Insights into the cell-wall dynamics in grapevine berries during ripening and in response to biotic and abiotic stresses.

The cell wall (CW) is the dynamic structure of a plant cell, acting as a barrier against biotic and abiotic stresses. In grape berries, the modifications of pulp and skin CW during softening ensure flexibility during cell expansion and determine the final berry texture. In addition, the CW of grape berry skin is of fundamental importance for winemaking, controlling secondary metabolite extractability. Grapevine varieties with contrasting CW characteristics generally respond differently to biotic and abiotic stresses. In the context of climate change, it is important to investigate the CW dynamics occurring upon different stresses, to define new adaptation strategies. This review summarizes the molecular mechanisms underlying CW modifications during grapevine berry fruit ripening, plant-pathogen interaction, or in response to environmental stresses, also considering the most recently published transcriptomic data. Furthermore, perspectives of new biotechnological approaches aiming at modifying the CW properties based on other crops' examples are also presented.

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.

Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort.

BACKGROUND AND PURPOSE: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults. METHODS: Study participants from a University of Kentucky Alzheimer's Disease Research Center (UK-ADRC) community-based cohort of aging and dementia were used to test our hypothesis. There were 84 participants, 44 women and 40 men. Participants underwent physical examination, neurological examination, medical history, cognitive testing, and blood collection to determine plasma biomarker levels (Aß42/Aß40 ratio, total tau, Neurofilament Light chain (Nf-L), Glial Fibrillary Acidic Protein (GFAP)) and to isolate peripheral blood mononuclear cells (PBMCs). Flow cytometry was used to analyze PBMCs from study participants for effector and memory T cell populations, including CD4+ and CD8+ central memory T cells (TCM), Naïve T cells, effector memory T cells (TEM), and effector memory CD45RA+ T cells (TEMRA) immune cell markers. RESULTS: CD8+ TEMRAs were positively correlated with Nf-L and GFAP. We found no significant difference in CD8+ TEMRAs based on cognitive scores and no associations between CD8+ TEMRAs and AD-related biomarkers. CD4+ TEMRAs were associated with cognitive impairment on the MMSE. Gender was not associated with TEMRAs, but it did show an association with other T cell populations. CONCLUSION: These findings suggest that the accumulation of CD8+ TEMRAs may be a response to neuronal injury (Nf-L) and neuroinflammation (GFAP) during aging or the progression of AD and ADRD. As our findings in a community-based cohort were not clinically-defined AD participants but included all ADRDs, this suggests that TEMRAs may be associated with changes in systemic immune T cell subsets associated with the onset of pathology.

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.

Reduced Respiratory Syncytial Virus Load, Symptoms, and Infections: A Human Challenge Trial of MVA-BN-RSV Vaccine.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant disease burden in older adults. MVA-BN-RSV is a novel poxvirus-vectored vaccine encoding internal and external RSV proteins. METHODS: In a phase 2a randomized double-blind, placebo-controlled trial, healthy participants aged 18 to 50 years received MVA-BN-RSV or placebo, then were challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes. RSV symptoms were collected. Antibody titers and cellular markers were assessed before and after vaccination and challenge. RESULTS: After receiving MVA-BN-RSV or placebo, 31 and 32 participants, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (P = .017) for MVA-BN-RSV (median = 0.00) than placebo (median = 49.05). Total symptom scores also were lower (median = 2.50 and 27.00, respectively; P = .004). Vaccine efficacy against symptomatic, laboratory-confirmed or culture-confirmed infection was 79.3% to 88.5% (P = .022 and .013). Serum immunoglobulin A and G titers increased approximately 4-fold after MVA-BN-RSV vaccination. Interferon-γ-producing cells increased 4- to 6-fold after MVA-BN-RSV in response to stimulation with the encoded RSV internal antigens. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination. CONCLUSIONS: MVA-BN-RSV vaccination resulted in lower viral load and symptom scores, fewer confirmed infections, and induced humoral and cellular responses. CLINICAL TRIALS REGISTRATION: NCT04752644.

Effectiveness of Workplace Health Promotion (WHP) interventions in university employees: a scoping review.

