Preoperative physical performance as predictor of postoperative outcomes in patients aged 65 and older scheduled for major abdominal cancer surgery:A systematic review

Background: Abdominal cancer surgery is associated with considerable morbidity in older patients. Assessment of preoperative physical status is therefore essential. The aim of this review was to describe and compare the objective physical tests that are currently used in abdominal cancer surgery in the older patient population with regard to postoperative outcomes. Methods: Medline, Embase, CINAHL and Web of Science were searched until 31 December 2020. Non-interventional cohort studies were eligible if they included patients ≥65 years undergoing abdominal cancer surgery, reported results on objective preoperative physical assessment such as Cardiopulmonary Exercise Testing (CPET), field walk tests or muscle strength, and on postoperative outcomes. Results: 23 publications were included (10 CPET, 13 non-CPET including Timed Up & Go, grip strength, 6-minute walking test (6MWT) and incremental shuttle walk test (ISWT)). Meta-analysis was precluded due to heterogeneity between study cohorts, different cut-off points, and inconsistent reporting of outcomes. In CPET studies, ventilatory anaerobic threshold and minute ventilation/carbon dioxide production gradient were associated with adverse outcomes. ISWT and 6MWT predicted outcomes in two studies. Tests addressing muscle strength and function were of limited value. No study compared different physical tests. Discussion: CPET has the ability to predict adverse postoperative outcomes, but it is time-consuming and requires expert assessment. ISWT or 6MWT might be a feasible alternative to estimate aerobic capacity. Muscle strength and function tests currently have limited value in risk prediction. Future research should compare the predictive value of different physical instruments with regard to postoperative outcomes in older surgical patients

Head-to-head comparison of 14 prediction models for postoperative delirium in elderly non-ICU patients:an external validation study

OBJECTIVES: Delirium is associated with increased morbidity, mortality, prolonged hospitalisation and increased healthcare costs. The number of clinical prediction models (CPM) to predict postoperative delirium has increased exponentially. Our goal is to perform a head-to-head comparison of CPMs predicting postoperative delirium in non-intensive care unit (non-ICU) elderly patients to identify the best performing models. SETTING: Single-site university hospital. DESIGN: Secondary analysis of prospective cohort study. PARTICIPANTS AND INCLUSION: CPMs published within the timeframe of 1 January 1990 to 1 May 2020 were checked for eligibility (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). For the time period of 1 January 1990 to 1 January 2017, included CPMs were identified in systematic reviews based on prespecified inclusion and exclusion criteria. An extended literature search for original studies was performed independently by two authors, including CPMs published between 1 January 2017 and 1 May 2020. External validation was performed using a surgical cohort consisting of 292 elderly non-ICU patients. PRIMARY OUTCOME MEASURES: Discrimination, calibration and clinical usefulness. RESULTS: 14 CPMs were eligible for analysis out of 366 full texts reviewed. External validation was previously published for 8/14 (57%) CPMs. C-indices ranged from 0.52 to 0.74, intercepts from −0.02 to 0.34, slopes from −0.74 to 1.96 and scaled Brier from −1.29 to 0.088. Based on predefined criteria, the two best performing models were those of Dai et al (c-index: 0.739; (95% CI: 0.664 to 0.813); intercept: −0.018; slope: 1.96; scaled Brier: 0.049) and Litaker et al (c-index: 0.706 (95% CI: 0.590 to 0.823); intercept: −0.015; slope: 0.995; scaled Brier: 0.088). For the remaining CPMs, model discrimination was considered poor with corresponding c-indices <0.70. CONCLUSION: Our head-to-head analysis identified 2 out of 14 CPMs as best-performing models with a fair discrimination and acceptable calibration. Based on our findings, these models might assist physicians in postoperative delirium risk estimation and patient selection for preventive measures

Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older:A systematic review and meta-analysis

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients ≥70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54–0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies

The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses

During the highly pathogenic avian influenza (HPAI) H7N7 virus outbreak in The Netherlands in 2003, 88 infected persons suffered from mild illnesses, and 1 died of pneumonia. Here, we studied which of the 14 amino acid substitutions observed between the fatal case (FC) virus and a conjunctivitis case (CC) virus determined the differences in virus pathogenicity. In virus-attachment experiments, the CC and FC viruses revealed marked differences in binding to the lower respiratory tract of humans. In a mouse model, the hemagglutinin (HA) gene of the FC virus was a determinant of virus tissue distribution. The lysine at position 627 of basic polymerase 2 (PB2) of the FC virus was the major determinant of pathogenicity and tissue distribution. Thus, remarkable similarities were revealed between recent HPAI H5N1 and H7N7 viruses. We conclude that the influenza virus HA and PB2 genes should be the prime targets for molecular surveillance during outbreaks of zoonotic HPAI viruses

