Search

BackgroundPatients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies.MethodsMultinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created.ResultsA total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9–42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11–24) and 21% (IQR, 15–33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/.ConclusionsOur clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

Objective: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC). Patients and methods: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien–Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis. Results: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15months (range 3–41) for the entire cohort with a median survival of 15months (95% CI 10.1–19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62–17.23, p = 0.164). Conclusion: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome.

Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Results From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33–83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1–7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4–58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). Conclusions The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

Simple Summary Mastitis is a costly disease and needs to be identified as soon as possible to reduce the negative effect on milk quality and quantity and to maximize the chance of cure when an antimicrobial therapy is applied. Bacteriological diagnosis is expensive and not easily available in some areas, therefore approaches to reduce the number of samples to be taken, focusing the interest on cows with higher chances to have an intramammary infections are desirable. The results of our study based on a large database of quarter milk samples analyses including bacteriological analysis, total (SCC) and differential (DSCC) cell count in the first 5–30 days after calving suggest a new and sustainable approach. Indeed, a marker (PLCC) calculated by multiplying SCC and DSCC showed to have the lowest cost when applied to identify udder quarters at risk to have an intramammary infection due to major pathogens. Moreover, this approach as well as the one based on SCC became a benefit when the prevalence of these infections exceeds 10%, and it be of high interest, when selective dry cow therapy is applied, to improve animal health at the herd level. Abstract Milk differential somatic cells count (DSCC), made possible under field conditions by the recent availability of a high-throughput milk analyzer may represent an improvement in mastitis diagnosis. While an increasing number of studies reports data on DSCC on individual cow samples, very few concerns DSCC from quarter milk samples. This paper reports for the first time the results of a retrospective study aiming to assess the performance of total (SCC), DSCC, and a novel calculated marker (PLCC) measured on quarter milk samples as a method to identify cows at risk for intramammary infection (IMI) in the first 30 days after calving. Overall, 14,586 valid quarter milk samples (3658 cows) taken in the first 30 days of lactation were considered. Quarters with major pathogens (MP) IMI, as expected, showed significantly higher means for SCC, DSCC, and PLCC. The accuracy, sensitivity, and specificity of the diagnosis based on different cut-offs calculated by ROC analysis are relatively close among DSCC, PLCC, and SCC (up to cut-off of 200,000 cells/mL). However, decision-tree analysis which includes the costs of analysis, but also the costs of the actions taken after test results showed as PLCC has the lowest cost among the three markers, and PLCC and SCC are cost effective when MP prevalence is higher than 6–10%. This diagnostic approach is of high interest particularly when selective dry cow therapy is applied to improve animal health at the herd level.

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. Results: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. Conclusions: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.

Item does not contain fulltext PURPOSE: The diagnostic strategy implementing multiparametric magnet resonance tomography (mpMRI) and targeted biopsies (TB) improves the detection and characterization of significant prostate cancer (PCa). We aimed to assess the clinical usefulness of systematic biopsies (SB) in the setting of patients having a pre-biopsy positive MRI. METHODS: A review of the literature was performed in March 2018. All studies investigating the performance of SB in addition to TB (all techniques) were assessed, both in the biopsy-naive and repeat biopsy setting. RESULTS: Evidence demonstrates that TB improves the detection of index-significant PCa compared with SB alone, in both initial and repeat biopsy settings. However, the combination of both TB and SB improved the overall (around 30%) and significant (around 10%) PCa detection rates as compared with TB alone. Significant differences between both biopsy approaches exist regarding cancer location favoring SB for the far lateral sampling, and TB for the anterior zone. Main current pitfalls of pure TB strategy are the learning curve and experience required for mpMRI reading and biopsy targeting, as well as the precision assessment in TB techniques. CONCLUSION: A pure TB strategy omitting SB leads to the risk of missing up to 15% of significant cancer, due to limitations of mpMRI performance/reading and of precision during lesion targeting. SB remain necessary, in addition to the TB, to obtain the most accurate assessment of the entire prostate gland in this sub-group of patients at risk of significant disease.

