Search

Elucidating the infection dynamics that lead to severe respiratory syncytial virus (RSV) pneumonia and hospitalization among young children are critical. We explored the role of infection parity as well as age in months for RSV-associated hospitalization among young children in Japan.We used a sequential transmission catalytic model to capture the transmission mechanisms of RSV among infants in an endemic state. We investigated data on the age-dependent seroprevalence and incidence rate of hospitalization in Japan, and jointly estimated the age-specific risk of hospitalization during primary RSV infection and relative risk of hospitalization during secondary infection in children aged5 years.The estimated risk of hospitalization with primary infection was 0.08 (95% CI: 0.05-0.14) in infants aged 0-2 months. The estimated relative risk of hospitalization owing to secondary infection was 0.18 (95% CI: 0.01-2.04).Our simple models successfully captured the infection dynamics of RSV among young children in Japan. The age group of early infancy may be most vulnerable to infection and hospitalization, offering key insights into future vaccinations. The burden of hospitalization from secondary infection may be less important in young children.

We sought to develop and validate age-specific instruments for measuring early childhood resilience at ages 3, 5 and 8 in the Taiwan Birth Cohort Study, a national longitudinal study.Using data from 18,553 mother-infant pairs, we conducted exploratory factor analysis (EFA) on a simple random half of our sample. We then used the remaining half of these data for confirmatory factor analysis (CFA) to further assess the fit of 3 CFA models (ie, first-order, second-order, and bifactor). Psychometric properties, distributions, and inter-item and inter-factor correlations of each instrument were also evaluated.EFA and CFA showed that the bifactor model of resilience (which included a general resilience factor and 5 specific factors) had the best fit for all 3 resilience scales, with 19 items at year 3, 18 items at year 5, and 19 items at year 8. All 3 resilience scales showed good psychometric properties, including construct validity, internal consistency, and normal distributions. For predictive validity, we found that in the face of adversity (measured by the High Risk Family Score), individuals with high resilience scores at age 3 had better general health scores at ages 3, 5, and 8 compared to those with low resilience scores.We describe the development and validation of age-appropriate survey instruments to assess resilience in young children at the population level. These instruments can be used to better understand how resilience can impact child health over time, and to identify key factors that can foster resilience.

What is the blastocyst conversion rate in embryo cryopreservation cycles, per year of female age?Retrospective cohort study including patients undergoing their first ovarian stimulation cycle at our center with planned freeze-all strategy January 1st, 2014-June 30th, 2020. Primary outcome was blastocyst conversion rate. Secondary outcomes included mature oocyte and fertilization rates. Patients were stratified by year of age to assess oocyte yield and embryo development outcomes.3,362 patients were included. The median blastocyst conversion rate in patients ≤30 was 66.7% (interquartile range 50.0-86.6) and remained statistically comparable through age 40 with a significant decline among ages ≥41 (41-years: marginal effect (ME) -5.2% (-9.7 to -0.7); 42-years: ME -9.6% (-14.3 to -4.8); 43-years: ME -7.7% (-12.8 to -2.6); ≥44-years: ME -20.8% (-26.5 to -15.1)). For the entire cohort, the median mature oocyte rate was 81.8% and the median fertilization rate was 81.8%. The mature oocyte and fertilization rates remained statistically comparable for each year of age except age ≥44 which had a statistically significantly increased mature oocyte rate (ME 4.4% (1.3 to 7.5)) and statistically significantly decreased fertilization rate (ME -5.8% (-9.8 to -1.9)) CONCLUSIONS: In embryo cryopreservation cycles, the blastocyst conversion rate remained statistically comparable through age 40 followed by a statistically significant decline for patients ≥41; however, the mature oocyte and fertilization rates were not impacted by increasing age until age ≥44. Even in women ≥44, over 40% of fertilized oocytes developed to blastocyst. Overall, this information is useful when counseling patients during the embryo culture stage regarding predicted blastocyst yield.

To validate the application of Corrective Adjustment Procedures for removing Relative Age Effects in youth athletic contexts, this study estimated the longitudinal relationships between decimal age (chronological and relative) and performance in male and female long jumpers. Using trendlines, Corrective Adjustment Procedures were applied, and Relative Age Effect distributions associated with performance attainment were re-examined.Retrospective longitudinal design examining competitive long-jump data between 2005 and 2019.In Part I, participants were 689 junior Italian long jumpers (age range = 11.01-17.99 years; 56.6% females) who participated in ≥three events. Longitudinal modelling and regression equations quantified the sex-specific relationships between decimal age and long jump performance. In Part II, equations were utilised to adjust individual performance within an independent sample (N = 13,639; 50.1% females) of age-matched jumpers. Relative Age Effect distributions within attainment levels (i.e., Top 25-10%) were examined based on raw and correctively adjusted performance.Irrespective of sex, Relative Age Effects were prevalent across all age-groups with medium-large effect sizes at 12-17 (males and females) and 12-17 years (females) of age (Cramer's V range = 0.07-0.28). Relative Age Effect bias magnitude also increased with attainment level (i.e., Top 25-10%). Following Corrective Adjustment Procedure application, typical Relative Age Effects were removed with non-significant deviations in relative age distributions regardless of sex or age-group or attainment level (Top 25 or 10%).Findings provide efficacy for Corrective Adjustment Procedure application to remove Relative Age Effects across youth long jumping events. Corrective Adjustment Procedures suggest potential in improving performance evaluation, identification of technically skilled performers, and sporting experiences.

According to a classic result in evolutionary biodemography, selection on age-specific survival invariably declines with reproductive age. The result assumes proportional changes in survival and a constant environment. Here, we look at selection on age-specific survival when changes are still proportional but the environment fluctuates. We find that selection may or may not decline with reproductive age depending on how exactly survival is proportionally altered by mutations. However, interpreted in neutral terms, the mathematics behind the classic result capture a general property that the genetics of populations with age structure possess both in a constant and in a fluctuating environment.