Sensitive Detection of p65 Homodimers Using Red-Shifted and Fluorescent Protein-Based FRET Couples

BACKGROUND: Fluorescence Resonance Energy Transfer (FRET) between the green fluorescent protein (GFP) variants CFP and YFP is widely used for the detection of protein-protein interactions. Nowadays, several monomeric red-shifted fluorescent proteins are available that potentially improve the efficiency of FRET. METHODOLOGY/PRINCIPAL FINDINGS: To allow side-by-side comparison of several fluorescent protein combinations for detection of FRET, yellow or orange fluorescent proteins were directly fused to red fluorescent proteins. FRET from yellow fluorescent proteins to red fluorescent proteins was detected by both FLIM and donor dequenching upon acceptor photobleaching, showing that mCherry and mStrawberry were more efficient acceptors than mRFP1. Circular permutated yellow fluorescent protein variants revealed that in the tandem constructs the orientation of the transition dipole moment influences the FRET efficiency. In addition, it was demonstrated that the orange fluorescent proteins mKO and mOrange are both suitable as donor for FRET studies. The most favorable orange-red FRET pair was mKO-mCherry, which was used to detect homodimerization of the NF-kappaB subunit p65 in single living cells, with a threefold higher lifetime contrast and a twofold higher FRET efficiency than for CFP-YFP. CONCLUSIONS/SIGNIFICANCE: The observed high FRET efficiency of red-shifted couples is in accordance with increased Förster radii of up to 64 A, being significantly higher than the Förster radius of the commonly used CFP-YFP pair. Thus, red-shifted FRET pairs are preferable for detecting protein-protein interactions by donor-based FRET methods in single living cells

Hampered Foraging and Migratory Performance in Swans Infected with Low-Pathogenic Avian Influenza A Virus

It is increasingly acknowledged that migratory birds, notably waterfowl, play a critical role in the maintenance and spread of influenza A viruses. In order to elucidate the epidemiology of influenza A viruses in their natural hosts, a better understanding of the pathological effects in these hosts is required. Here we report on the feeding and migratory performance of wild migratory Bewick's swans (Cygnus columbianus bewickii Yarrell) naturally infected with low-pathogenic avian influenza (LPAI) A viruses of subtypes H6N2 and H6N8. Using information on geolocation data collected from Global Positioning Systems fitted to neck-collars, we show that infected swans experienced delayed migration, leaving their wintering site more than a month after uninfected animals. This was correlated with infected birds travelling shorter distances and fuelling and feeding at reduced rates. The data suggest that LPAI virus infections in wild migratory birds may have higher clinical and ecological impacts than previously recognised

Low preoperative skeletal muscle density is predictive for negative postoperative outcomes in older women with ovarian cancer

Objective. To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.Methods. A multicenter, retrospective cohort study was performed in women >= 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index = 2).Conclusion. Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making. (C) 2021 The Author(s). Published by Elsevier Inc.Cervix cance

Physical and Pharmacological Restraints in Hospital Care:Protocol for a Systematic Review

Background: Physical and pharmacological restraints, defined as all measures limiting a person in his or her freedom, are extensively used to handle unsafe or problematic behavior in hospital care. There are increasing concerns as to the extent with which these restraints are being used in hospitals, and whether their benefits outweigh their potential harm. There is currently no comprehensive literature overview on the beneficial and/or adverse effects of the use of physical and pharmacological restraints in the hospital setting. Methods: A systematic review of the existing literature will be performed on the beneficial and/or adverse effects of physical and pharmacological restraints in the hospital setting. Relevant databases will be systematically searched. A dedicated search strategy was composed. A visualization of similarities (VOS) analysis was used to further specify the search. Observational studies, and if available, randomized controlled trials reporting on beneficial and/or adverse effects of physical and/or pharmacological restraints in the general hospital setting will be included. Data from included articles will be extracted and analyzed. If the data is suitable for quantitative analysis, meta-analysis will be applied. Discussion: This review will provide data on the beneficial and/or adverse effects of the use of physical and pharmacological restraints in hospital care. With this review we aim to guide health professionals by providing a critique of the available evidence regarding their choice to either apply or withhold from using restraints. A limitation of the current review will be that we will not specifically address ethical aspects of restraint use. Nevertheless, the outcomes of our systematic review can be used in the composition of a multidisciplinary guideline. Furthermore, our systematic review might determine knowledge gaps in the evidence, and recommendations on how to target these gaps with future research. Systematic Review Registration: PROSPERO registration number: CRD42019116186

Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia:Endoscopic Findings and Long-Term Mortality

INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation