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Rapid diagnostics provide actionable information for patient care at the time and site of an encounter with the health care system. The mainstay of infectious diseases care is early detection (case finding) and treatment completion, but for many, it is hard to identify positive individuals, as is the case of infection with low burden in schistosomiasis, a parasitic disease common in the tropics and subtropics. We developed a new, accurate, and fast Dot blot methodology (iDot) to indirectly detect Schistosoma mansoni in individuals with very low parasite burden using urine samples. Accuracy of 0.74 was obtained with a significant difference between negative and positive patients and a substantial agreement was found when iDot was compared with five available methods. Our analysis also revealed the superiority of iDot in detecting negative individuals from non-endemic sites, thus, presenting the lowest rate of false positives. This new method called iDot is convenient and suitable for qualitative and quantitative detection of schistosomiasis in individuals with low parasite burden.

Background Nursing home (NH) residents have been dramatically affected by COVID-19, with extremely high rates of hospitalization and mortality. Aims To describe the features and impact of an assistance model involving an intermediate care mobile medical specialist team (GIROT, Gruppo Intervento Rapido Ospedale Territorio) aimed at delivering “hospital-at-nursing home” care to NH residents with COVID-19 in Florence, Italy. Methods The GIROT activity was set-up during the first wave of the pandemic (W1, March–April 2020) and became a structured healthcare model during the second (W2, October 2020–January 2021). The activity involved (1) infection transmission control among NHs residents and staff, (2) comprehensive geriatric assessment including prognostication and geriatric syndromes management, (3) on-site diagnostic assessment and protocol-based treatment of COVID-19, (4) supply of nursing personnel to understaffed NHs. To estimate the impact of the GIROT intervention, we reported hospitalization and infection lethality rates recorded in SARS-CoV-2-positive NH residents during W1 and W2. Results The GIROT activity involved 21 NHs (1159 residents) and 43 NHs (2448 residents) during W1 and W2, respectively. The percentage of infected residents was higher in W2 than in W1 (64.5% vs. 38.8%), while both hospitalization and lethality rates significantly decreased in W2 compared to W1 (10.1% vs 58.2% and 23.4% vs 31.1%, respectively). Discussion Potentiating on-site care in the NHs paralleled a decrease of hospital admissions with no increase of lethality. Conclusions An innovative “hospital-at-nursing home” patient-centred care model based on comprehensive geriatric assessment may provide a valuable contribution in fighting COVID-19 in NH residents.

To investigate the test-retest reliability and measurement error of the Brazilian version of the modified Gait Efficacy scale (mGES-Brazil) in individuals who have had stroke.The mGES-Brazil was applied on two occasions, five to seven days apart, in a research laboratory setting. Test-retest reliability and measurement error, which included the standard error of measurement (SEM), smallest detectable change (SDC), and analysis of the limits of agreement by the Bland-Altman plots, were examined.Fifty individuals who have had stroke (18 men), with a mean age of 64 ± 11 years, were evaluated. All individual items showed good reliability (Intra-class Correlation Coefficient - ICCThe mGES-Brazil demonstrated to be reliable to be applied within clinical and research contexts for the assessment of changes in walking confidence of individuals who have had stroke. Changes in mGES scores ≥8 points reflect real changes.

Background The COVID‐19 pandemic has put a strain on health systems. Predictors of adverse outcomes need to be investigated to properly manage COVID‐19 patients. The Braden Scale (BS), commonly used for the assessment of pressure ulcer risk, has recently been proposed to identify frailty. Objective To investigate the predictive utility of the BS for prediction of in‐hospital mortality in a cohort of COVID‐19 patients admitted to non‐ICU wards. Methods We conducted a retrospective single‐center cohort study evaluating all patients with SARS‐CoV‐2 infection consecutively admitted over a 2‐month period (from March 6 to May 7, 2020) to the COVID‐19 general wards of our institution. Demographic, clinical, and nursing assessment data, including admission BS, were extracted from electronic medical records. Univariable and multivariable logistic regression models were used to explore the association between the BS score and in‐hospital death. Results Braden Scale was assessed in 146 patients (mean age 74.7 years; 52% males). On admission, 46 had a BS ≤ 15, and 100 patients had a BS > 15. Mortality among patients with BS ≤ 15 was significantly higher than in patients with BS > 15 (45.7% vs. 16%; p

Functional mobility (FM) is the ability of people to move in different environments, including at home, at work, and in the community, in order to perform functional activities or tasks, independently and safely. Objective: The aim of the present study was to investigate which motor and/or non-motor symptoms (severity of the motor symptoms, depressive symptoms, and fatigue) have the greatest impact on FM assessed by Modified Parkinson Activity Scale (mPAS) in individuals with Parkinson’s disease (PD). Method: The outcome of interest was FM assessed by mPAS, which includes 14 activities covering three domains (chair transfers, gait akinesia, and bed mobility). Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, Beck Depression Inventory (BDI), and Parkinson’s Disease Fatigue Scale-16 (PFS-16) were used. Results: Forty-four individuals (age: 65±11 years) with PD (PD duration: 7±4 years) were eligible to take part in this cross-sectional, exploratory study. The motor symptoms alone explained 36% (F= 17.85, p

Background The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences. Study Design and Methods The effects of two types of RCC (RCC‐A, RCC‐B) on transfusion regime were compared in a non‐blinded, prospective, randomized, two‐period, and crossover clinical trial. RCC‐A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC‐B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion‐dependent thalassemia (TDT). Results RCC‐A contained 63.9 (60.3–67.8) grams of hemoglobin per unit (median with 1st and 3rd quartile), RCC‐B 54.5 (51.0–58.2) g/unit. Fifty‐one patients completed the study. With RCC‐B, the average pre‐transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7–16.3) days, the number of RCC units transfused per year 39.3 (35.4–47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC‐A, the average pre‐transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0–18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1–42.5) (−11.4%, effect size −1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p

Background Falls, which are common events after stroke, may lead to activity limitations and increased dependence. It is important to identify which commonly employed clinical measures could differentiate individuals, who are fallers from the non-fallers. Aim To investigate specific cut-off values of clinical measures that could discriminate fallers and non-fallers individuals with chronic stroke. Method This cross-sectional study involved 105 community-dwelling individuals with stroke. The primary outcome was report of falls over the last six months. The clinical predictors included measures of mobility (walking speed, stair ascent/descent cadences, time to perform the Timed Up and Go test, and ABILOCO) and the Fall Efficacy Scale - International (FES-I) scores. To identify which measures were able to detect between-group differences, independent Student's t-tests were employed. For measures which were able to discriminate fallers from the non-fallers, the Receiver Operating Characteristics (ROC) and the Area Under the ROC Curve (AUC) were calculated. Results Out of the 105 participants (61 men), 41% reported falls over the previous 6 months. Stair ascent cadence, ABILOCO, and FES-I scores significantly differentiated the groups, but only the FES-I demonstrated acceptable discriminatory ability (AUC = 0.71). The optimal FES-I cut-off score was 28 points (sensitivity = 0.71; specificity = 0.57; positive predictive value = 51%; and negative predictive value = 74%). Conclusions The FES-I demonstrated good discriminatory ability to classify individuals with chronic stroke, who were fallers from the non-fallers. The use of the established cut-off value of 28 points is recommended and may help clinical reasoning and decision-making in stroke rehabilitation.

