Search

Aims Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels. Methods and results A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia. Conclusion In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Background Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR 2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR Conclusions The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria. Graphic abstract

Background: Mind wandering—that is, a shift in the contents of thought away from an ongoing task—can have detrimental consequences for students' reading comprehension. To date, no evidence is available on the effects of text-to-speech solutions on rates of mind wandering during reading. Objectives: The study aimed to evaluate the effects of text-to-speech technology on frequency of mind wandering and reading comprehension in young students with dyslexia (20) and typical development (50). Methods: Students were presented, on a personal computer, texts and comprehension questions in two modalities: self-paced silent reading and text-to-speech reading. Comprehension scores and mind wandering occurrence were considered. A battery of cognitive tasks and questionnaires on mind wandering and emotional traits was also included. Results: There were no differences in baseline rates of mind wandering between the two groups. In the text-to-speech condition, both groups showed better reading comprehension and reduced rates of mind wandering. Students with dyslexia were significantly more on task in the text-to-speech condition compared to the self-paced reading condition. Implications: These results suggest that text-to-speech might represent a reading solution that allows students with Dyslexia to diminish mind wandering during text-to-speech reading.

Aims In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. Materials and methods Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. Results After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09–5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17–6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52–14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. Conclusion Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

Background & Aims Nonpedunculated colorectal polyps are normally endoscopically removed to prevent neoplastic progression. Delayed bleeding is the most common major adverse event. Clipping the resection defect has been suggested to reduce delayed bleedings. Our aim was to determine if prophylactic clipping reduces delayed bleedings and to analyze the contribution of polyp characteristics, extent of defect closure, and antithrombotic use. Methods An individual patient data meta-analysis was performed. Studies on prophylactic clipping in nonpedunculated colorectal polyps were selected from PubMed, Embase, Web of Science, and Cochrane database (last selection, April 2020). Authors were invited to share original study data. The primary outcome was delayed bleeding ≤30 days. Multivariable mixed models were used to determine the efficacy of prophylactic clipping in various subgroups adjusted for confounders. Results Data of 5380 patients with 8948 resected polyps were included from 3 randomized controlled trials, 2 prospective, and 8 retrospective studies. Prophylactic clipping reduced delayed bleeding in proximal polyps ≥20 mm (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.88; number needed to treat = 32), especially with antithrombotics (OR, 0.59; 95% CI, 0.35–0.99; number needed to treat = 23; subgroup of anticoagulants/double platelet inhibitors: n = 226; OR, 0.40; 95% CI, 0.16–1.01; number needed to treat = 12). Prophylactic clipping did not benefit distal polyps ≥20 mm with antithrombotics (OR, 1.41; 95% CI, 0.79–2.52). Conclusions Prophylactic clipping reduces delayed bleeding after resection of nonpedunculated, proximal colorectal polyps ≥20 mm, especially in patients using antithrombotics. No benefit was found for distal polyps. Based on this study, patients can be identified who may benefit from prophylactic clipping. (PROSPERO registration number CRD42020104317.)

OBJECTIVES: We aimed to assess patterns of care delivered to older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), and to analyze the use of geriatric assessment (GA) and assessment of quality of life (QoL).MATERIALS AND METHODS: Members of the head and neck cancer group and the older task force of the European Organisation for Research and Treatment of Cancer (EORTC), members the European Head and Neck Society and members of national groups in Europe were asked to complete a questionnaire about treatment delivered, use of GA, and QoL assessment in older patients with LA-HNSCC.RESULTS: Investigators from 111 centers replied, including 90 (81.1%) academic centers, 16 (14.4%) community hospitals, and 5 (4.5%) private clinics. Large differences in treatment patterns were found. For instance, for oropharyngeal carcinoma, one third of the centers indicated that they treat 40% of older patients with chemoradiation. Fourteen centers (12.6%) routinely perform GA, while 43 centers (38.7%) never do, and 39 centers (35.1%) sometimes do. QoL is assessed on a routine basis in one fifth of the centers.CONCLUSIONS: Large differences exist across institutions in the patterns of care delivered to older patients with LA-HNSCC. Prospective studies are required to learn how GA can guide treatment decisions, and how QoL and treatment outcome can be improved. For that, consensus on standard of care is essential.

