Advanced Paternal Age in Focus: Unraveling Its Influence on Assisted Reproductive Technology Outcomes.

As global demographics shift toward increasing paternal age, the realm of assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), faces new challenges and opportunities. This study provides a comprehensive exploration of the implications of advanced paternal age on ART outcomes. Background research highlights the social, cultural, and economic factors driving men toward later fatherhood, with a focus on the impact of delayed paternity on reproductive outcomes. Methods involve a thorough review of existing literature, centering on changes in testicular function, semen quality, and genetic and epigenetic shifts associated with advancing age. Study results point to intricate associations between the father's age and ART outcomes, with older age being linked to diminished semen quality, potential genetic risks, and varied impacts on embryo quality, implantation rates, and birth outcomes. The conclusions drawn from the current study suggest that while advanced paternal age presents certain risks and challenges, understanding and mitigating these through strategies such as sperm cryopreservation, lifestyle modifications, and preimplantation genetic testing can optimize ART outcomes. Future research directions are identified to further comprehend the epigenetic mechanisms and long-term effects of the older father on offspring health. This study underscores the need for a comprehensive approach in navigating the intricacies of delayed fatherhood within the context of ART, aiming for the best possible outcomes for couples and their children.

Evaluating the Impact of Benign Prostatic Hyperplasia Surgical Treatments on Sexual Health.

Benign prostatic hyperplasia (BPH), a prevalent condition in older men, is often managed through various surgical interventions. This narrative review aims to explore the impact of these surgical treatments on sexual function, a critical aspect of patient quality of life often overlooked in BPH management. The methodology encompassed a thorough review of contemporary surgical techniques for BPH, including prostate resection, enucleation, vaporization, and minimally invasive therapies such as UroLift, Rezum, and Aquablation. Additionally, the focus was on patient-centered outcomes, with a special emphasis on sexual health following surgery. Findings reveal that, while surgical interventions effectively alleviate BPH symptoms, they often have significant repercussions in sexual function, including erectile and ejaculatory dysfunction. However, emerging techniques demonstrate potential in preserving sexual function, underscoring the need for patient-centric treatment approaches. The study highlights the complex interplay between BPH surgery and sexual health, with minimally invasive treatments showing promise in balancing symptom relief and sexual function preservation. In conclusion, the study advocates for an integrated, interdisciplinary approach to BPH treatment, emphasizing the importance of considering sexual health in therapeutic decision-making. This narrative review suggests a paradigm shift towards minimally invasive techniques could optimize patient outcomes, marrying symptom relief with quality-of-life considerations. The need for further research in this domain is evident, particularly in understanding long-term sexual health outcomes following different surgical interventions for BPH.

Diagnostic Challenges and Management of Acquired Hemophilia A Presenting as Gross Hematuria: A Case Report.

Acquired hemophilia A (AHA) is a rare autoimmune disorder marked by autoantibodies against coagulation factor VIII, leading to bleeding complications. This case report explores a unique presentation of AHA, initially manifested as gross hematuria, a symptom often encountered in healthcare settings with a broad range of differential diagnoses. The background of this study highlights the rarity of AHA and its diverse clinical presentations. The case involves a 62-year-old man with no history of bleeding disorders, presenting with gross hematuria and later developing severe anemia and ecchymoses. Methods employed in the evaluation included urological assessments such as cystoscopy and computed tomography, alongside hematological investigations, which later revealed a prolonged activated partial thromboplastin time (aPTT) and a critically low factor VIII level, indicative of AHA. Results showed a lack of early recognition of coagulation abnormalities, underscoring the need for comprehensive initial assessments in cases of unexplained hematuria. The patient's management at a specialized Hemophilia Center involved inhibitor eradication therapy and management of acute bleeding episodes, resulting in significant clinical improvement. The conclusions drawn from this case emphasize the importance of considering rare conditions like AHA in the differential diagnosis of hematuria and the necessity for a broad diagnostic approach. It advocates for heightened awareness and early coagulation studies in unexplained cases of hematuria to prevent delayed diagnoses and improve patient outcomes. This case contributes to the understanding of AHA's clinical variability and the critical nature of early and comprehensive diagnostic approaches in hematuria evaluation.

