Characterization of Postoperative Recovery After Cardiac Surgery- Insights into Predicting Individualized Recovery Pattern

Understanding the patterns of postoperative recovery after cardiac surgery is important from several perspectives: to facilitate patient-centered treatment decision making, to inform health care policy targeted to improve postoperative recovery, and to guide patient care after cardiac surgery. Our works aimed to address the following: 1) to summarize existing approaches to measuring and reporting postoperative recovery after cardiac surgery, 2) to develop a framework to efficiently measure patient-reported outcome measures to understand longitudinal recovery process, and 3) to explore ways to summarize the longitudinal recovery data in an actionable way, and 4) to evaluate whether addition of patient information generated through different phases of care would improve the ability to predict patient’s outcome. We first conducted a systematic review of the studies reporting on postoperative recovery after cardiac surgery using patient-reported outcome measures. Our systematic review demonstrated that the current approaches to measuring and reporting recovery as a treatment outcome varied widely across studies. This made synthesis of collective knowledge challenging and highlighted key gaps in knowledge, which we sought to address in our prospective cohort study. We conducted a prospective single-center cohort study of patients after cardiac surgery to measure their recovery trajectory across multiple domains of recovery. Using a digital platform, we measured patient recovery in various domains over 30 days after surgery to visualize a granular evolution of patient recovery after cardiac surgery. We used a latent class analysis to facilitate identification of dominant trajectory patterns that had been obscured in a conventional way of reporting such time-series data using group-level means. For the pain domain, we identified 4 trajectory classes, one of which was a group of patients with persistently high pain trajectory that only became distinguishable from less concerning group after 10 days. Therefore, we obtained a potentially actionable insights to tailoring individualized follow-up timing after surgery to improve the pain control. The prospective study embodied several important features to successfully conducting such studies of patient-reported outcomes. This included the use of digital platform to facilitate efficient data collection extending after hospital discharge, iteratively improving the protocol to optimize patient engagement including evaluation of potential barriers to survey completion, and using latent class analysis to identify dominant patterns of recovery trajectories. We outlined these insights in the protocol manuscript to inform subsequent studies aiming to leverage such a digital platform to measure longitudinal patient-centered outcome. Finally, we evaluated the potential value of incorporating health care data generated in the different phases of patient care in improving the prediction of postoperative outcomes after cardiac surgery. The current standard of risk prediction in cardiac surgery is the Society of Thoracic Surgeons’ (STS) risk model, which only uses patient information available preoperatively. We demonstrated through prediction models fitted on the national STS risk model for coronary artery bypass graft surgery that the addition of intraoperative variables to the conventional preoperative variable set improved the performance of prediction models substantially. Using machine learning approach to such a high-dimensional dataset proved to be marginally important. This work demonstrated the potential value and importance of being able to leverage health care data to continuously update the prediction to inform patient outcomes and guide clinical care. Our work collectively advanced knowledge in several key aspects of postoperative recovery. First, we highlighted the knowledge gap in the existing literature through characterizing the variability in the ways such studies had been conducted. Second, we designed and described a framework to measure postoperative recovery and an analytical approach to informatively characterize longitudinal patient recovery. Third, we employed these designs in a prospective cohort study to measure and analyze recovery trajectories and described clinical insights obtained from the study. Finally, we demonstrated the potential value of a dynamic risk model to iteratively improve its predictive performance by incorporating new data generated as the patient progresses through the phase of care. Such a platform has the potential to individualize patient’s post-acute care in a data-driven manner

Perioperative Neurocognitive Disorder: State of the Preclinical Science.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research

Preliminary study comparing parent and child functioning by intervention for adolescent idiopathic scoliosis

