Nomogram to predict feeding intolerance in critically ill children.

Feed intolerance (FI) is significantly associated with poor prognosis in critically ill patients. This study aimed to understand the characteristics of children with FI and identify the factors predicting FI in critically ill children. This retrospective cohort study was conducted between January 2017 and June 2022 in the Pediatric Intensive Care Unit of a specialized children's hospital. Eighteen factors, including age, body mass index for age z-score (BAZ) < -2, paediatric index of mortality (PIM)3 score, Glasgow coma scale score, mechanical ventilation (MV), enteral nutrition delay, vasoactive drugs, sedatives, sepsis, heart disease, neurological disease, hypokalemia, arterial PH < 7.35, arterial partial pressure of oxygen (PaO2), blood glucose, hemoglobin, total protein, and albumin, were retrieved to predict FI. The outcome was FI during PICU stay. During the study period, a total of 854 children were included, of which 215 children developed FI. Six predictors of FI were selected: PIM3 score, MV, sepsis, hypokalemia, albumin, and PaO2. Multivariate logistic regression analysis showed that higher PIM3 score, MV, sepsis, hypokalemia, and lower PaO2 were independent risk factors for FI, whereas higher albumin was an independent protective factor for FI. The C-index of the predictive nomogram of 0.943 was confirmed at internal validation to be 0.940, indicating a good predictive value of the model. Decision curve analysis shows good clinical applicability of the nomogram in predicting FI.    Conclusion: The nomogram was verified to have a good prediction performance based on discrimination, calibration, and clinical decision analysis. What is Known: • Research has demonstrated that gastrointestinal (GI) dysfunction is not only a fundamental element of Multiple Organ Dysfunction Syndrome (MODS), but also the initiator of MODS. • Previous study has demonstrated a significant association between FI and poor prognosis in critically ill patients. What is New: • We excluded patients with primary gastrointestinal tract disease from our study, and we observed an incidence of FI of 25.2% in the Pediatric Intensive Care Unit (PICU). • Our study revealed that PIM3 score, MV, sepsis, hypokalemia, albumin, and PaO2 are significant predictors of FI.

Paternal Occupation and Delirium Risk in Older Adults: A Potential Marker of Early-Life Exposures.

Background and Objectives: Delirium is a common disorder among older adults following hospitalization or major surgery. Whereas many studies examine the risk of proximate exposures and comorbidities, little is known about pathways linking childhood exposures to later-life delirium. In this study, we explored the association between paternal occupation and delirium risk. Research Design and Methods: A prospective observational cohort study of 528 older adults undergoing elective surgery at two academic medical centers. Paternal occupation group (white collar vs. blue collar) served as our independent variable. Delirium incidence was assessed using the Confusion Assessment Method (CAM) supplemented by medical chart review. Delirium severity was measured using the peak CAM-Severity score (CAM-S Peak), the highest value of CAM-S observed throughout the hospital stay. Results: Blue-collar paternal occupation was significantly associated with a higher rate of incident delirium (91/234, 39%) compared with white-collar paternal occupation (84/294, 29%), adjusted odds ratio OR (95% confidence interval [CI]) = 1.6 (1.1, 2.3). All analyses were adjusted for participant age, race, gender, and Charlson Comorbidity Index. Blue-collar paternal occupation was also associated with greater delirium severity, with a mean score (SD) of 4.4 (3.3), compared with white-collar paternal occupation with a mean score (SD) of 3.5 (2.8). Among participants reporting blue-collar paternal occupation, we observed an adjusted mean difference of 0.86 (95% CI = 0.4, 1.4) additional severity units. Discussion and Implications: Blue-collar paternal occupation is associated with greater delirium incidence and severity, after adjustment for covariates. These findings support the application of a life-course framework to evaluate the risk of later-life delirium and delirium severity. Our results also demonstrate the importance of considering childhood exposures, which may be consequential even decades later.

Psychometric Properties of a Delirium Severity Score for Older Adults and Association With Hospital and Posthospital Outcomes.

