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Spinocerebellar ataxias (SCAs) are characterized by substantial phenotypic variability. Among them, SCA42 is a rare non-expansion entity presenting with slowly progressive cerebellar syndrome but whose clinical spectrum may be also wider. A 53-year-old male presented with progressive myoclonus-ataxia and intellectual disability. Genetic screening revealed a novel c.3835G > A (p. Asp1279Asn) variant in the CACNA1G gene. SCA42 is a rare non-expansion SCA caused by mutations in CACNA1G on chromosome 17q21, encoding the Ca(V)3.1, a low-threshold voltage-gated T-type calcium channel. The novel variant we identified is potentially involved in channel activity. This case expands the knowledge regarding CACNA1G-associated phenotype and highlights the importance of genetic screening in myoclonus-ataxia disorders. [ABSTRACT FROM AUTHOR]

Purpose: to assess the utility of response monitoring to enzalutamide by using [68Ga]Ga-PSMA PET in mCRPC patients treated with enzalutamide as first-line therapy. Methods: patients underwent [68Ga]Ga-PSMA PET less than 8 weeks before and 3 months after starting enzalutamide. On the basis of EAU/EANM criteria, patients were categorized as PSMA responders (PET-R) or PSMA non-responders (PET-NR), whilst, based on PSA, they were classified as biochemical responders (PSA-R) or non-responders (PSA-NR). Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method. Results: 69 patients were considered fully evaluable. We observed 47.8% of concordance between [68Ga]Ga-PSMA PET and PSA monitoring at 3 months after starting enzalutamide. For discordant cases, the PSA reduction has a weak impact on PFS and a significant impact on OS in PET-NR patients, whilst this change has no impact either for PFS and OS in PET-R ones. Conclusions: [68Ga]Ga-PSMA PET could be a useful imaging tool for monitoring response to enzalutamide in mCRPC patients, being more informative than PSA in this setting, and possibly better guiding clinicians in therapeutic decisions. [ABSTRACT FROM AUTHOR]

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152. Highlights: This is a systematic review of the prevalence of antidepressant prescriptions for depression in the UK adult population. We found prevalence rates between 30.8% and 95% and a lack of reporting of reporting of depression severity, which questions the adherence to severity-based treatment strategy recommended by NICE. The focus of this study is limited to the adult population in the United Kingdom. The possible use of overlapping datasets for the included studies advises against data pooling. [ABSTRACT FROM AUTHOR]

Background: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy. Objective: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study. Patients and Methods: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan–Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Results: Median OS and PFS were 12.7 (95% CI 10.2–14.1) and 7.9 (95% CI 6.4–9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1–11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia. Conclusions: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab. [ABSTRACT FROM AUTHOR]

Background: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment. Materials and methods: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses. Results: A total of 571 patients with a median age of 61 years (range 17–85) were included in the analysis. With a median follow-up of 22.1 (1.0–89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders. Conclusion: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5–95% CI:1.13–7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis. [ABSTRACT FROM AUTHOR]

Context: The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications. Methods: We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion. Results: Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient. [ABSTRACT FROM AUTHOR]

Background: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. Objective: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. Methods: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan–Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Results: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9–71.3) versus 20.8 (95% CI 12.6–24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31−0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1–40.5) and 13.0 months (95% CI 6.6–23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3–22.4) and 4.9 months (95% CI 3.0–8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). Conclusions: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. Patients and Methods: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. Results: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1–2 or 3–4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). Conclusions: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Balneotherapy includes practices and methods using medically and legally recognized mineral-medicinal waters, muds and natural gases from natural springs for therapeutic purposes. One of the most widely used method in balneotherapy is bathing with thermal mineral water. In the course of the years, scientific community has produced an increasing number of evidences that this practice is an effective method for treating signs and symptoms of several pathologies such as rheumatic, cardiovascular and dermatological diseases. This systematic review is aimed at evaluating the effect of balneotherapy with thermal water baths as a treatment to manage signs and symptoms of patients affected by all types of dermatological diseases. The systematic review was conducted according to the PRISMA Statement, and its protocol was registered on PROSPERO platform (CRD42022295913). The research was performed on the databases Pubmed, Scopus, Web of Science and Cochrane. We included clinical trials evaluating the effects of balneotherapy using thermal mineral water baths for managing dermatological diseases in humans, published in English and Italian language. Eight studies were included, seven of them enrolled adults affected by psoriasis and one studied atopic dermatitis patients. The common result of all the articles included was a clear improvement of signs and symptoms of psoriasis and eczematous diseases after use of thermal mineral water baths. These effects seem to be strictly related to physical and chemical properties of thermal water used for balneotherapy. However, studies in this field are still limited to support robust evidence of the effectiveness of balneotherapy using thermal mineral water baths and often their quality is low. Thus, new clinical studies need to be carried out, using more correct methods for conducting the studies and for processing statistical data. [ABSTRACT FROM AUTHOR]

