Cognitive dysfunction in patients treated with androgen deprivation therapy: a multimodality functional imaging study to evaluate neuroinflammation

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. METHODS: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. RESULTS: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. CONCLUSIONS: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI

TUXEDO: a phase I/II trial of cetuximab with chemoradiotherapy in muscle‐invasive bladder cancer.

Objective To assess the feasibility and preliminary efficacy of adding cetuximab to standard chemoradiotherapy for muscle-invasive bladder cancer. Patients and Methods TUXEDO was a prospective, single-arm, open-label, phase I/II trial conducted in six UK hospitals. Cetuximab was administered with an initial loading dose of 400 mg/m2 on Day 1 of Week −1, and then seven weekly doses of 250 mg/m2. The radiotherapy schedule was 64 Gy/32F with Day 1 mitomycin C (12 g/m2) and 5-fluorouracil (500 mg/m2/day) over Days 1–5 and Days 22–26. Patients with T2-4aN0M0 urothelial cancer and a performance status of 0–1 were eligible. Prior neoadjuvant therapy was permitted. The Phase I primary outcome was impact on radiotherapy treatment completion and toxicity experienced during treatment. The Phase II primary outcome was local control at 3 months post treatment. Results Between September 2012 and October 2016, 33 patients were recruited; seven in Phase I, 26 in Phase II. Three patients in Phase II were subsequently deemed ineligible and received no trial therapy. Eight patients discontinued cetuximab due to adverse effects. The patients’ median (range) age was 70.1 (60.6–75.1) years, 20 had a performance status of 0, 27 were male and 26 had already received neoadjuvant chemotherapy. In Phase I, all patients completed planned radiotherapy, with no delays or dose reductions. Of the 30 evaluable patients in Phase II, 25 had confirmed local control 3 months after treatment (77%, 95% confidence interval 58–90). During the trial there were 18 serious adverse events. The study was halted due to slow accrual. Conclusion Phase I data demonstrate it is feasible and safe to add cetuximab to chemoradiotherapy. Exploratory analysis of Phase II data provides evidence to consider further clinical evaluation of cetuximab in this setting

Inter-observer variability in contouring the penile bulb on CT images for prostate cancer treatment planning

Several investigations have recently suggested the existence of a correlation between the dose received by the penile bulb (PB) and the risk of erectile dysfunction (ED) after radical radiotherapy for clinically localized prostate carcinoma

Evaluating the Effect of Androgen Deprivation Therapy on Sleep Disturbances in Prostate Cancer Patients

Introduction and Objectives: An argument exists between stopping Antiplatelet or Anticoagulant (AP or AC) agents perioperatively to reduce the risk of bleeding complications and continuing the drug to protect against the risk of cardiovascular events during Transurethral Resection of Bladder Tumors (TURBT). And we search a few articles about TURBT in patients receiving AP or AC therapy. We aimed at conducting a systematic review and meta-analysis to evaluate the safety and efficacy of continued AP or AC therapy perioperatively in patients performing TURBT

Syndromic algorithms for detection of gambiense human African trypanosomiasis in South Sudan.

BACKGROUND: Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan. METHODOLOGY/PRINCIPAL FINDINGS: Symptom data from 462 patients (27 cases) presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss), with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9-92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4-8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive. CONCLUSIONS/SIGNIFICANCE: In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be validated elsewhere

Análise comparativa dos histogramas de dose e volume entre planejamentos tridimensionais conformados e convencionais não conformados na radioterapia do câncer de próstata Comparative analysis of dose-volume histograms between 3D conformal and conventional non-conformal radiotherapy plannings for prostate cancer

OBJETIVO: Analisar, comparativamente, doses de radiação em volumes alvos e órgãos de risco entre planejamentos conformados e não conformados em pacientes com câncer de próstata. MATERIAIS E MÉTODOS: No presente trabalho foram analisados planejamentos de 40 pacientes portadores de câncer de próstata. Foram realizados planejamentos conformados, não conformados isocêntricos e não conformados utilizando a distância fonte-superfície, simulados para cada caso, para comparação das doses em volumes alvos e órgãos de risco. Para a comparação foram analisados os histogramas de dose e volume para volumes alvos e órgãos de risco. RESULTADOS: As medianas das doses foram significativamente menores no planejamento conformado analisando-se os seguintes volumes no reto: 25%, 40% e 60%. As medianas das doses foram significativamente menores no planejamento conformado analisando-se os seguintes volumes na bexiga: 30% e 60%. As doses medianas foram significativamente menores no planejamento conformado analisando-se as articulações coxofemorais direita e esquerda. As doses máximas, médias e medianas no volume alvo clínico e no volume alvo planejado foram significativamente maiores no planejamento conformado. CONCLUSÃO: O presente estudo demonstrou que por meio do planejamento conformado em pacientes com câncer de próstata é possível entregar doses maiores no volume alvo e doses menores em órgãos de risco.<br>OBJECTIVE: The present study was aimed at comparing conformal and non-conformal radiotherapy plans designed for patients with prostate cancer, by analyzing radiation doses in target volumes and organs at risk. MATERIALS AND METHODS: Radiotherapy plans for 40 patients with prostate cancer were analyzed. Conformal, conformal isocentric and non-conformal plans utilizing the source-surface distance were simulated for each of the patients for comparison of radiation dose in target volumes and organs at risk. For comparison purposes, dose-volume histograms for target volumes and organs at risk were analyzed. RESULTS: Median doses were significantly lower in the conformal planning, with 25%, 40% and 60% volumes in the rectum and 30% and 60% in the bladder. The median doses were significantly lower in the conformal planning analyzing the right and left coxofemoral joints. Maximum, mean and median doses in the clinical target volume and in the planned target volume were significantly higher in the conformal planning. CONCLUSION: The present study has demonstrated that the conformal radiotherapy planning for prostate cancer allows the delivery of higher doses to the target volume and lower doses to adjacent healthy tissues

Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support

Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor.We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb > 50 mg/dL was used as a marker of severe hemolysis.154 patients received ECMO for cardiac (n = 115) or pulmonary (n = 39) indications. Patients' mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p = 0.026), lower 24-hour lactic acid (p = 0.023), shorter ECMO duration (P = 0.01), fewer RBC transfusions on ECMO (p = 0.008) and lower level of PFHb 24-hours post ECMO implantation (p = 0.029). 24-hour PFHb > 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p = 0.002. A Cox proportional hazard analysis identified PFHb > 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 - 8.8, p = 0.011).PFHb > 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis