Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial.

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.

Male reproductive health after 3 months from SARS-CoV-2 infection: a multicentric study.

PURPOSE: While SARS-CoV-2 infection appears not to be clinically evident in the testes, indirect inflammatory effects and fever may impair testicular function. To date, few long-term data of semen parameters impairment after recovery and comprehensive andrological evaluation of recovered patients has been published. The purpose of this study was to investigate whether SARS-CoV-2 infection affect male reproductive health. METHODS: Eighty patients were recruited three months after COVID-19 recovery. They performed physical examination, testicular ultrasound, semen analysis, sperm DNA integrity evaluation (TUNEL), anti-sperm antibodies (ASA) testing, sex hormone profile evaluation (Total testosterone, LH, FSH). In addition, all patients were administered International Index of Erectile Function questionnaire (IIEF-15). Sperm parameters were compared with two age-matched healthy pre-COVID-19 control groups of normozoospermic (CTR1) and primary infertile (CTR2) subjects. RESULTS: Median values of semen parameters from recovered SARS-CoV-2 subjects were within WHO 2010 fifth percentile. Mean percentage of sperm DNA fragmentation (%SDF) was 14.1 ± 7.0%. Gelatin Agglutination Test (GAT) was positive in 3.9% of blood serum samples, but no positive semen plasma sample was found. Only five subjects (6.2%) had total testosterone levels below the laboratory reference range. Mean bilateral testicular volume was 31.5 ± 9.6 ml. Erectile dysfunction was detected in 30% of subjects. CONCLUSION: Our data remark that COVID-19 does not seem to cause direct damage to the testicular function, while indirect damage appears to be transient. It is possible to counsel infertile couples to postpone the research of parenthood or ART procedures around three months after recovery from the infection.

Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19.

STUDY QUESTION: How is the semen quality of sexually active men following recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? SUMMARY ANSWER: Twenty-five percent of the men with recent SARS-Cov-2 infections and proven healing were oligo-crypto-azoospermic, despite the absence of virus RNA in semen. WHAT IS KNOWN ALREADY: The presence of SARS-CoV-2 in human semen and its role in virus contagion and semen quality after recovery from coronavirus disease 2019 (COVID-19) is still unclear. So far, studies evaluating semen quality and the occurrence of SARS-CoV-2 in semen of infected or proven recovered men are scarce and included a limited number of participants. STUDY DESIGN, SIZE, DURATION: A prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV2 was performed. Four biological fluid samples, namely saliva, pre-ejaculation urine, semen, and post-ejaculation urine, were tested for the SARS-CoV-2 genome. Female partners were retested if any specimen was found to be SARS-CoV-2 positive. Routine semen analysis and quantification of semen leukocytes and interleukin-8 (IL-8) levels were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Questionnaires including International Index of Erectile Function and Male Sexual Health Questionnaire Short Form were administered to all subjects. The occurrence of virus RNA was evaluated in all the biological fluids collected by RT-PCR. Semen parameters were evaluated according to the World Health Organization manual edition V. Semen IL-8 levels were evaluated by a two-step ELISA method. MAIN RESULTS AND THE ROLE OF CHANCE: After recovery from COVID-19, 25% of the men studied were oligo-crypto-azoospermic. Of the 11 men with semen impairment, 8 were azoospermic and 3 were oligospermic. A total of 33 patients (76.7%) showed pathological levels of IL-8 in semen. Oligo-crypto-azoospermia was significantly related to COVID-19 severity (P < 0.001). Three patients (7%) tested positive for at least one sample (one saliva; one pre-ejaculation urine; one semen and one post-ejaculation urine), so the next day new nasopharyngeal swabs were collected. The results from these three patients and their partners were all negative for SARS-CoV-2. LIMITATIONS, REASONS FOR CAUTION: Although crypto-azoospermia was found in a high percentage of men who had recovered from COVID-19, clearly exceeding the percentage found in the general population, the previous semen quality of these men was unknown nor is it known whether a recovery of testicular function was occurring. The low number of enrolled patients may limit the statistical power of study. WIDER IMPLICATIONS OF THE FINDINGS: SARS-CoV-2 can be detected in saliva, urine, and semen in a small percentage of men who recovered from COVID-19. One-quarter of men who recovered from COVID-19 demonstrated oligo-crypto-azoospermia indicating that an assessment of semen quality should be recommended for men of reproductive age who are affected by COVID-19. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Tadalafil Alone or in Combination with Tamsulosin for the Management for LUTS/BPH and ED.