The use of intravesical hyaluronic acid in the management of symptomatic premenopausal women with pseudomembranous trigonitis: Are symptoms related to cystoscopy and pathological findings?

OBJECTIVES: To determine the effectiveness and safety of intravesical hyaluronic acid (HA) in symptomatic women with trigonitis and to correlate the severity of symptoms with the endoscopic and histological findings. METHODS: Thirty-seven patients (aged 20-46 years) were enrolled. All patients had cystoscopy and biopsy of the bladder trigone followed by intravesical instillations of sodium HA once weekly for 10 weeks and then once monthly for the next 10 months. Clinical response was evaluated by Pain and Urgency/Frequency (PUF) Symptom Scale, visual analog scale (VAS) for pain and urgency and functional bladder capacity. A repeat cystoscopy and biopsy were performed at the end of the treatment. Symptoms and cystoscopy and pathological findings were compared before and after treatment. RESULTS: The average initial score for pain was reduced from 5.5 to 2.8 (P < 0.001) at 10 weeks and further to 2.4 (P < 0.001) at 12 months and the score for urgency from 6.9 to 3.8 (P < 0.001) and further to 3.3 (P < 0.001). The average PUF score initially decreased from 20.5 to 12.1 (P < 0.001) and then further to 10.1 (P = 0.21). The mean functional bladder capacity increased from 125 to 204 mL (P < 0.001). No association was found between baseline PUF score and cystoscopy findings (P = 0.87). The PUF score was not changed significantly between patients with improved cystoscopy and those with stable findings (P = 0.74). No significant changes were reported between initial and final biopsies. CONCLUSIONS: Intravesical HA appeared to be effective and well tolerated, although a clear relationship between symptoms and trigonitis was not confirmed.

Computed Tomography-Guided Percutaneous Microwave Ablation for Renal Cell Carcinoma: Impact of Tumor Size on the Progression Survival Rates.

The aim of the present study was to evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma (RCC) along with identifying prognostic factors affecting the progression survival rate. Institutional database retrospective research identified 69 patients with a biopsy proven solitary T1a (82.6%) or TIb (17.4%) RCC who have underwent percutaneous CT-guided MWA. Kaplan-Meier survival estimates for events were graphed and Cox regression analysis was conducted. Mean patient age was 70.4 ± 11.5 years. Mean size of the lesions was 3 ± 1.3 cm. Mean follow up time was 35.6 months (SD = 21.1). The mean progression free survival time from last ablation was 84.2 months. For T1a tumors, the cumulative progression free survival rate for 1, 6, 12 and 36 months were 100% (SE = 0%), 91.2% (SE = 3.7%), 91.2% (SE = 3.7%) and 87.5% (SE = 4.4%); the recurrence free survival rate for T1a RCC was 94.9%. For T1b tumors, the cumulative progression free survival rate for 1, 6, 12 and 36 months were 100% (SE = 0%), 63.6% (SE = 14.5%), 63.6% (SE = 14.5%) and 63.6% (SE = 14.5%). Grade 1 complications were recorded in 5 (7.2%) patients. Significantly greater hazard for progression was found in cases with a tumor size > 4 cm (HR = 9.09, p = 0.048). No statistically important difference regarding tumor progression was recorded between T1a tumors with a diameter ≤3 cm and >3 cm. In summary, the results of the present study show that CT guided percutaneous MWA is an effective technique for treatment of T1a renal cell carcinomas, irrespective of tumor size. T1b tumors were associated with higher progression rates.

Referral for "Neoadjuvant Chemotherapy" for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes.

