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Background People with severe mental illnesses (SMI) have a mortality rate two times higher compared to the general population, with a decade of years of life lost. In this randomized controlled trial (RCT), we assessed in a sample of people with bipolar disorder, major depressive disorder, and schizophrenia spectrum disorder, the efficacy of an innovative psychosocial group intervention compared to a brief psychoeducational group intervention on patients’ body mass index (BMI), body weight, waist circumference, Framingham and HOMA-IR indexes. Methods This is a multicentric RCT with blinded outcome assessments carried out in six Italian university centers. After recruitment patients were randomized to receive a 6-month psychosocial intervention to improve patients’ physical health or a brief psychoeducational intervention. All recruited patients were assessed with standardized assessment instruments at baseline and after 6 months. Anthropometric parameters and blood samples have also been collected. Results Four-hundred and two patients with a diagnosis of bipolar disorder (43.3%), schizophrenia or other psychotic disorder (29.9%), or major depression (26.9%) were randomly allocated to the experimental (N = 206) or the control group (N = 195). After 6 months, patients from the experimental group reported a significant reduction in BMI (odds ratio [OR]: 1.93, 95% confidence intervals [CI]: 1.31–2.84; p p p Conclusions The experimental group intervention was effective in improving the physical health in SMI patients. Further studies are needed to evaluate the feasibility of this intervention in real-world settings.

In subjects with schizophrenia (SCZ), the disorganization dimension is a strong predictor of real-life functioning. "Conceptual disorganization" (P2), "Difficulty in abstract thinking" (N5) and "Poor attention" (G11) are core features of the disorganization factor, evaluated using the Positive and Negative Syndrome Scale. The heterogeneity of this dimension and its overlap with neurocognitive deficits are still debated. Within the multicenter study of the Italian Network for Research on Psychoses, we investigated electrophysiological and neurocognitive correlates of disorganization and its component items to assess the heterogeneity of this dimension and its possible overlap with neurocognitive deficits. Resting state EEG was recorded in 145 stabilized SCZ and 69 matched healthy controls (HC). Spectral amplitude was averaged in ten frequency bands. Neurocognitive domains were assessed by MATRICS Consensus Cognitive Battery (MCCB). RAndomization Graphical User software explored band spectral amplitude differences between groups and correlations with disorganization and MCCB scores in SCZ. Correlations between disorganization and MCCB scores were also investigated. Compared to HC, SCZ showed increased delta, theta, and beta 1 and decreased alpha 2 activity. A negative correlation between alpha 1 and disorganization was observed in SCZ. At the item level, only "N5" showed the same correlation. MCCB neurocognitive composite score was associated with disorganization, "P2" and "N5". Our findings suggest only a partial overlap between disorganization and neurocognitive impairment. The association of alpha 1 with the "N5" item suggests that some aspects of disorganization could be underpinned by the impairment of basic neurobiological functions that are only partially evaluated using MCCB.

Our manuscript aims to: 1) assess physical health in a sample of patients with severe mental disorders; and 2) identify the psychopathological and psychosocial characteristics associated with an increased likelihood of having a poor physical health. The study, funded by the Italian Ministry of Education, has been carried out in psychiatric outpatient units of six Italian University sites. All recruited patients have been assessed through standardized assessment instruments. Moreover, anthropometric parameters have been obtained at recruitment and a blood samples have been collected to assess cardiometabolic parameters. Four-hundred and two patients with a primary diagnosis of bipolar disorder (43.3%), schizophrenia or other psychotic disorder (29.9%), or major depression (26.9%) were recruited. Internalized stigma, psychosocial functioning, quality of life, psychiatric hospitalizations, depressive/anxiety and manic symptoms and cognition were those domains more strongly associated with poor metabolic parameters, including high body mass index, HOMA and Framingham indexes and waist circumference. There were no statistically significant differences among the three diagnostic groups. Our findings highlight the importance of perceived stigma and quality of life on patients’ physical health. This should be taken into account when developing plans for reducing the mortality rate in patients with severe mental disorders.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia. In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Exploring Psychiatric Features of Patients with Long-Term Vomiting after Bariatric Surgery Vomiting is a common side effect of bariatric surgery, occurring in the short and long-term post-operative period. Multiple factors cause chronic vomiting in bariatric patients such as surgical complications and maladaptive eating patterns. To date, psychiatric features associated with vomiting after bariatric surgery has been poorly and not specifically investigated. We explored possible socio-demographic and psychiatric differences (age, gender, marital status, psychiatric comorbidities, impulsivity, body image dissatisfaction, binge eating, depression, quality of life) of those patients who vomit over at least the first year post-operatively compared with those without vomiting. Sixty-one participants were enrolled, 37 women and 24 men; mean age was 45.45 (SD=9.88) and mean BMI was 46.51 (SD=7.29). The “vomiting” group comprised 18 individuals with at least one weekly episode of long-term vomiting. Clinical psychiatric evaluation and psychometric assessment were performed before and one year after bariatric surgery. The “vomiting” and “non-vomiting” groups did not differ in age, gender, marital status, types of surgical procedure, and % of Excess BMI Loss. Models of rm-ANOVA revealed significant “time” (pre vs. post-surgery) effects, meaning improvement of body mass index (BMI), body dissatisfaction, depression, binge eating, impulsiveness, and quality of life after surgery; “time” × “group” (vomiting vs. non vomiting) effects were not significant, revealing no differences between “vomiting” and “non vomiting” groups. This study didn’t find a relationship between long-term vomiting and psychiatric features. Post-operative vomiting may not require psychiatric additional interventions. If the irrelevance of psychiatric mechanism will be confirmed, the identification of factors associated with vomiting which are amenable of psychological interventions, will help the improvement of the multidisciplinary approach to bariatric patients. In particular, the development of healthy eating patterns, the adherence to nutritional recommendations can benefit from a thoughtful mental health care.

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC). Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan–Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence. Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0–24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients. The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.

