Non-cholera Vibrio spp. invasive infections in the summer following May 2023 flood disaster in Romagna, Italy: a case series.

Non-cholera Vibrio spp. includes ubiquitous organisms living in aquatic environments. Their occurrence is associated with global warming and meteorological disasters. In May 2023 the Romagna region, Italy, was affected by severe floods. In the following 15 weeks we observed 5 patients with invasive infections caused by V. vulnificus (3/5) and V. harveyi (2/5). All patients (median age 77 years) had medical comorbidities and shared exposure to seawater. Two patients needed surgery; 2 died. In conclusion, we observed an increased burden of Vibrio spp. invasive infections after May 2023 floods, affecting old patients with predisposing medical conditions.

Food and Aeroallergen Sensitization, Eosinophils Levels and Risk of Atopic Dermatitis in Abuja.

BACKGROUND: The barrier dysfunction of atopic dermatitis (AD) promotes epicutaneous sensitization to aeroallergens. This study aimed to evaluate the prevalence of food and aeroallergen sensitization in AD and to explore the relationship between allergen sensitization and the personal or family history of allergic rhinitis, conjunctivitis, asthma, eosinophil count, and AD severity of Nigerian patients. METHODS: Children and adults with AD who visited the dermatology clinic were included in this study. AD diagnosis was made using the modified Hanifin and Rajka criteria, and severity was rated and graded using the Scoring Atopic Dermatitis (SCORAD) index. Skin-prick test for 14 allergens (5 food and 9 aeroallergens) was used to assess IgE sensitization. To look for significant relationships, chi-square and odds ratio were used. RESULTS: Sensitization to at least one allergen was observed in 65.8% of the patients, sensitization to aeroallergen was 85% and to foods was 15%. More patients had concomitant allergic conjunctivitis (n=29) and only three had asthma. The mean age of onset of AD was 10.6±12.9 years, ranging from 2 months to 51 years, and a family history of atopy was observed in 49.4%. Majority had moderate AD and normal eosinophil count. Allergen sensitization in AD patients was significantly associated with the age of patients but not with personal or family history of allergic rhinitis, conjunctivitis, asthma, eosinophil count or AD severity. CONCLUSION: Analysis of our result showed a high prevalence of food and aeroallergen sensitization in AD. Sensitization was not influenced by the presence of other allergic diseases, eosinophils and the severity of AD.

CONTEXTE: La dysfonction de la barrière cutanée de la dermatite atopique (DA) favorise la sensibilisation épicutanée aux aéroallergènes. Cette étude visait à évaluer la prévalence de la sensibilisation alimentaire et aéroallergénique dans la DA et à explorer la relation entre la sensibilisation aux allergènes et les antécédents personnels ou familiaux de rhinite allergique, conjonctivite, asthme, le taux d'éosinophiles et la sévérité de la DA chez les patients nigérians. MÉTHODES: Les enfants et les adultes atteints de DA qui ont visité la clinique dermatologique ont été inclus dans cette étude. Le diagnostic de la DA a été établi en utilisant les critères modifiés de Hanifin et Rajka, et la gravité a été évaluée et classée à l'aide de l'indice de ScoringAtopic Dermatitis (SCORAD). Le test cutané aux 14 allergènes (5 alimentaires et 9 aéroallergènes) a été utilisé pour évaluer la sensibilisation IgE. Pour rechercher des relations significatives, le chi carré et le rapport de cotes ont été utilisés. RÉSULTATS: Une sensibilisation à au moins un allergène a été observée chez 65,8% des patients, la sensibilisation aux aéroallergènes était de 85% et aux aliments de 15%. Plus de patients présentaient une conjonctivite allergique concomitante (n=29) et seulement trois avaient de l'asthme. L'âge moyen de début de la DA était de 10,6 ± 12,9 ans, allant de 2 mois à 51 ans, et des antécédents familiaux d'atopie ont été observés chez 49,4%. La majorité avait une DAmodérée et un taux d'éosinophiles normal. La sensibilisation aux allergènes chez les patients atteints de DA était significativement associée à l'âge des patients, mais pas aux antécédents personnels ou familiaux de rhinite allergique, conjonctivite, asthme, au taux d'éosinophiles ou à la gravité de la DA. CONCLUSION: L'analyse de nos résultats a montré une prévalence élevée de la sensibilisation alimentaire et aéroallergénique dans la DA. La sensibilisation n'était pas influencée par la présence d'autres maladies allergiques, d'éosinophiles et de la sévérité de la DA. Mots-clés: Dermatite atopique, sensibilisation alimentaire et aéroallergénique, maladies atopiques, éosinophiles, sévérité de la dermatite atopique. Severity of atopic dermatitis Short title:Allergen sensitization in atopic dermatitis.

