Wilcoxon Test For Paired Samples Research Articles

Intra-abdominal infection after tumor surgery: tigecycline combined with β-lactam antibiotics versus tigecycline alone

BackgroundsTigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus β-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery.MethodsThis was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student’s t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication.ResultsIn total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time.ConclusionsTigecycline plus β-lactam wasn’t superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.

O-020 What is the recovery time for sperm parameters in men who have suffered a mild Covid-19 infection?

Abstract Study question What is the time required in men who have suffered a mild Covid-19 infection, for the seminal parameters to be restored to the pre-Covid values? Summary answer The effect of Covid-19 infection on the concentration and sperm motility is clearly confirmed and is maintained over time, at least beyond 100 days. What is known already Although several studies have been performed on the effect of SARS-CoV-2 on reproductive health in the short term vs. healthy controls, and the negative effect on sperm parameters has been demonstrated, there is a scarcity of data showing the degree to which the virus affects the semen parameters in one group of patients after coronavirus infection compared to before infection. Moreover, there are no conclusive data regarding the long-term effects of SARS-CoV-2 on semen parameters. Study design, size, duration This prospective study was carried out in 6 reproductive centers between February 2020 and October 2022 including 45 male patients with a confirmed diagnosis of mild COVID-19. For each of the semen parameters (volume, sperm count, active and total motility, normal morphology, and vitality) a standardized index was calculated by dividing the value of the parameter from the subsequent semen analysis by that from the semen analysis of the same individual prior to infection. Participants/materials, setting, methods The median age of the participants was 31 years, proving the absence of a relationship between age and any of the parameters analyzed. The post-Covid test was performed between 17 and 516 days after infection, with a median of 100 days. The time elapsed between both samples was a median of 238 days. The effect of time on the affectation of semen parameters was studied, setting 100 days as the cut-off point. Main results and the role of chance There were significant differences in semen parameters before and after COVID-19 in terms of semen volume, sperm concentration, progressive motility, total motility, and vitality which decreased significantly (p &amp;lt; 0,05) after SARS-CoV-2 infection compared to the pre-infection values. Morphology was not significantly affected. The total sperm count is the most clearly affected seminal parameter. Half of the individuals (median) obtained a total count in the second sample less than 57% of the initial one. Considering the time of spermatogenesis, the subjects were separated into two groups: those who performed the semen analysis in the first 100 days after infection and those who performed it later. No differences in any parameter were found between the two groups with U Mann-Withney test. Using the Wilcoxon test for paired samples, it was demonstrated that the deleterious effect of infection on sperm concentration and motility not only does not improve with time, but it becomes more significant in late sperm analysis, performed more than one hundred days after the infection. Limitations, reasons for caution It should be mentioned that impairment of semen parameters may not be due to a direct effect of the SARS-CoV-2 virus. There are likely to be additional factors that contribute to long-term sperm parameters decrease, but whose identity is currently unknown. Wider implications of the findings The present study revealed the long-term impacts of SARS-CoV-2 on various parameters of sperm quality even with a mild infection. Further efforts should be made to study the long-time effects of COVID-19 infection on male reproduction. Trial registration number Not Applicable

251-OR: The Impact of Identifying Sleep with a Fitbit on Calculated Rates of Nocturnal Hypoglycemia—The Hypo-Metrics Study

Consensus defines nocturnal hypoglycemia as occurring between 00:00 and 06:00 hrs. However, this may introduce bias, as for many, these hours only partially match real sleeping hours. Therefore, we compared rates of hypoglycemia while asleep (defined by Fitbit Charge 4) to rates of conventionally-defined nocturnal hypoglycemia. Hypo-METRICS study participants wore a Fitbit charge 4 and blinded FreeStyle Libre glucose monitor for up to 70 days. Every hypoglycemia episode (≤70mg/dL or ≤54mg/dL for ≥15 min) was classified as ‘asleep’ or ‘awake’ based on Fitbit sleep intervals and ‘nocturnal’ (00:00-06:00 hrs) or ‘day-time’. We compared weekly sensor-detected hypoglycemia (SDH) rates whilst asleep to nocturnal SDH rates using a paired sample Wilcoxon test. We included 542 participants (269 with type 1 diabetes, median (IQR) age 56 (44-66) years, HbA1c 7.3%(6.7-7.9), with 69 (65-70) nights with sleep data/participant). Sleep duration was 6.1 (5.2-6.8) hours. Median weekly rates of SDH while asleep were higher than rates of nocturnal SDH both ≤70mg/dL (1.3 (0.6-2.5) vs 0.9 (0.4-1.8), p&amp;lt;0.001) and ≤54mg/dL (0.4 (0.2-0.9) vs 0.3 (0.1-0.7), p&amp;lt;0.001). Stratifying by type of diabetes did not change the direction or magnitude of the differences in SDH rates. Using clock time to estimate nocturnal hypoglycemia underestimates hypoglycemia whilst asleep by up to a third. Using activity trackers such as Fitbit to identify sleep offers a novel way to estimate hypoglycemia whilst asleep to better reflect lived experience of nocturnal hypoglycemia. Disclosure G.Martine-edith: Other Relationship; Novo Nordisk A/S. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. E.Renard: Consultant; Abbott Diabetes, Dexcom, Inc., AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Roche Diabetes Care. S.R.Heller: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker's Bureau; Novo Nordisk, Medtronic. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. Hypo-resolve consortium: n/a. P.Divilly: None. N.Zaremba: None. U.Soeholm: Employee; Novo Nordisk A/S. A.Kingsnorth: None. Z.Mahmoudi: Employee; Novo Nordisk. M.Gomes: Employee; Novo Nordisk A/S. B.E.De galan: Research Support; Novo Nordisk. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)

