Background: The coronavirus disease (COVID-19) pandemic imposed diverse challenges on the health care system. Morbidity and mortality of non-COVID-19 emergencies might also have changed because hospitals may not be able to provide optimal care due to restructured resources and uncertainties how to deal with potentially infected patients. It has been recommended to stratify treatment of cardiovascular emergencies according to cardiovascular risk. However, data on the prevalence of asymptomatic SARS-CoV-2 infection in patients presenting with cardiac emergencies remain scarce.Methods: We retrospectively analyzed patients' data from a tertiary cardiology department between April 15 and May 31, 2020. All patients were screened on admission for COVID-19 symptoms using a questionnaire and body temperature measurements. All hospitalized patients were routinely screened using nasopharyngeal swab testing.Results: In total, we counted 710 urgent and emergency admissions. Nasopharyngeal swab tests were available in 689 (97%) patients, 409 and 280 of which presented as urgent and emergency admissions, respectively. Among 280 emergency admissions, none tested positive for SARS-CoV-2.Conclusion: In cardiac emergency patients which were screened negative for COVID-19 symptoms, the prevalence of SARS-CoV-2 infection in regions with a modest overall prevalence is low. This finding might be helpful to better determine timing of emergency procedures and reasonable usage of protective equipment during the COVID-19 crisis and the future. The coronavirus disease COVID-19) pandemic imposed diverse challenges on health care providers and hospitals. For instance, hospitals needed to rapidly redistribute and reorganize resources to treat acutely ill COVID-19 patients while keeping up with other emergencies. At the same time outmost attention had to be spent on containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to protect other patients and staff. Apart from rising numbers of COVID-19 patients, a change in the presentation pattern of non-COVID emergencies was observed. In that light, it was recently shown that hospital admissions for acute coronary syndrome (ACS) declined during the pandemic 9 pandemi. Apart fWe here sought to investigate the prevalence of SARS-CoV-2 infections in asymptomatic patients presenting with cardiac emergencies.The study protocol was approved by the institutional ethics committee (323/20 S) and conforms to the ethical guidelines of the 1975 Declaration of Helsinki. We retrospectively analyzed patients' data from a tertiary cardiology department which provides 24/7 interventional cardiac care between April 15 and May 31, 2020 .All patients were screened on admission for COVID-19 symptoms using a questionnaire and had their body temperature measured (ear thermometer). Patients were assigned as COVID-19 asymptomatic when none of the following criteria were met: body temperature ≥38.1°C, coughing, shortness of breath, runny nose, sore throat, or body aches. Additionally, patients were asked whether they had been in contact to a confirmed COVID-19 case or a patient suffering from fever and coughing without proven SARS-CoV-2 infection. Patients reporting shortness of breath were also regarded as COVID-19 asymptomatic if they did not report one of the other criteria. COVID-19 asymptomatic patients were required to wear standard surgical masks (no N95 or FFP2-3) throughout the entire stay. Hospital staff was also required to wear standard surgical masks at all times. These protective measurements were recently shown to reduce in particular the risk of SARS-CoV-2 infection for healthcare workers  since April 15, 2020. Patients without COVID-19 symptoms were only planned to be tested at admission. Repeated testing was performed if patients developed symptoms or if a more recent test result was required for transferal to other treatment facilities.Until May 31, 2020, a total of 710 patients presented and were included this analysis. In the total cohort, only one patient was diagnosed to be SARS-CoV-2 positive . The patThis result needs to be reviewed in the context of the overall SARS-CoV-2 prevalence in the respective region during the observation period. During the study period, ~300 cases per 100,000 citizens were reported in the Free State of Bavaria. Thus, our data indicate that in cardiac emergency patients which were screened negative for COVID-19 symptoms, the prevalence of SARS-CoV-2 infection in regions with a modest overall prevalence is low. Under these circumstances, our findings indicate that a delay/deferral of emergency procedures due to waiting for SARS-CoV-2 test results may not be justified in emergency patients which are screened asymptomatic for COVID-19, but have an unclear SARS-CoV-2 infectious status. While our finding is in line with a recent report from Iceland, where in a random-sample screening of the population, 0.6% tested positive for SARS-CoV-2 .In summary, the frequency of asymptomatic SARS-CoV-2 carriers among cardiac emergency patients is low when the overall prevalence of COVID-19 is modest. Consequently, emergency but also elective procedures may safely be carried out without delay and waiting for SARS-CoV-2 test results. Importantly, the safety of personnel and patients may be further increased by implementation of rapid or point-of-care tests which despite potential drawbacks  recentlOur study was performed during a time period in which the prevalence of COVID-19 in Bavaria was rather low and our findings are therefore inherently not applicable in regions with higher prevalence. It was also previously shown that the highest sensitivity of SARS-CoV-2 was reached bronchoalveolar lavage fluid  and we mThe original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Technische Universität München. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.AK and HBS designed the study. TK, JW, TG, and HS contributed data. TK, AK, and HBS drafted the manuscript. All authors were involved in critically revising the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Introduction: Salivary gland malignancies are rare tumors with a heterogenous histological and clinical appearance. Previously, we identified multiple prognostic factors in patients with parotid cancer and developed prognostic indices which have repeatedly been validated internationally, demonstrating their general applicability and lasting relevance. Recently, nomograms gained popularity as a prognostic tool. Thus, in this research we aimed to construct nomograms based on our previous validated prognostic models.Material and Methods: Nomograms were constructed using the previously reported dataset of 168 patients with parotid cancer which was used to develop pre- and postoperative prognostic scores, PS1 and PS2, respectively. Concordance indices for PS1 and PS2 were previously estimated at 0.74 and 0.71, respectively, and are in line with other, widely accepted oncological nomograms.Results: Pre- and postoperative nomograms predicting 2- and 5-year tumor recurrence-free survival probability are presented. All previously multivariately identified and validated prognostic factors, are incorporated . Examples of clinical application and interpretation are given.Conclusions: The presented prognostic nomograms for predicting 2- and 5-year tumor recurrence-free probability in patients with parotid cancer are powerful, user-friendly, visual tools and are based on internationally validated prognostic indices. They allow for a reliable prognostic assessment and result in a more individualized estimate of the risk for recurrence than the prognostic grouping based on PS1 and PS2. This facilitates assigning trial-patients to risk groups, and may assist in therapeutic decision making and determining appropriate follow-up intervals in clinical practice. Salivary gland malignancies (SGM) are a rare entity with an incidence which varies geographically between 0.05 and 1.9 per 100.000 per year . In BelgFor parotid carcinoma, 10 year disease specific survival rates after treatment in major centers range from 47 to 69%, depending on population, study and disease characteristics . For theTo this purpose, we previously developed prognostic indices for patients with parotid cancer who receive surgical treatment, radiotherapy and/or chemotherapy . ClinicaRecently, the use of nomograms as a practical prognostic tool has become increasingly popular. Prognostic nomograms are visual representations of a complex mathematical formula or model, allowing for a more individualized risk assessment . For parThe predictive nomograms were constructed from the original dataset that was used to develop the previously presented indices. This dataset included a retrospective cohort of 168 patients with a pathologically confirmed diagnosis of a malignant parotid tumor who visited the Netherlands Cancer Institute during the period from January 1, 1973 until December 31, 1994 . Of thisPreviously, clinical T classification, clinical N classification, pain, age at diagnosis, skin invasion, facial nerve dysfunction, perineural growth, and positive surgical margins were identified as prognostic factors for tumor recurrence using a multivariate proportional hazards analysis . As theyIn the previously reported prognostic indices, tumor size and regional lymphatic spread was described using T- and N-classification, respectively, from the UICC TNM 4th edition . Since tPrognostic nomograms for 2- and 5-year tumor recurrence-free probability in a pre- and post-operative setting were constructed using the rms-package in RStudio software , a graphical user-interface for R programming language  is the baseline hazard function for tumor recurrence, corresponding to the risk of tumor recurrence when all covariates are zero, which was estimated from the original dataset  and their corresponding regression coefficients . The regression coefficients, which equal the natural logarithm of the hazard ratios, were used to construct the variable axes in the nomogram with each value correlating to a number of points from 0 to 100. Finally, total points accounting for cumulative hazard were translated to predicted tumor recurrence probability using the baseline hazard function  and post-operative (PS2) prognostic scores; . By drawExample 2 considers a 58-year old male patient with a 52 mm (cT3), cN0, cM0 low grade muco-epidermoid carcinoma with no pain, no facial nerve dysfunction nor skin invasion, which on the postoperative pathology report shows no perineural invasion and negative surgical margins . Using tConsidering example 1, according to the previously developed PS1 score, the patient would be classified in group 4 with a 22.8%  5-year tumor recurrence-free survival probability. The predictive nomogram now provides a more individualized and higher pre-operative prognostic estimate of a 27% chance of being recurrence-free at 5-year follow-up, which still lies within the 95% confidence interval. In example 2, the patient would be classified prognostic group PS2 = 2, corresponding to an 82.5%  chance of being tumor free at 5 years. The 5-year tumor recurrence-free interval probability according to the postoperative prognostic nomogram is in line with this but indicates an individualized 84% chance of being cured at 5 years after standard of care treatment, in this case surgery and adjuvant radiotherapy. It provides a somewhat more specific answer to the patient's question of how likely the performed treatment is to cure the disease.Currently, the most widely-used prognostic tool for all solid tumors, including SGM, is the TNM staging system . This syIn line with the current gaining popularity of nomograms and based on the multivariate analysis that resulted in the validated prognostic indices, we now present user-friendly nomograms for estimating 2- and 5-year tumor recurrence-free interval probability after standard of care treatment of patients with parotid cancer.Recently, three other interesting prognostic nomograms regarding tumor recurrence following SGM treatment have been developed, all from a single center cohort.Authors from the Memorial Sloan Kettering Cancer Center (MSKCC) presented nomograms predicting 5 year recurrence probability after treatment for all major SGM, based on a multivariate analysis including age, grade, vascular and perineural invasion, and nodal metastasis . ValidatThe Taiwanese group also developed their own nomogram for salivary gland tumor recurrence based on tumor size, nodal involvement, perineural invasion, tumor grade, lymphatic invasion and smoking status . ValidatMore recently, Mannelli et al. presented a postoperative prognostic nomogram for 5 year parotid cancer recurrence probability, with excellent CI as well  . VariablP < 0.001), which is also described in recent literature  and limitations. Also, the effects of nomogram-assisted decisions on patient satisfaction and clinical outcome still remain unclear .One last limitation of the currently presented nomograms is that the initial multivariate model was based on the 1992 TNM classification . Over thIn the future, research incorporating other possibly important prognostic variables such as patient comorbidity, histological subtypes and underlying genetic mechanisms  can improve prognostication models . PerformIn conclusion, the presented prognostic nomograms provide a scientifically based and externally validated prediction of 2- and 5-year recurrence-free interval after standard of care treatment in patients with parotid cancer, in a pre- or postoperative setting. They are user-friendly visual representations of complex prognostic models to aid in individual prognostication, clinical decision making, and may serve as a basis for risk stratification in clinical trials.vincent.vanderpoorten@uzleuven.be.The data analyzed in this study is subject to the following licenses/restrictions: The data upon which the research is performed are available upon reasonable request to the corresponding author provided that (1) an EC approved research protocol can be presented and (2) all collaborating centers agree to share the data. Requests to