Combined levothyroxine and testosterone treatment for restoring erectile dysfunction in propylthiouracil-induced hypothyroid rats.

BACKGROUND: Sexual dysfunction may indicate severe endocrine diseases. Recent research has suggested a link between hypothyroidism, low testosterone (T) levels, and erectile dysfunction (ED); however, the exact cause is unknown. AIM: We sought to investigate possible beneficial effects of levothyroxine and T alone or in combination on ED in propylthiouracil (PTU)-induced hypothyroid rats. METHODS: Adult Wistar rats (n = 35) were divided into 5 groups: control, PTU-induced hypothyroidism, PTU + levothyroxine, PTU + Sustanon (a mixture of 4 types of T: propionate, phenylpropionate, isocaproate, and decanoate) and PTU + levothyroxine + Sustanon. PTU was given in drinking water for 6 weeks. Four weeks after PTU administration, levothyroxine (20 µg microgram kg/day, oral) and Sustanon (10 mg/kg/week, intramuscular) were given for 2 weeks. Serum levels of total T, triiodothyronine (T3), and thyroxine (T4) were determined. In vivo erectile response and in vitro relaxant responses were measured. Localization of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and phosphodiesterase type 5 (PDE5) were determined using immunohistochemical analysis. The relative area of smooth muscle to collagen was measured using Masson trichrome staining. OUTCOMES: Outcome variables included in vivo erectile function, in vitro relaxant and contractile responses of corpus cavernosum (CC) strips; protein localization of eNOS, nNOS, and PDE5; and smooth muscle content in penile tissue. RESULTS: The rat model of hypothyroidism showed a significant decline in serum levels of total T, T3, and T4. Levothyroxine increased T3 and T4 levels, whereas Sustanon normalized only total T levels. Combined treatment enhanced all hormone levels. Rats with hypothyroidism displayed the lowest erectile response (P < 0.001 vs controls). Combined treatment returned reduced responses, while partial amelioration was observed after levothyroxine and Sustanon treatment alone. Acetylcholine (P < 0.01 vs controls), electrical field stimulation (P < 0.001 vs controls), and sildenafil-induced relaxant responses (P < 0.05 vs controls) were decreased in the CC strips from hypothyroid rats. The combined treatment increased the reduction in relaxation responses. Levothyroxine and Sustanon restored decreases in eNOS and nNOS expression in the hypothyroid group. There was no significant difference in PDE5 expression among groups. Monotreatment partially enhanced reduced smooth muscle mass, while combined therapy completely recovered. CLINICAL IMPLICATIONS: The combination of thyroid hormones and T is likely to be a therapeutic approach for treatment of hypothyroidism-induced ED in men. STRENGTHS AND LIMITATIONS: Beneficial effects of levothyroxine and Sustanon treatment were shown in vitro and in vivo in PTU-induced hypothyroid rats. The main limitation of the study was the lack of measurement of androgen-sensitive organ weights and luteinizing hormone, follicle-stimulating hormone, and prolactin levels. CONCLUSION: These findings demonstrate that neurogenic and endothelium-dependent relaxation responses are reduced by hypothyroidism, which is detrimental to T levels and erectile responses. Levothyroxine and Sustanon combination medication was able to counteract this effect.

Antibiotics in the Treatment of Uncomplicated Cystitis: A Google Trends Analysis.

INTRODUCTION: Using Google Trends (GT) data, the trend variations for the most common antibiotics used to treat uncomplicated cystitis were analyzed by time and region since 2004. METHODS: GT was used to create a "line-graph" that shows how interest in a topic in certain locations has grown or decreased over time. The relative search volume, which is displayed on a scale of 0-100, was used to index the search values for specific phrases. Nitrofurantoin (NFN), fosfomycin (FOS), trimethoprim (TMP), pivmecillinam (PIV), and cefadroxil are among the antibiotics recommended by the European Association of Urology (EAU) and the American Urological Association for the treatment of uncomplicated cystitis. Using the "global" inquiry category, the data was searched "worldwide" from 1 February 2004 to 31 December 2021. RESULTS: In the regression analysis, all antibiotics exhibited positive trends (p < 0.05). With a steady rise in popularity, NFN is the most popular antibiotic today. Search trend for cefadroxil stayed nearly stable until 2012, the rate of rise in the last 10 years increased, and cefadroxil is the second most popular antibiotic. In the previous 5 years, there was a decline in interest in TMP. In recent years, there was an increase in the trends for FOS and PIV. CONCLUSION: Clinicians and patients all around the world increasingly use the web to search for antibiotic therapies for uncomplicated cystitis. Antibiotics used to treat uncomplicated cystitis have various trends in different continents throughout the world. The web trends seem to be compatible with daily use.

