Impact of cultural and genetic structure on food choices along the Silk Road.

The complex interplay between genetics, culture, and environment forms an individual's biology, influencing their behavior, choices, and health. However, to what extent information derived from this intertwined network could be quantitatively summarized to provide a glance at an individual's lifestyle is difficult to say. Here, we focused on dietary preferences as cultural proxies and genome-wide data of 543 individuals from six historical Silk Road countries: Georgia, Armenia, Azerbaijan, Uzbekistan, Kazakhstan, and Tajikistan. These lands favored the dispersal of innovations, foods, and DNA halfway across Eurasia, thus representing an ideal subject to explore interactions of cultural factors and genetic ancestry. We used discriminant analysis of principal components to infer cultural clusters, where mixed memberships are allowed. Five different clusters emerged. Of these, clusters 1 and 3, driven by aversion to pork and alcoholic beverages, mirrored genetic admixture patterns with the exception of Azerbaijan, which shares preferences supported by Islamic culture with Eastern countries. Cluster 3 was driven by protein-rich foods, whose preference was significantly related to steppe pastoralist ancestry. Sex and age were secondary clustering factors, with clusters formed by male and young individuals being related to alcohol preference and a reduced liking for vegetables. The soft clustering approach enabled us to model and summarize the individual's dietary information in short and informative vectors, which show meaningful interaction with other nondietary attributes of the studied individuals. Encoding other cultural variables would help summarize an individual's culture quantitatively, thus ultimately supporting its inclusion as a covariate in future association studies.

Prolonged 14-day continuous infusion of high-dose ifosfamide for patients with relapsed and refractory high-grade osteosarcoma: a retrospective multicentre cohort study.

BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. PATIENTS AND METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities. CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.

Surgical treatment of popliteomeniscal fascicles tears is associated with better patient-reported outcome measures. A systematic review and meta-analysis.

PURPOSE: Popliteomeniscal fascicles (PMFs) are a component of the popliteal hiatus complex in the knee, and their injury primarily affects young athletes participating in sports activities involving twisting movements. The identification of PMFs tears presents a challenge, often accompanied by lateral pain and a locking sensation. The objective of this systematic review (SR) and meta-analysis is to enhance the suspicion and recognition of PMFs tears, aiming to facilitate the treatment of this condition, particularly in symptomatic young patients. METHODS: A comprehensive search, focused on studies examining PMFs injuries and their treatment, was conducted in four databases, PubMed, Scopus, Embase, and Web of Science. The ROBINS-I tool was used to evaluate the risks of bias. The PRISMA flow diagram was used to conduct the research and select the included studies. A meta-analysis was conducted for the Lysholm score, the Tegner Activity Scale, and the subjective IKDC score. The present SR and meta-analysis was registered on PROSPERO. RESULTS: Five clinical studies were included in the final analysis, comprising 96 patients. All the patients underwent a preoperative MRI assessment and a diagnostic arthroscopy to detect the PMFs tears, with a subsequent surgical procedure either open or arthroscopically performed. Surgery was associated with the resolution of symptoms. A statistically significant improvement in the Lysholm score (p: 0.0005) and the subjective IKDC score (p: 0.003) after the surgical procedure with respect to the preoperative evaluation was found. CONCLUSION: This SR and meta-analysis showed a significant improvement in the Lysholm score and subjective IKDC score following surgery for PMFs tears. However, controversy persists regarding the optimal surgical approach, with current literature favoring arthroscopic procedures. LEVEL OF EVIDENCE: IV.

Healthcare Professional Communication on Sexual Health: A Report from the Italian Working Group on Adolescents and Young Adults with Cancer.