Background Aerobic exercise improves endothelial function and arterial stiffness after myocardial infarction (MI), but the effects of isometric exercise on cardiovascular parameters are still uncertain. We aimed to assess the effects of one session of aerobic or isometric exercise on flow-mediated dilation (FMD) and pulse wave velocity (PWV) in post-MI volunteers undergoing percutaneous coronary intervention (PCI). Methods Twenty post-MI patients undergoing PCI were randomized to aerobic (AE, n = 10) or isometric (IE, n = 10) exercise groups. We evaluated cardiac structure and function (echocardiographic); carotid plaque presence (ultrasound). FMD and PWV were measured 10 min before and 10 min after the intervention: a single session of moderate-intensity AE (30 min; ratings 12–14 on Borg’s scale or 50–60% HRreserve) or handgrip IE (four two-minute bilateral contractions; 30% maximal voluntary contraction; 1-min rest). Generalized estimating equations (Bonferroni post-hoc) was used to assess differences (p ≤ 0.050). Results FMD improved only in the AE group (Δ = 4.9%; p = 0.034), with no difference between groups after exercise. Even after adjustment (for baseline brachial artery diameter) the effectiveness of AE remained (p = 0.025) with no change in the IE group. PWV was slightly reduced from baseline in the AE group (Δ = 0.61 m/s; p = 0.044), and no difference when compared to the IE group. Peripheral vascular resistance decreased in AE versus IE (p = 0.050) and from baseline (p = 0.014). Conclusions Vascular measurements (FMD and PWV) improved after a single session of AE. There are apparently no benefits following a session of IE. Trial registration http://www.clinicaltrials.gov and ID number NCT04000893.

The aim of this study (NCT04343053) is to investigate the relationship between platelet activation, myocardial injury, and mortality in patients affected by Coronavirus disease 2019 (COVID-19). Fifty-four patients with respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled as cases. Eleven patients with the same clinical presentation, but negative for SARS-CoV-2 infection, were included as controls. Blood samples were collected at three different time points (inclusion [T1], after 7 ± 2 days [T2] and 14 ± 2 days [T3]). Platelet aggregation by light transmittance aggregometry and the circulating levels of soluble CD40 ligand (sCD40L) and P-selectin were measured. Platelet biomarkers did not differ between cases and controls, except for sCD40L which was higher in COVID-19 patients (p = .003). In COVID-19 patients, P-selectin and sCD40L levels decreased from T1 to T3 and were higher in cases requiring admission to intensive care unit (p = .004 and p = .008, respectively). Patients with myocardial injury (37%), as well as those who died (30%), had higher values of all biomarkers of platelet activation (p

Introduction: Studies have shown that a hemodynamic-guided therapy improves the post operative outcomes of high-risk patients.This study, evaluated if a short period through minimally invasive hemodynamic monitoring, pressure recording analytical method (PRAM), on admission to a post-cardiac surgery step-down unit (SDU), may identify patients at higher risk of 6-month adverse events after cardiac surgery. Methods: From December 2016-May 2017,173 patients were admitted in SDU within 24-48 hours of major cardiac surgery procedure, and submitted to clinical, laboratoristic and echocardiographic evaluation and a 1-hour PRAM recording to obtain a "biohumoral snapshot" of individual patient’s.156 173 patients (17 patients were lost at follow-up) were phone interviewed six months after surgery,to evaluate, as a composite end-point, the adverse events during follow-up. A multivariable logistic regression analysis was used to identify a model clinical-biohumoral (CBM) and clinical-biohumoral hemodynamics (CBHM). Results: No data from past clinical history and no conventional risk score (EuroScore II, STS score)independently predicted the risk of 6-month major events in our study. The risk of adverse events at six-month follow-up was directly related, in the CBM, to sustained post-operative cardiac arrhythmias, higher values of NT-proBNP and of arterial pH; inversely related to values of hs-C-reactive protein (hs-CRP) and, in the CBHM, to low values of cardiac cycle efficiency (CCE) and dP/dtmax. Conclusion: Our study although limited by its observational nature and by the limited number of patients enrolled, showed that a short period of minimally invasive hemodynamic monitoring increased the accuracy to identify patients at major risk of mid-term events after cardiac surgery.

Introduction COVID-19, a respiratory illness due to SARS-CoV-2 coronavirus, was first described in December 2019 in Wuhan, rapidly evolving into a pandemic. Smoking increases the risk of respiratory infections; thus, cessation represents a huge opportunity for public health. However, there is scarce evidence about if and how smoking affects the risk of SARS-CoV-2 infection. Methods We performed an observational case–control study, assessing the single-day point prevalence of smoking among 218 COVID-19 adult patients hospitalized in seven Italian nonintensive care wards and in a control group of 243 patients admitted for other conditions to seven COVID-19-free general wards. We compared proportions for categorical variables by using the χ 2 test and performed univariate and multivariate logistic regression analyses to identify the variables associated with the risk of hospitalization for COVID-19. Results The percentages of current smokers (4.1% vs 16%, p = .00003) and never smokers (71.6% vs 56.8%, p = .0014) were significantly different between COVID-19 and non-COVID 19 patients. COVID-19 patients had lower mean age (69.5 vs 74.2 years, p = .00085) and were more frequently males (59.2% vs 44%, p = .0011). In the logistic regression analysis, current smokers were significantly less likely to be hospitalized for COVID-19 compared with nonsmokers (odds ratio = 0.23; 95% confidence interval, 0.11–0.48, p < .001), even after adjusting for age and gender (odds ratio = 0.14; 95% confidence interval, 0.06–0.31, p < .001). Conclusions We reported an unexpectedly low prevalence of current smokers among COVID-19 patients hospitalized in nonintensive care wards. The meaning of these preliminary findings, which are in line with those currently emerging in literature, is unclear; they need to be confirmed by larger studies. Implications An unexpectedly low prevalence of current smokers among patients hospitalized for COVID-19 in some Italian nonintensive care wards is reported. This finding could be a stimulus for the generation of novel hypotheses on individual predisposition and possible strategies for reducing the risk of infection from SARS-CoV-2 and needs to be confirmed by further larger studies designed with adequate methodology.