An update on the current status and future prospects of erectile dysfunction following radical prostatectomy.

BACKGROUND: Radical prostatectomy (RP) and radiation treatment are standard options for localized prostate cancer. Even though nerve-sparing techniques have been increasingly utilized in RP, erectile dysfunction (ED) due to neuropraxia remains a frequent complication. Erectile function recovery rates after RP remain unsatisfactory, and many men still suffer despite the availability of various therapies. OBJECTIVE: This systematic review aims to summarize the current treatments for post-RP-ED, assess the underlying pathological mechanisms, and emphasize promising therapeutic strategies based on the evidence from basic research. METHOD: Evaluation and review of articles on the relevant topic published between 2010 and 2021, which are indexed and listed in the PubMed database. RESULTS: Phosphodiesterase type 5 inhibitors, intracavernosal and intraurethral injections, vacuum erection devices, pelvic muscle training, and surgical procedures are utilized for penile rehabilitation. Clinical trials evaluating the efficacy of erectogenic drugs in this setting are conflicting and far from being conclusive. The use of androgen deprivation therapy in certain scenarios after RP further exacerbates the already problematic situation and emphasizes the need for effective treatment strategies. CONCLUSION: This article is a detailed overview focusing on the pathophysiology and mechanism of the nerve injury developed during RP and a compilation of various strategies to induce cavernous nerve regeneration to improve erectile function (EF). These strategies include stem cell therapy, gene therapy, growth factors, low-intensity extracorporeal shockwave therapy, immunophilins, and various pharmacological approaches that have induced improvements in EF in experimental models of cavernous nerve injury. Many of the mentioned strategies can improve EF following RP if transformed into clinically applicable safe, and effective techniques with reproducible outcomes.

Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats.

BACKGROUND: Effects of human umbilical cord blood (HUCB) as a valuable source for stem cell-based therapies have not been studied in persistent post-5-alpha reductase inhibitors (5ARI) erectile dysfunction (PPED). AIM: To determine the effect of intracavernosal injection of HUCB mononuclear cells (MNCs) on ED associated with dutasteride treatment. METHODS: Twenty five adult male Sprague-Dawley rats were divided into 5 groups (n = 5 per group): (i) control, (ii) 8-week dutasteride (0.5 mg/kg/day, in drinking water), (iii) 12-week dutasteride, (iv) 8-week dutasteride+HUCB-MNCs (1 × 106) and (v) 12-week dutasteride+HUCB-MNCs. HUCB-MNCs were administered intracavernosally after eight weeks of dutasteride treatment. Experiments were performed at 4 weeks following the injection of HUCB-MNCs. Erectile responses and isometric tension of corpus cavernosum (CC) were measured. The protein expressions of phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), hypoxia-inducible factor (HIF)-1α and smooth muscle/collagen contents in penile tissue were evaluated by Western blotting, immunohistochemistry, and Masson's trichrome staining, respectively. MAIN OUTCOME: In vivo erectile function, in vitro relaxant and contractile responses of CC, protein expression and localization of PDE5, eNOS, nNOS, HIF-1α, and smooth muscle content in penile tissue. RESULTS: Erectile responses in the dutasteride-treated groups were significantly decreased compared with controls (P < .001), persisting after 4-wk of washout. HUCB-MNCs restored diminished intracavernosal pressure responses, acetylcholine-, sodium nitroprusside-, sildenafil-induced relaxations, and increased phenylephrine and electrical field stimulation (EFS)-induced contractions. Decreased EFS-induced relaxations in dutasteride-treated groups were not restored by HUCB-MNCs. Increased PDE5 and reduced nNOS expressions in dutasteride groups were restored by HUCB-MNCs in the 12-week dutasteride group. eNOS and HIF-1α protein expression and serum total and free testosterone  levels were similar among groups. HUCB-MNCs reversed the decreased smooth muscle/collagen ratio in dutasteride-treated tissues. There was a significant increase in PDE5 and HIF-1α staining in 8-week dutasteride animals. CLINICAL TRANSLATION: This study demonstrates the corrective potential of HUCB-MNCs on some persistent structural and functional deterioration caused by 5ARI treatment in rats, which may encourage further evaluation of HUCB-MNCs in men with PPED. STRENGTHS AND LIMITATIONS: Therapeutic application of intracavernosal HUCB-MNCs is a novel approach for the rat model of post-5ARI ED. Lack of serum and tissue dihydrotestosterone measurements, vehicle injections and characterization of the cells remain limitations of our study. CONCLUSION: The persistent ED after prolonged administration of dutasteride in rats is reversed by HUCB-MNC treatment, which holds promise as a realistic therapeutic modality for this type of ED. Oztekin CV, Yilmaz-Oral D, Kaya-Sezginer E, et al. Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats. J Sex Med 2021;18:889-899.