OBJECTIVE: The purpose of this study is to assess whether there are significant differences between pre-surgical and bracing patients with Adolescent Idiopathic Scoliosis (AIS) in parent and child functioning including pre-operative pain, pre-operative anxiety, parent pain catastrophizing, and parent protectiveness over child's pain symptoms. METHODS: Eligible patients were recruited from the Boston Children's Hospital Orthopedics Department. Retrospective chart reviews were conducted to identify patients aged ten through seventeen with AIS who were recommended for brace treatment or spinal fusion surgery. The study included thirty-five participants and their parents, seventeen pre-surgical participants and eighteen bracing participants. REDcap questionnaires were sent to parents and their children to fill out. The questionnaires included the following measures of interest for this study: Adult Responses to Children's Symptoms (ARCS), the Pain Catastrophizing Scale (PCS), the Multidimensional Anxiety Scale for Children (MASC), and the Numeric Rating Scale (NRS) for pain. One-way ANOVAs were used to determine if there were statistically significant differences between the two groups on the following variables: age and sex of the child, sex of the parent, race and ethnicity of the parent and child, degree of curvature of the spine (Cobb angle), and on the above mentioned parent and child measures. RESULTS: The group demographics were representative of the typical AIS population. Significant differences in age, Cobb angle, and sex of the child were determined between groups and represent potential confounding factors. There was a significant difference between groups for PCS magnification and a trend towards significance for PCS helplessness and the total PCS score. Other measure differences were statistically insignificant. CONCLUSIONS: Potential differences in parent and child measures were assessed to investigate parent and child functioning in the context of two medical interventions used to treat AIS. Bracing treatment and spinal fusion surgery were chosen with the intent to determine if the severity of an intervention has adverse effects on parent and child functioning. It is important to consider these results in a preliminary context due to the small sample size. Nonetheless, the results suggest that pre-surgical patients and their families are affected differently by the additional stressors and life-altering factors that come with spinal fusion surgery. There seems to be greater emphasis placed on their child's pain as well as a sense of helplessness. Both factors may have adverse effects on their child's ability to cope with the stress of surgery, which may also translate into a more difficult recovery period

Health Care for Older Adults

In recent decades, life expectancy has been increasing. This is a historical milestone in the history of humanity. We have never lived so long before. In these circumstances, giving the best care to older adults efficiently is one of the greatest challenges of developed countries. This book explores different initiatives that result in the improvement of health conditions of older adults, such as multicomponent physical exercise programs, interventions that try to avoid loneliness and social isolation, and multidisciplinary assessment, and the treatment of frailty and other geriatric syndromes, of the elderly in various settings such as the Emergency Unit, Orthogeriatrics, and Oncogeriatrics. This book offers different manuscripts to readers, each trying to improve life satisfaction, quality of life, and life expectancy in older adults in different scenarios. It is up to us to achieve these goals. We are sure that these interesting chapters will contribute to improving clinical practices. Following the completion of the Special Issue "Health Care for Older Adults" for the international Journal of Environmental Research and Public Health, the Guest Editors felt the satisfaction of having reached 18 published manuscripts and the possibility of transforming this volume into a book. This book was born from the need to show how health and social advances have increased human longevity as never before. We live longer, knowing more and more the epigenetic mechanisms of this longevity, as extended aging also coexists with the least favorable aging trajectories. Among them, a syndrome stands out from the gerontological and geriatric perspective: frailty. Due to the pandemic, a social problem has increased its presence in clinical practice: ageism. Older adults have found it difficult to access the necessary clinical resources due to the simple matter of age. However, at this moment, we are able to detect and to reverse frailty. In the same way, we should aim to prevent loneliness and social isolation, involved in social frailty. Geriatric syndromes are underdiagnosed and undertreated, but clinical and geriatric knowledge provide diagnostic tools and non-pharmacological approaches to prevent and to treat them. All health professionals working together in an interdisciplinary team could improve the clinical practices to develop a quality health care for older adults, improving their life satisfaction and quality of life perception too

QUANTITATIVE PROTEOMIC ANALYSES OF HUMAN PLASMA: APPLICATION OF MASS SPECTROMETRY FOR THE DISCOVERY OF CLINICAL DELIRIUM BIOMARKERS