Carbapenem consumption is a major driver for selection and spread of carbapenem-resistant Enterobacterales (CRE). We assessed the impact of a carbapenem-focused multimodal antimicrobial stewardship program (ASP) in the internal medicine unit of a medium-size acute-care hospital.We compared the percentage of inappropriate carbapenem prescriptions and the proportion of carbapenem treated patients registered in a 12-month pre-intervention and in a 24-month post-intervention period by using an interrupted time series analysis. The consumption of carbapenems, expressed in defined daily doses (DDD), was also assessed. As a secondary objective, the incidence of infections by carbapenem-resistant Klebsiella pneumoniae (CRKP) and the percentage of CRKP invasive isolates in the same time periods were compared.After the ASP intervention, the mean monthly percentage of inappropriate carbapenem prescriptions dropped from 59% to 25%, and the mean monthly proportion of carbapenem treated patients decreased from 3% to 1%. The interrupted time series analysis confirmed a significant decrease in the percentage of inappropriate carbapenem prescriptions (-41.6%, p = 0.0262) and in the proportion of carbapenem treated patients (-2.1%, p 0.0001). Carbapenem consumption decreased from 5.2 to 1.6 DDD x 100 patient-days. The incidence of CRKP infections remained unchanged (29.1 × 100,000 patient-days vs 28.9 × 100,000 patient-days, p = 0.9864) and the percentage of CRKP invasive isolates decreased, though not significantly, from 36.4% to 13.3% (p = 0.3478).The implementation of a carbapenem-focused ASP was effective at limiting the inappropriate use of carbapenems and was associated with a significant decrease in carbapenem consumption. Such effects were sustained during a 24-month post-intervention period.

Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

Certain muscle groups strength directly influence walking speed (WS), and the lower strength of the paretic side is significantly associated with lower WS of individuals after stroke. Studies that have investigated the association between the average of lower limb strength and the WS in individuals are scarce. Therefore, it is important to determine whether the strength could explain walking performance due to some muscle weakness could be compensated by the strength of others, mainly because all muscles act in group, not isolated. Objective: To investigate the association between WS and lower limbs muscle strength, and to identify whether an individual muscle group or the average strength of lower limb would best predict WS and walking speed reserve (WSR) in individuals with stroke. Methods: Sixty-four community-dwelling individuals with chronic stroke have their maximum isometric strength (hip flexors/extensors/abductors, knee flexors/extensors, and ankle dorsiflexors/plantarflexors) and self-selected and fast WS (10m walk test) measured. WSR was considered as the difference between the fast and self-selected speed. Results: Average strength of the paretic limb accounted for 19% and 20% of the variance in self-selected and fast WS, respectively. Plantarflexor strength of the paretic, knee and hip flexors of the non-paretic side explained alone 27% of the WSR scores and plantarflexor strength of the paretic side alone explained 15%.Conclusion: Average muscle strength of the paretic side contributed to self-selected and fast WS. Plantarflexor strength of the paretic side, knee and hip flexors of the non-paretic side contributed with the WSR of chronic stroke individuals.

Background The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. For all confirmed or suspected cases of COVID-19, data about concomitant disease, ongoing therapies, and comorbidities were also reported. Results A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort twenty-six patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. 125 of 12807 patients (1.0%) with exposure to a patient with COVID-19 under quarantine or active health surveillance, were reported. Conclusion The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen "cytokine storm" of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Background: Although numerous patient specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalasemic syndromes in COVID-19 patients remains poorly understood. Aims: We studied the outcomes of 137 COVID-19 patients with a history of Transfusion Dependent Thalassemia (TDT) and non-Transfusion Dependent Thalassemia (NTDT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalasemia. Results: The mean age of thalassemia patients included in our study was 41±16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 25% of thalassemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to the an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassemia group compared to the matched cohort with no history of thalassemia. Amongst thalassemia patients in general, the NTDT group exhibited a higher rate of hospitalization compared to the TDT group (p=0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the NTDT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassemia (either TDT or NTDT) was found to be independently associated with reduced all-cause mortality. Conclusions: The presence of thalassemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models. Trial Registration for sources of data extraction: NCT: 04334291, 04746066 Funding Statement: This study was funded by a non-conditioned grant from FUNDACION INTERHOSPITALARIA PARA LA INVESTIGACION CARDIOVASCULAR, FIC. (Madrid, Spain). This nonprofit institution had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the paper for publication. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the Ethics Committees in all of the centers involved (Banjarmasin, Bari, Cagliari, Catania, Ferrara, Gela, Genoa, Getafe, Guadalajara, Legan, Madrid, Mannheim, Milan, Monza, Naples, Olbia, Padua, Pavia, Ragusa, Rome, Salerno, Turin, Valladolid and Verona).

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents.

Background Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients’ health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients’ reported health instruments for use in routine clinical practice. Methods At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. Results Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p

Purpose: To evaluate the awareness of ophthalmologists about assessing the mental health of patients and usefulness of the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) survey. Methods: This web-based survey was performed in 2020 at an eye hospital in Saudi Arabia. Participants included ophthalmologists and physicians. Participants were queried on the need to assess mental health of patients, usefulness of the screening tool, and barriers to assessment. Their responses were graded on a Likert scale and Rasch analysis was performed. Results: Of the 100 participants, 72 were aware of assessing mental health of eye patients and 82 expressed about limited skills for such assessment. The median score for perceived usefulness of the PHQ-9 as screening tool to suspect depression was −1.0 (inter quartile range, −1.0: 0.0) [Mean Rasch score = −0.735]. The median score of perceived usefulness for the GAD-7 as screening tool to suspect anxiety was −1.0 (inter quartile range, −1.0: 0.0) [Mean Rasch score = −0.695]. The PHQ-9 related score was significantly correlated to “30–39 years” age group (Kruskal Wallis p = 0.04) and non-Saudi professionals (Mann Whitney p = 0.005). The GAD-7 related score was significantly correlated to non-Saudi professionals (Mann Whitney p = 0.04). The mental health related score was significantly and negatively correlated to the “40–59 years” age group (Kruskal Wallis p = 0.04). Conclusions: Although awareness of mental health assessment was high, eyecare professionals felt with inadequate training for performing the screening. PHQ-9 seems to be more acceptable to screen for depression than GAD-7 for screening anxiety.

Background Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses. Objective In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea. Methods We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks. Discussion Our study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings. Trial registration ClinicalTrials.gov NCT04161339. Registered on November 2019.

