Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism: a systematic review by the EAU Sexual and Reproductive Health Guidelines panel.

Surgical treatments for ischemic priapism (IP) include shunts or penile implants. Non-ischemic priapism (NIP) is usually the result of penile/perineal trauma causing an arterial fistula and embolisation may be required. We conducted a systematic review on behalf of the EAU Sexual and Reproductive health Guidelines panel to analyse the available evidence on efficacy and safety of surgical modalities for IP and NIP. Outcomes were priapism resolution, sexual function and adverse events following surgery. Overall, 63 studies (n = 923) met inclusion criteria up to September 2021. For IP (n = 702), surgery comprised distal (n = 274), proximal shunts (n = 209) and penile prostheses (n = 194). Resolution occurred in 18.7-100% for distal, 5.7-100% for proximal shunts and 100% for penile prostheses. Potency rate was 20-100% for distal, 11.1-77.2% for proximal shunts, and 26.3-100% for penile prostheses, respectively. Patient satisfaction was 60-100% following penile prostheses implantation. Complications were 0-42.5% for shunts and 0-13.6% for IPP. For NIP (n = 221), embolisation success was 85.7-100% and potency 80-100%. The majority of studies were retrospective cohort studies. Risk of bias was high. Overall, surgical shunts have acceptable success rates in IP. Proximal/venous shunts should be abandoned due to morbidity/ED rates. In IP > 48 h, best outcomes are seen with penile prostheses implantation. Embolisation is the mainstay technique for NIP with high resolution rates and adequate erectile function.

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.

Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

A new cause of ischaemic priapism: Synthetic cannabinoids.

Priapism is a urological emergency that needs early intervention and may lead to irreversible cavernosal damage. Ischaemic priapism is the most common type, which is frequently idiopathic and commonly associated with haematological diseases, medications or recreational drugs. Synthetic cannabinoids (SCs) have been increasingly used all over the world, particularly among young-adult population. SCs can cause severe adverse effects on several organ systems. However, there are no studies in the literature which have stated the possible relationship between using of SCs and priapism. We present a case of 28-year-old man who was diagnosed with a 58-hr lasting priapism after regular administrations of SCs. The priapism did not resolve neither after applying aspiration with irrigation nor shunt surgery. Finally, penile prosthesis implantation was performed as last treatment option. The SCs have been increasingly used among young population in recent years; therefore, new SC-related ischaemic priapism cases might be encountered in the emergency departments.

Neutrophilic NLRP3 inflammasome-dependent IL-1ß secretion regulates the γδT17 cell response in respiratory bacterial infections.

Traditionally regarded as simple foot soldiers of the innate immune response limited to the eradication of pathogens, neutrophils recently emerged as more complex cells endowed with a set of immunoregulatory functions. Using a model of invasive pneumococcal disease, we highlighted an unexpected key role for neutrophils as accessory cells in innate interleukin (IL)-17A production by lung resident Vγ6Vδ1+ T cells via nucleotide-binding oligomerization domain receptor, pyrin-containing 3 (NLRP3) inflammasome-dependent IL-1ß secretion. In vivo activation of the NLRP3 inflammasome in neutrophils required both host-derived and bacterial-derived signals. Elaborately, it relies on (i) alveolar macrophage-secreted TNF-α for priming and (ii) subsequent exposure to bacterial pneumolysin for activation. Interestingly, this mechanism can be translated to human neutrophils. Our work revealed the cellular and molecular dynamic events leading to γδT17 cell activation, and highlighted for the first time the existence of a fully functional NLRP3 inflammasome in lung neutrophils. This immune axis thus regulates the development of a protective host response to respiratory bacterial infections.

Duration of priapism is associated with increased corporal oxidative stress and antioxidant enzymes in a rat model.

Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with resultant corporal fibrosis. Studies reported decreased erectile recovery after treatment of priapism longer than 36 h. However, a recent study revealed that half of patients with 3 days of priapism achieved recovery after T-shunt, although mechanism remains unclear. We aimed to investigate the effect of priapism duration on oxidative stress and antioxidant enzymes. Twenty-four male rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4 represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy and blood withdrawal were performed to investigate levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and 4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but multivariable analysis revealed insignificant differences. Plasma MDA of the experimental groups was significantly higher than that of controls. There were no differences among groups in terms of other parameters. Increased antioxidant enzymes according to duration of priapism suggest that immediate treatment to relieve oxidative stress should be initiated in prolonged cases. However, further studies should be conducted to determine resistance mechanisms of the corpora to prolonged ischaemia.

