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.

Virtual surgical consultation during the COVID-19 pandemic: a patient-oriented, cross-sectional study using telephone interviews.

BACKGROUND: Health care delivery shifted rapidly during the COVID-19 pandemic, whereby virtual consultations replaced many face-to-face interactions. We sought to gather patient perspectives on their experiences with virtual surgical consultation, the advantages and disadvantages of this delivery method and their overall satisfaction with virtual appointments. METHODS: We conducted a patient-oriented, cross-sectional study. Adult patients (age > 18 yr) who had a virtual consultation with a participating general surgeon in Saskatoon, Saskatchewan, from April to May 2020 were eligible. We conducted telephone interviews using open- and close-ended questions. We used thematic analysis to determine themes from the qualitative data. As research team members, 2 patient partners were involved in identifying priorities, developing the research question, designing research methods, analyzing data and disseminating findings. We analyzed and presented quantitative data descriptively. RESULTS: We interviewed 45 participants from 7 general surgery practices; the average age was 62 years. Most participants lived outside Saskatoon and had virtual follow-up appointments. The 3 themes related to advantages of virtual consultations were convenience, cost savings and decreased exposure to pathogens. The 4 themes related to their disadvantages were that they were not as personal, the surgeon was not able to perform a physical examination, and there were issues with scheduling and issues with technology. Most participants were satisfied with the care they received (n = 41) and would be willing to use virtual consultation in the future (n = 31). INTERPRETATION: We found that virtual consultations are an effective and efficient way to deliver surgical care but are not appropriate for every situation and cannot completely replace face-to-face interactions. Our study identified the advantages and disadvantages of virtual surgical consultation to help better guide the delivery of virtual care in the future.

New insights into FAK structure and function in focal adhesions.

Focal adhesion kinase (FAK; also known as PTK2) was discovered three decades ago and is now recognised as a key player in the regulation of cell-matrix adhesion and mesenchymal cell migration. Although it is essential during development, FAK also drives invasive cancer progression and metastasis. On a structural level, the basic building blocks of FAK have been described for some time. However, a picture of how FAK integrates into larger assemblies in various cellular environments, including one of its main cellular locations, the focal adhesion (FA) complex, is only beginning to emerge. Nano-resolution data from cellular studies, as well as atomic structures from reconstituted systems, have provided first insights, but also point to challenges that remain for obtaining a full structural understanding of how FAK is integrated in the FA complex and the structural changes occurring at different stages of FA maturation. In this Review, we discuss the known structural features of FAK, the interactions with its partners within the FA environment on the cell membrane and propose how its initial assembly in nascent FAs might change during FA maturation under force.

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.

Five-year outcomes in trials comparing transcatheter aortic valve implantation versus surgical aortic valve replacement: a pooled meta-analysis of reconstructed time-to-event data.

OBJECTIVES: The incidence of outcomes in trials comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is expected to be different in the short and long term. We planned a meta-analysis of reconstructed time-to-event data from trials comparing TAVI and SAVR to evaluate their time-varying effects on outcomes. METHODS: We performed a systematic review of the literature from January 2007 through September 2021 on Medline, Embase, the Cochrane Central Register of Controlled Trials and specialistic websites, including randomized trials with allocation to TAVI or SAVR that reported at least 1-year follow-up and that graphed Kaplan-Meier curves of end points. The comparisons were done with grouped frailty Cox models in a landmark framework and fully parametric models. RESULTS: Seven trials were included (7770 participants). TAVI showed a lower incidence of the composite of death or stroke in the first 6 months [risk-stratified hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.56-0.77, P-value <0.001], with an HR reversal after 24 months favouring SAVR (risk-stratified HR 1.25; 95% CI 1.08-1.46; P-value 0.003). These outcomes were confirmed for all-cause death (risk-stratified HR after 24 months 1.18; 95% CI 1.03-1.35; P-value 0.01). TAVI was also associated with an increased incidence of rehospitalization after 6 months (risk-stratified HR 1.42; 95% CI 1.06-1.91; P-value 0.018) that got worse after 24 months (risk-stratified HR 1.67; 95% CI 1.24-2.24; P-value <0.001). CONCLUSIONS: Although it could appear that there is no difference between TAVI and SAVR in the 5-year cumulative results, TAVI shows a strong protective effect in the short term that runs out after 1 year. TAVI becomes a risk factor for all-cause mortality and the composite end point after 24 months and for rehospitalization after 6 months.

Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response.