The biomarker discovery pipeline is a multi-step endeavor to identify potential diagnostic or prognostic markers of a disease. Although the advent of modern mass spectrometers has revolutionized the initial discovery phase, a significant bottleneck still exists when validating discovered biomarkers. In this doctoral research, I demonstrate that the discovery, verification and validation of biomarkers can all be performed using mass spectrometry and apply the biomarker pipeline to the context of clinical delirium. First, a systematic review of recent literature provided a birds-eye view of untargeted, discovery proteomic attempts for biomarkers of delirium in the geriatric population. Here, a comprehensive search from five databases yielded 1172 publications, from which eight peer-reviewed studies met our defined inclusion criteria. Despite the paucity of published studies that applied systems- biology approaches for biomarker discovery on the subject, lessons learned and insights from this review was instrumental in the study designing and proteomics analyses of plasma sample in our cohort. We then performed a targeted study on four biomarkers for their potential mediation role in the occurrence of delirium after high-dose intra-operative oxygen treatment. Although S100B calcium binding protein (S100B), gamma enolase (ENO2), chitinase-3-like protein 1 (CHI3L1) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) have well-documented associations with delirium, we did not find any such associations in our cohort. Of note, this study demonstrates that the use of targeted approaches for the purposes of biomarker discovery, rather than an untargeted, systems-biology approach, is unavoidably biased and may lead to misleading conclusions. Lastly, we applied lessons learned and comprehensively profiled the plasma samples of delirium cases and non-delirium cases, at both pre- and post-surgical timepoints. We found 16 biomarkers as signatures of cardiopulmonary bypass, and 11 as potential diagnostic candidates of delirium (AuROC = 93%). We validated the discovered biomarkers on the same mass spectrometry platform without the use of traditional affinity-based validation methods. Our discovery of novel biomarkers with no know association with delirium such as serum amyloid A1 (SAA1) and A2 (SAA2), pepsinogen A3 (PEPA3) and cathepsin B (CATB) shed new lights on possible neuronal pathomechanisms

Optimism and survivorship after esophageal cancer surgery

Dispositional optimism is a personality trait that represents generally favorable expectations about the future. The main aim of this thesis was to examine whether higher dispositional optimism was related to better subjectively reported outcomes and better objectively measured outcomes. We used a self-reported scale, Life Orientation Test-Revised (LOT-R), to measure dispositional optimism in this thesis, with a higher LOT-R sum score representing higher dispositional optimism. Data for the four studies included in this thesis were from a prospective, Swedish nationwide, and population-based cohort entitled “Oesophageal Surgery on Cancer patients - Adaptation and Recovery (OSCAR)”. Study I and II included 192 patients who underwent surgery for esophageal cancer during January 1, 2013 and February 28, 2018 in Sweden. Patients self-reported their dispositional optimism level at 1 year after surgery. At 1, 1.5, and 2 years after esophagectomy, patients repeatedly self-reported their psychological status and health related quality of life (HRQL). Latent growth curve model and linear mixed effects model were used in these two studies. We found that higher dispositional optimism predicted a lower risk of reporting clinically significant psychological distress (anxiety and/or depression) in study I. The odds ratio of reporting clinically significant psychological distress was 0.56 (95% confidence interval 0.40 to 0.79) for one unit increase in the LOT-R sum score. In Study II, we categorized patients into four subgroups with very high, moderately high, moderately low, and very low dispositional optimism based on the quartile of the LOT-R sum score. We found that patients with very high and moderately high dispositional optimism reported better HRQL in several aspects compared to patients with lower dispositional optimism. Study III included 180 patients who underwent surgery for esophageal cancer during January 1, 2013 and February 28, 2018 in Sweden. Patients self-reported their psychological status and HRQL repeatedly at 1, 1.5, and 2 years after esophagectomy. We used fixed effects regression model with adjustment for all time-invariant covariates and observed time-varying confounders, and found that psychological distress was associated with worse HRQL in several aspects. Study IV included 335 patients who underwent surgery for esophageal cancer between January 1, 2013 and December 31, 2019 in Sweden. Patients were followed up until the date of death or until December 31, 2020, whichever occurred first. Cox proportional hazards regression was used. We found that among patients with early and intermediate pathological tumor stages (Tis-II) and with follow-up period before the COVID-19 pandemic, the adjusted hazard ratio for all-cause mortality was 0.89 (95% confidence interval 0.81 to 0.98) for one unit increase in the LOT-R sum score. However, this association was not statistically significant for patients with tumor pathologically staged III-IV (hazard ratio 0.99, 95% confidence interval 0.92 to 1.07) and/or during the COVID-19 pandemic (hazard ratio 1.08, 95% confidence interval 0.94 to 1.25). In conclusion, before the COVID-19 pandemic, higher dispositional optimism was associated with less self-reported clinically significant psychological distress and better HRQL; moreover, among patients with early and intermediate pathological tumor stages, higher dispositional optimism also predicted better overall survival. Measuring dispositional optimism may help identify vulnerable patients with potentially worse prognosis after surgery for esophageal cancer, thus contributing to the development of more tailored and timely interventions to improve postoperative survivorship

Risk Factors for Prolonged Mechanical Ventilation After Pulmonary Endarterectomy: 7 Years' Experience From an Experienced Hospital in China