BACKGROUND: Sexual function is an important concern for adolescent and young adult (AYA) with cancer. The aim of this study was to explore the attitude of Italian health care professionals who deal with AYA patients with cancer toward sexual health communication. MATERIALS AND METHODS: A 11-question survey was developed by the AIOM (Associazione Italiana di Oncologia Medica) and AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) AYA workgroup and sent to AIOM and AIEOP members. RESULTS: The sample comprised 360 respondents, 54.2% AIEOP and 45.8% AIOM members. Eighty percent were physicians, 14.5% nurses, 4.7% psychologists, and 0.8% other professionals. Medical oncologists are more used to investigate about AYA sexual health than pediatric oncologists (58.2% vs. 46.2%), even if pediatrics more frequently refer patients to specific and shared protocol (40% vs. 26.1%). Both AIOM and AIEOP participants mostly talk about sexual health only on request or occasionally (78.8% and 79%, respectively). Clinician-reported barriers to communication identified in this study are lack of preparation and embarrassment for both the categories, plus the presence/interference of parents for pediatrics and lack of time for medical oncologists. Overall, less than 5% of clinicians in our survey received specific training on potential sexual health issues in AYA patients with cancer and only 2% felt adequately prepared to speak about it. CONCLUSION: Sexual health is a key component of comprehensive care for AYA with cancer during treatments. This study highlighted the need of Italian providers for specific training and guidelines on sex-related health issues encountered by AYA patients.

Off-label and compassionate use of targeted anticancer therapies: The experience of an Italian pediatric cancer center.

INTRODUCTION: In Europe, despite recent advances in clinical development, most of the drugs currently used to treat childhood cancers are adult medicines, prescribed outside of the authorized indication. In this context, a monocentric retrospective cohort analysis was conducted, evaluating pediatric, adolescent, and young adult patients affected by onco-hematologic disease, treated with targeted therapies used off-label or as compassionate use. METHODS: The analysis was conducted on 45 patients aged less than or equal to 30 years with cancer, having received at least one targeted therapy prescribed as off-label or compassionate use at a large Italian pediatric center between January 1, 2016 and June 30, 2021. Data collected included information on the patient and tumor, data on off-label/compassionate treatment, and data on safety and efficacy. RESULTS: Total 25 out of 45 patients treated with off-label or compassionate targeted therapies were affected by onco-hematological diseases. Overall, 22 out of the 52 agents (42%) were prescribed in patients with relapsed neoplasm and 39% (20/52) in patients with refractory diseases. Complete response was observed in more than half (27/52) of treatments. At least one adverse reaction occurred in 76% (n = 22) of agents administered to patients with onco-hematological tumor and in 43% (n = 10) of agents prescribed to patients with solid tumor. CONCLUSION: This work aims to provide a snapshot of off-label and compassionate use prescriptions in a large Italian pediatric cancer center. This study confirms that targeted agents for unauthorized indications are often prescribed in pediatric patients with cancer, especially after disease relapse and that these treatments are mostly tolerable and effective.

Effectiveness of Workplace Health Promotion (WHP) interventions in university employees: a scoping review.

Workplace Health Promotion (WHP) interventions proved to be effective in several workplace contexts. Currently, the effectiveness of such interventions in the academic workplace is lacking, albeit evidence suggests similar patterns to those occurring in other workplace sectors. The aim of this study was to review WHP interventions in the university workplace that led to improve health- and work-related outcomes. Articles were selected using Pubmed, Web of Science, Scopus, Embase, PsycInfo, Cinhal and FSTA, using search strings focused on health- and/or work-related outcomes and involving University WHP interventions published between January 2010 and July 2021. The majority of the 12 studies selected reported positive results in their individuality, especially regarding health-related outcomes [biological such as weight loss, physical activity, mental health and lifestyle habits] and work-related outcomes concerning improvements either for the employee or for the working system. Studies on economic advantage and Return on Investment were limited and reported contrasting results. In conclusion, we have highlighted how the studies on effectiveness of WHP interventions in the university context are few and heterogeneous and need to be encouraged further research in order to build specific guidelines that are effective.