Item does not contain fulltext PURPOSE: To review the evidence addressing current controversies around prostate biopsy. Specific questions explored were (1) mpMRI targeted (TgBx) alone versus combined with systematic (SBx) biopsy; (2) cognitive versus software-based targeted biopsy; (3) transrectal or transperineal route (TP). METHODS: We performed a literature search of peer-reviewed English language articles using PubMed and the words "prostate" AND "biopsy". Web search was implemented by manual search. RESULTS: Prostate mpMRI is revolutionizing prostate cancer (PCa) diagnosis, and TgBx improves the detection of clinically significant (cs) PCa compared to SBx alone. The utility of combining SBx-TgBx is variable, but in non-expert centres the two should be combined to overcome learning curve-limitations. Whether SBx should be maintained in expert centres depends on what rate of missed cancer the urological community and patients are prone to accept; this has implications for insignificant cancer diagnosis as well. TgBx may be more precise using a software-based-approach despite cognitive TgBx proved non-inferior in some studies, and may be used for large accessible lesions. TP-biopsies are feasible in an in-office setting. Avoidance of the rectum and accessibility of virtually all prostate areas are attractive features. However, this has to be balanced with local setting and resources implications. Ongoing trials will shed light on unsolved issues. CONCLUSION: The prostate biopsy strategy should be tailored to local expertise, needs and resources availability. Targeted biopsy enhance the ratio between cs and insignificant cancer diagnosis, although some csPCa might be missed. Software-based TgBx are likely to be more precise, especially for new users, although the additional cost might be not justified in all cases. TPBx have ideal attributes for performing TgBx and avoiding infection, although this has resources implications.

The immune checkpoint inhibitors, a class of drugs able to block immune suppressive pathways in order to prime an anticancer immunity, revolutionized standard of care in platinum-refractory recurrent and/or metastatic head and neck carcinoma (R/M HNSCC). The PD-1/ PD-L1 axis is involved in the genesis, maintenance and progression of HNSCC and represents the target of checkpoint inhibitors. HNSCC is an immunosuppressive disease with a high inflammatory component in tumor microenvironment. Recent clinical trials showed that only a small subset of patients really benefits from immunotherapy. This review aims to highlight the five W-points of immunotherapy: why immunotherapy is promising in HNSCC, what is currently available in daily clinical practice, when immunotherapy can be integrated into the therapeutic strategy, where it can be useful according to predictive response biomarker, who, among patients, could get the best benefit from immunotherapy and how improve the achieved results.

// Filomena Morisco 1 , Silvia Camera 1 , Maria Guarino 1 , Raffaella Tortora 2 , Valentina Cossiga 1 , Anna Vitiello 1 , Gabriella Cordone 2 , Nicola Caporaso 1 , Giovan Giuseppe Di Costanzo 2 and Italian Liver Cancer (ITA.LI.CA) group 1 Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy 2 Hepatology Unit, “Cardarelli” Hospital, Naples, Italy Correspondence to: Filomena Morisco, email: filomena.morisco@unina.it Keywords: large HCC; laser ablation; TACE Received: December 13, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Background: Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively ( p 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively ( p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC.

Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P=.021), larger tumours (P=.038), better liver function (higher percentage of Child-Pugh class A [P=.007] and MELD&nbsp

CANDIPOP Project, the CANDI‐Bundle Group GEIRAS‐GEMICOMED (SEIMC) REIPI., [Background] Despite being considered a high‐risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized., [Methods] We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010‐2011) and the CANDI‐Bundle Study (2016‐2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all‐cause 7‐day mortality and/or persistent candidemia for ≥72 hours) and 30‐day mortality were investigated by univariate analysis., [Results] We included 55 episodes of post‐transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non‐susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30‐day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03‐0.85; P ‐value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03‐0.76; P ‐value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02‐0.89; P ‐value = .041) were protective for 30‐day mortality., [Conclusions] High rates of non‐albicans species and fluconazole non‐susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia., The CANDIPOP Project was supported by non‐restrictive research grants from Gilead Sciences, MSD, Astellas Pharma, and Pfizer. This study was cofounded by Fundación SEIMC‐GESIDA, by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III (co‐financed by the European Development Regional Fund [ERDF] >A way to achieve Europe>), and by the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). The CANDI‐Bundle Study was supported by “Plan Nacional de I + D+I” and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias [FIS] PI15/00744), Subdirección General de Redes y Centros de Investigación Cooperativa, Spanish Ministry of Science, Innovation and Universities, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016). MFR holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III.