Evolving the EN 1500 test method for alcohol-based hand rub closer to clinical reality by reducing the organic load on hands and enabling product to be applied to dry hands

The methods currently used in Europe and North America to evaluate the bactericidal efficacy of hand hygiene products have some limitations, e.g., in the selection of test organisms or the method of contamination, and none of the methods allows prediction of actual clinical efficacy. WHO has therefore proposed to develop methods that better reflect typical clinical reality. In a first experiment, we investigated two contamination methods (immersion according to EN 1500 and low-volume according to ASTM E2755) with the EN 1500 test organism Escherichia coli and using 60% v/v iso-propanol. The second experiment was for comparison of the two contamination methods with Enterococcus faecalis. Finally, the two test organisms were compared using the low-volume contamination method. Data within each experiment was statistically compared using the Wilcoxon test for paired samples and data from all experiments were combined and fit to linear mixed effects models. Mixed-effects analysis confirmed that the test organism and contamination method both impacted the pre-values and all three of these were factors that influenced log10 reductions. Higher pre-values resulted in significantly higher log10 reductions, immersion contributed to significantly higher log10 reductions, and E. coli affected significantly lower log10 reductions. An efficacy evaluation against E. faecalis with a low-volume contamination method could be considered as an alternative to the EN 1500 standard. This could help improve the clinical relevance of the test method with including a Gram-positive organism and reducing soil load which allows a product application closer to reality.

The Effect of Device-Controlled Breathing on the Pulse Arrival Time and the Heart Rate Asymmetry Parameters in Healthy Volunteers

Background: The development of wearables has facilitated the monitoring of biomedical parameters in everyday life. One of the most common sensors of these gadgets is the photoplethysmograph (PPG); hence, the proper processing and interpretation of the PPG signal are essential. Besides pulse rate detection, these devices—together with an ECG—compute the pulse arrival time (PAT), from which the actual beat-to-beat blood pressure can be estimated. The heart rate shows asymmetrical accelerations and decelerations, quantified by the parameters of heart rate asymmetry (HRA). In the present study, we investigated the influences of different breathing-patterns on the PATs and HRA parameters. Methods: The authors evaluated 5 min simultaneous respiratory-, ECG- and PPG-signal recordings of 35 healthy, young volunteers specifically expressing the following breathing patterns: metronome-controlled inspiration, and both inspiration and expiration controlled at 1:1 and 1:2 ratios, respectively. The records were analyzed by HRVScan_Merge v3.2 software. The PAT values were calculated at eight different reference points. The HRA parameters and the PAT values at different breathing patterns were compared using the Friedman test and post hoc Wilcoxon paired-sample test. Results: Porta- and Guzik-indices significantly increased at 1:1 breathing compared to 1:2 and single-paced breathing. PATs increased significantly in dual-paced series compared to single-paced series at each reference point. Conclusion: Based on our results, the increased PATs at dual-paced versus single-paced breathing may indicate the involvement of cognitive functions. The symmetrical respiration ratio increases the heart rate symmetry; however, this effect is not detectable in the periphery through the PATs.

Enhancing disaster response of emergency medical teams through "TEAMS 3.0" training package-Does the multidisciplinary intervention make a difference?

In the aftermath of disasters, Emergency Medical Teams (EMTs) are dispatched to help local rescue efforts. Although EMTs are recognized to be a critical component of the global health workforce, concerns have emerged over their functioning and effectiveness. For example, lack of cooperation and coordination between different EMTs has been a longstanding issue, resulting in fragmented disaster management. To enhance the provision of EMT's field teamwork, the Training for Emergency Medical Teams and European Medical Corps (TEAMS) project was established, and later further updated with novel scenarios and exercises (i.e., adapting EMT operations to a sudden disaster; becoming a modular team; reflecting on ethical dilemmas) in the complementary "TEAMS 3.0" project where a more comprehensive training package was developed. The aim of this study was to assess the effectiveness and quality of the TEAMS 3.0 training package in four training programs in Portugal, Germany, Norway, and Turkey. Participants completed a set of questionnaires designed to assess self-efficacy, teamwork, and quality of training. The results from all the trainings suggest an improvement for both teams' self-efficacy and teamwork. The mean score among all the participants (N = 100) for both the self-efficacy scale and teamwork scale was 3.217 (±0.223) prior to training and 3.484 (±0.217) following the training, and 2.512 (±1.313) prior to training and 3.281 (±0.864), respectfully, with statistically significant differences according to Wilcoxon paired samples test (p < 0.05). The quality of training is regarded as high and deemed as an appropriate tool package for addressing the objectives of the project and the perceived needs of EMT disaster deployment. Thus far, the TEAMS 3.0 project has demonstrated to be effective in promoting EMT teamwork capacities.