Density and duration of experimental human pneumococcal carriage.

The density and duration of pneumococcal carriage are considered to affect the likelihood of transmission and invasive disease. Because of its importance in both spreading and causing disease, carriage has been suggested as an endpoint in future vaccine studies. Culture is the current gold standard for detection, but may not be sensitive enough to detect changes at low density. Healthy adult volunteers received an intranasal inoculation of Streptococcus pneumoniae serotype 6B. Pneumococcal density in nasal washes collected at six time-points post-inoculation was determined by culture and quantitative PCR (qPCR). Natural pneumococcal carriers detected at initial screening were followed in parallel. In 331 nasal washes from 79 volunteers, the sensitivity and specificity of pneumococcal detection by qPCR, as compared with culture, were 92.3% and 75.9%. The estimation of pneumococcal density by culture and qPCR was highly correlated (rs  = 0.73, p <0.0001), although qPCR had a lower detection limit. Pneumococcal density fluctuated within a carriage episode, and occasionally fell below the detection limit of both methods. The duration of carriage episodes was underestimated when only one method was used. Similar fluctuations in density were observed in natural carriers. Pneumococcal carriage is a dynamic event. Culture and qPCR are complementary for surveying the density and duration of pneumococcal carriage episodes.

Prevalence of male pelvic dysfunction: results from the Turkish society of andrology male sexual health study group.

The objective of this study was to determine the prevalence of male pelvic dysfunction (MPD) and its correlation in men ≥40 years of age in a population-based study. This study was designed as a non-interventional, observational, cross-sectional field survey. Participating males of ≥40 years were randomly selected from 19 provinces of Turkey. All participants were asked to complete a survey including data regarding demographics, socio-economic status, socio-cultural factors, medical and sexual history, current medications, comorbidities and three validated questionnaires assessing lower urinary tract symptoms (International Prostate Symptom Score), erectile dysfunction (International Index of Erectile Function) and ejaculatory behaviour (Male Sexual Health Questionnaire-4). MPD was defined by combining abnormal scores calculated from all three questionnaires. All data were analysed statistically and p < 0.05 was accepted as significant. A total of 2730 males of ≥40 years (mean, 54.2 ± 10.6 years) were enrolled in this study. The prevalence of MPD was calculated as 24.4% among all participants. The prevalence of MPD was lowest at age between 40 and 49 years (9.1%) and highest at ≥70 years (76.6%), exhibiting correlation with age. Each decade of increase in age was associated with a 3.4-fold increase in presence of MPD. At logistic regression analyses; age, diabetes, hypertension, dyslipidemia, cardiovascular disease, obesity and lower income were found to be independent predictors for increased prevalence of MPD. This study reports prevalence of MPD as 24.4% in males of ≥40 years. Furthermore, age was found to be the main independent predictor of having MPD.

Efficacy and tolerability of udenafil in Turkish men with erectile dysfunction of psychogenic and organic aetiology: a randomized, double-blind, placebo-controlled study.