Objective We describe the evolution of the electroclinical picture of patients with different types of self-limited epilepsy of childhood (SLEC) occurring at the same or at different times with or without atypical evolutions as well as patients with SLEC associated with childhood absence epilepsy (CAE). Material and methods A multicenter, retrospective, descriptive study was conducted evaluating patients with SLEC who had focal seizures of different types of SLEC including atypical evolutions as well as SLEC associated with absence epilepsy seen at eight Argentinian centers between April 2000 and April 2019. Of 7705 patients with SLEC, aged between 2 and 14 years (mean, 7.5 years), of whom 2013 were female and 5692 male (ratio, 1:2.8), 5068 patients had SLECTS, 2260 patients had self-limited childhood occipital epilepsy Panayiotopoulos type (SLE-P), 356 had self-limited childhood occipital epilepsy Gastaut type (SLE-G), and 21 had self-limited epilepsy with affective seizures (SLEAS). Electroclinical features typical of more than one SLEC syndrome were recognized in 998 (13 %) children. Results We recognized three well-defined groups of patients. The most frequent association was SLE-P and SLECTS, the paradigmatic type, but associations of SLE-P and SLE-G, SLECTS and SLE-G, and SLEAS and SLE-P or SLECTS were also recognized. The second-most-common association was SLEC and an atypical evolution. In this group, the most frequent combination was SLECTS with its atypical evolution, opercular status epilepticus, epileptic encephalopathy with continuous spike‐and‐waves during slow sleep, or Landau-Kleffner syndrome. SLE-P and SLE-G associated with an atypical evolution were also identified. The third, less-frequent group had SLECTS, SLE-P, or SLE-G associated with CAE. These cases support the concept that the different types of SLEC are part of a self-limited childhood seizure susceptibility syndrome. Conclusion Our study demonstrated that 13 % of our patients with SLEC have with different types of SLEC occurring at the same or at different times with or without atypical evolutions - i.e. CSWSS - as well as patients with SLEC associated with CAE, supporting the concept of the self-limited childhood seizure susceptibility syndrome.

Purpose A mild delay in gross motor milestones and walking age has been reported in infants with clubfoot. The influence of different treatments on motor development has been poorly investigated. Some parents and physical therapists express concern that the Ponseti method (PM) and its constraints (abduction brace, casts) would affect development more than the French physical therapy method (FM) due to greater immobilization and lesser stimulation. The purpose of this study was to evaluate achievement of three motor milestones (pull-to-standing, cruising and independent walking) in two groups of clubfoot patients treated at two experienced institutes respectively with the PM and FM. Methods In all, 52 consecutive infants (full-term at birth, mean age at beginning of treatment 24.3 days (sd 10), mean Dimeglio score 12 (sd 3.4)) were prospectively enrolled (26 patients per centre) and followed up to walking age recording milestones. Results The two groups were not different in terms of age at the beginning of treatment (p = 0.067) and rate of tenotomy. Age at tenotomy was significantly lower in the PM group (p = 0.000). Severity (p = 0.004) and number of bilateral cases (p = 0.012) were higher in the PM group. A non-significant difference was found for age of achievement of pull-to-standing (p = 0.109), cruising (p = 0.253) and independent ambulation (p = 0.349) between the two groups. Overall, milestones were achieved approximately two months later than normal population. Sex, severity, laterality and need of tenotomy were not found to significantly influence milestones. Conclusion Our results confirmed that infants with clubfoot are expected to have a minimum delay in motor development. Infants treated with the PM and those treated with the FM did not show significant differences in gross motor milestones achievement at walking age. Level of Evidence Level II – Prospective comparative therapeutic studies

PURPOSE To determine the Duke Activity Status Index (DASI) cut-off scores and verify if they would be able to discriminate between chronic stroke individuals, who had poor, from those who had good functional capacity (FC). MATERIALS AND METHODS Cross-sectional study, where 92 individuals with chronic stroke had their FC measured by DASI scores and were classified into community and non-community walkers. Both the receiver operating characteristic and the area under the curve were used to determine the best DASI cut-off values that could discriminate between individuals, who had poor, from those who had good FC. Binary logistic regression analysis is used to investigate the ability of DASI scores in predicting community walkers. RESULTS DASI cut-off value of 31.95 showed to be sensitive and specific to differentiate between individuals, who had poor from good FC. The regression analysis revealed that the chance of individuals, who had better FC (≥ 31.95) be community walkers was 10.69 (95%CI:4-32.75) times higher than that of those who had poor FC (

BACKGROUND The ABILOCO is a self-reported questionnaire, specific for individuals with stroke, for the assessment of ability of locomotion. The ABILOCO has been investigated using the Rasch model and has shown satisfactory measurement properties. However, its test-retest reliability has not been investigated. OBJECTIVE To investigate the test-retest reliability, that is, agreement, systematic and random variability of the ABILOCO Questionnaire in individuals with chronic stroke. DESIGN A test-retest reliability study. SETTING Research laboratory. PARTICIPANTS Thirty-one individuals (21 men and 10 women; mean age, 60 years), who had poststroke hemiparesis. INTERVENTION Not applicable. MAIN OUTCOME MEASUREMENT The ABILOCO was applied twice, on two occasions, 5 to 7 days apart. Test-retest reliability was investigated, as follows: agreement by the calculation of intraclass correlation coefficients (ICCs); systematic variability by the change in the mean; random variability by the standard error of measurement (SEM) and smallest real difference (SRD). RESULTS Two outliers were identified in the sample. The ICC values for the whole sample were 0.76 (CI 95% 0.56 to 0.88), whereas the SEM (SEM%) and SRD (SRD%) were 0.55 (21%) and 1.52 (58%), respectively. CONCLUSION The ABILOCO showed to be reliable to be applied within clinical and research contexts for the assessment of changes in locomotion ability of a group of individuals with chronic stroke. However, it appears to be less suitable to detect changes at individual levels. LEVEL OF EVIDENCE III.

Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Infant massage (IM) can be considered an early intervention program that leads to the environmental enrichment framework. The effectiveness of IM to promote neurodevelopment in preterm infants has been proved, but studies on infants with early brain damage are still lacking. The main aim of this study was to assess the feasibility, acceptability and usability of IM, carried out by parents at home, on infants at high risk for Cerebral Palsy. An IM daily diary and an ad hoc questionnaire, called Infant Massage Questionnaire Parent-Infant Experiences (IMQPE), were developed. IMQPE consisted of a total of 30 questions, divided into 5 areas. The parents were trained to carry out the IM with a home-based course, conducted by an expert therapist. The intensive IM program was set according to a defined daily length of at least 20 min, with a frequency of at least 5 days per week for a total of 8 weeks. Data collection consisted in the selection of the variables around the characteristics, both of the infants and the mothers, IM dosage and frequency, different body parts of the infants involved and IMQPE scores. Variable selection was carried out by minimizing the Bayesian Information Criteria (BIC) over all possible variable subsets. Nineteen high-risk infants, aged 4.83 ± 1.22 months, received IM at home for 8 weeks. The massage was given by the infants' mothers with a mean daily session dose of 27.79 ± 7.88 min and a total of 21.04 ± 8.49 h. 89.74% and 100% of mothers performed the IM for the minimum daily dosage and the frequency recommended, respectively. All the families filled in the IMQPE, with a Total mean score of 79.59% and of 82.22% in General Information on IM, 76.30% in Infant's intervention-related changes, 76.85% in IM Suitability, 79.07% in Infant's acceptance and 83.52% in Time required for the training. Different best predictors in mothers and in infants have been found. These data provide evidence of the feasibility of performing IM at home on infants at high risk for CP. Study registration: www.clinicaltrial.com (NCT03211533 and NCT03234959).