Modifikovaná Harringtonova operace v terapii rozsáhlých nádorových defektů acetabula

PURPOSE OF THE STUDY The increasing prevalance of patients with metastatic bone cancer and their improved survival puts more emphasis on the quality of treatment of bone metastases. Although most pelvic lesions are treated non-operatively, extensive destruction of the acetabular segment poses a therapeutic challenge. A potential treatment option may be the modified Harrington procedure. MATERIAL AND METHODS At our department, this surgical procedure has been opted for in 14 patients (5 men and 9 women) since 2018. The mean age at the time of surgery was 59 years (range 42 to 73). Twelve patients suffered from metastatic cancer, one patient had a fibrosarcoma metastasis and one female patient presented with aggressive pseudotumor. Radiological and clinical followup of the patients was performed. Pain was assessed using the Visual Analogue Scale, and the Harris Hip Score and the MSTS score were used to evaluate the functional outcome. The paired samples Wilcoxon test was used to analyze the statistical significance of the difference. RESULTS The mean follow-up period was 25 months. At the time of assessment, ten patients were alive with the mean follow-up of 29 months (range 2 to 54 months) and four patients had died of cancer progression, with the mean follow-up being 16 months. No perioperative death or mechanical failure were reported. One female patient developed a hematogenous infection during febrile neutropenia, which was successfully managed with early revision and implant preservation. Statistically, a significant improvement in the MSTS (median 23) and HHS (median 86) functional scores compared to the preoperative values (MSTS median 2, p<0.01, r-effect size = 0.6; HHS preop median 0, p<0.005, r-effect size = -0.7) was observed. There was also a statistically significant reduction in pain (VAS postoperative median 1, VAS preoperative median 8, p<0.01, r-effect size = -0.6). All patients were capable of independent ambulation after the surgery, nine patients walked without support. DISCUSSION There are not many alternatives to this surgical procedure. Apart from non-operative palliative treatment, the options include ice cream cone prostheses or customized 3D implants which are, impractical in terms of time and cost. Our results are comparable to other studies, confirming the reproducibility and reliability of the method. CONCLUSIONS The Harrington procedure is an efective method for management of large acetabular tumor defects with good functional outcomes, an acceptable perioperative risk and a low risk of failure in the medium term, thus suitable also for patients with good cancer prognosis. Key words: umor, metastasis, acetabulum, pelvis, Harrington, reconstruction.

ECOG score as a barrier for clinical trial eligibility in the patient population with genitourinary cancer: Is it time to adapt this criterion to real-world data?

78 Background: ECOG score is a common eligibility criteria used in clinical trials (CT). Many CT recruit only patients in good physical condition (ie. minimal comorbidities and good performance status), which may misrepresent the real-world cancer population.This gap may result in safety and effectiveness data that may not be applicable to the real-world patient population. Furthermore, applying strict eligibility criteria augment a barrier for patient accrual to CT. In this study we analyzed the impact of ECOG performance status on Genitourinary (GU) oncology trials eligibility of patients who used the Trialjectory web-based platform. Methods: Trialjectory is an AI- based platform that matches cancer patients to CT based on a patient reported questionnaire that translates to an individual clinical profile. The profile includes disease status and stage, biomarkers, treatment history and comorbidities and demographics. Data from patients with prostate and urinary bladder cancer was analyzed. The number of matched trials per patient was determined based on the patient’s profile, location and travel preference. To assess the impact of ECOG score, we edited the data set to reflect a better performance status per patient. We used a paired samples Wilcoxon test to assess the association between decreasing the ECOG threshold and the number of matched CT. Results: Between May 2021 and August 2022 we analyzed 153 bladder cancer profiles with ECOG=2 and 71 with ECOG=3, and 90 and 27 prostate cancer profiles with ECOG=2 and ECOG=3, respectively. In a multiple regression analysis, high ECOG score was inversely and significantly associated with the number of matched trials per patient in prostate cancer (p=0.009), independent of cancer stage, patient ethnicity and gender; and in urinary bladder cancer (p=0.003), after adjustment for cancer stage, gender and ethnicity. Editing ECOG score from 2 to 1 resulted in a profound increase (233% for prostate cancer patients and 300% for urinary bladder cancer patients respectively) in the number of matched trials per patient, from a median of 3 trials to 7 and from 2 to 6 trials per patient respectively (V = 426, p-value &lt;0.0001 and V = 14, p-value = 0.0002 respectively). Among Bladder Cancer patients, editing the ECOG score from 3 to 2 resulted in an increase of 200%, from a median 1 to 2 matched CT (V = 291, p-value = 0.0002). Conclusions: The results reflect a high magnitude reduction in eligibility for patients with higher ECOG scores. Excluding these patients may result in skewed reporting on effectiveness-toxicity of drugs that may not be applicable for the real-world patient population augmenting a significant barrier for CT accrual amongst the proactive population who seek it.

Improvement in Nasal Obstruction and Quality of Life after Nasal Septoplasty with Turbinoplasty: A Pre- and Post-study.

