Search

Objective. Perforation of the gallbladder (PG) is a dreaded complication of an acute cholecystitis and is associated with increased morbidity and mortality. Cholecystocutaneous abscess (CCA) is an extremely rare complication. There is usually a history of cholecystolithiasis or neglected chronic gallbladder disease. We report a case of perforated gallbladder into the abdominal wall. Methods. A 65-year-old female, obese, was admitted to our department complaining of right upper quadrant abdominal pain. The diagnosis of acute cholecystitis was based on the clinical picture, laboratory test, and ultrasound findings. She was treated with oral antibiotics for 10 days and readmitted due to a painful, erythematous mass on the right subcostal region. An abdominal computed tomography showed the presence of a subparietal formation in communication with the gallbladder, and a gallbladder perforation was postulated. The treatment consisted of percutaneous drainage of the abdominal wall abscess followed by laparoscopic cholecystectomy in a two-stage protocol. Anatomical pathology analysis found chronic inflammation and excluded malignancy. The postoperative follow-up was uneventful. Discussion. This case demonstrates a very rare presentation of PG that created an abscess into the muscles of the abdominal wall. This kind of PG is rarely seen due to medicine improvements. When the conditions of the patient are good, rather than perform immediate surgery that could lead to serious complications, we propose a two-stage approach. Conclusion. CCA is a possible complication of gallbladder’s pathology that all surgeons have to know. There is no standard baseline management for this pathology, due to the few numbers of cases and to the differences in the quality of the patients’ illness. We suggest a two-stage approach with drainage of the abscess followed by laparoscopic cholecystectomy with abscess debridement.

Research in the UK suggests that multi-componential interventions focusing on language and pre-literacy skills can improve children’s reading and language skills. However, simple translations of such programmes may not produce equivalent effects in diverse communities. The reasons for this are multi-faceted and include factors beyond the rationale and content of the intervention programmes themselves. Understanding these factors is critical for creating programmes that will generalise across settings. In this review, we reflect upon challenges encountered in two reading and language intervention programmes in South America to identify community and cultural contextual factors that can influence the implementation and scalability of educational programmes. We use our findings to develop an education-specific framework to guide the development and implementation of high-quality evidence-based approaches to language and literacy intervention. Our model guides implementation practices in diverse contexts and stresses the importance of the evidence-base and communication.

To assess the feasibility and operative outcomes of RARP following colo-rectal surgery. A prospective database of patients undergoing RARP is maintained at our Institution since January 2015. We reviewed all patients undergoing RARP after previous colo-rectal surgery. Overall, 49 (7.4%) of 658 RARPs were performed after previous pelvic surgery, 14 (2.1%) of which following colo-rectal surgery after an interval of 5 years. (a) Colo-rectal surgery. Previous colo-rectal surgery included resection of the left colon (n = 6), and right colon (n = 4), and rectum (n = 4). Histopathology showed pT0-T2N0 in 5, pT3N0-1 in 3, and benign conditions in 4. Prostate-specific antigen (PSA) was elevated (4 ng/ml or greater) or slightly elevated (3.5-4 ng/ml) in 9 (65%) of 14 cases at the time of colo-rectal surgery. (b) Prostatectomy. Overall prostatectomy and adhesiolysis median operative times were 235 and 42 min, respectively. A robotic approach was accomplished in 11 cases with previous uncomplicated colo-rectal surgery; open conversion occurred in 3 cases. Risk factors for open conversion during RARP were: history of multiple or complicated abdominal surgery, previous open conversion, and hospital stay > 10 days. Postoperative complications included: anemization (n = 2), persistent drain output (n = 1), and urinary tract infection (n = 1). The robotic approach was successful in the case of previous uncomplicated colo-rectal surgery. The risk of intestinal injury during conversion might suggest a direct retropubic approach in case of previous multiple or complicated abdominal surgery. A planned elective colo-rectal surgery should include a thorough urologic evaluation, considering the risk of a subsequent prostate surgery.

Memristive devices, which combine a resistor with memory functions such that voltage pulses can change their resistance (and hence their memory state) in a nonvolatile manner, are beginning to be implemented in integrated circuits for memory applications. However, memristive devices could have applications in many other technologies, such as non–von Neumann in-memory computing in crossbar arrays, random number generation for data security, and radio-frequency switches for mobile communications. Progress toward the integration of memristive devices in commercial solid-state electronic circuits and other potential applications will depend on performance and reliability challenges that still need to be addressed, as described here.

Objective. In the theoretical framework of predictive coding and active inference, the brain can be viewed as instantiating a rich generative model of the world that predicts incoming sensory data while continuously updating its parameters via minimization of prediction errors. While this theory has been successfully applied to cognitive processes—by modelling the activity of functional neural networks at a mesoscopic scale—the validity of the approach when modelling neurons as an ensemble of inferring agents, in a biologically plausible architecture, remained to be explored. Approach. We modelled a simplified cerebellar circuit with individual neurons acting as Bayesian agents to simulate the classical delayed eyeblink conditioning protocol. Neurons and synapses adjusted their activity to minimize their prediction error, which was used as the network cost function. This cerebellar network was then implemented in hardware by replicating digital neuronal elements via a low-power microcontroller. Main results. Persistent changes of synaptic strength—that mirrored neurophysiological observations—emerged via local (neurocentric) prediction error minimization, leading to the expression of associative learning. The same paradigm was effectively emulated in low-power hardware showing remarkably efficient performance compared to conventional neuromorphic architectures. Significance. These findings show that: (a) an ensemble of free energy minimizing neurons—organized in a biological plausible architecture—can recapitulate functional self-organization observed in nature, such as associative plasticity, and (b) a neuromorphic network of inference units can learn unsupervised tasks without embedding predefined learning rules in the circuit, thus providing a potential avenue to a novel form of brain-inspired artificial intelligence.

Objective: To pilot the VIONE approach in a single Primary Care Patient Aligned Care Team (PACT). The authors aim for the Clinical Pharmacy Specialist (CPS) to perform 20 comprehensive medication reviews (CMRs) and the pilot PACT physician (PCP) to complete 200 VIONE discontinuations. Cost avoidance and CPS recommendations will also be analyzed. Polypharmacy is associated with increased risk of adverse drug events, falls, hospitalizations, and death. VIONE is a deprescribing tool that assists providers in identifying inappropriate medications. Design: Quality Improvement Setting: Single VA Health Care System (VAHCS) Participants: High-risk veterans in pilot PACT Interventions: The CPS educated the PCP regarding VIONE methodology and assisted with CMRs. When deprescribing was warranted, VIONE discontinuation reasons were selected in the Computerized Patient Record System (CPRS). Data were electronically stored in a national dashboard. Results: The authors identified 231 veterans at risk for polypharmacy-related adverse events. The PCP and CPS were able to reach 99 veterans and make 136 medication discontinuations between September 1, 2019, and March 1, 2020. The CPS performed 20 CMRs, resulting in 90 deprescribing recommendations. Thirty-eight CPS recommendations were accepted and contributed $18,835.95 to the sum annualized cost avoidance of $21,904.80. Conclusion: The VIONE methodology was successfully implemented in the pilot PACT. The utilization of the CPS was associated with an increased average number of medication discontinuations per veteran and contributed to cost avoidance.

Introduction/Background* High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 years. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab may be enhanced by concurrent chemoradiotherapy (CCRT). After the KEYNOTE-158 study, in which pembrolizumab showed durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/GOG 3047/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with CCRT for the treatment of high-risk, locally advanced cervical cancer. Methodology Approximately 980 patients with high-risk (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) + CCRT followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CCRT followed by 15 cycles of placebo Q6W. CCRT includes 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembrolizumab (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 years) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator and overall survival (OS). Secondary endpoints include PFS by blinded independent central review, PFS at 2 years, OS at 3 years, complete response at 12 weeks, objective response rate, PFS and OS by PD-L1 status, quality of life, and safety. Enrolment began May 2020 and is planned for 193 sites in 30 countries. Klikněte nebo klepněte sem a zadejte text.