Importance: The ability to rate delirium severity is key to providing optimal care for older adults, and such ratings would allow clinicians to target patients with severe delirium and monitor response to treatment, recovery time, and prognosis; assess nursing burden and staffing needs; and, ultimately, provide more appropriate patient-centered care. Current delirium severity measures have been limited in their content, gradations, and measurement characteristics. Objective: To examine the internal consistency, reliability, and validity for clinical outcomes of the DEL-S delirium severity score, a measure of delirium severity that was developed using advanced psychometric approaches, analogous to those of the Patient-Reported Outcomes Measurement Information System initiative. Design, Setting, and Participants: This prospective cohort study was conducted at a large academic medical center in Boston, Massachusetts. Adults aged 70 years or older who were admitted or transferred to medical or surgical services as either emergency or elective admissions were enrolled between October 20, 2015, and March 15, 2017, and were monitored for 1 year. Data analysis was performed from June 2020 to August 2021. Exposures: Delirium severity, measured by scores on the delirium severity score short-form (SF; 6 items, scored 0-13, with higher scores indicating more severe delirium) and long-form (LF; 17 items, scored 0-21), considered continuously and grouped into 5 categories. Main Outcomes and Measures: The primary outcomes were in-hospital outcomes, including length of stay and hospital costs, and posthospital (30, 90, and 365 days) outcomes, including death, health care costs, and rehospitalization. Results: The 352 participants had a median (IQR) age of 79.7 (74.6-85.5) years, 204 (58.0%) were women, and they were highly educated (median [IQR] duration of education, 14 [7-20] years). Patients in the highest delirium severity score SF group (scores 6-9) had a longer length of stay (13.3 vs 6.9 days; P for trend < .001), greater in-hospital costs ($57 700 vs $34 200), greater cumulative health care costs ($168 700 vs $106 500; P for trend = .01), and increased mortality at 1 year (50% vs 17%; P for trend = .02) compared with patients in the lowest delirium severity score SF group (score 0). Similar trends and significant findings were demonstrated for the delirium severity score LF. Conclusions and Relevance: These findings suggest that the delirium severity score provides an approach for measuring delirium severity that is associated with adverse clinical outcomes in a direct exposure-response association and that the delirium severity score may help advance patient-centered care for delirium.

Initial Clinical Characteristics of 146 Patients with COVID-19 Reported in Guizhou Province, China: A Survival Analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has caused an outbreak around the world. Early detection of severe illness is crucial for patients' survival. We analysed initial clinical characteristics of 146 patients with COVID-19 reported in Guizhou province, China to explore risk factors for transforming mild illness to severe. METHODOLOGY: Data of 146 laboratory-confirmed cases were collected and evaluated by the survival analysis of univariate and multivariate Cox proportional hazards model. RESULTS: On initial presentation, patients had fever (51.05%), dry cough (45.45%), headache (16.08%), shortness of breath (7.75%) and gastrointestinal symptoms (13.99%). Among 146 laboratory-confirmed cases, 30 patients (20.55%) had severe illness and needed Intensive Care Unit care for supportive treatment. The remaining patients (116, 79.45%) were non-severe cases. Nineteen (19/146, 13.01%) of 30 patients in the Intensive Care Unit had comorbidities, including hypertension (12, 40.00%), diabetes (5, 16.67%), cardiovascular disease (5, 16.67%) and pulmonary disease (4, 13.33%). For survival analysis, patients who had fever (HR = 3.30, 95% CI = 1.31, 8.29) and comorbidities (HR = 9.76, 95% CI = 4.28, 22.23) at baseline were more likely to be admitted into the Intensive Care Unit. Few variables were not related to the survival time of discharge from baseline to discharge and from Intensive Care Unit care to discharge. CONCLUSIONS: Severe patients with COVID-19 should be paid more attention. On initial symptoms, many patients did not have fever, but those with fever were more likely to be admitted to the Intensive Care Unit. Comorbidities were likewise a risk factor of severe COVID-19.

Association Between Perioperative Medication Use and Postoperative Delirium and Cognition in Older Adults Undergoing Elective Noncardiac Surgery.

BACKGROUND: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery. METHODS: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month. RESULTS: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed. CONCLUSIONS: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.

Recent advances in the study of a novel Omicron variant of SARS-CoV-2 / 中国热带医学

@#Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.