The benefit of adjuvant chemotherapy has been clearly established in the adjuvant setting for node-positive colon cancer. A number of trials in the adjuvant setting have analyzed the efficacy of multiple-agent combinations, including irinotecan, oxaliplatin, bevacizumab and cetuximab. Only oxaliplatin added to fluorouracil/capecitabine has been shown to be superior beyond a fluropyrimidine alone in the adjuvant setting. As such, standard treatment options include fluorouracil (FU) or capecitabine with or without oxaliplatin. However, oxaliplatin is associated with cumulative dose-dependent neurotoxicity, characterized by distal or perioral paresthesias or dysesthesias; for this reason, in this review we discuss the results of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) trial. The IDEA trail is the largest prospective clinical trial ever conducted in colorectal cancer, wherein patients were treated with either 3 months or 6 months of adjuvant chemotherapy. In the era of cancer gene expression-based subtyping, the Colorectal Cancer Subtyping Consortium has proposed a four-subgroup molecular classification system for colorectal cancer, consisting of CMS1 (immune), CMS2 (canonical), CMS3 (metabolic) and CMS4 (mesenchymal). In this review, we present and analyze the available data on efficacy and toxicity of the combination regimen approved for treatment of resected colon cancer, and discuss the questions of when, how and how long we need to treat such patients.

Contains fulltext : 215808.pdf (Publisher’s version ) (Open Access) PURPOSE: Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. METHODS: A literature search on December 15th 2017 was conducted using the Pubmed database. RESULTS: Functional imaging techniques like (68)Ga PSMA. (68)Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. CONCLUSIONS: Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.

Introduction: The urological community's opinion over focal therapy (FT) for prostate cancer (PCa) has never been assessed. Our aim was to investigate the current opinion on FT in the European urological community. Methods: A 25 -item questionnaire was devised according to the Cherries checklist and distributed through SurveyMonkey using a web link from November 2016 to October 2017. After a pilot validation (n=40 urologists), the survey was sent through EAU and 9 other national European urological societies mailing list. Twitter was also used. Results: We received 484 replies from 51 countries. Almost half (44.8%, n=217) stated FT would represent a step forward, and 52.0% (n=252) would suggest FT to a patient. Almost three-quarters (70.8%, n=343) agreed FT will become a standard option after improvements in patient selection (n=66) or when its effectiveness will be proven (n=78), or both (n=199). Most frequently used definition of FT was treatment of all significant (life -threatening) cancer foci whilst leaving untreated the rest of the gland (39.3%, n=190). FT use was considered as an alternative to whole -gland treatments by 29.7% (n=144), and to AS by 25.0% (n=121). On multivariate analysis, FT availability and publications were associated with a positive opinion on FT. Conversely, attending International congresses, treating high PCa volumes and high percentages of high -risk PCa was associated with a negative opinion. Conclusions: FT is considered as an attractive option for PCa treatment by the European urological community sampled by our survey. FT availability positively influences these thoughts. The present survey suggests whilst some early adopters already embraced FT, the relative majority of the urological community is prone to embrace FT in the near future, once current areas of debate are solved. (C) 2018 Elsevier Inc. All rights reserved.

Objective To detect and prevent urinary tract injuries in gynecological surgery. Methods A brief review of the literature about recognition and prevention of ureteral and bladder injuries. Results It is well known that factors as intra-operative bleeding, pelvic adhesions and infections, pelvic masses, endometriosis and obesity can make surgery difficult. For these reasons the study of the urinary tract and the use of ureteral catheters may be helpful when alterations of the urinary tract anatomy is suspected. However the surgeon should always operate under direct vision of the ureters with a judicious use of diathermy and taking care when separating bladder from the uterus where the blunt dissection is blind and dangerous. When there are some doubts about the integrity of ureters, the control with i.v. infusion of indigo-carmine or with ureteral catheters should be performed. The same applies for the bladder: the cystoscopy should be in the armamentarium of gynecological surgeons to control the ureteral efflux and the bladder integrity. To fill the bladder with methylene blue at the end of the surgery is also helpful in revealing, under the pressure, even very small lesions as well as partial thickness of the bladder that can cause a delayed fistula. Conclusions Surgeons' training is the most important factor in avoiding and detecting urinary tract injuries. This is important not only for the technique but also in the selection of patients, and then in planning the more appropriate pre-operative study and in recognizing the presence of injuries during surgery.

There is increasing evidence supporting the need for antifungal stewardship (AFS) programmes in order to promote appropriate antifungal use, improve diagnosis and quality of care, and decrease the costs of antifungal treatment. AFS programmes delivered by experienced teams can be efficacious and cost effective. However, there are a variety of challenges often faced during the implementation of AFS programmes which can present barriers to their success. These can include lack of dedicated personnel, lack of investment in new diagnostic and prescription tools, and misperception by other physicians.