access these datasets should be directed to Vincent Vander Poorten, VV was responsible for the initial concept of this paper. SP wrote the manuscript and made the figure outlines with the aid of VV. AL created the prognostic nomograms and provided feedback and suggestions from a statistical point of view. All other authors provided valuable feedback, suggestions, and corrections to improve the quality of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Risk and crisis communication plays an essential role in public health emergency responses. The COVID-19 pandemic has triggered spontaneous and intensive media attention, which has affected people’s adoption of personal preventive measures and their mental health.The aim of this study was to investigate the associations between exposure to COVID-19–specific information and mental health  and self-reported compliance with personal preventive measures (face mask wearing and hand sanitizing). We also tested whether these associations were moderated by thoughtful consideration of the veracity of the information to which people were exposed.A cross-sectional, closed web-based survey was conducted among a sample of 3035 factory workers at the beginning of work resumption following the COVID-19 outbreak in Shenzhen, China. A stratified two-stage cluster sampling design was used for recruitment. Multivariate linear and logistic regression models were used for the analyses.The prevalence of probable moderate-to-severe depression was 170/3035 (5.6%), while that of good or excellent sleep quality was 2110/3035 (69.5%). The prevalence of self-reported consistent face mask wearing in public places was 2903/3035 (95.7%), while that of sanitizing hands every time after returning from public spaces or touching public installations was 2151/3035 (70.9%). Of the 3035 respondents, 1013 to 1638 (33.3% to 54.0%) reported >1 hour of daily exposure to COVID-19–specific information through web-based media and television. After controlling for significant background variables, higher information exposure via television and via newspapers and magazines was associated with better sleep quality and higher compliance with hand sanitizing. Higher exposure via unofficial web-based media was associated with higher compliance with hand sanitizing but was also associated with higher depressive symptoms. In contrast, higher exposure through face-to-face communication was associated with higher depressive symptoms, worse sleep quality, and lower compliance with hand sanitizing. Exposure to information about positive outcomes for patients with COVID-19, development of vaccines and effective treatments, and heroic stories about frontline health care workers were associated with both better mental health and higher compliance with preventive measures. Higher overall information exposure was associated with higher depressive symptoms among participants who were less likely to carefully consider the veracity of the information to which they were exposed; it was also associated with better sleep quality among people who reported more thoughtful consideration of information veracity.This study provides empirical evidence of how the amount, sources, and contents of information to which people were exposed influenced their mental health and compliance with personal preventive measures at the initial phase of work resumption in China. Thoughtful consideration of information quality was found to play an important moderating role. Our findings may inform strategic risk communication by government and public health authorities during the COVID-19 pandemic. Risk and crisis communication plays an essential role in public health emergency responses . During In addition, people facing a public health emergency often experience a range of negative emotions. During the COVID-19 outbreak, the unknown cause of the disease, fatal outcomes, and interruption of daily routines likely increased levels of negative emotions . The COVThe importance of web-based media during public health emergencies has been increasing over time. Individuals have turned to web-based media during pandemics to find information related to safety precautions, news updates, and protective equipment. For example, during the SARS and MERS outbreaks, Chinese and South Korean people turned to the internet to find information that was unavailable on traditional media channels ,20. DuriPrevious studies have shown that people are likely to react emotionally rather than rationally during a disease outbreak . For exaThis study targeted workers who resumed work in China at the beginning of work resumption. Although the implementation of strict nationwide control measures  effectively controlled the pandemic, it severely damaged China’s economy . TherefoTo the best of our knowledge, there have been no studies investigating behavioral or mental health outcomes of exposure to COVID-19–specific information at the initial phase of work resumption following the COVID-19 outbreak. The objective of this study was to investigate the associations between COVID-19–specific information exposure and four outcome variables, including depression, sleep quality, self-reported consistent face mask wearing, and hand hygiene. The study also tested whether the associations between information exposure and outcomes varied as a function of thoughtful consideration of the veracity of information to which the participants were exposed.A cross-sectional, closed web-based survey was conducted from March 1 to 14, 2020, in Shenzhen, China. Approximately 65.1% of the residents of this city are internal migrants, and 34.3% are factory workers [We developed a web-based questionnaire using Questionnaire Star, a commonly used web-based survey platform in China. The link to access the web-based questionnaire was shared in WeChat, a popular messaging app. In addition to national guidelines, the Shenzhen government requested that each factory establish WeChat groups including all employees as part of the preparation for work resumption. A designated coordinator responsible for COVID-19 control in each factory facilitated the data collection. This coordinator posted the study information and the link to access the web-based questionnaire in the WeChat group and invited all eligible workers who had resumed work to participate. The coordinator also sent out reminders in the WeChat groups twice per week during the study period. These designated coordinators did not participate in the survey. The coordinators and participants were asked not to disseminate the survey access link to people outside their factories. Before starting the web-based survey, the participants read a statement indicating that participation was voluntary, refusal to participate would have no effect on them, the survey would not collect personal contacts or identifying information, and the data would be kept strictly confidential and would only be used for research purposes. Web-based informed consent was sought. Each individual WeChat account was allowed to access the web-based survey once. The