PURPOSE OF REVIEW: Aim of our systematic review is to evaluate and summarize the efficacy and safety of tadalafil alone or in combination with tamsulosin for the management of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). RECENT FINDINGS: Daily tadalafil, in particular 5 mg, according to retrieved studies, appears to be both safe and effective in treating LUTS/BPH and ED, compared with placebo or tamsulosin. The combination of daily tadalafil 5 mg and tamsulosin 0.4 mg allows a better improvement of LUTS compared with both the monotherapies, even if with an increased, but acceptable and tolerated, adverse events rate. After discontinuation of tamsulosin or tadalafil in patients previously treated with their combination, the improvement of LUTS retains significance compared with baseline. Tadalafil 5 mg should be considered a primary treatment option for patients with LUTS/BPH and ED. Evidence highlight an excellent tolerability, safety, and effectiveness profile, both alone or in combination with tamsulosin 0.4 mg. A better efficacy on LUTS relief has been observed for combination therapy, preserving also sexual function. The further switch to monotherapy allows to preserve LUTS relief, but tadalafil only is able to retain ED improvement. Our results support the evidence for a more and more tailored and modular LUTS treatment.

Do malignant diseases affect semen quality? Sperm parameters of men with cancers.

The advent of modern treatments together with the improvement of the surgical techniques has significantly increased 5-year survival rates of young patients with cancer. Although the deleterious effects of chemotherapy and radiation are well documented, controversies exist about the effect of cancer itself on semen parameters before treatment. We collected data on 236 patients representative of different types of cancers reoffered at our institution for sperm cryopreservation with the aim to correlate the pre-freeze semen parameters with type of cancer, disease stage and with semen quality of 102 fertile and healthy men. The median baseline semen parameters of all our patients with cancer are placed above the 5th percentile of the World Health Organization reference value, but the type of cancer may impact the sperm parameters. In testicular tumours and in Hodgkin lymphoma, we show a semen concentration statistically lower than in the fertile population, while in patients with other cancers, there is no difference with the healthy men. We found no correlation between semen quality and disease stage. Eighty-six per cent of our patients do not have children at the time of semen cryopreservation, and the only established clinical option for preserving fertility of these men is cryopreservation of spermatozoa.

Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study.

The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS.

The semen quality of the mobile phone users.

BACKGROUND: The increased use of mobile phones, the media's attention for general health, and the increase of idiopathic male infertility suggest to investigate the possible consequences of an excessive use of mobile phones on semen quality. AIM: To evaluate the conventional and some of the main biofunctional sperm parameters in healthy men according to the different use of the mobile phone. SUBJECTS AND METHODS: All the enrolled subjects in this study were divided into four groups according to their active cell phone use: group A= no use (no.=10 subjects); group B= <2 h/day (no.=16); group C= 2-4 h/day (no.=17); and group D= >4 h/day (no.=20). Among the subjects of the group D (>4 h/day), a further evaluation was made between the "trousers users"(no.=12) and "shirt users"(no.=8), and they underwent semen collection to evaluate conventional and biofunctional sperm parameters (density, total count, morphology, progressive motility, apoptosis, mithocondrial membrane potential, chromatin compaction, DNA fragmentation). RESULTS: None of the conventional sperm parameters examined were significantly altered. However, the group D and the trousers users showed a higher percentage of sperm DNA fragmentation compared to other groups. CONCLUSION: These results suggest that the sperm DNA fragmentation could represent the only parameter significantly altered in the subjects who use the mobile phone for more than 4 h/day and in particular for those who use the device in the pocket of the trousers.

Impact of different typologies of smoking on ovarian reserve and oocyte quality in women performing ICSI cycles: an observational prospective study.