Mayer–Rokitansy–Kuster–Hauser syndrome is the most common cause of congenital vaginal agenesis, occurring in one in every 1500–4000 female births, and to a lesser extent complete androgen insensitivity syndrome can also be diagnosed. Diagnosis is generally shocking for young patients and their relatives, and in certain cases psychological help is needed even for choosing the appropriate time to start therapy. Whichever strategy is planned, the patient’s collaboration is strongly necessary. Several therapeutic approaches have been proposed and each investigator generally claims that his/her own method is the most successful, but the small number of cases does not permit any definitive conclusions. In cases of failure of self-dilatation, which should be the first approach, a surgical approach is needed, and is chosen according to the surgeon’s experience and patient’s preference. In this article, the various nonoperative and operative techniques are reported, considering the advantages and disadvantages for...

The objective of our study was to evaluate the diagnostic accuracy of 3-T MRI in determining the depth of myometrial infiltration in patients with endometrial cancer.Fifty-two patients (43 postmenopausal) with histopathologically proven endometrial carcinoma underwent preoperative 3-T MRI. The following sequences were performed: axial T1 fast spin-echo (FSE); axial, parasagittal, and paracoronal T2 FSE; paracoronal 3D T1 inversion recovery gradient-echo after contrast administration; and parasagittal fat-suppressed T1 FSE. All patients underwent a hysterectomy. The MRI findings were compared with histopathology results. The quantity and degree of artifacts were evaluated.. MRI performed on a 3-T unit was in agreement with histopathology in assessing the depth of invasion in 86.4% (44/52) of the patients with a mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 83.5%, 93.9%, 77.8%, 92.2%, and 89.7%, respectively. Performance values were also assessed for single stages of myometrial infiltration. For the detection of an intramucosal lesion (MRI, 12/52; histopathology, 6/52), sensitivity was 100%; specificity, 86.9%; PPV, 50%; NPV, 100%; and accuracy, 88.5%. For the detection of myometrial infiltration that was less than 50% (MRI, 12/52; histopathology, 16/52), sensitivity was 62.5%; specificity, 94.4%; PPV, 83.3%; NPV, 85%; and accuracy, 84.6%. For the detection of myometrial infiltration that was greater than 50% (MRI, 28/52; histopathology, 30/52), sensitivity was 93.3%; specificity, 100%; PPV, 100%; NPV, 91.7%; and accuracy, 96.2%. The following artifacts were found: abdominal wall movement, nine patients (not affecting image quality); peristalsis, 16 patients (two deeply affecting, one affecting, and 13 scarcely affecting); magnetic susceptibility artifact, four patients (not affecting); chemical shift, 20 patients (four scarcely affecting and 16 not affecting); and dielectric effect, six patients (four deeply affecting and two affecting).In evaluating the depth of myometrial infiltration in patients with endometrial cancer, 3-T MRI showed high diagnostic accuracy-equivalent to that of 1.5-T MRI reported in the literature. Artifacts did not significantly affect image quality.

Polycystic ovary syndrome (PCOS) is a common endocrine disease that is frequently observed to be related to increased insulin resistance independent of body weight. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance.On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg orally twice daily) to better understand upon which basis of clinical and endocrine parameters metformin administration might be chosen as a putative therapeutic tool.A group of non-obese PCOS patients (n = 42) was enrolled after informed consent. They underwent an oral glucose tolerance test for insulin, glucose and C-peptide levels and provided blood samples for determination of plasma levels of luteinizing hormone (LH), follicle-stimulating hormone, prolactin, estradiol, androstenedione, 17-hydroxyprogesterone, insulin, cortisol and testosterone levels on two occasions: before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment.Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients. When subdividing PCOS patients according to insulin sensitivity (i.e. hyper- and normoinsulinemic subjects), a greater rate of positive endocrine changes was observed in hyperinsulinemic patients and the highest rate was observed in hyperinsulinemic hyperandrogenic subjects. Menstrual cyclicity was recovered in all patients under treatment.Our data show that metformin modulates ovarian function and greatly affects LH secretion through reduction of the hyperandrogenic condition. The highest rate of endocrine changes was observed in the hyperinsulinemic hyperandrogenic non-obese PCOS patients. Our study demonstrates that metformin administration is more appropriate in hyperinsulinemic hyperandrogenic non-obese PCOS patients.

