Multicentric Pediatric Stroke Code: Insight to the first years after implementation.

BACKGROUND: The development of unicentric pediatric acute stroke protocols has improved stroke diagnosis and treatment. The impact of the implementation of a multicentric Pediatric Stroke Code (PSC) remains unknown. AIM: to describe the characteristics of the PSC activations and identify clinical features associated with stroke compared to stroke mimics in children in whom a multicentric PSC had been activated and compare them to reported monocentric PSC results. METHODS: Observational, retrospective, case and control multicentric study, performed in the Pediatric Emergency Department (PED) of the three Primary Pediatric Stroke Centers (PPSCs) in Madrid (Spain). Study population corresponded to children between 28 days and 16 years old in whom PSC was activated that consulted or were referred to any of the PPSC PED between March 2019 and June 2022. The main outcome was to compare the characteristics of patients with final diagnosis of stroke versus stroke mimics, among all patients for which PSC had been activated. Logistic regression modeling was used to investigate associations between independent variables and stroke diagnosis. Odds ratio (ORs) and 95 % confidence intervals (95%CIs) were estimated. RESULTS: PSC was activated in 196 patients. Stroke was confirmed in 39 patients (19.9 %): 20 (10.2 %) had an ischemic stroke and 19 (9.7 %) a hemorrhagic stroke. Stroke mimics represented 80.1 % of the PSC activations. Migraine was the most frequent stroke mimic (38.3 %). Time from symptom onset to brain imaging was 233.00 min (IQR 153.00-373.00) when patients self-presented at the PPSC compared to 231.00 min (IQR 129.00-400.00) when PSC was triggered at other settings (p0.580). Five patients (25.3 %) were eligible for hyperacute recanalization treatment. Low level of consciousness (OR4.373, 95%IC 0.247-0.652, p < 0.001), sensory disruption/motor disability of face/limbs (OR3.633, 95%IC 0.103-0.349, p < 0.001), aphasia (OR2.311, 95%IC 0.023-0.284, p0.022) and altered mental status (OR2.517, 95%IC 0.043-0.357, p0.013) were associated with an increased probability of stroke. CONCLUSION: multicentric PSC achieved similar results to previously reported unicentric PSCs, showing the feasibility of such an organization.

Exploring the role of genetic variability and exposure to bisphenols and parabens on excess body weight in Spanish children.

Gene-environment interaction studies are emerging as a promising tool to shed light on the reasons for the rapid increase in excess body weight (overweight and obesity). We aimed to investigate the influence of several polymorphisms on excess weight in Spanish children according to a short- and long-term exposure to bisphenols and parabens, combining individual approach with the joint effect of them. This case-control study included 144 controls and 98 cases children aged 3-12 years. Thirty SNPs in genes involved in obesity-related pathways, xenobiotic metabolism and hormone systems were genotyped using the GSA microchip technology and qPCRs with Taqman® probes. Levels of bisphenols and parabens in urine and hair were used to assess short- and long-term exposure, respectively, via UHPLC-MS/MS system. LEPR rs9436303 was identified as a relevant risk variant for excess weight (ORDom:AAvsAG+GG=2.65, p<0.001), and this effect persisted across exposure-stratified models. For long-term exposure, GPX1 rs1050450 was associated with increased excess weight at low single paraben exposure (ORGvsA=2.00, p=0.028, p-interaction=0.016), whereas LEPR rs1137101 exhibited a protective function at high co-exposure (ORDom:AAvsAG+GG=0.17, p=0.007, p-interaction=0.043). ESR2 rs3020450 (ORDom:GGvsAG+AA=5.17, p=0.020, p-interaction=0.028) and CYP2C19 rs4244285 (ORDom:GGvsAG+AA=3.54, p=0.039, p-interaction=0.285) were identified as predisposing variants at low and high co-exposure, respectively. In short-term exposure, higher odds were observed for INSIG2 rs7566605 at high bisphenol exposure (ORCvsG=2.97, p=0.035, p-interaction=0.017) and for GSTP1 rs1695 at low levels (ORDom:AAvsAG+GG=5.38, p=0.016, p-interaction=0.016). At low and medium co-exposure, SH2B1 rs7498665 (ORAvsG=0.17, p=0.015, p-interaction=0.085) and MC4R rs17782313 (ORAvsG=0.10, p=0.023, p-interaction=0.045) displayed a protective effect, whereas ESR2 rs3020450 maintained its contributing role (ORGvsA=3.12, p=0.030, p-interaction=0.010). Our findings demonstrate for the first time that understanding the genetic variation in excess weight and how the level of exposure to bisphenols and parabens might interact with it, is crucial for a more in-depth comprehension of the complex polygenic and multifactorial aetiology of overweight and obesity.