Introduction Septoplasty and turbinoplasty are common surgical interventions used to relieve nasal obstructive symptoms. Since it is difficult to measure the degree of nasal blockage, current literature wonders about the frequent performance of these procedures. Objective To evaluate the perceived change in the nasal obstruction and the quality of life (QoL) of patients that underwent a septoplasty along with a turbinoplasty by applying subjective scales, to describe the correlation between those scales, and to study the impact of clinical factors in the postoperative outcomes. Methods Prospective observational study. The Nasal Obstruction Symptom Evaluation (NOSE), the Visual Analog Scale (VAS), and the Glasgow Benefit Inventory (GBI) were assessed. The paired sample Wilcoxon test was used to evaluate the difference between the pre- and postoperative surveys. The correlation coefficient between the subjective scales was calculated. A quantile regression was performed to evaluate the effect of surgery on the results adjusted for clinical and demographic variables. Results A total of 115 patients were interviewed. Postoperative NOSE scores were 45 points lower (95% confidence interval [CI]: - 53.53-- 35.46; p < 0.001) in comparison with the NOSE preoperative scores. Obesity was the only statistically significant factor associated with worse outcomes. Additionally, we found a high correlation between the NOSE and VAS scores and a negative correlation between the GBI and postoperative VAS scores. Conclusion Nasal septoplasty, when paired with a turbinoplasty, decreases nasal obstruction and improves QoL. Obesity was associated with worse results. There was a strong correlation between the NOSE and the VAS results and between the GBI and postoperative VAS results.

The role of air temperature in Legionella water contamination and legionellosis incidence rates in southern Italy (2018-2023).

Legionnaires' disease is caused by inhalation or aspiration of small water droplets contaminated with Legionella, commonly found in natural and man-made water systems and in moist soil. Over the past 5 years, notification rates of this disease have almost doubled in the European Union (EU) / European Environmental Agency (EEA), from 1.4 in 2015 to 2.2 cases per 100,000 population in 2019. Some studies show that the greater presence of the microorganism in the water network and the increase in cases of legionellosis could be related to the variations in some environmental factors, such as air temperature, which may influence the water temperature. Climate change is currently a prominent topic worldwide because of its significant impact on the natural environment. It is responsible for the increase in numerous waterborne pathologies. The purpose of this study was to correlate the air temperature recorded in Apulia region from January 2018 to April 2023 with the presence of Legionella in the water networks of public and private facilities and the incidence rates of legionellosis during the same period. During the period from January 2018 to April 2023, water samples were collected from facilities involved in legionellosis cases and analyzed for Legionella. During the same period, all the cases notified to the regional epidemiological observatory (OER-Apulia) were included in this study. Statistical analyses were conducted using the Shapiro-Wilk test to determine whether the Legionella load was distributed normally, the Wilcoxon rank sum test to compare the air temperatures (average and range) of the negative and positive samples for Legionella detection, and the multivariate analysis (Poisson regression) to compare the Legionella load with the water sample temperature, average air temperature, and temperature range on the day of sampling. The Wilcoxon test for paired samples was used to compare legionellosis cases between the warmer and colder months. Overall, 13,044 water samples were analyzed for Legionella and 460 cases of legionellosis were notified. Legionella was isolated in 20.1% of the samples examined. The difference in the air temperature between negative samples and positive samples was statistically significant (p-value < 0.0001): on days when water samples tested positive for Legionella a higher temperature range was observed than on days when water samples tested negative (p-value = 0.004). Poisson regression showed a direct correlation between Legionella load, water temperature, and average air temperature. The incidence of legionellosis cases in warmer months was higher than in colder months (p-value = 0.03). Our study highlights a significant increase in the load of Legionella in the Apulian water network, and an association between warmer temperatures and legionellosis incidence. In our opinion, further investigations are needed in different contexts and territories to characterize the epidemiology of legionellosis, and to explain its extreme variability in different geographical areas and how these data may be influenced by different risk factors.

960 EARLY ONSET OF SUBTLE LIVER DAMAGE IN TTR AMYLOIDOSIS PATIENTS TREATED WITH TAFAMIDIS

Abstract Background misfolded transthyretin amyloid fibrils can deposit in the myocardium causing transthyretin amyloid cardiomyopathy (ATTR-CM). Tafamidis has become recently available for the treatment of ATTR-CM, but to date very few data about its possible side effects have been published. Aims to investigate the potential liver toxicity of Tafamidis 61 mg/day in a group of patients affected by wild type ATTR-CM treated in our department. Materials and Methods 14 consecutive patients with wild-type ATTR-CM were treated with Tafamidis accordingly to the classical recommendations. The patients’ liver function was checked through transaminases and gammaGT determination at baseline and for the first six months and their changes analysed with the non-parametric Wilcoxon test for paired samples. Results mean age of the patients included (13 males and a female) was 78 years. Baseline transaminases were all within the normal range (median GOT level 25.0 U/L - IQR 19.0-29.0; median GPT levels 24.0 U/L - IQR 15.0-27.0) and remained stable for the first two months (median GOT at 2 months 25.5 U/L - IQR 19.0-28.0; median GPT at 2 months 22.5 U/L – IQR 16.0-27.0). Median GGT baseline level was 138.0 U/L (IQR 58.0-204.0) and raised to 142.0 U/L (IQR 56.0-270.0) after a two-month therapy (p&amp;lt;0.01). The further follow-up confirmed a similar trend in the first six month of treatment, with a linear and constant increase of gammaGT levels. Conclusions even not clinically relevant, the wild-type ATTR-CM patients included in our analysis showed all a subtle increase of gammaGT values after only two months of Tafamidis treatment, which was confirmed at six months. This observation underlines the potential hepatotoxicity of the drug, thus confirming the recommendations of strict and regular liver function analysis provided by the manufacturer.