OBJECTIVE Adiponectin is an exclusively adipose tissue-derived protein. Low plasma adiponectin levels have been found in hypertensive men. Our objective was to evaluate whether low first-trimester plasma adiponectin values were predictive of hypertensive disorders later in pregnancy. METHODS A nested case-control study was carried out on a cohort of 1,842 pregnant women who participated in the first-trimester Down syndrome screening program; 34 developed preeclampsia and 48 gestational hypertension. A control group of 82 nonhypertensive uneventful pregnancies was selected. Plasma adiponectin was determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS Adiponectin median concentrations in the group which subsequently became hypertensive were significantly lower than those in the control group (7.6 versus 13.0 microg/mL) (P < .001). When the 2 hypertensive subgroups were considered, the plasma adiponectin median value in the preeclampsia group was significantly lower than that in the gestational hypertension group (6.6 versus 9.3 microg/mL) (P = .01). Regression analysis showed an inverse correlation between plasma adiponectin concentrations and maternal age, gestational age, body mass index, systolic blood pressure, and proteinuria. Approximately 34% of hypertensive pregnancies, compared with 7% of controls (P < .001), had plasma adiponectin concentrations less than 6.4 microg/mL (mean value of lower quartile of distribution among control patients). After adjusting for maternal age, all these women experienced a 6.6-fold (95% confidence interval 2.5-17.8) increased risk of pregnancy hypertension, compared with those women who had higher concentrations. CONCLUSION Our findings suggest a strong association between hypoadiponectinemia and the risk of hypertensive disorders in pregnancy, especially with preeclampsia.

Acta Obstet Gynecol Scand 2002; 81: 540-543. © Acta Obstet Gynecol Scand 2002 Background. To evaluate maternal serum Multiple of Median inhibin-A in mid-trimester blood samples of women who subsequently developed preeclampsia, gestational hypertension and intrauterine growth restriction and controls. Also, to verify whether this marker is related to these pathological conditions. Methods. Retrospective analysis of serum samples from a bank of stored serum, originally taken for Down's syndrome screening over 15-18 weeks, was performed. The sample consisted of 20 patients with gestational hypertension, 20 patients with preeclampsia, 10 patients with intrauterine growth restriction and 40 controls. Results. No statistically significant difference of inhibin-A Multiple of Median values between the control group and the preeclamptic or gestational hypertension groups was found. There was a statistically significant elevation in the intrauterine growth restriction group in comparison with the control group, and...

Background Pneumonia frequently affects solid organ transplant (SOT) recipients, with high morbidity and mortality. However, the few studies on pneumonia in this population are mainly retrospective, single-center, and long-term studies, or include patients with only one type of SOT or a specific etiology. We performed a point prevalence study to investigate epidemiology, diagnosis, therapy, and outcome of pneumonia in an unselected SOT population. Methods Italian and Spanish transplant centers were invited to report on all SOT recipients with pneumonia treated during 2 separate weeks (1 each in February and June 2012). Results In total, 35 centers (18 in Italy, 17 in Spain) agreed to participate and collected 54 cases. The incidence of pneumonia was 10.1 episodes/1000 recipients/year. Pneumonia was classified as late (>6 months) in 70.4% of cases. Pneumonia was also classified as community-acquired (CAP), healthcare-associated (HCAP), and hospital-acquired (HAP) pneumonia in 40.7%, 38.9%, and 20.4% of cases, respectively. An attempt to microbiological diagnosis (≥1 sample) was made in 94.4% of patients, with a diagnostic yield of 60.7%. Causative agents included bacteria (87.1%), virus (29%), and fungi (6.4%). A multidrug-resistant bacterium was isolated in 18.2%, 40%, and 100% of patients with CAP, HCAP, and HAP (P = 0.007), respectively. Overall, 11.1% of patients were admitted to the intensive care unit, 3.7% developed graft rejection, and graft function deteriorated in 18.5%. In-hospital mortality was 1.9%. Conclusion Pneumonia remains a frequent problem in SOT recipients, although it occurs later in patients who are in better physical health. Therefore, harmful pathogens and worse outcome are less common than previously thought.

Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals. Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate its economic impact. During the first year of the AFS a bundle of non-interventional measures were implemented. During the second year an infectious diseases specialist visited 453 patients receiving candins, liposomal amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an interrupted time series (ITS) analysis. The main prescribing departments were haematology (35%), medical departments (23%), and intensive care units (20%). Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial visit, diagnostic advice was provided in 40% of cases. The most common therapeutic recommendations were to de-escalate the antifungal drug (17%) or to suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8 million to US$2.9 million over the first 2 years, generating net savings of US$407,663 and US$824,458 per year after considering the cost of additional staff required. The ITS analyses showed a significant economic impact after the first 12 months of the intervention (p 0.042 at month 13), which was enhanced in the following 24 months (p 0.006 at month 35). The number of defined daily doses decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to 16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside intervention is an efficacious and cost-effective approach that optimizes the use of AF drugs.