Primary testicular lymphoma is an uncommon testicular tumour. We present a case of a primary non-Hodgkin lymphoma of the testis, describing its clinical and pathological features and discussing our treatment strategy. A 68-year-old man showed a firm erythematous testicular mass within the right emiscrotum. Subsequent ultrasonography demonstrated a right inferior pole testicular mass with disomogenously hypoecogenic. The patient was submitted to inguinal orchidectomy. Light microscopy demonstrated the classic appearance of a diffuse large B-cell lymphoma. The immunohistochemical study showed tumour cells intensively positive for CD45, Ki67 and CD20. No evidence of extra-testicular involvement by lymphoma was found. At 6 months, a TC-PET showed a clinical relapse in lung and abdominal lymphonodes, while clinical examination demonstrated a single, indolent and erythematous nodule in the left foot. The histologic analysis confirmed diagnosis of CD-20 positive B-cell lymphoma. The patient was treated with an anti-CD 20 monoclonal antibody (rituximab) alone every 3 weeks. After 3 months a complete response was observed in all sites of disease. The patient was free from disease at 12 months follow-up.

Magnetic resonance imaging (MRI) provides an in vivo assessment of cortical and subcortical regions affected in Parkinson's disease (PD). This review summarizes the most important conventional and non-conventional MRI techniques applied in this field. Standard neuroimaging techniques have played a marginal role in the diagnosis and follow-up of PD, essentially being used only to discriminate atypical syndromes from PD, to exclude secondary causes such as vascular lesions, and to confirm the absence of specific imaging features found in atypical parkinsonisms. However, non-conventional MRI techniques, i.e. new neuroimaging approaches such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI, may allow the detection of structural, functional and metabolic changes useful not only for differential diagnosis, but also for early diagnosis and outcome and treatment monitoring in PD. In addition, we illustrate the advantages of high-field MRI over lower magnetic fields, highlighting the great potential of advanced neuroimaging techniques.

To evaluate the SAPS 3 score predictive ability of hospital mortality in a large external validation cohort.Prospective observational study.A total of 28,357 patients from 147 Italian ICUs joining the Project Margherita national database of the Gruppo italiano per la Valutazione degli interventi in Terapia Intensiva (GiViTI).None.Evaluation of discrimination through ROC analysis and of overall goodness-of-fit through the Cox calibration test.Although discrimination was good, calibration turned out to be poor. The general and the South-Europe Mediterranean countries equations overestimated hospital mortality overall (SMR values 0.73 with 95% CI 0.72-0.75 for both equations) and homogeneously across risk classes. Overprediction was confirmed among important subgroups, with SMR values ranging between 0.47 and 0.82.The result strictly supported by our data is that the SAPS 3 score calibrates inadequately in a large sample of Italian ICU patients and thus should not be used for benchmarking, at least in Italian settings.

Several studies have shown that HLA-B8,DR3 positive subjects may display T cell dysfunctions. Recently, a soluble form of the receptor for IL-2 (sIL-2R) has been demonstrated in human sera and in vitro-stimulated culture supernatant from human T lymphocytes. In the present paper we report sIL-2R serum levels and sIL-2R production from peripheral blood mononuclear cells in HLA-B8,DR3 positive subjects. We found that HLA-B8,DR3 positive subjects have the highest values of serum sIL-2R, but comparing the values of these subjects with those of negative ones no significant difference was observed. As regards the in vitro production of sIL-2R, no difference exists for unstimulated cultures, whereas after stimulation, the HLA-B8,DR3 positive subjects showed the lowest values compared with negative ones. It is noteworthy that these changes are observed in autoimmune diseases linked to this HLA phenotype.

Prostate cancer that no longer responds to hormonal manipulation can be defined as hormone-refractory prostate cancer. Until recently, there has been no standard chemotherapeutic approach for hormone-refractory prostate cancer. The major benefits of chemotherapy in the treatment of the disease are palliative in nature, in terms of reduction of pain and use of analgesics and improvement of performance status, as followed in the most recent trials. Phase III studies are necessary to better evaluate the efficacy of the different regimens, because several old studies suffer for methodological deficits. There is a promising activity of new drug combinations, such as vinca alkaloids and taxanes. Phase I and II trial are testing combinations of classic chemotherapeutic agents and biologic drugs, and the first results appear interesting. In this article, recent advances in the treatment of hormone-refractory prostate cancer using chemotherapeutic regimens are critically reviewed.

Endometrial cancer is the most common gynecologic malignancy arising from the endometrium. Identification of serum biomarkers could be beneficial for its early diagnosis. We have used 2D-Difference In Gel Electrophoresis (2D-DIGE) coupled with Mass Spectrometry (MS) procedures to investigate the serum proteome of 15 patients with endometrial cancer and 15 non-cancer subjects. We have identified 16 proteins with diagnostic potential, considering only spots with a fold change in %V ≥ 1.5 or ≤0.6 in intensity, which were statistically significant (p &lt, 0.05). Western blotting data analysis confirmed the upregulation of CLU, ITIH4, SERPINC1, and C1RL in endometrial and exosome cancer sera compared to those of control subjects. The application of the logistic regression constructed based on the abundance of these four proteins separated the controls from the cancers with excellent levels of sensitivity and specificity. After a validation phase, our findings support the potential of using the proposed algorithm as a diagnostic tool in the clinical stage.

Although both docetaxel and androgen-receptor-axis-targeted (ARAT) agents have yielded survival improvements in combination with androgen deprivation therapy (ADT) compared to ADT alone in metastatic castration-sensitive prostate cancer (mCSPC) patients, the optimal therapeutic choice remains to be established. We analyzed estimates of the hazard ratios for death (OS-HRs) in patients treated in the first-line setting enrolled in the GETUG-AFU15, CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN trials. Overall, men with mCSPC receiving ADT with vs. without either an ARAT agent or docetaxel as first-line systemic therapy showed a pooled OS-HR of 0.69 (95 % CI: 0.61−0.78), with significant heterogeneity (p = 0.045, I2 = 52.5 %). Network meta-analysis showed an OS-HR in patients receiving an ARAT agent vs. docetaxel of 0.78 (95 %CI: 0.67−0.91). In conclusion, the evidence analysed indicates that an ARAT agent may provide improved OS outcomes compared to docetaxel. Prospective randomized trials are warranted.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p

Background: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown. Methods: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy. Results: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities. Conclusions: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful.