Endothelial Cell Activation Enhances Thromboinflammation in Vitt

Aim: Vaccine induced thrombosis thrombocytopenia (VITT) syndrome is a rare complication of ChAdOx1 vaccination for COVID19. VITT shares similarities with heparin induced thrombocytopenia (HIT). In both VITT and HIT, patients develop antibodies against platelet factor 4 (PF4) which promote platelet activation and thrombosis. Involvement of the endothelium in the pathogenic process has been described for HIT. Binding of HIT antibodies to PF4/glycosaminoglycan complexes on the surface of endothelial cells leads to their activation and increased procoagulant activity (Madeeva, J Thromb Haemost, 2016). However, the contribution of the endothelium to VITT has not been described. Here, we evaluate the effect of VITT plasma or serum on endothelial cell activation and thromboinflammation using an endothelialized biochip. Method: Serum and plasma samples were received from patients fulfilling clinical criteria of VITT including venous and/or arterial thrombosis, thrombocytopenia <150 x 10^3/uL, D-dimer >5-fold of upper limit of normal within 4-42 days after 1st dose of ChAdOx1 vaccine (termed "Clinical VITT") and from healthy, age and sex matched, ChAdOx1 vaccinated individuals within the same timeframe from vaccination (termed "Vaccine controls"). PF4 ELISA and VITT functional assays were performed on all samples (Lee, Blood Adv, 2022). Human umbilical vein endothelial cells (HUVECs) were treated with heat inactivated serum or plasma in the presence of peptide GPRP. Polydimethylsiloxane microfluidic straight channels were seeded with HUVECs (Endochip) and treated with VITT or control serum and compared with TNF alpha treatment. The endothelial surface expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P-selectin, tissue factor (TF) and von Willebrand factor (vWF) were measured by immunostaining in the presence or absence of native platelet factor 4 (PF4). In some experiments HUVECs were treated with ChAdOx1 vaccine or vehicle for 48-120h. Thromboinflammation was measured by fluorescence area of antibody-stained platelets, neutrophils and fibrin on the Endochip after perfusion of recalcified blood from HIT antibody-reactive healthy volunteers (Morel-Kopp, J Thromb Haemost, 2016) at a shear rate of 100s-1. Results: Samples from 10 patients presenting with clinically confirmed VITT were paired with samples from 10 vaccinated individuals. Clinical VITT samples were separated into negative and positive for both PF4 ELISA and VITT functional assay (defined as VITT ELISA positive and VITT ELISA negative, Panel A). Endothelial cell surface expression of P-selectin was increased after 12 h incubation with 25% v/v VITT serum or plasma compared with samples from AZ vaccinated non-VITT individuals (median integrated intensity/cell 8065 vs 3515 a.u, p=0.03). The expression of TF was significantly increased by addition of PF4 to the VITT plasma (median integrated intensity/cell 42038 vs 14881 a.u., p=0.01 by Mann Whitney test). ChAdOx1 treatment of HUVECs at 1:1000 dilution induced the expression of spike protein but did not significantly enhance thromboinflammation compared with media, as assessed by the perfusion of whole blood through the Endochip. Treatment of the Endochip with VITT serum, without the addition of PF4, significantly increased the adhesion of platelets compared with control serum (median 2.2-fold, p=0.002), neutrophils (2.5-fold, p=0.003) and fibrin (5.4-fold, p=0.002 by Wilcoxon paired samples test (Panel B). There was no difference in the thromboinflammatory response between ELISA negative and positive group (Panel B). Conclusion: Endothelial inflammation contributes to the prothrombotic tendency in VITT in an in vitro model of thromboinflammation. VITT serum induces the endothelial expression of P-selectin and TF. Endothelial inflammation may explain thrombotic events in cerebral or splanchnic veins of vaccinated individuals without detectable anti-PF4 antibodies by ELISA or platelet-based VITT functional assays. Endothelialised biochips have diagnostic potential for detecting immune prothrombotic tendencies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A randomized dietary intervention to increase colonic and peripheral blood SCFAs modulates the blood B- and T-cell compartments in healthy humans