Gestrinone has been shown to reduce uterine volume and stop bleeding in women with uterine leiomyomata. In the present study, we demonstrated a reduction in the volume of uterine myomas and in the uterine artery blood perfusion over a 6-month period of gestrinone administration in premenopausal women.

Background: Since the early 1980s, epidemiological evidence has suggested a connection between low calcium intake and preeclampsia The purpose of this meta-analysis is to summarize current evidence regarding calcium supplementation during pregnancy in predicting preeclampsia and associated maternal– fetal complications. Methods: Literature revision of all RCT (random allocation of calcium versus placebo) available in MEDLINE/ PUBMED up to 2/29/2012 regarding calcium supplementation during pregnancy for preventing preeclampsia. We used the Mantel-Haenszel’s Method for four subgroup of patients: Adequate calcium intake; Low calcium intake; Low risk of preeclampsia; High risk of preeclampsia. We considered p < 0.05 as significant. Results: There is no consensus in Literature about: (1) the efficacy of calcium supplementation in the prevention of preeclampsia, (2) other/adverse/long-term effects of calcium supplementation in pregnancy. Conclusions: Preeclampsia is likely to be a multifactorial disease. However, inadequate calcium intake represents a factor associated with an increased incidence of hypertensive disease. The results of our meta-analysis demonstrate that the additional intake of calcium during pregnancy is an effective measure to reduce the incidence of preeclampsia, especially in populations at high risk of preeclampsia due to ethnicity, gender, age, high BMI and in those with low baseline calcium intake.

In Qatar, there is evidence of underuse of the immunization services despite easy access to health care. We therefore undertook a prospective study to determine the vaccination status and, more importantly, the reasons for inadequate immunization of a group of 255 preschool children attending the outpatient care facilities in Doha. A questionnaire was used to obtain relevant information, including parent's educational background. Sixty-six percent of the children were fully immunized for their age group, 12% were partially immunized, and 12% were not immunized. Eighty-eight percent had received their first dose of DPT/OPV, but only 57% had received their first booster by 18 months of age; 76% had received three doses of DPT/OPV. The main reasons for nonimmunized status were misinformation and lack of awareness in parents about vaccination. Parental oversight, misinformation, and medical deferral were the main reasons for partial immunization. Parents of unimmunized children were often illiterate. In Qatar, establishment of an aggressive ongoing public education campaign, as well as strict implementation of the World Health Organization's Expanded Programme on Immunization's policy of screenign all children at every health care contact for the need for vaccination, should substantially increase immunization coverage. Implementation of a recall system for defaulters should also lead to improved immunization rates.

To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of PCOS patients.Controlled clinical study.PCOS patients in a clinical research environment.20 overweight PCOS patients were enrolled after informed consent.All patients underwent hormonal evaluations and an oral glucose tollerance test (OGTT) before and after 12 weeks of therapy (Group A (n = 10): myo-inositol 2 gr. plus folic acid 200 mug every day; Group B (n = 10): folic acid 200 mug every day). Ultrasound examinations and Ferriman-Gallwey score were also performed.Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio.After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid.Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.

Objective To present the results obtained in 104 cases of vaginal aplasia resolved with self-dilatation or with surgical procedures such as the McIndoe or Williams operations. Design Retrospective study. Setting Departments of obstetrics and gynecology of universities in Bologna, Modena, and Messina, Italy. Patient(s) One hundred four cases of vaginal aplasia. Intervention(s) Self-dilatation and surgical procedures such as the McIndoe or Williams operations. Main Outcome Measure(s) Outcome of the treatment. Result(s) From 1977 to 2002, 104 cases of vaginal agenesis were treated. The mean age of the treated patients was 16.5 years old (range, 13–18 years). After 6 months of self-dilatation, 41 subjects obtained a new cavity of about 10–12 cm in length. In 14 patients, a space ranging from 3 to 5 cm was obtained. The technique failed in 49 patients. Fourteen patients underwent the Williams surgical procedure, while the remaining 49 patients underwent to the McIndoe procedure. All patients were successfully treated, and the only complication, a rectovaginal fistula that was repaired, occurred in one case of the McIndoe operation. Conclusion(s) Self-dilatation should be the first approach because of its high success rate; the Williams surgical approach should be chosen when self-dilatation partially fails or when previous surgical attempts are unsuccessful. Finally, the McIndoe procedure and its variants should be used when self-dilatation completely fails.