Development of an accelerometer age- and sex-specific approach based on population-standardized values for physical activity surveillance: A proof of concept.

BACKGROUND: A shift from self-reports to wearable sensors for global physical activity (PA) surveillance has been recommended. The conventional use of a generic cut-point to assess moderate-to-vigorous PA (MVPA) is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions. This study aimed to develop age- and sex-specific (age-sex) cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality. METHODS: A total of 7601 participants (20-85+ years) were drawn from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys (NHANES). Minutes per week of MVPA were assessed with a hip-worn accelerometer. Counts per minute (CPM) were used to define an age- and sex-specific target intensity, representing the intensity each person should be able to reach based on their age and sex. Age- and sex-specific MVPA cut-points were defined as any activity above 40% of the target intensity. These population- and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach. For comparison, we also calculated MVPA with a generic cut-point of 1952 CPM. Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with all-cause mortality (ascertained through December 2015). RESULTS: Both approaches indicated that 37% of the sample met the 150+ min/week guideline. The generic cut-point approach showed a trend to inactivity with age, which was less pronounced using the age-sex cut-points. Overall mortality rates were comparable using generic cut-point (hazard ratio (HR) = 0.61, 95% confidence interval (95%CI): 0.50‒0.73) or age-sex cut-points (HR = 0.57, 95%CI: 0.50‒0.66) for the entire sample. The generic cut-point method revealed an age- and sex-related gap in the benefits of achieving 150+ min/week of MVPA, with older adults showing an 18% greater reduction in mortality rates than younger adults, and a larger difference in women than in men. This disparity disappeared when using age-sex-specific cut-points. CONCLUSION: Our findings underscore the value of age-sex cut-points for global PA surveillance. MVPA defined with age-sex thresholds was associated with all-cause mortality and the dose‒response was similar for all ages and sexes. This aligns with the single recommendation of accumulating 150+ min/week MVPA for all adults, irrespective of age and sex. This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts.

The Relationship between the Mediterranean Diet and Vascular Stiffness, Metabolic Syndrome, and Its Components in People over 65 Years of Age.

OBJECTIVES: The aim of the study was to examine the relationship between the Mediterranean diet (MD) and vascular stiffness and metabolic syndrome (MetS), as well as its components in individuals over the age of 65, overall and by sex. METHODS: The subjects of the study were people over 65 years of age, with a full record of all variables analyzed from the EVA, MARK, and EVIDENT studies. Data from 1280 subjects with a mean age of 69.52 ± 3.58 years (57.5% men) were analyzed. The MD was recorded with the validated 14 item MEDAS questionnaire. MetS was defined following the guidelines of the joint scientific statement from the Programa Nacional de Educación sobre el Colesterol III. Vascular stiffness was evaluated with the VaSera VS-1500® device by measuring the cardio-ankle vascular index (CAVI) and the brachial-ankle pulse wave velocity (baPWV). RESULTS: The mean MEDAS score was 6.00 ± 1.90, (5.92 ± 1.92 in males, 6.11 ± 1.88 in females; p = 0.036). CAVI: 9.30 ± 1.11 (9.49 ± 1.05 males, 9.03 ± 1.13 females; p = <0.001). baPWV: 15.82 ± 2.56 (15.75 ± 2.46 males, 15.92 ± 2.68 females; p = <0.001). MetS was found in 51% (49% males, 54% females; p = 0.036). Subjects with MetS had lower MD adherence and higher vascular stiffness values than subjects without MetS. Overall, we found a negative association with MD score and the number of MetS components (ß = -0.168), with glycemia (ß = -0.007), triglycerides (ß = -0.003), waist circumference (ß = -0.018), CAVI (ß = -0.196) and baPWV (ß = -0.065), and a positive association with HDL cholesterol (ß = 0.013). Regarding sex, associations followed the same direction but without reaching statistical significance with blood glucose and triglycerides in females and with HDL cholesterol and waist circumference in males. CONCLUSIONS: The results indicate that greater adherence to the Mediterranean diet decreases vascular stiffness and the percentage of subjects with MetS, although results differed in the association with MetS components by sex.

How secure can we expect the surveillance policies to be after the implementation in T1 polyps with carcinoma?

Approximately 7% of the polyps resected endoscopically have an adenocarcinoma focus, with no previous endoscopic evidence of malignancy. This raises the question of whether endoscopic resection has been curative. Furthermore, there is no consensus on what the endoscopic and histological criteria for good prognosis are, the appropriate follow-up strategy and what are the long-term results. The aim of the retrospective study by Fábián et al was to evaluate the occurrence of local relapse or distant metastasis in those tumors that were resected endoscopically compared to those that underwent oncologic surgery. They concluded that, regardless of the treatment strategy chosen, there was a higher recurrence rate than described in the literature and that adherence to follow-up was poor. The management approach for an endoscopically benign polyp histologically confirmed as adenocarcinoma depends on the presence of any of the previously described poor prognostic histological factors. If none of these factors are present and the polyp has been completely resected en bloc (R0), active surveillance is considered appropriate as endoscopic resection is deemed curative. These results highlight, once again, the need for further multicentric clinical practice studies to obtain more evidence for the purpose of establishing appropriate treatment and follow-up strategies.

When Bell's Palsy Is Cancer: Avoiding Misdiagnosis and Its Implications.

BACKGROUND: Facial paralysis due to cancer can be misdiagnosed as Bell's palsy. This study aims to clearly identify and quantify diagnostic differentiators and further evaluate the prognostic implications of misdiagnosis. METHODS: Adult patients older than 18 years with facial palsy of unknown or cancerous etiology presenting between 2009 and 2023 were reviewed. Patient characteristics, examination findings, and clinical course were compared between facial paralysis patients with cancer misdiagnosed as Bell's palsy (Cancer-Bell's-Palsy group) and patients correctly diagnosed with Bell's palsy (Bell's-Palsy group). Additionally, morbidity and mortality were compared between facial paralysis patients with cancer initially misdiagnosed with Bell's palsy and facial paralysis patients initially correctly diagnosed with cancer (Cancer-Palsy group). RESULTS: Two-hundred and forty-three patients participated including 43 Cancer-Palsy, 18 Cancer-Bell's-Palsy, and 182 Bell's-Palsy patients. Cancer-Bell's-Palsy patients were significantly less likely than Bell's-Palsy patients to develop synkinesis (odds ratio [OR] = 0.0042; 95% confidence interval [CI]: [0.0005-0.0339]; p < 0.0001), significantly more likely to experience gradual onset facial paralysis (OR = 1,004.69; 95% CI: [54.40-18,555.77]; p < 0.0001), and significantly more likely to have additional nonfacial cranial nerve neuropathies (OR = 49.98; 95% CI: [14.61-170.98]; p < 0.0001). Cancer-Bell's-Palsy patients were more likely than Cancer-Palsy patients to have a greater than 6-month period from initial cancer-attributable symptom onset to cancer diagnosis (OR = 47.62; 95% CI: [9.26-250.00]; p < 0.001), stage IV cancer (OR: 12.36; 95% CI: 1.49-102.71; p = 0.006), and decreased duration of life after cancer diagnosis (median [interquartile range], 40.0 [87.0] vs. 12 [56.3] months, respectively; p = 0.025). CONCLUSION: Facial paralysis related to cancer must be differentiated from Bell's palsy, as misdiagnosis leads to delayed intervention and poorer prognosis. Gradual onset facial palsy, multiple cranial nerve neuropathies, lack of synkinesis, and lack of improvement were nearly definitive differentiators for underlying cancer.

Cost analysis of oncological outpatient neurosurgery under general anesthesia with Hospital-at-Home based postoperative care.