Male infertility and urological tumors: Pathogenesis and therapeutical implications.

Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.

The impact of COVID-19 outbreak on urolithiasis emergency department admissions, hospitalizations and clinical management in central Italy: a multicentric analysis. / El impacto de la COVID-19 en las admisiones al servicio de urgencias, hospitalizaciones y manejo clínico de la urolitiasis en el centro de Italia: análisis multicéntrico.

INTRODUCTION AND OBJECTIVES: We aimed to evaluate how the corona virus disease of 2019 (COVID-19) outbreak influenced emergency department (ED) admissions for urolithiasis, hospitalizations and clinical management of the hospitalized patients. PATIENTS AND METHODS: We conducted a multicentric retrospective analysis of ED admissions in three high volume urology departments (one directly involved in COVID-19 patients management and two not involved) in Rome - Italy between March and April 2020 and in the same period of 2019. Statistical analysis was conducted on the number of admissions for urolithiasis, rate of complications, hospitalization and the type of treatment received. RESULTS: 304 patients were included in the analysis. A significant reduction in the global number of patients admitted to ED for urolithiasis between 2019 and 2020 (48.8%) was noted. Moreover, regarding the choice of treatment of hospitalized patients, a statistically significant increase of stone removal procedures versus urinary drainage was reported in 2020 (p = 0.015). CONCLUSIONS: During the COVID-19 pandemic in Rome there has been a significant reduction of emergency admissions for urolithiasis. Patients admitted to ED had more complications, more frequently need hospitalization and regarding clinical management early stone removal was preferred over urinary drainage only. All the urologists should be aware that in the next months they could face an increased number of admissions for urolithiasis and manage more complicated cases.

Intravenous thrombolysis in stroke mimics: results from the SITS International Stroke Thrombolysis Register.

BACKGROUND AND PURPOSE: Patients with stroke mimics (SM), i.e. conditions with stroke-like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions. METHODS: We included IVT-treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003-2017, examined with magnetic resonance imaging 22-36 h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST), Second European Co-operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3 months. RESULTS: Of 10 436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5-10) vs. 8 (5-14), P < 0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% (P < 0.001), SICH NINDS in 0.5% vs. 3.9% (P < 0.001), SICH ECASS II in 0.2% vs. 2.1% (P = 0.007) and SICH SITS-MOST in 0% vs. 0.5% (P = 0.28). Modified Rankin Scale score 0-1 at 3 months was present in 84.1% vs. 57.7% (P < 0.001) and death within 3 months in 2.6% vs. 5.4% (P = 0.028) of mimics and stroke patients, respectively. CONCLUSIONS: This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.

Cohort event monitoring of patients treated for uncomplicated malaria with artemisinin-based combination therapies in selected hospitals and community pharmacies in Nigeria.

AIMS AND OBJECTIVES: The study was designed with the broad objective of determining the safety profile of artemisinin-based combination therapies amongst Nigerian population. PATIENTS AND METHODS: This was a cohort event monitoring (CEM) programme involving monitoring adverse events (AEs) in malaria patients treated with either artemether-lumefantrine (AL) or artesunate-amodiaquine (AA) in healthcare facilities in Nigeria. The study involved continuous enrolment of patients with malaria and treated with either AL or AA at the various sites until a total cohort of 600 patients were enrolled at each site. Patients were monitored from the onset of therapy, and on days 3 and 7 from the first day of treatment to identify AEs that may occur. RESULTS: A total of 6102 AEs were recorded in 10,259 patients monitored during the programme. Of 4896 patients who received AA, 4233 (86.5%) patients reported at least one AE while 1869 (34.8%) AEs out of 5363 patients who received AL were reported (P = 0.010). The predominant incidence of each specific AE reported in each group among the patients who received AA and AL includes body weakness 30.8%/7.5%, dizziness 10.3%/3.9%, restlessness 5.02/1.12%, vomiting 3.5/1.03% and drowsiness 3.1/1.5% for AA and AL, respectively. There were more AEs among patients with co-morbid conditions and patients in the younger age groups (9-<15 years), P = 0.000. CONCLUSIONS: Various types of AEs were seen and documented during the CEM programme. The findings suggested that the AA/AL monitored during this programme was generally safe and remarkably well tolerated among the Nigerian populations.

Systematic review and meta-analysis of non RCT's on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit.