web-based survey platform performed completeness checks before each questionnaire was submitted. Participants were able to review and change their responses using a Back button. Upon completion of the survey, an electronic coupon of ¥10 (US $1.30) was sent to each participant. All data were stored in the server of the survey platform and were protected by a password. Only the corresponding authors had access to the database. Of 4158 workers who had resumed work in these factories on March 1, 2020, 3035 completed the web-based survey. The overall response rate was 73.0%. Ethics approval was obtained from the Seventh Affiliated Hospital, Sun Yat-sen University (reference: KY-2020-005-001).Sociodemographic data such as age, gender, highest education level, marital status, monthly personal income, status as frontline workers or management staff, and type of factories the respondents were working in were collected.Five items assessed daily average time (hours) of COVID-19–specific information exposure through different sources from January 24 (the first day of the Chinese New Year holiday) through the survey date. Sources of health information included official web-based media (media accounts of government institutions), unofficial web-based media (media accounts of private organizations or self-published accounts), television, newspapers and magazines, and face-to-face communication. The Overall Information Exposure Scale was constructed by summing the individual item scores . A higher score on the scale indicated exposure to a higher amount of COVID-19–specific information.Participants were also asked to report their frequencies of exposure to information on the eight most popular topics related to COVID-19 during the outbreak . These topics included statistics about the COVID-19 pandemic , positive information about governmental responses to COVID-19 , negative information about governmental responses to COVID-19 , information about the development of vaccines and effective treatments, heroic stories about frontline health care workers, positive information about patients with COVID-19 , negative information about patients with COVID-19 , and information about negative impacts of the COVID-19 pandemic on the economy .A single item assessed the frequency of thoughtful consideration of the veracity of health information: “When you viewed information about COVID-19, how often did you carefully think about its veracity?” . This variable was treated as a moderator.Mental HealthDepressive symptoms were measured using the validated Chinese version of the 9-item Patient Health Questionnaire (PHQ-9) . ParticiGlobal sleep quality over a 7-day recall period was measured using a single-item Sleep Quality Scale with a rating range from 0 to 10. A higher score indicated better sleep quality. The original score was then recoded into four categories: 1=poor or terrible (0-3), 2=fair (4-6), 3=good (7-9), and 4=excellent (10) . This inParticipants were asked to report the frequency at which they wore face masks in the workplace and in other public settings (public places and transportation) in the past month . A composite variable of “consistent face mask wearing” was created to represent respondents who reported wearing a face mask every time both in the workplace and in other public settings . Participants also reported the frequency at which they sanitized their hands using soaps, liquid soaps, or alcohol-based hand sanitizers after returning from public spaces or touching public installations and equipment  . This item was also recoded into a binary variable of “sanitizing hands every time” .P value <.05 indicating statistical significance.The characteristics of all studied variables were described first. The associations between independent variables  and mental health outcomes  were tested using multivariable linear regression analysis; the associations between the independent variables and behavioral outcomes (self-reported consistent face mask wearing and sanitizing hands every time) were tested using multivariate logistic regression analysis. Background characteristics that were significantly associated with the dependent variables were adjusted for in the regression models. Adjusted unstandardized coefficients (B) or adjusted odds ratios (AORs) and their 95% CIs were reported. An interaction term was further created by multiplying overall information exposure and thoughtful consideration of information veracity, and this term was included in the multivariable linear and logistic regression models to test its significance. SPSS version 24 (IBM Corporation) was used to conduct all analyses, with a two-sided Over half of the 3035 participants were <30 years of age , male , married , had attained an education level lower than college or university , had a monthly income level lower than ¥5000 (US $714) , were frontline workers , and were working in an electronic device manufacturing factory  .Of the 3035 participants, 1638 (54.0%), 1057 (34.8%), and 1013 (33.3%) had been exposed to COVID-19–specific information via official web-based media, unofficial web-based media, and television for >1 hour per day, respectively. Smaller proportions reported a daily exposure of >1 hour via newspaper  and face-to-face communication . Regarding the contents of the information, over half of the 3035 participants were always exposed to statistics about the COVID-19 pandemic , positive information about governmental responses to COVID-19 , and heroic stories about frontline health care workers . Only 1065 of the 3035 participants (35.1%) always thought carefully about the veracity of the COVID-19–specific information .Mental Health and Self-Reported Compliance With Personal Preventive MeasuresThe prevalence of probable moderate to severe depression was 170/3035 (5.6%), and that of good or excellent sleep quality was 2110/3035 (69.5%) . RegardiIn the univariate analysis, age, marital status, education level, monthly personal income, status as frontline worker or manager, and factory type were significantly associated with depressive symptoms and sleep quality .P=.006). Specifically, higher exposure via unofficial web-based media  and face-to-face communication  was associated with higher depressive symptoms. Exposure to negative information about patients with COVID-19  and about effects on the economy  was associated with higher depressive symptoms, while exposure to information about development of vaccines and effective treatments was associated with lower depressive symptoms   .P=.01). Specifically, exposure via face-to-face communication was associated with poorer sleep quality , while exposure via television  and newspapers and magazines  was associated with better sleep quality. Exposure to negative information about patients with COVID-19  and negative impacts on the economy  was associated with poorer sleep quality. In contrast, exposure to heroic stories about frontline health care workers  and positive information about patients with COVID-19  was associated with better sleep quality.A higher