BACKGROUND: The optimal age for endorectal pull-through (ERPT) surgery in infants with short-segment Hirschsprung disease varies, with a trend toward earlier surgery. However, it is unclear if the timing of surgery impacts functional outcomes. We undertook the present study to determine the optimal timing of ERPT in infants with short-segment Hirschsprung disease. METHODS: The NCBI PubMed database was searched for English-language manuscripts published between 2000–2019 analyzing functional outcomes for patient following the initial Soave ERPT for short-segment Hirschsprung disease. Raw data from these studies was obtained from the corresponding author for each manuscript. We combined data from these papers with our own institutional data and performed a meta-analysis. RESULTS: A total of 780 infants were included in our meta-analysis. Constipation occurred in 1.0–31.7%, soiling 1.3–26.0%, anastomotic stricture 0.0–14.6%, and anastomotic leak 0.0–3.4%. Regarding age at ERPT, younger infants at the time of initial corrective surgery had higher rates of soiling, stricture, and leak. On sub-group analysis, patients

This systematic review study and meta-analysis sought to estimate the prevalence of malnutrition and nutritional deficiencies in children with cerebral palsy (CP).This is a systematic review and meta-analysis.The systematic review was conducted according to the PRISMA guidelines. The articles were chosen using the PubMed, Embase, Scopus, Web of Science, Cochrane Library, SciELO, and Lilacs databases and the bibliographical reference lists of the articles. No limitations were placed on the time of publication, but the articles had to include children from 0 to 18 years old with CP who presented the prevalence of malnutrition and nutritional deficiencies. The methodological quality of the articles was assessed using the verification list for analytical cross-sectional studies, the Newcastle-Ottawa scale, and the Cochrane Collaboration tool for randomized studies. The meta-analysis of proportions was conducted based on the prevalence data for malnutrition or nutritional deficiencies. The study is registered in PROSPERO under CRD number 42020175068.Sixty-seven articles (N = 453,804) published between 1986 and 2019 were included. Most of the articles presented a low risk of bias and no publication was excluded for quality reasons. The most widely used anthropometric index for diagnosing nutritional status was weight-to-age and the estimated prevalence of malnutrition was 40% (95% CI = 28.0-53.0). Nutrient deficiency was investigated by nine publications, with hypocalcemia and reduced serum concentrations of zinc, copper, and vitamin D being reported the most.We found a high rate of malnutrition in the population in this review, moreover, we suggest that some nutritional deficiencies are associated with food deficit and that the socio-economic and age factors of these children may relate with the poor nutritional outcome. This makes monitoring and personalized nutritional management necessary, in accordance with the characteristics and particularities of children with CP.

Sleep comorbidities are common, and sometimes severe, for children with early-life epilepsies (ELEs). Yet, there is a paucity of data regarding the profile of these sleep disturbances and their complications.Participants registered with the Rare Epilepsy Network (REN) were queried about sleep via online questionnaires. Descriptive statistics and logistic regression were performed.Median age of the 356 children was 56 months (interquartile range 30 to 99), 56% were female, and 53% (188/356) endorsed a sleep concern. Frequent nighttime awakenings (157 of 350; 45%), difficulty falling asleep (133 of 350; 38%), and very restless sleep (118 of 345; 34%) were most endorsed. Nocturnal seizures were associated with sleep concerns and were reported in 75% (268 of 356) of children. Of the children with nocturnal seizures, 56% (118 of 268) had sleep concerns. Of the children without nocturnal seizures, 43% (38 of 88) had sleep concerns. Sleep concerns were most common in dup15q syndrome (16 of 19; 84%). Children aged 4 to ≤10 years (adjusted odds ratio [aOR] 16.1; 95% confidence interval [CI] 2.0, 131.0) and 10 to13 years (aOR 22.2; 95% CI 2.6, 188.6) had a greater odds of having a sleep concern compared with children aged ≤6 months. Female sex appeared protective for sleep concerns (aOR 0.6; 95% CI 0.4, 0.9). The association between sleep concerns and nocturnal seizures was weaker when adjusted for sex and age category in a logistic regression model.Reported sleep concerns are highly prevalent in children with ELEs and persist with age, in contrast to what is expected in healthy children. There may be unmet sleep-related clinical needs in children with ELEs.

Objectives To investigate the general population’s view on artificial intelligence (AI) in medicine with specific emphasis on 3 areas that have experienced major progress in AI research in the past few years, namely radiology, robotic surgery, and dermatology. Methods For this prospective study, the April 2020 Online Longitudinal Internet Studies for the Social Sciences Panel Wave was used. Of the 3117 Longitudinal Internet Studies For The Social Sciences panel members contacted, 2411 completed the full questionnaire (77.4% response rate), after combining data from earlier waves, the final sample size was 1909. A total of 3 scales focusing on trust in the implementation of AI in radiology, robotic surgery, and dermatology were used. Repeated-measures analysis of variance and multivariate analysis of variance was used for comparison. Results The overall means show that respondents have slightly more trust in AI in dermatology than in radiology and surgery. The means show that higher educated males, employed or student, of Western background, and those not admitted to a hospital in the past 12 months have more trust in AI. The trust in AI in radiology, robotic surgery, and dermatology is positively associated with belief in the efficiency of AI and these specific domains were negatively associated with distrust and accountability in AI in general. Conclusions The general population is more distrustful of AI in medicine unlike the overall optimistic views posed in the media. The level of trust is dependent on what medical area is subject to scrutiny. Certain demographic characteristics and individuals with a generally positive view on AI and its efficiency are significantly associated with higher levels of trust in AI.

To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice. Vaccinated adult mice were better protected than aged mice after challenge with 2009 H1N1 virus, experiencing less morbidity and having lower pulmonary virus titers. The age-associated decline in immunity and protection was consistently greater among females than males, with the reduction in immunity and protection for aged as compared with adult females often being the sole comparison driving the overall age-associated significant differences. The age-associated reduction in stalk-based immunity in females was not, however, associated with changes in estradiol. To determine if the better antibodies in adults could be utilized to protect aged mice, serum was passively transferred from vaccinated adult mice into naïve sex-matched aged mice. Even with transferred serum from young adult mice, aged females still suffered greater morbidity than aged males. These data suggest there are sex-dependent effects of aging on cHA-based universal influenza virus vaccine-induced immunity that cannot be reversed through transfer of serum from young animals. The lack of consideration of sex-specific effects of aging on immunity could hinder efforts toward universal vaccines.

Low-level alcohol consumption is commonly perceived as being inconsequential or even beneficial for overall health, with some reports suggesting that it may protect against dementia or cardiovascular risks. However, these potential benefits do not preclude the concurrent possibility of negative health outcomes related to alcohol consumption. To examine whether casual, non-heavy drinking is associated with premature brain aging, we utilized the Brain-Age Regression Analysis and Computational Utility Software package to predict brain age in a community sample of adults [n = 240, mean age 35.1 (±10.7) years, 4 8% male, 4 9% African American]. Accelerated brain aging was operationalized as the difference between predicted and chronological age (“brain age gap”). Multiple regression analysis revealed a significant association between previous 90-day alcohol consumption and brain age gap (β = 0.014, p = 0.023). We replicated these results in an independent cohort [n = 231 adults, mean age 34.3 (±11.1) years, 55% male, 28% African American: β = 0.014, p = 0.002]. Our results suggest that even low-level alcohol consumption is associated with premature brain aging. The clinical significance of these findings remains to be investigated.

