Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma. METHODS: We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants were aged 18 years or older, with previously untreated advanced pleural mesothelioma, with an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) to intravenous chemotherapy (cisplatin [75 mg/m2] or carboplatin [area under the concentration-time curve 5-6 mg/mL per min] with pemetrexed 500 mg/m2, every 3 weeks for up to 6 cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years). The primary endpoint was overall survival in all randomly assigned patients; safety was assessed in all randomly assigned patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02784171, and is closed to accrual. FINDINGS: Between Jan 31, 2017, and Sept 4, 2020, 440 patients were enrolled and randomly assigned to chemotherapy alone (n=218) or chemotherapy with pembrolizumab (n=222). 333 (76 %) of patients were male, 347 (79%) were White, and median age was 71 years (IQR 66-75). At final analysis (database lock Dec 15, 2022), with a median follow-up of 16·2 months (IQR 8·3-27·8), overall survival was significantly longer with pembrolizumab (median overall survival 17·3 months [95% CI 14·4-21·3] with pembrolizumab vs 16·1 months [13·1-18·2] with chemotherapy alone, hazard ratio for death 0·79; 95% CI 0·64-0·98, two-sided p=0·0324). 3-year overall survival rate was 25% (95% CI 20-33%) with pembrolizumab and 17% (13-24%) with chemotherapy alone. Adverse events related to study treatment of grade 3 or 4 occurred in 60 (27%) of 222 patients in the pembrolizumab group and 32 (15%) of 211 patients in the chemotherapy alone group. Hospital admissions for serious adverse events related to one or more study drugs were reported in 40 (18%) of 222 patients in the pembrolizumab group and 12 (6%) of 211 patients in the chemotherapy alone group. Grade 5 adverse events related to one or more drugs occurred in two patients on the pembrolizumab group and one patient in the chemotherapy alone group. INTERPRETATION: In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma. FUNDING: The Canadian Cancer Society and Merck & Co.

A systematic review about the importance of neuropsychological features in heart failure: is at heart the only failure?

Heart failure can lead to cognitive impairment that is estimated to be present in over a quarter of patients. It is important to intervene at a cognitive level to promote brain plasticity through cognitive training programs. Interventions transformed by technology offer the promise of improved cognitive health for heart failure patients. This review was conducted on studies evaluating the role of cognitive rehabilitation in patients with heart failure. We examined clinical trials involving patients with heart failure. Our search was performed on Pubmed, Web of Science and Cochrane library databases. Of the initial 256 studies, 10 studies met the inclusion criteria. Cognitive rehabilitation training has important implications for the treatment and prevention of cognitive decline in heart failure patients with significant recovery for delayed recall memory and a significant time effect for total recall memory and delayed, psychomotor speed and IADL performance. It is important to include the assessment of cognitive functioning in the routine clinical examinations of patients with heart failure, discover the relationship between cognitive function and heart failure, and target cognitive rehabilitation programs that promote brain plasticity.

Identification of haemocytes and histological examination of gills of the spiny oyster Spondylus gaederopus (Linnaeus, 1758).

In the framework of investigations aimed to detect new available bioindicators in marine environment, haemolymph cells and ctenidia of the Mediterranean spiny oyster, Spondylus gaederopus, have been investigated. Haemocyte count and characterisation, phagocytosis and superoxide anion production and enzyme activity assays, have been carried out. TEM observations have been performed. After gross anatomy observations, cito-histological determinations have been carried out, especially focused on ctenidia structure and function. Main results concerned the relatively low number of circulating cells, and the rich in granules granulocytes, most of which were lysosomes. Release of lysosomal enzymes was confirmed a shared trait inside bivalves. Glycogen deposits as probable result of conversion of bacteria carbohydrates, have been detected, as well as the occurrence of both acidophilic and basophilic haemocytes. Phagocytosis, both in granulocytes and agranulocytes, has been recorded, together with the production of superoxide anion. Haemocytes were found positive to acid phosphatase, alkaline phosphatase, ß-glucuronidase, chloroacetylesterase and arylsulphatase. Ctenidia showed a complex organization, including two demibranch to each ctenidium, two different kinds of lamellae filament and specialized structures as ciliated disks connecting filaments in "eutherorhabdic ctenidia". The occurrence of three different types of mucous cells in the same region of ordinary filaments has been underlined. Such features, suggesting high resistance to environmental stress and disease, allow to consider spiny oysters as promising bioindicators, although deserving of further investigations to evaluate the physiological responses to stress in controlled conditions. Present data, moreover, providing basic information on the biology of S. gaederopus, notably implement the present knowledge on the Mediterranean spiny oysters, whose under-evaluated ecological role should be carefully considered.