Polyphosphate (polyP) is a polymer of hundreds of phosphate residues present in all organisms. In mammals, polyP is involved in crucial physiological processes, including coagulation, inflammation, and stress response. However, after decades of research, the metabolic enzymes are still unknown. Here, we purify and identify Nudt3, a NUDIX family member, as the enzyme responsible for polyP phosphatase activity in mammalian cells. We show that Nudt3 shifts its substrate specificity depending on the cation; specifically, Nudt3 is active on polyP when Zn2+ is present. Nudt3 has in vivo polyP phosphatase activity in human cells, and importantly, we show that cells with altered polyP levels by modifying Nudt3 protein amount present reduced viability upon oxidative stress and increased DNA damage, suggesting that polyP and Nudt3 play a role in oxidative stress protection. Finally, we show that Nudt3 is involved in the early stages of embryo development in zebrafish.

[Episode-based bundled payment model: evaluation of medical costs for early operable breast cancer]. / Financement à l'épisode de soins : évaluation du coût d'une chirurgie première pour cancer du sein précoce.

INTRODUCTION: Episode-based bundled payment model is actually opposing to fee-for-service model, intending to incentivize coordinated care. The aims of these study were to determine episode-based costs for surgery in early breast cancer patients and to propose a payment model. METHODS: OPTISOINS01 was a multicenter prospective study including early breast cancer patients from diagnosis to one-year follow up. Direct medical costs, quality and patient reported outcomes were collected. RESULTS: Data from 604 patients were analyzed. Episode-based costs for surgery were higher in case of: planned radical surgery (OR=9,47 ; IC95 % [3,49-28,01]; P<0,001), hospitalization during more than one night (OR=6,73; IC95% [2,59-17,46]; P<0,001), home hospitalization (OR=11,07 ; IC95 % [3,01-173][3,01-54][3,01-543][3,01-54,33]; P<0,001) and re-hospitalization (OR=25,71 ; IC95 % [9,24-89,17; P<0,001). The average cost was 5 268 € [2 947-18 461] when a lumpectomy was planned and 7408 € [4 222-22 565] in case of radical mastectomy. Bootstrap method was applied for internal validation of the cost model showing the reliability of the model with an area under the curve of 0,83 (95 % CI [0,80-0,86]). Care quality and patient reported outcomes were not related to the costs. DISCUSSION: This is the first report of episode-based costs for breast cancer surgery. An external validation will be necessary to validate our payment model.

A new layer of phosphoinositide-mediated allosteric regulation uncovered for SHIP2.

The Src homology 2 containing inositol 5-phosphatase 2 (SHIP2) is a large multidomain enzyme that catalyzes the dephosphorylation of the phospholipid phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3 ) to form PI(3,4)P2 . PI(3,4,5)P3 is a key lipid second messenger controlling the recruitment of signaling proteins to the plasma membrane, thereby regulating a plethora of cellular events, including proliferation, growth, apoptosis, and cytoskeletal rearrangements. SHIP2, alongside PI3K and PTEN, regulates PI(3,4,5)P3 levels at the plasma membrane and has been heavily implicated in serious diseases such as cancer and type 2 diabetes; however, many aspects of its regulation mechanism remain elusive. We recently reported an activating effect of the SHIP2 C2 domain and here we describe an additional layer of regulation via the pleckstrin homology-related (PHR) domain. We show a phosphoinositide-induced transition to a high activity state of the enzyme that increases phosphatase activity up to 10-15 fold. We further show that PI(3,4)P2 directly interacts with the PHR domain to trigger this allosteric activation. Modeling of the PHR-phosphatase-C2 region of SHIP2 on the membrane suggests no major inter-domain interactions with the PHR domain, but close contacts between the two linkers offer a possible path of allosteric communication. Together, our data show that the PHR domain acts as an allosteric module regulating the catalytic activity of SHIP2 in response to specific phosphoinositide levels in the cell membrane.

Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes.

AIM: Cetuximab is a standard-of-care treatment for KRAS wild-type metastatic colorectal cancer (mCRC), but it may also be effective in a subgroup of KRAS mutant patients by its immunomodulatory activity. Here, we explore if KIR (killer cell immunoglobulin-like receptor) genotyping can provide a significant added value in the clinical outcome of patients with KRAS mutant mCRC based on cetuximab treatment. METHODS: We included 69 patients with histologically confirmed mCRC and KRAS mutation, positive EGFR expression, and Eastern Cooperative Oncology Group performance status ≤2. Based on KIR gene content, haplotype (A or B) was defined and genotypes (AA or Bx) were grouped for each patient. RESULTS: We demonstrated with new evidence the immunomodulatory activity of cetuximab in patients with KRAS mutant mCRC. Patients with homozygous genotypes (AA or BB) showed shorter 12-month progression-free survival (PFS12) and poorer overall survival (OS) than those with heterozygotes (AB). Moreover, multivariate analysis confirmed stratification of patients based on genotype was an independent marker of PFS12 (HR 2.16) and the centromeric and telomeric distribution of KIRs was an independent predictor of both PFS12 (HR 2.26) and OS (HR 1.93) in patients with mCRC with KRAS mutation treated with cetuximab. CONCLUSIONS: Selection of patients with mCRC based on their KIR genotypes opens a therapeutic opportunity for patients with KRAS mutation, and it should be tested in clinical trials in comparison with other alternatives with scarce benefit. TRIAL REGISTRATION NUMBER: NCT01450319, EudraCT 2010-023580-18.

