The Impact of Flavonoid Supplementation on Serum Oxidative Stress Levels Measured via D-ROMs Test in the General Population: The PREVES-FLAVON Retrospective Observational Study.

BACKGROUND: Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. METHODS: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. RESULTS: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term. CONCLUSIONS: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Possible Implications of Managing Alexithymia on Quality of Life in Parkinson's Disease: A Systematic Review.

Alexithymia, characterized by difficulty in recognizing and verbalizing emotions, is reported to be more prevalent in subjects with Parkinson's disease (PD) than in the general population. Although it is one of the nonmotor symptoms of PD, alexithymia is often overlooked in clinical practice. The aim of this systematic review is to investigate the prevalence of alexithymia in PD, assess its impact on quality of life, and explore the rehabilitation approaches for alexithymia. Research articles, selected from PubMed, Scopus, and Web of Science, were limited to those published in English from 2013 to 2023. The search terms combined were "Alexithymia," "Parkinson's disease,", and "Quality of life." Current literature review indicates that alexithymia is commonly assessed using the Toronto Alexithymia Scale (TAS-20), and it is associated with deficits in visuospatial and executive functions. Presently, rehabilitation interventions for alexithymia are scarce, and their effectiveness remains controversial. Future research should focus on developing comprehensive assessments and rehabilitation strategies for emotional processing, considering its significant impact on the quality of life of both patients and caregivers.

The role of MRgFUS in the treatment of neuropsychiatric disorders: a state of the art.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) is a contemporary non-invasive ablative procedure that utilizes high- or low-intensity ultrasound, guided and monitored by magnetic resonance imaging (MRI). While MRgFUS has been established as an effective treatment for conditions like essential tremor and tremor-dominant Parkinson's disease, it has recently emerged as a safe and promising ablative minimally invasive procedure for the management of treatment-resistant psychiatric disorders. Indeed, despite the availability of various pharmacological and behavioral therapies, a subset of psychiatric patients remains refractory to conventional treatments. EVIDENCE ACQUISITION: To assess the feasibility and safety of MRgFUS in psychiatric disorders, a comprehensive literature search in PubMed and Scopus databases was conducted, resulting in the inclusion of five relevant articles in this review. EVIDENCE SYNTHESIS: While data on this innovative procedure are still limited, MRgFUS demonstrates potential as a safer and less invasive surgical technique for treating these disorders. CONCLUSIONS: Continued research efforts and data validation are imperative to establish MRgFUS as an additional, minimally invasive procedure for treatment-resistant psychiatric patients in the near future.

Psychological Factors Affecting Assertiveness in Subjects with Parkinson's Disease.

Background/Objectives: Assertiveness, defined as the positive affirmation of oneself, encompasses the ability to refuse requests, express anger, disagree or oppose others, show affection, and uphold personal beliefs without causing conflict. Deficits in assertive behavior are often linked to pathological changes in the basal ganglia and prefrontal dopaminergic systems, commonly observed in Parkinson's disease (PD), and are predictive of poor clinical outcomes. Psychological factors such as mood alterations and cognitive dysfunction may also impact assertiveness. This study investigated the psychological factors influencing assertiveness in individuals with PD. Methods: A cross-sectional study was conducted, involving 160 patients with PD attending a movement disorders outpatient clinic. The participants underwent assessment using a battery of standardized neuropsychological tests to evaluate cognitive function, assertiveness, mood, dysarthria, and quality of life (QoL). Results: All dimensions of assertiveness correlated with depression and anxiety. Individuals experiencing mood disturbances may struggle to express themselves assertively. Similarly, some dimensions of assertiveness correlated also with the QoL, indicating that, overall, well-being affects assertive behavior. Gender emerged as a significant influencer of assertiveness across all dimensions. Specifically, in subjects with PD, the male gender was associated with lower scores in assertiveness compared to women. No significant correlations were found between assertiveness and dysarthria. Conclusions: The findings highlight the importance of adopting a holistic approach to PD management, addressing not only motor symptoms but also psychological challenges which patients may encounter in their daily lives.

Exploring a Novel Approach to Spare Classic Chemotherapy in HER2-Low, ER-Positive Breast Cancer Based on Trastuzumab Deruxtecan Combined with Endocrine Therapy.

BACKGROUND: Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy. OBJECTIVE: This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer. METHODS: We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects. CONCLUSIONS: This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.

The Role of Treatment-Related Parameters and Brain Morphology in the Lesion Volume of Magnetic-Resonance-Guided Focused Ultrasound Thalamotomy in Patients with Tremor-Dominant Neurological Conditions.