Human Monocyte-Derived Dendritic Cells Are the Pharmacological Target of the Immunosuppressant Flavonoid Silibinin.

Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) remain to be elucidated. In this study, we have attempted to ascertain whether Silibinin influences the maturation, cytokine production, and antigen-presenting capacity of human monocyte-derived DC. We show that Silibinin significantly suppresses the upregulation of costimulatory and MHC molecules in LPS-stimulated mature DC and inhibits lipopolysaccharide (LPS)-induced interleukin (IL)-12, IL-23, and TNF-α production. Furthermore, Silibinin impairs the proliferation response of the allogenic memory CD4 T lymphocytes elicited by LPS-matured DC and their Th1/Th17 profile. These findings demonstrate that Silibinin displays immunosuppressive activity by inhibiting the maturation and activation of human DC and support its potential application of adjuvant therapy in the treatment of autoimmune diseases.

Anti-Inflammatory Effects of 1,25(OH)2D/Calcitriol in T Cell Immunity: Does Sex Make a Difference?

Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about the mechanisms underlying this anti-inflammatory effect and the potential sex differences of calcitriol immune regulation. Hence, the aim of this study was to investigate whether calcitriol could act differently in modulating T cell immunity of age-matched male and female healthy donors. We analyzed the effects of calcitriol in T lymphocytes from healthy women and men on the expression levels of the vitamin D receptor (VDR) and pro- and anti-inflammatory cytokine production. We showed that a treatment with calcitriol induced a significant increase in the VDR expression levels of activated T lymphocytes from male and female healthy subjects. Moreover, we found that calcitriol significantly reduced the expression level of pro-inflammatory cytokines IL-17, INF-γ and TNF-α in the T lymphocytes of both sexes. Notably, we observed that calcitriol induced a significant increase in the expression level of anti-inflammatory cytokine IL-10 only in the T lymphocytes from female healthy donors. In conclusion, our study provides new insights regarding the sex-specific anti-inflammatory role of calcitriol in T cell immunity.

Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: There is a preclinical rationale for inhibiting angiogenesis in mesothelioma. We aimed to assess the efficacy and safety of the anti-VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated malignant pleural mesothelioma. METHODS: RAMES was a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial done at 26 hospitals in Italy. Eligible patients were aged 18 years or older, had Eastern Cooperative Oncology Group performance status 0-2, and histologically proven malignant pleural mesothelioma progressing during or after first-line treatment with pemetrexed plus platinum. Patients were randomly assigned (1:1) to receive intravenous gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks plus either intravenous placebo (gemcitabine plus placebo group) or ramucirumab 10 mg/kg (gemcitabine plus ramucirumab group) on day 1 every 3 weeks, until tumour progression or unacceptable toxicity. Central randomisation was done according to a minimisation algorithm method, associated with a random element using the following stratification factors: ECOG performance status, age, histology, and first-line time-to-progression. The primary endpoint was overall survival, measured from the date of randomisation to the date of death from any cause. Efficacy analyses were assessed in all patients who had been correctly randomised and received their allocated treatment, and safety analyses were assessed in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03560973, and with EudraCT, 2016-001132-36. FINDINGS: Between Dec 22, 2016, and July 30, 2018, of 165 patients enrolled 161 were correctly assigned and received either gemcitabine plus placebo (n=81) or gemcitabine plus ramucirumab (n=80). At database lock (March 8, 2020), with a median follow-up of 21·9 months (IQR 17·7-28·5), overall survival was longer in the ramucirumab group (HR 0·71, 70% CI 0·59-0·85; p=0·028). Median overall survival was 13·8 months (70% CI 12·7-14·4) in the gemcitabine plus ramucirumab group and 7·5 months (6·9-8·9) in the gemcitabine plus placebo group. Grade 3-4 treatment-related adverse events were reported in 35 (44%) of 80 patients in the gemcitabine plus ramucirumab group and 24 (30%) of 81 in the gemcitabine plus placebo group. The most common treatment-related grade 3-4 adverse events were neutropenia (16 [20%] for gemcitabine plus ramucirumab vs ten [12%] for gemcitabine plus placebo) and hypertension (five [6%] vs none). Treatment-related serious adverse events were reported in five (6%) in the gemcitabine plus ramucirumab group and in four (5%) patients in the gemcitabine plus placebo group; the most common was thromboembolism (three [4%] for gemcitabine plus ramucirumab vs two [2%] for gemcitabine plus placebo). There were no treatment-related deaths. INTERPRETATION: Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favourable safety profile. This combination could be a new option in this setting. FUNDING: Eli Lilly Italy. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Evaluation of nutritional adequacy in adult patients with Crohn's disease: a cross-sectional study.

PURPOSE: Inadequate oral intake may play an important role in the onset of malnutrition in patients with Crohn's disease (CD). The aims of this cross-sectional study were: (1) to compare dietary intake in clinically active and quiescent CD patients, and (2) to assess patients' nutritional adequacy relative to the dietary reference values (DRVs) for the Italian population using LARN (Livelli di Assunzione di Riferimento di Nutrienti ed energia per la popolazione italiana). METHODS: Patients aged between 18 and 65 years with a diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record. Disease activity was clinically defined using the Crohn's disease activity index (CDAI). RESULTS: Overall, 117 patients, 71 males and 46 females, with a mean age of 39.6 ± 13.8 years and a mean body weight of 65.4 ± 11.8 kg, were ultimately included. Our findings showed that the amount of nutrients was similar between patients with active and quiescent disease. The mean intake of macronutrients was adequate, except for fiber, while dietary micronutrients were insufficient. Median intakes of sodium, phosphorus, and fluorine met LARN recommendations in both sexes, and the DRVs were accomplished by many patients (53/117; 104/117 and 98/117, respectively). Interestingly, dietary amounts of iron and zinc were barely acceptable in males but not in females. However, a few of the patients (< 15) met the LARN for potassium, calcium, and magnesium, regardless of sex and CDAI. With respect to vitamins, no relevant difference was found between the active and quiescent groups, and none of them met recommended values in both sexes. CONCLUSIONS: This study showed that the assessment of dietary intake can be crucial for optimizing dietary intervention with focused nutrition counseling, to improve nutritional status in CD patients.

Effectiveness of Social Media Approaches to Recruiting Young Adult Cigarillo Smokers: Cross-Sectional Study.