OBJECTIVE: Within the last few years smoking activities, as well as infertility, have increased in Italy, and so has the consumption of alternative cigarette devices among women of childbearing age. The aim of this observational study was to evaluate the impact of the consumption of cigarettes and alternatives devices, such as electronic cigarettes and heat-not-burn (HnB) products, on infertile women performing in vitro fertilization (IVF), in specific on the quality of oocytes retrieved in women performing intracytoplasmic sperm injection (ICSI) cycles. PATIENTS AND METHODS: Prospective observational longitudinal study involving 410 women referring to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, from 2019-2022. All the women enrolled filled out an elaborate questionnaire investigating smoking consumption, before the beginning of ovarian stimulation by antagonist protocol, ovarian pick-up, and subsequent ICSI technique. The outcomes of the study were the evaluation of clinical and ICSI features between the groups of smokers and non-smokers: the number of retrieved oocytes, immature oocytes, and fertilization rate were confronted between the two groups and between cigarette smokers vs. e-cigarette and heat-not-burn (HnB) products smokers. RESULTS: Clinical parameters were comparable between the group of smokers compared to one of the non-smokers, except for anti-Müllerian hormone (AMH), which was statistically lower in smokers (p<0.05). Regarding IVF hormonal stimulations it appears that the total dose of gonadotropin was statistically lower in the non-smoker's group, compared to smokers (1850±860 UI vs. 1,730±780 p<0.05). Regarding ICSI techniques interestingly the number of oocytes retrieved was lower in the smokers' group compared to non-smokers (5.21±0.9 vs. 6.55±3.5, p<0.001), and the number of empty zona pellucida oocytes was statistically higher in the smokers' group (0.51±0.1 vs. 0.2±0.1, p<0.05). On the other hand, the fertilization rate (FR) was statistically higher in non-smokers compared to the smokers' group (72.16±3.05 vs. 68.12±2.21, p=0.03). Out of the 203 smokers, overall, any statistically significant difference, regarding ICSI results, has been found between the group of cigarette smokers, compared to the group of e-cigarettes plus HnB products smokers. CONCLUSIONS: Smoking negatively impacts human fertility, leading to a reduction of ovarian reserve and ovarian quality, which can negatively impact results in women performing ICSI cycles. Despite the limitation of the study, our results underline that consumption of cigarette alternative devices seems to have a similar negative impact on the quantity and quality of oocytes retrieved in ICSI cycles. Clinicians should emphasize the reduction of exposure to harmful substances derived from the combustion of tobacco smoking, as well as alternative devices, in women of childbearing age.

Effect of vardenafil on semen parameters in infertile men: a pilot study evaluating short-term treatment.

BACKGROUND: Severeal in vivo and in vitro studies have been carried out in order to evaluate the efficacy of long-term treatment with phosphodiesterase type-5 (PDE5) inhibitors (PDE5i) on spermatogenesis, but the results are still controversial. AIM: To evaluate the effects of vardenafil on seminal parameters of infertile men after a short-term treatment. MATERIALS/SUBJECTS AND METHODS: A total of 205 male subjects were randomized to receive a single dose of vardenafil 10 mg (73 men, group B), a single dose of vardenafil 10 mg every other day for 15 days (67 men, group C), and no treatment (65 men, group A). Semen parameters were evaluated before and after the end of the treatment in each of group A, B, and C, respectively. Additionally, an IIEF- 5 questionnaire was administered to all patients with erectile dysfunction (ED) before and after each treatment period. RESULTS: The semen parameters in groups B and C has shown a significant increase in percentage forward motility after vardenafil administration as compared with baseline (p<0.001). In group C, we observed an increase in the mean semen volume and an improvement in the mean total sperm concentration (p<0.001) as compared with baseline. CONCLUSIONS: We showed the efficacy of vardenafil in the treatment of ED and, on a large series of infertile patients, the positive effect on sperm motility after a single-dose administration. It also showed that after 15 days of treatment on alternate days is also achieved an improvement in sperm concentration.

Extraction of DNA from soil using nanoparticles by magnetic bioseparation.

AIMS: To develop a simple, rapid and inexpensive soil DNA extraction protocol. METHODS AND RESULTS: The protocol relies on the use of superparamagnetic silica-magnetite nanoparticles for the isolation and purification of DNA from soil samples. DNA suitable for use in molecular biology applications was obtained from a number of soil samples. CONCLUSIONS: The DNA extracted using the tested method successfully permitted the PCR amplification of a fragment of the bacterial 16S rDNA gene. The extracted DNA could also be restriction endonuclease digested. SIGNIFICANCE AND IMPACT OF THE STUDY: The protocol reported here is simple and permits rapid isolation of PCR-ready soil DNA. The method requires only small quantities of soil sample, is scalable and suitable for automation.

Meta-analysis of metabolic syndrome and prostate cancer.

BACKGROUND: Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features. METHODS: A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4-5 according to the novel prostate cancer grading system). Also the association between MetS and individual MetS components with pathological Gleason Score⩾8, extra-capsular extension, seminal vesicle invasion, positive surgical margins and biochemical recurrence (defined as two consecutive PSA values ⩾0.2 ng ml-1 after radical prostatectomy) was evaluated. RESULTS: 24 studies were selected including a total of 132 589 participants of whom 17.35% had MetS. There was a slight association between MetS and PCa incidence (odds ratio (OR)=1.17 (1.00-1.36), P=0.04) and between high-grade PCa and MetS (OR= 1.89 (1.50-2.38), P<0.0001) but the studies were statistically heterogeneous. No association was found between MetS components and PCa risk except for hypertension. MetS was significantly associated with pathologic Gleason Score⩾8 (OR= 1.77 (1.34-2.34); P<0.01), extra-capsular extension (OR=1.13 (1.09-1.18); P<0.01), seminal vesicle invasion (OR=1.09 (1.07-1.12); P<0.01), positive surgical margins (OR=1.67 (1.47-1.91); P<0.01) and biochemical recurrence (OR=1.67 (1.04-2.69); P<0.01). CONCLUSIONS: The presence of MetS is associated with worse oncologic outcomes in men with PCa, in particular with more aggressive tumor features, and biochemical recurrence.