OBJECTIVE: To (1) determine the prevalence and type of sepsis-related neuroimaging abnormalities evident on clinically-indicated brain magnetic resonance imaging (MRI) in children with sepsis and (2) test the association of these abnormalities with mortality, new disability, length of stay (LOS), and MRI indication. DESIGN: Retrospective cohort study. SETTING: Single, large academic pediatric intensive care unit (PICU). PATIENTS: Pediatric patients with sepsis between 1/1/2012 and 6/30/2018 with a clinically-indicated brain MRI obtained within 60 days of sepsis onset. MEASUREMENTS AND RESULTS: Two radiologists systematically reviewed the first post-sepsis brain MRI and determined which abnormalities were sepsis-related by consensus. Standard descriptive statistics were used to compare outcomes of PICU mortality, new disability, and PICU LOS in patients with versus without sepsis-related MRI abnormalities. 140 patients underwent clinically-indicated brain MRI within 60 days of sepsis onset. PICU mortality was 7%. Thirty patients had ≥1 sepsis-related MRI abnormality yielding a prevalence of 21% (95% CI 15%, 28%). Among those patients, 53% (16/30) had sepsis-related white matter signal abnormalities, 53% (16/30) sepsis-related ischemia, infarction, or thrombosis and 27% (8/30) sepsis-related posterior reversible encephalopathy. Patients with ≥1 sepsis-related MRI abnormality had increased mortality (17% vs 5%; p=0.04), new neurologic disability at PICU discharge (32% vs 11%; p=0.03) and longer PICU LOS (median 18 vs 11 days; p=0.04) compared to patients without sepsis-related MRI abnormalities. CONCLUSIONS: In children with sepsis and a clinically-indicated brain MRI, twenty-one percent had a sepsis-related MRI abnormality. Sepsis-related MRI abnormalities were associated with increased mortality, new neurologic disability, and longer PICU LOS.

To describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups.A quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling.The additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P.0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as RThis practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.

Objective The study objective was to evaluate the short- and long-term outcomes of patients with ischemic cardiomyopathy after surgical ventricular restoration and to identify risk factors related to poor results. Methods Between August 2002 and April 2016, 62 patients affected by ischemic cardiomyopathy underwent surgical left ventricular restoration at our unit. Patients' mean age at operation was 63 years (39-79 years). Mean ejection fraction was 29.6%. The Surgical Treatment for Ischemic Heart Failure trial criteria have been used as indications for surgery. Fifty-seven patients (91%) received surgical myocardial revascularization. Mitral valve repair was performed in 39 patients (63%). The surgical technique consisted of the classic Dor operation or a different approach reducing the equatorial diameter of the left ventricle and avoiding the use of a patch. The data were analyzed retrospectively for perioperative results and short- and long-term clinical outcomes. Results One patient died of noncardiac causes within 30 days (1.6%). All-cause death occurred in 36 patients (58%) during follow-up (0.6-14.7 years; median follow-up time, 7.02 years), of whom 15 died of cardiac causes. Age, need for preoperative intra-aortic balloon pump, reduction less than 35% of postoperative left ventricular end-diastolic and end-systolic volumes, type of surgical technique, and ejection fraction less than 25% were identified as risk factors for late cardiac mortality. Perioperative levosimendan administration and presence of preoperative moderate to severe mitral regurgitation influenced early and intermediate-term outcomes, but no statistical relevance on long-term results was demonstrated. Conclusions Patients with ischemic dilative cardiomyopathy have favorable short- and long-term outcomes after ventricular restoration. Age, preoperative ejection fraction less than 25%, inadequate left ventricular surgical reverse remodeling, and type of surgical technique negatively affect long-term survival.

Background: There is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes. Methods: A descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K+, Na+, Cl-, and Ca2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxicischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures. Results: Sixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K+]CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na+]CSF, [Cl-]CSF, and [Ca2+]CSF were less consistent among subgroups. Conclusions: Here we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function. (C) 2021 Elsevier Inc. All rights reserved.

BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/ml) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination.Our data suggest that a significant proportion of pediatric HTx recipients have no detectable antibody response after SARS-CoV-2 vaccination and support the recommendation to complete the vaccination series prior to HTx in those pediatric patients waiting for HTx.

ST-elevation myocardial infarction (STEMI) survivors have a heightened risk of developing heart failure (HF). The magnitude of this risk with the advent of primary percutaneous coronary intervention is less characterized. We aimed to examine the incidence and predictors of incident HF and all-cause mortality in a contemporary STEMI cohort. We performed a retrospective analysis of 700 consecutive patients with STEMI treated with primary percutaneous coronary intervention at a tertiary hospital. The primary outcome was the occurrence of HF during follow-up. HF was defined by HF hospitalization or the presence of congestion that led to de novo prescription or up-titration of diuretics in the outpatient clinic. The secondary outcome was defined by the occurrence of HF or all-cause mortality. During a median follow-up period of 43.6 months, HF events occurred in 110 patients (15.7%), 34 (4.8%) managed as outpatient and 76 (10.9%) requiring hospitalization. Left ventricular ejection fraction (LVEF)50% was present in 76% of those who developed HF. Age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.01 to 1.06), diabetes (HR 1.85, 95% CI 1.12 to 3.05), door-to-balloon time (HR 1.002, 95% CI 1.000 to 1.003), Killip-Kimball class ≥II (HR 2.24, 95% CI 1.32 to 3.80) and LVEF50% (HR 1.71, 95% CI 1.01 to 2.92) were independent predictors. All-cause mortality incidence was 8.7%. HF was independently associated with a threefold increased risk of dying (HR 3.52, 95% CI 1.85 to 6.69, p0.001). In conclusion, a substantial proportion of contemporary patients with STEMI develop HF, which triplicates the risk of dying. Older age, diabetes and LVEF50% independently predicted the development of HF and all-cause death.

Background: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. Methods: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3–4 months to 6–9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4–6 months to 18–36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. Findings: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0–15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77–0·89], p

Overweight induced by high-fat diet (HFD) represents one of the major health concerns in modern societies, which can cause lasting peripheral and central metabolic disorders in all age groups. Specifically, childhood obesity could lead to life-long impact on brain development and functioning. On the other hand, environmental enrichment (EE) has been demonstrated to be beneficial for learning and memory. Here, we explored the impact of high-fat diet on olfaction and organization of olfactory bulb cells in adolescent mice, and the effect of EE intervention thereon. Puberty mice (3-week-old) fed with HFD for 10 weeks exhibited poorer odor sensitivity and olfactory memory relative to controls consuming standard chows. The behavioral deficits were rescued in the HFD group with EE intervention. Neuroanatomically, parvalbumin (PV) interneurons in the olfactory bulb (OB) were reduced in the HFD-fed animals relative to control, while EE intervention also normalized this alteration. In contrast, cells expressing calbindin (CB), doublecortin (DCX) in the OB were not altered. Our findings suggest that PV interneurons may play a crucial role in mediating the HFD-induced olfactory deficit in adolescent mice, and can also serve a protective effect of EE against the functional deficit.

