Unraveling the Dietary Puzzle: Exploring the Influence of Diet, Nutraceuticals, and Supplements on Bladder Cancer Risk, Outcomes, and Immunotherapy Efficacy: Insights from the BLOSSOM Study and Beyond.

Bladder cancer is considered a global health concern characterized by significant morbidity and mortality rates. The complex relationship between diet and bladder cancer is examined, with a specific focus on the role of diet in risk, outcomes, and treatment efficacy. Attention is drawn to the burgeoning field of immunotherapy in bladder cancer treatment, and the possible influence of diet on its outcomes is explored. While evidence remains limited, prior studies in other cancer types have suggested a potential connection between diet and immunotherapy response. To address this knowledge gap, the ongoing BLOSSOM study is presented, which aims to investigate the link between dietary factors, lifestyle, and the effectiveness of immunotherapy in patients with non-muscle-invasive bladder cancer. Ongoing efforts to decipher the intricate relationship between diet and bladder cancer care are highlighted, emphasizing the quest to unravel the dietary puzzle for the improvement of bladder cancer management.

Changes in cerebral cortex activity during a simple motor task after MRgFUS treatment in patients affected by essential tremor and Parkinson's disease: a pilot study using functional NIRS.

Objective.Magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) is a non-invasive thermal ablation method that involves high-intensity focused ultrasound surgery (FUS) and Magnetic Resonance Imaging for anatomical imaging and real-time thermal mapping. This technique is widely employed for the treatment of patients affected by essential tremor (ET) and Parkinson's disease (PD). In the current study, functional near-infrared spectroscopy (fNIRS) was used to highlight hemodynamics changes in cerebral cortex activity, during a simple hand motor task, i.e. unimanual left and right finger-tapping, in ET and PD patients.Approach.All patients were evaluated before, one week and one month after MRgFUS treatment.Main results.fNIRS revealed cerebral hemodynamic changes one week and one month after MRgFUS treatment, especially in the ET group, that showed a significant clinical improvement in tremor clinical scores.Significance.To our knowledge, our study is the first that showed the use of fNIRS system to measure the cortical activity changes following unilateral ventral intermediate nucleus thalamotomy after MRgFUS treatment. Our findings showed that therapeutic MRgFUS promoted the remodeling of neuronal networks and changes in cortical activity in association with symptomatic improvements.

Do patients with PD benefit from music assisted therapy plus treadmill-based gait training? An exploratory study focused on behavioral outcomes.

Purpose: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, presenting not only with motor symptoms (resting tremor, bradykinesia, and muscular rigidity), but also with cognitive and behavioral problems that need to be addressed in a rehabilitation setting. Aim of the study was to evaluate the effects of a combined rehabilitative approach, using gait training coupled to music-based therapy, on cognitive and behavioral function in a sample of patients with PD.Materials and Methods: Forty patients, meeting the inclusion criteria, were enrolled in this study and were randomly divided into two groups. The control group (CG) underwent traditional over ground gait training, whilst the experimental group (EG) underwent gait training with the Biodex Gait Trainer 3 (a treadmill integrated with music therapy). Each subject was evaluated at baseline (T0) and after the training (T1), using specific neuropsychological and motor function tests.Results: The EG presented higher outcomes scores concerning mood and quality of life in all subscales of Psychological General Well-Being Index (i.e. anxiety, depression, health, vitality and positivity) and subscales of Brief-COPE, with regard to behavioral disengagement, positive reframing, planning, acceptance and use of emotional support, as compared to the CG. Moreover, a significant improvement in motor functioning, with regard to static and dynamic balance, was found in the EG.Conclusion: Music-based gait training rehabilitation may be considered an effective strategy to improve behavioral performances, coping strategies and rehabilitation outcomes in patients with PD.

Walking to your right music: a randomized controlled trial on the novel use of treadmill plus music in Parkinson's disease.