BACKGROUND: The prevalence of social media use among youth and young adults suggests it is an appropriate platform for study recruitment from this population. Previous studies have examined the use of social media for recruitment, but few have compared platforms, and none, to our knowledge, have attempted to recruit cigarillo users. OBJECTIVE: The purpose of this study was to examine the effectiveness of different social media platforms and advertisement images for recruiting cigarillo users aged 14-28 years to complete a cigarillo use survey. METHODS: We obtained objective data for advertisement impressions for a 39-week social media recruitment campaign. Advertisements were targeted to users based on their age, geography, and interests. Effectiveness was defined as the percentage of approved surveys per advertising impression. Chi-square tests were performed to compare the effectiveness of different advertisement images and platforms. RESULTS: Valid survey completers (n=1089) were predominately older (25-28 years old, n=839, 77%). Of the 1089 survey completers, 568 (52%) identified as male, 335 (31%) as African American, and 196 (18%) as Hispanic. Advertisements delivered via Facebook/Instagram were more effective than Twitter; 311/1,027,738 (0.03%) vs 661/2,998,715 (0.02%); χ21=21.45, N=4,026,453); P<.001. Across platforms, ads featuring exclusively an image of cigarillos were more effective (397/682,994, 0.06%) than ads with images of individuals smoking (254/1,308,675, 0.02%), individuals not smoking (239/1,393,134, .02%), and groups not smoking (82/641,650, 0.01%); χ23133.73, N=4,026,453; P<.001. CONCLUSIONS: The campaign was effective in recruiting a diverse sample representative of relevant racial/ethnic categories. Advertisements on Facebook were more effective than Twitter. Advertisements that featured an image of a cigarillo were consistently the most effective and should be considered by others recruiting cigarillo users via social media.

Acute effects of neonicotinoid insecticides on Mytilus galloprovincialis: A case study with the active compound thiacloprid and the commercial formulation calypso 480 SC.

Pesticides can enter aquatic environments potentially affecting non-target organisms. Unfortunately, the effects of such substances are still poorly understood. This study investigated the effects of the active neonicotinoid substance thiacloprid (TH) and the commercial product Calypso 480 SC (CA) (active compound 40.4% TH) on Mytilus galloprovincialis after short-term exposure to sublethal concentrations. Mussels were tested for seven days to 0, 1, 5 and 10 mg L-1 TH and 0, 10, 50 and 100 mg L-1 CA. For this purpose, several parameters, such as cell viability of haemocytes and digestive cells, biochemical haemolymph features, superoxide dismutase (SOD) and catalase (CAT) enzymatic activity of gills and digestive gland, as well as histology of such tissues were analysed. The sublethal concentrations of both substances lead to abatement or completely stopping the byssal fibres creation. Biochemical analysis of haemolymph showed significant changes (P < 0.01) in electrolytes ions (Cl-, K+, Na+, Ca2+, S-phosphor), lactate dehydrogenase (LDH) enzyme activity and glucose concentration following exposure to both substances. The TH-exposed mussels showed significant imbalance (P < 0.05) in CAT activity in digestive gland and gills. CA caused significant decrease (P < 0.05) in SOD activity in gills and in CAT activity in both tissues. Results of histological analyses showed severe damage in both digestive gland and gills in a time- and concentration-dependent manner. This study provides useful information about the acute toxicity of a neonicotinoid compound and a commercial insecticide on mussels. Nevertheless, considering that neonicotinoids are still widely used and that mussels are very important species for marine environment and human consumption, further researches are needed to better comprehend the potential risk posed by such compounds to aquatic non-target species.

Foster care, syndemic health disparities and associations with HIV/STI diagnoses among young adult substance users.

OBJECTIVES: Foster care history is associated with many health and social problems, including sexual risk behaviours, HIV and other sexually transmitted infections (STIs). This cross-sectional study compares sexual risk behaviours among a sample of young adult substance users in Miami (N=602) with and without foster care histories. METHODS: Participants completed a comprehensive assessment which included sections on foster care, sexual risk behaviours and related health and social problems. Logistic regression was used to examine the relationship between foster care history, associated syndemic vulnerabilities and increased likelihood of having a prior HIV/STI diagnosis. RESULTS: Bivariate analyses indicated that foster care alumni were more likely to report a prior HIV/STI diagnosis, higher condomless sex frequencies, being high on alcohol or drugs during sex, sexual victimisation and a history of homelessness compared with other participants in the sample (p<0.05). Multivariate analyses revealed that foster care history, sexual victimisation and group sex participation are associated with a prior HIV/STI diagnosis (p<0.05). Group sex participation doubled the odds of a prior HIV/STI diagnosis for foster care alumni, compared with other participants (p<0.5). CONCLUSIONS: This exploratory study identifies characteristics that distinguish foster care alumni from non-alumni and signals the need to better serve the sexual and related health needs of individuals with foster care histories. Clinicians and healthcare providers should provide foster care alumni with detailed HIV/STI risk reduction information and resources and services to address related syndemic vulnerabilities (eg, victimisation and homelessness).