PURPOSE: The current literature on the impact of different urinary diversions on patients' health related quality of life (HR-QoL) showed a marginally better quality of life scores of orthotopic neobladder (ONB) compared to ileal conduit (IC). The aim of this study was to update the review of all relevant published studies on the comparison between ONB and IC. MATERIALS AND METHODS: Studies were identified by searching multiple literature databases, including MEDLINE, CINAHL, the Cochrane Library, PubMed Data were synthesized using meta-analytic methods conformed to the PRISMA statement. RESULTS: The current meta-analysis was based on 18 papers that reported a HR-QoL comparison between IC and ONB using at least a validate questionnaire. Pooled effect sizes of combined QoL outcomes for IC versus ONB showed a slight, but not significant, better QoL in patients with ONB (Hedges' g = 0.150; p = 0.066). Patients with ileal ONB showed a significant better QoL than those with IC (Hedges' g = 0.278; p = 0.000); in case series with more than 65% males, ONB group showed a slight significant better QoL than IC (Hedges' g = 0.190; p = 0.024). Pooled effects sizes of all EORTC-QLQ-C30 aspects showed a significant better QoL in patients with ONB (Hedges' g = 0.400; p = 0.0000). CONCLUSIONS: This meta-analysis of not-randomized comparative studies on the impact of different types of urinary diversions on HR-QoL showed demonstrated a significant advantage of ileal ONB compared to IC in terms of HR-QoL.

Histopathological findings and proliferative activity of canine sebaceous gland tumours with a predominant reserve cell population.

Sebaceous gland tumours represent the third most common skin tumours in dogs, but diagnostic criteria for tumours with basal differentiation (i.e. sebaceous epithelioma) are poorly defined and there is lack of correlation with biological behaviour. The aim of this study was to identify the main histological criteria associated with malignancy in 30 canine sebaceous gland tumours with a predominant reserve cell population. For each case, tumour proliferative activity was assessed by determining mitotic index and the Ki67/MIB-1 index. Additional histological features included endophytic or exophytic growth, proportion of reserve/intermediate/mature cells, connection to the epidermis, nuclear characteristics, peripheral invasion, neoplastic emboli and necrosis. Mitotic and Ki67 indexes were variable, but correlated (R = 0.66; P < 0.001), and both were significantly higher in infiltrative tumours (P = 0.018 and P < 0.001, respectively). No significant difference in histological features was observed between tumours comprised of more or less than 90% reserve cells, nor among tumours showing proliferative activity in sebocytes. This study suggests that high proliferative activity and peripheral invasion should be considered the most significant parameters for the differentiation between benign and malignant sebaceous gland tumours. Furthermore, the incidence of circumanal gland and testicular tumours in these dogs was significantly higher compared with an age-matched control population, suggesting a potential androgen-related pathway for the tumourigenesis of canine sebaceous gland neoplasms.

Previous infection and the risk of ischaemic stroke in Italy: the IN2 study.

BACKGROUND AND PURPOSE: There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population. METHODS: This was a prospective case-control study involving 11 Italian stroke units. Controls were age- and sex-matched with cases, represented by patients admitted to hospital for acute ischaemic stroke. For each participant classical vascular risk factors and previous inflammatory and infectious events up to 1 month before were registered. Blood samples were collected to analyse inflammatory markers and titres of antibodies against C. pneumoniae. RESULTS: A total of 1002 participants were included (mean age 69 years) with 749 ischaemic stroke patients. Infections occurred within 1 month previously in 12% of the entire sample with a higher prevalence in the case group (14.4% vs. 3.9%). At multivariate analysis of the seropositivity of IgA antibodies against C. pneumoniae increased the risk of stroke significantly (relative risk 2.121; 95% confidence interval 1.255-3.584) and an early previous infection (up to 7 days before the event) contributed to a rise in probability of acute cerebral ischaemia (relative risk 3.692; 95% confidence interval 1.134-6.875). CONCLUSIONS: Early previous infections and persistent chronic infection of C. pneumoniae could contribute to increase the risk of ischaemic stroke significantly, in the elderly especially.

The clinical use of statistical permutation test methodology: a tool for identifying predictive variables of outcome.