Recently, one observational study showed that patients with ST-segment elevation myocardial infarction (STEMI) without standard cardiovascular risk factors were associated with increased mortality compared with patients with risk factors. This unexpected result should be evaluated in other populations including those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and chronic coronary syndrome (CCS). Among 30,098 consecutive patients undergoing first coronary revascularization in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort-2 and 3, we compared clinical characteristics and outcomes between patients with and without risk factors stratified by their presentation (STEMI n = 8,312, NSTE-ACS n = 3,386, and CCS n = 18,400). Patients with risk factors were defined as having at least one of the following risk factors: hypertension, dyslipidemia, diabetes, and current smoking. The proportion of patients without risk factors was low (STEMI: 369 patients [4.4%], NSTE-ACS: 110 patients [3.2%], and CCS: 462 patients [2.5%]). Patients without risk factors compared with those with risk factors more often had advanced age, low body weight, and malignancy and less often had history of atherosclerotic disease and prescription of optimal medical therapy. In patients with STEMI, patients without risk factors compared with those with risk factors were more often women and more often had atrial fibrillation, long door-to-balloon time, and severe hemodynamic compromise. During a median of 5.6 years follow-up, patients without risk factors compared with those with risk factors had higher crude incidence of all-cause death. After adjusting confounders, the mortality risk was significant in patients with CCS (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01 to 1.49, p = 0.04) but not in patients with STEMI (HR 1.06, 95% CI 0.89 to 1.27, p = 0.52) and NSTE-ACS (HR 1.07, 95% CI, 0.74 to 1.54, p = 0.73). In conclusion, among patients undergoing coronary revascularization, patients without standard cardiovascular risk factors had higher crude incidence of all-cause death compared with those with at least one risk factor. After adjusting confounders, the mortality risk was significant in patients with CCS but not in patients with STEMI and NSTE-ACS.

Background The incidence of and risk factors for chyle leak, as defined by the 2017 International Study Group on Pancreatic Surgery, remain unknown. Methods MEDLINE, EMBASE, and Scopus were systematically searched for studies of patients undergoing pancreatectomy that reported chyle leak according to the 2017 International Study Group on Pancreatic Surgery definition. The primary outcomes were the incidence of overall and clinically relevant chyle leak. A random-effects pairwise meta-analysis was used to calculate the incidence of chyle leak. Results Thirty-five studies including 7,083 patients were included in the meta-analysis. The weighted incidence of overall chyle leak was 6.8% (95% confidence interval 5.6–8.2), and clinically relevant chyle leak was 5.5% (95% confidence interval 3.8–7.7). Pancreaticoduodenectomy, total pancreatectomy, and distal pancreatectomy were associated with a CL incidence of 7.3%, 4.3%, and 5.8%, respectively. Fourteen individual risk factors for chyle leak were identified from included studies. Younger age, low prognostic nutritional index, para-aortic node manipulation, lymphatic involvement, and post-pancreatectomy pancreatitis were significantly associated with chyle leak, all from individual studies. Conclusion The incidence of overall chyle leak and clinically relevant chyle leak after pancreatic surgery, as defined by the 2017 International Study Group on Pancreatic Surgery, is 6.8% and 5.5%, respectively. Several risk factors for chyle leak were identified in the present review; however, larger high-quality studies are needed to more accurately define these risks.

OBJECTIVE: To determine short-term outcomes of patients with alcohol-associated cirrhosis (ALC) admitted to the ICU compared to other etiologies of liver disease. In addition, we investigate whether quick sequential organ failure assessment (qSOFA) accurately predicts presence of sepsis and in-hospital mortality in critically ill patients with various etiologies of cirrhosis. METHODS: A retrospective cohort of 1,174 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Outcomes of interest included survival rates within the ICU, post-ICU in-hospital, or at 30 days post-ICU discharge. RESULTS: 578 patients were found to have alcohol-associated cirrhosis (ALC) with 596 in non-ALC group. There was no significant difference in ICU mortality rates in ALC vs. non-ALC cohorts (10.2% vs 11.7%, P=.40). However, patients with ALC had significantly higher post-ICU in-hospital death (10.0% vs 6.5%, P =.04) as well as higher mortality at 30-day post-ICU discharge (18.7% vs 11.2%, P

The purpose of the first two editions of the guidelines for external radiotherapy procedures, published in 2007 and 2016 respectively, was to issue recommendations aimed at optimising, harmonising and standardising practices. The purpose of this third edition, which includes brachytherapy, is identical while also taking into account recent technological improvements (intensity modulation radiation therapy, stereotactic radiotherapy, and three-dimension brachytherapy) along with findings from literature. Part one describes the daily use of general principles (quality, security, image-guided radiation therapy); part two describes each treatment step for the main types of cancer.

Background Proctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. Methods In total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. Results The rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P Conclusion Technical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.

Quantifying the detection rate of the widely used quantitative RT-PCR (RT-qPCR) test for severe acute respiratory syndrome coronavirus 2 and its dependence on patient demographic characteristics and disease progression is key in designing epidemiologic strategies. Analyzing 843,917 test results of 521,696 patients, a “positivity period” was defined for each patient between diagnosis of coronavirus disease 2019 and the last positive test result. The fraction of positive test results within this period was then used to estimate detection rate. Regression analyses were used to determine associations of detection with time of sampling after diagnosis, patient demographic characteristics, and viral RNA copy number based on RT-qPCR cycle threshold values of the next positive test result. The overall detection rate in tests performed within 14 days after diagnosis was 83.1%. This rate was higher at days 0 to 5 after diagnosis (89.3%). Furthermore, detection rate was strongly associated with demographic characteristics, with an odds ratio of 0.58 (95% CI, 0.53 to 0.63) for women over men and 0.74 (95% CI, 0.72 to 0.75) for patients 10 years younger. Finally, the detection rate with the Allplex 2019-nCoV RT-qPCR kit was associated, at the single-patient level, with viral RNA copy number (P value