Analysis of clinical factors associated with intraoperative and postoperative complications of retrograde intrarenal surgery.

The aim of this study was to evaluate the factors affecting intraoperative and postoperative complications in retrograde intrarenal surgery. In this retrospective cohort study, 706 retrograde intrarenal surgery procedures administered to 617 patients were reviewed. Intraoperative and postoperative complications were classified according to the modified Satava and modified Clavien classification systems. The stone-free rate was 407 (57.6%) and the success rate was 528 (74.8%). Intraoperative complications were observed in 215 (30.5%) patients. The most common intraoperative complication was mild bleeding 60(8.5%), while the only independent risk factor associated with intraoperative complications was the presence of residual stones. Postoperative complications were observed in 190 (26.9%) patients. The most common postoperative complication was fever requiring antipyretic drugs 60(8.6%), while independent risk factors associated with postoperative complications were the presence of residual stones and solitary kidney.

Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model.

AIMS: To evaluate the impacts of hydrogen sulfide (H2 S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). METHODS: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2 S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. RESULTS: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2 S levels, while combined therapy completely recovered. CONCLUSIONS: The combination therapy with H2 S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2 S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms.

The beneficial effect of clove essential oil and its major component, eugenol, on erectile function in diabetic rats.

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K+ channels independently NO signalling pathway.

Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.

Don't miss it: Extremity-located cyst hydatid may mimic soft tissue tumors.

OBJECTIVES: In this study, we present our experience in patients with hydatid cysts located intramuscularly. PATIENTS AND METHODS: Between May 2018 and May 2023, a total of 11 patients (3 males, 8 females; mean age: 29.1±13.6 years; range, 8 to 56 years) with intramuscular hydatid cysts were retrospectively analyzed. Demographic data, laboratory values, serological test results, location and size of the cyst, radiological imaging findings, and complications were recorded. RESULTS: The mean follow-up was 44.3±17.3 (range, 5 to 60) months. The mean mass size at the time of admission was 5.4±3.3 (range, 2 to 14) cm. Serologic tests were positive in the majority of cases (72.7%). Eosinophilia was negative in 72.7% patients. The rate of isolated muscle involvement was 81.8%. The rate of lower extremity involvement was 72.7%. The most common involvement was leg (36.4%), thigh (18.2%), and shoulder (18.2%). One patient developed compartment syndrome after cyst rupture during neoadjuvant antihelmintic therapy. There was no recurrence in any of the patients. CONCLUSION: Hydatid cysts should be considered in the differential diagnosis of slowly growing, deeply located, painless soft tissue masses, particularly in endemic areas. Although it is a rare complication, compartment syndrome may develop after spontaneous cyst rupture. Neoadjuvant antihelmintic chemotherapy can reduce complications. The combination of total surgical excision and chemotherapy yields successful results in the treatment of hydatid cysts located in the muscle.