Udenafil is a potent phosphodiesterase type-5 inhibitor (PDE5) previously shown in studies conducted in populations of Eastern-Asian ethnicity, to significantly improve sexual function, in addition to a favourable safety profile. The purpose of this study was to evaluate the efficacy and safety of udenafil for the treatment of erectile dysfunction (ED), for the first time in a non-Eastern-Asian population. In this multicentre, randomized, double-blind, parallel, placebo-controlled study conducted in five centres in Turkey, 118 eligible subjects were randomized to receive udenafil 100 mg taken as on-demand or matching placebo for an 8-week treatment period. The primary efficacy variable was the change from baseline of the International Index of Erectile Function Questionnaire-Erectile Function Domain (IIEF-EFD) score, secondary efficacy variables were changes from baseline in IIEF Questionnaire Domains' 2-5 scores (Intercourse Satisfaction, Orgasmic Function, Sexual Desire, Overall Sexual Satisfaction) and IIEF Questionnaire Grand Total score, changes from baseline in penetration success rates (SEP2) and intercourse completion rates (SEP3) and evaluation of responses to the global assessment question (GAQ). Patients treated with udenafil demonstrated significantly higher increase in the IIEF-EFD scores compared with placebo-treated subjects [4.0 (95% CI: 1.3-6.6; p = 0.003)]. Similarly, greater improvements were observed in the scores for SEP2 [0.65 (95% CI: 0.02-1.3, p = 0.043)], SEP3 [0.9 (95% CI: 0.3-1.5, p = 0.003)] and two other IIEF Questionnaire Domains (Domain 4: Sexual Desire, Domain 5: Overall Sexual Satisfaction). The proportion of positive responses to the GAQ was greater in the udenafil compared to the placebo group (72.2% vs. 49.1%, p = 0.014). The most frequent treatment-emergent adverse events were headache, flushing and rhinorrhea, all of mild or moderate severity. This is the first study to demonstrate in a non-Eastern-Asian population that udenafil 100 mg taken as on-demand can effectively improve erectile function and is well tolerated.

Investigation of mutations in the synaptonemal complex protein 3 (SYCP3) gene among azoospermic infertile male patients in the Turkish population.

To investigate possible mutations and/or single nucleotide polymorphisms in the synaptonemal complex protein 3 (SYCP3) gene among nonobstructive azoospermic infertile males in a Turkish population, 75 nonobstructive azoospermic infertile male patients were included in the study. These patients were unrelated to each other and had 46,XY chromosome structure without Y microdeletion. In addition, 75 individuals whose fertility was proven by reproduction were enrolled in the study as controls. Nine exon deep intronic primers belonging to the SYCP3 gene were designed and amplified by PCR, and the nucleotide sequences were identified by DNA sequence analysis. DNA sequence analysis was used to detect mutations and/or single nucleotide polymorphisms in the SYCP3 gene. No mutations were detected in the 9 exons of SYCP3. A total of eleven variations, however, were detected: seven have been identified in the NCBI SNP database, whereas four have not. On the basis of the results, we agree with the idea that SYCP3 mutations are not associated with the genetic susceptibility for meiotic arrest in infertile male patients with nonobstructive azoospermia in the Turkish population and that further studies investigating the other components of the synaptonemal complex protein (SYCP1, SYCP2) should be conducted.

Decorin as a new treatment alternative in Peyronie's disease: preliminary results in the rat model.

The purpose of this study is to investigate the effect of decorin, a naturally occurring proteoglycan with anti-transforming growth factor beta (TGF-ß) activity, on the rat model of Peyronie's disease (PD). Twenty-five adult male Sprague-Dawley rats were divided in three groups: I) TGF-ß (0.5 µg) injected (n: 8); II) TGF-ß injected and decorin treated (n: 8); and III) controls (n: 9). Decorin (0.5 µg per day) was given with intracavernous injection on the second, third, fourth and fifth day following TGF-ß injection. All rats underwent electrical stimulation of the cavernous nerve after 6 weeks. Intracavernosal and arterial blood pressures were measured during this procedure. Cross-sections of the rat penises were examined using Mason trichrome and H&E stains. Statistical analyses were carried out using one-way anova. Histopathological examinations confirmed the Peyronie's-like condition in TGF-ß-injected rats, which exhibited a thickening of the tunica albuginea (TA), when compared to controls. Disorganisation of collagen on the TA was also prominent in TGF-ß-injected rats, but not in decorin-treated and control rats. Decorin-treated rats showed significantly higher maximal intracavernosal pressure (MIP) responses to cavernous nerve stimulation, when compared to group 1 (P < 0.05). Our results indicate that decorin antagonises the effects of TGF-ß in the rat model of PD and prevents diminished erectile response to cavernous nerve stimulation.

Pneumococcal neuraminidase A: an essential upper airway colonization factor for Streptococcus pneumoniae.