Objective We analyzed the records of 198 patients with West syndrome (WS) seen at a single pediatric neurology center in Argentina between June 2004 and June 2017. Five patients with infection-related spontaneous remission of the electroclinical manifestations were identified. Methods The following parameters were investigated: personal and family history, clinical characteristics of the seizures - mainly spasms - and EEG findings, type of treatment, and outcome. The inclusion criteria for WS were epileptic spasms (ES) in clusters, hypsarrhythmia, and mental deterioration. Infants with ES without hypsarrhythmia and other epileptic encephalopathies with ES were excluded. Results Five children, four boys and one girl, met the inclusion criteria of WS with spontaneous remission after a viral infection. The etiology of ES was unknown in four patients and one had a structural etiology. All patients had spontaneous remission of the ES and normalization of the EEG following acute upper respiratory infection in four and exanthema subitum in one; all of them had fever between 38.5 and 40 °C. Conclusion We report five patients with spontaneous remission of WS following acute viral infection, associated with a respiratory virus in four and exanthema subitum in one.

Objective Here we present cases of focal epilepsy with affective symptoms analyzing seizure characteristics, EEG pattern, treatment, and outcome. Methods A multicenter, descriptive, retrospective study was conducted evaluating 18 patients with self-limited epilepsy who presented with seizures with affective symptoms seen between April 2000 and April 2018 at eight Argentinian centers. Results Eighteen patients had focal seizures with affective symptoms; all of them had affective symptoms characterized by sudden fright or terror and screaming. Seizures started with manifestations of sudden fright or terror manifested by a facial expression of fear; consciousness was mildly impaired in 15/18 patients. Eleven of the patients also had autonomic manifestations, such as pallor, sweating, and abdominal pain. In addition, four of these 11 patients had ictus emeticus and one also presented with unilateral deviation of the eyes and head. Speech arrest, salivation, glottal noises, and chewing or swallowing movements were observed in 2/18 patients at the onset of the affective seizures. Two others also had mild asymmetric dystonic seizures involving both hands and arms. Three patients had tonic deviation of the mouth involving the lips and tongue as well pharyngeal and laryngeal muscles, resulting in anarthria and drooling. Two patients had brief hemifacial focal clonic seizures. Conclusion Affective manifestations associated or not with motor and/or autonomic manifestations and associated with typical EEG features of the idiopathic focal epilepsies of childhood is a particular presentation of self-limited focal epilepsy in childhood.

Early diagnosis of SARS-CoV-2 is essential to limiting the spread of the virus and managing infected patients during hospitalization. The sensitivity of RT-qPCR is contested by the fact that it is time-consuming, executed by trained technicians in proper environment for material extraction. Here, we evaluated the first SARS-CoV-2 antigen test recommended by the World Health Organization at September, 2020 as an alternative for immediate diagnosis of symptomatic and suspected patients at a hospital in Brazil during the epidemic peak. All patients were submitted to RT-qPCR and rapid antigen test using nasopharyngeal swabs rigorously collected at the same time. Demographics, baseline comorbidities, symptoms and outcomes were considered. Prediction analysis revealed that previous stroke, chronic obstructive pulmonary disease, desaturation and tachypnea were the most relevant determinants of the death of COVID-19 patients. Comparison between the rapid antigen test and RT-qPCR revealed an overall PPV of 97%, extended to 100% when performed between 4 and 15 days of symptoms, with an accuracy of 90-91% from days 1 to 7 and a ‘Substantial’ agreement. The rapid antigen test presented no inconclusive result. Among the discordant results and RT-qPCR inconclusives, 72% presented bilateral multifocal ground-glass opacities on imaging and other exams alterations. The median time to obtain RT-qPCR results was 83.6 hours, against 15 minutes for the rapid test, precious time for deciding on patient isolation and management. Knowledge of the risk factors and a rapid diagnosis upon patient admission is critical to reduce mortality of COVID-19 patients, hospital internal costs and in-hospital transmission.

ObjectiveTo describe the clinical, neurological, neuroimaging and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center.MethodsWe retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020.ResultsFifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2) or severe (3), pConclusionIn our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19.Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile.Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay.Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels.Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention.Clinical Trial Registration:ClinicalTrials.gov identifier NCT04343053.

Unlike age-matched men, premenopausal women benefit from cardiovascular protection. Estrogens protect against apoptosis of endothelial cells (ECs), one of the hallmarks of endothelial dysfunction leading to cardiovascular disorders, but the underlying molecular mechanisms remain poorly understood. The inflammatory cytokine TNFα causes EC apoptosis while dysregulating the Notch pathway, a major contributor to EC survival. We have previously reported that 17β-estradiol (E2) treatment activates Notch signaling in ECs. Here, we sought to assess whether in TNFα-induced inflammation Notch is involved in E2-mediated protection of the endothelium. We treated human umbilical vein endothelial cells (HUVECs) with E2, TNFα, or both and found that E2 counteracts TNFα-induced apoptosis. When Notch1 was inhibited, this E2-mediated protection was not observed, whereas ectopic overexpression of Notch1 diminished TNFα-induced apoptosis. Moreover, TNFα reduced the levels of active Notch1 protein, which were partially restored by E2 treatment. Moreover, siRNA-mediated knockdown of estrogen receptor β (ERβ), but not ERα, abolished the effect of E2 on apoptosis. Additionally, the E2-mediated regulation of the levels of active Notch1 was abrogated after silencing ERβ. In summary, our results indicate that E2 requires active Notch1 through a mechanism involving ERβ to protect the endothelium in TNFα-induced inflammation. These findings could be relevant for assessing the efficacy and applicability of menopausal hormone treatment, because they may indicate that in women with impaired Notch signaling, hormone therapy might not effectively protect the endothelium.