We compared two technology configurations (relying on a smartphone, indoor motion sensors, and mini speakers) for helping people with intellectual disability and visual impairments independently manage functional occupational engagement. One of the configurations (a) provided a verbal instruction for each of the objects the participant was to collect within every session, (b) delivered auditory spatial cues to guide the participant to the area where the object could be found, and (c) repeated the instruction once the area was reached. The other configuration differed in that it did not involve any instruction repetition once the participant had reached the area with the object to collect. Six participants used both technology configurations with two or three pairs of activities. One activity of each pair was carried out using the configuration with instruction repetition while the other was carried out using the configuration without instruction repetition, according to an alternating treatments design with a crossover phase. The mean frequency of correct responses with the configuration involving instruction repetition (a) exceeded 17.6 (out of a maximum possible of 18) for all participants, and (b) was significantly higher than the mean frequency obtained with the configuration without instruction repetition. The configuration with instruction repetition may be an effective tool for supporting functional occupation of people with intellectual disability and visual impairments.

Purpose This review was intended to provide an overall picture of work conducted during the last decade to assess the impact of behavioral intervention strategies on people with disorders of consciousness (i.e., comatose state, vegetative state/unresponsive wakefulness, or minimally conscious state). The intervention strategies considered were those not based on music or including music as a component of the intervention package. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist, a scoping review was carried out to identify and provide a synthesis of eligible studies published in English during the 2010-2021 period. Three databases (i.e., PubMed, PsycINFO, and Web of Science) were employed for the literature search. Results Forty studies met the inclusion criteria. Those studies were grouped into three categories based on whether they assessed the effects of: (i) verbal stories/messages, (ii) multiple stimulation, and (iii) response-contingent stimulation. Then, a narrative synthesis of the studies of each of the three categories was provided to specify the types of patients involved, the intervention and assessment conditions implemented, and the outcome attained. Conclusions The evidence reported in most of the studies might be considered encouraging and convincing. Even so, it might be very difficult to view the evidence of the various studies cumulatively and make general/conclusive statements due to a number of differences in the intervention conditions applied.Implications for rehabilitationAn informative picture of the studies using behavioral interventions with people with disorders of consciousness is essential to any professional working in the area.Such picture can be highly useful in providing a view of the intervention strategies used for those people, of the variations existing within and across strategies, and of the evidence available.An analysis of the strategies, their implementation and their effects may provide new insights for improving those strategies and eventually increasing their impact.The individuals charged with the implementation process (e.g., family members or nurses) may have a relevant influence on the overall impact of the strategy.

The number of people suffering from dementia in the world is progressively increasing due to the expansion of the geriatric population in which this clinical condition is more frequent. The appearance of a variable degree of cognitive decline up to full-blown dementia does not, however, represent the inevitable fate of those who age, as the studies conducted in the centenarians clearly indicate. Indeed, the age-specific incidence of dementia has progressively decreased in many geographical areas, probably due to an improvement in lifestyles and health care. In fact, a growing number of scientific evidence shows how chronic exposure over the course of life, starting from young adulthood, to various risk factors—arterial hypertension, diabetes mellitus, obesity, tobacco smoke, sleep disorders—contribute significantly to the development of cognitive decline and dementia in the course of senescence. These risk factors, in fact, can trigger and amplify the various neuropathological mechanisms underlying the development of decline, progressively reducing the functional reserve of the brain. Although definitive evidence deriving from ad hoc intervention studies is not currently available, it is legitimate to assert that the early control of cardiovascular risk factors can represent today the most effective tool for the prevention of dementia.