Streptococcus pneumoniae colonizes the upper respiratory tract from where the organisms may disseminate systemically to cause life threatening infections. The mechanisms by which pneumococci colonize epithelia are not understood, but neuraminidase A (NanA) has a major role in promoting growth and survival in the upper respiratory tract. In this article we show that mutants of S. pneumoniae D39 deficient in NanA or neuraminidase B (NanB) are abrogated in adherence to three epithelial cell lines, and to primary nasopharyngeal cells. Adherence levels were partly restored by nanA complementation in trans. Enzymic activity of NanA was shown to be necessary for pneumococcal adherence to epithelial cells, and adherence of the nanA mutant was restored to wild-type level by pre-incubation of epithelial cells with Lactococcus lactis cells expressing NanA. Pneumococcal nanA or nanB mutants were deficient in biofilm formation, while expression of NanA on L. lactis or Streptococcus gordonii promoted biofilm formation by these heterologous host organisms. The results suggest that NanA is an enzymic factor mediating adherence to epithelial cells by decrypting receptors for adhesion, and functions at least in part as an adhesin in biofilm formation. Neuraminidase A thus appears to play multiple temporal roles in pneumococcal infection, from adherence to host tissues, colonization, and community development, to systemic spread and crossing of the blood-brain barrier.

Death is associated with complement C3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis.

UNLABELLED: Pneumococcal meningitis can lead to death or serious neurological sequelae as a result of the host inflammatory response. We investigated the association between host response protein expression and outcome in patients with pneumococcal meningitis. Cerebrospinal fluid (CSF) was obtained from 80 patients with pneumococcal meningitis (40 nonsurvivors and 40 survivors) and 10 normal controls. Candidate proteins were analyzed for an association with survival. Complement C3 levels were 5-fold lower in nonsurvivors than in survivors (P < 0.05). This C3 reduction was not associated with lower levels in serum, indicating a compartmentalized CSF response. Transferrin levels were significantly higher in CSF (but not serum) from nonsurvivors than in CSF from survivors, suggestive of blood-brain barrier damage. Classical apoptosis proteins caspase 3 and apoptosis-inducing factor were not present in CSF. Expression of creatine kinase BB in clinically infected CSF suggested neuronal necrosis, but there was no clear association between level of expression and clinical outcome. Increased blood-brain barrier permeability and complement C3 depletion may have a role in determining outcome from bacterial meningitis. Therapeutic use of citicoline or caspase inhibitors is unlikely to have beneficial effects in patients with meningitis. IMPORTANCE: We previously identified proteins associated with clinical outcome in patients diagnosed with pneumococcal meningitis in a pilot proteomics study of cerebrospinal fluid (CSF). In this article, we have quantitatively assayed specific proteins identified from this previous proteomics analysis along with proteins associated with cell death by using Western blotting.

The most commonly altered type of Peyronie's disease deformity under oral colchicine treatment is lateral curvature that mostly shifts to the dorsal side.

The aim of the present study was to evaluate changes in clinical characteristics of Peyronie's disease (PD) patients under oral colchicine treatment in comparison with the initial clinical evaluation with a special emphasis on patients with altered deformity after treatment. A total of 118 patients under oral treatment with colchicine for at least 3 months in the acute phase of PD were retrospectively evaluated with combined infection and stimulation test. PD patients were followed up in four groups according to the clinical course of the deformity: improved, remained unchanged, deteriorated deformities or altered localisation of the deformity. Among 116 patients who completed the treatment, penile curvatures improved in 27.6% (n = 32), remained unchanged in 39.7% (n = 46) and deteriorated in 12.1% (n = 14) of the patients after a follow-up of 8.6 ± 3.2 (6-17) months, while localisation of the deformities changed in 20.7% (n = 24) of the patients. In this group, the initial side of the deformities were lateral, ventral, ventrolateral in 41.6% (n = 10), 29.1% (n = 7) and 8.3% (n = 2) of the patients and of hourglass and notching type (n = 4, 16.6%) respectively. Six (60%) patients with lateral, five (71.4%) with ventral curvatures completed their follow-up period with dorsal curvatures. In conclusion, lateral curvature is the most commonly altered deformity that mostly shifts to the dorsal sise of the penis after colchicine therapy.

Invasive Streptococcus pneumoniae trigger platelet activation via Toll-like receptor 2.