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=.

SARS-CoV-2 RNA identification in nasopharyngeal swabs: issues in pre-analytics.

Objectives: The direct identification of SARS-CoV-2 RNA in nasopharyngeal swabs is recommended for diagnosing the novel COVID-19 disease. Pre-analytical determinants, such as sampling procedures, time and temperature storage conditions, might impact on the end result. Our aim was to evaluate the effects of sampling procedures, time and temperature of the primary nasopharyngeal swabs storage on real-time reverse-transcription polymerase chain reaction (rRT-PCR) results. Methods: Each nasopharyngeal swab obtained from 10 hospitalized patients for COVID-19 was subdivided in 15 aliquots: five were kept at room temperature; five were refrigerated (+4 °C); five were immediately mixed with the extraction buffer and refrigerated at +4 °C. Every day and for 5 days, one aliquot per condition was analyzed (rRT-PCR) for SARS-CoV-2 gene E and RNaseP and threshold cycles (Ct) compared. To evaluate manual sampling, 70 nasopharyngeal swabs were sampled twice by two different operators and analyzed separately one from the other. Results: A total of 6/10 swabs were SARS-CoV-2 positive. No significant time or storage-dependent variations were observed in SARS-CoV-2 Ct. Re-sampling of swabs with SARS-CoV-2 Ct lower than 33 resulted in highly reproducible results (CV=2.9%), while a high variability was observed when Ct values were higher than 33 (CV=10.3%). Conclusions: This study demonstrates that time and temperature of nasopharyngeal swabs storage do not significantly impact on results reproducibility. However, swabs sampling is a critical step, and especially in case of low viral load, might be a potential source of diagnostic errors.

An enhanced recovery program in colorectal surgery is associated with decreased organ level rates of complications: a difference-in-differences analysis.

BACKGROUND: Perioperative care has lacked coordination and standardization. Enhanced recovery programs (ERPs) have been shown to decrease aggregate complications across surgical specialties. We hypothesize that the sustained implementation of an ERP will be associated with a decrease in a broad range of complications at the organ system level. STUDY DESIGN: Adult patients undergoing elective colorectal procedures between 1/2011 and 10/2016 were included. Patients were stratified based on exposure to a sustained ERP (7/2014-10/2016) after an 18-month wash-in period in a pre-post analysis. The primary outcome was 30-day complication rate by organ category as collected by National Surgical Quality Improvement Program (NSQIP) abstractors. Demographic and other patient level data were collected. Complication rates were compared using multivariable regression employing a differences-in-differences (DiD) approach using the national NSQIP PUF file to account for secular trends. RESULTS: A total of 1182 patients were included in this study, with 47% treated in an ERP. The two groups were similar in age, gender, race, BMI, comorbidity index, and procedure type. In a multivariable DiD analysis, significant reductions were seen in surgical site infection (OR 0.30; 95% CI 0.20-0.43), postoperative pulmonary complications (OR 0.46; 95% CI 0.24-0.90), transfusion (OR 0.27; 95% CI 0.15-0.51), urinary tract infections (OR 0.34; 95% CI 0.18-0.66), sepsis (OR 0.35; 95% CI 0.20-0.61), and cardiac complications (OR 0.10; 95% CI 0.01-0.84). A reduction in return to the operating room and 30-day readmission was also observed. Median length of stay (LOS) decreased from 5.2 to 3.5 days (p < 0.001). No significant changes occurred for acute kidney injury and hematologic complications. CONCLUSION: An ERP was associated with reduced complication rates across a wide range of organ categories and > 1.5-day reduction in LOS in a colorectal surgery population.