Epidemiological Survey of First Human Brucellosis Outbreak Caused by the Sika Deer (Cervus nippon) - Guizhou Province, China, 2019.

What is already known on this topic? Brucellosis is a zoonotic infectious disease caused by Brucella spp. The main source of infection in human brucellosis is sick animals, mainly including sheep, goat, and cattle, but sika deer (Cervus nippon) can also cause human brucellosis. The first human brucellosis case in Guizhou Province was reported in 2009, and no brucellosis outbreak was reported caused by sika deer ever before. What is added by this report? This is the first reported outbreak of human brucellosis caused by sika deer in Guizhou Province. Inappropriate regulation of animal movement may be the main driver of introducing and spreading brucellosis in southern areas. The ability to diagnose brucellosis in both humans and animals was weak in the county where the outbreak took place. What are the implications for public health practice? It was suggested to prioritize occupational protection and health education for sika deer breeders. The inspection of the movement of animals and the reimbursement policy need to be improved.

Development and internal validation of a predictive model of cognitive decline 36 months following elective surgery.

INTRODUCTION: Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery. METHODS: We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non-cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut. RESULTS: In a hold-out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r-square (R2 ) of .31. Prediction of "rapid" decliners as a group achieved an area under the curve (AUC) of .75. CONCLUSION: Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.

Homocysteine restrains hippocampal neurogenesis in focal ischemic rat brain by inhibiting DNA methylation.

Ischemic stroke represents a major cause of mortality worldwide. An elevated level of homocysteine (Hcy) is recognized as a powerful risk factor of ischemic stroke. We previously reported that Hcy induces cytotoxicity and proliferation inhibition in neural stem cells (NSCs) derived from the neonatal rat hippocampus in vitro. However, the toxic potential of Hcy on NSCs and its underlying mechanisms are not entirely clear in ischemic brain. Since DNA methylation is critical for establishing the diverse cell fates in the central nervous system, we hypothesized that negative effect of Hcy (an intermediate in the one-carbon metabolism) on neurogenesis might be link to DNA methylation in ischemic stroke. In our study, the rats in Hcy intervention group were intraperitoneally injected with 2% Hcy solution (5 mL/kg/d) for 7 consecutive days before MCAO surgery until they were sacrificed. Our study indicated that Hcy inhibited NSCs self-renewal capacity, which was exhibited by lowering the number of DCX+/BrdU+ and NeuN+/BrdU+ in ischemic brain hippocampus. A reduction in the activity of the DNA methyltransferases (DNMTs), total methylation level and the number of 5mC+/NeuN+ and DCX+/5mC+ cells was observed in Hcy-treated ischemic brains. Additionally, Hcy also induced an increase in S-adenosylhomocysteine (SAH), and a decrease in the ratio of S-adenosylmethionine (SAM) to SAH. These results suggest that the alterations in DNA methylation may be an important mechanism by which Hcy inhibits neurogenesis after stroke. Hcy-induced DNA hypomethylation may be mainly caused by a reduction in the DNMT activity which is regulated by the concentrations of SAM and SAH. Maintaining normal DNA methylation by lowering Hcy level may possess therapeutic potential for promoting neurological recovery and reconstruction after stroke.

Epidemiologic Characteristics of COVID-19 in Guizhou Province, China.

INTRODUCTION: At the end of 2019, the COVID-19 broke out, and spread to Guizhou province in January of 2020. METHODOLOGY: To acquire the epidemiologic characteristics of COVID-19 in Guizhou province, we collected data from 169 laboratory-confirmed COVID-19 related cases. We described the demographic characteristics of the cases and estimated the incubation period, serial interval and the effective reproduction number. We also presented two representative case studies in Guizhou province: Case Study 1 was an example of the asymptomatic carrier; while Case Study 2 was an example of a large and complex infection chain that involved four different regions, spanning three provinces and eight families. RESULTS: Two peaks in the incidence distribution associated with COVID-19 in Guizhou province were related to the 6.04 days (95% CI: 5.00 - 7.10) of incubation period and 6.14±2.21 days of serial interval. We also discussed the effectiveness of the control measures based on the instantaneous effective reproduction number that was a constantly declining curve. CONCLUSIONS: As of February 2, 2020, the estimated effective reproduction number was below 1, and no new cases were reported since February 26. These showed that Guizhou Province had achieved significant progress in preventing the spread of the epidemic. The medical isolation of close contacts was consequential. Meanwhile, the asymptomatic carriers and the super-spreaders must be isolated in time, who would cause a widespread infection.