Background High-risk locally advanced cervical cancer (CC) has a poor prognosis, and >50% of patients recur in 2 years. Concurrent chemoradiotherapy (CRT) may enhance the immunostimulatory activity of the PD-1 inhibitor pembrolizumab. After KEYNOTE-158, in which pembrolizumab demonstrated durable antitumor activity, pembrolizumab monotherapy was approved for patients with PD-L1–positive recurrent or metastatic CC who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo-controlled study evaluating pembrolizumab with concurrent CRT in locally advanced CC. Trial design Approximately 980 patients with high-risk, locally advanced, histologically confirmed CC who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg Q3W + CRT (5 cycles [with optional 6th cycle] of cisplatin 40 mg/m2 Q1W + external beam radiotherapy [EBRT] followed by brachytherapy) followed by 15 cycles of pembrolizumab 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. Randomization is stratified by planned EBRT type, cancer stage at screening, and planned total radiotherapy dose. Treatment will continue until patient receives ≤20 cycles of pembrolizumab (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 years) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints include PFS at 2 years, OS at 3 years, complete response at 12 weeks, ORR, PFS and OS in PD-L1–positive patients, and safety. Enrollment is ongoing.

Background: To evaluate the intermediate perioperative outcomes, rate of complications and functional data after XPS 180-W Greenlight photoselective laser vaporization (PVP) compared with transurethral resection of the prostate (TURP) in a prospective non-randomized single centre study. Methods: We analyzed a prospectively-maintained database collecting data on 100 patients undergoing surgical treatment of BPH (50 consecutive PVP and 50 consecutive TURP). All complications, recorded and graduated according to the Clavien Dindo system and the clinical, operative, perioperative variables were compared. The functional outcomes, International Prostate Symptom Score (IPSS), max flow rate (Qmax) and Prostate Specific Antigen (PSA), were recorded preoperatively and at 1 year of follow up. Results: Age, prostate volume, use of anticoagulants or antiplatelets, ASA score and operative time were comparable in the two groups. The reduction in the hemoglobin levels (0.46 vs 1.8 g/dL), the catheterization time (1.2 vs 3.2 days), the hospital stay (1.7 vs 3.8 days) and rate of transfused patients (0 vs 8%), were significantly lower for PVP. Transient re-catherization (6 vs 26%) was significantly lower for PVP. The IPSS and Qmax at 1 year showed no significant difference. The rate of repeat TURP/PVP was higher in the TURP group (0 vs 10%). Reduction of PSA, that reflects the major reduction of prostate volume, was statistically greater in PVP group respect TURP group (p = 0.001). Conclusions: PVP has advantages in terms of perioperative safety and major complications than TURP. Functional outcomes at 1 year of follow-up were comparable.

Objective: To evaluate the efficacy of a combination of Hibiscus extract, vegetable proteases and Commiphora myrrha extract in the prophylaxis of symptomatic episode in women affected by recurrent urinary tract infections (rUTIs). Materials and methods: In this phase II clinical trial, all patients with history and diagnosis of rUTI were enrolled. All patients underwent the following treatment schedule: 1 tablet in the morning and 1 tablet in the evening for 7 days and, then, 1 tablet in the evening for 10 days (1 cycle every each month, for 6 months) of a combination of Hibiscus extract, vegetable proteases and Commiphora myrrha extract. At the baseline, all patients underwent urologic visit with quality of life (QoL) questionnaires and mid-stream urine culture. After 3 and 6 months, all patients underwent urologic visit, urine culture and QoL questionnaires evaluation. Results: Fifty-five women were enrolled (mean age 49.3; range: 28-61). At the enrollment time, the most common pathogen was Escherichia coli (63.7%). The median number of UTI per 6 months was 5 (IQR: 4-9). At the end of the second follow-up evaluation, 25 women did not reported any symptomatic episode of UTI (49%), 18 reported less than 2 episodes (35.3%), while 8 reported more than 2 episodes (15.7%). However, at the first and second follow-up evaluation the clinical statistically significant improvement (QoL) was reported by 38/51 (74.5%) (p < 0.001 from baseline) and 43/51 (84.3%) (p < 0.001 from baseline) women, respectively. The median number of UTI decreased to 2 (IQR: 0-3). At the end of the follow-up period, 30/51 had sterile urine (58.8%), while 21/51 (41.2%) reported a transition from symptomatic UTI to asymptomatic bacteriuria. Conclusions: In conclusion, this treatment, in motivated patients, is able to prevent symptomatic UTI symptomatic episode and improve patient’s QoL.