Introduction Hepatocellular Carcinoma (HCC) is characterized, in Western countries, by higher incidence and mortality rates in the older adult population. In frail patients, limited therapeutic resources are available due to limited expected benefit concerning the risk of treatment-related toxicity. The aim of our study is to evaluate the role of Stereotactic Body Radiotherapy (SBRT) in the clinical management of older old adults (age ≥ 80 years) HCC patients and to identify predictors of efficacy and toxicity. Material and Methods Clinical and treatment-related data of older old adults HCC patients treated with SBRT at our institution were retrospectively reviewed. Statistical analysis was carried out to identify variables correlated with impaired outcome and toxicity. Results Forty-two patients were included, accounting for 63 treated tumors. Median age was 85 (range 80–91) years. Median Charlson Comorbidity Index (CCI) and G8 scores were 10 (range 7–16) and 11 (range 8–14), respectively. SBRT was administered to a median BED10 of 103 Gy10. Median follow-up interval was 11 (range 3–40) months. Two years Local Control (LC), Progression-Free Survival (PFS), and Overall Survival (OS) were 93%, 31%, and 43%, respectively. Acute toxicity occurred in 28% (n = 13) of treatments. A G8 score > 10 was associated with improved survival (p = 0.045), while a CCI ≥10 was correlated with increased acute toxicity (p = 0.021). Conclusions SBRT is a safe and effective option in older old adults HCC patients. A comprehensive geriatric assessment (CGA) is advised before treatment decisions to select optimal candidates for SBRT.

Objective We report a probable case of multiple skeletal dysplasia observed in a Late Iron Age young adult male. Materials The individual studied belongs to a Late Iron Age necropolis from Switzerland. The skeletal elements are well preserved Methods Macroscopic and radiographic assessment. Results The individual shows evidence of both craniofacial and mandibular deformation. Developmental defects are also visible with effects on the general shape and articular surfaces of both humeri, as well as the left femur and tibia. Conclusion We propose that the lesions observed are manifestations of skeletal dysplasia, such as pseudo-achondroplasia or multiple epiphyseal dysplasia. Significance This is the first recorded case of multiple skeletal dysplasia in an Iron Age necropolis in Switzerland, questioning the integration of physically compromised individuals in La Tene society. Limitations Examination of other skeletal dysplasias from archaeological contexts provides support for this diagnosis. Suggestions for future research The integration of individuals with disabilities in La Tene societies is still poorly understood and further research is needed to better characterize these communities.

Introduction: One of the most feared side effects of radiotherapy (RT) in the setting of breast cancer (BC) patients is cardiac toxicity. This side effect can jeopardize the quality of life (QoL) of long-term survivors. The impact of modern techniques of RT such as deep inspiration breath hold (DIBH) have dramatically changed this setting. We report and discuss the results of the literature overview of this paper. Materials and methods: Literature references were obtained with a PubMed query, hand searching, and clinicaltrials.gov. Results: We reported and discussed the toxicity of RT and the improvements due to the modern techniques in the setting of BC patients. Conclusions: BC patients often have a long life expectancy, thus the RT should aim at limiting toxicities and at the same time maintaining the same high cure rates. Further studies are needed to evaluate the risk–benefit ratio to identify patients at higher risk and to tailor the treatment choices.

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

In our institution, a prospective observational trial testing micro-RNA (miRNA) and ARV7 mutational status in metastatic, castration resistant prostate cancer (mCRPC), is currently recruiting (PRIMERA trial, NCT04188275). A pre-planned interim analysis was performed when 50% of the planned accrual was reached. In this report, we explored the predictive value of Circulating Tumor Cell (CTC) detection in mCRPC patients undergoing 1st line therapy. Moreover, ARV7, ARFL, PSMA and PSA expression on CTC was reported to explore potential correlation with patient prognosis and response to therapy. PRIMERA is a prospective observational trial enrolling mCRPC patients undergoing standard treatment (ARTA + ADT) after I line ADT failure. Clinical and pathological features were collected. Outcomes selected for this preliminary analysis were time to castration resistance (TTCR), PSA at 8 weeks after ARTA therapy start, PSA drop at 8 weeks, Overall PSA drop, PSA nadir. Correlation between these outcomes and CTC detection was tested. Expression of ARV7, ARFL, PSA and PSMA was explored in CTC+ patients to assess their prevalence in this cohort and their impact on selected outcomes. Median TTCR was significantly shorter in CTC+ vs CTC− patients (32.3 vs 75 months, respectively, p = 0.03) and in ARFL+ vs ARFL− patients (30.2 vs 51.1 months, respectively, p = 0.02). ARV7, PSMA and PSA expression on CTC had no impact on median TTCR, nor on biochemical response to therapy. Patients in whom CTC and ARFL expression were detected had significant reduced TTCR. However, PSA response was not influenced by CTCs detection and specific biomarkers expression.