overall amount of COVID-19–specific information exposure was associated with better sleep quality , negative information about governmental responses , heroic stories about frontline health care workers , and positive information about patients with COVID-19  were positively associated with this outcome.After adjusting for these significant background characteristics, the overall or source-specific amount of COVID-19–specific information exposure was not significantly associated with consistent face mask wearing. Exposure to statistics about the COVID-19 pandemic  and specific exposure through official web-based media, unofficial web-based media, television, and newspapers and magazines, with AORs ranging from 1.07 (95% CI 1.00-1.15) to 1.21 (95% CI 1.11-1.32), were positively associated with sanitizing hands every time, while a negative association was found for exposure through face-to-face communication . Exposure to all eight information topics was positively associated with this outcome, with AORs ranging from 1.09 (95% CI 1.01-1.18) to 1.36 (95% CI 1.24-1.49)  .P=.047) and sleep quality . Overall amount of information exposure was associated with higher depressive symptoms among participants who were less likely to consider the veracity of the information to which they were exposed; this association was not significant among those who were more likely to consider the veracity of this information. In contrast, overall amount of information exposure was associated with better sleep quality among participants who were more likely to consider the veracity of the information to which they were exposed; this association was not significant among those who were less likely to consider the veracity of this information  . The preOur findings suggest that the COVID-19 pandemic triggered intensive media responses, as our participants had been exposed to large amounts of COVID-19–specific information every day following the outbreak in China. Web-based media and television were the most common information sources, while newspapers and magazines and face-to-face communication were less common. These findings are consistent with previous reports, which showed a substantial increase in the use of web-based media and television following the COVID-19 outbreak .Consistent with previous studies ,24, we fIt was interesting to find that information exposure through official web-based media was associated with better hand hygiene but did not affect mental health status. In China, these media outlets are operated by governmental organizations and disseminate similar information to traditional media. However, instead of one-way communication, official web-based media platforms are interactive and allow readers to leave comments. We speculate that people viewed both positive and negative feedback for specific topics, which may have offset the positive influence on mental health. Information exposure through unofficial web-based media sources was likely to have both positive and negative aspects, as it motivated personal preventive measures but triggered mental health problems at the same time. These findings are similar to studies conducted during the 2015 MERS outbreak in South Korea ,24. CompInformation exposure through face-to-face communication was limited, probably due to strict control measures implemented by the Chinese government to curb the COVID-19 pandemic . However, the influence of face-to-face communication cannot be neglected. Higher levels of information exposure through this source were associated with decreased levels of hand hygiene and poorer mental health. It is likely that false and unverified information was disseminated by face-to-face communication during the pandemic. Studies have shown that “bottom-up” misinformation accounted for a significant proportion of information sharing between laypersons during the COVID-19 pandemic . The conOur study covered eight types of COVID-19–related content that were active topics attracting public attention from the Chinese population during the pandemic ,46. ExpoThe measure of thoughtful consideration inherently assessed the participants’ motivation to scrutinize information quality but also the ability to acquire, discern, and understand accurate health information -51. DuriOur findings may inform strategic risk communication by government and public health authorities during the COVID-19 outbreak and future public health emergencies to build public trust and facilitate prevention without amplifying panic. Future risk communication related to COVID-19 in China should make use of official web-based media and traditional media platforms; increase dissemination of information about patient rehabilitation, development of effective treatments and vaccines, and heroic deeds of frontline health care workers; and inform the public about effective strategies to reactivate the economy. Pilot testing of communication campaign messages among the target audience is also recommended. Furthermore, it is imperative to invest in building communication capacity to combat the crisis of misinformation. Government and public health authorities should proactively identify misinformation, provide clarifications, and empower the public with adequate skills to critically evaluate the veracity of information.The present study has some limitations. First, causal relationships between information exposure and the studied outcomes cannot be determined due to the cross-sectional design. Reverse relationships are possible; for example, individuals with mental distress may spend more time searching for COVID-19–related information . Second,This study provides empirical evidence of how different dimensions of COVID-19–specific information exposure influenced mental health status and compliance with personal preventive measures at the initial phase of work resumption in China. Thoughtful consideration of the veracity of information played an important role in moderating the associations between information exposure and mental health. These findings can help improve crisis communication during the response to the ongoing pandemic.


There has been little investigation of how life-course social mobility is linked to Disability-Free Life Expectancy (DFLE). We report novel analysis of the HILDA survey examining how DFLE trends differs by three markers of socio-economic position (SEP): early-life , midlife , and late-life (area-disadvantage). All women, irrespective of their educational level, gained years with disability (Age 65: Low education=1.5 and High education=2.5 years). Similar results were obtained by level of occupation, but women with low occupation showed small declines in LE (-0.8 years), all being losses in DFLE. Only women in the most advantaged areas gained DFLE. For men, higher levels of any marker of SEP were associated with DFLE gains that were larger than, or comparable to, gains in years lived with disability, although lower education was associated only with gains in years lived with disability. DFLE trends differ by SEP marker more in women than men.