Incomplete recovery of erectile function in rat after discontinuation of dual 5-alpha reductase inhibitor therapy.

AIM: The association of 5-alpha reductase inhibitor (5ARI) therapy and sexual dysfunction has been reported. Some patients claim persistent erectile dysfunction despite long-term discontinuation of 5ARI treatment. The aim of this study was to assess erectile function after cessation of 5ARI therapy using a rat model. METHODS: Twenty-six adult male Sprague-Dawley rats were randomized into three groups: (i) control (N = 10); (ii) 8-week dutasteride treatment (0.5 mg/rat/day, in drinking water, N = 8); and (iii) 6-week dutasteride treatment followed by a 2-week washout period (N = 8). The experiments were performed after 8 weeks from the initiation of treatment in all groups. In vivo erectile activity and in vitro contractile and relaxant responses of cavernosal smooth muscle were investigated. RESULTS: In vivo erectile activity (intracavernosal pressure [ICP]/mean arterial pressure [MAP] and total ICP) in treatment groups were significantly decreased compared with controls (ICP/MAP: P < 0.001 for 2.5 v, 5 v, and 7.5 v; total ICP: P < 0.001 for 5 v and P < 0.01 for 7.5 v). Acetylcholine-induced relaxations were diminished in treatment groups (P < 0.05). Relaxant responses to electrical field stimulation (EFS) were decreased in the 8-week treatment group (P < 0.05) but were similar to controls in the washout group. Sodium nitroprusside (SNP)-induced endothelium-independent relaxations were reduced in the 8-week dutasteride treatment group (P < 0.01), while these responses were restored in the washout group. The contractile responses to the alpha1-adrenergic agonist phenylephrine were decreased in treatment groups compared with controls (P < 0.01). Direct neurogenic contractile responses in the dutasteride groups were significantly lower than controls between 1 and 15 Hz frequencies (but not at 20 Hz) and washout partially restored the responses at 10 and 15 Hz. CONCLUSION: Discontinuation of dutasteride improved the relaxant responses to EFS and SNP, while cholinergic and adrenergic responses remained depressed. Our findings suggest a time-dependent detriment of dutasteride on erectile function. The withdrawal/washout effect of 5ARIs on parameters of human sexual function warrants further investigation.

Relationship between bladder outlet obstruction and prostatic indentation, prostatic urethral length, and bladder-prostatic urethral angle.

OBJECTIVE: To evaluate the relationship between prostatic anatomical factors and pressure flow studies (PFSs). METHODS: The study was designed with 41 patients. PFS was applied to every patient. The Qmax value and voided volume during uroflowmetry were recorded. The PdetQmax values during PFS were recorded and obstruction indices were calculated. Prostate volume, prostatic indentation, prostatic urethral length, and bladder-prostatic urethral angle were determined by transrectal ultrasonography. RESULTS: The mean age of the participants was 66.2 years. The mean maximum flow value was detected as 9.91 ± 4.92 ml/s, and the mean average flow value as 4.89 ± 2.54 ml/s. The mean obstruction index of the patients was found to be 75.27 ± 46.96. There was a positive linear relationship between obstruction index and PSA, prostate volume, prostatic urethral length, and prostatic indentation (r: 0.341, p: 0.029; r: 0.363, p: 0.020; r: 0.386, p: 0.013; and r: 0.479, p: 0.002, respectively). No significant relationship was found between obstruction index and bladder-prostatic urethral angle. CONCLUSION: Prostatic urethral length and prostatic indentation are associated with the degree of bladder outlet obstruction. Further studies involving a higher number of patients are needed to calculate the accuracy of these parameters.

Impact of COVID-19 on male urogenital health: Success of vaccines.

Throughout 2021, the scientific and medical communities were concentrated on dealing with the acute morbidity and mortality induced by the COVID-19 pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We reviewed the present data for adverse effects of COVID-19 on the different parts of the male urogenital system during the dynamic situation of the COVID-19 pandemic. With the approval of COVID-19 vaccinations, there is a ray of hope at the end of this dark tunnel and a chance to look ahead for the management of long-term consequences in males with urogenital illness. A multidisciplinary investigation of these cases could provide information for establishing and optimizing treatment protocols.

