Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK-ADRC cohort.

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)- and neurodegeneration-related (Aß40, Aß42, Aß42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD-inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum. DISCUSSION: Unique AD-inflammatory biomarker correlations in a community-based cohort reveal a new avenue for utilizing plasma-based biomarkers in the assessment of AD and related dementias. HIGHLIGHTS: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker-biomarker associations vary through aging and dementia. Six AD (Aß40, Aß42, Aß42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro-inflammatory and anti-inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia.

Factors and Barriers to Goals-of-Care Conversations for Patients With Cancer and Inpatient Mortality.

PURPOSE: Conversations about personal values and goals of care (GOC) at the end of life are essential in caring for patients with advanced cancer. However, GOC conversations may be influenced by patient and oncologist factors during transitions of care. METHODS: We electronically administered surveys to medical oncologists of inpatients who died from May 1, 2020, to May 31, 2021. Primary outcomes included oncologists' knowledge of inpatient death, anticipation of patient death, and recollection of GOC discussions. Secondary outcomes, including GOC documentation and advance directives (ADs), were collected retrospectively from electronic health records. Outcomes were analyzed for association with patient, oncologist, and patient-oncologist relationship factors. RESULTS: For 75 patients who died, 104/158 (66%) surveys were completed by 40 inpatient and 64 outpatient oncologists. Eighty-one oncologists (77.9%) were aware of patients' deaths, 68 (65.4%) anticipated patients' deaths within 6 months, and 67 (64.4%) recalled having GOC discussions before or during the terminal hospitalization. Outpatient oncologists were more likely to report knowledge of patient death (P < .001), as were those with longer therapeutic relationships (P < .001). Inpatient oncologists were more likely to correctly anticipate patient death (P = .014). Secondary outcomes revealed 21.3% of patients had documented GOC discussions before admission and 33.3% had ADs; patients with a longer duration of cancer diagnosis were more likely to have ADs (P = .003). Oncologist-reported barriers to GOC included unrealistic expectations from patients or family (25%) and decreased patient participation because of clinical conditions (15%). CONCLUSION: Most oncologists recalled having GOC discussions for patients with inpatient mortality, yet documentation of serious illness conversations remained suboptimal. Further studies are needed to examine barriers to GOC conversations and documentation during transitions of care and across health care settings.

Examining the association between blood-based biomarkers and human post mortem neuropathology in the University of Kentucky Alzheimer's Disease Research Center autopsy cohort.

INTRODUCTION: Clinically, detection of disease-causing pathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) is limited to magnetic resonance imaging and positron emission tomography scans, which are expensive and not widely accessible. Here, we assess angiogenic, inflammatory, and AD-related plasma biomarkers to determine their relationships with human post mortem neuropathology. METHOD: Plasma samples were analyzed using a digital immunoassay and pathological evaluation was performed by University of Kentucky Alzheimer's Disease Research Center neuropathologists. The association of plasma markers with neuropathology was estimated via proportional odds and logistic regressions adjusted for age. RESULTS: Included cases (N = 90) showed increased tau/amyloid beta (Aß)42 ratio, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor A (VEGF-A), and placental growth factor (PlGF) were positively associated with higher level of AD neuropathological change, while higher Aß42/Aß40 ratio was inversely associated. Higher PlGF, VEGF-A, and interleukin 6 were inversely associated with chronic cerebrovascular disease, while Aß42/Aß40 ratio was positively associated. DISCUSSION: Our results provide support for the continued study of plasma biomarkers as a clinical screening tool for AD and VCID pathology.

Palliative Care Exposure Relative to Predicted Risk of Six-Month Mortality in Hospitalized Adults.