OBJECTIVES Vascular surgery patients commonly have several comorbidities that cumulatively lead to a frailty status. The cumulative comorbidities disproportionately increase the risk of adverse events and are also associated with worsened long-term prognosis. In recent years, several tools have been elaborated with the objective of quantifying a patient's frailty. One of them is the modified frailty index-5 (mFI-5), a simplified and easy to use index. There is scarce data regarding its value as a prognostic factor in aortoiliac occlusive disease. The aim of this work is to validate mFI-5 as a potential postoperative prognostic indicator in this population. METHODS From January 2013 to January 2020, 109 patients who underwent elective revascularizations, either endovascular or open surgery, having Trans-Atlantic Inter-Society Consensus II type D aortoiliac lesions in a tertiary and a regional hospital were selected from a prospective vascular registry. Demographic data was collected including diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, arterial hypertension requiring medication and functional status. The 30-day and subsequent long-term surveillance outcomes were also collected including major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality were assessed in the 30-days post-procedure and in the subsequent long-term surveillance period. The mFI-5 was applied to this population to evaluate the prognostic impact of this frailty marker on mortality and morbidity. RESULTS In the long-term follow-up, mFI-5 was significantly associated with MACE (hazard ratio [HR] 2.469; 95% confidence interval [CI]: 1.267-4.811; P = 0.008) and all-cause mortality (HR 2.585; 95% CI: 1.270-5.260; P = 0.009). However, there was no significant association with 30-day outcomes. Along with the presence of chronic kidney disease, mFI-5 was the prognostic factor better able of predicting MACE. No prognostic value was found regarding short-term outcomes. CONCLUSION The mFI-5 index may have a role in predicting long term outcomes, namely MACE and all-cause mortality, in the subset of patients with extensive aortoiliac occlusive disease. Its ease of use can foster its application in risk stratification and contribute for the decision-making process.

The issue of radiation-induced cancers must be taken into consideration during therapeutic irradiations. Risk factors for radiation-induced cancer include: the age of the patients, the volumes irradiated, the presence of risk cofactors and the exposure of critical organs. Those should be part of the therapeutic decision, in terms of indication, as well as choice of the radiotherapy technique (including repositioning systems). We present the update of the recommendations of the French society for radiation oncology on the modalities for preventing radiation-induced cancers.

Summary Background Many children who develop tuberculosis are thought to be missed by diagnostic and reporting systems. We aimed to estimate paediatric tuberculosis incidence and underreporting between 2013 and 2019 in countries representing more than 99% of the global tuberculosis burden. Methods We developed a mathematical model of paediatric tuberculosis natural history, accounting for key mechanisms and risk factors for infectious exposure (HIV, malnutrition, and BCG non-vaccination), the probability of infection given exposure, and progression to disease among infected individuals. We extracted paediatric population estimates from UN Population Division data, and we used WHO estimates for adult tuberculosis incidence rates. We parameterised this model for 185 countries and calibrated it using data from countries with stronger case detection and reporting systems. Using this model, we estimated trends in paediatric incidence, and the proportion of these cases that are diagnosed and reported (case detection ratio [CDR]) for each country, age group, and year. Findings For 2019, we estimated 997 500 (95% credible interval [CrI] 868 700–1 163 100) incident tuberculosis cases among children, with 481 000 cases (398 400–587 400) among those aged 0–4 years and 516 500 cases (442 900–608 000) among those aged 5–14 years. The paediatric CDR was estimated to be lower in children aged 0–4 years (41%, 95% CrI 34–50) than in those aged 5–14 years (63%, 53–75) and varied widely between countries. Estimated CDRs increased substantially over the study period, from 18% (15–20) in 2013 to 53% (45–60) in 2019, with improvements concentrated in the Eastern Mediterranean, South-East Asia, and Western Pacific regions. Over the study period, global incidence was estimated to have declined slowly at an average annual rate of 1·52% (1·42–1·66). Interpretation Paediatric tuberculosis causes substantial morbidity and mortality, and these data indicate that cases (and, thus, probably associated mortality) are currently substantially underreported. These findings reinforce the need to ensure prompt diagnosis and care for children developing tuberculosis, strengthen reporting systems, and invest in research to develop more accurate and easy-to-use diagnostics for paediatric tuberculosis in high-burden settings. Funding National Institutes of Health., Editorial note: the Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.

In the intensive care unit, delirium is a major contributor to morbidity and mortality in adult patients. Patients with delirium have been shown to have increased length of stay, decreased functional outcomes, and increased risk for requiring placement at the time of discharge. In addition, decreased cognitive function and dementia have been shown to be long-term complications from delirium. The mainstay of treatment and prevention include therapy- and behavioral-based interventions, including frequent orientation, cognitive stimulation, mobilization, sleep restoration, and providing hearing and visual aids. Refractory delirium may require pharmacologic intervention with antipsychotics or alpha-2 agonists.

Patients with continuous flow destination therapy (DT) left ventricular assist devices (LVAD) comprise a heterogeneous population. We hypothesized that phenotypic clustering of individuals with DT LVADs by their implantation characteristics will be associated with different long-term risk profiles. We analyzed 5,999 patients with continuous flow DT LVADs in Interagency Registry for Mechanically Assisted Circulatory Support using 18 continuous variable baseline characteristics. We Z-transformed the variables and applied a Gaussian finite mixture model to perform unsupervised clustering resulting in identification of 4 phenogroups. Survival analyses considered the competing risk for cumulative incidence of transplant or the composite end point of death or heart transplant where appropriate. Phenogroup 1 (n = 1,163, 19%) was older (71 years) and primarily white (81%). Phenogroups 2 (n = 648, 11%) and 3 (n = 3,671, 61%) were of intermediate age (70 and 62 years), weight (85 and 87 kg), and ventricular size. Phenogroup 4 (n = 517, 9%) was younger (40 years), heavier (108 kg), and more racially diverse. The cumulative incidence of death, heart transplant, bleeding, LVAD malfunction, and LVAD thrombosis differed among phenogroups. The highest incidence of death and the lowest rate of heart transplant was seen in phenogroup 1 (p0.001). For adverse outcomes, phenogroup 4 had the lowest incidence of bleeding, whereas LVAD device thrombosis and malfunction were lowest in phenogroup 1 (p0.001 for all). Finally, the incidence of stroke, infection, and renal dysfunction were not statistically different. In conclusion, the present unsupervised machine learning analysis identified 4 phenogroups with different rates of adverse outcomes and these findings underscore the influence of phenotypic heterogeneity on post-LVAD implantation outcomes.

The adult human heart has limited regenerative capacity. As such, the massive cardiomyocyte loss due to myocardial infarction leads to scar formation and adverse cardiac remodeling, which ultimately results in chronic heart failure. Direct cardiac reprogramming that converts cardiac fibroblast into functional cardiomyocyte-like cells (also called iCMs) holds great promise for heart regeneration. Cardiac reprogramming has been achieved both in vitro and in vivo by using a variety of cocktails that comprise transcription factors, microRNAs, or small molecules. During the past several years, great progress has been made in improving reprogramming efficiency and understanding the underlying molecular mechanisms. Here, we summarize the direct cardiac reprogramming methods, review the current advances in understanding the molecular mechanisms of cardiac reprogramming, and highlight the novel insights gained from single-cell omics studies. Finally, we discuss the remaining challenges and future directions for the field.