BACKGROUND: Rhythmic Auditory Stimulation (RAS) can compensate for the loss of automatic and rhythmic movements in patients with idiopathic Parkinson's disease (PD). However, the neurophysiological mechanisms underlying the effects of RAS are still poorly understood. We aimed at identifying which mechanisms sustain gait improvement in a cohort of patients with PD who practiced RAS gait training. METHODS: We enrolled 50 patients with PD who were randomly assigned to two different modalities of treadmill gait training using GaitTrainer3 with and without RAS (non_RAS) during an 8-week training program. We measured clinical, kinematic, and electrophysiological effects of both the gait trainings. RESULTS: We found a greater improvement in Functional Gait Assessment (p < 0.001), Tinetti Falls Efficacy Scale (p < 0.001), Unified Parkinson Disease Rating Scale (p = 0.001), and overall gait quality index (p < 0.001) following RAS than non_RAS training. In addition, the RAS gait training induced a stronger EEG power increase within the sensorimotor rhythms related to specific periods of the gait cycle, and a greater improvement of fronto-centroparietal/temporal electrode connectivity than the non_RAS gait training. CONCLUSIONS: The findings of our study suggest that the usefulness of cueing strategies during gait training consists of a reshape of sensorimotor rhythms and fronto-centroparietal/temporal connectivity. Restoring the internal timing mechanisms that generate and control motor rhythmicity, thus improving gait performance, likely depends on a contribution of the cerebellum. Finally, identifying these mechanisms is crucial to create patient-tailored, RAS-based rehabilitative approaches in PD. TRIAL REGISTRATION: NCT03434496 . Registered 15 February 2018, retrospectively registered.

Metabolic changes in de novo Parkinson's disease after dopaminergic therapy: A proton magnetic resonance spectroscopy study.

The aim of this study was to assess metabolic changes in the motor cortex in de novo Parkinson's disease (PD) patients before and after therapy with ropinirole. Twenty de novo drug-naïve PD patients and 15 healthy controls underwent conventional magnetic resonance imaging and proton magnetic resonance spectroscopy imaging ((1)H-MRSI). The resonance intensities of N-acetylaspartate (NAA) and choline (Cho) were normalized for the resonance intensities of creatine (Cr). At baseline, lower NAA/Cr and NAA/Cho ratios and higher Cho/Cr ratios were found in the motor cortex of PD patients compared with controls (p<0.001). Ten months after ropinirole treatment, PD patients showed a significant clinical improvement in the UPDRS motor sub-scores (p<0.001) and an increase of NAA/Cr and NAA/Cho ratios (p<0.006 and p=0.01, respectively). A highly significant correlation between NAA/Cr and NAA/Cho ratios and UPDRS motor sub-scores was observed (r=-0.981 and r=-0.983, respectively). We could argue that the ropinirole efficacy to improve the motor performances is the result of partial restoration of neuronal functions, due to the increase of NAA in motor cortex.

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.

Economic evaluation of everolimus versus sorafenib for the treatment of metastatic renal cell carcinoma after failure of first-line sunitinib.

BACKGROUND: A recent indirect comparison study showed that sunitinib-refractory metastatic renal cell carcinoma (mRCC) patients treated with everolimus are expected to have improved overall survival outcomes compared to patients treated with sorafenib. This analysis examines the likely cost-effectiveness of everolimus versus sorafenib in this setting from a US payer perspective. METHODS: A Markov model was developed to simulate a cohort of sunitinib-refractory mRCC patients and to estimate the cost per incremental life-years gained (LYG) and quality-adjusted life-years (QALYs) gained. Markov states included are stable disease without adverse events, stable disease with adverse events, disease progression, and death. Transition probabilities were estimated using a subset of the RECORD-1 patient population receiving everolimus after sunitinib, and a comparable population receiving sorafenib in a single-arm phase II study. Costs of antitumor therapies were based on wholesale acquisition cost. Health state costs accounted for physician visits, tests, adverse events, postprogression therapy, and end-of-life care. The model extrapolated beyond the trial time horizon for up to 6 years based on published trial data. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The estimated gain over sorafenib treatment was 1.273 LYs (0.916 QALYs) at an incremental cost of $81,643. The deterministic analysis resulted in an incremental cost-effectiveness ratio (ICER) of $64,155/LYG ($89,160/QALY). The probabilistic sensitivity analysis demonstrated that results were highly consistent across simulations. CONCLUSIONS: As the ICER fell within the cost per QALY range for many other widely used oncology medicines, everolimus is projected to be a cost-effective treatment relative to sorafenib for sunitinib-refractory mRCC.