CONTEXT: The optimal strategy for implementing mortality-predicting algorithms to facilitate clinical care, prognostic discussions, and palliative care interventions remains unknown. OBJECTIVES: To develop and validate a real-time predictive model for 180 day mortality using routinely available clinical and laboratory admission data and determine if palliative care exposure varies with predicted mortality risk. METHODS: Adult admissions between October 1, 2013 and October.1, 2017 were included for the model derivation. A separate cohort was collected between January 1, 2018 and July 31, 2020 for validation. Patients were followed for 180 days from discharge, and logistic regression with selected variables was used to estimate patients' risk for mortality. RESULTS: In the model derivation cohort, 7963 events of 180 day mortality (4.5% event rate) were observed. Median age was 53.0 (IQR 24.0-66.0) with 92,734 females (52.5%). Variables with strongest association with 180 day mortality included: Braden Score (OR 0.83; 95% CI 0.82-0.84); admission Do Not Resuscitate orders (OR 2.61; 95% CI 2.43-2.79); admission service and admission status. The model yielded excellent discriminatory ability in both the derivation (c-statistic 0.873; 95% CI 0.870-0.877; Brier score 0.04) and validation cohorts (c-statistic 0.844; 95% CI 0.840-0.847; Brier score 0.072). Inpatient palliative care consultations increased from 3% of minimal-risk encounters to 41% of high-risk encounters (P < 0.01). CONCLUSION: We developed and temporally validated a predictive mortality model for adults from a large retrospective cohort, which helps quantify the potential need for palliative care referrals based on risk strata. Machine learning algorithms for mortality require clinical interpretation, and additional studies are needed to design patient-centered and risk-specific interventions.

Is newer always better?: comparing cost and short-term outcomes between laparoscopic and robotic right hemicolectomy.

BACKGROUND: Enthusiasm is high for expansion of robotic assisted surgery into right hemicolectomy. But data on outcomes and cost is lacking. Our objective was to determine the association between surgical approach and cost for minimally invasive right hemicolectomy. We hypothesized that a robot approach would have increased costs (both economic and opportunity) while achieving similar short-term outcomes. METHODS: We performed a retrospective cohort analysis with a simulation of operating room utilization at a quaternary care, academic institution. We enrolled patients undergoing minimally invasive right hemicolectomy from November 2017 to August 2019. Patients were categorized by the intended approach- laparoscopic or robotic. The primary outcome was the technical variable direct cost. Secondary outcomes included total cost, supply cost, operating room utilization, operative time, conversion, length of stay and 30-day post-operative outcomes. RESULTS: 79 patients were included in the study. A robotic approach was used in 22% of the cohort. The groups differed significantly only in etiology of surgery. Robotic surgery was associated with a 1.5 times increase in the technical variable direct cost (p < 0.001), increased supply cost (2.6 times; p < 0.001) and increased total cost (1.3 times; p < 0.001). Significant differences were observed in median room time (Robotic: 285 min vs. Laparoscopic: 170 min; p < 0.001) and procedure time (Robotic: 203 min vs. Laparoscopic: 118 min; p < 0.001). There were no differences observed in post-operative outcomes including length of stay or readmission. In a simulation of OR utilization, 45 laparoscopic right hemicolectomies could be performed in an OR in a month compared to 31 robotic cases. CONCLUSIONS: Robotic right hemicolectomy was associated with increased costs with no improvement in post-operative outcomes. In a simulation of operating room efficiency, a robotic approach was associated with 14 fewer cases per month. Practitioners and administrators should be aware of the increased cost of a robotic approach.

Improving Mortality Attribution in Otolaryngology - Head and Neck Surgery.

OBJECTIVE/HYPOTHESIS: Mortality attribution can have significant implications for reimbursement, hospital/department rankings, and perceptions of safety. This work seeks to compare the accuracy of externally assigned diagnosis-related group (DRG)-based service line mortality attribution in otolaryngology to an internal review process that assigns mortality to the teams that cared for a patient during hospitalization. STUDY DESIGN: Retrospective case series. METHODS: Mortality events at Vanderbilt University Medical Center (VUMC) from 2012 to 2018 were compared. Included events were assigned to the otolaryngology service line (OSL) via the following methods: an external agency (Vizient) using DRG, utilization management assignment based on the service that provided care at admission (admission service), discharge (discharge service), or throughout hospitalization (major service line), or through the internal VUMC mortality review committee. Internal review was considered the standard for comparison. RESULTS: Of the 28 mortality events assigned to OSL by the DRG-based external method, nine (32%) were actually attributable to OSL. Of the 23 total mortality events attributable to OSL at our institution, external DRG-based review captured nine (39%). The designation of major service during hospitalization was correct 95% of the time and captured 87% of mortality events. Differences between external and internal attribution methods were statistically significant (P < .001). CONCLUSIONS: DRG-based models are frequently utilized but can be inaccurate when attributing mortality for an individual otolaryngology department. Otolaryngology mortalities appear to be captured and assigned more accurately by assigning deaths to the service that renders the majority of care during hospitalization. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1805-E1810, 2021.