OBJECTIVES: To identify the predictive variables affecting the outcome after radical surgery for bladder cancer by a newer statistical methodology, i.e. nonparametric combination (NPC). METHODS: A multicenter study enrolled 1,312 patients who had undergone radical cystectomy for bladder cancer in 11 Italian oncological centers from January 1982 to December 2002. A statistical analysis of their medical history and diagnostic, pathological and postoperative variables was performed using a NPC test. The patients were included in a comprehensive database with medical history and clinical and pathological data. Five-year survival was used as the dependent variable, and p values were corrected for multiplicity using a closed testing procedure. The newer nonparametric approach was used to evaluate the prognostic importance of the variables. All of the analyses were performed using routines developed in MATLAB© and the significance level was set at α = 0.05. RESULTS: A significant prognostic predictive value (p < 0.01) for tumor clinical staging, hydronephrosis, tumor pathological staging, grading, presence of concomitant carcinoma in situ, regional lymph node involvement, corpora cavernosa invasion, microvascular invasion, lymphatic invasion and prostatic stroma involvement was found. CONCLUSIONS: The NPC test could handle any type of variable (categorical and quantitative) and take into account the multivariate relation among variables. This newer methodology offers a significant contribution in biomedical studies with several endpoints and is recommended in presence of non-normal data and missing values, as well as solving high-dimensional data and problems relating to small sample sizes.

Size of bladder cancers: correlation among different types of measurement.

OBJECTIVE: It was the aim of this study to evaluate the accuracy of the measurement of tumor size comparing the objective size with that measured by preoperative cystoscopy, by preoperative ultrasound (US) and with the diameter described by the operator before the transurethral resection. PATIENTS AND METHODS: This study included 100 patients with bladder papillary endoscopic features of single or multiple neoplasms who were candidates for transurethral resection. The sizes of the same neoplasms measured during preoperative cystoscopy, preoperative US and described by the operator before the transurethral resection were evaluated. A statistical analysis of the errors of measurement was performed if compared with an objective measurement done with an ureteral catheter. RESULTS: The statistical analysis of the data shows that there are no substantial differences between the objective and subjective measurement, and therefore, the measurements reported by individual operators are reliable. On the contrary, the diameters given by preoperative cystoscopy and US differ significantly from the objective measurement. CONCLUSIONS: This study shows that the most reliable measurement is the subjective measurement made directly by the urologist in the operating room.

Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to avoid early cystectomy?.

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Value of current chemotherapy and surgery in advanced and metastatic bladder cancer.

The aim of the present paper was to review findings from the most relevant studies and to evaluate the value of current chemotherapy and surgery in advanced unresectable and metastatic bladder cancer. Studies were identified by searching the MEDLINE® and PubMed® databases up to 2011 using both medical subject heading (Mesh) and a free text strategy with the name of the known individual chemotherapeutic drug and the following key words: 'muscle-invasive bladder cancer', 'chemotherapeutics agents', and 'surgery in advanced bladder cancer'. At the end of our literature research we selected 141 articles complying with the aim of the review. The results showed that it has been many years since the MVAC (methotrexate, vinblastine, adriamycin, cisplatin) regimen was first developed. The use of cisplatin-based combination chemotherapy is associated with significant toxicity and produces long-term survival in only approximately 15-20% of patients. Gemcitabine + cisplatin represents the gold standard in the treatment of metastatic bladder cancer. In conclusion, the optimal approach in the management of advanced urothelial cancer continues to evolve. Further progress relies on the expansion of research into tumor biology and an understanding of the underlying molecular 'fingerprints' that can be used to enhance diagnostic and therapeutic strategies. Cisplatin-based therapy has had the best track record thus far.

Evidence for bovine besnoitiosis being endemic in Italy--first in vitro isolation of Besnoitia besnoiti from cattle born in Italy.

Until 2009, bovine besnoitiosis had never been considered endemic in Italy and the only report on the disease in this country referred to animals imported from France shortly before. However, recently, an autochthonous outbreak of bovine besnoitiosis was reported in four herds located at the intersection of the borders between Emilia-Romagna, Toscana and Marche (Northern Apennine Mountains), which has led to an increased awareness concerning this disease. The present study describes a further outbreak of bovine besnoitiosis in Italy. The afflicted herd was a dairy herd with no evidence for contact with cattle from regions known to be endemic for bovine besnoitiosis. The farm investigation was initiated after a three-year old Holstein Friesian dairy cow with generalized thickening and lichenification of the skin was diagnosed with bovine besnoitiosis. The clinical diagnosis was confirmed by gross pathology, histopathology, serology and PCR. Bradyzoites released from tissue cysts obtained from the skin of this animal enabled the first in vitro isolation of Besnoitia besnoiti in Italy. This isolate was named Bb-Italy1. Sequencing of a 2118 bp spanning region including the complete internal transcribed spacer 1 and parts of the 18S and the 5.8S rRNA gene from DNA extracted from skin-derived zoites revealed a 99.9% identity to sequences known for other B. besnoiti isolated from cattle in Europe. Two GKO mice which had been inoculated intraperitoneally with bovine skin-derived bradyzoites became ill 7 days post inoculation. Parasitophorous vacuoles with multiplying zoites were observed in the cell culture inoculated with peritoneal fluids of these mice and a B. besnoiti infection in the mice and in the cell culture could be confirmed by real-time PCR. A serological investigation in the afflicted herd using immunoblots and an immunofluorescent antibody test (IFAT) revealed an overall herd seroprevalence of 9.7% (31/321), whereas within the female animals older than 2 years 17.0% (29/171) of the dams were tested positive. With one exception, an imported cow from Germany, all the seropositive animals were born in Italy. In connection with previously described autochthonous cases of bovine besnoitiosis the case described herein suggests that bovine besnoitiosis should be considered endemic in Italy.