Restorative effects of red onion (Allium cepa L.) juice on erectile function after-treatment with 5α-reductase inhibitor in rats.

Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P < 0.001;0.26 ± 0.03, P < 0.01) as compared to control rats (4542.60 ± 429.19 mmHg, 0.51 ± 0.05), which was normalized after the intracavernous administration of onion (3288.60 ± 185.45 mmHg, 0.58 ± 0.04). Onion markedly induced relaxant responses in control (72.5 ± 4.7) and dutasteride-treated (66.5 ± 2.7) groups after precontraction with phenylephrine. Relaxation responses to onion were partially inhibited after precontraction with KCl (32.5 ± 3.1, P < 0.001). The relaxant responses to ACh (14.9 ± 4.2, P < 0.01) were diminished in dutasteride-treated CC) compared to control CC (59.8 ± 3.4), which was enhanced after the incubation with onion (36.6 ± 4.8). There were no differences in relaxation response to SNP among all groups. However, relaxation response to SNP was reduced in dutasteride-treated CC at 1 µM (P < 0.05) and 10 µM dosages (P < 0.001), which was partially increased after the incubation with onion at 10 µM dosage (P < 0.01). The presence of onion did not change the reduction in EFS-caused relaxation in the dutasteride-treated group. The current data suggest that red onion juice has a restorative effect on erectile function and endothelium-dependent relaxation response following the treatment of dutasteride.

Stage-by-stage effects of surgical margin status on biochemical failure after radical prostatectomy in patients with clinically localized prostate cancer.

PURPOSE: To evaluate the effects of pathological stage and surgical margin status on biochemical failure rates after radical prostatectomy (RP). MATERIALS AND METHODS: The records of 205 patients who underwent RP for clinically localized prostate cancer (CaP) were evaluated. Known risk factors for biochemical failure (BF) were analyzed using univariate and multivariate logistic regression analysis. The effects of surgical margin status together with pathological stage on BF were evaluated. p values lower than 0.05 were accepted to be statistically significant. RESULTS: Pathological stage, positive surgical margin (PSM), seminal vesicle invasion, lymph node involvement, biopsy Gleason score and postoperative Gleason score were the factors associated with BF in univariate analysis. Logistic regression analysis revealed that pT3a patients with PSM had a significant BF rate when compared to pT2 patients with a negative surgical margin (NSM) (OR 7.46, p = 0.002). pT3a patients with a NSM had a similar BF rate to that of pT2 patients with PSM. CONCLUSIONS: pT2 patients with PSM had a similar biochemical prognosis to that of pT3a patients without PSM, implicating that a PSM may have a negative effect on prognosis similar to that of extracapsular invasion.

Single ventricle cardiac defect.

Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view.

The Effects of Androgens on Cardiometabolic Syndrome: Current Therapeutic Concepts.

