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BACKGROUND: The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone, etc.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine has been shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and also enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it has therapeutic effects on negative symptoms. The present study presents a series of cases suggesting the efficacy of combining clozapine and oxytocin for the reduction of positive and negative symptoms. This work contributes to schizophrenia treatment research by reporting a novel, integrated pharmacological approach to treatment-resistant schizophrenia. METHODS: Retrospective chart reviews were conducted on the charts of 15 patients with treatment-resistant schizophrenia. The patients were all admitted to the persistent psychotic disorder unit at a private hospital between May 2014 and September 2017. The average treatment duration was 2.7 months with a range between 1 and 9 months. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 15 patients after they had failed to improve in three different trials of other antipsychotic medications. Intranasal oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 11 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to the risk of intranasal substance use in all the patients, oxytocin was administered sublingually to ensure adequate and less variable absorption of the neuropeptide. RESULTS: Over the course of treatment, PANSS scores reflected significant changes (p

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Background The prevalence of schizophrenia in the United States ranges between 0.5% and 1%. This difficult-to-treat disorder is marked by the presentation of symptoms that are both positive (i.e. hallucinations) and negative (i.e. blunted affect), as well as disturbances in cognition and affect. Several second-generation antipsychotics (i.e. olanzapine, risperidone.) have been utilized for their varying effects on the symptoms of schizophrenia, yet 20% to 60% of patients with schizophrenia are considered treatment-resistant. While clozapine is shown to be the most effective antipsychotic, negative symptoms commonly persist in clozapine-treated patients. Research shows that oxytocin has neuromodulatory effects on social perception and enhances empathy and attentional engagement in individuals with schizophrenia, suggesting it may have therapeutic effects on negative symptoms. The present study presents a pilot prospective research study evaluating the efficacy of combining clozapine and sublingual oxytocin for the reduction of positive and negative symptoms. Methods Prospective research study evaluated 25 treatment resistant schizophrenic patients who were admitted to the persistent psychotic disorder unit at a private hospital, with an average treatment duration of 2.9 months with a range between 1 and 9 months. All have been followed as outpatient for up to 30 months after discharge. All patients were 18 years or older and met the DSM-5 criteria for schizophrenia. The Positive and Negative Syndrome Scale (PANSS) was used to assess the efficacy of the combination treatment. Clozapine was prescribed to all 25 patients after they had failed to improve in three different trials of other antipsychotic medications. Sublingual oxytocin (10 IU 2x per day; 20 IU 3x per day) was prescribed to 25 of the patients only after the improvement in positive symptoms on the PANSS with clozapine had plateaued. Due to a history of intranasal substance use in all the patients, oxytocin was administered sublingual to ensure adequate and less variable absorption of the neuropeptide. Results A time-series analysis demonstrated a significant decrease in PANSS scores across admission, stabilization of clozapine and stabilization of oxytocin (p Discussion The combined effect extends the current research of augmenting sublingual oxytocin and clozapine for individuals with previously treatment-resistant symptoms. Though each patient benefitted from clozapine alone, negative symptoms persisted. Patients, their families, and treatment program staff all observed a significant reduction in the patients’ anxiety and an improvement in the patients’ relatedness. While this case series cannot establish that oxytocin is responsible for the clinical improvements seen here, it does suggest that it may improve negative symptoms and social functioning in patients with treatment-resistant schizophrenia showing incomplete improvement with clozapine alone. The present study suggests the need for future research to explore the possibility that oxytocin can mitigate the negative symptoms of schizophrenia.

Background: A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b ( 10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. Objective: Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. Design, setting, and participants: Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. Intervention: Patients underwent either radical or partial nephrectomy. Measurements: Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. Results and limitations: In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend < 0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. Conclusions: The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

International audience; Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.