OBJECTIVE: This study evaluates the efficiency and cost-effectiveness of an oncological outpatient neurosurgery (OON) protocol using Enhanced Recovery After Surgery (ERAS) principles in a European healthcare setting. Additionally, it assesses the impact of incorporating Hospital at Home (HaH) for perioperative follow-up on program efficiency and costs. METHODS: We analyzed a case cohort of patients who underwent OON with HaH-based postoperative follow-up for tumor removal or biopsy at a tertiary care center since 2019. A control cohort treated under standard inpatient care was also examined. Costs associated with surgery and postoperative care were meticulously calculated for both groups. RESULTS: The case (n=17) and control (n=38) cohorts had comparable demographics and clinical profiles. Surgical costs, including operating room, anesthesia, and surgeon fees, were similar across groups. However, post-operative monitoring was significantly shorter for the outpatient cohort, leading to reduced observation costs (p<0.001). While the duration of follow-up care was similar, outpatient follow-up via HaH was more cost-effective, reducing overall surgery costs by approximately €2958 per patient (p<0.001) compared to inpatient care. No significant differences were observed in costs related to treatment, radiology, or lab tests between groups. CONCLUSIONS: Outpatient neurosurgery with HaH follow-up offers substantial cost savings without compromising care quality in a public health setting. Inpatient care's higher costs are largely due to bed utilization, while the integration of HaH does not add significant costs, making it a viable alternative for postoperative management.

Dietary bisphenols exposure as an influencing factor of body mass index.

BACKGROUND: Over the past three decades, there has been a significant increase in the prevalence and incidence of overweight and obesity worldwide. The obesogen hypothesis suggests that certain external agents may affect pathways related to fat accumulation and energy balance by stimulating fat cell differentiation and proliferation. Previous research has indicated that exposure to bisphenol A (BPA) and some of its analogues may influence fat accumulation by promoting the transformation of preadipocytes into adipocytes. This study aimed to assess the possible contribution of dietary bisphenol exposure to the odds of developing overweight and obesity in a sample of Spanish children according to sex. METHODS: Dietary and anthropometric data were collected from 179 controls and 124 cases schoolchildren aged 3-12 years. Dietary exposure to BPA and bisphenol S (BPS) was assessed using a food consumption frequency questionnaire. Logistic regression models were used to assess the influence of dietary exposure to bisphenols on overweight and obesity stratified by sex. RESULTS: For females, cases had significantly higher exposure to BPA from meat and eggs compared to controls (median = 319.55, interquartile range (IQR) = 176.39-381.01 vs 231.79 (IQR) = 162.11-350.19, p-value = 0.046). Diet quality was higher for controls (6.21 (2.14) vs 4.80 (2.24) p < 0.001) among males independently of a high or low exposure to bisphenols. However, higher diet quality was observed for female controls with an high exposure of total bisphenols (6.79 (2.04) vs 5.33 (2.02) p = 0.031). Females exposed to high levels of BPA from meat and eggs had higher likelihood of being overweight and obese (adjusted Odds Ratio = 2.70, 95% confidence interval = 1.00 - 7.32). However, no consistent associations were found in males. CONCLUSIONS: High BPA levels from meat and eggs were positively associated with overweight and obesity in females. The dietary intake of BPA in the schoolchildren in the present study was much higher than the acceptable daily intake established by EFSA for the last year.

Should we measure quality of life among people with HIV? A multicentre survey of physicians' opinions in Spain.

OBJECTIVES: We assessed the opinions of physicians caring for people with HIV (PWH) from the multicentre Spanish CoRIS cohort regarding the assessment of health-related quality of life (HRQoL). METHODS: We designed an online self-administered questionnaire comprising 27 structured questions across four domains: (i) sociodemographic and clinical data; (ii) usefulness of measuring HRQoL; (iii) information, training and resource needed; and (iv) whether and how HRQoL should be measured. Physicians completed the questionnaire between April and June 2023. RESULTS: Of 131 physicians surveyed [53.8% men, median age 52 years (interquartile range: 42-60)], 90.9% and 88.6% agreed that measuring HRQoL is useful for both PWH and medical decision-making, respectively. However, 67.2% needed training on what HRQoL is and how to measure it, 79.4% required information on validated tools, and 80.9% felt that clinical guidelines are needed. Overall, 90.1% of physicians agreed that HRQoL should be measured among PWH. Most physicians (82.8%) supported using specific scales for PWH, with 74.1% recommending annual measurement, 49.1% suggesting that nurses from HIV units conduct the assessments, and 43.1% favouring personal interviews during medical visits. At the time of the survey, 55.3% of physicians did not measure HRQoL in any patients due to time or resource constraints (75.8%). CONCLUSIONS: Despite the recognized importance of HRQoL measurement in PWH, Spanish physicians encounter barriers such as time constraints and limited resources. Developing clear guidelines, using tailored scales, and integrating digital tools along with multidisciplinary support could enhance routine HRQoL assessments and improve patient-centred care.