BACKGROUND: Utilization of neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer in everyday practice differs from that of clinical trials. We describe the patterns of referral for "neoadjuvant chemotherapy", treatment and outcomes in a multidisciplinary tumor board. METHODS: This was an observational study. Patients referred for neoadjuvant chemotherapy received 4 cycles of dose-dense gemcitabine/cisplatin and were then assessed for definitive local therapy. Patients had a minimum follow-up of 2 years. Primary objective was a 3-year disease-free survival rate. RESULTS: Forty-six patients (clinical stages II: 28, IIIA: 9, IIIB: 4, IVA: 3, missing: 2) were included. Following chemotherapy, 30 underwent radical cystectomy, 8 radiotherapy and 8 no further therapy. Pathological downstaging was observed in 14 (46.6%) of the 30 patients who underwent radical cystectomy; clinical TNM staging was correlated with disease-free survival in the whole population, while clinical and pathological stages, as well as pathological downstaging, were correlated with disease-free survival in patients undergoing radical cystectomy. Three-year disease-free survival rates for the whole cohort and for patients undergoing radical cystectomy were 67.3% (95% confidence interval [CI]: 51-79.2) and 65.2 (95% CI: 44.9-79.6), respectively. CONCLUSION: Real-world muscle invasive bladder cancer patients who receive neoadjuvant chemotherapy are characterized by more advanced diseases and less frequent radical surgery than those included in clinical trials. Nevertheless, outcomes were comparable and, therefore, offering patients with stage II-IVA muscle invasive bladder cancer neoadjuvant chemotherapy after assessment by multidisciplinary tumor boards should be strongly encouraged.

Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study.

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients' adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment.

Progression into sepsis: an individualized process varying by the interaction of comorbidities with the underlying infection.

BACKGROUND: Development of sepsis is a process with significant variation among individuals. The precise elements of this variation need to be defined. This study was designed to define the way in which comorbidities contribute to sepsis development. METHODS: Three thousand five hundred nine patients with acute pyelonephritis (AP), community-acquired pneumonia (CAP), intraabdominal infections (IAI) or primary bacteremia (BSI) and at least two signs of the systemic inflammatory response syndrome were analyzed. The study primary endpoint was to define how comorbidities as expressed in the Charlson's comorbidity index (CCI) and the underlying type of infection contribute to development of organ dysfunction. The precise comorbidities that mediate sepsis development and risk for death among 18 comorbidities recorded were the secondary study endpoints. RESULTS: CCI more than 2 had an odds ratio of 5.67 for sepsis progression in patients with IAI between significantly higher than AP and BSI. Forward logistic regression analysis indicated seven comorbidities that determine transition into sepsis in patients with AP, four comorbidities in CAP, six comorbidities in IAI and one in BSI. The odds ratio both for progression to sepsis and death with one comorbidity or with two and more comorbidities was greater than in the absence of comorbidities. CONCLUSIONS: The study described how different kinds of infection vary in the degree to which they lead to sepsis. The number of comorbidities that enhances the risk of sepsis and death varies depending on the underlying infections.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result

Abstract Introduction: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a positive second biopsy in males considered for re-biopsy. Material and Methods: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testosterone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. Results: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). Conclusion: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result.

INTRODUCTION: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a posi¬tive second biopsy in males considered for re-biopsy. MATERIAL AND METHODS: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testos¬terone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. RESULTS: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). CONCLUSION: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Outcome of patients with nonmetastatic muscle-invasive bladder cancer not undergoing cystectomy after treatment with noncisplatin-based chemotherapy and/or radiotherapy: a retrospective analysis.

Transurethral resection of bladder tumor (TURBT), radiotherapy, chemotherapy, or combinations can be used in patients with muscle-invasive bladder cancer (MIBC) not undergoing cystectomy. Nevertheless, unfitness for cystectomy is frequently associated with unfitness for other therapeutic modalities. We report the outcome of patients with MIBC who did not undergo cystectomy and did not receive cisplatin-based chemotherapy. Selection criteria for the study were nonmetastatic MIBC, no cystectomy, no cisplatin-based chemotherapy. Chemotherapy and/or radiotherapy should have been used aside from TURBT. Forty-nine patients (median age 79), managed between April 2001 and January 2012, were included in this analysis. Median Charlson Comorbidity Index was 5, while 76% were unfit for cisplatin. Treatment included radiotherapy (n = 7), carboplatin-based chemotherapy (n = 25), carboplatin-based chemotherapy followed by radiotherapy (n = 10), and radiochemotherapy (n = 7). Five-year event-free rate was 26% (standard error [SE] = 7) for overall survival, 23% (SE = 7) for progression-free survival, and 30 (SE = 8) for cancer-specific survival (CSS). Patients who were treated with combination of radiotherapy and chemotherapy had significantly longer CSS compared to those treated with radiotherapy or chemotherapy only (5-year CSS rate: 16% [SE 8] vs. 63% [SE 15], P = 0.053). Unfit-for-cystectomy patients frequently receive suboptimal nonsurgical treatment. Their outcome was poor. Combining chemotherapy with radiotherapy produced better outcomes and should be prospectively evaluated.

Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells.

Expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in localized prostate cancer.

OBJECTIVE: To explore the correlation between the expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in prostate cancer (PCa) and its clinicopathological data including tumor grade and clinical stage. METHODS: The expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin was examined in 157 cases of PCa and adjacent normal prostatic tissue by immunohistochemical assay, and the correlation with clinicopathological features was analyzed. RESULTS: Expressions of α5-integrin, α7-integrin, and Ε-cadherin in PCa were lower than those in normal prostatic tissues (P<0.05). N-cadherin expression was higher in cancer prostatic tissue than in normal prostatic tissues (P<0.05). The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but it was not associated with positive surgical margins and patient age. The increased expression of N-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but not to age and positive surgical margins. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also positively correlated with that of α5-integrin and α7-integrin. CONCLUSION: The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin and abnormal expression of N-cadherin play an important role in the occurrence and development of PCa. The results indicate that these have potential values in the diagnosis and are predictable indices in the proliferation of PCa.

The Role of PCA 3 as a Prognostic Factor in Patients with Castration-resistant Prostate Cancer (CRPC) Treated with Docetaxel.

AIM: To investigate potential fluctuations in prostate cancer antigen 3 (PCA 3) scores in castration-resistant prostate cancer (CRPC) patients treated with docetaxel and investigate the assay as a potential prognostic factor. PATIENTS AND METHODS: This was a prospective observational cohort study. Inclusion criteria included patients on hormonal treatment who were recently diagnosed with CRPC. Exclusion criteria included patients previously having radical treatment (surgery or radiotherapy) and patients who have completed the first cycle of chemotherapy. All urine samples were collected and analyzed using the Progensa® assay. Samples were collected before starting chemotherapy and at 12 months. A prospective database was created including routine blood tests, prostate staging and prostate-specific antigen (PSA) levels throughout the study period. The effects of chemotherapy were also recorded. RESULTS: Between January 2010 and February 2013, 12 patients were included in the study out of an initial cohort of 23 patients with CRPC. Mean follow-up was 14.8 months. Mean age at CRPC diagnosis was 73.8 years (±3.6 SD). Mean Gleason score was 8, with PSA 84.23 ng/ml (±158 SD). Mean duration of androgen deprivation treatment (ADT) was 45.16 months (±34.9 SD). Mean time to castrate-resistant state was 46.58 months (±35.3 SD). All twelve (n=12, 100%) patients had non-assessable PCA 3 scores at baseline and at 12 months follow-up. As a direct consequence, statistical analysis was not performed as the anticipated change in PCA 3 scores was not identified and correlation between measurable differences was not possible. All patients tolerated chemotherapy and completed the scheduled cycles with no serious adverse effects. CONCLUSION: To our knowledge, this is the first prospective study to demonstrate lack of expression of PCA3 in CRPC, with the result apparently not influenced by chemotherapy. There appears to be a strong association between hormonal treatment and lack of PCA 3 expression. It is still unknown whether disease progression per se affects PCA 3 scores. The gradual reduction and eventual complete non-expression of PCA 3 with ongoing treatment and disease progression provide an insight towards molecular pathways that may be connected to castration-resistant state.

Estrogen receptor (α and ß) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population.

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(ß)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(ß) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(ß) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(ß) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(ß) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.

Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study.

INTRODUCTION/BACKGROUND: The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. PATIENTS AND METHODS: Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. RESULTS: One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. CONCLUSION: CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials.

Immunomodulatory intervention with interferon-γ in Escherichia coli pyelonephritis.