Background: Prolonged mechanical ventilation (PMV) is common after cardiothoracic surgery, whereas the mechanical ventilation strategy after pulmonary endarterectomy (PEA) has not yet been reported. We aim to identify the incidence and risk factors for PMV and the relationship between PMV and short-term outcomes.Methods: We studied a retrospective cohort of 171 who undergoing PEA surgery from 2014 to 2020. Cox regression with restricted cubic splines was performed to identify the cutoff value for PMV. The Least absolute shrinkage and selection operator regression and logistic regressions were applied to identify risk factors for PMV. The impacts of PMV on the short-term outcomes were evaluated.Results: PMV was defined as the duration of mechanical ventilation exceeding 48 h. Independent risk factors for PMV included female sex (OR 2.911; 95% CI 1.303–6.501; P = 0.009), prolonged deep hypothermic circulatory arrest (DHCA) time (OR 1.027; 95% CI 1.002–1.053; P = 0.036), increased postoperative blood product use (OR 3.542; 95% CI 1.203–10.423; P = 0.022), elevated postoperative total bilirubin levels (OR 1.021; 95% CI 1.007–1.034; P = 0.002), increased preoperative pulmonary artery pressure (PAP) (OR 1.031; 95% CI 1.014–1.048; P < 0.001) and elongated postoperative right ventricular anteroposterior dimension (RVAD) (OR 1.119; 95% CI 1.026–1.221; P = 0.011). Patients with PMV had longer intensive care unit stays, higher incidences of postoperative complications, and higher in-hospital medical expenses.Conclusions: Female sex, prolonged DHCA time, increased postoperative blood product use, elevated postoperative total bilirubin levels, increased preoperative PAP, and elongated postoperative RVAD were independent risk factors for PMV. Identification of risk factors associated with PMV in patients undergoing PEA may facilitate timely diagnosis and re-intervention for some of these modifiable factors to decrease ventilation time and improve patient outcomes