Neuromodulation of Executive Dysfunction in Patients with Acute Stroke Using Transcranial Direct Current Stimulation: Study Protocol for a Triple-Blind, Randomized Sham-Controlled Trial.

Research on the benefits of non-invasive brain stimulation in stroke patients to improve executive functions is scarce. The objective of this study was to investigate the effectiveness of transcranial direct current stimulation (tDCS) in combination with cognitive training for the rehabilitation of executive functions in acute and subacute stroke patients as well as to explore the underlying physiological mechanisms. A triple-blinded, randomized-controlled clinical trial will be conducted involving 60 stroke patients with frontal or basal ganglia lesions and a Montreal Cognitive Assessment (MoCA) score less than 26. Participants will be randomly assigned to receive active tDCS (anode over the left dorsolateral prefrontal cortex, cathode at the right supraorbital region, 20 min at 2 mA) or sham tDCS in a 1:1 ratio for 10 sessions, followed by targeted executive function training. The primary efficacy outcome will be the MoCA score, while secondary outcomes will include the five-digit test (inhibitory control), the Digit Span Task (working memory), the abbreviated version of the Wisconsin Card Sorting test (cognitive flexibility), modified Rankin scale (functional state), Beck-II depression inventory, apathy evaluation scale, and the WHOQOL-BREF (quality of life), assessed immediately after the intervention and at 1, 3, 6, and 12 months post-intervention. Additionally, resting-state functional connectivity and blood biomarkers, such as neurotrophins, growth factors, and inflammatory molecules, will be evaluated before and after the intervention. This study will contribute to the investigation of the efficacy of tDCS in rehabilitating executive functions in acute and subacute stroke patients. The multidimensional approach utilized in this study, which includes analysis of resting-state connectivity and neuroplasticity-related blood biomarkers, is expected to provide insights into the underlying brain mechanisms involved in the rehabilitation of dysexecutive syndrome.

Shorter prostatic urethral length in preoperative Magnetic Resonance Imaging is associated with higher risk of climacturia following robot-assisted laparoscopic radical prostatectomy.

Climacturia is defined as the leakage of urine during orgasm and it is an adverse effect of radical prostatectomy. Our goal was to determine if various preoperative MRI pelvic floor measurements were associated with the risk of climacturia following robot-assisted laparoscopic radical prostatectomy. For this purpose, we conducted a prospective study involving 57 patients who underwent robot-assisted laparoscopic radical prostatectomy. MRI measurements were analysed by 2 urologists and 2 radiologists. Follow-up was carried out at 3, 6, and 12 months using the Parra orgasmic function questionnaire. We analysed all measurements, along with other patient, surgery, and tumour characteristics, classifying patients into two groups based on the presence or absence of climacturia. A logistic regression model was applied among statistically significant variables. STROBE recommendations were taken into consideration. Shorter prostatic urethral length was associated with higher risk of climacturia at 3 months, OR = 0.83 (95%CI 0.688-0.98) (p = 0.024). Patients with climacturia at 6 months had greater median urethral width [12.66 mm, interquartile range (IQR): 11.77-13.55 vs 12.13 mm, IQR 11.08-13.18] (p = 0.02). Patients with climacturia at 12 months had a higher proportion of preoperative lower urinary tract symptoms (57.14% vs. 20%) (p = 0.026). In the logistic regression, the history of lower urinary tract symptoms was associated with a higher risk of climacturia, OR = 6.07 (95% CI 1.342-26.03) (p = 0.023). In conclusion, shorter prostatic urethral length in preoperative MRI and a history of lower urinary tract symptoms were associated with a higher risk of climacturia following robot-assisted laparoscopic radical prostatectomy.

Progression in central blood pressure and hemodynamic parameters and relationship with cardiovascular risk factors in a Spanish population. EVA follow-up study.