Patients with locally advanced penile squamous-cell carcinoma have a poor prognosis. No difference in survival was noted when using chemotherapy before or after surgery. Uncertainties persist regarding the optimal management of these patients, and new treatments are urgently required, particularly for patients at highest risk, with bilateral and/or pelvic lymph node involvement. BACKGROUND: The prognosis of patients with locally advanced penile squamous-cell carcinoma is primarily related to the extent of lymph node metastases. Surgery alone yields suboptimal results, and there is a paucity of data on these patients’ outcomes. PATIENTS AND METHODS: This retrospective study evaluated patients who received neoadjuvant or adjuvant chemotherapy from 1990 onward at 12 centers. Cox models were used to investigate prognostic factors for relapse-free survival and overall survival (OS). RESULTS: Among the 201 included patients, 39 (19.4%) had disease of T3-4 and N0 clinical stage; the remaining patients had clinical lymph node involvement (cN+). Ninety-four patients received neoadjuvant chemotherapy (group 1), 78 received adjuvant chemotherapy (group 2), and 21 received both (group 3). Eight patients for whom the timing of perioperative chemotherapy administration was unavailable were included in the Cox analyses. Forty-three patients (21.4%) received chemoradiation. Multivariate analysis for OS (n = 172) revealed bilateral disease (P = .035) as a negative prognostic factor, while pelvic cN+ tended to be nonsignificantly associated with decreased OS (P = .076). One-year relapse-free survival was 35.6%, 60.6%, and 45.1% in the 3 groups, respectively. One-year OS was 61.3%, 82.2%, and 75%, respectively. No significant differences were seen on univariable analyses for OS between the groups (P = .45). Platinum type of chemotherapy and chemoradiation were not significantly associated with any outcome analyzed. CONCLUSION: Benchmark survival estimates for patients receiving perioperative chemotherapy for locally advanced penile squamous-cell carcinoma have been provided, with no substantial differences observed between neoadjuvant and adjuvant administration. This analysis may result in improved patient information, although prospective studies are warranted.

Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well- to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.

Until very recently, docetaxel was the only approved agent in castration-resistant prostate cancer (CRPC) and other effective therapeutic options are urgently needed. In recent years, several new agents with promising activity and a favourable toxicity profile have been developed and clinically investigated in the fields of hormonal, cytotoxic, targeted and immune therapy. In particular, recent results from two large phase III trials of sipuleucel-T and cabazitaxel show that these two agents significantly prolong overall survival in CRPC. Indeed, sipuleucel-T has recently been approved by the US FDA for the treatment of CRPC. Many other pharmaceuticals, which are presented in this review, have been investigated recently or are being investigated in phase III trials and might prove to be effective in the future. Reviewed articles are discussed in light of the innovations in study design brought by the Prostate Cancer Clinical Trials Working Group (PCWG2), which updated the Prostate-Specific Antigen Working Group (PCWG1) guidelines, in order to allow better identification of potentially active drugs in clinical trials.

Aims. We determined whether c-kit proto-oncogene is expressed in prostate cancer and whether its expression is related with biochemical relapse in high risk localized prostate cancer patients. Methods. c-Kit expression was evaluated by immuno-histochemistry in 94 prostate cancer samples from patients treated by radical prostatectomy followed by adjuvant hormonal therapy because all patients had a pT3a stage (initially cT2 stage). All patients presented a O7 Gleason score and a O10 pre-operative PSA value. We evaluated association between c-kit positive staining and disease free survival. Results. In 26 of 94 prostate cancer, we found an epithelial positive c-kit expression. The epithelial expression was found in the peripheral zone of prostate tissue. 13/94 relapsed and, although not statistically significant (p 0.055), a trend to a higher risk of relapse among the c-kit positive samples was observed in our series of prostate cancer patients. Conclusions. Our study is only an initial experience and it is necessary to consider a higher number of patients to clarify whether c-kit is really an independent predictor for disease recurrence. Further study in this area will help to understand whether anti c-kit drugs could become an effective complement to the armamentarium of prostate cancer therapies. q 2004 Elsevier Ltd. All rights reserved.

Approximately 40% of males with low Gleason grade clinically localized prostate cancer (PCa) at biopsy were finally diagnosed with high Gleason grade PCa at radical prostatectomy (RP). Therefore, a more reliable assessment of the Gleason grade prior to RP is required. Readily available modalities such as circulating biomarkers may be useful for this purpose. The aim of this study was to evaluate the ability of preoperative interleukin 6 (IL‑6) and its soluble receptor (sIL‑6R), as well as urokinase-type plasminogen activator (u-PA), its receptor (u-PAR) and the inhibitor (PAI-1) to predict Gleason score upgrading. A total of 51 PCa patients with biopsy Gleason score ≤7 were studied. IL‑6 and sIL‑6R, uPA, uPAR and PAI-1 preoperative serum levels were determined. Differences in the median and mean values of the preoperative blood levels of all biomarkers between patients with and without Gleason score upgrading were tested. The prognostic performance of each biomarker was further assessed by means of receiver operating characteristic (ROC) curves. The results showed the sIL‑6R and sIL‑6R/IL-6 ratio median levels to be significantly higher in patients who had Gleason score upgrading from ≤7 at biopsy to >7 at RP (p=0.024 and p=0.011, respectively). The ROC curve revealed that sIL‑6R and the sIL‑6R/IL‑6 ratio identified subjects at a high risk of upgrading [area under curve (AUC)=0.80 and AUC=0.83, respectively] with similar sensitivity and higher specificity for the ratio. The findings suggest that preoperative sIL‑6R and sIL‑6R/IL‑6 ratio determination in serum are useful as prognostic biomarkers in PCa patients.

Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant glioma (MG), with a median survival time of 12-15 months, despite current best treatment based on surgery, radiotherapy and systemic chemotherapy. Many potentially active therapeutic agents are not effective by systemic administration, because they are unable to cross the blood-brain barrier (BBB). As intracerebral administration bypasses the BBB, it increases the number of drugs that can be successfully delivered to the brain, with the possibility of minor systemic toxicity and better effectiveness. This review summarizes the results of the extensive clinical research conducted on intracerebral therapy. Biodegradable drug carriers, implantable subcutaneous reservoirs and convection-enhanced delivery (CED) represent the main techniques for intracerebral delivery, while conventional chemotherapy agents, radiolabeled antibodies and receptor-targeted toxins are the main classes of drugs for intracerebral therapy. At the present time, biodegradable carmustine wafers, commercialized as Gliadel(®), are the only FDA-approved treatment for intracerebral chemotherapy of MG, but intracavitary delivery of mitoxantrone and radiolabeled antitenascin antibodies via implantable reservoirs has yielded promising results in uncontrolled trials. The pressure-driven flow generated by CED can potentially distribute convected drugs over large volumes of the brain, independently on their intrinsic diffusivity. Nevertheless, prominent technical problems, like backflow, are yet to be properly addressed and contributed to the disappointing results of two phase III trials that investigated CED of cintredekin besudotox and TransMid™ in patients with recurrent GBM.

Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.

BACKGROUND: To the authors' knowledge, no previous studies have been reported with the combination of paclitaxel and oral cyclophosphamide in patients with metastatic bladder cancer. A phase 1/2 study was conducted of paclitaxel in combination with oral cyclophosphamide for patients with advanced urothelial bladder cancer who had been previously treated with gemcitabine/cisplatin chemotherapy as first-line metastatic treatment. METHODS: This was a single-arm phase 1/2 study. Patients were treated with paclitaxel and oral cyclophosphamide at 3-week intervals until disease progression or irreversible toxicity occurred. Primary endpoints were to determine the maximum tolerated doses (MTD) and objective response rate; secondary endpoints were safety, time to disease progression (TTP), and overall survival (OS). RESULTS: Forty-four patients were enrolled. Dose levels of paclitaxel of 175 mg/m2 (Day 1) and cyclophosphamide of 50 mg (Days 1-7 orally) (dose level I) of a 21-day cycle were tolerated without dose-limiting toxicities (DLTs). At a cyclophosphamide dose of 100 mg (dose level II) the MTD was exceeded; 3 of 6 patients experienced a DLT (grade 3 constipation and grade 4 neutropenia and thrombocytopenia [toxicities were graded using National Cancer Institute Common Toxicity Criteria (version 3.0)]). Dose level I was expanded and determined to be the MTD. A total of 32 patients were treated at dose level I in the phase 2 portion. Partial responses were observed in 31% of patients (10 of 32 patients; 95% confidence interval [95% CI], 17%-45%). Grade 1/2 vomiting, peripheral neuropathy, and neutropenia were the most common side effects, noted in 11 (34%), 8 (25%), and 10 (31%) patients, respectively. The median TTP was 5 months (95% CI, 2 months-7.5 months) and the median OS was 8 months (95% CI, 4 months-14 months). CONCLUSIONS: The combination of paclitaxel and cyclophosphamide is well tolerated and associated with promising efficacy. Further trials are needed to confirm these preliminary results. Cancer 2009. © 2008 American Cancer Society.

Objective: To demonstrate laparoscopic surgical management of parametrial ectopic pregnancy. Design: Video presentation of laparoscopic nerve-sparing treatment of parametrial pregnancy. Setting: Tertiary university center. Patient(s): A 33-year-old patient, nullipara at 8 weeks of gestation, with no comorbidity and no previous surgery, was admitted to a spoke hospital for acute abdominal pain. During hospitalization, a transvaginal gynecologic ultrasound revealed pregnancy with ectopic localization. Free pelvic fluid was detected, and a subsequent diagnostic laparoscopy was performed because of worsening symptoms. During the procedure, hemoperitoneum drainage was instituted and American Society of Reproductive Medicine stage III pelvic endometriosis was diagnosed. A round formation approximately 3 cm in diameter was found at the left posterior parametrium (Fig. 1). Due to the pregnancy position and β-human chorionic gonadotropic (β-hCG; 820 mUI /mL) values, conservative treatment was chosen. Thus, methotrexate at 50 mg/m2 body surface area was administered. A second dose of methotrexate was administered seven days after the first one, and the β-hCG increased to 1068 mUI. On day 14 after treatment, the β-hCG was 1053 mUI/mL. Therefore, surgical treatment was chosen, and the patient was transferred to our center. An ultrasound assessment confirmed the ectopic pregnancy with a live fetus in the left posterior parametrium. Intervention(s): The patient underwent operative laparoscopy to remove the ectopic pregnancy. Surgery was performed using a 3-dimensional optical system (TIPCAM 1, S D3-LINK; Karl Storz SE & Co., Tuttlingen, Germany). After drainage of the hemoperitoneum, the gestational sac was identified in the left posterior parametrium. The uterus, tubes, and ovaries showed normal morphology. Pelvic endometriosis was confirmed. After accessing the left pelvic retroperitoneum with the medial and lateral pararectal spaces’ opening and development, ipsilateral ureterolysis was necessary to isolate the parametrial pregnancy in close contact with it. Coagulation and sectioning of the deep uterine veins were essential to control hemostasis. Identification of the left hypogastric nerve, which was partially infiltrated by the chorionic villi, and the pelvic splanchnic nerves, was required to safeguard them (Fig. 2). Subsequently, the surgeon decided to place a ureteral stent to prevent urologic complications. Main Outcome Measure(s): The laparoscopic approach proved to be safe and feasible to manage parametrial pregnancy. Result(s): The pregnancy was removed entirely. The patient was discharged 72 hours after the procedure with an uneventful postoperative course. The histologic report confirmed the diagnosis of parametrial pregnancy on decidualized endometriotic tissue. The β-hCG serum level became negative in 20 days. Conclusion(s): Extrauterine pregnancies represent one of the leading causes of maternal death in the first trimester and constitute approximately 1%–2% of total pregnancies. Of these percentages, only 5%–8.3% are nontubal. Cases of abdominal pregnancy are even rarer, estimated at

Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients.A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3-60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%).In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31-1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86-3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS.In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients.