Fatty acids profiling reveals potential candidate markers of semen quality.

Previous reports showed altered fatty acid content in subjects with altered sperm parameters compared to normozoospermic individuals. However, these studies focused on a limited number of fatty acids, included a short number of subjects and results varied widely. We conducted a case-control study involving 155 patients allocated into four groups, including normozoospermia (n = 33), oligoasthenoteratozoospermia (n = 32), asthenozoospermia (n = 25), and varicocoele (n = 44). Fatty acid profiling, including 30 species, was analyzed by a validated gas chromatography (GC) method on the whole seminal fluid sample. Multinomial logistic regression modeling was used to identify the associations between fatty acids and the four groups. Specimens from 15 normozoospermic subjects were also analyzed for fatty acids content in the seminal plasma and spermatozoa to study the distribution in the two compartments. Fatty acids lipidome varied markedly between the four groups. Multinomial logistic regression modeling revealed that high levels of palmitic acid, behenic acid, oleic acid, and docosahexaenoic acid (DHA) confer a low risk to stay out of the normozoospermic group. In the whole population, seminal fluid stearic acid was negatively correlated (r = -0.53), and DHA was positively correlated (r = 0.65) with sperm motility. Some fatty acids were preferentially accumulated in spermatozoa and the highest difference was observed for DHA, which was 6.2 times higher in spermatozoa than in seminal plasma. The results of this study highlight complete fatty acids profile in patients with different semen parameters. Given the easy-to-follow and rapid method of analysis, fatty acid profiling by GC method can be used for therapeutic purposes and to measure compliance in infertility trials using fatty acids supplements.

Role of Clostridium difficile in childhood diarrhea.

To investigate the etiologic role of Clostridium difficile in childhood acute diarrhea, stool specimens from 618 children with diarrhea and 135 controls without enteric symptoms were examined by cell culture assay for the presence of free toxin B. This toxin was found in 4.2% of the fecal specimens examined without finding a significant difference between cases and controls, suggesting no causal relationship between diarrhea and the presence of free C. difficile toxin B. C. difficile strains isolated from toxin B-positive specimens were characterized by cytotoxin and enterotoxin production and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EDTA-extracted proteins. All but two isolates produced toxin B and toxin A and the remaining were negative for both toxins. Polyacrylamide gel electrophoresis analysis showed eight electrophoretic types, none of them was clearly related with the cases of diarrhea. The majority of isolates from children with diarrhea did not belong to types previously observed in adults with pseudomembranous colitis or antibiotic-associated diarrhea. This study provides additional evidence that C. difficile is not involved in the etiology of childhood diarrhea.

[The cardiological evaluation in patients undergoing to Day Surgery: when is indicated]. / La consulenza cardiologica nei pazienti da sottoporre ad intervento chirurgico in regime di Day Surgery: quando è indicate.

AIM: Guidelines established preoperative cardiac management of the patient undergoing non-cardiac surgery in hospitalization. Regarding the patients undergoing the surgery in DS, the management is not defined. Aim of this study was to evaluate the appropriateness of the cardiological consultation requested by the patients undergoing surgery with this method. MATERIALS AND METHODS: We examined the request of cardiological evaluation for patient admitted to DS of Sant'Andrea Hospital in Rome. We have considered: age, sex, clinic history, simpthomatology, electrocardiogram, cardiovascular objectivity, hemodynamic stability, comorbidity, therapy, type of the surgery, the motivation of the request. RESULTS: Of 2350 patients, 495 patients (21%) have been undergone the preoperative cardiologic consultation. The request was resulted as unnecessary for 432 (87.2%) patients, appropriate for 63 (12.7%): 4 that had the ischemic heart disease without knowing this, 6 with severe hypertension; 2 with mitral valve prolapse and valvular regurgitation; 34 with congestive heart failure; 6 with the alterations in EKG : 3 with "Brugada pattern"; 1 with Pace Maker (PMK) that had to be reprogrammed before the operation; 3 under dual antiplatelet therapy; 7 that were taking the oral anticoagulant therapy. Cardiac complications occurred just in one case with patient suffering dilated cardiomyopathy, diabetes and hypertension; during the cataract surgery was presented the abrupt increase of blood pressure and left ventricular failure. CONCLUSIONS: Preoperative cardiologic evaluation results as useless in most patients. However, in some particular situations had allowed the diagnosis of heart disease for the patients who did not know to have it.