Le infezioni delle vie urinarie costituiscono un problema clinico frequente in tutte le età. L'ecografìa è uno strumento prezioso nella diagnosi e nel management delle infezioni, consentendo di diagnosticare rapidamente complicanze e fattori predisponenti. Questa review passa in rassegna gli aspetti ecografìci delle infezioni della vescica, della prostata, delle vesci-cole seminali, dei didimi, degli epididimi e dello scroto, fornendo un pratico strumento di consultazione rapida al nefrologo.

SummaryWhat is known and objective Paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD) is a direct-acting antiviral (DAA) approved for the treatment of chronic hepatitis C virus. We report on a probable interaction between PrOD with ribavirin and warfarin. Case description Two weeks after the start of PrOD with ribavirin, the patient's international normalized ratio (INR) became subtherapeutic. Eleven weeks into therapy and following a 125% total increase in the weekly warfarin dose, therapeutic INR was achieved. Thirteen days after DAA therapy was completed and discontinued, the patient's INR became critically supratherapeutic. What is new and conclusion Patients on PrOD plus ribavirin with warfarin should have INR followed closely upon initiation and discontinuation of therapy due to a probable drug interaction.

Objectives: We evaluated the efficacy of sutureless laparoscopic partial nephrectomy (LPN), using a fibrin gel in order to minimize renal ischemia time and preserve kidney function. Materials and Methods: Nineteen patients (mean age 58.3 ± 7.1) undergoing sutureless LPN using a fbrin gel were compared with a control group consisting of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing. Intraand post-operative data for the two groups were compared. The following parameters were recorded: patient demographics, Charlson Comorbidity Index, tumor characteristics according to the RENAL score, warm ischemia and operative times, estimated blood loss, mean hospital stay, post-operative complications referring to the Clavien-Dindo classification, renal function parameters pathologic and follow-up data. The main outcome measure was renal ischemia time and maintenance of kidney function. Results: Median warm ischemia time was 13 minutes (range 11-19) in the group treated with fibrin gel and 19 (range 17- 29) in the control group, with a statistically significant difference (p < 0.001). The two groups were homogeneous in terms of the Charlson Comorbidity Index (4.6 vs 4.8) and RENAL score (9.6 vs 9.4). Median operative time differed significantly in the two groups, 183 minutes (range 145-218) in the group treated with fibrin gel and 201 (range 197-231) in the control group (p < 0.001). A negative surgical margin was reported in 18 patients (94.7%) in the group treated with fibrin gel and in 21 patients (100%) in the control group. No difference in renal function was found between the two groups. Conclusions: Sutureless LPN with fibrin gel can reduce warm ischemia and total operative time while preserving kidney function.

Three cluster C Myoviridae bacteriophages that infect Bacillus cereus group bacteria were isolated from soil collected in the mid-Atlantic region using B. thuringiensis subsp. kurstaki as a host. Bacillus phages HonestAbe, Anthony, and Taffo16 each shared 90% or higher average nucleotide identities within their subclusters.

Objective: To evaluate the efficacy of a phytotherapic combination of L-Methionine associated with Hibiscus sabdariffa and Boswellia serrata for treatment of acute episodes of uncomplicated urinary tract infections (UTI) in women affected by recurrent UTIs. Materials and methods: In this randomized phase III clinical trial, adult females with uncomplicated UTI were enrolled into one of the following treatment groups: Group A: phytotherapic combination 1 tablet in the morning and 1 tablet in the evening for 7 days; Group B: Short term antibiotic treatment according to international guidelines recommendations. At baseline, all patients were evaluated by a urologist and quality of life (QoL) questionnaires and mid-stream urine culture. Same clinical and laboratory investigations were repeated at each follow-up visit. Results: Forty-six patients were enrolled in Group A and 47 in Group B. At the first follow-up (30 days), both groups showed a statistically significant improvement in quality of life scores as compared with baseline assessment [Group A: (QoL 94.3 VS 98.5 p < 0.001); Group B: (QoL 94.5 VS 98.7 p < 0.001)]. An improvement from baseline was also seen at the second followup evaluation after 3 months [Group A: (QoL 94.3 VS 99.1 p < 0.001); Group B: (QoL 94.5 VS 98.1 p < 0.001)]. At the second follow-up visit, a statistically significant difference in QoL was reported between the two groups (99.1 VS 98.1; p < 0.003) and a transition from UTI to asymptomatic bacteriuria (ABU) was observed 12 of 46 (26%) patients in Group A, while no patients in Group B demonstrated ABU (p = 0.007). Conclusions: Here, we demonstrated that this phytotherapic combination is able, in comparison to antibiotic treatment, to improve patients quality of life, reducing symptoms in acute setting and preventing the recurrences. Interestingly, a significantly higher proportion of patients in the phytotherapy group had ABU after three months. Our findings are of great interest in an antibiotic stewardship perspective.