An adjusted indirect comparison of everolimus and sorafenib therapy in sunitinib-refractory metastatic renal cell carcinoma patients using repeated matched samples.

OBJECTIVE: To date, no trial data exist comparing treatment outcomes for everolimus versus sorafenib. The current analysis indirectly compares the overall survival (OS) benefit of everolimus and sorafenib as second-line treatment options. RESEARCH DESIGN AND METHODS: A single-arm sorafenib study is selected as a basis to match an everolimus sunitinib-refractory subpopulation of the RECORD-1 trial. Only patients with clear cell histology are included. An adjusted matching approach is taken where 1000 repeated random samples matched to the sorafenib population on risk score distribution are produced, and a 95% CI around the mean of all sampled median OS is generated. MAIN OUTCOME MEASURES: The main outcome measures include adjusted median OS and progression-free survival. RESULTS: In all, 45 clear cell histology sorafenib patients and 1000 samples of N=41 sunitinib-refractory everolimus patients are considered for analysis. After adjusted matching, the estimated median OS benefit is 32.0 [corrected] weeks (95% CI: 22, 64) and 81.5 weeks (95% CI:78, 86) for sorafenib and everolimus patients, respectively. CONCLUSION: Results suggest that sunitinib-refractory metastatic renal cell carcinoma patients treated with everolimus may experience significantly improved OS outcomes compared to those treated with sorafenib. However, because this is not a randomized controlled trial, the results should be interpreted as those from an observational study.

Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic renal cell carcinoma.

BACKGROUND: Sunitinib and everolimus have been approved for first- and second-line treatment, respectively, in metastatic renal cell carcinoma (mRCC). The role of sorafenib, which is approved for second-line treatment after cytokines failure, is presently to be defined. OBJECTIVE: To determine whether third-line sorafenib after sequential use of sunitinib and mammalian target of rapamycin inhibitors (everolimus or temsirolimus) is feasible and effective. DESIGN, SETTING, AND PARTICIPANTS: One hundred fifty medical records of patients with mRCC treated with first-line sunitinib between January 2006 and January 2010 were reviewed at four participating centers. Data regarding patients treated with the sequence sunitinib-everolimus or temsirolimus-sorafenib were extracted. Central analysis of radiographic images was performed using RECIST criteria to determine progression-free survival (PFS) and overall response rate (oRR) to sorafenib treatment. MEASUREMENTS: PFS and oRR to sorafenib were the primary end points. Secondary outcomes were safety and overall survival (OS). RESULTS AND LIMITATIONS: Thirty-four patients were eligible for the study. A median PFS of 4 mo (range: 3-6 mo) and a median OS of 7 mo since sorafenib treatment (range: 6-10 mo) were reported. Of the patients, 23.5% showed response to sorafenib, with an overall disease control rate (complete responses plus partial responses plus stable disease) of 44%. Selection bias, data incompleteness, and absence of study design are inevitable limitations of the study, although central review can strengthen the quality of presented data. CONCLUSIONS: Third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line everolimus or temsirolimus, with no patients interrupting sorafenib because of toxicity or lack of compliance. Prospective, placebo-controlled trials are completely lacking and are required in this setting.

Effects of the ErbB1/ErbB2 kinase inhibitor GW2974 on androgen-independent prostate cancer PC-3 cell line growth and NSE, chromogranin A and osteopontin content.

Prostate cancer is one of the most frequently diagnosed cancer in men. Treatment by radical prostatectomy, radiotherapy and anti-androgen drugs is successful in patients with localized cancer. However, prolonged androgen deprivation often leads to hormone refractory condition, associated with disease relapse. ErbB1 and ErbB2 activity has been correlated with androgen-independence. We determined the effects of GW2974, a dual inhibitor of ErbB-1 and ErbB-2 tyrosine kinase activity, on growth, NSE, chromogranin A and osteopontin cytosol content in the androgen-independent prostate cancer cell line PC-3. We found that PC-3 cell growth was inhibited by GW2974, whereas NSE and chromogranin A cell contents were stimulated and osteopontin cytosol level was not affected. The present data may have clinical implications for the treatment of advanced prostate cancer.

Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer.

PURPOSE: No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. PATIENTS AND METHODS: Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). RESULTS: All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). CONCLUSION: Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.

Four-year outcome of a prospective randomised trial comparing bipolar plasmakinetic and monopolar transurethral resection of the prostate.

BACKGROUND: No data have been published on the midterm efficacy of bipolar transurethral resection of the prostate (TURP). OBJECTIVE: To evaluate 4-yr results from a prospective randomised trial comparing bipolar TURP with standard monopolar TURP. DESIGN, SETTING, AND PARTICIPANTS: Seventy patients with symptomatic benign prostatic hyperplasia were enrolled in this prospective randomised controlled trial in a tertiary-care institution. Inclusion criteria were age > 50 yr, good performance status, urinary retention, International Prostate Symptom Score (IPSS) > or = 18, and maximal flow rate (Q(max)) < or = 15 ml/s. Exclusion criteria were prostate volume < 30 cm(3), documented or suspected prostate cancer, neurogenic bladder, bladder stone or diverticula, urethral stricture, and maximal bladder capacity > 500 ml. INTERVENTION: Patients underwent standard or bipolar plasmakinetic TURP performed by the same surgeon using the same surgical technique. MEASUREMENTS: Treatment efficacy was evaluated at 1, 2, 3, and 4 yr by comparing urinary flow rates, IPSS, and estimated postvoid residual (PVR) urine volume. Midterm complications were also recorded. RESULTS AND LIMITATIONS: The number of dropouts was not statistically significantly different in the two groups (p=0.2). The significant improvements in both groups were maintained at 4 yr for the IPSS, quality of life score, Q(max), and PVR versus baseline values. The main outcome variables at 4 yr for bipolar and monopolar TURP were mean IPSS 6.9 and 6.4 (p=0.58); mean Q(max) 19.8 ml/s and 21.2 ml/s (p=0.44), and mean PVR volume 42 ml and 45 ml (p=0.3). Overall, 2 of 32 (6.2%) and 3 of 31 (9.6%) patients required reoperation because of late complications (p=0.15). The major study limitation was the small sample size. CONCLUSIONS: This study represents the secondary, midterm analysis of a previously published trial. Our 4-yr data confirm our initial positive findings for the efficacy and safety of bipolar plasmakinetic TURP. Larger well-designed studies are needed to corroborate these findings.

Gyrus bipolar versus standard monopolar transurethral resection of the prostate: a randomized prospective trial.

OBJECTIVES: To compare bipolar plasmakinetic (PK) with standard monopolar transurethral resection of the prostate (TURP). METHODS: A total of 70 patients were prospectively randomized into two groups: 35 patients underwent PK TURP with the Gyrus device, and 35 patients underwent standard monopolar TURP. We evaluated the time to catheter removal and hospital discharge, operating time, blood loss, postoperative irrigation, complications, urinary flow rates, symptom relief, and postvoid residual volumes. RESULTS: At baseline, the study groups were comparable in age, prostate volume, mean prostate-specific antigen value, International Prostate Symptom Score, quality-of-life score, flow rate, and postvoid residual volume. The mean catheterization time was 72 and 100 hours in the PK and standard groups, respectively. This difference was statistically significant (P <0.05), as was the difference in the time to hospital discharge. No difference was found in the mean resection time, amount of resected tissue, or variations in hemoglobin and sodium levels. The improvement in flow rate, postvoid residual volume, International Prostate Symptom Score, and quality-of-life score was comparable between the two groups at 12 months of follow-up. CONCLUSIONS: In our experience, PK TURP showed comparable perioperative results to those obtained with standard TURP, but with more favorable postoperative outcomes. The resection time and blood loss were similar between the two groups, but the need for continuous bladder irrigation after surgery and time to catheter removal and hospital discharge were significantly shorter in the PK group.