BACKGROUND: The progression of Central Blood Pressure (CBP) values and central hemodynamic parameters and its relationship with cardiovascular risk factors is quite unknown. We sought to investigate this association in a Spanish adult population without cardiovascular diseases. METHODS: Prospective observational research with a five-year follow-up. Randomly sampled 501 individuals (mean age 56±14 years, 50.3% women). After five years, 480 individuals had a follow-up. Measurements taken using the SphygmoCor® (AtCor Medical Pty Ltd., Head Office,West Ryde, Australia), following all the recommendations established in the "International task force"1, giving an estimate of central blood pressure relative to measured brachial blood pressure (type 1 device). RESULTS: Progressions during follow-up: central systolic blood pressure (cSBP): 4.16±13.71 mmHg; central diastolic blood pressure (cDBP): 2.45±11.37 mmHg; central pulse pressure (cPP): 1.72±12.43 mmHg; pulse pressure amplification (PPA): 2.85±12.20 mmHg; ejection duration (ED): 7.00±47.87 ms; subendocardial viability ratio (SEVR): -8.04±36.24%. In multiple regression analysis: cSBP positively associated with: BMI (ß=0.476); waist size (ß=0.159); number of cigarettes per day (ß=0.192). Inversely associated with peripheral systolic blood pressure (ß=-0.282). cDBP increase positively associated with number of cigarettes per day (ß=0.174). Inversely associated with peripheral diastolic blood pressure (ß=-0.292). cPP increase positively associated with BMI (ß=0.330). Inversely associated with peripheral pulse pressure (ß=-0.262). PPA increase positively associated with: BMI (ß=0.276); number of cigarettes per day (ß=0.281). ED progress inversely associated with basal plasma glucose (ß=-0.286). CONCLUSIONS: All measures increased except for SEVR. Progressions in CBP and PPA were positively associated with anthropometric parameters and number of cigarettes and CBP inversely associated with peripheral blood pressure, although this association was different according to sex.

Comparison of objectively measured and estimated cardiorespiratory fitness to predict all-cause and cardiovascular disease mortality in adults: A systematic review and meta-analysis of 42 studies representing 35 cohorts and 3.8 million observations.

BACKGROUND: Cardiorespiratory fitness (CRF) is a powerful health marker recommended by the American Heart Association as a clinical vital sign. Comparing the predictive validity of objectively measured CRF (the "gold standard") and estimated CRF is clinically relevant because estimated CRF is more feasible. Our objective was to meta-analyze cohort studies to compare the associations of objectively measured, exercise-estimated, and non-exercise-estimated CRF with all-cause and cardiovascular disease (CVD) mortality in adults. METHODS: Systematic searches were conducted in 9 databases (MEDLINE, SPORTDiscus, Embase, Scopus, PsycINFO, Web of Science, PubMed, CINAHL, and the Cochrane Library) up to April 11, 2024. We included full-text refereed cohort studies published in English that quantified the association (using risk estimates with 95% confidence intervals (95%CIs)) of objectively measured, exercise-estimated, and non-exercise-estimated CRF with all-cause and CVD mortality in adults. CRF was expressed as metabolic equivalents (METs) of task. Pooled relative risks (RR) for all-cause and CVD mortality per 1-MET (3.5 mL/kg/min) higher level of CRF were quantified using random-effects models. RESULTS: Forty-two studies representing 35 cohorts and 3,813,484 observations (81% male) (362,771 all-cause and 56,471 CVD deaths) were included. The pooled RRs for all-cause and CVD mortality per higher MET were 0.86 (95%CI: 0.83-0.88) and 0.84 (95%CI: 0.80-0.87), respectively. For both all-cause and CVD mortality, there were no statistically significant differences in RR per higher MET between objectively measured (RR range: 0.86-0.90) and maximal exercise-estimated (RR range: 0.85-0.86), submaximal exercise-estimated (RR range: 0.91-0.94), and non-exercise-estimated CRF (RR range: 0.81-0.85). CONCLUSION: Objectively measured and estimated CRF showed similar dose-response associations for all-cause and CVD mortality in adults. Estimated CRF could provide a practical and robust alternative to objectively measured CRF for assessing mortality risk across diverse populations. Our findings underscore the health-related benefits of higher CRF and advocate for its integration into clinical practice to enhance risk stratification.

The critical role of cardiorespiratory fitness in disease prevention.