To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension.The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16-45 years, diagnosis of gestational hypertension without proteinuria (patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine (20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a.m. to 10 a.m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08:00, 12:00, 16:00 and 20:00 h.Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo (systolic values F = 8.59, p0.005; diastolic values F = 3.36; p0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic (F = 5.42, p0.005) and diastolic (F = 2.20, p0.005) blood pressure values.In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.

The aim of the present study was to examine the relationship between Mullerian-inhibiting substance (MIS) levels and metabolic characteristics in women with polycystic ovary syndrome. Increased ovarian MIS production may exert a paracrine negative control on follicle growth sufficiently to prevent selection of a dominant follicle.

Cervical atresia is an extremely rare malformation. Its incidence is not well known and management is controversial. The surgical technique and results of utero-vaginal anastomosis in 3 women affected by cervical atresia are described.

Objective: Intravaginal estriol (E3) effectively improves postmenopausal genito-urinary disturbances, without stimulating endometrial proliferation. The aim of the present study was to evaluate the effect of intravaginal estriol (E3) plus nasal spray salmon calcitonin (sCT), to improve neurovegetative symptoms and to prevent the decline of bone mineral density (BMD) of postmenopausal women. Methods: Two hundred and fourteen (214) healthy postmenopausal women were treated for 12 months with: (1) E3 (0.5 mg every other day) + Ca (0.5 g/day); (2) E3 + Ca + sCT (50 IU × 2/day); (3) sCT + Ca; (4) Ca. Climacteric complaints, such as hot flushes and sweating, BMD at the distal 1 10 of the radius, analyzed by dual photon absorptiometry, urinary excretion of hydroxyproline and serum alkaline phosphatase were evaluated at baseline and every 6 months. At the same time, patient compliance and drug tolerability were evaluated. Results: E3 but not sCT, improved hot flushes and sweating. E3 blunted but not completely counteracted the BMD decline observed in women treated with only Ca, and reduced urinary hydroxyproline excretion. sCT markedly increased BMD values and reduced both urinary hydroxyproline excretion and serum alkaline phosphatase. These effects were not potentiated by E3 coadministration. All treatments were well tolerated. Conclusions: Present data indicate that the combined administration of intravaginal E3 and sCT may represent an alternative therapeutic regimen for those postmenopausal women who do not accept or have contraindications to classical hormone replacement therapy.

Epidermal growth factor receptor (EGF-R) has been implicated in the growth of endometrial cancer. In the present study, immunostaining of EGF-R was investigated in different endometrial cancer histotypes. For this purpose 34 surgical samples of primary endometrial carcinoma were studied using monoclonal anti-EGF-R antibody. The endometrial carcinomas were classified according to the International Society of Gynaecological Pathology (I.S.G.P.). EGF-R expression was observed in: 1 of 5 classical endometrioid adenocarcinomas (AE), in 8 of 9 endometrial adenocarcinomas with benign squamous metaplasia (AA), and in 3 of 14 adenosquamous adenocarcinomas (AS). In mucinous (M) and serous papillary adenocarcinoma (SP) EGF-R immunostaining was not observed. The EGF-R positivity was observed in endometrial cancer with squamous (SQ) differentiation, especially in those with benign SQ metaplasia. These results suggest that EGF-R immunostaining is related to the endometrial cancer histotype regardless of the tumor grade or extent of miometrial invasion.

The unpredictable response of endometriosis to steroids and its recurrence after therapy, led us to hypothesize a possible further control of this pathology by factors other than steroids. The presence of estrogen, progesterone and epidermal growth factor receptors (ER, PR, EGFr) was evaluated using immunohistochemistry before and after therapy with Danazol or a gonadotropin-releasing hormone analogue (GnRHa), Buserelin. EGFr, ER and PR were present in 100% of endometrial specimens, and in 71%, 29% and 49% of endometriotic implants, respectively. Danazol and GnRHa reduced immunohistochemical staining for EGFr antisera in the endometrial and endometriotic specimens. About 21% of endometriosis were EGFr positive and ER negative, suggesting a potential role of epidermal growth factor in growth and maintenance of endometrial ectopia.