SCFAs have immune-modulating effects in animal models of disease. However, there is limited evidence that this may occur in humans. This study aimed to determine the effects of increased exposure to SCFAs via dietary manipulation on colonic fermentation and adaptive immune cells. Twenty healthy young adults (18-45 y of age) underwent a blinded randomized crossover dietary intervention, consuming a high-SCFA diet and a matched low-SCFA diet for 21-d with a 21-d washout in between. SCFAs were provided through resistant starch, inulin, and apple cider vinegar. Blood and 3-d total fecal output were collected at baseline and at the end of each diet. GC was used to measure fecal and plasma SCFA. Flow cytometry was used for peripheral blood immunophenotyping. According to a paired samples Wilcoxon test, the high-SCFA diet was associated with significantly higher fecal SCFA concentrations [median (IQR); 86.6 (59.0) compared with 75.4 (56.2) µmol/g, P = 0.02] and lower fecal ammonia concentrations [26.2 (14.7) compared with 33.4 (18.5) µmol/g, P = 0.04] than the low-SCFA diet. Plasma propionate [9.87 (12.3) compared with 4.72 (7.6) µmol/L, P = 0.049] and butyrate [2.85 (1.35) compared with 2.02 (1.29) µmol/L, P = 0.03] were significantly higher after the high-SCFA diet than after the low-SCFA diet. Blood total B cells [184 (112) compared with 199 (143) cells/µL, P = 0.04], naive B cells [83 (66) compared with 95 (89) cells/µL, P = 0.02], Th1 cells [22 (19) compared with 29 (16) cells/µL, P = 0.03], and mucosal-associated invariant T cells [62 (83) compared with 69 (114) cells/µL, P = 0.02] were significantly lower after the high-SCFA diet than the low-SCFA diet. Increasing colonic and peripheral blood SCFA has discrete effects on circulating immune cells in healthy humans following 3-wk intervention. Further studies (e.g., in patients with inflammatory disease) are necessary to determine whether 1) these changes have immunomodulatory effects, 2) they are therapeutically beneficial, and 3) prolonged intake might be required. This trial is registered at the Australian New Zealand Clinical Trials Registry as ACTRN12618001054202.

How Fast Can Nurses Learn Therapeutic Communication Skills? A Pilot Study on Brief Hypnotic Communication Training Conducted with Oncology Nurses

Objective: This project aimed to train nurses on an oncology unit in hypnotic communication to reduce treatment-related pain and anxiety in their patients. A pilot study was conducted to assess changes in hypnotic communication behaviors associated with the training. Methods: Nurses were recruited and their interactions during a simulated patient admission for treatment (before and after training) were recorded. Hypnotic communication skills were assessed by independent reviewers using a training checklist listing different hypnotic communication techniques and a validated assessment scale (Sainte-Justine Hypnotic Communication Assessment Scale, SJ-HCAS). Results: Seven nurses were evaluated. Wilcoxon paired-sample tests (pre–post) reported significant improvement with large effect sizes in the total score of the training grid (P = 0.034, r = 0.832) and significant improvement with large effect sizes in the relational (P = 0.018, r = 0.930) and total (P = 0.021, r = 0.903) scores of the SJ-HCAS. Conclusion: This pilot study shows promising results regarding the effectiveness of hypnotic communication training for nurses. These acquired skills could translate into improved treatment experience with patients and could be transferred to other professionals and settings in the health care system.

The Influence of Social Network Content on the Perception of Smiles-A Randomized Controlled Trial.

Background: This randomized trial’s objective was to investigate the impact of social network content on the perception of smiles among specialists, doctors, students of dental medicine, and laypeople. Method: A sample of 360 respondents was shown 7 digitally altered photographs of smiles (85.63% female, 14.37% male). Dental specialists, dentists, dental students (first to third year and fourth to sixth year), and laypeople made up the sample. Respondents were asked to rank the images on a scale of 1 to 10, starting with the least appealing and moving up to the most attractive, using a Google Form. Respondents were divided into experimental and control groups at the end of the following month by random selection. The experimental group followed an Instagram profile posting two images of beautiful smiles for seven days, while the control group received no intervention at all. Both groups then completed the same questionnaire again. The comparison of esthetic scores between the experimental and control group was performed using the Mann–Whitney U-test and the difference in test responses between the starting point of the measurement and after exposure to perfect content on social media within individual groups was tested with the Wilcoxon paired-samples test. When comparing the absolute difference of scores, the Mann–Whitney U-test and the Kruskal–Wallis test were used. Results: Respondents in the experimental group rated the rounded embrasures of the incisors with lower esthetic scores compared to the control group that was not exposed to images on the Instagram social network. In those exposed to Instagram (experimental group), laypeople showed significantly greater satisfaction with their own smile after the exposure to Instagram, whereas no such difference was present in the control group. Conclusions: The content of social networks potentially has an influence on smile perception, most visible in the perception of incisal embrasures and self-perception of smile.