Interventions concerning prevention promotion in the workplace, involving activities targeting lifestyle habits, nutrition and/or physical activity as well as general wellbeing, are growing and becoming more common due to their benefits on health and work outcomes. The aim of this review was to investigate the effectiveness of such interventions in the university workplace context to help create directed guidelines for their correct implementation in this setting. Although it was difficult to draw peculiar conclusions due to the heterogeneity of the programs described in the studies, the overall positivity of the results and the perspective university environment, outlook that the implementation of multicomponent and multilevel interventions would improve employees' wellness and favor universities' welfare.

Highly cross-linked polyethylene versus conventional polyethylene in primary total knee arthroplasty: comparable clinical and radiological results at a 10-year follow-up.

PURPOSE: Highly crosslinked polyethylene (HXLPE) was introduced in total knee arthroplasty (TKA) to reduce wear and consequent revisions for loosening due to conventional polyethylene (CPE) wear. This study aims to analyse whether HXLPE is as safe as CPE and could improve the TKA clinical and radiological results in a long-term follow-up. METHODS: This retrospective study included all consecutive starting series of 223 patients with severe primary knee osteoarthritis (OA), with a minimum follow-up of 10 years treated between July 1st, 2007, and July 31st, 2010. After excluding patients who did not respect the inclusion and exclusion criteria, 128 patients were included in the analysis of this study. The patients were then divided into two groups according to the type of polyethylene (PE) implanted: CPE or HXLPE liners. All patients were evaluated for clinical and radiological parameters, causes and revision rates related to the type of PE implanted. RESULTS: HXLPE appears to be as safe as CPE in TKA, reporting no higher revisions for osteolysis, prosthesis loosening, infection, and mechanical failure. Nevertheless, no statistically significant differences were found between the two groups in the clinical and radiological outcomes evaluated. CONCLUSIONS: Clinical, radiological results, and revision rates are similar between HXLPE and CPE in TKA after 10 years of follow-up, although HXLPE benefits remain controversial. LEVEL OF EVIDENCE: III.

Outcome of liver transplantation with grafts from brain-dead donors treated with dual hypothermic oxygenated machine perfusion, with particular reference to elderly donors.

Prompted by the utilization of extended criteria donors, dual hypothermic oxygenated machine perfusion (D-HOPE) was introduced in liver transplantation to improve preservation. When donors after neurological determination of death (DBD) are used, D-HOPE effect on graft outcomes is unclear. To assess D-HOPE value in this setting and to identify ideal scenarios for its use, data on primary adult liver transplant recipients from January 2014 to April 2021 were analyzed using inverse probability of treatment weighting, comparing outcomes of D-HOPE-treated grafts (n = 121) with those preserved by static cold storage (n = 723). End-ischemic D-HOPE was systematically applied since November 2017 based on donor and recipient characteristics and transplant logistics. D-HOPE use was associated with a significant reduction of early allograft failure (OR: 0.24; 0.83; p = .024), grade ≥3 complications (OR: 0.57; p = .046), comprehensive complication index (-7.20 points; p = .003), and improved patient and graft survival. These results were confirmed in the subset of elderly donors (>75-year-old). Although D-HOPE did not reduce the incidence of biliary complications, its use was associated with a reduced severity of ischemic cholangiopathy. In conclusion, D-HOPE improves postoperative outcomes and reduces early allograft loss in extended criteria DBD grafts.

Colorectal cancer chemotherapy: can sex-specific disparities impact on drug toxicities?

PURPOSE: Given the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy. METHODS: We performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity. RESULTS: According association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005). CONCLUSION: According to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients' biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.

A deep learning approach for Spatio-Temporal forecasting of new cases and new hospital admissions of COVID-19 spread in Reggio Emilia, Northern Italy.