Identifying strengths in youths at substance use treatment admission.

Background: Clinicians have been required to assess client strengths at substance use treatment admission for two decades. Yet little is known about identified strengths in this population that could make it easier for clients to accept having this illness. Objectives: This study explored the profile of clients' strengths and whether strengths varied by background characteristics and constructive use of time. Methods: Data were collected with validated instruments at treatment admission. Substance dependent youths (N = 195, 52% female, aged 14-17, 30% minority), their legal guardians, and admission counselors completed an open-ended prompt about client strengths. Qualitative responses of identified strengths were coded by theme. Univariate comparisons linked count of identified strengths and patient characteristics. Results: Youths had an average of three identified strengths (SD = 1.99) at admission, and 9% did not identify any strengths. Interpersonal strengths were most prevalent (73%), followed by generic intelligence (45%), and grit (31%). Female gender, not having a parent with a high school diploma, narcotic dependence, and shorter duration of consecutive days sober were associated with fewer strengths. Conclusion: Highly sociable, hard-working, and smart were prominent strengths in the sample. Each day sober corresponded with more identified strengths, which may encourage those in early recovery. Identifying strengths can help clients find meaningful sober recreation and may be particularly useful tools for girls and those with low parental education. Developing standards for using identified strengths in treatment planning and consensus on the taxonomy of strengths are topics for future research.

Residential Proximity to Electronic Dance Music Nightclubs and Associations with Substance Use, Sexual Behaviors, and Related Problems.

This study examines the association between proximity of place of residence to preferred nightclub and substance use, sexual risk behaviors, and related problems, among a sample of 498 young adult substance users in Miami who report regular nightclub participation. Hierarchal linear models and logistic regressions were constructed to examine the impact of residential proximity to preferred nightclub on risk behaviors. Compared with participants residing in closer proximity to their preferred nightclub, participants residing further away reported higher intensities of alcohol and cocaine use (p < .01), greater condomless vaginal sex frequencies (p < .001), and more substance dependence symptoms (p < .05). Conversely, participants residing in closer proximity to their preferred nightclub had higher likelihood of arrest history (p < .05) than participants residing further away. Results suggest that participants residing further from their preferred nightclubs may be more invested in the nightclub outing and, therefore, engage in more risk behaviors.

Alone on the Inside: The Impact of Social Isolation and Helping Others on AOD Use and Criminal Activity.

Because addiction is a socially isolating disease, social support for recovery is an important element of treatment planning. This study examines the relationship between social isolation, giving and receiving social support in Alcoholics Anonymous during treatment, and post-treatment outcomes among juvenile offenders court-referred to addiction treatment. Adolescents (N = 195) aged 14 to 18 years were prospectively assessed at treatment admission, treatment discharge, 6 months, and 12 months after treatment discharge. The influence of social isolation variables on relapse and severe criminal activity in the 12-months post-treatment was examined using negative binomial logistic regressions and event history methods. Juveniles entering treatment with social estrangement were significantly more likely to relapse, be incarcerated, and commit a violent crime in the 12-months post-treatment. Giving help to others in Alcoholics Anonymous during treatment significantly reduced the risk of relapse, incarceration, and violent crime in the 12-months post-treatment whereas receiving help did not.

Impaired Enterohormone Response Following a Liquid Test Meal in Gastrectomized Patients.

BACKGROUND: Total gastrectomy (TG) is responsible for symptoms or disturbance of alimentary status (changes in body weight, food intake per meal and frequency of meal per day) which, in turn are responsible for weight loss and malnutrition. The study evaluates the gut hormone responses in totally gastrectomized (TG) patients after a liquid meal test. METHODS: Twenty total gastrectomized cancer-free patients (12 M, 8 F, 56.4 ± 10.2 years, BMI 21.4 ± 2.2 kg/m2) and 10 healthy volunteers (4 M, 6 F, 48.0 ± 12.7 years, BMI 26.7 ± 3.0 kg/m2 ) drank a liquid meal (1.25 kcal/mL) at the rate of 50 mL/5' min for a maximum of 30 min. Satiety score was assessed and blood sample was taken at different time points. RESULTS: The time response course, particularly for insulin, glucose-like pepetide-1, and cholecystokinin, significantly differed between TG patients and controls. CONCLUSIONS: Our results may help to better understand hormone responses triggered by the faster arrival of nutrients in the small bowel and to explain some post-TG symptoms.

Evaluation of Functionality and Biological Responses of Mytilus galloprovincialis after Exposure to Quaternium-15 (Methenamine 3-Chloroallylochloride).

Although the irritant effects of quaternium-15 have been established, little is known about the toxicological consequences induced by this xenobiotic on aquatic invertebrates. The present article reports toxicological, histological and physiological effects of quaternium-15 following the exposure of Mytilus galloprovincialis for 18 days at three different concentrations (0.1, 1.0 and 2.0 mg/L). The results demonstrate that at higher concentrations histological damages to M. galloprovincialis gills occur, like melanosis, light exfoliations, increase of mucus production and infiltrative inflammation. In addition digestive gland cells of M. galloprovincialis, were not able to perform the regulation volume decrease (RVD) owing to osmotic stress following the exposure to the preservative. Overall, this first study on quaternium-15 highlights that it can jeopardize both the morphology and vital physiological processes in marine invertebrates, depending on the duration of exposure and the concentration of the preservative, indicating that further studies are necessary to increase our knowledge about the effects of this substance, commonly added to our products of daily use.

Low Other-Regard and Adolescent Addiction.

Although 12-step literature posits inconsiderate behaviors to characterize alcoholics and addicts, there is little data to support this association among adolescent populations. Using a matched-pair study design with 579 youth aged 14-18 (52% female, 30% minority), a significant, dose-response relationship was found between greater alcohol and drug use severity and increased likelihood of driving under the influence, having unprotected sex with and without a history of sexually transmitted incidence, and low volunteerism among boys. Findings suggest that alcohol and drug use severity is associated with poor awareness of the impact of behaviors on others.

Pei regimen: a therapeutic option in small cell lung cancer? A retrospective monoinstitutional analysis of 46 consecutive cases.

OBJECTIVES: Combination chemotherapy is very active in small cell lung cancer (SCLC), although no improvement in overall survival (OS) has been done in the last 25 years, with Cisplatin-Etoposide (PE) still considered the world-wide standard, with an average median survival of about 7-8 months in patients with extended disease (ED). In 1995, a randomized trial of the Hoosier Group in 171 ED patients showed a significant advantage in overall survival in patients treated with PEI (Cisplatin, Etoposide and Ifosfamide), compared to PE. Despite that, PEI regimen has not become a commonly used regimen in SCLC. MATERIALS AND METHODS: Here we present a retrospective analysis of 46 consecutive patients (30 males and 16 females) with SCLC that were treated at our Institution with PEI regimen: Cisplatin 20 mg/m2, Etoposide 75 mg/m2 and Ifosfamide 1200 mg/m2, day 1 to 4, every 3 weeks. Patients received a total of 219 cycles of chemotherapy, with a mean of 4,7 cycles per patient. Median age was 63 (range 59-70); performance status (PS) was 0 in 29 patients (63%), 1 in 13 patients (28%) and 2 in 4 patients (9%). RESULTS: In 19 limited disease (LD) patients partial response (PR) rate was 74%, and complete response (CR) was 16%. In 27 ED patients we observed 63% of PR and 26% of CR. Median time to progression (TTP) was 15.2 months in LD and 7.1 months in ED with median overall survival (OS) of 28.2 and 11.8 months, respectively. Toxicity was manageable, with a high dose intensity. CONCLUSIONS: PEI regimen, in our opinion, may be a possible therapeutic option, with high activity and an acceptable toxicity profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02324296 . INSTITUTIONAL REVIEW BOARD THAT APPROVED THE STUDY: Institutional review board of Reggio Emilia, Azienda Ospedaliera S.Maria Nuova/IRCCS.