Performance Stabilizes During A 20-second Test Of Rapid Medial-lateral Weight-shifting Function In Older Adults

Performance on the Rapid Alternating Stair Tap Test (RASTT) relates well with lab-based measures of medial-lateral (ML) motion and consistency of step timing in older adults. It may have clinical utility for fall risk assessment. The RASTT forces ML weight-shifting motion due to the need to alternate single-leg stance from side-to-side while alternating foot tapping on a step. The duration of the test is of interest; the test aims to evaluate rapid movement capability and needs to be short enough to allow rapid performance to be maintained. PURPOSE: To determine whether stepping characteristics change during the 20-second RASTT. METHODS: Older adult participants (n = 75, mean age: 79.8 years, age range: 70-96 years) with a broad range of functional capacity participated in this study. Acceleration was measured with a triaxial wireless accelerometer affixed to a belt around the lower back while participants alternated each foot tapping the center of a step in front of them and then stepping back to the floor as many times as safely possible within 20 seconds. Three familiarization trials were conducted, with one minute of rest in between. Signal events were used to identify steps and calculate mean step time during the trial, the standard deviation (SD) of step time, and acceleration magnitude and variability (mean and SD of the per-step peak-to-peak ML acceleration). The difference in these outcome measures between the first and second half of the 20-second testing period was evaluated using a paired samples Wilcoxon test, as the data were not normally distributed. RESULTS: Mean step time and mean per-step peak-to-peak ML acceleration did not differ between the first and the second half of the trial. Small reductions occurred between the first to the second half of the trial for step time SD (median [IQR]: 0.061 [0.071] to 0.047 [0.064] s, Z = -2.054, p = 0.04) and SD of the per-step ML peak-to-peak acceleration (0.143 [0.115] to 0.142 [0.145] g, Z = 2.017, p = 0.044). CONCLUSION: Rhythmicity of stepping increased and the ML acceleration variability reduced over the course of the 20-second trial. This indicates that the duration of the trial allowed the control of motion to stabilize over the course of the test, observed as less variable step time and less variable peak ML acceleration, without being long enough to cause step time to slow.

Mental health symptoms 1 year after the COVID-19 outbreak in Spain: The role of pre-existing mental disorders and their type

BackgroundThe type of pre-existing disorder might determine changes in mental health symptoms (i.e., anxiety, depression) during the COVID-19 pandemic and influence the effect of psychological factors (e.g., social support, resilience, stress) on such symptoms. MethodsLongitudinal data from two assessments (June-2020 and February/March-2021) collected through telephone interviews (Spanish general population) were analysed. Outcome variables included anxiety (GAD-7) and depressive symptoms (PHQ-8). Psychological factors included COVID-perceived stress (adapted COVID-perceived risk scale), social support (OSSS-3), and resilience (CD-RISC). Pre-existing mental conditions (3 groups: mood, anxiety, and comorbid depression+anxiety) were assessed using the CIDI checklist. Changes in anxiety and depressive symptoms between baseline and follow-up were assessed with the paired samples Wilcoxon test. Tobit regression and interaction models were conducted to test associations between psychological factors and these symptoms in follow-up. ResultsFinal sample included 1942 participants (mean age 49.6 yrs., ±16.7; 51.7 % females). Anxiety symptoms increased in all groups except for those with pre-existing mood conditions. Depressive symptoms only increased in those without pre-existing mental disorders and in those with pre-existing anxiety. Higher baseline resilience, increases in social support, and decreases in COVID-perceived stress were associated with lower anxiety and depressive symptoms. The type of pre-existing mental disorder did not modify these associations. LimitationsLack of pre-pandemic data and the limited number of pre-existing mental conditions. ConclusionsHaving pre-pandemic mental disorders is associated with different patterns of anxiety and depressive symptoms during the pandemic. COVID-related stress, social support, and resilience are key factors in improving mental health regardless of the mental diagnosis.

High-Flow Nasal Cannula and Standard Oxygen in Acute Hypoxemic Respiratory Failure Due to COVID-19.

The evidence regarding benefits of high-flow nasal cannula (HFNC) in patients with COVID-19 is controversial. The aim of this study was to evaluate the impact of HFNC in comparison with standard oxygen therapy on the frequency of endotracheal intubation at 28 d in subjects with acute hypoxemic respiratory failure (AHRF) secondary to SARS-CoV-2 infection. A retrospective, age- and sex-matched-paired, cohort study was conducted in subjects with moderate-to-severe AHRF. Intervention group was treated with HFNC, and control group was treated with standard oxygen therapy. Baseline characteristics and clinical evolution were analyzed. Mantel-Haenszel test was used for categorical variables. Paired samples Wilcoxon test was used for quantitative variables. Multivariate analysis was performed using conditional multiple logistic regression. Eighty-four subjects were included. The median time from admission to progression of oxygen therapy to FIO2 ≥ 0.5 or HFNC was 1 (interquartile range [IQR] 0-3) d. PaO2 /FIO2 at the time of oxygen therapy progression showed a median of 150.5 (IQR 100.0-170.0) for the entire sample and was lower in HFNC group compared with control group (median 135 [IQR 96-162] vs median 158 [IQR 132-174], respectively, P = .02). Endotracheal intubation at 28 d was observed in 54.8% HFNC and 73.8% standard oxygen (unadjusted odds ratio 0.38 [95% CI 0.13-1.07], P = .069). In the multivariate analysis, presence of dyspnea at hospital admission, Sequential Organ Failure Assessment score, and PaO2 /FIO2 at time of progression of oxygen therapy to FIO2 ≥ 0.5 was identified as confounding factors for the association between the intervention group and the outcome. Use of HFNC was not an independent predictor of endotracheal intubation frequency after adjusting confounders (odds ratio 0.26 [95% CI 0.04-1.51], P = .13). In this study, HFNC therapy in subjects with AHRF secondary to COVID-19 was not an independent predictor of endotracheal intubation, compared with standard oxygen therapy, after adjusting for confounders.