Association Between End-of-Life Conversations in Nursing Homes and End-of-Life Care Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: Less aggressive end-of-life (EOL) care has been observed when health care professionals discuss approaching EOL and preferences about life-sustaining treatments with nursing home (NH) residents or their families. We performed a comprehensive systematic review to evaluate the association between health care professionals-residents and health care professionals-family EOL conversations and EOL care outcomes. DESIGN: Systematic review with meta-analysis. SETTING AND PARTICIPANTS: Seven databases were searched in December 2017 to find studies that focused on health care professionals-residents (without oncologic disease) and health care professionals-family EOL conversations and aimed to explore the impact of EOL conversations on resident's or family's EOL care outcomes. MEASURES: Random effects meta-analyses with subsequent quality sensitivity analysis and meta-regression were performed to assess the effects of EOL conversations on the decision to limit or withdraw life-sustaining treatments. A funnel plot and Eagger test were used to assess publication bias. RESULTS: 16 studies were included in the qualitative and 7 in the quantitative synthesis. Health care professionals-family EOL conversations were positively associated with the family's decision to limit or withdraw life-sustaining treatments (odds ratio = 2.23, 95% confidence interval: 1.58-3.14). The overall effect of health care professionals-family EOL conversations on the family's decision to limit or withdraw life-sustaining treatments remained stable in the quality sensitivity analysis. In the meta-regression, family members with a higher level of education were less influenced by EOL conversations with health care professionals when making decisions about limiting or withdrawing life-sustaining treatments. No publication bias was detected (P = .4483). CONCLUSIONS/IMPLICATIONS: This systematic review shows that EOL conversations promote palliative care. Structured conversations aimed at exploring NH resident preferences about EOL treatment should become routine. NH administrators should offer health care professionals regular training on EOL conversations, and resident-centered care that involves residents and their families in a shared decision-making process at EOL needs to be promoted.

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.

Optimizing Tailored Communications for Health Risk Assessment: A Randomized Factorial Experiment of the Effects of Expectancy Priming, Autonomy Support, and Exemplification.

BACKGROUND: Health risk assessments with tailored feedback plus health education have been shown to be effective for promoting health behavior change. However, there is limited evidence to guide the development and delivery of online automated tailored feedback. OBJECTIVE: The goal of this study was to optimize tailored feedback messages for an online health risk assessment to promote enhanced user engagement, self-efficacy, and behavioral intentions for engaging in healthy behaviors. We examined the effects of three theory-based message factors used in developing tailored feedback messages on levels of engagement, self-efficacy, and behavioral intentions. METHODS: We conducted a randomized factorial experiment to test three different components of tailored feedback messages: tailored expectancy priming, autonomy support, and use of an exemplar. Individuals (N=1945) were recruited via Amazon Mechanical Turk and randomly assigned to one of eight different experimental conditions within one of four behavioral assessment and feedback modules (tobacco use, physical activity [PA], eating habits, and weight). Participants reported self-efficacy and behavioral intentions pre- and postcompletion of an online health behavior assessment with tailored feedback. Engagement and message perceptions were assessed at follow-up. RESULTS: For the tobacco module, there was a significant main effect of the exemplar factor (P=.04); participants who received exemplar messages (mean 3.31, SE 0.060) rated their self-efficacy to quit tobacco higher than those who did not receive exemplar messages (mean 3.14, SE 0.057). There was a three-way interaction between the effect of message conditions on self-efficacy to quit tobacco (P=.02), such that messages with tailored priming and an exemplar had the greatest impact on self-efficacy to quit tobacco. Across PA, eating habits, and weight modules, there was a three-way interaction among conditions on self-efficacy (P=.048). The highest self-efficacy scores were reported among those who were in the standard priming condition and received both autonomy supportive and exemplar messages. In the PA module, autonomy supportive messages had a stronger effect on self-efficacy for PA in the standard priming condition. For PA, eating habits, and weight-related behaviors, the main effect of exemplar messages on behavioral intentions was in the hypothesized direction but did not reach statistical significance (P=.08). When comparing the main effects of different message conditions, there were no differences in engagement and message perceptions. CONCLUSIONS: Findings suggest that tailored feedback messages that use exemplars helped improve self-efficacy related to tobacco cessation, PA, eating habits, and weight control. Combining standard priming and autonomy supportive message components shows potential for optimizing tailored feedback for tobacco cessation and PA behaviors.

Polyphosphate is a key factor for cell survival after DNA damage in eukaryotic cells.

Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised. In contrast, when polyP levels are ectopically increased, yeast cells become more resistant to DNA damage. More importantly, we show that when polyP is reduced in HEK293 mammalian cell line cells and in human dermal primary fibroblasts (HDFa), these cells become more sensitive to DNA damage, suggesting that the protective role of polyP against DNA damage is evolutionary conserved. In conclusion, we present polyP as a molecule involved in resistance to DNA damage and suggest that polyP may be a putative target for new approaches in cancer treatment or prevention.