BACKGROUND: Sepsis is the most common manifestation of invasive pneumococcal disease and is characterized by a severe systemic inflammatory state that leads to circulatory compromise or end organ malperfusion or dysfunction. Patients suffering from sepsis often display low platelet counts characterized by thrombocytopenia as a result of platelet activation. OBJECTIVE: To investigate the mechanism through which platelets become activated in sepsis upon binding to Streptococcus pneumoniae. PATIENTS AND METHODS: We determined S. pneumoniae inducible platelet reactivity using light transmission aggregometry. Dense granule secretion was measured by luminometry using a luciferin/luciferase assay. RESULTS: Streptococcus pneumoniae induced platelet aggregation in a strain-dependent manner. Induction of aggregation was not attributable to capsule serotype, as unencapsulated strains also induced platelet aggregation. Platelet aggregation was not associated with pneumolysin toxin, as a pneumolysin-deficient mutant of S. pneumoniae induced aggregation equally as well as the parent strain. Platelet aggregation also occurred in the absence of plasma proteins or antibody, and was GPIIbIIIa dependent but aspirin independent. Toll-like receptor 2 (TLR2) is present on platelets and acts as a receptor for gram-positive bacterial lipoteichoic acid and peptidoglycan. Inhibition of TLR2 but not TLR4 (also present on platelets) completely abolished platelet aggregation. S. pneumoniae-induced platelet aggregation resulted in activation of the PI3kinase/RAP1 pathway, leading to integrin GPIIbIIIa activation and dense granule release. CONCLUSIONS: Our results demonstrate a novel interaction between S. pneumoniae and TLR2, which results in platelet activation that is likely to contribute to the thrombotic complications of sepsis.

Pneumococcal protein PavA is important for nasopharyngeal carriage and development of sepsis.

Summary The pneumococcal cell surface protein PavA is a virulence factor associated with adherence and invasion in vitro. In this study we show in vivo that PavA is necessary for Streptococcus pneumoniae D39 colonization of the murine upper respiratory tract in a long-term carriage model, with PavA-deficient pneumococci being quickly cleared from nasopharyngeal tissue. In a pneumonia model, pavA mutants were not cleared from the lungs of infected mice and persisted to cause chronic infection, whereas wild-type pneumococci caused systemic infection. Hence, under the experimental conditions, PavA-deficient pneumococci appeared to be unable to seed from lung tissue into blood, although they survived in blood when administered intravenously. In a meningitis model of infection, levels of PavA-deficient pneumococci in blood and brain following intercisternal injection were significantly lower than wild type. Taken collectively these results suggest that PavA is involved in successful colonization of mucosal surfaces and in translocation of pneumococci across host barriers. Pneumococcal sepsis is a major cause of mortality worldwide so identification of factors such as PavA that are necessary for carriage and for translocation from tissue to blood is of clinical and therapeutic importance.

Photosystem II functionality and antioxidant system changes during leaf rolling in post-stress emerging Ctenanthe setosa exposed to drought.

We studied the changes in antioxidant system and chlorophyll fluorescence parameters in post-stress emerging Ctenanthe setosa (Rosc.) Eichler (Marantaceae) plants (PSE plants) having reduced leaf area under drought stress causing leaf rolling and re-watering. PSE plants were compared to primary stressed plants (PS) in previous studies. The parameters were measured at different visual leaf rolling scores from 1 to 4 (1 is unrolled, 4 is tightly rolled and the others is intermediate form). Water potentials and stomatal conductance of leaves were gradually decreased during leaf rolling. Similarly, maximum quantum efficiency of open PS II center and quantum yield of PS II decreased during the rolling period. Non-photochemical quenching of chlorophyll fluorescence decreased at score 2 then increased while photochemical quenching did not change during leaf rolling. Electron transport rate decreased only at score 4 but approximately reached to score 1 level after re-watering. Superoxide dismutase activity was not constant at all leaf rolling scores. Ascorbate peroxidase, catalase and glutathione reductase activities generally tended to increase during leaf rolling. Lipid peroxidation and H 2 O 2 content increased at score 2 but decreased at the later scores. On the other hand, O 2 .- production increased during the rolling period. After re-watering of the plants having score 4 of leaf rolling, antioxidant enzyme activities were lower than those of score 1. Other physiological parameters also tended to reach the value of score 1. The results indicated that PSE plants gained drought tolerance by reducing leaf area effectively induced their antioxidant systems and protected the photosynthesis under drought stress similar to PS plants.