Background Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with ‘pneumonia’ the year previously. Methods We conducted a medical record review of patients admitted with Covid-19 and a pulmonary infiltrate and compared them with patients diagnosed with pneumonia admitted in the prior year before the pandemic. Data abstracted included baseline demographics, comorbidities, signs and symptoms, laboratory and microbiological results, and imaging findings. Outcomes were bacterial infections and mortality. Patients presenting with and without Covid-19 were compared using univariable and multivariable analyses. Results There were 1398 and 1001 patients admitted through the emergency department (ED) with and without Covid-19 respectively. Compared with non-Covid-19 patients, those with Covid-19 were younger (61±18 vs. 65±25 years, P

Objective: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. Methods: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (

Objective To systematically describe the short stature of patients with Diamond-Blackfan anemia and to explore factors affecting the height development of patients with Diamond-Blackfan anemia. Study design This cross-sectional study was conducted at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and the height, weight, and clinical data of 129 patients with Diamond-Blackfan anemia were collected from June 2020 to September 2020. Results The median height-age-z score (HAZ) of children affected by Diamond-Blackfan anemia was −1.54 (−6.36-1.96). Short stature was found in 37.98% of the patients. Specific Diamond-Blackfan anemia growth curves were developed for weight, height, and body mass index, separately for male and female patients. Multivariable logistic regression models showed that female sex (aOR 4.92; 95% CI 1.29-18.71; P = .0195), underweight (aOR 10.41, 95% CI 1.41-76.98, P = .0217), cardiovascular malformations (aOR 216.65; 95% CI 3.29-14279.79; P = .0118), and RPL11(aOR 29.14; 95% CI 1.18-719.10; P = .0392) or RPS26 (aOR 53.49; 95% CI 1.40-2044.30; P = .0323) mutations were independent risk factors for short stature. In the subgroup of patients who were steroid-dependent, patients with a duration of steroid therapy over 2 years (OR 2.95; 95% CI 1.00-8.66; P = .0494) or maintenance dose of prednisone >0.1 mg/kg per day (OR 3.30; 95% CI 1.02-10.72; P = .0470) had a higher incidence of short stature. Conclusions Patients with Diamond-Blackfan anemia had a high prevalence of short stature. The risk of short stature increased with age and was associated with sex, underweight, congenital malformations, and RPL11 or RPS26 mutations. The duration of steroid therapy and maintenance dose of steroid was significantly associated with the incidence of short stature in steroid-dependent patients with Diamond-Blackfan anemia.

Contemporary data on the prevalence and incidence of aortic stenosis (AS) and aortic valve replacement (AVR) in patients initiating dialysis are scarce. This observational cohort study aimed to estimate (1) the point prevalence of AS and AVR at dialysis start and (2) the AS incidence and associated factors prospective to dialysis initiation. The study included 14,550 patients initiating dialysis registered in the Swedish Renal Registry between 2005 and 2018. AS was defined by the International Statistical Classification of Diseases, Tenth Revision codes, and AVR by the surgical procedure codes. Associations between covariates and outcomes were assessed in Cox regression models. The median age was 68 (57 to 77), 66% were males, and the point prevalence of AS and AVR was 3.4% and 1.1%, respectively. In those without known AS/AVR at dialysis initiation (n = 14,050), AS was diagnosed in 595 patients (incidence 16.3/1000 person-years, 95% confidence interval [CI] 15.1 to 17.7/1,000 person-years) during a median follow-up of 2.7 years (interquartile range 1.1 to 5.7). In adjusted Cox regression models, higher age (hazard ratio [HR] 1.03, 95% CI 1.02 to 1.04), male gender (HR 1.51, 95% CI 1.25 to 1.83), atrial fibrillation (HR 1.32, 95% CI 1.06 to 1.64), and hypertension (HR 1.65, 95% CI 1.03 to 2.65) were associated with incident AS. Peritoneal dialysis patients had a nonsignificant trend toward higher AS risk compared with hemodialysis (HR 1.18, 95% CI 0.99 to 1.40). About 20% of patients (n = 113) diagnosed with incident AS underwent AVR (incidence 3.1/1000 person-years, 95% CI 2.6 to 3.7/1,000). Only the male gender was associated with AVR (HR 2.07, 95% CI 1.30 to 3.30). In conclusion, the prevalence and incidence of AS and AVR in patients initiating dialysis are high. A fifth of newly diagnosed AS underwent AVR after dialysis onset.

Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.

OBJECTIVES This study aimed to evaluate the most updated worldwide distribution, risk factors, and temporal trends of cervical cancer for different countries and age groups. METHODS The Global Cancer Observatory database was retrieved for the age-standardized rates (ASRs, per 100,000 persons) for incidence and mortality of cervical cancer in 2018. The associations with risk factors were examined by multivariable regression analysis, adjusting for human development index (HDI) and gross domestic products (GDP) per capita. Joinpoint regression analysis was used to calculate the 10-year annual average percent change (AAPC) for incidence and mortality. RESULTS A total of 568,847 new cases (ASR, 13.1) and 311,365 deaths (ASR, 6.9) of cervical cancer were reported globally in 2018. The highest incidence and mortality were observed in Southern Africa (ASRs, 43.1 and 20.0) and countries with low HDI (ASRs, 29.8 and 23.0). Countries with higher incidence and mortality had lower HDI (β = -8.19, 95% CI -11.32 to -5.06, p

Evidence on the efficacy and safety of low-dose direct oral anticoagulant (DOAC) in older patients with nonvalvular atrial fibrillation is still scarce. We conducted a single-center prospective registry of patients with nonvalvular atrial fibrillation treated with DOACs: the DIRECT registry (n = 2,216; follow-up, 407 ± 388 days, UMIN000033283). The whole population was divided into 2 groups: the older group (age ≥80 years, n = 548) versus the younger group (age80 years, n = 1,668). Primary safety and efficacy end points were major bleeding according to the International Society on Thrombosis and Haemostasis criteria, and stroke or systemic embolism (SSE), respectively. Effects of known risk factors and low-dose DOAC on major bleeding and SSE were assessed using a multivariable Cox proportional hazards model. In the older group, low-dose DOAC was associated with lower bleeding events (hazard ratio 0.279, 95% confidence interval 0.087 to 0.892, p = 0.031) but was not associated with increased SSE (p = 0.894). In the younger group, low-dose DOAC was neither associated with risk of major bleeding nor SSE (both p 0.05). In conclusion, in older patients, low-dose DOAC was associated with reduced risk of major bleeding without compromising its efficacy.