The effect of adding goal-directed hemodynamic management for elective patients in an established enhanced recovery program for colorectal surgery: results of quasi-experimental pragmatic trial.

BACKGROUND: Recent literature has demonstrated that hemodynamic instability in the intraoperative period places patients at risk of poor outcomes. Furthermore, recent studies have reported that stroke volume optimization and protocolized hemodynamic management may improve perioperative outcomes, especially surgical site infection (SSI), in certain high-risk populations. However, the optimal strategy for intraoperative management of all elective patients within an enhanced recovery program remains to be elucidated. METHODS: We performed a pre-post quasi-experimental study to assess the effect of adding goal-directed hemodynamic therapy to an enhanced recovery program (ERP) for colorectal surgery on SSI and other outcomes. Three groups were compared: "Pre-ERP," defined as historical control (before enhanced recovery program); "ERP," defined as enhanced recovery program using zero fluid balance; and "ERP+GDHT," defined as enhanced recovery program plus goal-directed hemodynamic therapy. Outcomes were obtained through our National Surgical Quality Improvement Program participation. RESULTS: A total of 623 patients were included in the final analysis (Pre-ERP = 246, ERP = 140, and ERP + GDHT = 237). Demographics and baseline clinical characteristics were balanced between groups. We did not observe statistically significant differences in SSI or composite complication rates in unadjusted or adjusted analysis. There was no evidence of association between study group and 30-day readmission. American Society of Anesthesiologists status ≥ 3 and open surgical approach were significantly associated with increased risk of SSI, composite complication, and 30-day readmission (p < 0.05 for all) in all groups. CONCLUSIONS: There was no evidence that addition of goal-directed hemodynamic therapy for all patients in an enhanced recovery program for colorectal surgery affects the risk of SSI, composite complications, or 30-day readmission. Further research is needed to investigate whether there is benefit of goal-directed hemodynamic therapy for select high-risk populations. TRIAL REGISTRATION: NCT03189550. Registered 16 June 2017-Retrospectively registered, https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT03189550&cntry=&state=&city=&dist=.

Ketorolac Use and Anastomotic Leak in Elective Colorectal Surgery: A Detailed Analysis.

BACKGROUND: Recent population-level analyses have linked ketorolac use to adverse outcomes. However, its use is also associated with decreased opioids and faster return of bowel function. OBJECTIVE: This study aims to assess the association between ketorolac and anastomotic leak. We hypothesize that receiving at least 1 dose of ketorolac will not be associated with anastomotic leak in elective colorectal surgery. DESIGN: This is a retrospective, observational cohort study of a prospectively collected data base. Anastomotic leak rates and other patient outcomes were adjusted for patient-level factors and then compared via a multivariable logistic regression. A secondary analysis assessed a dose-response association with anastomotic leak. SETTING: This study was conducted at a tertiary care colorectal surgery service. PATIENTS: Consecutive patients undergoing elective colorectal surgery with a nondiverted anastomosis were identified from 2012 to 2016. INTERVENTION: Exposure was defined as any administration of ketorolac during the perioperative time period. MAIN OUTCOME MEASURES: The primary outcome measured was anastomotic leak. RESULTS: A total of 877 patients met inclusion criteria. Of these, 479 (54.6%) were women, and the median age was 55 years. Overall, 566 (64.5%) patients were exposed to ketorolac. In the cohort, 27 (3.1%) patients experienced an anastomotic leak. In an unadjusted analysis, there was no association between ketorolac exposure and anastomotic leak (ketorolac: 3.1% vs no ketorolac: 3.3%; p = 0.84). This persisted in a multivariable model (OR, 0.98; 95% CI, 0.38-2.57; p = 0.98). Neither AKI (OR, 3.24; 95% CI, 0.51-20.6; p = 0.21), return to the operating room (OR, 1.07; 95% CI, 0.40-2.85; p = 0.88), nor readmission (OR, 1.03; 95% CI, 0.59-1.80; p = 0.93) was associated with ketorolac use. In a secondary analysis of patients receiving ketorolac, there was no association between total ketorolac dosing and anastomotic leak (OR, 0.99; 95% CI, 0.99-1.00; p = 0.20). LIMITATIONS: This study was a retrospective review, and there was a low incidence of anastomotic leak. CONCLUSION: Ketorolac exposure was associated with neither anastomotic leak nor other important postoperative outcomes. See Video Abstract at http://links.lww.com/DCR/A784.