Evidence for bovine parafilariosis in Italy: first isolation of Parafilaria bovicola (Tubangui, 1934) from autochthonous cattle.

In May and July 2010 and in March 2011, the presence of multiple bleeding nodules at the level of the neck, shoulders, withers, back and rump in five cattle from three herds in north-central Italy were observed. A diagnosis of parafilariosis was made. Fragments of adult females of Parafilaria bovicola could be identified from the derma of three to five bioptic extirpates. Larvated eggs and free larvae were observed in serohemorrhagic exudates. This paper is the first report of the occurrence of parafilariosis in Italy and subsequent to the various outbreaks reported, it can now be said that bovine parafilariosis is also currently present in Italy.

Silencing of GSTP1, a prostate cancer prognostic gene, by the estrogen receptor-ß and endothelial nitric oxide synthase complex.

We recently identified in prostate tumors (PCa) a transcriptional prognostic signature comprising a significant number of genes differentially regulated in patients with worse clinical outcome. Induction of up-regulated genes was due to chromatin remodeling by a combinatorial complex between estrogen receptor (ER)-ß and endothelial nitric oxide synthase (eNOS). Here we show that this complex can also repress transcription of prognostic genes that are down-regulated in PCa, such as the glutathione transferase gene GSTP1. Silencing of GSTP1 is a common early event in prostate carcinogenesis, frequently caused by promoter hypermethylation. We validated loss of glutathione transferase (GST) P1-1 expression in vivo, in tissue microarrays from a retrospective cohort of patients, and correlated it with decreased disease-specific survival. Furthermore, we show that in PCa cultured cells ERß/eNOS causes GSTP1 repression by being recruited at estrogen responsive elements in the gene promoter with consequential remodeling of local chromatin. Treatment with ERß antagonist or its natural ligand 5α-androstane-3ß,17ß-diol, eNOS inhibitors or ERß small interference RNA abrogated the binding and reversed GSTP1 silencing, demonstrating the direct involvement of the complex. In vitro, GSTP1 silencing by ERß/eNOS was specific for cells from patients with worse clinical outcome where it appeared the sole mechanism regulating GSTP1 expression because no promoter hypermethylation was present. However, in vivo chromatin immunoprecipitation assays on fresh PCa tissues demonstrated that silencing by ERß/eNOS can coexist with promoter hypermethylation. Our findings reveal that the ERß/eNOS complex can exert transcriptional repression and suggest that this may represent an epigenetic event favoring inactivation of the GSTP1 locus by methylation. Moreover, abrogation of ERß/eNOS function by 3ß-adiol emphasizes the significance of circulating or locally produced sex steroid hormones or their metabolites in PCa biology with relevant clinical/therapeutic implications.

Uso de bioterápico no controle de pasteurelose em cunicultura: relato de caso / Use of biotherapeutics in control of pasteurellosis in rabbits: a case report

A pasteurelose é uma das principais doenças em cuniculturas, podendo provocar significativas perdas. O emprego de bioterápico é tratamento utilizado na ciência homeopática na qual pode se empregar o próprio agente etiológico para estimular o animal a sair da inércia e tornar-se novamente equilibrado. O resultado indicou que o bioterápico utilizado na cunicultura foi eficaz no tratamento da doença na dinamização 12CH.

Paclitaxel-hyaluronic acid for intravesical therapy of bacillus Calmette-Guérin refractory carcinoma in situ of the bladder: results of a phase I study.

PURPOSE: Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Guérin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Guérin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Guérin. MATERIALS AND METHODS: A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Guérin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. RESULTS: No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. CONCLUSIONS: Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Guérin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed.

[Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives]. / La deprivazione androgenica nel carcinoma prostatico: evidenze cliniche e prospettive future.

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.