O tumor estromal gastrointestinal e uma neoplasia rara que afeta as celulas intersticiais cajais devido a disfuncao nos genes KIT ou PDGFRA. E considerado um tumor mesenquimal raro, mas comum no trato digestivo. O objetivo foi analisar um tratamento, epidemiologia e imunolocalizacao da proteina KIT e a atuacao do enfermeiro em relacao aos pacientes com GIST. Os criterios de inclusao foram laudos anatomopatologicos expedidos pelo servico de Anatomia Patologica da UNIFESP / EPM, a partir de 2010, com diagnostico de GIST. Vinte e uma escolhidos foram selecionados para analise imunohistoquimica do KIT. Entre as mulheres, 54,6% tinham mais de 60 anos e entre os homens 90%. A localizacao mais comum entre as mulheres foi o estomago com 63,7%, enquanto nos homens, o estomago teve a mesma porcentagem do intestino (40%). A imunohistoquimica mostrou positividade para C-KIT em 81,8% das mulheres e 90% dos homens. O tamanho medio da lesao foi de 5,58 cm e 3,8 cm nas mulheres e nos homens, respectivamente. A presenca de necrose foi verificada em 27,3% das mulheres e 30% dos homens. A morfologia mais prevalente foi uma celula fusiforme com aproximadamente 70% em mulheres e homens. Dos 21 casos, tres pacientes morreram, dois tiveram recidiva e, em cinco casos, foi realizado tratamento adjuvante com mesilato de imatinibe. Para a atuacao da enfermeira na frente do paciente com GIST, foi necessario confirmar a expressao da proteina KIT, o que permite um diagnostico diferencial. A analise da incidencia e da epidemiologia dessa populacao agregada aos enfermeiros agregar mais conhecimentos sobre esse tumor.

IntroduccionRecurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache in which secondary causes have first been excluded.Case ReportWoman, 52 years old, no comorbidity. In 2001 she presented sudden onset intense (8-10) throbbing left-sided unilateral headache that irradiated to the ipsilateral eye. The crisis lasted for 04 days, without nausea, vomit, photophobia or phonophobia. The intensity of the pain was alleviated with 1g of dipyrone and sodium naproxen in one daily oral dose of 550 mg, without analgesics excess. About two days after the end of the crisis the patient noticed left-sided palpebral ptosis and vertical diplopy preceded by retro-orbital ipsilateral twinge pain. The neurological exam showed fixed mydriasis, left-sided hypotropia and exotropia, compatible with the compromising of the 3rd ipsilateral nerve CN III. At the occasion, the patient was submitted to laboratorial exams of the cerebrospinal fluid, CT scan of the orbit and the skull, digital cerebral angiography of the four vessels, with no abnormalities. Cranial MRI showed enhanced cisternal segment of the left side third nerve. In 2004, 2006, 2008 and 2010 the patient presented the same clinical manifestations, having been treated with 1mg/kg methylprednisolone with full relief in 15 days. However, on the last episode in june of 2019, the patient presented only leftsided oculomotor manifestation, showing residual vertical diplopy after 06 months of pulse therapy. At the moment, she is taking 5 mg of Prednisone, via oral, in protocol of weaning off and ambulatorial follow up at the specialized center of cephalalgy.CommentsA case of RPON was described, diagnosed according to the ICHD-3. However, the patient presented unusual clinical aspects and age of symptoms onset. Unlike the descripitions found in literature, the first crisis occurred at the age 33. Besides, in the last event, only ocular manifestation ocurred, without cephalalgy, with persistent vertical diplopya, after pulse therapy and treatment with via oral steroids and 06 month- follow up. A case of RPON with atypical clinical manifestations and incomplete response to the treatment with steroids must be pointed out.

IntroductionCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent hereditary cause of brain ischemic small vessel disease (1). Migraine with aura (MA) is typically the presenting and most common clinical feature of CADASIL. The estimated prevalence of MA in CADASIL ranges from 20 to 40% (2).Case Report43-year-old woman, with previous history of hypertension, diabetes, and episodic migraine with visual aura, suffered three episodes of hemihyposthesia in 2016, 2017 and 2018 (one on her right and the other two on her left). In the last of these episodes, she reported worsening of the visual acuity of her right eye, and developed chronic migraine. Brain MRI showed extensive areas of confluent T2 hyperintensity in the white matter, as well as in the nucleocapsular and bilateral thalamic regions. In all three episodes the patient was treated with IV or oral corticosteroids and had partial improvement of the symptoms. The patient had familiar history of relatives who had suffered multiple strokes.DiscussionThe diagnosis of multiple sclerosis was firstly considered due to the evolution in clinical attacks and the response to corticotherapy. However, the patient’s family history, MRI findings and previous diagnosis of migraine with visual aurea lead to the suspicion of CADASIL. This diagnosis was ultimately confirmed through genetic testing that showed C> T variation in NOTCH3 gene. Migraine was successfully treated with greater occipital nerve blocks and topiramate.Final CommentCADASIL stroke-like attacks remain a therapeutic challenge. It is possible that corticosteroid treatment may benefit these patients by reducing the inflammatory process that results from blood-brain barrier breakdown. More studies are needed to evaluate the efficacy and safety of corticotherapy in this population.

BackgroundThe role of non-invasive positive pressure ventilation (NIPPV) in COVID-19 patients with acute hypoxemic respiratory failure (AHRF) is uncertain. This study was aimed to assess the effectiveness and safety of NIPPV in patients with COVID-19-associated AHRF admitted to non-ICU wards.MethodsWe retrospectively evaluated all COVID-19 patients consecutively admitted to the COVID-19 general wards of a medium-size Italian hospital, from March 6 to May 7, 2020. Healthcare workers (HCWs) caring for COVID-19 patients were monitored, undergoing naso-pharyngeal swab for SARS-CoV-2 in case of onset of COVID-19 symptoms, and periodic SARS-CoV-2 screening serology.ResultsOverall, 50 of 143 patients (mean age 74.6 years) were treated with NIPPV, and 22 (44%) were successfully weaned. Due to limited life expectancy, 25 (50%) of 50 NIPPV-treated patients received a “do not intubate” order. Among these, only 6 (24%) were weaned from NIPPV. Of the remaining 25 NIPPV-treated patients, 16 (64%) were successfully weaned, 9 (36%) underwent delayed endotracheal intubation and, among these, 3 (33.3%) died. NIPPV success was predicted by the use of corticosteroids (OR 15.4, p 0.013), the PaO2/FiO2 ratio measured 24-48 hours after NIPPV initiation (OR 1.02, p 0.015), and the presence of a “do not intubate” order (OR 0.03, p 0.020). During the study period, 2 of 124 (1.6%) HCWs caring for COVID-19 patients were diagnosed with mild SARS-CoV-2 infection.ConclusionsApart from patients with limited life expectancy, NIPPV was effective in a substantially high percentage of patients with COVID-19-associated AHRF. The risk of SARS-CoV-2 infection among HCWs was low.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais Objective: To explore the relationships between clinical measures and the ability to increase walking speed in ambulatory people with chronic stroke and to identify which measures would best predict walking speed reserve. Methods: An exploratory, cross-sectional study was conducted with 114 individuals with chronic stroke. The outcome of interest was walking speed reserve, defined as the difference between individuals’ comfortable and maximal walking speeds. Predictors were characteristics of the participants (age, sex, time since stroke, relative lower-limb dominance) and motor impairments (tonus, strength, and motor coordination). Results: The characteristics of the participants did not significantly correlate with walking speed reserve. All measures of motor impairments, i.e., tonus, strength, and motor coordination, were significantly correlated with walking speed reserve (p