This study aimed at reporting our first experience with robotic laparoendoscopic single-site radical prostatectomy (R-LESS-RP) with single-site VesPa platform (Intuitive Surgical Inc.). A 68-year-old-man presenting with a cT1c adenocarcinoma Gleason Score 3 + 4 = 7 in 4/12 bilateral cores underwent a transperitoneal robotic LESS-RP with a single-site Vespa platform. Initial PSA, prostate weight, and body mass index (BMI) were 4.4 ng/ml, 45 g, and 25, respectively. Instruments and camera cross within the Single-Site port; the da Vinci System software detects and reassigns the user's hands with the instruments position. The single-site port is inserted through a 2-cm intraumbilical incision. The robotic 8.5 mm scope and two surgical curved instruments (fenestrated bipolar forceps and cautery hook) are introduced through the ports and used for most of the procedure, whereas a wristed needle driver on the right hand is used for the reconstructive steps. An additional 12 mm port (Air Seal, SurgiQuest) is placed in a midline between the umbilicus and the right iliac spine in order to facilitate table assistance during surgery and to place a drain at the end of the procedure. Operative time and blood loss were 300 min and 400 mL, respectively. The postoperative course was uneventful. The drain and the catheter were removed on days 1 and 6, respectively. The patient experienced a temporary mild stress incontinence (one pad at sixth month) and erectile dysfunction. Our first robotic laparoendoscopic single-site radical prostatectomy (R-LESS-RP) with the single-site VesPa platform was associated with acceptable operative times and perioperative outcome. This procedure is feasible without complications, provided that a proper patient selection has occurred. Limited movements together with the lack of the fourth robotic arm require a considerable expertise in robotic surgery. Some tricks can help overcome technical limitations. The Robotic LESS-RP reduces in some measure the limitations of conventional LESS RP, although further refinement of the robotic instruments is necessary.

Background Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and is often diagnosed at advanced stages. The current standard of care (SOC) for advanced EOC is primary debulking surgery (PDS) followed by adjuvant carboplatin/paclitaxel chemotherapy (CT). Although SOC may be effective initially, most patients experience relapse within 3 years after treatment. Combination therapy with PD-1 inhibitor pembrolizumab (pembro) plus PARP inhibitor niraparib resulted in efficacy in patients with platinum-resistant, relapsed OC in the phase 1/2 study TOPACIO/KEYNOTE-162. The PARP inhibitor olaparib is approved for women with newly diagnosed BRCA-mutated OC, as well as for platinum-sensitive, recurrent OC regardless of BRCA1/2 status. Pembro plus CT followed by olaparib maintenance therapy is being investigated in ENGOT-ov43/KEYLYNK-001 (NCT03740165), a phase 3, randomized, double-blind, active- and placebo-controlled study for first-line treatment of women with BRCA1/2-nonmutated advanced EOC. Trial design Women with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be randomized 1:1:1 after one lead-in cycle of CT to receive pembro + CT followed by olaparib maintenance; pembro + CT followed by placebo; or placebo + CT followed by placebo. Stratification factors include surgery status (residual tumor after PDS [yes/no] or planned interval debulking), planned bevacizumab use (yes/no), and PD-L1 combined positive score (CPS; Clinical trial identification NCT03740165. Legal entity responsible for the study Merck & Co., Inc. Funding Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure K. Fujiwara: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharpe & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy: Takeda; Honoraria (self): Bayer; Honoraria (self): Daiichi Sankyo; Honoraria (self): Janssen Oncology; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): Zeria Pharmaceutical; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Kaken Pharmaceutical; Research grant / Funding (institution): Oncotherapeutics; Research grant / Funding (institution): Shionogi. I.B. Vergote: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Merck Sharp & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genmab; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Advisory / Consultancy, Research grant / Funding (institution): Oncoinvent; Advisory / Consultancy: Roche; Advisory / Consultancy: Sotio; Travel / Accommodation / Expenses: Takeda; Research grant / Funding (institution): Amgen. J. Sehouli: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Honoraria (self): Olympus; Honoraria (self): JohnsonJ Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Teva Pharmaceutical Industries Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharpe & Dohme Corp.; Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. P. Zola: Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Roche. R.M. Wenham: Research grant / Funding (self), Shareholder / Stockholder / Stock options: Ovation Diagnostics; Advisory / Consultancy, Speaker Bureau / Expert testimony: TESARO, Inc.; Advisory / Consultancy: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Clovis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: Mersana Therapeutics; Research grant / Funding (self): TapImmune; Research grant / Funding (self): Merck; Research grant / Funding (self): Prescient Therapeutics. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: GlaxoSmithKline. S. Lheureux: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): TESARO, Inc.; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Regeneron. K. Hasegawa: Honoraria (self), Research grant / Funding (self): Daiichi-Sankyo; Honoraria (self): Chugai; Honoraria (self), Advisory / Consultancy: Merck Sharpe & Dohme Corp.; Honoraria (self): AstraZeneca; Research grant / Funding (self): Yakult Honsha; Research grant / Funding (self): Pfizer. C-H. Lai: Research grant / Funding (self): Roche; Research grant / Funding (self): TTY Biopharm. A. Gonzalez-Martinez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Merck Sharpe & Dohme Corp.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): TESARO, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmama. Q. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. S.M. Keefe: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. M. Puglisi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. All other authors have declared no conflicts of interest.