Cardiorespiratory fitness (CRF) has been increasingly recognized in recent years as an important predictor of risk for adverse outcomes in numerous chronic conditions. In fact, a growing body of epidemiological and clinical evidence demonstrates that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, hyperlipidemia, and type 2 diabetes. Moreover, adding CRF to these traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The utility of CRF now extends far beyond all-cause and cardiovascular mortality to include the prevention and treatment of numerous other chronic conditions; CRF has been demonstrated to have a mitigating influence in as many as 40 such conditions. Herein we discuss the impact of CRF in the prevention of chronic disease in both adults and children. This discussion includes recent data on interactions between CRF and aging, obesity, statin use, incidence of diabetes, and the impact of CRF and physical activity patterns in adolescents including mental health, scholastic achievement, and cardiometabolic health. Finally, we discuss how CRF, as an essential vital sign, can be implemented in clinical practice.

A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6.

BACKGROUND: In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC). OBJECTIVES: To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (groups 1 and 2), fixed-dose cemiplimab in mCSCC (group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (group 6). METHODS: Patients received cemiplimab (3 mg/kg intravenously every 2 weeks [groups 1 and 2]) or cemiplimab (350 mg intravenously [groups 3 and 6]) every 3 weeks. The primary end point was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments. RESULTS: At 42.5 months, ORR for groups 1-3 (n = 193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for group 6 (n = 165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were groups 1-3: 31.1% and group 6: 34.5%. LIMITATIONS: Nonrandomized study, nonsurvival primary end point. CONCLUSION: EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC.

Impact of Cardiorespiratory Fitness on COVID-19-Related Outcomes: The Exercise Testing and Health Outcomes Study (ETHOS).

OBJECTIVE: To assess the association between cardiorespiratory fitness (CRF) and COVID-19-related health outcomes including mortality, hospitalization, and mechanical ventilation. PATIENTS AND METHODS: In a retrospective analysis of 750,302 patients included in the Exercise Testing and Health Outcomes Study, we identified 23,140 who had a positive result on COVID-19 testing between March 2020 and September 2021 and underwent a maximal exercise test in the Veterans Affairs Health Care System between October 1, 1999 to September 3, 2020. The association between CRF and risk for severe COVID-19 outcomes, including mortality, hospitalization due to COVID-19, and need for intubation was assessed after adjustment for 15 covariates. Patients were stratified into 5 age-specific CRF categories (Least-Fit, Low-Fit, Moderate-Fit, Fit, and High-Fit), based on peak metabolic equivalents achieved. RESULTS: During a median of follow-up of 100 days, 1643 of the 23,140 patients (7.1%) died, 4995 (21.6%) were hospitalized, and 927 (4.0%) required intubation for COVID-19-related reasons. When compared with the Least-Fit patients (referent), the Low-Fit, Moderate-Fit, Fit, and High-Fit patients had hazard ratios for mortality of 0.82 (95% CI, 0.72 to 0.93), 0.73 (95% CI, 0.63 to 0.86), 0.61 (95% CI, 0.53 to 0.72), and 0.54 (95% CI, 0.45 to 0.65), respectively. Patients who were more fit also had substantially lower need for hospital admissions and intubation. Similar patterns were observed for elderly patients and subgroups with comorbidities including hypertension, diabetes, cardiovascular disease, and chronic kidney disease; for each of these conditions, those in the High-Fit category had mortality rates that were roughly half those in the Low-Fit category. CONCLUSION: Among patients positive for COVID-19, higher CRF had a favorable impact on survival, need for hospitalization, and need for intubation regardless of age, body mass index, or the presence of comorbidities.

Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Rapid SARS-CoV-2 sensing through oxygen reduction reaction catalysed by Au@Pt/Au core@shell nanoparticles.