Twenty-four hirsute women were treated with an inversal sequential scheme of cyproterone acetate, 50 mg/d by oral route from the 1st to the 15th day of the menstrual cycle, along with 100 micrograms/24 h of 17 beta-estradiol transdermally administered from days 1 to 21, for nine cycles at weekly intervals. The acne and seborrhea as well as hirsutism showed a significant improvement in all subjects studied. The plasma testosterone and dehydroepiandrosterone sulfate decrease from 1.5 +/- 1.3 ng/mL and 6.9 +/- 1.3 micrograms/mL to 0.5 +/- 0.03 ng/mL and 2.7 +/- 1.7 micrograms/mL, respectively. Similar values were observed in subjects with idiopathic hirsutism during the treatment. The metabolic parameters, as well as the plasma levels of sex hormone-binding globulin, appeared unaffected by the therapy. Furthermore, the luteinizing hormone and follicle-stimulating hormone secretion was strongly inhibited from the first cycle of treatment. In conclusion, considering the good clinical results and the avoidance of any hepatic effect, this association should be taken into account in the treatment of hirsutism, especially in case of oral estrogen intolerance.

A combined measles, mumps, rubella, and varicella vaccine produced seroconversions for all four components similar to that found if measles, mumps, and rubella vaccine or live varicella vaccine were given separately. In addition, those exposed to varicella were completely protected or had only a mild rash. Moreover, the reaction rates were not increased if the vaccines were combined. The somewhat lower and delayed serologic response to live varicella vaccine as compared with the combined measles, mumps, rubella, and varicella may have been due to the small amount of varicella vaccine virus used or to its degree of attenuation. Persistence of antibody was observed 1 year postimmunization.

Clinical manifestations of chickenpox have occurred in individuals known to have seroconverted after vaccination against varicella. To determine whether these "breakthroughs" might be due to the absence of specific antibodies, we tested sera from vaccinees before or at the time of exposure to varicella for antibodies to the three major glycoproteins of varicella-zoster virus (VZV). Protection could not be correlated with the presence or level of any of these antibodies. Levels of antibodies to glycoproteins before onset of zoster were similar to those in sera of individuals who had had varicella previously and did not develop varicella after household exposure. Thus, protection against infections with VZV cannot be explained by the presence of specific antibodies to glycoproteins.

The purpose of this study was to evaluate the increases in plasma levels of E1, E1S and E2 during constant infusion of dehydroepiandrosterone (D) in premenarchal girls (PG) and in normal menstruating women (AW). Unlabelled D was infused for 48 h in 10 premenarchal girls and in 10 normal menstruating women. Plasma levels of D, estrone (E1), estrone sulfate (E1S) and estradiol (E2) were measured before and during 48 h infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of E1, E1S and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of D were found significantly lower in premenarchal girls than in normal menstruating women. MCRD was found significantly higher in premenarchal girls than in normal menstruating women (2565 +/- 467 L/day versus 1317 +/- 242 L/day, p less than 0.01). Administration of D increased the plasma levels of E1 and E1S in the group of normal menstruating women but not in the premenarchal girls. Considering all subjects studied, the increases in plasma levels of E1 and E1S during the infusion of D were significantly correlated with body weight (p less than 0.01 and p less than 0.001, respectively). From these results, we conclude that in premenarchal+ girls there is: a reduced peripheral contribution of D to E1 and E1S, and/or a higher MCRE1 and MCRE1S than in normal menstruating women.

Plasma estrone sulphate ( E1S ) and estrone (E1) concentrations were determined in healthy postmenopausal women and in postmenopausal women with endometrial cancer, matched for body weight, age, and years since menopause. E1S levels (mean +/- SD) were significantly higher (P less than 0.05) in cancer patients with normal weight (511 +/- 200 pg/ml) than in control subjects (303 +/- 99 pg/ml). E1S levels were also higher in obese cancer patients (691 +/- 328 pg/ml) than in obese control subjects (610 +/- 139 pg/ml). Both cancer groups showed similar plasma E1 levels as compared with their respective controls. The E1S /E1 ratio was higher in both groups of cancer patients than in control subjects. These data suggest that estrogen conjugates should be taken into account during studies on estrogen balance and endometrial cancer.

Eczema herpeticum (EH) is a potentially life-threatening complication that may occur in children with atopic dermatitis. The clinical and laboratory features of EH as seen in 14 children are reported. The mean age of affected children was 34 months. A rapid viral diagnosis was made in 72 percent of patients. In one-third of patients there was a history of herpes labialis in one or other parent in the previous week. In 28 percent of the children, EH was initially thought to be an exacerbation or impetiginization of the underlying dermatitis. Eleven of 14 children were treated with acyclovir (intravenously in eight, orally in three). All patients recovered without sequelae.