TPS5603 Background: There is a significant unmet need to develop new regimens for BRCA1/2-nonmutated advanced ovarian cancer (OC). The PARP inhibitor olaparib is approved for women with platinum-sensitive, recurrent OC regardless of BRCA1/2 status and, more recently, for newly diagnosed women with BRCA-mutated OC. In the TOPACIO/KEYNOTE-162 study, the combination of the PD-1–blocking antibody pembrolizumab (pembro) and niraparib demonstrated efficacy in platinum-resistant relapsed OCirrespective of BRCA1/2 status. ENGOT-OV43/KEYLYNK-001 (ClinicalTrials.gov, NCT03740165) is a phase 3, randomized, double-blind, active- and placebo-controlled study of pembro plus paclitaxel-carboplatin chemotherapy (CT) followed by olaparib maintenance for first-line treatment of patients with BRCA1/2-nonmutated advanced epithelial OC (EOC). Methods: Patients with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be stratified by surgery status (no residual tumor after primary debulking surgery [PDS], residual tumor after PDS, or planned interval debulking), bevacizumab use, and PD-L1 status (combined positive score < 10 or ≥10). After one lead-in cycle of CT, patients will be randomized 1:1:1 to receive: CT + pembro followed by olaparib maintenance; CT + pembro followed by placebo; or CT + placebo followed by placebo. The CT regimen will be administered for 5 cycles, and pembro 200 mg Q3W will be administered for 35 infusions. Olaparib 300 mg BID maintenance therapy will start after the end of CT as concomitant treatment with pembro until discontinuation or for 2 years if the patient has a complete response. Bevacizumab use is permitted at investigator’s discretion and determined prerandomization. Primary endpoints are investigator-assessed progression-free survival (PFS) per RECIST 1.1 criteria and overall survival. Key secondary endpoints are PFS per RECIST 1.1 assessed by blinded independent central review, PFS after next-line treatment, and safety. Enrollment is currently ongoing. Clinical trial information: NCT03740165.

This study investigated the daily lives of obese children and their families to better understand factors influencing weight-related behaviors. A multiple case study design was implemented with 6 obese children and their families. Participant observations occurred in different settings from when the children woke until they went to bed, yielding approximately 95 hours of data per family. Lack of parenting skills and role modeling, environments encouraging poor weight-related behaviors, low self-awareness and enjoyment of sedentary activities were common themes. Child obesity involves a complex set of factors interacting to place a child at risk of developing weight problems.