PURPOSE: To determine the best predictor of lesion volume induced by magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy in patients with tremor-dominant symptoms in Parkinson's disease (PD) and essential tremor (ET) patients. METHODS: Thirty-six neurological patients with medication-refractory tremor (n°19 PD; n°17 ET) were treated using a commercial MRgFUS brain system (Exablate Neuro 4000, Insightec) integrated with a 1.5 T MRI unit (Sigma HDxt; GE Medical System). Linear regression analysis was used to determine how the demographic, clinical, radiological (Fazekas scale), volumetric (total GM/WM/CSF volume, cortical thickness), and MRgFUS-related parameters [Skull Density Ratio (SDR), n° of transducer elements, n° of sonications, skull area, maximal energy delivered (watt), maximal power delivered (joule), maximal sonication time delivered, maximal mean temperature reached (T°C_max), accumulated thermal dose (ATD)] impact on ventral intermediate (VIM)-thalamotomy-related 3D volumetric lesions of necrosis and edema. RESULTS: The VIM thalamotomy was clinically efficacious in improving the tremor symptoms of all the patients as measured at 1 week after treatment. Multiple regression analysis revealed that T°C_max and n° of transducer elements were the best predictors of the necrosis and edema volumes. Moreover, total WM volume also predicted the size of necrosis. CONCLUSIONS: Our study provides new insights into the clinical MRgFUS procedures that can be used to forecast brain lesion size and improve treatment outcomes.

Gender minorities in breast cancer - Clinical trials enrollment disparities: Focus on male, transgender and gender diverse patients.

BACKGROUND: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials. METHODS: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC. RESULTS: We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group. We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone. Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001. CONCLUSIONS: We confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials.

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.

A Retrospective Study of Cemiplimab Effectiveness in Elderly Patients with Squamous Cell Carcinoma of the Skin: Insights from a Real-Life Scenario.

INTRODUCTION: This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin. METHODS: The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes. RESULTS: Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1). CONCLUSION: These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC 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.

REM Sleep Behavior Disorder and Cognitive Functions in Parkinson's Patients: A Systematic Review.

Sleep disorders, such as REM sleep behavior disorder (RBD) and excessive daytime sleepiness, are among the most common non-motor symptoms in subjects with Parkinson's disease (PD). Sleep disorders have a major negative impact on the quality of life of patients and their caregivers. In addition, REM sleep behavior disorder is an important risk factor for cognitive impairment in PD. This systematic review was conducted on studies investigating the influence of RBD on cognitive performance in PD subjects. We searched the PubMed and Scopus databases, screened the references of the studies included, and reviewed articles for additional citations. From the first 244 publications, we included only 11 studies that met the search criteria. The results showed that sleep disorders in PD were associated with impaired executive functions, visual-constructive abilities, reduced attention, and episodic verbal memory, and could predict the possible risk of developing dementia.

Effective Management of Nasal Vestibule Squamous Cell Carcinoma with Cemiplimab: A Case Report.

Nasal vestibule squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options. This case report presents an 83-year-old female with SCC of the nasal vestibule who was ineligible for surgery or radiotherapy due to various factors. The patient was successfully treated with cemiplimab, a systemic anti-PD-1 antibody, resulting in a remarkable tumor reduction without any observed side effects. This is the first reported case of nasal vestibule SCC treated with cemiplimab, highlighting its potential as a promising therapeutic option.

Feasibility of cabazitaxel in octogenarian prostate cancer patients.

Background: To evaluate the effectiveness and safety of cabazitaxel in castration-resistant prostate cancer patients aged ≥80 years, we performed a retrospective study on a sample of patients from 11 Italian cancer centers. Materials and methods: Fifty-seven patients aged ≥80 years were treated with cabazitaxel after previous failure with docetaxel; 39 completed a comprehensive geriatric assessment questionnaire (34 fit and 5 vulnerable) and 8 patients (14%) had an Eastern Cooperative Oncology Group performance status (PS) ≥2, while most had a PS of 0-1 (86%). Cabazitaxel was administered at a dose of 25 mg/m2 in 30 (52%) patients and 20 mg/m2 or adapted schedules in 27 (48%) patients. These schedules were adopted mainly in patients ≥85 years (75%), with a PS ≥2 (87.5%), and those classified as vulnerable (100%). Results: The duration of treatment was 4.8 months and was comparable in all subgroups; disease control rate was reported in 36 patients (63%); prostate-specific antigen response was recorded in 18 patients (31.5%). Median overall survival was 13.1 months regardless of age (<85/≥85 years), but overall survival was reduced in vulnerable (7.2 months) and PS ≥ 2 patients (6.8 months). The most frequently documented grade 3-4 toxicities were neutropenia (14%) and diarrhea (10.5%). Six patients (10.5%) dropped out due to severe toxicity. Conclusions: Octogenarian patients can be treated with cabazitaxel with reduced doses or alternative schedules that are associated with less toxicity and fewer treatment interruptions. Comprehensive geriatric assessment could facilitate more appropriate patient selection.

Comparison of laparoscopic partial nephrectomy performed with AirSeal® system vs. standard insufflator: results from a referral center.