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults.

INTRODUCTION: The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. METHODS: Participants (n = 59) were free of clinical dementia, age ≥ 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were A = amyloid beta (Aß)42 <175 pg/mL or Aß42/40 ratio <0.07; T = p-tau >80 pg/mL; and N = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively. RESULTS: Aß42, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67), P = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores. DISCUSSION: The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium.

Machine Learning to Develop and Internally Validate a Predictive Model for Post-operative Delirium in a Prospective, Observational Clinical Cohort Study of Older Surgical Patients.

BACKGROUND: Our objective was to assess the performance of machine learning methods to predict post-operative delirium using a prospective clinical cohort. METHODS: We analyzed data from an observational cohort study of 560 older adults (≥ 70 years) without dementia undergoing major elective non-cardiac surgery. Post-operative delirium was determined by the Confusion Assessment Method supplemented by a medical chart review (N = 134, 24%). Five machine learning algorithms and a standard stepwise logistic regression model were developed in a training sample (80% of participants) and evaluated in the remaining hold-out testing sample. We evaluated three overlapping feature sets, restricted to variables that are readily available or minimally burdensome to collect in clinical settings, including interview and medical record data. A large feature set included 71 potential predictors. A smaller set of 18 features was selected by an expert panel using a consensus process, and this smaller feature set was considered with and without a measure of pre-operative mental status. RESULTS: The area under the receiver operating characteristic curve (AUC) was higher in the large feature set conditions (range of AUC, 0.62-0.71 across algorithms) versus the selected feature set conditions (AUC range, 0.53-0.57). The restricted feature set with mental status had intermediate AUC values (range, 0.53-0.68). In the full feature set condition, algorithms such as gradient boosting, cross-validated logistic regression, and neural network (AUC = 0.71, 95% CI 0.58-0.83) were comparable with a model developed using traditional stepwise logistic regression (AUC = 0.69, 95% CI 0.57-0.82). Calibration for all models and feature sets was poor. CONCLUSIONS: We developed machine learning prediction models for post-operative delirium that performed better than chance and are comparable with traditional stepwise logistic regression. Delirium proved to be a phenotype that was difficult to predict with appreciable accuracy.

Neighborhood-Level Social Disadvantage and Risk of Delirium Following Major Surgery.

BACKGROUND/OBJECTIVES: Delirium is a common postoperative complication associated with prolonged length of stay, hospital readmission, and premature mortality. We explored the association between neighborhood-level characteristics and delirium incidence and severity, and compared neighborhood- with individual-level indicators of socioeconomic status in predicting delirium incidence. DESIGN: A prospective observational cohort of patients enrolled between June 18, 2010, and August 8, 2013. Baseline interviews were conducted before surgery, and delirium/delirium severity was evaluated daily during hospitalization. Research staff evaluating delirium were blinded to baseline cognitive status. SETTING: Two academic medical centers in Boston, MA. PARTICIPANTS: A total of 560 older adults, aged 70 years or older, undergoing major noncardiac surgery. INTERVENTION: The Area Deprivation Index (ADI) was used to characterize each neighborhood's socioeconomic disadvantage. MEASUREMENTS: Delirium was assessed using the Confusion Assessment Method (CAM) long form. Delirium severity was calculated using the highest value of CAM Severity score (CAM-S) occurring during daily hospital assessments (CAM-S Peak). RESULTS: Residing in the most disadvantaged neighborhoods (ADI > 44) was associated with a higher risk of incident delirium (12/26; 46%), compared with the least disadvantaged neighborhoods (122/534; 23%) (risk ratio (RR) (95% confidence interval (CI)) = 2.0 (1.3-3.1). The CAM-S Peak score was significantly associated with ADI (Spearman rank correlation, ρ = 0.11; P = .009). Mean CAM-S Peak scores generally rose from 3.7 to 5.3 across levels of increasing neighborhood disadvantage. The RR (95% CI) values associated with individual-level markers of socioeconomic status and cultural background were: 1.2 (0.9-1.7) for education of 12 years or less; 1.3 (0.8-2.1) for non-White race; and 1.7 (1.1-2.6) for annual household income of less than $20,000. None of these individual-level markers exceeded the ADI in terms of effect size or significance for prediction of delirium risk. CONCLUSIONS: Neighborhood-level makers of social disadvantage are associated with delirium incidence and severity, and demonstrated an exposure-response relationship. Future studies should consider contextual-level metrics, such as the ADI, as risk markers of social disadvantage that can help to guide delirium treatment and prevention.