The diffusion of SiC devices is limited by higher manufacturing cost than Silicon devices. The big impact on costs comes from the SiC substrate. Cost reduction can be obtained in two ways: the use of low miscut substrates to reduce the material loss and the use of 150 mm substrate to increase the material utilization rate and to use existing silicon 150 mm production lines. Physical vapor transport (PVT) sublimation technique is the main SiC ingot production technology 1–3 which gives very short crystal compared to Silicon. Standard off-cut angle of 4 ◦ oriented � 0001� introduces a loss of material during the wafering phase lowering number of substrates per ingot with the increase of diameter. To increase substrate yield from each ingot and reduce the cost of final substrate will be advisable to use 150 mm substrate with a 2 ◦ off-cut angle.

The objective of this is to compare the surgical outcomes of partial nephrectomy (PN), performed via three different approaches: robot-assisted (RAPN), laparoscopic (LPN), and open (OPN), in a single non-academic regional center. The data of patients undergoing PN at our Department from 2005 to 2016 were prospectively collected. A logistic regression model adjusted for preoperative variables (age, tumor size, creatinine and hemoglobin, ASA and Padua scores) was performed to evaluate whether transfusion, conversion, and postoperative complication rate were influenced by the surgical approach. Overall 270 patients underwent PN: analysis included 253 cases (RAPN = 110, LPN = 70, OPN = 73). Preoperative variables did not differ significantly among the three groups. Shorter operative (130 vs 180 and 200′) and ischaemia (12 vs 23 and 22′) times and longer hospital stay (8 vs 7 and 6 days) were found in the OPN group as compared to LPN and RAPN, respectively. The RAPN group included a higher rate of pT1b (31.8 vs 14.2 and 15%) and malignant histotype (90 vs 82.9 and 68.5%) as compared to LPN and OPN, respectively. Clavien Grade III–IV complications were lower in the RAPN (7.2%) as compared to OPN (12.3%) and LPN (17.1%) groups. Multivariate analysis showed a lower risk for conversion, transfusion and overall complications in the RAPN group versus LPN and OPN. The surgical approach affects the perioperative outcomes in a regional setting. The advantages of RAPN over OPN (lower risk of conversion, transfusion, and overall complications) are extended over LPN as well, although OPN offered faster operative and ischemia times at the expense of greater blood loss and hospital stay.

The epidemiology of prostatitis-like symptoms is not totally understood. It has been estimated that the prevalence of prostatitis-like symptoms ranges from 2 % to as high as 16 % in men in the community. The majority of all published studies have important limitations that should be taken into account. Here, we discuss the latest epidemiological acquisitions in terms of prevalence, incidence, and microbiological findings. Moreover, the role of atypical pathogens, such as Chlamydia trachomatis and mycoplasmata, will be discussed.

BACKGROUND: This study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA). PATIENTS AND METHODS: A retrospective analysis of toxicity data from patients treated in phase I trials of MTAs was carried out to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk factors associated with grade 3 or more toxicity. RESULTS: Data from 687 patients [median age, 59.1 years (range 12.5-85.5)] treated in 36 trials were analysed. Two hundred and eleven patients were of Eastern Cooperative Oncology Group performance status (PS) zero, 432 of PS one, 38 of PS two and 6 unknown. The rate of grade 3 and 4 events was 14.1% (n=97) and 1.9% (n=13), respectively. Twenty-four percent of events were gastrointestinal, 22% constitutional and 20% metabolic. PS two was associated with a higher risk of toxicity [odds ratio (OR), 2.6; 95% confidence interval (CI) 1.1-6.1; P=0.032] as was receiving >100% of maximum tolerated dose or maximum administered dose (OR 2.5; CI 1.6-3.9; P

Background: The aim of this study was to assess if F-18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)-CT scanning could minimise the time non-responding patients were exposed to erlotinib (Tarceva (R)). Methods: Patients were selected for clinical factors that would predict response to erlotinib. A FDG PET-CT and diagnostic contrast-enhanced (traditional) CT scan were carried out at baseline, and then a FDG PET-CT at 6 weeks and a traditional CT at 12 weeks were repeated. The primary end-point was rate of early progression in patients after 6 weeks, of which a minimum 12 out of 35 were required to make the study worthwhile. The responses at 6 (PET-CT) and 12 weeks (traditional CT) were compared and correlated with symptomatic response at both these time points. Results: Forty seven patients were recruited with 38 and 33 patients assessable by FDG PET-CT at 6 weeks and traditional CT at 12 weeks, respectively. There was good correlation between Partial response (PR) at both time points and all 10 patients who had a PR at 12 weeks had a PR at 6 weeks. Of the 13 patients with progressive disease (PD) at 12 weeks, seven had PD at 6 weeks and could have had their treatment stopped early. No evaluable patient with stable disease (SD) (8/38) or PD (9/38) on FDG PET-CT at 6 weeks went on to have a later response. Symptomatic response at 6 or 12 weeks did not correlate well with objective response on scanning at either time point. Conclusions: The primary end-point of this study was met as >12 (15/38) patients could have stopped treatment early on the basis of the FDG PET-CT scan result. A FDG PET-CT evaluable response of SD or PD at 6 weeks does predict future lack of response. No correlation was found between response and symptomatic response at either 6 or 12 weeks. (C) 2011 Elsevier Ltd. All rights reserved.