The development of rapid, accurate, sensitive, and low-cost diagnostic methods for COVID-19 detection in real-time is the unique way to control infection sources and monitor illness progression. In this work, we propose an electrochemical biosensor for the rapid and accuracy diagnosis of COVID-19, through the determination of ORF1ab specific sequence. The biosensor is based on the immobilization of a thiolated sequence partially complementary (domain 1) to ORF1ab on gold screen-printed electrodes and the use of bifunctional Au@Pt/Au core@shell nanoparticles modified with a second thiolated sequence partially complementary to ORF1ab (domain 2) as electrochemical indicator of the hybridization of DNA sequences. The synthesized Au@Pt/Au nanoparticles consist of an Au core, a shell of Pt (Au@Pt NPs), that provides an excellent electrocatalytic activity toward the oxygen reduction reaction (ORR) even after formation of hybrid biomaterials by modification, through the Au protuberances growth on the NPs surface, with an oligonucleotide with recognition ability. The ORR electrochemical activity, enhanced by the label element (Au@Pt/Au NPs), has been employed, for the first time, as indicator of the hybridization event. Based on this strategy, target sequences of the SARS-CoV-2 virus have been detected with a detection limit of 32 pM. The selectivity of the biosensor was confirmed by analysing ORF1ab sequence in the presence of DNA sequences from other viruses. The biosensor has been successfully applied to the direct detection of the virus in non-amplified samples of nasopharyngeal swabs from infected and non-infected patients. Results compare well with those obtained through RT-qPCR but our method is more rapid since does not need any amplification process.

Effects of combined aerobic and resistance training on the inflammatory profile of children with overweight/obesity: A randomized clinical trial.

BACKGROUND: We assessed the effects of a 20-week combined (aerobic and resistance) exercise training programme on the inflammatory profile of prepubertal children with overweight or obesity. METHODS: Totally 109 participants (10.1 ± 1.1 years, 41% girls) were randomly allocated to an exercise or control group. Adiponectin, C-reactive protein, epidermal growth factor, insulin-like growth factor-1, interleukin (IL)-1ß, IL-6, leptin, tumour necrosis factor-α and vascular endothelial growth factor A (VEGFA) were analysed in plasma. Total white blood cell (WBC) count and immune subpopulations (eosinophils, basophils, neutrophils, lymphocytes and monocytes) were also determined. RESULTS: No intervention effect was found for any of the analysed biomarkers (all p ≥ 0.05). We observed a significant sex by intervention interaction for IL-1ß (p = 0.03). When stratifying the sample by sex, the exercise programme induced a significant effect on IL-1ß levels (mean Z-score difference, 0.66 [95% confidence interval 0.32-1.01]) in girls, but not in boys. A lower number of girls in the exercise group showed a meaningful reduction in IL-1ß (i.e., ≥0.2 standard deviations) than in the control group (15% vs. 85%, p = 0.01). CONCLUSIONS: This exercise programme failed to improve the inflammatory profile in prepubertal children with overweight/obesity. Future studies should explore the effect of longer exercise interventions and in combination with diet.

Effects of exercise on bone marrow adipose tissue in children with overweight/obesity: role of liver fat.

CONTEXT: Exercise reduces adiposity, but its influence on bone marrow fat fraction (BMFF) is unknown; nor is it known whether a reduction in liver fat content mediates this reduction. OBJECTIVES: (i) To determine whether incorporating exercise into a lifestyle program reduces the lumbar spine (LS)-BMFF, and (ii), to investigate whether changes in liver fat mediate any such effect. DESIGN: Ancillary analysis of a two-arm, parallel, non-randomized clinical trial. SETTING: Primary care centres in Vitoria-Gasteiz (Spain). PARTICIPANTS: A total of 116 children with overweight/obesity were assigned to a 22-week family-based lifestyle program (control group [n=57]) or the same program plus an exercise intervention (exercise group [n=59]. INTERVENTIONS: The compared interventions consisted of a family-based lifestyle program (two 90-minute sessions/month) and the same program plus supervised exercise (three 90-minute sessions/week). MAIN OUTCOMES AND MEASURES: The primary outcome examined was the change in LS-BMFF between baseline and 22 weeks, as estimated by MRI. The effect of changes in hepatic fat on LS-BMFF were also recorded. RESULTS: Mean weight loss difference between groups was 1.4±0.5 kg favour of the exercise group. Only the children in the exercise group experienced a reduction in LS-BMFF (effect size [Cohen d] -0.42, CI: -0.86, -0.01). Importantly, 40.9% of the reductions in LS-BMFF were mediated by changes in percentage hepatic fat (indirect effect: ß=-0.104, 95%CI=-0.213, -0.019). The impact of changes in hepatic fat on LS-BMFF was independent of weight loss. CONCLUSIONS AND RELEVANCE: The addition of exercise to a family-based lifestyle program designed to reduce cardiometabolic risk improves bone health by reducing LS-BMFF in children with overweight or obesity. This beneficial effect on bone marrow appears to be mediated by reductions in liver fat.