New Delirium Severity Indicators: Generation and Internal Validation in the Better Assessment of Illness (BASIL) Study.

BACKGROUND: Delirium is a common and preventable geriatric syndrome. Moving beyond the binary classification of delirium present/absent, delirium severity represents a potentially important outcome for evaluating preventive and treatment interventions and tracking the course of patients. Although several delirium severity assessment tools currently exist, most have been developed in the absence of advanced measurement methodology and have not been evaluated with rigorous validation studies. OBJECTIVE: We aimed to report our development of new delirium severity items and the results of item reduction and selection activities guided by psychometric analysis of data derived from a field study. METHODS: Building on our literature review of delirium instruments and expert panel process to identify domains of delirium severity, we adapted items from existing delirium severity instruments and generated new items. We then fielded these items among a sample of 352 older hospitalized patients. RESULTS: We used an expert panel process and psychometric data analysis techniques to narrow a set of 303 potential items to 17 items for use in a new delirium severity instrument. The 17-item set demonstrated good internal validity and favorable psychometric characteristics relative to comparator instruments, including the Confusion Assessment Method - Severity (CAM-S) score, the Delirium Rating Scale Revised 98, and the Memorial Delirium Assessment Scale. CONCLUSION: We more fully conceptualized delirium severity and identified characteristics of an ideal delirium severity instrument. These characteristics include an instrument that is relatively quick to administer, is easy to use by raters with minimal training, and provides a severity rating with good content validity, high internal consistency reliability, and broad domain coverage across delirium symptoms. We anticipate these characteristics to be represented in the subsequent development of our final delirium severity instrument.

Older Patients with Alzheimer's Disease-Related Cortical Atrophy Who Develop Post-Operative Delirium May Be at Increased Risk of Long-Term Cognitive Decline After Surgery.

BACKGROUND: Older surgical patients with Alzheimer's disease (AD) dementia and delirium are at increased risk for accelerated long-term cognitive decline. OBJECTIVE: Investigate associations between a probabilistic marker of preclinical AD, delirium, and long-term cognitive decline. METHODS: The Successful Aging after Elective Surgery cohort includes older adults (≥70 years) without dementia who underwent elective surgery. 140 patients underwent preoperative magnetic resonance imaging and had≥6 months cognitive follow-up. Cortical thickness was measured in 'AD-Signature' regions. Delirium was evaluated each postoperative day by the Confusion Assessment Method. Cognitive performance was assessed using a detailed neuropsychological battery at baseline; months 1, 2, and 6; and every 6 months thereafter until 36 months. Using either a General Cognitive Performance composite (GCP) or individual test scores as outcomes, we performed linear mixed effects models to examine main effects of AD-signature atrophy and the interaction of AD-signature atrophy and delirium on slopes of cognitive change from post-operative months 2-36. RESULTS: Reduced baseline AD-signature cortical thickness was associated with greater 36-month cognitive decline in GCP (standardized beta coefficient, ß = -0.030, 95% confidence interval [-0.060, -0.001]). Patients who developed delirium who also had thinner AD signature cortex showed greater decline on a verbal learning test (ß = -0.100 [-0.192, -0.007]). CONCLUSION: Patients with the greatest baseline AD-related cortical atrophy who develop delirium after elective surgery appear to experience the greatest long-term cognitive decline. Thus, atrophy suggestive of preclinical AD and the development of delirium may be high-risk indicators for long-term cognitive decline following surgery.