Extracellular vesicles (EVs) are nanosized vesicles released from most cell types that play a key role in cell-to-cell communication by carrying DNA, non-coding RNAs, proteins and lipids out of cells. The composition of EVs depends on the cell or tissue of origin and changes according to their pathophysiological conditions, making EVs a potential circulating biomarker of disease. Additionally, the natural tropism of EVs for specific organs and cells has raised the interest in their use as delivery vehicles. In this review, we provide an overview of EV biogenesis, isolation and characterization. We also discuss EVs in the context of endothelial pathophysiology, summarizing the current knowledge about their role in cell communication in quiescent and activated endothelial cells. In the last part, we describe the potential use of EVs as delivery vehicles of bioactive compounds and the current strategies to load exogenous cargo and to functionalize EVs to drive them to a specific tissue.

Background and aims Diabetes has consistently been shown to increase risk for cognitive decline. Cognitive deficits may occur at the very earliest stages of diabetes. We sought to estimate the determinants of memory function in a group of middle-aged obese subjects with prediabetes or newly-diagnosed type 2 diabetes mellitus. Methods and results Sixty-two obese patients in treatment with metformin-with prediabetes (n = 41) or newly diagnosed T2DM (n = 21), were studied. Short- and long-term memory function was assessed through a neuropsychological assessment consisting of two tests and a composite domain z score was calculated. Cardiometabolic variables, such as abdominal MRI quantification of subcutaneous (SAT) and visceral (VAT) adipose tissue content, and of intra-hepatocellular lipid content, as well as insulin sensitivity (Matsuda Index, HOMA-IR) and beta cell performance (Beta Index), by multiple sampling, 8-point oral glucose tolerance test, were also evaluated. Age, non-alcoholic fatty liver disease (NAFLD), and lnHOMA-IR together explained 18% (R square) of the variance in memory domain. Including NAFLD increased the explained variance by 8% and including lnHOMA-IR by 9.1%, whereas the contribution of age and other factors was negligible. Conclusion Preventing and managing insulin resistance in precocious and possibly earlier stages of diabetes might provide benefit in slowering down future cognitive decline.

Purpose In head and neck squamous cell carcinoma (HNSCC), the potential mitigating effect of complementary medicine interventions such as acupuncture for radiation-induced toxicity is unknown. This study aimed to assess the impact of acupuncture on the incidence and degree of severity of common radiation-induced side effects. Methods In accordance with pre-specified PICO criteria, a systematic review was performed. Two electronic databases (Medline and Embase) were searched over a 10-year time frame (01/01/10 to 30/09/20). Patients undergoing a curatively intended, radiation-based treatment for histologically confirmed squamous cell carcinoma of the nasopharynx, oropharynx, larynx, hypopharynx and oral cavity represented the target population of our study. Accurate information on the acupuncture methodology was reported. All included articles were evaluated to identify any potential source of bias Results Five papers were included in our qualitative analysis, for a total of 633 subjects. Compliance to per-protocol defined schedule of acupuncture sessions was high, ranging from 82 to 95.9%. Most patients (70.6%) were randomly allocated to receive acupuncture for its potential preventive effect on xerostomia. The large heterogeneity in study settings and clinical outcomes prevented from performing a cumulative quantitative analysis, thus no definitive recommendations can be provided. Conclusions Although shown to be feasible and safe, no firm evidence currently supports the use of acupuncture for the routine management of radiation-induced toxicity in HNSCC.

Background High-grade gliomas are among the most aggressive central nervous system primary tumors, with a high risk of recurrence and a poor prognosis. Re-operation, re-irradiation, chemotherapy are options in this setting. No-best therapy has been established. Bevacizumab was approved on the basis of two Phase 2 trials that evaluated its efficacy in patients with recurrent glioblastoma. Materials and methods We have retrospectively review data of patients with high-grade glioma treated at our institution that undergone radiological or histological progression after at least one systemic treatment for recurrent disease. Bevacizumab was administered alone or in combination with chemotherapy until disease progression or unacceptable toxicity. Bevacizumab regimen was analyzed to assess PFS and OS. Histological, molecular and clinical features of the entire cohort were collected. Results We reviewed data from 92 patients, treated from April 2009 to November 2019, with histologically confirmed diagnosis of high-grade gliomas and recurrent disease. A PFS of 55.2%, 22.9% and 9.6% was observed at 6, 12 and 24 months, respectively. Performance status, age at diagnosis ( 65 ys.) and use of corticosteroids during bevacizumab therapy were strongly associated with PFS. The OS was 74.9% at 6 months, 31.7% at 12 months, 10.1% at 24 months. In our cohort, 51.1% were long-term responders (PFS > 6 months). Globally, bevacizumab treatment was well tolerated. Conclusion Our analysis confirms the efficacy of bevacizumab in recurrent high-grade glioma patients with an acceptable toxicity profile, in keeping with its known safety in the literature.