Objectives: This study aimed to evaluate any correlations between baseline creatinine clearance and the development of grade 3/4 toxicities during treatment within oncology phase I trials of molecularly targeted agents where entry criteria mandate a serum creatinine of ≤1.5 × the upper limit of normal. Methods: Documented toxicity and creatinine clearance (calculated by the Cockcroft-Gault formula) from all patients treated with molecularly targeted agents in the context of phase I trials within our centre over a 5-year period were analyzed. Results: Data from 722 patients were analyzed; 116 (16%) developed at least one episode of grade 3/4 toxicity. Patients who developed a late-onset (>1 cycle) grade 3/4 toxicity had a lower creatinine clearance than those who did not (82.69 ml/min vs. 98.97 ml/min; p = < 0.001). Conclusion: Creatinine clearance (even when within normal limits) should be studied as a potential factor influencing late toxicities in the clinical trials of molecularly targeted anti-cancer drugs.

The aim of this paper was to describe and test a social cognitive model of physical activity tailored for adolescent girls. Participants were 1518 girls (aged 13.6 ± 0.02 years) from 24 secondary schools in New South Wales, Australia. Useable accelerometer (≥10 hours day(-1) on at least 3 days) and questionnaire data were obtained from 68% of this sample (N = 1035). Participants completed questionnaires assessing psychological, behavioural, social and environmental correlates of activity. The theoretical model was tested using structural equation modelling in AMOS. The model explaining accelerometer counts per minute was an adequate-to-good fit to the data (Tucker-Lewis Index = 0.89, the comparative fit index = 0.97 and the root mean square of approximation = 0.098; 90% confidence interval = 0.075-0.122) but explained only 5% of the variance in activity. There were significant model pathways from self-efficacy (r = 0.11, P = 0.01), school environment (r = 0.07, P = 0.02) and physical self-worth (r = 0.07, P = 0.04) to accelerometer counts. Although the proposed model provided an adequate-to-good fit to the data, it explained a small portion of the variance. Shared method variance may explain the larger portions of variance explained in previous studies. Future studies are encouraged to evaluate theories of physical activity behaviour change using objective measures of physical activity.

Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.

Topotecan, a topoisomerase 1 inhibitor (topo1-i), is a semi-synthetic derivative of camptothecan with well-established cytotoxic properties. It is licensed for the treatment of relapsed, sensitive small cell lung cancer (SCLC) and for second line treatment in ovarian cancer. Studies have also shown this drug to be an effective first line treatment for SCLC with either cisplatin or in combination with a topoisomerase 2 inhibitor (topo2-i), etoposide; both combinations have shown similar efficacy. Oral and parenteral formulations of topotecan have proven to be equivocal in relapsed SCLC patients. The parenteral form showed reduced rates of severe haematological toxicities and better symptom control than an anthracycline combination (CAV). In relapsed SCLC, a randomised phase III trial of oral topotecan versus best supportive care showed a statistically significant increase in overall survival. In the second line treatment of non-small cell lung cancer (NSCLC), oral topotecan was not inferior to the current standard iv docetaxel for 1 year survival rates. Worthwhile potential investigations include combining oral topotecan with other oral agents to design treatments for different lines of therapy. The new oral formulation of topotecan also lends itself to testing with small molecule tyrosine kinase inhibitors. The myelosuppressive toxicity profile needs to be vigorously monitored and managed. The trials with oral topotecan have also highlighted the need to reassess the utility of the terms ‘sensitive’ and ‘resistant’ in the selection of patients with relapsed small cell lung cancer.