Multi-omics analysis of locally advanced esophageal cell squamous carcinoma treated with radio-chemotherapy.

e16106 Background: The incidence rate of esophageal cell squamous carcinoma (ESCC) increases every year worldwide. Although the molecular characteristics of locally advanced esophageal carcinoma have been extensively studied, TCR evolution dynamics before and after treatment in patients with ESCC undergoing radical radiotherapy and chemotherapy are unknown. Methods: In this study, we performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on tumor tissues from 11 ESCC patients who received radiotherapy and chemotherapy. T cell receptor (TCR) sequencing was performed in 33 ESCC blood samples, which included three time points: pre-treatment, on-treatment and post-treatment. We compared TCR clonality and Shannon index among the pre-treatment, on-treatment and post-treatment ESCC patients using paired samples Wilcoxon test. The t test was uesd for statistical analysis comparing the clonality and clonal frequency between patients with mutant and wild-type gene. Results: The median TMB is 3.32 mutations/Mb (range 1-6 muts/Mb). We identified nine significantly mutant genes including TP53 (100%), MUC17 (55%), FLG (45%), FLG2 (36%), FOXN1 (27%), HIST1H1E (18%), VN1R1 (18%), RIPK3 (9%), and ZNF628 (9%). Clonality was significantly increased from pre-treatment to post-treatment (p = 0.008) and from on-treatment to post-treatment (p = 0.04). Two patients exhibited an continuous increase of TCR CDR3 (CHCLPAED_AGGGELFF) frequency in post-treatment compared to on-treatment patients. Three patients had elevated level of CDR3 amino acid sequence (CASSLDSNQPQHF) after treatment. To explore the effect of the mutant gene on the TCR clonal pattern, we found that the baseline clonality and clonal frequency in mutant FAT1 (MUT) were significantly lower than that in wild-type (WT) patients (p = 0.044 and p = 0.013, respectively), while they were not significant after treatment between FAT1-MUT and WT patients. Intriguily, in FAT1-MUT patients, the clonality and clonal frequency underwent therapy were higher than that at baseline. The results suggested that the FAT1-MUT patients might be sensitive to treatment and FAT1 might contribute to immune response upon radio-chemotherpay. During radio-chemotherapy, the clonality and clonal frequency in INTS1-MUT and LCT-MUT patients had the similar phenomenon to the FAT1-MUT patients. Interestingly, a higher clonal frequency was observed after radiotherapy and chemotherapy than that of pre-treatment (p = 0.0086) in patients with mutant KMT2D (an epigenetic modifier coding lysine methyl transferase 2D). Conclusions: TCRs is clonal expansion after radiotherapy and chemotherapy in ESCC, suggesting an immune-activated microenvironment after radio-chemotherapy. Our multi-omics analysis provided the basic TCRs dynamics and its genomic and epigenomic association during the radio-chemotherapy of esophageal cell squamous carcinoma.

Woody species dynamics in Sheka Forest Biosphere Reserve, Southwest Ethiopia

Understanding the dynamics of woody species diversity is the foundation for designing sustainable biodiversity management strategies. Despite an extensive history of cross-sectional ecological studies, scientific gen on the dynamics of woody species diversity over time and space is rare and mostly unexplored in the last remaining Eastern Afromontane Forests. This study aimed to examine the spatial and temporal dynamics of woody species composition, structure, and diversity in the Sheka Forest Biosphere Reserve (SFBR). Data were collected from a total of 43 permanent plots with a dimension of 10 m × 50 m that were laid along the altitudinal gradient. In both 2000 and 2021, the same permanent plots were used and the same approach was followed. Diversity indices and Wilcoxon paired-sample test were employed for the comparison of changes. One hundred one woody species that belong to 84 genera and 41 families and 62 woody species that belong to 54 genera and 32 families were recorded in 2000 and 2021, respectively. During the present study, 47 woody species from the 2000 inventory list including three endemics were not encountered, while eight new species were recorded. The aggregated density and total basal area of woody species decreased from 2590 ± 536 ha−1 to 2454 ± 300 ha−1, and 101.3 m2ha−1 to 72m2ha−1, respectively. The dominant woody species was Ficus sur in 2000, while it was shifted to Coffea arabica in 2021. Woody species richness, evenness, and diversity significantly reduced during the study period. In the mid and lower altitudes with lower slope gradients, where settlement and agricultural expansion were prevalent, the greatest decline in woody species richness, diversity, and evenness, and highest turnover were recorded. Unsustainable use for construction, energy production, creation of job opportunities (income generation), as well as the conversion of forestland to farmland resulted in the rapid decline and massive turnover of woody species diversity. It is important to develop and execute comprehensive sustainable forest management strategies, which include diversification of energy sources and use of energy-saving technologies, strengthening tree planting and management practices for household use and income generation, and diversification of eco-friendly livelihood options. The conservation of endemic and priority species is indispensable to maintaining ecosystem integrity and species diversity.