Background Ozone effects on lung function are particularly important to understand in the context of the air pollution-health outcomes epidemiologic literature, given the complex relationships between ozone and other air pollutants with known lung function effects. Research Question What has been learned about the association between ozone exposures and lung function from epidemiology studies published from 2013 through 2020? Study Design and Methods On March 18, 2018, and September 8, 2020, PubMed was searched using the terms health AND ozone, filtering to articles in English and about humans, from 2013 or later. An additional focused review searching for ozone AND (lung function OR FEV1 OR FVC) was performed June 26, 2021. Articles were selected for this review if they reported a specific relationship between a lung function outcome and ozone exposure. Results Of 3,271 articles screened, 53 ultimately met criteria for inclusion. A systematic review with assessment of potential for bias was conducted, but a meta-analysis was not carried out because of differences in exposure duration and outcome quantification. Consistent evidence exists of small decreases in children’s lung function, even associated with very low levels of short-term ozone exposure. The effects on adult lung function from exposure to low-level, short-term ozone are less clear, although ozone-associated decrements may occur in the elderly. Finally, long-term ozone exposure decreases both lung function and lung function growth in children, although few new studies have examined long-term ozone and lung function in adults. Interpretation Much of this literature involves concentrations below the current US Environmental Protection Agency’s National Ambient Air Quality Standard of 70 parts per billion over an 8-h averaging time, suggesting that this current standard may not protect children adequately from ozone-related decrements in lung function.

The Ross procedure is rarely considered in older patients. The aim of this study is to compare the perioperative and long-term outcomes of patients aged 50 years and older with younger patients after the Ross procedure.Between 1992 and 2018, 455 patients underwent the Ross procedure utilizing the inclusion technique. Patients with redo surgery, nonaortic procedures, and unsupported root replacement were excluded. The remaining were matched for native valve morphology, valve lesion, and annular manipulation and yielded 96 matched pairs. Preoperative and operative characteristics, perioperative outcomes, survival rates, valve-related adverse events, and valve hemodynamics were assessed.There was no in-hospital mortality. The median follow-up was 11 years for both cohorts. Overall survival at 15 years was similar: 99% (95% confidence interval [CI] 89.8%-99.8%) for patients aged ≥50 years and 98% (95% CI 89.3-99.7%) for younger patients. Patients 50 years and older had a notable freedom from Ross-related reintervention at 15 years: 94% (95% CI 84.8%-97.7%) vs 90% (95% CI 80.2%-95.6%) in younger patients. The mixed model analysis revealed that being 50 years and older was not significantly associated with higher autograft gradient or regurgitation. Interestingly, being 50 years and older correlated with decreased allograft regurgitation and stenosis.Older patients undergoing the Ross procedure had comparable outcomes to younger patients. Patients aged 50 years and over who are high-functioning with minimal comorbidities should be considered for the Ross procedure.

BACKGROUND Current trauma activation guidelines do not clearly address age as a risk factor when leveling trauma patients. Glasgow coma scale (GCS) and mode of injury play a major role in leveling trauma patients. We studied the above relationship in our elderly patients presenting with traumatic head injury. METHODS This study was a retrospective analysis of patients who presented to the emergency department with traumatic brain injuries. We classified the 270 patients into two groups. Group A was 64 years and younger, and group B was 65 years and older. Their GCS, ISS, age, sex, comorbidities, and anticoagulant use were abstracted. The primary outcome was mortality and length of stay. The groups were compared using an independent student's t-test and Chi-square analysis. The Cox regression analysis was used to analyze differences in the outcome while adjusting for the above factors. RESULTS There were 140 patients in group A, and 130 patients in group B who presented to the ED with a GCS of 14-15 and an ISS of below 15. The mean ISS significantly differed between group A (6.2 ± 6.8) vs (7.9 ± 3.2) in group B (p

Objectives: We examined the use and long-term outcomes of vaginal hysterectomy for women with early-stage endometrial cancer. Methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women with stage I-II endometrial cancer treated with primary hysterectomy from 2000-2015. Multivariable models were developed to examine clinical, demographic, and pathologic factors associated with performance of TVH. The association between route of hysterectomy and cancer specific and overall survival was examined using multivariable Cox proportional hazards models. Results: A total of 19,212 patients including 837 (4.6%) who underwent TVH were identified. Performance of vaginal hysterectomy declined from 4.5% in 2000 to 2.2% in 2015 (P 80 years old (aRR=1.60; 95% CI, 1.30-1.97) were more likely to undergo TVH. There was no association between either overall co-morbidity (Charlson index) or any individual comorbidities and performance of TVH. Women with high grade tumors were less likely to undergo TVH. Five-year survival was 78.4% (95% CI: 77.6-79.2) in those who underwent abdominal hysterectomy, 83.3% (95% CI: 82.1-84.4) in those who had a laparoscopic hysterectomy and 80.9% (95% CI: 77.8-83.5) in those who underwent TVH. In multivariable models, there was no adverse impact between TVH and either overall (HR=1.06; 95% CI, 0.94-1.19) or cancer-specific (HR=0.95; 95% CI, 0.70-1.28) survival. Download : Download high-res image (83KB) Download : Download full-size image Conclusions: Use of vaginal hysterectomy for stage I/II endometrial cancer has decreased in the U.S. Chronologic age is the greatest predictor of performance of TVH. Performance of TVH does not negatively impact survival for women with early-stage endometrial cancer.

Patients with human immunodeficiency virus (HIV) infection are at increased risk of cardiovascular disease, but studies on HIV as a risk factor for cardiac arrest in the general population are lacking. We aimed to examine the association of HIV infection with out-of-hospital cardiac arrests (OHCAs). We used the Office of Statewide Health Planning and Development data to evaluate HIV infection as a predictor of OHCA in all California emergency department encounters from 2005 to 2015, adjusting for age, gender, race, income, obesity, smoking, alcohol, substance abuse, hypertension (HTN), diabetes, coronary artery disease, congestive heart failure (CHF), atrial fibrillation, and chronic kidney disease (CKD). We also determined patient characteristics modifying these associations by including interaction terms in multivariable-adjusted models. In 18,542,761 patients (mean age 47 ± 20 years, 53% women, 43,849 with HIV) followed for a median 6.8 years, 133,983 new OHCA events occurred. Incidence rates in patients with HIV were higher than in patients without HIV (1.99 vs 1.16 OHCA events per 1,000-person-years follow-up). After multivariable adjustment, HIV was associated with a 2.5-fold higher risk of OHCA (hazard ratio 2.47, 95% confidence interval 2.29 to 2.66, p

This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.