Tehohoitopotilaiden neuromonitorointi

In critical illness the risk of neurological insults is high, whether because of the illness itself, or as a treatment complication. As a result, the length of hospital stay and the risk of both further morbidity and mortality are all roughly doubled. One of the major challenges is the inability to monitor a sedated, mechanically ventilated patient’s neurological symptoms during intensive care treatment, due to a lack of reliable methods. The aims of this thesis research were to identify and test potential non-invasive methods, which would be predictive of neurological outcome, showing potential as neuromonitoring methods of critical care patients unable to self-report. As a guiding theme, all tested methods could be applied to actual critical care with relative ease. Patients were included from two groups with a notably high incidence of neurological complications, namely acute liver failure patients with hepatic encephalopathy (I), and aortic surgery patients operated during hypothermic circulatory arrest (II). The first group included 20 patients, and the latter 30 patients. Late mortality and quality of life was assessed for the aortic surgery patients (III), and the postoperative development of certain blood biomarkers (IV). The tested non-invasive neuromonitoring methods included electroencephalogram (EEG) variables from frontal or fronto-temporal abbreviated monitoring, frontal near-infrared spectroscopy, transcranial Doppler ultrasound measurements of the intracranial blood flow, and finally biomarkers. The last included established biomarkers with an association with neurological complications, namely neuron-specific enolase, and protein S100β, and several interesting biomarkers normally associated with tumours and pancreatitis. Of the tested methods, the frontal EEG variables showed greatest promise, but the addition of the temporal channels did not increase sensitivity. Spectral EEG variables were predictive of the stage of hepatic encephalopathy (I), while a novel EEG variable called wavelet subband entropy was predictive of neurological outcome (I). The hemispheric asymmetry of frontal EEG was reasonably predictive of neurological outcome after aortic surgery (II). None of the other tested methods were predictive of outcome (I, II, IV), except protein S100β, which was significantly higher in the poor outcome group 48 to 72 hours after hypothermic circulatory arrest (II). The quality of life of aortic surgery patients was good after 5 to 8 years, and comparable with the general population of chronically ill patients (III). The aim of this explorative research was to identify and test non-invasive neuromonitoring methods, suitable for use in critical care. Based on the results, frontal EEG variables are promising and predict the grade of hepatic encephalopathy and neurological outcome. The other tested methods were not predictive of neurological outcome. The long-term quality of life of aortic surgery patients is very good, despite the high risk for neurological complications.Kriittisissä sairauksissa neurologisen komplikaation riski on suuri, sekä itse kriittisen sairauden että varsinaisen hoidon seurauksena. Haittatapahtuman johdosta sairaalahoidon kesto sekä sairastuvuuden ja kuolleisuuden riskit kaksinkertaistuvat. Yksi suurimmista haasteista on luotettavien menetelmien puute, joilla voitaisiin arvioida mekaanisen hengitystuen varassa olevan ja rauhoittavia lääkkeitä saavan potilaan neurologisia oireita tehohoidon aikana. Tämän väitöskirjatyön tarkoituksena oli tunnistaa ja testata lupaavia ei-kajoavia menetelmiä, jotka ennustaisivat neurologista lopputulosta, ja jotka soveltuisivat kriittisesti sairaan tehohoitopotilaan neuromonitorointiin. Kantavana teemana kaikki testatut menetelmät voitaisiin soveltaa kliiniseen työhön suhteellisen helposti. Potilaita kerättiin kahteen ryhmään, joissa neurologisten komplikaatioiden esiintyvyys on huomattavan suuri. Ensimmäinen ryhmä käsitti akuuttia maksan vajaatoimintaa ja hepaattista enkefalopatiaa sairastavat potilaat (I), toinen hypotermisen verenkierron pysäytyksen aikana rinta-aortan leikkauksen läpikäyvät potilaat (II). Ensimmäiseen ryhmään kuului 20 potilasta, jälkimmäiseen 30 potilasta. Aorttaleikatuilta potilailta arvioitiin myös elämänlaatua sekä myöhäiskuolleisuutta (III), lisäksi tiettyjen biomerkkiaineiden aorttaleikkauksen jälkeistä kehitystä ja soveltuvuutta neuromonitorointiin arvioitiin yhdessä osatyössä (IV). Tutkimuksessa arvioituihin ei-kajoaviin neuromonitorointimenetelmiin lukeutuivat otsa- ja ohimolohkon elektroenkefalografia (EEG), lähi-infrapunaspektroskopia, transkraniaalinen Doppler-ultraäänimittaus sekä verestä mitattavat biomerkkiaineet. Biomerkkiaineet kattoivat sekä vakiintuneita aivovauriota heijastavia merkkiaineita (hermostoperäinen enolaasi, proteiini S100β) että useita mielenkiintoisia merkkiaineita, jotka liittyvät kasvaintauteihin ja haimatulehdukseen. Testatuista menetelmistä otsalohkon EEG muuttujat olivat lupaavia, mutta ohimolohkon EEG lisääminen ei parantanut menetelmien herkkyyttä. EEG spektrimuuttujat ennustivat hepaattisen enkefalopatian astetta (I) luotettavasti, kun taas kokeellinen EEG-muuttuja (aalloke-alitaajuuden entropia) ennusti luotettavasti neurologista lopputulosta akuutin maksan vajaatoimintaa sairastavilla potilailla (I). Otsalohkon aivopuoliskojen EEG-rekisteröinnin hetkellinen epäsymmetria ennusti kohtalaisella tarkkuudella neurologisten päätetapahtumien esiintymisen aorttaleikatuilla potilailla (II). Muut testatut menetelmät eivät ennustaneet neurologista lopputulemaa (I, II, IV), paitsi proteiini S100β, joka oli merkittävästi korkeampi 48–72 tuntia leikkauksen jälkeen niillä potilailla, joiden neurologinen toipuminen oli huono (IV). Aorttaleikattujen potilaiden elämänlaatu oli hyvä 5–8 vuotta leikkauksen jälkeen ja verrattavissa kroonisesti sairaan väestön elämänlaatuun (III). Tämän kartoittavan tutkimuksen tarkoituksena oli tunnistaa ja testata ei-kajoavia neuromonitorointimenetelmiä, jotka soveltuvat tehohoitoon. Tulosten perusteella otsalohkon EEG-muuttujat ennustavat hepaattisen enkefalopatian astetta sekä potilaan neurologista toipumista. Muut testatut menetelmät eivät ennustaneet neurologista toipumista luotettavasti. Aorttaleikattujen potilaiden pitkäaikainen (5–8 vuoden) terveyteen liittyvä elämänlaatu on erittäin hyvä, vaikka leikkaukseen liittyy korkea aivovaurion riski