BACKGROUND: Since February 2020, the COVID-19 epidemic has rapidly spread throughout Italy. Some studies showed an association of environmental factors, such as PM10, PM2.5, NO2, temperature, relative humidity, wind speed, solar radiation and mobility with the spread of the epidemic. In this work, we aimed to predict via Deep Learning the real-time transmission of SARS-CoV-2 in the province of Reggio Emilia, Northern Italy, in a grid with a small resolution (12 km × 12 km), including satellite information. METHODS: We focused on the Province of Reggio Emilia, which was severely hit by the first wave of the epidemic. The outcomes included new SARS-CoV-2 infections and COVID-19 hospital admissions. Pollution, meteorological and mobility data were analyzed. The spatial simulation domain included the Province of Reggio Emilia in a grid of 40 cells of (12 km)2. We implemented a ConvLSTM, which is a spatio-temporal deep learning approach, to perform a 7-day moving average to forecast the 7th day after. We used as training and validation set the new daily infections and hospital admissions from August 2020 to March 2021. Finally, we assessed the models in terms of Mean Absolute Error (MAE) compared with Mean Observed Value (MOV) and Root Mean Squared Error (RMSE) on data from April to September 2021. We tested the performance of different combinations of input variables to find the best forecast model. FINDINGS: Daily new cases of infection, mobility and wind speed resulted in being strongly predictive of new COVID-19 hospital admissions (MAE = 2.72 in the Province of Reggio Emilia; MAE = 0.62 in Reggio Emilia city), whereas daily new cases, mobility, solar radiation and PM2.5 turned out to be the best predictors to forecast new infections, with appropriate time lags. INTERPRETATION: ConvLSTM achieved good performances in forecasting new SARS-CoV-2 infections and new COVID-19 hospital admissions. The spatio-temporal representation allows borrowing strength from data neighboring to forecast at the level of the square cell (12 km)2, getting accurate predictions also at the county level, which is paramount to help optimise the real-time allocation of health care resources during an epidemic emergency.

Gender-specific side effects of chemotherapy in pancreatic cancer patients.

Pancreatic carcinoma incidence showed a significant increase in men over the last few years and the prognosis remains poor. Patients are treated with different pharmacological plans with no evidence about gender-specific adverse effects. We aimed to investigate differences in the incidence of chemotherapy side effects in the treatment of pancreatic cancer, to provide insights toward a personalized assistance based in individual needs. The sample population is composed of 207 patients. Regression model highlighted the predictive role of female gender for alopecia, constipation, hand-foot syndrome, and epigastric pain. Also, considering single therapeutic schemes, gender differences have been reported. Moreover, evaluating the effect of age, a general reduced risk of toxicity has been reported in younger patients. To personalize chemotherapy and increase patient survival rate and life quality during the therapy, gender medicine and pharmacology studies are recommended.

Rehabilitation in children and adolescents undergoing stem cell transplantation: A pilot study focused on motor performance.

OBJECTIVES: The aim of this pilot trial is evaluating the preliminary effectiveness of two in-hospital interventions in the maintenance of motor performance in children/adolescents undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives investigated the interventions' feasibility, impact on fatigue and to what degree the subjects' maintained their ankle dorsiflexion range of movement (ROM), functional mobility, muscle strength and flexibility. METHODS: This trial included 5- to 18-year-old participants, affected by oncological and non-oncological diseases during hospitalisation for autologous/allogenic HSCT. The subjects were assigned to an exercise group (EG), or a counselling group based on a cluster model based on inpatient timeframe. The EG subjects performed strengthening, stretching and aerobic exercises for 30 min/5 days a week. Both groups followed rehabilitation counselling indications (RCI), 7 days a week. RESULTS: Forty-nine participants were enrolled (median age = 12.9 years) (EG n = 36). In both groups the participants maintained their baseline motor performance and ankle ROM, and the children/adolescents and parents reduced their levels of fatigue. However, the interventions were not effective in maintaining strength. CONCLUSION: In maintaining the subjects' motor performance, the RCI results are significant because they pave the way for the application in clinical practice contexts where there are poor rehabilitation resources. Clinical Trials registration NCT03842735.

Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic - A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI).

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

Comparable results between crosslinked polyethylene and conventional ultra-high molecular weight polyethylene implanted in total knee arthroplasty: systematic review and meta-analysis of randomised clinical trials.