Nondepolarizing Neuromuscular Blocking Agents, Reversal, and Risk of Postoperative Pneumonia.

BACKGROUND: Residual postoperative paralysis from nondepolarizing neuromuscular blocking agents (NMBAs) is a known problem. This paralysis has been associated with impaired respiratory function, but the clinical significance remains unclear. The aims of this analysis were two-fold: (1) to investigate if intermediate-acting NMBA use during surgery is associated with postoperative pneumonia and (2) to investigate if nonreversal of NMBAs is associated with postoperative pneumonia. METHODS: Surgical cases (n = 13,100) from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who received general anesthesia were included. The authors compared 1,455 surgical cases who received an intermediate-acting nondepolarizing NMBA to 1,455 propensity score-matched cases who did not and 1,320 surgical cases who received an NMBA and reversal with neostigmine to 1,320 propensity score-matched cases who did not receive reversal. Postoperative pneumonia incidence rate ratios (IRRs) and bootstrapped 95% CIs were calculated. RESULTS: Patients receiving an NMBA had a higher absolute incidence rate of postoperative pneumonia (9.00 vs. 5.22 per 10,000 person-days at risk), and the IRR was statistically significant (1.79; 95% bootstrapped CI, 1.08 to 3.07). Among surgical cases who received an NMBA, cases who were not reversed were 2.26 times as likely to develop pneumonia after surgery compared to cases who received reversal with neostigmine (IRR, 2.26; 95% bootstrapped CI, 1.65 to 3.03). CONCLUSIONS: Intraoperative use of intermediate nondepolarizing NMBAs is associated with developing pneumonia after surgery. Among patients who receive these agents, nonreversal is associated with an increased risk of postoperative pneumonia.

Intraoperative Care Transitions Are Not Associated with Postoperative Adverse Outcomes.

BACKGROUND: Whether anesthesia care transitions and provision of short breaks affect patient outcomes remains unclear. METHODS: The authors determined the number of anesthesia handovers and breaks during each case for adults admitted between 2005 and 2014, along with age, sex, race, American Society of Anesthesiologists physical status, start time and duration of surgery, and diagnosis and procedure codes. The authors defined a collapsed composite of in-hospital mortality and major morbidities based on primary and secondary diagnoses. The relationship between the total number of anesthesia handovers during a case and the collapsed composite outcome was assessed with a multivariable logistic regression. The relationship between the total number of anesthesia handovers during a case and the components of the composite outcome was assessed using multivariate generalized estimating equation methods. Additionally, the authors analyzed major complications and/or death within 30 days of surgery based on the American College of Surgeons National Surgical Quality Improvement Program-defined events. RESULTS: A total of 140,754 anesthetics were identified for the primary analysis. The number of anesthesia handovers was not found to be associated (P = 0.19) with increased odds of postoperative mortality and serious complications, as measured by the collapsed composite, with odds ratio for a one unit increase in handovers of 0.957; 95% CI, 0.895 to 1.022, when controlled for potential confounding variables. A total of 8,404 anesthetics were identified for the NSQIP analysis (collapsed composite odds ratio, 0.868; 95% CI, 0.718 to 1.049 for handovers). CONCLUSIONS: In the analysis of intraoperative handovers, anesthesia care transitions were not associated with an increased risk of postoperative adverse outcomes.

Patient Complaints and Adverse Surgical Outcomes.