Objectives: To determine whether COX-2, bcl-2 and neoangiogenesis are related to human prostate cancer relapse after definitive surgical treatment and progression toward androgen independence and to evaluate the association between the patterns of these tumoral biomarkers and other standard clinico-pathological parameters (such as Gleason score, PSA, TNM stage). Materials and methods: We retrospectively analyzed the records on 126 prostate cancer samples from patients treated at our University Hospital from 1995 to 2002. The 72 patients with clinically localized disease (group 1) had undergone radical prostatectomy. Another 54 patients (group 2) had metastatic androgen-independent disease. Archived material relating to the subjects was then immunostained for bcl-2, COX-2 and CD-31, using an anti-bcl-2 monoclonal primary antibody, an anti-COX-2 polyclonal rabbit antibody and an anti-CD-31 monoclonal mouse antibody to evaluate neoangiogenesis (MVD, microvessel density). Results: We found that bcl-2, COX-2 and MVD expression increased from group 1 to group 2. The intergroup difference was significant only for high MVD (P

Web Services are becoming the prominent paradigm for distributed computing and electronic business. Web services composition is an emerging paradigm for enabling application integration within and across organization boundaries and for building complex Value Added Services (VAS). Different languages are emerging to describe web services composition, but no effort has been dedicated to systematically evaluating the capabilities and limitations of these languages and to formally define their constructs semantics, in order to allow a well defined execution of pattern describing web services interactions. The work of this paper intends to analyze in-depth the Business Process Execution Language for Web Services (BPEL4WS), presenting a new methodology used to state in a formal way which workflow patterns can be executed by using the BPEL4WS constructs.

Background: Spondylodiscitis can be a rare complication of gynecological surgery, typically of procedures involving the sacrum and the sacrospinous ligament. This report presents a case of spondylodiscitis arising after a laparoscopic sacrocolpopexy with a mesh. We also review the literature finding 52 cases of spondylodiscitis following sacrocolpopexy and (or) rectopexy with or without a mesh.Methods: We performed a comprehensive search from the electronic databases MEDLINE (Pubmed), Scopus, Web of Science, Embase, CINAHL, and Google Scholar from 1990 to February 2021 in order to identify case reports or case series reporting on spondylodiscitis after rectopexy or sacrocolpopexy.Results: We identified 52 total postoperative spondylodiscitis. We examined the mean age of patients, the surgical history, the time from initial surgery to spondylodiscitis, the presenting symptoms, the diagnostic tools, the medical and surgical treatment, the type of mesh used, the surgical access, and the possible causes of spondylodiscitis.Conclusions: Diagnosis of spondylodiscitis may be challenging. From our review emerges that recurrent pelvic pain and lumbosciatalgia may be signals of lumbar spondylodiscitis. Magnetic resonance is the gold standard examination for spondylodiscitis. Surgical practice needs to be improved further in order to establish the best procedure to minimize the incidence of this complication. Awareness of symptoms, timely diagnosis, and treatment are fundamental to prevent irreversible complications.

Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.

Background This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. Methods 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. Results PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. Conclusions Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT – Napoli – 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it

Objective Many therapies have been proposed for cervical pregnancy (CP) treatment; however, there is no consensus on the best practice to adopt, mainly owing to the rarity of this condition and the lack of randomized controlled trials. Therefore, there are no clinical practice guidelines for the management of this patient set. We presented an English literature review about the hysteroscopic management of CP. Data Sources The literature review was performed according to the Preferred Reporting Items for Scoping Reviews. The search strategy aimed at identifying cases from the first patients tracked down to those diagnosed in May of 2021. We searched in PubMed, Scopus, Google Scholar, and MEDLINE databases. Mesh terms used included “Cervical Pregnancy,” “Hysteroscopy,” “Ectopic pregnancy,” and “Resectoscopy.” Method of Study Selection Case reports of randomized controlled trials, prospective controlled studies, prospective cohort studies, retrospective studies, case series, and case reports were considered eligible. Review, Letters to the Editor, and abstracts accepted at conferences were ruled out. Tabulation, Integration, and Results We found a total of 3572 articles in all analyzed databases. A total of 2480 articles viewed were duplicated and therefore ruled out. After screening and excluding nonpertinent articles, 109 were assessed for eligibility, and 19 were included in the analysis. All articles were single case reports, small case series with no criteria selection, randomization, or study planning. We classified them as follows: cases treated with 10 mm resectoscope, with or without pretreatments of previous CP hysteroscopic approach, and cases resolved with 5 mm hysteroscopy, with or without pretreatments of previous CP hysteroscopic approach. Conclusion The hysteroscopic method represents a feasible and safe approach to the CP treatment, although there are still some aspects to be clarified, such as the pretreatment need and the instruments’ type and sizes based on the beta-subunit of human chorionic gonadotropin, pregnancy age, and dimension.

Purpose: The aim of the study is to compare the accuracy of unstructured preoperative Computed Tomography (CT) reports from non-tertiary diagnostic centers with intraoperative findings in a large cohort of patients with Chronic Otitis Media (COM) undergone surgery.Methods: From 2012 to 2019, a total number of 301 patients were considered for our purposes. All patients with clinical evidence of COM had preoperative non-contrast high resolution CT scan of the temporal bone in non-tertiary diagnostic centers, performed within 3 months before surgery.Results: The accuracy of CT reports was analyzed in terms of nature, anatomical site, disease extension, bony erosion, vascular structures abnormalities relevant to surgical planning, and Eustachian tube patency. Compared to post-surgical findings, CT reporting critical analysis revealed a tendency to overestimation of bony erosion, coupled to underestimated description of facial canal/lateral semi-circular canal, vascular structures, and Eustachian tube.Conclusion: Discrepancies between CT reports and surgical findings in middle ear opacification can be at least in part due to limited expertise of general radiologists in ENT neuroimaging. To limit this lack of information and the limited accuracy of middle ear structures depiction, here we propose a structured checklist to adopt in the case of a temporal bone CT scan for COM, in order to optimize the communication with surgeons and provide all the crucial information for an accurate surgical planning.