The intakes of FODMAP-rich foods were calculated as portions and the intakes were divided into two consumption categories. Patients with high consumption of FODMAP-rich foods had diarrhoea more frequently than those with low consumption (for lactose-rich foods the odds ratio (OR) was 2.63, P = 0.03; and for other FODMAP-rich foods 1.82, P = 0.20). Patients with high consumption of both lactose-rich and other FODMAP-rich foods had an over 4-fold risk of developing diarrhoea as compared to those with low consumption of both . These results were confirmed in multivariate models. Conclusion: Consumption of lactose-rich foods results in an increased risk of diarrhoea during adjuvant therapy for colorectal cancer, especially when the consumption of other FODMAP-rich foods is also high. Chemotherapy-induced mucosal injury of the small intestine may interfere with the enzymes and transporters responsible for the hydrolysis and absorption of dietary carbohydrates causing diarrhoea, abdominal discomfort and pain. The aim of this study was to investigate the association between the consumption of foods rich in FODMAPs  and gastrointestinal symptoms in patients receiving adjuvant therapy for colorectal cancer. The patients ( Cytotoxic chemotherapy may damage the gastrointestinal tract mucosa and cause mucosal inflammation, oedema, ulceration and tissue atrophy. Chemotherapy-associated gastrointestinal toxicity often manifests as diarrhoea, abdominal discomfort and pain; it may also lead to treatment interruptions and even discontinuation ,2. A mucAdjuvant 5-fluorouracil chemotherapy for colorectal cancer may be associated with reversible hypolactasia and secondary lactose intolerance  but the A specific diet developed to alleviate symptoms of patients with the irritable bowel syndrome, called the FODMAP-restriction diet, aims to reduce the intake of poorly absorbed (fermentable) oligo-, di- and monosaccharides and polyols (FODMAPs), specifically fructans , galacto-oligosaccharides, raffinose, lactose, fructose and polyols  . LactoseIt is well-known that chemotherapy and radiotherapy exert toxic effects on the intestinal mucosa . Indeed,The extent to which lactose and other poorly absorbed short chain carbohydrates contribute to the gastrointestinal adverse effects evoked by 5-fluorouracil, the cornerstone for gastrointestinal cancer treatments in both the adjuvant and metastatic setting, or other chemotherapeutic agents is unknown. The objective of this study was to investigate whether the consumption of foods rich in FODMAPs would be associated with gastrointestinal symptoms during adjuvant therapy for colorectal cancer.Lactobacillus rhamnosus GG intervention in an attempt to reduce chemotherapy-associated adverse effects . All 52 subjects had FODMAP-rich foods in their diet, with the median intake being 5.5 portions/day  at baseline before cycle I and 5.4 portions/day (range 0–13.8) during cycle III.Based on the food diaries, 47 (90%) out of the 52 subjects consumed lactose-rich foods, with their median intake being 3.2 dL/day  at baseline before cycle I and 2.9 dL/day  during cycle III. As expected, lactose intolerant patients (those with hypolactasia or who had a borderline finding in the lactose tolerance test at baseline) consumed less lactose-rich foods during both periods than lactose tolerant patients [when considering both periods simultaneously, mean difference (95% CI) −2.0 dL/day (−3.5 to −0.6), P = 0.01) and those who consumed a moderate amount had an intermediate risk, 2.31  as compared with those with the lowest consumption. Flatulence was less frequent among those with a high intake of lactose-rich foods therapy than those consuming less than the median . A dose ch foods .No statistically significant differences in gastrointestinal symptoms were found in the univariate analysis in patients who consumed FODMAP-rich foods above (High) or below (Low) the median amount  nor whenAccording to the composite variable analysis, patients who consumed both lactose-rich and FODMAP-rich foods above the median (High) amount had a higher risk (OR 4.16) of developing diarrhoea during chemo(radio)therapy in comparison to those whose intake of both lactose-rich and FODMAP-rich foods was below the median (Low) amount . PatientIn addition to the type of food consumed, also other factors were significantly associated with diarrhoea during therapy in the univariable analyses and, therefore, these factors were included in a multivariable analysis. In the final model, diarrhoea was explained by a high consumption of both lactose-rich and FODMAP-rich foods and the presence of lactose intolerance at baseline, whereas if the patient was a methane producer, this was a protective factor . AccordiWe investigated whether consumption of foods rich in poorly absorbed short chain carbohydrates would be associated with gastrointestinal symptoms during adjuvant therapy for colorectal cancer. We found a clinically relevant increase in the risk of diarrhoea in those patients who consumed significant amounts of lactose-rich foods, especially if they also consumed FODMAP-rich foods  and irinotecan and can be life-threatening . In a raIn conclusion, patients who consumed high amounts of lactose and other FODMAPs had more diarrhoea during adjuvant therapy of colorectal cancer as compared to patients who consumed low amounts of lactose and FODMAPs. A diet low in lactose and FODMAPs may thus be a means to prevent and/or to alleviate the severity of the diarrhoea occurring during adjuvant therapy. This hypothesis warrants further evaluation in a prospective randomised study.