To examine the acute effects of aerobic exercise (AE), resistance exercise (RE) or combined exercise (CE) on flow-mediated dilation (FMD), progenitor cells (PCs), endothelial progenitor cells (EPCs), oxidative stress markers and endothelial-cell derived microvesicles (EMVs) in patients with hypertension. This is a randomized, parallel-group clinical trial involving an intervention of one session of three different modalities of exercise. Thirty-three males (43 ± 2y) were randomly divided into three groups: a session of AE (n = 11, 40 min, cycle ergometer, 60% HRR); a session of RE (n = 11, 40 min, 4 × 12 lower limb repetitions, 60% 1-RM); or a session of CE (n = 11, 20-min RE + 20-min AE). FMD was assessed 10 min before and 10, 40 and 70 min post-intervention. Blood samples were collected at the same time points (except 40 min). FMD were similar in all groups and from baseline (within each group) after a single exercise bout (AE, RE or CE). At 70 min, RE group showed higher levels of PCs compared to the AE (81%) and CE group (60%). PC levels were reduced from baseline in all groups (AE: 32%, p = 0.037; RE: 15%, p = 0.003; CE: 17%, p = 0.048). The levels of EPCs, EMVs and oxidative stress were unchanged. There were no acute effects of moderate-intensity exercise on FMD, EPCs, EMVs and oxidative stress, but PCs decreased regardless of the exercise modality. Individuals with controlled hypertension do not seem to have impaired vascular function in response to a single exercise bout.

Few data are available on the validity of "Sepsis-3" criteria in identifying patients with sepsis in internal medicine wards (IMWs). Real-life data about this topic and on the prevalence of sepsis in IMWs could be useful for improving hospital organization.To assess the validity of "Sepsis-3" criteria in identifying patients with community-onset sepsis in IMWs. Secondary objectives: to evaluate the prevalence of these patients in IMWs and to compare "Sepsis-3" and "Sepsis-1" criteria.Multicenter, prospective, observational, cohort study, carried out in 22 IMWs of Tuscany (Italy). All patients admitted to each of the study centers over a period of 21-31 days were evaluated within 48 hours; those with clinical signs of infection were enrolled. The main outcome was in-hospital mortality.2,839 patients were evaluated and 938 (33%) met the inclusion criteria. Patients with sepsis diagnosed according to "Sepsis-3" were 522, representing 55.6% of patients with infection and 18.4% of all patients hospitalized; they were older than those without sepsis (79.4±12.5 vs 74.6±15.2 years, p0.001). In-hospital mortality was significantly higher in patients with sepsis compared to others (13.8% vs 4.6%; p0.001). "Sepsis-3" criteria showed greater predictive validity for in-hospital mortality than "Sepsis-1" criteria (AUROC=0.71; 95%CI, 0.66-0.77 vs 0.60; 95%CI 0.54-0.66; p=0.0038)."Sepsis-3" criteria are able to identify patients with community-onset sepsis in IMWs, whose prevalence and in-hospital mortality are remarkably high. Medical departments should adapt their organization to the needs for care of these complex patients.

Background Arterial hypertension has a direct association with endothelial dysfunction and major cardiovascular events. There is evidence showing the benefits of aerobic exercise on flow-mediated dilation (FMD) in hypertensive individuals but little is known about the effect of autonomic nervous system (ANS) activation on FMD of the brachial artery in response to different types of exercise in this specific population. This study aims to examine the effects of ANS activation on FMD of the brachial artery in response to exercise in hypertensive individuals following a session of different types of exercise including aerobic exercise (AE), resistance exercise (RE), or combined exercise (CE). Methods Thirty-nine hypertensive volunteers aged 35 to 55 years will be randomly assigned to two exercise sessions: AE (40 min on a cycle ergometer at 60% of HR reserve), RE (4 lower limb sets with 12 repetitions at 60% 1-RM for 40 min), or CE (RE for 20 min + AE for 20 min). Each exercise group will be randomized to receive either an α1-adrenergic blocker (doxazosin 0.05 mg/kg−1) or placebo. Ultrasound measurement of FMD is performed 10 min before and 10, 40, and 70 min after exercise. ANS activation is monitored using a Finometer and measurements are taken during 10 min before each FMD assessment. Arterial stiffness is assessed by pulse wave velocity (PWV) analysis using a Complior device. Discussion We expect to demonstrate the effect of ANS activation on FMD of the brachial artery in hypertensive individuals in response to different types of exercise. This study may give some insight on how to improve exercise prescription for hypertension management. Trial registration https://clinicaltrials.gov and ID "NCT04371757". Registered on May 1, 2020.

Background In January/2020 the respiratory disease caused by the new coronavirus was declared as an international public health emergency. In Brazil, until June 22nd there were 1,11 million confirmed cases. In this context, the Telehealth Network of Minas Gerais (TNMG), a large-scale public telehealth service, acted quickly to assist professionals and the population in coping with the disease, mainly in low resource settings. Aim To report the experience of a Brazilian public telehealth service in actions to manage COVID-19 and its impacts. Methods Experience report. Results The TNMG developed 15 infographics and 16 web lectures for health professionals and general population about key themes, such as respiratory syndromes, personal care and ventilatory support. Two of them were live, seen in real time by 13,422 professionals, mainly nurses (63.8%) and doctors (31.1%), from 45 medical specialties (most family physicians-34.0%), in all Brazilian states, especially the Southeast region (58.5%). All lectures were uploaded on TNMG's Youtube channel, each one reaching 5,300 viewers on average. Specific to support health professionals: 2 guidelines were developed - one for primary care units and other to emergency/intensive care; a category for offline (second opinion) teleconsultations was created for doubts about coronavirus; and a list with 39 Frequently Asked Questions (FAQs) was developed. For the general population: 65 FAQs were developed; a health team from a low resource setting was trained to provide online teleconsultations; and a chatbot was released to automatically answer COVID-19 related doubts and/or evaluate a user's health condition, indicating if emergency medical care was needed. All resources are freely available on TNMG's website and on its social networks. Conclusions Telehealth tools had a notable acceptance and were shown to be an effective way to disseminate information for professionals and lay population throughout the country. Key messages Telehealth tools have been proven to be an effective strategy to promote health education, for both professionals and the general population. Telemedicine plays a fundamental role on dealing with public health issues, especially on low resource settings.