Objective: To compare perioperative and oncologic surgical outcomes during laparoscopic partial nephrectomy (LPN) performed by standard carbon dioxide insufflation, with those from surgeries in which the AirSeal® intelligent insufflation system was used for renal tumors. Materials and methods: A total of 27 patients with renal tumor were identified, 14 underwent LPN with AirSeal® (group A) and 13 LPN with standard insufflator (group B), respectively. Demographic baseline characteristics were similar in the two groups. Results: The size of the tumor was largest in group B (29.64 vs. 32.1 mm). The mean operative time was shorter in the AirSeal® group [group A: mean 109.0 min, median 107.5 min, interquartile range (IQR) 85; group B: mean 121.0 min, median 120.0 min, IQR 50.0]. Positive margin rates were absent in the two groups. Estimated blood loss presented a difference in the perioperative period (group A: mean 1.5 g/dL, median 1.45 g/dL; group B: mean 2.15 g/dL, median 2.2 g/dL). Time to ischemia was found to be shorter in group A with a median of 18 min compared to a median of 20 min in group B. No subcutaneous emphysema, pneumothorax, and pneumomediastinum cases occurred in either group. A postoperative complication developed in one patient requiring superselective embolization. Conclusion: In selected patients, our preliminary surgical experience has shown that the LPN procedure performed with the aid of the AirSeal® intelligent insufflation system can be used to treat even medium-/high-complexity kidney lesions, with a reduction in operating times, lower rates of complications, and perioperative blood loss. Clinical trial registration: AirSealV1.

Predictors of Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Several programmed death ligand-1 (PD1/L1) immune checkpoint inhibitors (ICIs) are approved in urothelial carcinoma (UC). PATIENTS AND METHODS: To address the need for predictors of the efficacy of ICIs in metastatic urothelial carcinoma (mUC), randomized controlled trials of PD1/L1 inhibitors alone or in combination with chemotherapy in this patient population were systematically reviewed, and differences in ICI-associated survival outcomes according to available baseline variables were quantitatively assessed. RESULTS: The quantitative analysis included 6524 patients with mUC. No visceral metastatic site (HR 0.67; 95% CI, 0.76-0.90) and high PDL-1 expression (HR 0.74; 95% CI, 0.640.87) were significantly associated with a reduced risk of death. CONCLUSION: Treatment with an ICI-containing regimen was associated with a reduced risk of death in mUC patients, which was associated with PDL-1 expression and metastatic site. Further research is warranted.

Comparing cardiovascular adverse events in cancer patients: A meta-analysis of combination therapy with angiogenesis inhibitors and immune checkpoint inhibitors versus angiogenesis inhibitors alone.

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted.

PREVES: A Population-Based Survey Focused on Cancer and Nutrition.

INTRODUCTION: Approximately a third of cancer-related deaths are attributable to modifiable factors. METHODS: As a pilot experience, a cross-sectional survey was conducted in 8,000 citizens residing in four different municipalities of the Salerno province (Sarno, Pagani, San Valentino Torio, and San Marzano sul Sarno) to investigate key lifestyle and dietary habits. RESULTS: A total of 703 of participants (8.7%) reported a history of malignancy. Alarmingly, 30.5% declared to be a current smoker, while 78.8% did not report any kind of physical activity. Encouragingly, 64.5% declared to be abstemious, and 83.0% declared to consume fruit and vegetables every day, while 4.7% and 31.9% declared not to consume meat and fried food, respectively, at any time. Never-consumers of fruit and vegetables had higher odds of having a history of colorectal cancer (OR = 5.01; 95% CI = 1.46-17.15; p = 0.01). CONCLUSIONS: The PREVES study has served to prove the validity of an operational model allowing to integrate hospital and territorial healthcare services, which we expect to be applied at a larger scale. Key information regarding dietary and lifestyle habits of the investigated population was obtained. Larger studies conducted using more accurate approaches to investigate diet, such as 24-h recalls and food frequency questionnaires, are warranted.

The Role of Telemedicine in the Treatment of Cognitive and Psychological Disorders in Parkinson's Disease: An Overview.

BACKGROUND: This literature review evaluates the use and efficacy of telemedicine in cognitive and psychological treatment in Parkinson's disease. METHODS: Studies performed between 2016 and 2021 that fulfilled inclusion criteria were selected from PubMed, Scopus, Cochrane, and Web of Science databases. All articles were evaluated by title, abstract, and text. All studies that examined the cognitive and psychological/psychotherapy treatment of patients with Parkinson's disease by telemedicine were included. RESULTS: Telehealth improved cognitive status and emotional/behavioral disorders in this population, and had positive effects on the patients' and caregivers' quality of life. CONCLUSIONS: Our literature review supports the development and efficacy of cognitive and psychological treatment with telemedicine, but the methodology of the study must be reviewed considering its limitations so as to highlight the benefits and risks of treatment via telemedicine.