The aim of the present study was to individuate and compare specific machine learning algorithms that could predict postoperative anterior elevation score after reverse shoulder arthroplasty surgery at different time points. Data from 105 patients who underwent reverse shoulder arthroplasty at the same institute have been collected with the purpose of generating algorithms which could predict the target. Twenty-eight features were extracted and applied to two different machine learning techniques: Linear regression and support vector regression (SVR). These two techniques were also compared in order to define to most faithfully predictive. Using the extracted features, the SVR algorithm resulted in a mean absolute error (MAE) of 11.6° and a classification accuracy (PCC) of 0.88 on the test-set. Linear regression, instead, resulted in a MAE of 13.0° and a PCC of 0.85 on the test-set. Our machine learning study demonstrates that machine learning could provide high predictive algorithms for anterior elevation after reverse shoulder arthroplasty. The differential analysis between the utilized techniques showed higher accuracy in prediction for the support vector regression. Level of Evidence III: Retrospective cohort comparison; Computer Modeling. [ABSTRACT FROM AUTHOR]

Perovskite solar cells promise to be part of the future portfolio of photovoltaic technologies, but their instability is slow down their commercialization. Major stability assessments have been recently achieved but reliable accelerated ageing tests on beyond small-area cells are still poor. Here, we report an industrial encapsulation process based on the lamination of highly viscoelastic semi-solid/highly viscous liquid adhesive atop the perovskite solar cells and modules. Our encapsulant reduces the thermomechanical stresses at the encapsulant/rear electrode interface. The addition of thermally conductive two-dimensional hexagonal boron nitride into the polymeric matrix improves the barrier and thermal management properties of the encapsulant. Without any edge sealant, encapsulated devices withstood multifaceted accelerated ageing tests, retaining >80% of their initial efficiency. Our encapsulation is applicable to the most established cell configurations (direct/inverted, mesoscopic/planar), even with temperature-sensitive materials, and extended to semi-transparent cells for building-integrated photovoltaics and Internet of Things systems. The instability of perovskite solar cells hinders their commercialization. Here, authors report an industrially compatible strain-free encapsulation process based on lamination of highly viscoelastic semi-solid/highly viscous liquid encapsulant adhesive to reduce thermomechanical interfacial stress. [ABSTRACT FROM AUTHOR]

We prove a set of sum rules needed for KK-graviton pair production from matter in orbifolded extra-dimensional models. The sum rules can be found in full generality by considering the properties of solutions to the Sturm-Liouville problem, which describes the wave functions and the masses of the KK-gravitons in four dimensions. They ensure cancellations in the amplitudes of the processes mentioned above which considerably reduce their growth with s in the high-energy limit. This protects extra-dimensional theories from the low-scale unitarity problems that plague other theories with massive spin-2 particles. We argue that such relations are valid for a broader category of models thus generalizing our previous results that were limited to the large μ limit of the Randall-Sundrum model. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. Methods: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. Results: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). Conclusions: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk. [ABSTRACT FROM AUTHOR]

Previously unknown postharvest rots in Packham's Triumph pear were detected in a batch of long-term cold-stored fruit during 2022 in North Patagonia, Argentina. Rots were characterized according to their symptoms and the causal agent was isolated and identified through cultural and molecular methods. Pathogenicity tests were performed on different pear cultivars both at 20 °C and under storage conditions (0 °C − 95% RH). Koch's postulates were fulfilled by re-isolation of the pathogen. Our results indicated that Phacidiopycnis pyri was the causal agent of postharvest rot in the fruit examined. This would constitute the first report of P. pyri as a causal agent of postharvest decay in Argentina. [ABSTRACT FROM AUTHOR]

Generalist species, which exploit a wide range of food resources, are expected to be able to combine available resources as to attain their specific macronutrient ratio (percentage of caloric intake of protein, lipids and carbohydrates). Among mammalian predators, the red fox Vulpesvulpes is a widespread, opportunistic forager: its diet has been largely studied, outlining wide variation according to geographic and climatic factors. We aimed to check if, throughout the species' European range, diets vary widely in macronutrient composition or foxes can combine complementary foods to gain the same nutrient intake. First, we assessed fox's intake target in the framework of nutritional geometry. Secondly, we aimed to highlight the effects of unbalanced diets on fox density, which was assumed as a proxy for Darwinian fitness, as assessed in five areas of the western Italian Alps. Unexpectedly, the target macronutrient ratio of the fox (52.4% protein-, 38.7% lipid- and 8.9% carbohydrate energy) was consistent with that of hypercarnivores, such as wolves and felids, except for carbohydrate intakes in urban and rural habitats. The inverse relation between density and the deviation of observed macronutrient ratios from the intake target suggests that fox capability of surviving in a wide range of habitats may not be exempt from fitness costs and that nutrient availability should be regarded among the biotic factors affecting animal abundance and distribution. [ABSTRACT FROM AUTHOR]