Management of benign prostatic hyperplasia: role of phosphodiesterase-5 inhibitors.

Several studies have highlighted a strong association between benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED), particularly in elderly men. Many epidemiological trials, such as in vitro and in vivo studies, have reported the emerging role of metabolic syndrome, including abdominal obesity, impaired glucose metabolism, hypertriglyceridemia, low high-density lipoprotein cholesterol, and hypertension, in the development and progression of urinary and sexual symptoms. Moreover, many authors have focused their studies on the identification of all the shared pathogenetic mechanisms of LUTS/BPH and ED, including alteration of cyclic guanosine monophosphate and RhoA-ROCK pathways or vascular and neurogenic dysfunction. All these are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Therefore, several trials have recently been designed to evaluate the role of PDE5-Is alone or in combination with conventional treatment for BPH, such as α-adrenergic blockers, in men affected by LUTS/BPH, with or without ED. Different PDE5-Is are in clinical use worldwide and currently six of them are licensed for the oral treatment of ED. All these compounds differ in pharmacokinetic factors, with influence on drug action, and subsequently in the overall safety and efficacy profile.

PDE5-Is for the Treatment of Concomitant ED and LUTS/BPH.

Epidemiologic data in adult men exhibit a strong relationship between erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), indicating that men affected by ED should also be investigated for LUTS/BPH and those presenting with storage or voiding LUTS should be investigated for co-morbid ED. Common pathophysiolgical mechanisms underlying both LUTS/BPH and ED, including alteration of NO/cGMP or RhoA/Rho-kinase signaling and/or vascular or neurogenic dysfunction, are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Several randomized controlled trials and only a few reviews including all commercially available PDE5-Is demonstrated the safety and efficacy of these drugs in the improvement of erectile function and urinary symptoms, in patients affected either by ED, LUTS, or both conditions.

Metabolic syndrome and lower urinary tract symptoms: the role of inflammation.

BACKGROUND: Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities.Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens. METHODS: A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker. RESULTS: Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm(3) (hazard ratio (HR) = 3.268, P < 0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Q(max)): 8.6 vs 10.1, P = 0.008 and average flow rate (Q(ave)): 4.6 vs 5.3, P = 0.033, respectively), and higher obstructive urinary symptoms score (P = 0.064). A positive correlation among both IS-GD and IPSS Score was also observed (adjusted r = 0.172, P = 0.008 and adjusted r = 0.128, P = 0.050). CONCLUSIONS: MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.

[Splenic infarction after warfarin discontinuation during atrial fibrillation]. / Infarto splenico: rara complicanza tromboembolica di fi brillazione atriale.

We describe a case of patient with splenic infarction, admitted to our department for sudden abdominal pain and fever after discontinuation of anticoagulant therapy for atrial fibrillation, complicating a dilated myocardiopathy and mechanical prosthetic valve. Diagnosis of splenic infarction was made by enhanced-contrast computed tomography, while ultrasounds and radiography were negative. Anticoagulant therapy, gold-standard treatment, was followed by fast clinical improvement. Moreover, splenic infarction should be considered in all cases of acute or chronic pain in left hypochondrium and especially in patients with emboligenous cardiopathies or atrial fibrillation, the most common arrhythmia source of peripheral embolism in clinical practice.

Susceptibility patterns and characterization of beta-lactamases in clinical isolates of Bacteroides fragilis.

Strains of Bacteroides fragilis isolated from clinical specimens are known to be frequently resistant to penicillins or cephalosporins. The production of beta-lactamases is the major mechanism in this resistance. Up to now at least five types of beta-lactamase enzymes have been described in the Bacteroides fragilis group. The purpose of this study was to evaluate the susceptibility to different antibiotics and the prevalence of the beta-lactamase types among 100 Bacteroides fragilis strains isolated from clinical specimens in Italy. MICs of 11 antibiotics were determined by the reference agar dilution method and by the new E test (AB Biodisk, Sweden). Results showed an acceptable correlation between the MICs determined for most strains, although those obtained by the E test tended to be lower. In the beta-lactam resistant strains the enzyme activity and isoelectric points were determined on crude enzyme extract.