One factor that affects surgical team performance is unprofessional behavior exhibited by the surgeon, which may be observed by patients and families and reported to health care organizations in the form of spontaneous complaints. The objective of this study was to assess the relationship between patient complaints and adverse surgical outcomes. A retrospective cohort study used American College of Surgeons National Surgical Quality Improvement Program data from an academic medical center and included 10 536 patients with surgical procedures performed by 66 general and vascular surgeons. The number of complaints for a surgeon was correlated with surgical occurrences (P < .01). Surgeons with more patient complaints had a greater rate of surgical occurrences if the surgeon's aggregate preoperative risk was higher (ß = .25, P < .05), whereas there was no statistically significant relationship between patient complaints and surgical occurrences for surgeons with lower aggregate perioperative risk (ß = -.20, P = .77).

Using the National Surgical Quality Improvement Program and the Tennessee Surgical Quality Collaborative to improve surgical outcomes.

BACKGROUND: Led by the Tennessee Chapter of the American College of Surgeons, in May 2008 a 10-hospital collaborative was formed between the Tennessee Chapter of ACS, the Tennessee Hospital Association, and the BlueCross BlueShield of Tennessee Health Foundation. We hypothesized that by forming the Tennessee Surgical Quality Collaborative using the National Surgical Quality Improvement Program (NSQIP) system to share surgical process and outcomes data, overall patient surgical outcomes would improve. STUDY DESIGN: All NSQIP data from the 10-hospital collaborative for the time periods January to December 2009 (period 1) and January to December 2010 (period 2) were collected. Data on 20 categories of postoperative complications and 30-day mortality were compared between periods. Complication comparisons and hospital costs associated with complications were calculated per 10,000 procedures. Statistical analysis was performed by Z-test. RESULTS: There were 14,205 total surgical cases in period 1 and 14,901 surgical cases in period 2. Between periods (per 10,000 cases) there were significant improvements in superficial surgical site infections (-19%, p = 0.0005), on ventilator longer than 48 hours (-15%, p = 0.012), graft/prosthesis/flap failure (-60%, p < 0.0001), acute renal failure (-25%, p = 0.023), and wound disruption (-34%, p = 0.011). Although mortality (per 10,000) was higher in period 2 (237.6 vs 232.3), no statistical difference was noted. Net costs avoided between these periods were calculated as $2,197,543 per 10,000 general and vascular surgery cases. CONCLUSIONS: Data organization and scrutiny are the initial steps of process improvement. Participation in our regional surgical quality collaborative resulted in improved outcomes and reduced costs. Although the mechanisms for these changes are likely multifactorial, the collaborative establishes communication, process improvement, and frank discussion among the members as best practices are identified and shared and standardized processes are adopted.

Regional differences in the force-frequency relation of human left ventricular myocardium in mitral regurgitation: implications for ventricular shape.

Sphericalization of the left ventricular (LV) chamber shape in patients with mitral regurgitation (MR) contributes to increased LV wall stress and energy consumption. On the basis of previous observations, we hypothesized the existence of regional differences in the force-frequency relation (FFR) within the LV that may contribute to its shape. Accordingly, in the present study, we assessed regional variation in the FFR in patients undergoing surgery for chronic, nonischemic MR with class II-III heart failure symptoms and related our findings to the in vivo LV shape. FFRs (steady-state isometric twitches, 0.2-3.4 Hz, 37 degrees C) were evaluated in MR myocardium from the LV subepicardial free wall (MR-FW) and papillary muscle (MR-PM) and from the subepicardial free wall in coronary artery bypass graft patients with normal LV contraction patterns [nonfailing (NF)]. Ascending slope, optimal stimulation frequency, and maximal twitch tension of the FFR were depressed in MR-FW and MR-PM compared with NF (P < 0.05). FFR depression was greater in MR-PM than in MR-FW. Between 107 and 134 beats/min, twitch tension became weaker in MR-PM, whereas it increased in MR-FW. Elevation of intracellular cAMP with forskolin eliminated FFR depression in MR-FW but not in MR-PM. MR-PM also had a 35% lower myosin heavy chain content and slowed twitch kinetics. In MR patients, the echocardiographic end-diastolic LV shape (end-diastolic eccentricity index = long axis/short axis) correlated with the ratio of ascending FFR slopes such that the end-diastolic eccentricity index increased 10% per 15% increase in slope ratio (r = 0.88, P = 0.01). These regional differences in the frequency dependence of contractility between the free wall and papillary myocardium may contribute to changes in LV shape in MR as well as during exercise.