A convincing explanation of the smallness of neutrino masses is represented by the Type-I Seesaw mechanism, where the two measured neutrino mass differences can be generated by introducing at least two right-handed neutrinos. In an ultraviolet complete model, it is possible to dynamically generate the heavy Majorana scale through the spontaneous symmetry breaking of a global Abelian symmetry and the most economical realisation consists in coupling the two exotic neutral leptons to a singlet complex scalar field. The associated Goldstone boson is often dubbed as Majoron, which may achieve a non-vanishing mass by means of a small term that explicitly breaks the Abelian symmetry. In a generic model, the neutrino and Majoron mass generation mechanisms are completely uncorrelated. In this paper, instead, we reduce the landscape of possible models proposing a unique, minimal and predictive framework in which these two types of masses are strictly tied and arise from the same source. Bounds from various terrestrial and astrophysical experiments are discussed. [ABSTRACT FROM AUTHOR]

Background: The risk of developing and worsening chronic kidney disease (CKD) is associated with unhealthy dietary patterns. Food insecurity is defined by a limited or uncertain availability of nutritionally adequate and safe food; it is also associated with several chronic medical conditions. The aim of this systematic review is to investigate the current knowledge about the relationship between food insecurity and renal disease. Methods: We selected the pertinent publications by searching on the PubMed, Scopus, and the Web of Science databases, without any temporal limitations being imposed. The searching and selecting processes were carried out through pinpointed inclusion and exclusion criteria and in accordance with the Prisma statement. Results: Out of the 26,548 items that were first identified, only 9 studies were included in the systemic review. Eight out of the nine investigations were conducted in the US, and one was conducted in Iran. The studies evaluated the relationship between food insecurity and (i) kidney disease in children, (ii) kidney stones, (iii) CKD, (iv) cardiorenal syndrome, and (v) end stage renal disease (ESRD). In total, the different research groups enrolled 49,533 subjects, and food insecurity was reported to be a risk factor for hospitalization, kidney stones, CKD, ESRD, and mortality. Conclusions: The relationship between food insecurity and renal disease has been underestimated. Food insecurity is a serious risk factor for health problems in both wealthy and poor populations; however, the true prevalence of the condition is unknown. Healthcare professionals need to take action to prevent the dramatic effect of food insecurity on CKD and on other chronic clinical conditions. [ABSTRACT FROM AUTHOR]

Purpose: Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ). Methods: Italian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated. Results: Answers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered. Conclusion: Italian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules. [ABSTRACT FROM AUTHOR]

Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients' IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5—ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28–37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to compare single-row suture-anchors (SA) versus transosseous arthroscopic (TO) technique in the treatment of patients with rotator cuff tears in terms of clinical structural outcomes at atleast 24 months of follow-up. Methods: The systematic review was performed according to "PRISMA guidelines" (Preferred Reporting Items for Systematic Reviews and Meta-analyses), in order to identify all the studies comparing clinical, both subjective and objective, outcomes with 24 months follow-up minimum in patients undergoing arthroscopic RC repair with the SR and TO technique. OVID-MEDLINE®, Cochrane, SCOPUS and PubMed were searched from January 2010 to October 2022 to identify relevant studies, using the following key words, that were combined together to achieve maximum search strategy sensitivity: "Rotator cuff tear" OR "repair" OR "shoulder" OR "reconstruction" OR "suture" OR "arthroscopic" OR "single-row" OR "transosseous". Results: Six papers were finally analyzed in this meta-analysis. The weighted mean difference on Constant scores and for ASES for studies considering suture-anchors (SA) group showed good outcomes. The weighted mean difference of Constant scores and of ASES for TO (transosseous) group showed good outcomes. The weighted mean difference of CONSTANT for TO versus SA groups showed no differences in the outcomes of SA and TO techniques for the repair of Rotator Cuff Tears at minimum 24 months follow-up. Conclusions: The Arthroscopic transosseous rotator cuff repair technique and SA (suture-anchor) technique both lead to significant short-term improvement and satisfactory subjective outcome scores with low complication/failure rates. No differences were found in the final outcome between the two techniques. [ABSTRACT FROM AUTHOR]

Purpose: Shoulder stiffness (SS) is a condition characterised by active and passive restricted glenohumeral range of motion, which can occur spontaneously in an idiopathic manner or be associated with a known underlying aetiology. Several treatment options are available and currently no consensus has been obtained on which treatment algorithm represents the best choice for the patient. Herein we present the results of a national consensus on the treatment of primary SS. Methods: The project followed the modified Delphi consensus process, involving a steering, a rating and a peer‐review group. Sixteen questions were generated and subsequently answered by the steering group after a thorough literature search. A rating group composed by professionals specialised in the diagnosis and treatment of shoulder pathologies rated the question–answer sets according to the scientific evidence and their clinical experience. Results: Recommendations were rated with an average of 8.4 points out of maximum 9 points. None of the 16 answers received a rating of less than 8 and all the answers were considered as appropriate. The majority of responses were assessed as Grade A, signifying a substantial availability of scientific evidence to guide treatment and support recommendations encompassing diagnostics, physiotherapy, electrophysical agents, oral and injective medical therapies, as well as surgical interventions for primary SS. Conclusions: A consensus regarding the conservative and surgical treatment of primary SS could be achieved at a national level. This consensus sets basis for evidence‐based clinical practice in the management of primary SS and can serve as a model for similar initiatives and adaptable guidelines in other European countries and potentially on a global scale. Level of Evidence: Level I. [ABSTRACT FROM AUTHOR]

Background: PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations. Objective: We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC. Patients and Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs). Results: Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected. Conclusions: In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC. [ABSTRACT FROM AUTHOR]

Purpose of the Review: This paper delves into the emerging realm of T1 mapping, exploring recent innovations and their relevance across several cardiac diseases. Recent Findings: T1 mapping with cardiovascular magnetic resonance (CMR) imaging has emerged as a valuable tool for cardiac disease evaluation, offering diagnostic, therapeutic, and prognostic insights. Tissue characterization using parametric mapping methods holds the promise of identifying and quantifying both focal and diffuse changes in myocardial structure, which cannot be adequately assessed through late gadolinium enhancement (LGE). Summary: CMR imaging, particularly LGE, has enhanced cardiac tissue characterization. However, the detection of diffuse interstitial fibrosis remains challenging, necessitating the exploration of alternative techniques. T1 mapping could probably represent a game changer in the evaluation of diffuse and focal fibrosis in multiple cardiovascular conditions. [ABSTRACT FROM AUTHOR]

Background: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. Methods: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. Results: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. Conclusions: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most commonly diagnosed cancer but the management of advanced prostate cancer remains a therapeutic challenge, despite the survival benefits imparted by several therapeutic discoveries targeting different molecular pathways. The mechanisms of resistance to androgen deprivation and tumour progression to lethal metastatic variants are often regulated by androgen receptor (AR) bypass mechanisms and/or neuroendocrine differentiation. Moreover, recent data also suggested the involvement of adaptive and innate infiltrated immune cells in prostate tumour progression. Improvements in cancer genome analyses contributed to a better understanding of antitumour immunity and provided solutions for targeting highly cancer-specific neoantigens generated from somatic mutations in individual patients. In this review, we investigated the current knowledge on the interplay between cancer development and the complex mechanisms of immune regulation. Particularly, we focused on the role of tumour immune microenvironment, generally characterised by strong barriers for immunotherapy, and we discuss the rationale for the potential application of single agent and combination immune-targeting strategies that could lead to improved outcomes. Careful selection based on clinical and genomic factors may allow identification of patients who could benefit from this treatment approach in multiple settings (from localised to advanced prostate tumour) and in different histological subtypes (from adenocarcinoma to neuroendocrine prostate cancer). [ABSTRACT FROM AUTHOR]

This systematic review is aimed to evaluate the effects of balneotherapy with thermal mineral water for managing the symptoms and signs of osteoarthritis located at any anatomical site. The systematic review was conducted according to the PRISMA Statement. The following databases were consulted: PubMed, Scopus, Web of Science, Cochrane Library, DOAJ and PEDro. We included clinical trials evaluating the effects of balneotherapy as a treatment for patients with osteoarthritis, published in English and Italian language, led on human subjects. The protocol was registered in PROSPERO. Overall, 17 studies have been included in the review. All of these studies were performed on adults or elderly patients suffering from osteoarthritis localized to knees, hips, hands or lumbar spine. The treatment assessed was always the balneotherapy with thermal mineral water. The outcomes evaluated were pain, palpation/pressure sensibility, articular tenderness, functional ability, quality of life, mobility, deambulation, ability to climb stairs, medical objective and patients' subjective evaluation, superoxide dismutase enzyme activity, serum levels of interleukin-2 receptors. The results of all the included studies agree and demonstrated an improvement of all the symptoms and signs investigated. In particular, pain and quality of life were the main symptoms evaluated and both improved after the treatment with thermal water in all the studies included in the review. These effects can be attributed to physical and chemical-physical properties of thermal mineral water used. However, the quality of many studies resulted not so high due and, consequently, it is necessary to perform new clinical trial in this field using more correct methods for conducting the study and for processing statistical data. [ABSTRACT FROM AUTHOR]

The Berry curvature provides a powerful tool to unify several branches of science through their geometrical aspect: topology, energy bands, spin and vector fields. While quantum defects–phase vortices and skyrmions–have been in the spotlight, as rotational entities in condensates, superfluids and optics, their dynamics in multi-component fields remain little explored. Here we use two-component microcavity polaritons to imprint a dynamical pseudospin texture in the form of a double full Bloch beam, a conformal continuous vortex beyond unitary skyrmions. The Berry curvature plays a key role to link various quantum spaces available to describe such textures. It explains for instance the ultrafast spiraling in real space of two singular vortex cores, providing in particular a simple expression–also involving the complex Rabi frequency–for their intricate velocity. Such Berry connections open new perspectives for understanding and controlling highly-structured quantum objects, including strongly asymmetric cases or even higher multi-component fields. Phase vortices and skyrmions manifest as rotational entities in condensates, superfluids, and optics, typically revealed by the analysis of the Berry curvature. Via two-component microcavity polaritons, the authors imprint a dynamical pseudospin texture to the emitted light, generating a continuous vortex with two ultrafast spiraling cores. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to evaluate the caffeinated Energy Drinks (EDs) consumption among a large sample of Italian undergraduates and its association with some of the major lifestyle risk factors. Methods: Students attending twelve public Italian universities were involved between October 2021 and May 2022. Information on socio-demographic characteristics, ED consumption, and on health-related behaviors of participants was collected by the use of a web-based questionnaire. Results: A total of 2165 students participated in the study and 15.2% of them reported having used caffeinated EDs in the last six months, mainly once a month (41.5%). In comparison with non-users, ED users showed a higher proportion of males (p < 0.001) and a higher father's educational level (p = 0.003), came mainly from Northern universities (p = 0.004) and life sciences degree courses (p < 0.001). Besides, ED users reported higher BMI values (p = 0.003), more particular dietary regimens (p < 0.001), higher levels of weekly moderate–vigorous physical activity (p < 0.001) and participation in sports (p < 0.001) and in team sports (p = 0.003), and higher proportion of smokers (p < 0.001) and alcohol drinkers (p = 0.005). ED use was negatively related with female gender (OR 0.546; 95% CI 0.374–0.798), the Mediterranean diet (OR 0.587; 95% CI 0.362–0.951) and coming from the center of Italy (OR 0.500; 95% CI 0.275–0.909) and positively associated with tobacco smoke (OR 1.712; 95% CI 1.176–2.492) and participation in a team sport (OR 1.686; 95% CI 1.051–2.707). Conclusion: These findings could encourage figures engaged in education to increase the students' awareness on this issue in order to prevent the excessive use of EDs and associated unhealthy behaviors, especially in the most interested subgroups. [ABSTRACT FROM AUTHOR]

Background: Immuno-oncology combinations have achieved survival benefits in patients with metastatic renal cell carcinoma (mRCC). Objective: The ARON-1 study (NCT05287464) was designed to globally collect real-world data on the use of immuno-combinations as first-line therapy for mRCC patients. Patients and Methods: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of mRCC treated with first-line immuno-combination therapies were retrospectively included from 47 International Institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit (OCB). Results: A total of 729 patients were included; tumor histology was clear-cell RCC in 86% of cases; 313 patients received dual immuno-oncology (IO + IO) therapy while 416 were treated with IO-tyrosine kinase inhibitor (IO + TKI) combinations. In the overall study population, the median OS and PFS were 36.5 and 15.0 months, respectively. The median OS was longer with IO+TKI compared with IO+IO therapy in the 616 patients with intermediate/poor International mRCC Database Consortium (IMDC) risk criteria (55.7 vs 29.7 months; p = 0.045). OCB was 84% for IO+TKI and 72% for IO + IO combination (p < 0.001). Conclusions: Our study may suggest that immuno-oncology combinations are effective as first-line therapy in the mRCC real-world context, showing outcome differences between IO + IO and IO + TKI combinations in mRCC subpopulations. Clinical Trial Registration: NCT05287464. [ABSTRACT FROM AUTHOR]

Purpose: To assess caregivers’ characteristics and influence of the presence or absence of the caregiver on clinical outcomes of older (≥70 years) metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (ABI) or enzalutamide (ENZ). Methods: Patients from the Meet-URO 5 ADHERE study were assessed with a 5-item caregiver evaluation questionnaire focusing on the presence, age, degree of kinship, working status and qualification of the caregiver. We investigated the association between the presence of a caregiver and the clinical characteristics and outcomes of enrolled patients. Results: No differences were found in the main clinical characteristics between patients with or without a caregiver, except for a lower median G8 score (p = 0.0453) in the caregiver group. A longer radiographic PFS (rPFS) was observed in the group without a caregiver, with a trend towards more prolonged overall survival (OS) in the same group. Conclusion: Our work suggests a detrimental effect of caregivers in managing older mCRPC patients treated with ABI or ENZ, especially those identified as frail by the geriatric G8 screening score. Further work is needed to identify and address patients’ vulnerability areas, which could have a detrimental effect on prognosis. [ABSTRACT FROM AUTHOR]

In everyday activities, humans move alike to manipulate objects. Prior works suggest that hand movements are built by a limited set of basic building blocks consisting of a set of common postures. However, how the low dimensionality of hand movements supports the adaptability and flexibility of natural behavior is unknown. Through a sensorized glove, we collected kinematics data from thirty-six participants preparing and having breakfast in naturalistic conditions. By means of an unbiased analysis, we identified a repertoire of hand states. Then, we tracked their transitions over time. We found that manual behavior can be described in space through a complex organization of basic configurations. These, even in an unconstrained experiment, recurred across subjects. A specific temporal structure, highly consistent within the sample, seems to integrate such identified hand shapes to realize skilled movements. These findings suggest that the simplification of the motor commands unravels in the temporal dimension more than in the spatial one. [ABSTRACT FROM AUTHOR]

We study the freeze-in of gravitationally interacting dark matter in extra dimensions. Focusing on a minimal dark matter candidate that only interacts with the SM via gravity in a five-dimensional model we find that a large range of dark matter and Kaluza-Klein graviton masses can lead to the observed relic density. The preferred values of the masses and the strength of the interaction make this scenario very hard to test in terrestrial experiments. However, significant parts of the parameter space lead to warm dark matter and can be tested by cosmological and astrophysical observations. [ABSTRACT FROM AUTHOR]

The neutral anomalies in B decays are analysed in terms of the tree-level exchange of an axion-like-particle (ALP), within the effective field theory framework. The complete two-dimensional parameter space for ALP couplings to electrons and muons is explored. The solutions to RK and to the two energy bins of R K ∗ are confronted with the impact of ALP exchange on other observables (meson oscillations, leptonic and semileptonic decays of B mesons including searches for new resonances, astrophysical constraints), as well as with the theoretical domain of validity of the effective theory. Solutions based on ALPs heavier than B mesons, or lighter than twice the muon mass, are shown to be excluded. In contrast, the exchange of on-shell ALPs provides solutions to RK and/or R K ∗ within 2σ sensitivity which are technically compatible with those constraints. Furthermore, a “golden ALP mass” is identified at the frontier between the two energy bin windows of R K ∗ , which could simultaneously explain these two R K ∗ anomalies together with RK; this calls for the convenience of different energy binning which would easily clear up this (unlikely) possibility. The impact of smearing on data analysis is also discussed. When loop effects are taken into account, the solutions found can be in addition compatible with the data on the g − 2 of the electron but not simultaneously with those on the g − 2 of the muon. Furthermore, loop effects may require fine-tunings of some coupling values. [ABSTRACT FROM AUTHOR]

Purpose: The remodeling process following tooth extraction can be observed as horizontal and vertical bone reduction of the alveolar ridge. Preservation procedures such as alveolar ridge preservation (ARP) aim to maintain the 3D volume of the extraction site. This retrospective study analyzed differences in the hard and soft tissue changes in patients treated with either spontaneous healing or ARP. Methods: After tooth extraction, the patients were treated either by spontaneous socket healing (SH group) or with ARP using a xenograft and a resorbable membrane (ARP group). One week before and 6 months after extraction, the patients underwent cone beam computed tomography. A volumetric analysis was performed by superimposing the digital models of the two time points. Intraoral radiography was performed after implant placement, upon prosthesis delivery, and at 1-year post-treatment. An esthetic assessment was conducted using the Pink Esthetic Score (PES). The patients’ overall satisfaction with the implant restoration was investigated at 12 months. Results: Intragroup comparisons revealed significant differences between baseline and the 6-month follow-up in both groups at the measured locations (1 mm, 3 mm, and 5 mm below the most coronal aspect of the alveolar ridge) showing a reduction of the horizontal width (P < 0.05). Additionally, after treatment, the horizontal width at 1 mm was significantly different in the SH and ARP groups (P < 0.001), with mean changes of 2.03 ± 0.54 mm and 0.86 ± 0.49 mm, respectively. ARP was associated with an increased PES (11.6 ± 2.2) and a reduction in patients requiring additional grafting procedures in subsequent treatment phases (9% vs 26%; P = 0.11). Conclusions: In both groups, significant horizontal and vertical bone loss was observed after the extraction. ARP can reduce linear and volumetric shrinkage of the alveolar ridge, leading to improved outcomes. It can also simplify implant restoration. [ABSTRACT FROM AUTHOR]