Background: A valid malnutrition screening tool (MST) is essential to provide timely nutrition support in ambulatory cancer care settings. The aim of this study is to investigate the validity of the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) and the new Global Leadership Initiative on Malnutrition (GLIM) criteria as compared to the reference standard, the Patient-Generated Subjective Global Assessment (PG-SGA). Methods: Cross-sectional observational study including 246 adult ambulatory patients with cancer receiving in-chair intravenous treatment at a cancer care centre in Australia. Anthropometrics, handgrip strength and patient descriptive data were assessed. Nutritional risk was identified using MST and PG-SGA SF, nutritional status using PG-SGA and GLIM. Sensitivity (Se), specificity (Sp), positive and negative predictive values and kappa (k) were analysed. Associations between malnutrition and 1-year mortality were investigated by Cox survival analyses. Results: A PG-SGA SF cut-off score ≥5 had the highest agreement when compared with the PG-SGA . Malnutrition risk (PG-SGA SF ≥ 5) was 31% vs. 24% (MST). For malnutrition according to GLIM, the Se was 76% and Sp was 73%  when compared to PG-SGA. The addition of handgrip strength to PG-SGA SF or GLIM did not improve Se, Sp or agreement. Of 100 patients who provided feedback, 97% of patients found the PG-SGA SF questions easy to understand, and 81% reported that it did not take too long to complete. PG-SGA SF ≥ 5 and severe malnutrition by GLIM were associated with 1-year mortality risk. Conclusions: The PG-SGA SF and GLIM criteria are accurate, sensitive and specific malnutrition screening and assessment tools in the ambulatory cancer care setting. The addition of handgrip strength tests did not improve the recognition of malnutrition or mortality risk. In 2019, it is estimated that almost 145,000 new cases of cancer will be diagnosed in Australia . This isPatients with cancer often receive treatment in outpatient or ambulatory day care settings. To identify malnutrition risk in these patients, it is essential to choose an efficient nutritional screening tool suitable for ambulatory cancer patients. We know that many screening tools can lack clinical information, sensitivity, specificity and/or are not usable and applicable for busy cancer care centres in which there are high turnover rates of outpatients and limited human resources .A number of malnutrition screening tools exist, with the Malnutrition Screening Tool (MST) being the most commonly used in Australia. The MST has a good validity, sensitivity and specificity to identify malnutrition assessed using the Patient-Generated Subjective Global Assessment (PG-SGA) in ambulatory cancer care patients. The PG-SGA is widely used in clinical practice for assessing nutritional status of cancer patients. The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF), a component of the full PG-SGA, has recently been receiving new attention as a valid screening tool for nutritional risk  and meetInterestingly, to standardize the clinical practice of malnutrition diagnosis in clinical settings, the Global Leadership Initiative on Malnutrition (GLIM) recently proposed diagnostic criteria for malnutrition. The GLIM criteria are objective, global and based on consensus. The GLIM includes a combination of phenotypic  and etiologic  criteria for the diagnosis of malnutrition. The GLIM criteria have not yet been validated for identifying malnutrition in an ambulatory oncology population, nor its predictive value regarding survival in these patients. There is well established evidence of the PG-SGA’s ability to predict clinical outcomes including survival with well-nourished oncology patients having longer survival duration than malnourished patients ,15.It has also been shown that handgrip strength is reduced in cancer patients with malnutrition . HandgriTherefore, the aim of this study is to (1) evaluate the agreement, sensitivity and specificity of the PG-SGA SF and GLIM criteria to reference standard of PG-SGA, (2) investigate the added value of handgrip strength test to PG-SGA SF and GLIM to recognise malnutrition risk or malnutrition, (3) evaluate the patient experience and ease of completion of the patient-completed PG-SGA SF and (4) investigate the ability of these tools to predict patient outcomes such as mortality and hospitalisation and whether any tool is superior in this ability.We conducted a cross-sectional, observational study at the Mater Cancer Care Centre (MCCC) in Brisbane, QLD, Australia over one week in May 2018 and repeated over one week in March 2019. Patient outcome data were collected 12 months post initial data collection. The protocol received was approved as low risk research by the Human Research Ethics Committee of Mater Misericordiae Limited (HREC/18/MHS/101).Patients with cancer aged 18 years or older were included if they were receiving in-chair intravenous treatment at MCCC. People who were receiving treatment for a benign condition , receiving a blood transfusion only, waiting on hospital admission, or who declined to take part in this study were excluded from participation.Patients who consented to the study were asked to complete a paper-based PG-SGA SF and received basic verbal instructions (such as ‘tick the box that is applicable’) by trained staff. The PG-SGA SF consists of four boxes: box 1, questions regarding body weight (scored 0–5); box 2, food intake (score 0–4); box 3, symptoms affecting oral food intake (scored 0–23); and box 4, regarding activities and function. Based on findings from a previous Australian study , box 4 qA short questionnaire to assess ease of completion and time taken to complete the PG-SGA SF was provided to each patient in 2019. The questionnaire was based on previously developed tools  and inclIn line with established guidelines , all parTo diagnose malnutrition using the GLIM criteria, weight changes within six months (%) and body mass index (BMI) were calculated using patients’ weight history and height . Based oHandgrip strength tests were performed in the dominant hand using a hydraulic hand dynamometer . The patient performed the test in a seated position, with the shoulder abducted and neutrally rotated, elbow flexed at 90 degrees, forearm and wrist in a neutral position. Patients were instructed to perform three maximal isometric contractions. Patients took brief pauses between measurements. The maximal value was recorded to the nearest 0.1 kg, and was used to compare with the 10th percentile of age- and gender-dependent reference values . If patiPatient outcome measures were collected 12 months post initial study date and were obtained from the patient electronic medical record. This included mortality, number of hospital admissions during the 12-month period and length of stay of hospital admissions.2) and diagnosis (breast cancer vs. other types of cancer) were performed on the basis of available literature. The association between malnutrition diagnoses and hospital admissions (Y/N) and length of stay was investigated by logistic and linear regression analysis, respectively .Data analysis was completed using IBM SPSS software V.25.0 for Windows. A significance level of 5% was applied