AIM The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD). METHOD A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one-way analyses of variance or Kruskal-Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another. RESULTS An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = -.52, P

Objective: The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18β-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks. Study Design: Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 1:1 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days. Main outcome measure: The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function. Results: Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P

Introduction. Metastatic castration-resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, whereas detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRPC. Patients and methods. In this translational study, we employed flow cytometry to assess total, PTEN–, and AR-V7+ CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide. Results. CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN– CTC, and AR-V7+ CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [CI], 5.6-9) and 14.3 (95% CI, 12.8-20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), whereas median (interquartile range) PTEN– CTC count was 2 (0; 4) and median (interquartile range) AR-V7+ CTC count was 1 (0; 3). At baseline, ≥ 5 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P=.021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P =.003), whereas ≥ 2 versus < 2 PTEN– CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P=.001) and OS (HR, 2.36; 95% CI, 1.12-5; P=.025). Finally, ≥ 1 versus < 1 AR-V7+ CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P

Introduction: The global COVID-19 pandemic has affected the economy, daily life, and mental/physical health. The latter includes the use of electroencephalography (EEG) in clinical practice and research. We report a survey of the impact of COVID-19 on the use of clinical EEG in practice and research in several countries, and the recommendations of an international panel of experts for the safe application of EEG during and after this pandemic. Methods: Fifteen clinicians from 8 different countries and 25 researchers from 13 different countries reported the impact of COVID-19 on their EEG activities, the procedures implemented in response to the COVID-19 pandemic, and precautions planned or already implemented during the reopening of EEG activities. Results: Of the 15 clinical centers responding, 11 reported a total stoppage of all EEG activities, while 4 reduced the number of tests per day. In research settings, all 25 laboratories reported a complete stoppage of activity, with 7 laboratories reopening to some extent since initial closure. In both settings, recommended precautions for restarting or continuing EEG recording included strict hygienic rules, social distance, and assessment for infection symptoms among staff and patients/participants. Conclusions: The COVID-19 pandemic interfered with the use of EEG recordings in clinical practice and even more in clinical research. We suggest updated best practices to allow safe EEG recordings in both research and clinical settings. The continued use of EEG is important in those with psychiatric diseases, particularly in times of social alarm such as the COVID-19 pandemic., SCOPUS: ed.j, info:eu-repo/semantics/published

Background Previous outbreaks of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV) have been associated with unfavourable pregnancy outcomes. SARS-CoV-2 belongs to the human coronavirus family, and since this infection shows a pandemic trend it will involve many pregnant women. Aims This systematic review and meta-analysis aimed to assess the impact of coronavirus disease 19 (COVID-19) on maternal and neonatal outcomes. Sources PubMed, EMBASE, MedRxiv, Scholar, Scopus, and Web of Science databases were searched up to 8th May 2020. Articles focusing on pregnancy and perinatal outcomes of COVID-19 were eligible. Participants were pregnant women with COVID-19. Content The meta-analysis was conducted following the PRISMA and MOOSE reporting guidelines. Bias risk was assessed using the Joanna Briggs Institute (JBI) manual. The protocol was registered with PROSPERO (CRD42042020184752). Twenty-four articles, including 1100 pregnancies, were selected. The pooled prevalence of pneumonia was 89% (95%CI 70–100), while the prevalence of women admitted to the intensive care unit was 8% (95%CI 1–20). Three stillbirths and five maternal deaths were reported. A pooled prevalence of 85% (95%CI 72–94) was observed for caesarean deliveries. There were three neonatal deaths. The prevalence of COVID-19-related admission to the neonatal intensive care unit was 2% (95%CI 0–6). Nineteen out of 444 neonates were positive for SARS-CoV-2 RNA at birth. Elevated levels of IgM and IgG Serum antibodies were reported in one case, but negative swab. Implications Although adverse outcomes such as ICU admission or patient death can occur, the clinical course of COVID-19 in most women is not severe, and the infection does not significantly influence the pregnancy. A high caesarean delivery rate is reported, but there is no clinical evidence supporting this mode of delivery. Indeed, in most cases the disease does not threaten the mother, and vertical transmission has not been clearly demonstrated. Therefore, COVID-19 should not be considered as an indication for elective caesarean section.

We examined factors that may impact cabazitaxel treatment duration in a real-life setting in a compassionate use program, expanded access program, and prospective observational study in metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC previously treated with docetaxel (N = 1,621) received cabazitaxel 25 mg/m2 intravenously every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. The median number of cabazitaxel cycles was six (range, 1&ndash, 49), 708 patients (43.7%) received &gt, 6 cycles. Patients receiving &gt, 6 cycles tended to have a better Eastern Cooperative Oncology Group performance status of 0&ndash, 1 (p = 0.0017 for &le, 6 vs. &gt, 6 cycles). Overall, 348 patients (21.5%) were &ge, 75 years of age, 139 (39.9%) received &gt, 6 cycles. The main reason for discontinuation was disease progression, however, in patients receiving 1&ndash, 2 cycles, the main reason for discontinuation was adverse events. Only 52 patients (3.2%) progressed during cycles 1&ndash, 2. Cabazitaxel was well tolerated in these studies, which included some elderly and frail patients, offering clinicians an important treatment option in the management of mCRPC. Proactive management of adverse events may allow patients to receive a higher number of cabazitaxel cycles and derive greater benefit.