Purpose: Acute kidney injury (AKI) frequently complicates hospitalization and is associated with in-hospital mortality (IHM). It has been reported a seasonal trend in different clinical conditions. The aim of this study was to evaluate the possible relationship between seasons of the year and IHM in elderly hospitalized patients with AKI. Methods: We selected all admissions complicated by AKI between 2000 and 2015 recorded in the Italian National Hospital Database. ICD-9-CM code 584.xx identified subjects with age ≥ 65 years and age, sex, comorbidity burden, need of dialysis treatment and IHM were compared in hospitalizations recorded during the four seasons. Moreover, we plotted the AKI observed/expected ratio and percentage of mortality during the study period. Results: We evaluated 759,720 AKI hospitalizations (mean age 80.5 ± 7.8 years, 52.2% males). Patients hospitalized with AKI during winter months had higher age, prevalence of dialysis-dependent AKI, and number of deceased patients. In whole population IHM was higher in winter and lower in summer, while the AKI observed/expected ratio demonstrated two peaks, one in summer and one in winter. Logistic regression analysis demonstrated that parameters such as age, autumn, winter, comorbidity burden were positively associated with IHM. Conclusion: We conclude that a seasonality exists in AKI, however, relationship between seasons and AKI could vary depending on the aspects considered. Both autumn and winter months are independent risk factors for IHM in patients with AKI regardless of age, sex and comorbidity burden. On the contrary, summer time reduces the risk of death during hospitalizations with AKI. [ABSTRACT FROM AUTHOR]

Background: Early colorectal cancer (ECC) is defined as T1NXM0 colorectal cancer (CRC). Although a non-negligible number of T1-CRCs presents metastatic lymph-nodes, local excision is increasingly proposed as alternative to radical resection. Several criteria have been suggested to identify low-risk T1-CRC, but recommendations on this topic are still heterogeneous. This study aims to identify criteria associated with N+ T1-CRC, to select patients to undergo (or not) local excision. Methods: A retrospective analysis of demographic, clinical, and histology criteria of 122 consecutive T1-CRC patients undergoing radical resection at Parma University Hospital between 2000 and 2018 has been performed. Results: Lymph-node metastasis (LNM) was observed in 15/122 patients (12.3%). No LNM was observed among well-differentiated (G1) tumors (0/37), while 10/65 (15.4%) G2 cases as well as 5/20 (25%) G3 patients presented LNM. G1 was associated with absence of LNM (p = 0.013). After excluding G1 patients, the rate of N + T1-CRC was 17.6% (15/85). LNM was observed in 4/8 (50%) patients with lymphovascular invasion (LVI) and in 11/77 (14.2%) without LVI. LVI resulted being associated with LNM (p < 0.042). LNM was reported in 28.3% of cases with a tumor infiltration >4.25 mm (13/46), compared to 5.1% in cases with an infiltration ≤4.25 mm (2/39) (p = 0.012). In Cox regression analysis, the higher hazard ratio (HR) was reported for the LVI + and infiltration >4.25 mm (HR 24.849). Conclusions: In patients with ECC (pT1NXM0), good differentiation (G1), absence of lymphovascular invasion (LVI-), and tumor radial infiltration ≤4.25 mm may allow performing local resection and avoiding radical surgery. [ABSTRACT FROM AUTHOR]

The treatment landscape for metastatic castration-resistant prostate cancer has evolved extremely in recent years and several drug classes are now available. Nonetheless, the lack of validated predictive biomarkers makes therapeutic choice and the best sequential approach difficult. The location of the metastatic site could be a valid criterion for choosing among the treatment options available. Although bone remains the most frequent metastatic site and a possible target for many drugs, recent data suggest a profound shift in the disease spectrum with visceral metastases increasing incidence. This review describes the presently available and ongoing therapies for patients with CRPC and bone metastases, focusing on the role of bone metastases as a possible driver for selecting therapies in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Data from the "Trattamento Ormonale nello Scompenso CArdiaco" (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry. Methods: At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM. Results: 337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV–V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels. Conclusions: Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF. [ABSTRACT FROM AUTHOR]

Background: Drug-drug interactions are a major concern in oncology and may potentially affect the outcome of patients with cancer.Objective: In this study, we aimed to determine whether the concomitant use of statins, metformin, or proton pump inhibitors affects survival in patients with metastatic renal cell carcinoma treated with first-line combination therapies.Methods: Medical records of patients with documented metastatic renal cell carcinoma between January 2016 and November 2021 were reviewed at 17 participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. Patients were assessed for overall survival, progression-free survival, and overall clinical benefit. Univariate and multivariate analyses were conducted to explore the association of variables of interest with overall survival and progression-free survival.Results: A total of 304 patients receiving dual immunotherapy (51%) or immunotherapy/vascular endothelial growth factor-tyrosine kinase inhibitor (49%) combinations were eligible for inclusion in this retrospective study. Statin use was a significant prognostic factor for longer overall survival in a univariate analysis (hazard ratio 0.48, 95% confidence interval 0.26-0.87; p = 0.016) and a multivariate analysis (hazard ratio 0.48, 95% confidence interval 0.31-0.74; p < 0.001) and was significantly associated with an overall clinical benefit (83% in statin users vs 71% in non-users; p = 0.045). Otherwise, the use of metformin or proton pump inhibitors did not affect the outcome of these patients.Conclusions: Our study suggests a prognostic impact of statin use in patients receiving first-line immuno-oncology combinations. The mechanism of this interaction warrants further elucidation. [ABSTRACT FROM AUTHOR]