Purpose The purpose of this paper is to review studies that evaluated technology-based prompting systems for supporting participants with dementia or acquired cognitive impairment in their performance of multistep daily tasks. Design/methodology/approach A scoping review was conducted to identify eligible studies through a search of four electronic databases, that is, PubMed, PsycINFO, Web of Science and Institute of Electrical and Electronics Engineers. Findings The search, which covered the 2010–2020 period, led to the identification of 1,311 articles, 30 of which were included in the review. These articles evaluated six different types of prompting systems: context-aware, automatic computer prompting, context-aware, mediated computer prompting, teleoperated robot prompting, self-operated augmented reality prompting, self-operated computer or tablet prompting and time-based (preset) computer, tablet or smartphone prompting. Originality/value Technology-aided prompting to help people with dementia or acquired cognitive impairment perform relevant multistep daily tasks is considered increasingly important. This review provides a picture of the different prompting options available and of their level of readiness for application in daily contexts.

Purpose Immune checkpoint inhibitors have opened a new scenario in the treatment of cancer. These agents can elicit adverse events, which may affect different systems and organs, including the endocrine system. The aims of this study were to evaluate the impact of the anti-PD-1 molecules nivolumab and pembrolizumab on endocrine toxicity and on patient outcome. Methods A retrospective and multicentre study was designed, which involved a total of 251 patients affected by different tumors (mostly non-small cell lung cancer, 68.92% and melanoma, 24.30%) and treated with the PD-1 inhibitors nivolumab (61.35%) or pembrolizumab (38.65%) for up to 60 months. Clinical and biochemical data were recorded until July 31, 2020. Results Endocrine toxicity occurred in 70 out of 251 patients (27.89%). It was mostly related to thyroid dysfunction and in 75% of cases occurred within 6 months from the beginning of therapy. A previous endocrine morbidity and female gender were predictors of endocrine toxicity. There was no association between endocrine dysfunction and patient outcome. However, when all toxicities (i.e., endocrine and non endocrine) were considered, a significant association with progression-free survival and overall survival was found. Conclusions Thyroid alterations are frequently observed in cancer patients treated with anti PD-1 drugs, particularly in women and in the presence of a previous endocrinopathy. We suggest that regular thyroid assessment should be performed in these patients, especially in the first months of therapy. Finally, the onset of side effects, related to anti PD-1 agents, appears to be associated with a better outcome.

Wet age-related macular degeneration (w-AMD) represents the leading cause of visual impairment in the elderly in the developed countries. Intravitreal antivascular endothelial growth factor (VEGF) drugs are currently considered as the first-line treatment option for treating w-AMD; however, the frequent injection intervals have lit the way to investigate novel anti-VEGF agents allowing a more extended treatment regimen. Brolucizumab is a single-chain antibody fragment targeting all the isoforms of VEGF-A. Phase III HAWK and HARRIER trials have shown a longer durability and superior anatomical outcomes as compared with the standard of care by adopting a quarterly regimen for treating w-AMD. Brolucizumab has been approved in Europe, USA, and Japan for the management of w-AMD.This article presents an overview of w-AMD and investigates the progress of brolucizumab through clinical trials. It offers insights into where brolucizumab may be placed in the current market of anti-VEGF agents and its potential advantages over the previous molecules adopted for treating w-AMD.The possibility of administering brolucizumab with more dilated treatment intervals represents an important advantage to decrease the treatment burden and improve patient compliance. Brolucizumab represents a possible drug switching option in non-responding patients to other anti-VEGF drugs.

Neuronal activity in the brain reflects an excitation–inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation–inhibition balance.

