orchitis with large areas of aspermatogenic seminiferous tubules in which only spermatogonia and Sertoli cells with cytoplasmic vacuolization remained attached to the tubular wall. None of the untreated (N) or control (C) rats revealed pathological alterations. Sixty percent decrease in testis weight was observed in rats with EAO compared with N or C groups. A 3-fold increase in serum FSH levels was observed in rats with EAO compared with N or C groups (19.8+/-3.7 vs 5.6+/-0.3 and 5.9+/-0.1 ng/ml respectively). A significant decrease in inhibin B levels was observed in rats with EAO when compared with N or C groups (40+/-4.6 vs 207+/-38.8 and 221.4+/-28.6 pg/ml respectively). An inverse correlation between inhibin B and FSH serum levels and a direct correlation between inhibin B and testis weight were found. Strong expression of the inhibin alpha-subunit in Sertoli cells of untreated and control rats was observed; this subunit was undetectable or poorly detectable in rats with orchitis. Positive staining for the inhibin alpha-subunit was also observed in Leydig cells of all groups studied. In conclusion, using a model of autoimmune orchitis our results show that circulating inhibin B levels and inhibin alpha-subunit expression in Sertoli cell cytoplasm closely correlate with the degree of damage of the germinal epithelium.

Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats.

A single intraperitoneal injection of lipopolysaccharide (LPS) causes a biphasic suppression of testicular steroidogenesis in adult rats, with inhibition at 6 h and 18-24 h after injection. The inhibition of steroidogenesis is independent of the reduction in circulating LH that also occurs after LPS treatment, indicating a direct effect of inflammation at the Leydig cell level. The relative contributions to this inhibition by intratesticular versus systemic responses to inflammation, including the adrenal glucocorticoids, was investigated in this study. Adult male Wistar rats (eight/group) received injections of LPS (0.1 mg/kg i.p.), dexamethasone (DEX; 50 microg/kg i.p.), LPS and DEX, or saline only (controls), and were killed 6 h, 18 h and 72 h later. Treatment with LPS stimulated body temperature and serum corticosterone levels measured 6 h later. Administration of DEX had no effect on body temperature, but suppressed serum corticosterone levels. At the dose used in this study, DEX alone had no effect on serum LH or testosterone at any time-point. Expression of mRNA for interleukin-1beta (IL-1beta), the principal inflammatory cytokine, was increased in both testis and liver of LPS-treated rats. Serum LH and testosterone levels were considerably reduced at 6 h and 18 h after LPS treatment, and had not completely recovered by 72 h. At 6 h after injection, DEX inhibited basal IL-1beta expression and the LPS-induced increase of IL-1beta mRNA levels in the liver, but had no effect on IL-1beta in the testis. The effects of DEX on IL-1beta levels in the liver were no longer evident by 18 h. In LPS-treated rats, DEX caused a significant reversal of the inhibition of serum LH and testosterone at 18 h, although not at 6 h or 72 h. Accordingly, DEX inhibited the systemic inflammatory response, but had no direct effect on either testicular steroidogenesis or intra-testicular inflammation, at the dose employed. These data suggest that the inhibition of Leydig cell steroidogenesis at 6 h after LPS injection, which was not prevented by co-administration of DEX, is most likely due to direct actions of LPS at the testicular level. In contrast, the later Leydig cell inhibition (at 18 h) may be attributable to extra-testicular effects of LPS, such as increased circulating inflammatory mediators or the release of endogenous glucocorticoids, that were inhibited by DEX treatment. These data indicate that the early and late phases of Leydig cell inhibition following LPS administration are due to separate mechanisms.

Essential pathogenic role for endogenous interferon-gamma (IFN-gamma) during disease onset phase of murine experimental autoimmune orchitis. I. In vivo studies.

We previously found that immunization of CH3/He male mice with syngeneic testicular germ cells (TGC) without the aid of any adjuvants was sufficient to induce DTH to TGC and experimental autoimmune orchitis (EAO). To evaluate the role of endogenous IFN-gamma in this model, C3H/He mice immunized subcutaneously with TGC on days 0 and 14 received a single injection of anti-murine IFN-gamma MoAb on day 15, 20 or 25. On day 45, DTH to TGC was tested, testis specimens were collected for histological examination, and blood samples collected for IFN-gamma measurement. The results showed that whilst MoAb treatment on day 15 or 25 did not influence DTH responses, EAO development, and appearance of IFN-gamma in the circulation, treatment on day 20 significantly suppressed all of them. Thus, a single injection with anti-IFN-gamma MoAb may successfully down-regulate testicular autoimmunity, provided that the treatment is given at an optimal time point during disease development.

Acute experimental unilateral orchitis in the rabbit and its effect on fertility.

We examined the nature of contralateral damage following unilateral orchitis to see if an immunologically mediated mechanism was present. Experimentally induced orchitis in 18 white New Zealand rabbits were examined and compared to 20 in the control groups. Serum antisperm antibody presence and bilateral testicular biopsies (Johansen biopsy score, mean seminiferous tubule diameter) were examined and pregnancy rates were noted. Acute orchitis seemed to be a causative factor in production of antisperm antibody and the presence of antisperm antibody caused histologic changes in contralateral testicles and therefore impaired fertility.