Rationale: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin's influence on mood and cognition. Objectives: We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers. Methods: Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected. Results: Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F1,51 = 4.99, p = 0.03), but also an increase in anxiety scores (F1,51 = 5.37, p = 0.02). An exploratory analysis of the females' subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured. Conclusions: We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies. Trial registration: Clinicaltrials.gov: NCT04652089. [ABSTRACT FROM AUTHOR]

Purpose: Sepsis is a life-threating organ dysfunction caused by a dysregulated host response to infection. Being a time-dependent condition, the present study aims to compare a recently established score, i.e., modified quick SOFA (MqSOFA), with other existing tools commonly applied to predict in-hospital mortality. Methods: All cases of sepsis and septic shock consecutively observed at St. Anna University Hospital of Ferrara, Italy, from January 2017 to December 2018 were included in this study. Each patient was evaluated with MqSOFA, lactate assay, NEWS and qSOFA. Accurate statistical and logistic regression analyses were applied to our database. Results: A total of 1001 consecutive patients with sepsis/septic shock were retrieved. Among them, 444 were excluded for incomplete details about vital parameters; thus, 556 patients were eligible for the study. Data analysis showed that MqSOFA, NEWS and lactate assay provided a better predictive ability than qSOFA in terms of in-hospital mortality (p < 0.001). Aetiology-based stratification in 5 subgroups demonstrated the superiority of NEWS vs. other tools in predicting fatal outcomes (p = 0.030 respiratory, p = 0.036 urinary, p = 0.044 abdominal, p = 0.047 miscellaneous and p = 0.041 for indeterminate causes). After Bonferroni's correction, MqSOFA was superior to qSOFA over respiratory (p < 0.001) and urinary (p < 0.001) aetiologies. Age was an independent factor for negative outcomes (p < 0.001). Conclusions: MqSOFA, NEWS and lactate assay better predicted in-hospital mortality compared to qSOFA. Since sepsis needs a time-dependent assessment, an easier and non-invasive score, i.e., MqSOFA, could be used to establish patients' outcome in the emergency setting. [ABSTRACT FROM AUTHOR]

Lichenoid reactions are one of the most frequently observed toxicities with anticancer agents and, recently, a rapid emergence of immunotherapies in oncology has hastened the need to better characterize their unique toxicity profiles, particularly for less common skin toxicities, including anogenital lichen sclerosus et atrophicus (LSA). This case series describes four patients with advanced cancer (one melanoma, two lung cancers, and one kidney tumor) developing LSA lesions while receiving an immunotherapy. Medical records from 2017 to 2020 were retrospectively reviewed. Two patients received pembrolizumab, anti-programmed cell death-1 (PD-1), one nivolumab, anti-programmed cell death-1 (PD-1), and one ipilimumab, an immune checkpoint inhibitor. LSA emerged after a median of 3 months (range, 2–4 months) from starting immunotherapy. All LSA cases were grade 2. Three cases occurred on the penis and one case on the anus. All patients improved after a specific treatment for LSA, and no LSA-related antineoplastic treatment interruption/life-threatening condition were reported. To date, this is the first case series of LSA lesions associated with immunotherapy. Early LSA recognition and management is helpful in cancer patients on immunotherapy allowing a long survival and treatment response. [ABSTRACT FROM AUTHOR]

Bound states in the continuum (BICs)1–3 are peculiar topological states that, when realized in a planar photonic crystal lattice, are symmetry-protected from radiating in the far field despite lying within the light cone4. These BICs possess an invariant topological charge given by the winding number of the polarization vectors5, similar to vortices in quantum fluids such as superfluid helium and atomic Bose–Einstein condensates. In spite of several reports of optical BICs in patterned dielectric slabs with evidence of lasing, their potential as topologically protected states with theoretically infinite lifetime has not yet been fully exploited. Here we show non-equilibrium Bose–Einstein condensation of polaritons—hybrid light–matter excitations—occurring in a BIC thanks to its peculiar non-radiative nature, which favours polariton accumulation. The combination of the ultralong BIC lifetime and the tight confinement of the waveguide geometry enables the achievement of an extremely low threshold density for condensation, which is reached not in the dispersion minimum but at a saddle point in reciprocal space. By bridging bosonic condensation and symmetry-protected radiation eigenmodes, we reveal ways of imparting topological properties onto macroscopic quantum states with unexplored dispersion features. Such an observation may open a route towards energy-efficient polariton condensation in cost-effective integrated devices, ultimately suited for the development of hybrid light–matter optical circuits.Using a patterned waveguide, a Bose–Einstein condensate of polaritons is realized in a bound state in the continuum, with a low condensation threshold density that occurs at a dispersion saddle point. [ABSTRACT FROM AUTHOR]