Purpose This paper provides a review of studies that evaluated technology devices to sustain various forms of mobility in older people with cognitive impairment or dementia and mobility problems (e.g., inability to ambulate or difficulties to orient with consequent failures to reach relevant destinations). Methods A literature search was performed for English language articles indexed in PubMed, PsycINFO, and Web of Science. This search was then supplemented with an ancestral and forward search. The search covered the period ranging between January 2010 and October 2020. Results Twenty-seven articles were included in the review. They were divided into four groups according to whether they aimed to promote (a) supported ambulation, (b) use of safe power wheelchair, (c) ambulation guided by orientation cues, and (d) ambulation with GPS-based assistance. The studies were coded in terms of the objective pursued, technology used, participants involved, strategies applied to assess the technology, and outcome reported. Conclusion A variety of technology devices are available to address the mobility problems of older people with cognitive impairment or dementia. The devices' accessibility and usability differ widely. Data on their impact are still largely preliminary and new systematic research is needed.IMPLICATIONS FOR REHABILITATIONA variety of mobility problems may afflict older people with cognitive impairment or dementia and curtail their opportunities to freely move indoor or outdoor.Technology devices have been developed to (a) promote forms of supported ambulation, (b) facilitate safe use of power wheelchairs, (c) deliver orientation/navigation cues, and (d) ensure tracking and possible assistance.The technology devices differ in terms of accessibility and affordability, with some of them readily available and others at a developmental stage.Data on the effectiveness of the various technology devices in reducing the impact of the mobility problems are still largely preliminary and new systematic research is needed.

Aim: Since 20 February 2020, Lombardy has been one of the most affected areas worldwide by the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate work and psychological impact of COVID-19 on Lombardy radiation therapy (RT) residents in the first 3 months of the outbreak (first lockdown). Methods: An online questionnaire (22 multiple choice questions) via Microsoft Forms was administered on 30 May 2020 to RT residents. Results: Nineteen Lombardy RT residents responded to the survey. Nineteen percent of residents underwent a nasal swab and 11% were quarantined. Seventeen residents (89%) reported an increase in workload. Twelve residents (63%) did not find any difference in terms of work distress; worsening was highlighted in 5 cases (26%). The majority has never considered the possibility of stopping work due to excessive stress (89%). Almost all the residents experienced self- or relative-referred apprehension (95%). Ninety-five percent reported having missed extra-work social relationships. Most of the sample noted worsening sleep quality and difficulty concentrating (69%). No residents requested psychological support, even if provided by the hospital. Conclusion: Overall, the residents adapted to the new workplace scenario, although some health risks and well-being challenges have been reported. An extension of the survey to all Italian RT residents endorsed by Italian Association of Radiotherapy and Clinical Oncology “Young AIRO” will allow an evaluation of COVID-19 impact on a national level. A second survey is planned to underline differences between the first lockdown and the current situation of the pandemic.

Over the past few decades, the world population has increased dramatically including a large number of elderly people. This explosion in population aging comes with a rising number of older adults ...

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

Objective Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events. Methods The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes. Results Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group. Conclusion Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.

Over recent years, managing hypertension in older people has gained increasing attention, with reference to very old, frailer individuals. In these patients, hypertension treatment may be challenging due to a higher risk of hypotension-related adverse events which commonly overlaps with a higher cardiovascular risk. Additionally, frailer older adults rarely satisfy inclusion criteria of randomized clinical trials, which determines a substantial lack of scientific data. Although limited, available evidence suggests that the association between blood pressure and adverse outcomes significantly varies at advanced age according to frailty status. In particular, the negative prognostic impact of hypertension seems to attenuate or even revert in individuals with older biological age, e.g., patients with disability, cognitive impairment, and poor physical performance. Consequently, "one size does not fit all" and personalized treatment strategies are needed, customized to individuals' frailty and functional status. Similar to other cardiovascular diseases, hypertension management in older people should be characterized by a geriatric approach based on biological rather than chronological age and a geriatric comprehensive evaluation including frailty assessment is required to provide the most appropriate treatment, tailored to patients' prognosis and health care goals. The aim of this review was to illustrate the importance of a patient-centered geriatric approach to hypertension management in older people with the final purpose to promote a wider implementation of frailty assessment in routine practice.