PURPOSE: Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly crosslinked polyethylene (HXLPE) has been proven effective in reducing osteolysis and loosening revisions while improving long-term survival and performance in total hip arthroplasty; nevertheless, this superiority is not demonstrated in TKA. The aim of this systematic review and meta-analysis was to examine whether HXLPE improved overall survival and postoperative functional and radiological outcomes compared to conventional polyethylene (CPE) in TKA. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a literature search of five databases (PubMed, Medline, Scopus, Science Direct and Embase) was made. A PICOS model was performed. The initial screening identified 2541 studies. Each eligible clinical article was analysed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE). Only randomised clinical trials (RCTs) of LoE 1 and 2 were included. The methodological quality of the articles was assessed using the Risk of Bias 2 (RoB 2) tool. RESULTS: Six clinical studies were included in the final study. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2285 knees were included. Eight outcomes (total reoperations, reoperations for prosthesis loosening and infections, radiolucent lines, osteolysis, mechanical failure, postoperative KSS knee score and function score) were analysed. For none of them, a statistically significant difference was found about the superiority of HXLPE over CPE (p > 0.05). CONCLUSIONS: There were no statistically significant differences between HXLPE and CPE for TKA concerning clinical, radiological, and functional outcomes; nevertheless, HXLPE did not show higher failure rates or complications and can be safely used for TKA. LEVEL OF EVIDENCE: II.

Psychosocial factors associated with complicated grief in caregivers during COVID-19: Results from a preliminary cross-sectional study.

The COVID-19 pandemic has changed how end-of-life ceremonies are performed, affecting grief processing and bereavement experiences. In this study, caregivers of patients who died with COVID-19 during the first wave of the pandemic were asked to complete an online survey designed to detect psychosocial factors associated with the presence of complicated grief (CG). The results show CG present in 48.4% of caregivers. The marital and cohabitant status during lockdown, the perceived sense of guilt and depression levels were significantly associated with the presence of CG, whereas attendance at the funeral and social support were found to be significant protective factors.

Multiple origins and modularity in the spatiotemporal emergence of cerebellar astrocyte heterogeneity.

The morphological, molecular, and functional heterogeneity of astrocytes is under intense scrutiny, but how this diversity is ontogenetically achieved remains largely unknown. Here, by quantitative in vivo clonal analyses and proliferation studies, we demonstrate that the major cerebellar astrocyte types emerge according to an unprecedented and remarkably orderly developmental program comprising (i) a time-dependent decline in both clone size and progenitor multipotency, associated with clone allocation first to the hemispheres and then to the vermis(ii) distinctive clonal relationships among astrocyte types, revealing diverse lineage potentials of embryonic and postnatal progenitors; and (iii) stereotyped clone architectures and recurrent modularities that correlate to layer-specific dynamics of postnatal proliferation/differentiation. In silico simulations indicate that the sole presence of a unique multipotent progenitor at the source of the whole astrogliogenic program is unlikely and rather suggest the involvement of additional committed components.

Oversampling and replacement strategies in propensity score matching: a critical review focused on small sample size in clinical settings.

BACKGROUND: Propensity score matching is a statistical method that is often used to make inferences on the treatment effects in observational studies. In recent years, there has been widespread use of the technique in the cardiothoracic surgery literature to evaluate to potential benefits of new surgical therapies or procedures. However, the small sample size and the strong dependence of the treatment assignment on the baseline covariates that often characterize these studies make such an evaluation challenging from a statistical point of view. In such settings, the use of propensity score matching in combination with oversampling and replacement may provide a solution to these issues by increasing the initial sample size of the study and thus improving the statistical power that is needed to detect the effect of interest. In this study, we review the use of propensity score matching in combination with oversampling and replacement in small sample size settings. METHODS: We performed a series of Monte Carlo simulations to evaluate how the sample size, the proportion of treated, and the assignment mechanism affect the performances of the proposed approaches. We assessed the performances with overall balance, relative bias, root mean squared error and nominal coverage. Moreover, we illustrate the methods using a real case study from the cardiac surgery literature. RESULTS: Matching without replacement produced estimates with lower bias and better nominal coverage than matching with replacement when 1:1 matching was considered. In contrast to that, matching with replacement showed better balance, relative bias, and root mean squared error than matching without replacement for increasing levels of oversampling. The best nominal coverage was obtained by using the estimator that accounts for uncertainty in the matching procedure on sets of units obtained after matching with replacement. CONCLUSIONS: The use of replacement provides the most reliable treatment effect estimates and that no more than 1 or 2 units from the control group should be matched to each treated observation. Moreover, the variance estimator that accounts for the uncertainty in the matching procedure should be used to estimate the treatment effect.

Excess of all-cause mortality is only partially explained by COVID-19 in Veneto (Italy) during spring outbreak.

BACKGROUND: Italy has been the first European country to be affected by the COVID-19 epidemic which started out at the end of February. In this report, we focus our attention on the Veneto Region, in the North-East of Italy, which is one of the areas that were first affected by the rapid spread of SARS-CoV-2. We aim to evaluate the trend of all-cause mortality and to give a description of the characteristics of the studied population. METHODS: Data used in the analyses were released by the majority of municipalities and cover the 93% of the total population living in the Veneto Region. We evaluated the trend of overall mortality from Jan.01 to Jun.30. 2020. Moreover we compared the COVID-19-related deaths to the overall deaths. RESULTS: From March 2020, the overall mortality rate increased exponentially, affecting males and people aged > 76 the most. The confirmed COVID-19-related death rate in the Veneto region between Mar.01 and Apr.302020 is 30 per 100,000 inhabitants. In contrast, the all-cause mortality increase registered in the same months in the municipalities included in the study is 219 per 100,000 inhabitants. CONCLUSIONS: COVID-19 has a primary role in the increase in mortality but does not entirely explain such a high number of deaths. Strategies need to be developed to reduce this gap in case of future waves of the pandemic.

The COVID-19 Worsening Score (COWS)-a predictive bedside tool for critical illness.

OBJECTIVES: To evaluate the accuracy of a new COVID-19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness. METHODS: We conducted a single-center retrospective cohort development and internal validation study of the COVID-19 Worsening Score (COWS), based on a combination of the previously validated COVID-GRAM score (GRAM) variables and LUS. Adult COVID-19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables. RESULTS: Among 274 COVID-19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52-2.77; area under the curve [AUC], 0.63; 95% CI 0.676-0.634). The newly developed COVID-19 Worsening Score relies on five variables to classify high- and low-risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%-98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97-11.1). CONCLUSIONS: COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high-risk patients.

Should We Consider Deep Brain Stimulation Discontinuation in Late-Stage Parkinson's Disease?

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of "poor stimulation responders" among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. METHODS: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale <50 in medication on/stimulation on condition) treated with STN-DBS for at least 5 years underwent a crossover, double-blind, randomized evaluation of acute effects of stimulation. Physicians, caregivers, and patients were blinded to stimulation conditions. Poor stimulation responders (MDS-UPDRS part III change <10% between stimulation on/medication off and stimulation off/medication off) maintained the stimulation off/medication on condition for 1 month for open-label assessment. RESULTS: Thirty-six patients were included. The acute effect of stimulation was significant (17% MDS-UPDRS part III), with 80% of patients classified as "good responders." Seven patients were classified as "poor stimulation responders," and the stimulation was switched off, but in 4 cases the stimulation was switched back "on" because of worsening of parkinsonism and dysphagia with a variable time delay (up to 10 days). No serious adverse effects occurred. CONCLUSIONS: The vast majority of late-stage PD patients (92%) show a meaningful response to STN-DBS. Effects of stimulation may take days to disappear after its discontinuation. We present a safe and effective decisional algorithm that could guide physicians and caregivers in making challenging therapeutic decisions in late-stage PD. © 2020 International Parkinson and Movement Disorder Society.