INTRODUCTION: Cardiometabolic syndrome (CMS), as a bunch of metabolic disorders mainly characterized by type 2 diabetes mellitus (T2DM), hypertension, atherosclerosis, central adiposity, and abdominal obesity triggering androgen deficiency, is one of the most critical threats to men. Although many significant preclinical and clinical findings explain CMS, new approaches toward common pathophysiological mechanisms and reasonable therapeutic targets are lacking. AIM: To gain a further understanding of the role of androgen levels in various facets of CMS such as the constellation of cardiometabolic risk factors including central adiposity, dyslipidemia, insulin resistance, diabetes, and arterial hypertension and to define future directions for development of effective therapeutic modalities. METHODS: Clinical and experimental data were searched through scientific literature databases (PubMed) from 2009 to October 2019. MAIN OUTCOME MEASURE: Evidence from basic and clinical research was gathered with regard to the causal impact and therapeutic roles of androgens on CMS. RESULTS: There are important mechanisms implicated in androgen levels and the risk of CMS. Low testosterone levels have many signs and symptoms on cardiometabolic and glycometabolic risks as well as abdominal obesity in men. CLINICAL IMPLICATIONS: The implications of the findings can shed light on future improvements in androgen levels and add potentially predictive risk for CMS, as well as T2DM, abdominal obesity to guide clinical management in the early stage. STRENGTHS & LIMITATIONS: This comprehensive review refers to the association between androgens and cardiovascular health. A limitation of this study is the lack of large, prospective population-based studies that analyze the effects of testosterone treatment on CMS or mortality. CONCLUSION: Low testosterone levels have several common features with metabolic syndrome. Thus, testosterone may have preventive role in the progress of metabolic syndrome and subsequent T2DM, abdominal obesity, and cardiovascular disease and likely affect aging men's health mainly through endocrine and vascular mechanisms. Further studies are necessary to evaluate the therapeutic interventions directed at preventing CMS in men. Kirlangic OF, Yilmaz-Oral D, Kaya-Sezginer E, et al. The Effects of Androgens on Cardiometabolic Syndrome: Current Therapeutic Concepts. Sex Med 2020;8:132-155.

Correlation between upgrading of prostate biopsy and biochemical failure and unfavorable pathology after radical prostatectomy.

OBJECTIVE: To evaluate whether upgrading of the biopsy after radical prostatectomy (RP) affects disease outcome in terms of unfavorable pathology and biochemical failure. PATIENTS AND METHODS: We retrospectively evaluated the records of 174 patients who underwent RP. Prostate biopsy and RP specimen Gleason scores (GSs) and correlative clinical data were recorded, and a multivariate analysis was applied. RESULTS: Overall (138 patients), the disease of 69 men (50.0%) was upgraded, in 19 (13.8%) it was downgraded, and in 50 (36.2%) it had an identical biopsy and pathological GS. Accuracy rates were significantly higher for GS 8-10 compared to low GSs, with a concordance of 50.0 and 12.2%, respectively (p < 0.01). Multivariate analysis revealed the single independent prognostic factor for a non-organ-confined disease as a RP GS 8-10 (p = 0.035). The factors associated with a positive surgical margin were a biopsy GS 8-10 (p < 0.001) and the presence of biopsy score upgrading (p = 0.02). Biopsy GS >or=8 (p < 0.001) and presence of biopsy score upgrading (p = 0.009) were the two independent predictors of relapse after RP. CONCLUSION: This study demonstrated that biopsy upgrading was present in almost half of the patients who underwent RP and it was significantly related to positive surgical margins and biochemical relapse after RP.

Male Urogenital Disorders and Metabolic Syndrome: Possible Links, Characteristics and Potential Treatment Strategies.

BACKGROUND: Metabolic syndrome (MetS), as a cluster of metabolic derangements which are major risk factors for vascular disease is one of the most important threats to public health. Although the epidemiological and limited amount of basic science and clinical evidence link MetS to several male urogenital disorders, a holistic approach aiming to define common mechanistic pathways and new possible therapeutic targets are lacking. OBJECTIVE: The current review has focused on providing scientific evidence on the role of MetS and its components on male urogenital disorders and the definition of new therapeutic targets. METHOD: In this review, current clinical and basic science literature were assessed examining the role of MetS in etiology and pathogenesis of male urogenital disorders and performed through PubMed from 2000 to May 2017. RESULTS AND CONCLUSION: MetS shows an important association with common male urogenital disorders such as benign prostatic enlargement, lower urinary tract symptoms, erectile dysfunction, infertility and renal disease. MetS affects male urogenital system mainly through endocrine and vascular mechanisms. Obesity, hypogonadism, obesity-induced androgen deficiency, hyperinsulinemia and inflammation are the mechanisms commonly involved and may act as potential targets for MetS-male urogenital system interrelations. Future studies are needed to evaluate the therapeutic approaches for intervention in MetS-male urogenital disease relations.

The importance of prostate volume in prostate needle biopsy.