Workplace Health Promotion (WHP) interventions proved to be effective in several workplace contexts. Currently, the effectiveness of such interventions in the academic workplace is lacking, albeit evidence suggests similar patterns to those occurring in other workplace sectors. The aim of this study was to review WHP interventions in the university workplace that led to improve health- and work-related outcomes. Articles were selected using Pubmed, Web of Science, Scopus, Embase, PsycInfo, Cinhal and FSTA, using search strings focused on health- and/or work-related outcomes and involving University WHP interventions published between January 2010 and July 2021. The majority of the 12 studies selected reported positive results in their individuality, especially regarding health-related outcomes [biological such as weight loss, physical activity, mental health and lifestyle habits] and work-related outcomes concerning improvements either for the employee or for the working system. Studies on economic advantage and Return on Investment were limited and reported contrasting results. In conclusion, we have highlighted how the studies on effectiveness of WHP interventions in the university context are few and heterogeneous and need to be encouraged further research in order to build specific guidelines that are effective.

Interventions concerning prevention promotion in the workplace, involving activities targeting lifestyle habits, nutrition and/or physical activity as well as general wellbeing, are growing and becoming more common due to their benefits on health and work outcomes. The aim of this review was to investigate the effectiveness of such interventions in the university workplace context to help create directed guidelines for their correct implementation in this setting. Although it was difficult to draw peculiar conclusions due to the heterogeneity of the programs described in the studies, the overall positivity of the results and the perspective university environment, outlook that the implementation of multicomponent and multilevel interventions would improve employees' wellness and favor universities' welfare.

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.

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.

Experience, and gynaecological and reproductive health follow-up of young adult women who have undergone ovarian tissue cryopreservation.

RESEARCH QUESTION: What are the experience, and gynaecological and reproductive health outcomes in young adult women who have undergone ovarian tissue cryopreservation (OTC)? DESIGN: A retrospective observational study was conducted at a single institution between May 2019 and February 2021 including 87 women aged over 18 years undergoing OTC. Medical characteristics and questionnaire data collected more than 18 months after OTC were analysed. RESULTS: Close to 74% (n = 64/87) of women had a follow-up consultation and completed the questionnaire. Most women found the information provided on the OTC technique and the strategies proposed to restore fertility with ovarian tissue understandable and useful. The majority of patients thought that OTC had a positive impact on their well-being during disease treatment. Anti-Müllerian hormone serum concentration decreased significantly after treatment (P < 0.0001) and was significantly lower when patients received chemotherapy before OTC (P = 0.0039). The total cyclophosphamide equivalent dose was significantly higher in women with FSH concentrations above 25 IU/l after treatment (P = 0.0004). More than 70% of women who planned a pregnancy after the end of treatment succeeded, with a natural pregnancy rate close to 53%. Only nine patients (8.0%) underwent ovarian tissue transplantation for fertility restoration and six of them became pregnant and delivered at least once. CONCLUSION: Young adult women expressed a good satisfaction rate with OTC and that their experience had been beneficial. The usage rate of cryopreserved ovarian tissue remains low. The gynaecological and reproductive health follow-up consultation should be included in the supportive care provided following OTC.

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.

Postoperative Pulmonary Complications' Association with Sugammadex versus Neostigmine: A Retrospective Registry Analysis.

BACKGROUND: Postoperative residual neuromuscular blockade related to nondepolarizing neuromuscular blocking agents may be associated with pulmonary complications. In this study, the authors sought to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications in comparison with neostigmine. METHODS: Adult patients from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who underwent general anesthesia procedures between January 2010 and July 2019 were included in an observational cohort study. In early 2017, a wholesale switch from neostigmine to sugammadex occurred at Vanderbilt University Medical Center. The authors therefore identified all patients receiving nondepolarizing neuromuscular blockades and reversal with neostigmine or sugammadex. An inverse probability of treatment weighting propensity score analysis approach was applied to control for measured confounding. The primary outcome was postoperative pulmonary complications, determined by retrospective chart review and defined as the composite of the three postoperative respiratory occurrences: pneumonia, prolonged mechanical ventilation, and unplanned intubation. RESULTS: Of 10,491 eligible cases, 7,800 patients received neostigmine, and 2,691 received sugammadex. A total of 575 (5.5%) patients experienced postoperative pulmonary complications (5.9% neostigmine vs. 4.2% sugammadex). Specifically, 306 (2.9%) patients had pneumonia (3.2% vs. 2.1%), 113 (1.1%) prolonged mechanical ventilation (1.1% vs. 1.1%), and 156 (1.5%) unplanned intubation (1.6% vs. 1.0%). After propensity score adjustment, the authors found a lower absolute incidence rate of postoperative pulmonary complications over time (adjusted odds ratio, 0.91 [per year]; 95% CI, 0.87 to 0.96; P < .001). No difference was observed on the odds of postoperative pulmonary complications in patients receiving sugammadex in comparison with neostigmine (adjusted odds ratio, 0.89; 95% CI, 0.65 to 1.22; P = 0.468). CONCLUSIONS: Among 10,491 patients at a single academic tertiary care center, the authors found that switching neuromuscular blockade reversal agents was not associated with the occurrence of postoperative pulmonary complications.