Background Both docetaxel and androgen-receptor-axis-targeted (ARAT) agents are approved in metastatic castration-sensitive prostate cancer (mCSPC) patients. Predictive factors of therapy efficacy are lacking. Methods We included articles reporting data about randomized-controlled clinical trials (RCTs) testing an ARAT agent plus ADT vs. ADT. We aimed to obtain pooled estimates of efficacy outcomes and assess differences in pooled estimates of efficacy outcomes between sub-groups. Results A total of 5427 mCSPC patients enrolled in five RCTs were evaluable for OS (Overall Survival) and PFS (Progression-free survival). Pooled OS-HR (Hazard Ratio) was 0.66 (95 % CI: 0.60−0.74), while pooled PFS-HR was 0.46 (95 % CI: 0.40−0.53). Combined treatment with docetaxel was associated with differential OS outcomes, while tumor volume according to the CHAARTED criteria and visceral metastasis were associated with differential PFS outcomes. Conclusion Our results add evidence that ARAT agents improve OS in mCSPC and discourage their combined use with docetaxel in this setting.

Objectives Aim of this study is to refer a single center experience of laparoscopic or laparotomic assisted ureteral stenting without the use of imaging guidance. Study design We recruited 19 patients in the Institute for Maternal and Child Health in Trieste (Italy) who underwent ureteral stenting between June 2017 and December 2018 for suspicious ureteral injury during gynecological surgery. Ureteral stents insertions were performed in all cases using rigid cystoscopes, hybrid guidewire with a hydrophilic coating, and double loop ureteral stents; the ureters were skeletonized during surgery and stents were used to permit better visualization of the ureteral whole and to prevent complications connected with the ureteral devascularization and minor not recognized ureteral injuries. All the procedures were performed under a laparoscopic or laparotomic guide. Results No sign of acute kidney failure was reported during the post-operative kidney functions evaluation. The right position of the stents was confirmed in the first postoperative day by ultrasonographic imaging. No major complications related to the urinary tract have been detected. Ten patients stated stent related symptoms well controlled by analgesic therapies. All stents were removed by office cystoscopies one month later without reporting any complication. Conclusions Introducing fluoroscopy or ultrasonographic imaging into the operative field could be difficult and time-consuming. Instead, the laparoscopic and laparotomic guided ureteral stenting without the use of imaging currently used in the standard clinical practice of many institutions even without an official standardization in order to treat or prevent ureteral injuries after the surgery, seems to be safe and feasible.

Background Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37–0.72; p p 50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p Conclusions Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted.

// Daniele Santini 1 , Raffaele Ratta 2 , Francesco Pantano 1 , Delia De Lisi 1 , Marco Maruzzo 3 , Luca Galli 4,6 , Elisa Biasco 4 , Azzurra Farnesi 4 , Sebastiano Buti 5 , Cora Nanette Sternberg 6 , Linda Cerbone 6 , Giuseppe Di Lorenzo 7 , Silvia Spoto 8 , Michelle Sterpi 1 , Ugo De Giorgi 9 , Rossana Berardi 10 , Mariangela Torniai 10 , Andrea Camerini 11 , Francesco Massari 12 , Giuseppe Procopio 2 and Giuseppe Tonini 1 1 Campus Bio-Medico University of Rome, Department of Medical Oncology, Rome, Italy 2 Fondazione IRCCS, Istituto Nazionale dei Tumori, Oncology Unit 1, Milan, Italy 3 Istituto Oncologico Veneto, IOV-IRCCS, Medical Oncology 1 Unit, Padova, Italy 4 University Hospital of Pisa, Oncology Unit 2, Pisa, Italy 5 University Hospital of Parma, Medical Oncology, Parma, Italy 6 San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy 7 Department of Clinical Medicine & Surgery, Oncology Division, University Federico II, Naples, Italy 8 Campus Bio-Medico University of Rome, Department of Internal Medicine, Rome, Italy 9 IRCCS Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori, Department of Medical Oncology, Meldola, Italy 10 Universita Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Medical Oncology Unit, Ancona, Italy 11 Versilia Hospital and Istituto Toscano Tumori, Medical Oncology, Lido di Camaiore, Italy 12 S.Orsola-Malpighi Hospital, Division of Oncology, Bologna, Italy Correspondence to: Delia De Lisi, email: // Keywords : metastatic renal cell carcinoma (mRCC), oligoprogression, pazopanib, sunitinib, targeted therapy Received : April 25, 2016 Accepted : June 19, 2017 Published : August 07, 2017 Abstract Locoregional treatment with radical intent should be considered during therapy with targeted agents in patients with metastatic renal cell carcinoma (mRCC) in order to achieve a complete response, especially in the setting of an oligo-progression in one or more metastatic sites. We retrospectively enrolled 55 patients who experienced a disease oligo-progression after at least 6 months from the beginning of first-line therapy in one or more metastatic sites radically treated with locoregional treatments. Post-first-oligo-progression overall survival (PFOPOS) and post-first-oligo-progression free survival (PFOPFS) were evaluated. The global median PFOPOS and PFOPFS were 37 months and 14 months respectively. Patients who continued the same therapy after a locoregional treatment on a site of progression had a significantly longer mPFOPOS compared to patients who changed therapy (39 vs 11 months, p =0.014). An advantage in mPFOPOS was also observed in patients with a Memorial Sloan-Kettering Cancer Center (MSKCC) good risk score compared to patients of the intermediate risk group (39 vs 29 months, p =0.036); patients with bone metastases had a longer mPFOPOS compared to those with visceral metastases (not reached vs 31 months, p =0.045). The only independent predictor of poor prognosis, in terms of PFOPOS at multivariate analysis ( p =0.007), proved out to be change of treatment after first progression. In this paper we aim to illustrate that continuing the same systemic therapy, after a radical locoregional treatment on a site of progression, seems to be associated with a prolongation of mPFOPOS.

Background Guidelines and position papers indicate that allergen immunotherapy (AIT) is the only disease-modifying treatment, including prevention of the onset of new allergen sensitizations. However, this preventive effect was shown by only a few observational studies. Our aim was to systematically review the efficacy of AIT in preventing the onset of new allergen sensitizations. Methods Computerized bibliographic searches of MEDLINE, EMBASE, and the Cochrane Library (through June 2015) were supplemented with manual searches of reference lists. Observational studies or randomized controlled trials with a long-term observation period were included. Paired reviewers extracted data about study characteristics and assessed biases. The end-point was the risk difference in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy. The strength of the evidence was graded based on the risk of bias, consistency, and magnitude of effect, according to the GRADE Working Group's guide. Results Eighteen studies (1,049 children, 10,057 adults) met the inclusion criteria. The risk of bias was high in all but one study. Low evidence supports the position that AIT prevents the onset of new allergen sensitizations, with 10 out of 18 studies reporting a reduction of the onset of new sensitizations in patients treated with AIT vs. placebo. Small studies and studies with a shorter follow-up showed the highest benefit of AIT. Conclusions The overall evidence provides a low-grade level of the evidence supporting the efficacy of AIT in preventing the onset of new allergen sensitizations, but high-quality studies could change this estimate. This article is protected by copyright. All rights reserved

In the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has remarkably improved following the advent of the “targeted therapy” era. The expanding knowledge on the prominent role played by angiogenesis in RCC pathogenesis has led to approval of multiple anti-angiogenic agents such as sunitinib, pazopanib, axitinib, cabozantinib, sorafenib, and bevacizumab. These agents can induce radiological responses and delay cancer progression for months or years before onset of resistance, with a clinically meaningful activity. The need for markers of prognosis and efficacy of anti-angiogenic agents has become more compelling as novel systemic immunotherapy agents have also been approved in RCC and can be administered as an alternative to angiogenesis inhibitors. Anti PD-1 monoclonal antibody nivolumab has been approved in the second-line setting after tyrosine kinase inhibitors failure, while combination of nivolumab plus anti CTLA-4 monoclonal antibody ipilimumab has been approved as first-line therapy of RCC patients at intermediate or poor prognosis. In this review article, biomarkers of prognosis and efficacy of antiangiogenic therapies are summarized with a focus on those that have the potential to affect treatment decision-making in RCC. Biomarkers predictive of toxicity of anti-angiogenic agents have also been discussed.

Some commonly available patient or disease characteristics may be associated with progression-free survival (PFS) and overall survival (OS) in EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKIs (epidermal growth factor receptor - tyrosine kinase inhibitors). We performed a systematic review and meta-analysis of randomized control trials (RCTs) to explore differences in outcomes associated with EGFR-TKIs among subgroups of EGFR-mutant NSCLC patients. Pooled HRs for progression or death (PFS-HRs) and pooled HRs for death (OS-HRs) were compared among sub-groups defined according to baseline clinical and demographic variables as well as type of EGFR mutation. In the entire assessable population of 4465 EGFR-mutant NSCLC patients, significant interactions with PFS were found for gender (males vs. females; pooled ratio of the PFS-HRs = 1.2; 95% CI 1.12–1.56), smoking history (smokers vs. non-smokers; pooled ratio of the PFS-HRs = 1.26; 95% CI 1.05–1.51), and type of EGFR mutation (patients with exon 21 L858R mutation vs. exon 19 deletion; pooled ratio of the PFS-HRs = 1.39; 95% CI 1.18–1.63). Male patients, smokers and patients with EGFR exon 21 L858R mutation may derive less benefit from EGFR-TKIs compared to female patients, non-smokers and patients with EGFR exon 19 deletion.

Objectives: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non–muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB). Materials and methods: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival. Results: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20–1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99–1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio. Conclusions: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.

There is not a consensus on chronic pelvic pain definition; its common clinical characterization is a noncyclic pain perceived in the pelvic area that persists continuously or episodically for 3–6 months or longer and is unrelated to pregnancy. The prevalence of chronic pelvic pain ranges from 4 to 16 percent among fertile women but is very difficult to investigate because of lack of concordance on the definition and referral pattern. It has a great number of potential etiologies due to multiple components; indeed, differential diagnosis includes a wide range of pathologies involving various organs and functions. The most common causes of chronic pelvic pain involve gynecological, urological, gastrointestinal, and musculoskeletal diseases, followed by neurological and psychosocial disorders. However, in many cases nonspecific etiology can be identified. A correct evaluation of cause and, consequently, appropriate management of diagnosis and therapy require a targeted evaluation of the syndrome. The location and the characteristics of the pain, and the factors that provoke or alleviate it, are necessary to perform differential diagnosis. Moreover, an accurate physical examination is essential to achieve a correct evaluation of chronic pelvic pain, including complete abdominal and pelvic examinations, and psychosocial evaluation, with assessment for mental health issues and social disability. Diagnostic strategy should be targeted on symptoms, epidemiology, and physical examination, to avoid an excess of tests with increase of costs without any benefits. Some first-line screening tests for the most frequent causes of chronic pelvic pain are widely recommended, such as urinalysis, to exclude urinary tract infection, pregnancy test, and microbiologic tests for sexually transmitted infections. Imaging tests are not recommended routinely. Pelvic ultrasonography is the most common method used to investigate the pelvis and highlight the main organ-specific pathologies related to chronic pelvic pain, such as endometriosis, adenomyosis, or pelvic and adnexal masses. Indeed, magnetic resonance imaging should be performed in women suspected of having deep infiltrating endometriosis; computerized tomography scan can be performed when an unclear abdominal acute process is present or when acute enteritis or colitis is suspected; and pelvic venography can be suggested in case of pelvic venous congestion doubt, if skilled operators are available. Furthermore, anal manometry has a role in the suspicion of irritable bowel syndrome, and urodynamic testing could be used in women with bladder pain. Given the lack of specificity and the uncertainty on the mechanisms that cause the pain, the multifactorial nature of chronic pelvic pain should always be discussed with the patient, and management should be agreed with her from the beginning.

Background: Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). Objective: To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Design, setting, and participants: Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Interventions: Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Outcome measurements and statistical analysis: Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Results and limitations: Data were available from eight trials including 370 patients; two trials (n = 109) evaluated single-agent chemotherapy with docetaxel (n = 72) and cremophor-free paclitaxel (n = 37), and six trials (n = 261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n = 99 and n = 24), paclitaxel-cyclophosphamide (n = 32), paclitaxel-ifosfamide-nedaplatin (n = 45), docetaxelifosfamide-cisplatin (n = 26), and paclitaxel-epirubicin (n = 35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p = 0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Conclusions: Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC. Patient summary: This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.