Background: Hypertension remains highly prevalent in postmenopausal women, along with vascular dysfunction and increased oxidative stress. In such context, regular exercises, yoga practice, and slow breathing have been recommended to treat hypertension. However, the effects of the multiple components of yoga, including the respiratory techniques involved in the practice, on hypertension and on vascular and endothelial function have never been evaluated. Objective: This study aimed to investigate the additional effects of respiratory technique on vascular function and oxidative stress profile in hypertensive postmenopausal women (HPMWs) following yoga or stretching video classes. Study Design: Hypertensive postmenopausal women were recruited and randomized for 12 weeks, twice a week, of supervised yoga or stretching video classes of 75 min for 12 weeks associated or not with respiratory technique. Baseline and post-intervention measurements included pulse wave velocity (PWV), flow-mediated dilation (FMD), and oxidative stress parameters. Hypertensive postmenopausal women (59 ± 0.7 years) who ended the protocol were distributed into three groups: (1) control group (yoga or stretching, C, n = 14); (2) yoga + respiratory technique (Y+, n = 10); (3) stretching + respiratory technique (S+, n = 9). Results: Diastolic blood pressure and FMD [baseline: C: 6.94 ± 1.97%, Y+: 7.05 ± 1.65%, and S+: 3.54 ± 2.01% vs. post: C: 16.59 ± 3.46% (p = 0.006), Y+: 13.72 ± 2.81% (p = 0.005), and S+: 11.79 ± 0.99% (p = 0.0001)] have significantly increased in all groups when baseline and post-practice values were compared. However, resting heart rate and PWV [baseline: Y+: 10.44 ± 3.69 and S+: 9.50 ± 0.53 m/s vs. post: Y+: 9.45 ± 0.39 (p = 0.003) and S+: 8.02 ± 0.47 m/s (p = 0.003)] decreased significantly only in the Y+ and S+ groups (baseline vs. post). Systemic antioxidant enzyme activities (superoxide dismutase and catalase) increased in all groups, and hydrogen peroxide and lipoperoxidation reduced in Y+ and S+ (baseline vs. post). Conclusions: Twelve weeks of yoga or stretching video classes promoted positive changes in several outcomes generally regarded as cardiovascular risk factors in HPMWs, and these changes were even more pronounced by the association with respiratory technique.

Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil. Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

Because of Coronavirus Disease 2019 (COVID-19) pandemic, we were forced to cancel scheduled visits for nearly 150 patients followed in our heart failure (HF) outpatient clinic. Therefore, we structured a telephone follow-up, developing a standardized 23 item questionnaire from whom we obtained the Covid-19-HFscore. The questionnaire, was built to reproduce our usual clinical evaluation investigating patient’s social and functional condition, mood, adherence to pharmacological and non-pharmacological recommendations, clinical and hemodynamic status, pharmacological treatment and need to contact emergency services. The score was used as a clinical tool to define patients’ clinical stability and timing of the following telephone contact on the basis of the assignment to progressively increasing risk score groups: green (0-3), yellow (4-8) and red (≥9). Here we present our experience applying the score in the first thirty patients who completed the four weeks follow-up, describing baseline clinical characteristics and events that occurred in the period of observation., Summary: Here we present the development and preliminary results of the implementation of the Covid-19-HF score a new clinical tool for the telephonic management and follow-up of chronic heart failure patients during Covid-19 epidemic.

Purpose. COVID-19 displays a variety of clinical manifestations; in pauci-symptomatic patients olfactory (OD) and gustatory dysfunctions (GD) may represent the first or only symptom. To date, literature addressing these disorders is scarce. Aim of this study is to investigate the timing of recovery from OD and GD in a real-life COVID-19 population.Methods. We followed up by a phone interview the first 100 patients discharged a month earlier from three Italian non-intensive care wards.Results. All patients were Caucasian, mean age was 65 years, 60% were males. OD and GD were early symptoms reported by 29% and 41% of patients, respectively. Among the 42 symptomatic patients, the male/female ratio was 2:1; 83% reported an almost resolved dysfunction at follow-up. The recovery rate was not significantly different between males and females. The mean duration of OD and GD was 18 and 16 days, respectively. The mean recovery time from OD or GD resulted significantly longer for females than for males (26 vs 14 days, p=0.009). Among the 42 symptomatic, the mean age of males was significantly higher than that of females (66 vs 57 years, p=0.04), while the opposite was observed in the 58 asymptomatic patients (60 vs 73 years, p=0.0018).Conclusions. Recovery from OD or GD was rapid, occurring within 4 weeks in most patients. Chemosensory dysfunctions in women was less frequent, but longer lasting. The value of our study is its focus on a significantly older population than those previously described, and to add further data on gender differences.

Infants with perinatal brain injury are at high risk for Cerebral Palsy (CP). Progresses in detection of early signs of brain injury and of CP allow early intervention (EI) programs for improving the outcome of these infants. CareToy system (CT), developed within a European project (Trial Registration: NCT01990183), allows providing, by means of tele-rehabilitation, a highly personalized, family-centered, home-based EI for young infants, remotely managed by clinicians. CareToy, already used with pre-terms without brain injury, has been adapted for high-risk infants in a project funded by the Italian Ministry of Health, and the CareToy-Revised (CareToy-R) has been realized (Trial registration: NCT03211533 and NCT03234959). Before assessing its efficacy, it was crucial to evaluate the acceptability, usability, and feasibility of CareToy-R EI. Nineteen high-risk infants with perinatal brain injury, aged 5.95 ± 2.13 months (range 3.12–10.78 months), carried out an 8-week training with CareToy-R at home, performing customized playful activities with their parents, tailored to their rehabilitative needs, remotely managed by clinicians. The feasibility of training and study procedures was assessed through criteria derived from literature; acceptability and usability have been analyzed from data about individual training and an ad hoc questionnaire. All CareToy-R trainings were planned by the clinical staff with a daily personalized use for each infant between 30 and 45 min (mean 34.37 min). The amount of executed training by the infants was very high (daily mean 30.30 min), with no differences related to infant age, sex, and gestational age. All the nine feasibility criteria were achieved, family compliance to the project was very good, data collection was completed and the CareToy-R system worked properly and easily for parents. The answers to the questionnaire had a total mean score of 84.49% and they ranged from a minimum of 81.05% (in “easy to use” area) to a maximum of 86.49% (“changes due to the training” area), with no differences related to nationality or familiarity with technology of the mothers. This study reports preliminary evidence to the feasibility of a home-based EI with CareToy-R system in infants at high risk for CP. Results of the RCT will provide data about the potential effectiveness of this approach.

Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression, when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling, hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 &plusmn, 0.002 vs. 0.006 &plusmn, 0.0004, p &lt, 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-&beta, induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.