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In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage =T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240?mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR?=?0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.

In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage ≥T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240 mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR = 0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.

Although it has been well documented that sleep is required for human performance and alertness to recover from low levels after prolonged periods of wakefulness, it remains unclear whether they increase in a linear or asymptotic manner during sleep. It has been postulated that there is a relation between the rate of improvement in neurobehavioral functioning and rate of decline of slow-wave sleep and/or slow-wave activity (SWS/SWA) during sleep, but this has not been verified. Thus, a cross-study comparison was conducted in which dose-response curves (DRCs) were constructed for Stanford Sleepiness Scale (SSS) and Psychomotor Vigilance Task (PVT) tests taken at 1000 hours by subjects who had been allowed to sleep 0 hours, 2 hours, 5 hours or 8 hours the previous night. We found that the DRCs to each PVT metric improved in a saturating exponential manner, with recovery rates that were similar [time constant (T) approximately 2.14 hours] for all the metrics. This recovery rate was slightly faster than, though not statistically significantly different from, the reported rate of SWS/SWA decline (T approximately 2.7 hours). The DRC to the SSS improved much more slowly than psychomotor vigilance, so that it could be fit equally well by a linear function (slope = -0.26) or a saturating exponential function (T = 9.09 hours). We conclude that although SWS/SWA, subjective alertness, and a wide variety of psychomotor vigilance metrics may all change asymptotically during sleep, it remains to be determined whether the underlying physiologic processes governing their expression are different.

ABSTRACT: More complete data on the prevalence and types of urinary dysfunction in geriatric institutional patients are essential for the management of their urologic problems. Over a 13‐month period, a prospective study was conducted of all new admissions to a hospital for long‐term care. Eighty percent (277/347) of the newly admitted patients were geriatric (65 or older). Urinary dysfunction was identified in 69.3 percent of the geriatric group; 38.3 percent were incontinent, 20.2 percent bore a urinary diversion device, and 10.8 percent were symptomatic without incontinence. Obtaining reliable information about urologic status posed a significant problem, particularly as 27 percent of the subjects had a mental disorder, including organic brain syndrome or confusion. Thirty percent of all patients questioned were unable to give any history of their own health status. Questioning of both staff and patient to determine reliability of the data revealed that the given information was correct in 77 percent of patients who acknowledged genitourinary dysfunction, and in 83 percent of those who denied it. The study failed to elicit useful data concerning the specificity of symptoms, urologic history, diagnosis and management of urinary dysfunction in this series of geriatric patients under long‐term institutional care.

We examine disease control and patterns of failure for patients with adult paratesticular sarcoma treated with wide repeat excision and postoperative radiation for close margins.

A study of post-orchiectomy surveillance without radiation therapy was done in patients with histologically pure seminoma apparently confined to the testicle. Criteria for study entry included a negative physical examination, chest x-ray, bipedal lymphogram, excretory urogram, abdomino-pelvic computerized tomography scan and serum alpha-fetoprotein. Followup consisted of frequent clinical examination, repeat lymphograms, abdominal computerized tomography scans, chest x-rays and serum markers. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases beyond the testicle, sites of relapse, factors predictive of relapse, and over-all cure rate and treatment morbidity. Of 81 patients followed for 3 to 43 months (median 19 months) only 3 had relapse at 3, 5 and 18 months after orchiectomy with nonbulky retroperitoneal disease: 1 patient had disease 17 months after salvage infradiaphragmatic radiation therapy, 1 had an increase in beta-human chorionic gonadotropin 11 months after radiation therapy, presumably due to occult nonseminoma, and he is receiving chemotherapy, and 1 has not yet completed treatment. Further followup is necessary to determine ultimate survival, since a risk for later relapse exists. However, to date it does not appear as if the outcome has been compromised when surveillance was applied in place of routine adjuvant radiotherapy.

The aim of this study was to determine whether extracorporeal shock wave lithotripsy (ESWL) affected the viability of the infecting bacteria within a simulated struvite stone matrix. A strain, Proteus mirabilis 28cii, was prepared in three forms: (1) suspended in saline and urine, (2) artificially encapsulated by suspending in agar beads and (3) artificially encapsulated and mineralised by suspending in agar beads with calcium carbonate crystals. The preparations were placed in capped vials partially immersed in degassed water and held in the focal point of the Siemens Lithostar and given 1,000 shocks. Subsequent viability testing showed that bacteria suspended in urine were greatly affected by shock treatments (55% loss in viability), but incorporation into agar beads negated this effect (even if the cells were exposed to 2000 shocks). Mineralisation of the beads with calcium carbonate crystals caused a decrease in viability of 82% that was significantly different from controls. However, this still left 2.3×108 viable organisms (82% of 2.8×108), easily enough to form the focus for further infections. A series of control experiments carried out using an ultrasonic cell sonicator probe gave comparable results to those obtained with ESWL. These results demonstrate that ESWL treatment of infected stones must be accompanied by antimicrobial coverage.

Les mutations activatrices du FGFR3 sont fréquemment observées dans les tumeurs de vessie n’infiltrant pas le muscle mais peu étudiée dans les tumeurs infiltrantes. Des études in vitro ont montré qu’un traitement anti-FGFR3 réduit la croissance tumorale. Nous avons étudié l’hétérogénéité de la mutation de FGFR3 sur des échantillons des parties superficielles et profondes de tumeurs de vessie ainsi que dans les ganglions envahis.

The western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), recently expanded its range from the western United States into the Great Lakes region of the United States and Canada, threatening eastern dry bean production. Our objectives were to better understand the relationship between cutworm infestation and damage in dry beans, and to determine the best method and timing of insecticide application to reduce pick. Infesting with at least one egg mass per 1.5 m, or as few as two larvae per 0.3 m, of row resulted in significantly more pod damage and pick than in uninfested plots. By 14 d after hatch, larvae were no longer on plants during the daytime; direct observations revealed that fifth instars climbed plants to feed between 2100 and 0600 hours, illustrating the impractically of using larval counts to make management decisions. There was a strong linear relationship between pod damage and percent pick, making scouting for pod damage a viable alternative to egg or larval scouting. Aldicarb soil insecticide or thiamethoxam-treated seed did not reduce cutworm damage. Instead, plots treated with these insecticides had significantly more pick than control plots, perhaps related to increased canopy growth or fewer natural enemies. The pyrethroid λ-cyhalothrin provided excellent control of cutworm when sprayed up to 18 d after infestation. Pick was similar among plots sprayed once up to 18 d after infestation or sprayed four separate times. In a field study, λ-cyhalothrin residue on field-treated foliage was 100% effective at controlling caterpillars up to 14 d after application.

We present herein a previously unreported complication of an aneurysm developing in a balloon dilatation catheter used to dilate a track prior to percutaneous nephrolithotomy. Direct needle puncture of the balloon was required for removal of the catheter.

Twenty-four incontinent elderly institutionalized subjects with detrusor instability participated in a double-blind placebo-controlled trial of oxybutynin chloride. Patients were randomly assigned to oral oxybutynin 5 mg or placebo twice daily. Administration continued for 8 days; a 6-day washout period was followed by the alternative treatment. Incontinence was recorded using a bedside electronic monitor. Four subjects withdrew because of side-effects before completing the trial. There were no clinically significant differences between the oxybutynin and placebo treatments. Both groups experienced side-effects, of which dry mouth was the commonest. Thus, oxybutynin does not appear to be more effective than placebo for the treatment of incontinence in the presence of detrusor instability in elderly institutionalized people.