Does Alzheimer's Disease and Related Dementias Modify Delirium Severity and Hospital Outcomes?

OBJECTIVES: We examined the association between delirium severity and outcomes of delirium among persons with and without Alzheimer's disease and related dementias (ADRD). DESIGN: Prospective cohort study. SETTING: Academic tertiary medical center. PARTICIPANTS: A total of 352 medical and surgical patients. MEASUREMENTS: Delirium incidence and severity were rated daily using the Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) score during hospitalization. Severe delirium was defined as a CAM-S Short Form score in the highest tertile (3-7 points out of 7). ADRD status was determined by a clinical consensus process. Clinical outcomes included prolonged length of stay (>6 d), discharge to post-acute nursing facility, any decline in activities of daily living (ADLs) at 1 month from prehospital baseline, ongoing nursing facility stay, and mortality. RESULTS: Patients with ADRD (n = 85 [24%]) had a significantly higher relative risk (RR) for incident delirium (RR = 2.31; 95% confidence interval [CI] = 1.64-3.28) and higher peak CAM-S scores (mean difference = 1.24 points; CI = .83-1.65; P < .001). Among patients with ADRD, severe delirium significantly increased the RR for nursing facility stay (RR = 2.22; CI = 1.05-4.69; P = .04) and increased the RR for mortality (RR = 2.10; CI = .89-4.98; P = .09). Among patients without ADRD, severe delirium was associated with a significantly increased risk for all poor outcomes except mortality including prolonged length of stay in the hospital (RR = 1.47; CI = 1.18-1.82) and discharge to a post-acute nursing facility (RR = 2.17; CI = 1.58-2.98) plus decline in ADLs (RR = 1.30; CI = 1.05-1.60) and nursing facility stay at 1 month (RR = 1.93; CI = 1.31-2.83). CONCLUSION: Severe delirium is associated with increased risk for poor clinical outcomes in patients with and without ADRD. In both groups, severe delirium increased risk of nursing home placement. In patients with ADRD, delirium was more severe and associated with a trend toward increased mortality at 1 month. Although the increased risk remains substantial by RR, the study had limited power to examine the rarer outcome of death. J Am Geriatr Soc 68:1722-1730, 2020.

Identification of miRNAs as prognostic factors for esophageal squamous cell carcinoma.

Objective: The prognostic value of microRNAs for esophageal squamous cell carcinoma (ESCC) is still not be well identified. Methods: The microRNA expression profiles of 119 paired ESCC tissue samples and para-carcinoma tissues from GEO database under accession number of GSE43732. A mutation information based feature selection method was applied to identify the discriminative microRNAs between paired ESCC tissues and para-carcinoma tissues. Results: In para-carcinoma tissues, patients had better survival with higher has-miR-410 (log-rank p = 0.0123), has-miR-411-5p (log-rank p = 0.0152), has-miR-193b-5p (log-rank p = 0.0188) and has-miR-4486 (log-rank p = 0.0307) expression levels. When compared with para-carcinoma tissues, there has more correlations between miRNA expression levels and survival in tumor tissues. We identified 20 potential miRNAs associated with prognosis. Besides, a heatmap was draw to explore miRNA expression levels in tumor tissues and survival. Conclusions: The present study identified 24 miRNAs in 119 paired ESCC tissue samples and para-carcinoma tissues, including 4 miRNAs in para-carcinoma tissues and 20 in tumor tissues, respectively. The dysregulation of these miRNAs were associated with different outcomes. We thought this study could provide novel noninvasive early biomarkers for ESCC patients.

The Role of Inflammation after Surgery for Elders (RISE) study: Study design, procedures, and cohort profile.

INTRODUCTION: The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]-PBR28 positron-emission tomography imaging. METHODS: This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty-five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month. RESULTS: On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini-Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%). DISCUSSION: This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron-emission tomography with detailed clinical characterization of delirium, cognition, and functional status.

The Caregiver Burden of Delirium in Older Adults With Alzheimer Disease and Related Disorders.