Summary Background India faces a high burden of diabetes and hypertension. Currently, there is a dearth of economic evidence about screening programmes, affected age groups, and frequency of screening for these diseases in Indian settings. We assessed the cost effectiveness of population-based screening for diabetes and hypertension compared with current practice in India for different scenarios, according to type of screening test, population age group, and pattern of health-care use. Methods We used a hybrid decision model (decision tree and Markov model) to estimate the lifetime costs and consequences from a societal perspective. A meta-analysis was done to assess the effectiveness of population-based screening. Primary data were collected from two Indian states (Haryana and Tamil Nadu) to assess the cost of screening. The data from the National Health System Cost Database and the Costing of Health Services in India study were used to determine the health system cost of diagnostic tests and cost of treating diabetes or hypertension and their complications. A total of 962 patients were recruited to assess out-of-pocket expenditure and quality of life. Parameter uncertainty was evaluated using univariate and multivariable probabilistic sensitivity analyses. Finally, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with alternative scenarios of scaling up primary health care through a health and wellness centre programme for the treatment of diabetes and hypertension. Findings The incremental cost per QALY gained across various strategies for population-based screening for diabetes and hypertension ranged from US$0·02 million to $0·03 million. At the current pattern of health services use, none of the screening strategies of annual screening, screening every 3 years, and screening every 5 years was cost-effective at a threshold of 1-time per capita gross domestic product in India. In the scenario in which health and wellness centres provided primary care to 20% of patients who were newly diagnosed with uncomplicated diabetes or hypertension, screening the group aged between 30 and 65 years every 5 years or 3 years for either diabetes, hypertension, or a comorbid state (both diabetes and hypertension) became cost-effective. If the share of treatment for patients with newly diagnosed uncomplicated diabetes or hypertension at health and wellness centres increases to 70%, from the existing 4% at subcentres and primary health centres, annual population-based screening becomes a cost saving strategy. Interpretation Population-based screening for diabetes and hypertension in India could potentially reduce time to diagnosis and treatment and be cost-effective if it is linked to comprehensive primary health care through health and wellness centres for provision of treatment to patients who screen positive. Funding Department of Health Research, Government of India.

Transcatheter pulmonary valve (TPV) replacement (TPVR) has become the standard therapy for postoperative pulmonary outflow tract dysfunction in patients with a prosthetic conduit/valve, but there is limited information about risk factors for death or reintervention after this procedure.This study sought to evaluate mid- and long-term outcomes after TPVR in a large multicenter cohort.International registry focused on time-related outcomes after TPVR.Investigators submitted data for 2,476 patients who underwent TPVR and were followed up for 8,475 patient-years. A total of 95 patients died after TPVR, most commonly from heart failure (n = 24). The cumulative incidence of death was 8.9% (95% CI: 6.9%-11.5%) 8 years after TPVR. On multivariable analysis, age at TPVR (HR: 1.04 per year; 95% CI: 1.03-1.06 per year; P 0.001), a prosthetic valve in other positions (HR: 2.1; 95% CI: 1.2-3.7; P = 0.014), and an existing transvenous pacemaker/implantable cardioverter-defibrillator (HR: 2.1; 95% CI: 1.3-3.4; P = 0.004) were associated with death. A total of 258 patients underwent TPV reintervention. At 8 years, the cumulative incidence of any TPV reintervention was 25.1% (95% CI: 21.8%-28.5%) and of surgical TPV reintervention was 14.4% (95% CI: 11.9%-17.2%). Risk factors for surgical reintervention included age (0.95 per year [95% CI: 0.93-0.97 per year]; P 0.001), prior endocarditis (2.5 [95% CI: 1.4-4.3]; P = 0.001), TPVR into a stented bioprosthetic valve (1.7 [95% CI: 1.2-2.5]; P = 0.007), and postimplant gradient (1.4 per 10 mm Hg [95% CI: 1.2-1.7 per 10 mm Hg]: P 0.001).These findings support the conclusion that survival and freedom from reintervention or surgery after TPVR are generally comparable to outcomes of surgical conduit/valve replacement across a wide age range.

Brain age is a neuroimaging-based biomarker of aging. This study examined whether the difference between brain age and chronological age (brain-PAD) is associated with cognitive function at baseline and longitudinally. Participants were relatively healthy, predominantly white community-dwelling older adults (n = 531, aged ≥70 years), with high educational attainment (61% ≥12 years) and socioeconomic status (59% ≥75th percentile). Brain age was estimated from T1-weighted magnetic resonance images using an algorithm by Cole et al., 2018. After controlling for age, gender, education, depression and body mass index, brain-PAD was negatively associated with psychomotor speed (Symbol Digit Modalities Test) at baseline (Bonferroni p < 0.006), but was not associated with baseline verbal fluency (Controlled Oral Word Association Test), delayed recall (Hopkins Learning Test Revised), or general cognitive status (Mini-Mental State Examination). Baseline brain-PAD was not associated with 3-year change in cognition (Bonferroni p > 0.006). These findings indicate that even in relatively healthy older people, accelerated brain aging is associated with worse psychomotor speed, but future longitudinal research into changes in brain-PAD is needed.

Annual repeat influenza vaccination raises concerns about protective efficacy against mismatched viruses. We investigated the impact of heterologous prime-boost vaccination on inducing cross protection by designing recombinant influenza viruses with chimeric hemagglutinin (HA) carrying M2 extracellular domains (M2e-HA). Heterologous prime-boost vaccination of C57BL/6 mice with M2e-HA chimeric virus more effectively induced M2e and HA stalk specific IgG antibodies correlating with cross protection than homologous prime-boost vaccination. Induction of M2e and HA stalk specific IgG antibodies was compromised in 1-year old mice, indicating significant aging effects on priming subdominant M2e and HA stalk IgG antibody responses. This study demonstrates that a heterologous prime-boost strategy with recombinant influenza virus expressing extra M2e epitopes provides more effective cross protection than homologous vaccination.

Takotsubo syndrome (TTS) largely affects postmenopausal women but has been shown to carry increased mortality risk in men. We sought to evaluate nationwide in-hospital outcomes between men and women admitted with TTS to better characterize these disparities. Using the National Inpatient Sample database from 2011 to 2018, we identified a total of 48,300 hospitalizations with the primary diagnosis of TTS. The primary end point was in-hospital all-cause mortality. Secondary end points included in-hospital complications, length of stay, and discharge disposition. Men with TTS accounted for 8.9% of hospitalizations, were younger in age (62.0 ± 15.1 vs 66.8 ± 12.1 years, p