Sunitinib, pazopanib or sorafenib for the treatment of patients with late relapsing metastatic renal cell carcinoma.

PURPOSE: Late recurrence of renal cell carcinoma is not a rare event. In this retrospective study we investigate the clinicopathological features and the outcome of patients treated with sorafenib, sunitinib and pazopanib for late relapsing renal cell carcinoma. MATERIALS AND METHODS: Data were collected from 21 Italian centers involved in the treatment of metastatic renal cell carcinoma. Late relapse was defined as more than 5 years after initial radical nephrectomy. RESULTS: A total of 2,490 patients were screened and 269 (11%) were included in the study. First line therapy was sunitinib in 190 patients (71%), sorafenib in 58 (21%) and pazopanib in 21 (8%). Median progression-free survival was 20.0 months for sunitinib (95% CI 17.0-25.1), and 14.1 months for sorafenib (95% CI 11.0-29.0) and pazopanib (95% CI 11.2-not reported). On multivariate analysis MSKCC score and metastases to lymph nodes, liver and brain were associated with worst overall survival, while pancreatic metastases were associated with longer survival. Furthermore, age, MSKCC score and brain metastases were associated with worst progression-free survival. CONCLUSIONS: Patients with late relapsing renal cell carcinoma seem to present a characteristic pattern of metastatic spread without showing significant differences in terms of progression-free survival among sorafenib, sunitinib and pazopanib.

Social anxiety and peer helping in adolescent addiction treatment.

BACKGROUND: The developmental need to fit in may lead to higher alcohol and other drug use among socially anxious youths which exacerbates the drink/trouble cycle. In treatment, youths with social anxiety disorder (SAD) may avoid participating in therapeutic activities with risk of negative peer appraisal. Peer-helping is a low-intensity, social activity in the 12-step program associated with greater abstinence among treatment-seeking adults. This study examined the influence of SAD on clinical severity at intake, peer-helping during treatment, and outcomes in a large sample of adolescents court-referred to residential treatment. METHODS: Adolescents (N = 195; 52% female, 30% Black) aged 14 to 18 were prospectively assessed at treatment admission, treatment discharge, and 6 months after treatment discharge. Data were collected using rater-administered assessments, youth reports, clinician reports, medical charts, and electronic court records. The influence of SAD on peer-helping and outcomes was examined using hierarchical linear regression and event history methods. RESULTS: Forty-two percent of youths reported a persistent fear of being humiliated or scrutinized in social situations, and 15% met current diagnostic criteria for SAD. SAD onset preceded initial use for two-thirds of youths with SAD and substance dependency. SAD youths presented for treatment with greater clinical severity in terms of earlier age of first use (p < 0.01), greater lifetime use of heroin and polysubstance use (p < 0.05), incarceration history (p < 0.01), and lifetime trauma (p < 0.001). Twelve-step participation patterns during treatment did not differ between youths with and without SAD except for peer-helping, which was associated with reduced risk of relapse (p < 0.01) and incarceration (p < 0.05) in the 6 months posttreatment. CONCLUSIONS: This study found evidence of an association between SAD and earlier age of first use, greater lifetime use of heroin, incarceration history, and lifetime trauma. SAD was associated with higher service participation during treatment, which was associated with reduced risk of relapse and incarceration in the 6 months posttreatment. Findings indicate the benefits of service participation for juveniles with SAD which provides a nonjudgmental, task-focused venue for developing sober networks in the transition back into the community.