OBJECTIVES: To measure the burden of delirium in older adults with or without Alzheimer disease or related disorders (ADRDs). DESIGN: Prospective, observational cohort. SETTING: Inpatient hospital and study participants' homes. PARTICIPANTS: A subset (n = 267) of older medical and surgical patients and their caregivers enrolled in the Better Assessment of Illness study. MEASUREMENTS: Delirium burden was measured using the DEL-B instrument (range = 0-40, with higher scores indicating greater burden) in caregivers (DEL-B-C) and patients 1 month after hospitalization. Severity of cognitive impairment (Montreal Cognitive Assessment [MoCA]), delirium presence (Confusion Assessment Method [CAM]), and delirium severity (CAM-Severity [CAM-S]) were measured during hospitalization and at 1-month follow-up. ADRD diagnosis was determined by a clinical consensus process. RESULTS: For patients with (n = 56) and without (n = 211) ADRD, both DEL-B instruments had good internal consistency. DEL-B-C scores had a median (interquartile range) among caregivers of patients with and without ADRD of 9 (5-15) and 5 (1-11), respectively (P < .05). If the patient developed delirium, caregivers experienced greater burden (ß[delirium × ADRD] = -.29; P = .42), regardless of ADRD status. Further, caregiver burden was modestly correlated with patient MoCA scores (Spearman correlation coefficient, ρ = -0.18; P = .01). Patients with ADRD who developed delirium self-reported less burden than those without ADRD (ß[delirium × ADRD] = -.67; P = .044). As with caregivers, delirium burden was modestly correlated with patient MoCA score (ρ = -0.18; P = .005) and correlated with the CAM-S in patients without ADRD (ρ = 0.38; P < .001) but not for patients with ADRD (ρ = -0.07; P = .61). CONCLUSIONS: Delirium resulted in the same degree of increased caregiver burden regardless of whether a patient had ADRD, signifying delirium is equally stressful to caregivers, even among those with experience caring for someone with a chronic cognitive disorder. Delirium burden is only modestly associated with degree of cognitive impairment, suggesting that other aspects of delirium contribute to burden. J Am Geriatr Soc 67:2587-2592, 2019.

5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary arterial hypertension: A meta-analysis.

BACKGROUND: The influence of 5-HTT, BMPR2, EDN1, ENG, KCNA5 genes polymorphisms on susceptibility of pulmonary arterial hypertension remains uncertain. This meta-analysis is conducted for further study. METHODS: We conducted a literature search on PubMed and ISI web of science databases for searching relevant articles until November 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 17 articles with 2631 PAH subjects and 5139 controls were included in the final meta-analysis. Statistical software Stata13.0 was used for data-analysis. RESULTS: A significant relationship was found between the 5-HTT L/S polymorphism and PAH in all the genetic models [LL vs. SS: OR = 1.60, 95% CI, 1.11-2.32; LS vs. SS: OR = 1.55, 95% CI, 1.10-2.21; (LS + LL) vs. SS: OR = 1.56, 95% CI, 1.13-2.17; L vs. S: OR = 1.32, 95% CI, 1.08-1.62]. There were also associations of the SERT L/S polymorphism with IPAH and PAH in COPD [IPAH L/S: OR = 1.26, 95% CI, 1.01-1.57; PAH in COPD L/S: OR = 1.42, 95% CI, 1.04-1.94]. In addition, the results showed a statistically significant association between EDN1 rs5370 polymorphism and the risk of PAH in all the genetic models [TT vs. GG: OR = 3.32, 95% CI, 1.30-8.51; TG vs. GG: OR = 2.68, 95% CI, 1.54-4.66; (TG + TT) vs. GG: OR = 2.82, 95% CI, 1.69-4.71; T vs. G: OR = 2.43, 95% CI, 1.60-3.68]. However, the significant association was not found between BMPR2 rs1061157, KCNA5 rs10744676, ENG rs3739817 polymorphisms and the risk of PAH (all p > 0.05). CONCLUSIONS: 5-HTT L/S polymorphism and END1 rs5370 polymorphism were correlated with significantly increased risk of PAH. Moreover, L allele in 5-HTT gene increased susceptibility to IPAH and PAH in COPD.