OBJECTIVE: Although ultrasound-guided prostate needle biopsy is the gold standard method in the diagnosis of prostate cancer, biopsy schemes and the number of repeated biopsies are still controversial today. It is known that the rate of prostate cancer decreases with increasing prostate volume. In this study, we evaluated the effects of prostate volume on cancer detection in our patient series. MATERIAL AND METHODS: In our clinic, data for 992 patients who had gray zone PSA levels (2.5-10 ng/mL) and whose 10 core biopsies were taken between 2004 and 2010 were evaluated. Among them, 500 patients from whom 6 to 8 biopsies were taken, whose information was lacking and who had suspicious cancer findings after digital rectal examination were excluded from the study. Patient ages, free/total PSA levels (f/TPSA), PSA densities (PSAD), Gleason scores, and prostate volumes were compared between patients with (Group 1) or without biopsy-proven prostate cancer (Group 2). Student's t-test was used for statistical analysis. RESULTS: According to biopsy findings, prostate cancer was detected in 74 patients while no cancer was detected in 418 patients. The mean age of Groups 1, and 2 were 65±8.6, and 64±8.1 years, respectively The mean prostate volume in Groups 1, and 2 were 45±23 cc, and 58±26 cc, respectively. CONCLUSION: In line with the literature, the average prostate volume of the prostate cancer group was significantly lower. This supports the notion that cancer detection is more probable in small prostates than in high-volume prostates.

A Phase II Trial of Cetuximab, Gemcitabine, 5-Fluorouracil, and Radiation Therapy in Locally Advanced Nonmetastatic Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. A minority of patients present with localized disease and surgical resection still offers patients the only hope for long-term survival. Locally advanced pancreatic cancer is defined as surgically unresectable, but has no evidence of distant metastases. The purpose of this study is to evaluate the efficacy and safety of cetuximab in combination with gemcitabine and 5-FU along with radiation therapy in locally advanced non-resectable, pancreatic adenocarcinoma, using progression free survival as the primary end point. METHODS: This was a prospective, single arm, open label pilot phase II study to evaluate the anti-tumor activity of gemcitabine (200 mg/m(2) per week) and cetuximab (250 mg/m(2) per week after an initial 400 mg/m(2) loading dose) with continuous infusion 5-FU (800 mg/m(2) over 96 hours) and daily concurrent external beam radiation therapy (50.4 Gy total dose) for six weeks (cycle 1) in patients with non-metastatic, locally advanced pancreatic adenocarcinoma. Following neoadjuvant treatment, subjects were re-evaluated for response and surgical candidacy with restaging scans. After resection, or also if not resected; subjects received further therapy with four 28-day cycles (cycles 2-5) of weekly gemcitabine (1000 mg/m(2)) and cetuximab (250 mg/m(2)) on days 1, 8, and 15. RESULTS: Between 2006 and 2011, twenty-six patients were screened and eleven of them were enrolled in the study. Most common reasons for screen failures were having resectable disease, metastatic disease or co-morbidity. Ten patients were able to tolerate and complete cycle 1 of chemoradiotherapy. One patient stopped the study prematurely due to grade III diarrhea. All except this one patient received planned radiation therapy. The response evaluation after cycle 1 showed one Partial Response, eight Stable Disease and two Progressive Disease. Four patients subsequently underwent surgical resection of the tumor. All patients had R0 resections. There was one preoperative mortality due to multiple organ failure. Median progression free survival (PFS) for four resected patients was 9.0 months while for unresected patients median PFS was 7.1 months. Median overall survival (OS) for four resected patients was 47.4 months and for unresected patients median OS was 17.0 months. Most common adverse events were hematologic (27%). Only two patients developed grade 3 neutropenia. Most common treatment related non-hematologic adverse events were diarrhea (10 of 11), nausea (8 of 11) and skin rash (10 of 11 patients). Only 9.5% of all reported non-hematologic adverse events were grade 3 or higher. CONCLUSIONS: The combination of cetuximab, weekly gemcitabine and continuous infusion of 5-FU with radiotherapy was quite well tolerated with intriguing clinical benefit and survival results in carefully selected patients with locally advanced pancreatic adenocarcinoma. A trial with larger sample size will be necessary to confirm these results.