PURPOSE: We investigated the efficacy of recombinant human interferon-γ in experimental pyelonephritis due to Escherichia coli. MATERIALS AND METHODS: Pyelonephritis was induced by intrapelvic inoculation of bacteria after ureteral ligation in 38 rabbits assigned to 1 of 3 groups, including group 1-16 controls, group 2-14 rabbits treated with intravenous recombinant human interferon-γ and group 3-8 rabbits treated with intravenous recombinant human interferon-γ plus amikacin. Bacterial counts, cytokines and malondialdehyde were measured in blood. Peripheral blood mononuclear cells were isolated to measure TNFα transcripts, cytokine stimulation and apoptosis. Survival was recorded, and the tissue bacterial load and myeloperoxidase activity were measured after sacrifice. RESULTS: The mortality rate in groups 1, 2 and 3 was 66.7%, 25% and 12.5%, respectively. The circulating bacterial count and tissue bacterial load were less in group 2 than in group 1. Circulating malondialdehyde negatively correlated with the bacterial load of the spleen. Although the number of TNFα transcripts in circulating peripheral blood mononuclear cells did not differ, peripheral blood mononuclear cells isolated from group 2 at 48 hours produced much greater concentrations of tumor necrosis factor-α after stimulation with Pam3Cys. In parallel, the apoptosis rate of circulating monocytes was increased in group 2 at 48 hours. Lung myeloperoxidase activity at 24 hours, serving as indirect evidence of neutrophil infiltration, was decreased in group 2. CONCLUSIONS: Recombinant human interferon-γ administration prolonged survival in rabbits with experimental E. coli urosepsis. Its action was probably related to increased bacterial phagocytosis after modulation of oxidant status and reversal of monocyte immunoparalysis.

Variables affecting adolescent renal function in patients born with vesico-ureteric reflux.

OBJECTIVE: To examine whether factors in a child's perinatal history influence renal function in adolescence, using a cross-sectional study, as during the past two decades researchers have tried to ascertain whether factors such as low birth weight might be related to a decline in kidney function in adolescence, although published data for children born with vesico-ureteric reflux (VUR) remain insufficient. PATIENTS AND METHODS: Sixty-one children (20 boys and 41 girls), born between 1985 and 1989 in Greece and diagnosed with VUR, were assessed. A detailed personal and family history was taken and basic anthropometric variables were measured. Kidney function was calculated from serum creatinine levels, and the glomerular filtration rate (GFR), fractional excretion of sodium, albumin levels in urine, creatinine clearance, cystatin C level and the dimensions of each kidney were measured. RESULTS: The results showed a positive relationship of birth weight (P = 0.01) with blood pressure in adolescence in children diagnosed with any degree of VUR. Renal function seemed to be intact whatever the cause of VUR, the volume of the kidneys in adolescence (P = 0.386 and 0.483, respectively, for the right and left kidney) and the values of GFR (P = 0.105), creatinine clearance (P = 0.213) and cystatin C (P = 0.055). CONCLUSIONS: These results showed that although there is a positive association between blood pressure in adolescence and birth weight, in children born with VUR there was no deterioration in renal function. Kidneys seem to function normally regardless of the gestational age at birth.

Association of ERCC1 SNPs with outcome in platinum-treated patients with advanced urothelial cancer: a Hellenic Cooperative Oncology Group study.

AIM: The association between two polymorphisms of ERCC1 and treatment outcomes after platinum-based chemotherapy in patients with advanced urothelial cancer (UC) was examined. MATERIALS & METHODS: Genotyping of 19007C>T and 8092C>A polymorphisms was determined by PCR amplification and RFLP in 113 advanced UC patients, treated with platinum-based chemotherapy. RESULTS: Seventy eight patients (69%) were carriers of the 19007T polymorphic allele: 51 (45%) heterozygotes and 27 (24%) homozygotes. Fifty three (47%) patients were carriers of the 8092A polymorphic allele: the frequencies of C/A and A/A genotypes were 37% and 10%, respectively. The T/T genotype was independently associated with prolonged median cancer-specific survival (not-reached vs 14.8 months; p = 0.026). There was no interaction between T/T or any other genotype with the type of platinum derivative (cisplatin/carboplatin). CONCLUSION: 19007C>T, especially in its homozygotic state, but not 8092C>A polymorphism, could be a useful prognostic marker in advanced UC treated with platinum-based chemotherapy.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

INTRODUCTION: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. METHODS: A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. RESULTS: Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥ 17 and suPAR ≥ 12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥ 12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥ 17 and suPAR ≥ 12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort. CONCLUSIONS: A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.