The Attributable Mortality of Postoperative Bleeding Exceeds the Attributable Mortality of Postoperative Venous Thromboembolism.

BACKGROUND: Bleeding and venous thromboembolic disease are considered important sources of postoperative morbidity and mortality. Clinically, treatment of these 2 disorders is often competing. We sought to better understand the relative contributions of bleeding and venous thromboembolic disease to postoperative attributable mortality in a national cohort. METHODS: A retrospective analysis of the 2006-2017 American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was performed to assess the adjusted odds ratio and attributable mortality for postoperative bleeding and venous thromboembolism, adjusted by year. RESULTS: After adjustment for confounding variables, bleeding exhibited a high postoperative attributable mortality in every year studied. Venous thromboembolism appeared to contribute minimal attributable mortality. CONCLUSIONS: Bleeding complications are a consistent source of attributable mortality in surgical patients, while the contribution of venous thromboembolic disease appears to be minimal in this analysis. Further studies are warranted to better understand the etiology of this disparity.

Barriers to and Facilitators of Bedside Nursing Handover: A Systematic Review and Meta-synthesis.

BACKGROUND: Bedside nursing handover (BNH) has been recognized as a contributor to patient-centered care. However, concerns about its effectiveness suggest that contextual factors should be considered before and after BNH implementation. PURPOSE: This review aimed to identify, evaluate, and synthetize the qualitative literature on the barriers to and facilitators of BNH as experienced by nurses and patients. METHODS: The Joanna Briggs Institute meta-aggregation method was applied. A systematic search was performed to identify qualitative studies published from inception to June 30, 2020. Two independent researchers assessed methodological quality and extracted data. RESULTS: Twenty-four articles were included, comprising 161 findings, and 5 synthesized findings emerged with a moderate level of confidence. CONCLUSIONS: BNH ensures patient safety and increases satisfaction and recognition among patients and nurses. This evidence on the barriers to and facilitators of BNH could help health care providers who have implemented or plan to implement this practice.

The Impact of Functional Dependence and Related Surgical Complications on Postoperative Mortality.

PURPOSE: Functional dependency is a known determinant of surgical risk. To enhance our understanding of the relationship between dependency and adverse surgical outcomes, we studied how postoperative mortality following a surgical complication was impacted by preoperative functional dependency. METHODS: We explored a historical cohort of 6,483,387 surgical patients within the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). All patients ≥ 18 years old within the ACS-NSQIP from 2007 to 2017 were included. RESULTS: There were 6,222,611 (96.5%) functionally independent, 176,308 (2.7%) partially dependent, and 47,428 (0.7%) totally dependent patients. Within 30 days postoperatively, 57,652 (0.9%) independent, 15,075 (8.6%) partially dependent, and 10,168 (21.4%) totally dependent patients died. After adjusting for confounders, increasing functional dependency was associated with increased odds of mortality (Partially Dependent OR: 1.72, 99% CI: 1.66 to 1.77; Totally Dependent OR: 2.26, 99% CI: 2.15 to 2.37). Dependency also significantly impacted mortality following a complication; however, independent patients usually experienced much stronger increases in the odds of mortality. There were six complications not associated with increased odds of mortality. Model diagnostics show our model was able to distinguish between patients who did and did not suffer 30-day postoperative mortality nearly 96.7% of the time. CONCLUSIONS: Within our cohort, dependent surgical patients had higher rates of comorbidities, complications, and odds of 30-day mortality. Preoperative functional status significantly impacted the level of postoperative mortality following a complication, but independent patients were most affected.

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.

Hierarchical chirality expression of gemini surfactant aggregates via equilibrium between chiral nucleotide and nonchiral mono-anions.

The assembling behaviors of nonchiral dicationic amphiphilic molecules (gemini) in the presence of the mixture of chiral anionic nucleotides and nonchiral anions are investigated. We demonstrate that subtle balance of various physico-chemical parameters and the competition between chiral and nonchiral anions at the interface of gemini assemblies influences the expression of molecular chirality at the micrometer scale through the hierarchical molecular assembly.

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.

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.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. / Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica.

BACKGROUND AND AIM: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. MATERIAL AND METHOD: Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. RESULTS: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. CONCLUSION: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.