to detect statistical significance. For normally distributed continuous variables, independent t-tests were applied to compare means between malnutrition categories. PG-SGA SF values from 1 to 7 were each analysed to determine optimal cut-off values to determine malnutrition risk for this population. In order to compare the PG-SGA SF and GLIM with the reference instrument (PG-SGA), sensitivity, specificity and positive and negative predictive values for the PG-SGA SF and GLIM against PG-SGA were calculated and receiver operating characteristic (ROC) curves were generated. Kappa coefficient was assessed to investigate the rate of agreement between PG-SGA SF or GLIM and PG-SGA. To determine the validity of the PG-SGA SF, the professional standard 80% for sensitivity and 60% for specificity were determined based on the literature . The kapOut of 275 patients that were eligible, a total of 246 patients consented to participate in the study. The mean age was 61.9 ± 13.1 years, and 182 (74%) patients were female. The most common cancer diagnoses were breast (45%), gynaecological (13%) and colorectal (11%) .The MST had a sensitivity of 100% and a specificity of 90% (kappa: 0.737) when compared to the reference tool PG-SGA.The sensitivity and specificity for the different cut-off scores and percentiles of PG-SGA SF are depicted in When compared to the reference standard PG-SGA, malnutrition according to the GLIM criteria had a sensitivity of 76%, specificity of 73% and a ‘fair agreement’ (k = 0.323). When adding handgrip strength < 10th percentile of reference values, sensitivity and specificity for both PG-SGA SF and GLIM declined to around 20% and 95–96%, respectively and kappa declined to approximately 0.2 (poor to slight agreement).According to the MST, 60 patients (24%) were identified as at risk of malnutrition compared to 71 (31%) patients with PG-SGA SF ≥ 5 . There wn = 14).According to the PG-SGA assessed by the dietitian, the number of patients who identified as malnourished was 39 (16%), with 33 (13%) of those moderately (PG-SGA B) malnourished. According to the GLIM criteria for the diagnosis of malnutrition; 77 (35%) out of 220 patients were identified as malnourished . When handgrip strength was added to the GLIM criteria (HGS < 10th percentile), malnutrition prevalence was reduced to 7% , haematology  and colorectal cancer . In patients receiving chemotherapy agents with a moderate or high emetogenicity risk, more patients were malnourished (24%) compared to patients receiving low emetogenicity risk agents (10%) (p = 0.002). The most frequently reported nutrition impact symptom in the malnourished group was ‘no appetite’ , followed by ‘things taste funny or have no taste’  and ‘fatigue’ .Malnutrition according to the PG-SGA was identified across all BMI categories, with the lowest percentage of malnutrition in obese patients. Cancer types with the highest rates of malnutrition were respiratory (n = 28), compared to only 20% (n = 38) in well-nourished patients (p < 0.001).A reduced food intake in the past month was reported by 66 patients (29.5%). In malnourished patients, a food intake less than usual was reported by 80% (n = 101), and most found the questions easy to understand . Furthermore, 81% of patients thought the questions did not take too long to complete (n = 100) with most reporting it took five minutes or less to complete the PG-SGA SF .p = 0.019); this was not the case for moderate malnutrition according to GLIM, or for moderate or severe malnutrition (GLIM) when adding handgrip strength < 10th percentile of reference values.Multivariate analyses showed that malnutrition according to the GLIM criteria was associated with a 2-fold increased 1-year mortality risk, and a 4-fold increased risk when adding handgrip strength lower than the 10th percentile of reference value as a muscle strength parameter. However, these associations were borderline statistically significant . Severe p = 0.006 and p = 0.004). When including handgrip strength, the PG-SGA SF was not associated with 1-year mortality risk.Malnutrition risk according to the PG-SGA SF (both with cut-off ≥3 and ≥5) was associated with a 1.6 or 3.5 increased mortality risk, respectively (p = 0.004) for MST ≥ 2, and HR 10.4 (p < 0.001) for PG-SGA B and PG-SGA C. No associations were observed between number of hospital admissions or total length of stay in hospital during 1-year post initial assessment.The reference tools were both associated with 1-year mortality risk: hazard ratio (HR) 3.4 . This could be explained by the inclusion of nutrition impact symptoms in the PG-SGA SF. Nutrition impact symptoms were common in our cohort, with 29% of patients reporting at least one symptom in the last two weeks. The PG-SGA SF provides valuable information on nutrition impact symptoms, which alone succeeded in identifying patients at risk of malnutrition in previous studies ,30.It has been hypothesized that identifying nutrition impact symptoms, especially early in the cancer continuum, may facilitate pro-active malnutrition prevention . For exaPrevious studies have indicated that patient-led screening is quick and easy for patients to complete . In our Malnutrition prevalence in our population differed greatly according to which tool was used, with the GLIM criteria identifying two times the number of patients as malnourished compared to the PG-SGA 35% vs. 16%). PG-SGA is a subjective diagnostic tool that is validated, reliable and widely used in the oncology setting ,34,35. W% vs. 16%Furthermore, in our study a PG-SGA was only completed on patients who scored MST ≥ 2, with all other patients assumed as PG- SGA A (well nourished), whereas GLIM criteria were assessed for all patients. Finally, the PG-SGA is a subjective diagnostic tool, in contrast, GLIM is an objective measurement which determines patients with malnutrition using objective data and cut-offs, and not by clinician’s or patient’s judgement . This meHandgrip strength is a non-invasive, quick and easy method to assess peripheral muscle strength and has been proposed as an indicator of muscle wasting and malnutrition . In cancfound that malnutrition according to GLIM criteria with the addition of hand grip strength in hospitalised cancer patients is associated with higher mortality, specifically a 2–3-fold increase in mortality [There is well-established evidence of the PG-SGA’s ability to predict clinical outcomes, such as patient survival, postoperative complications, length of stay, quality of life and hospitalisation costs . Given tortality ,39. ThesThe principal limitation of our study was removal of the activity box (box 4) from the PG-SGA SF and therefore not using the tool as it was designed. This decision was based on findings by Abbott et al.,  showing Another major limitation of our study was that all patients with MST <2 were assumed as well- nourished PG-SGA A. As this study was initially completed as part of the annual malnutrition prevalence auditing, the usual procedure was to progress to PG-SGA only if MST ≥2. To enable analysis of data, all patients with MST <2 were then assumed as PG-SGA A. This may have incorrectly labelled patients as well-nourished when in fact they could have been malnourished.Additionally, the study was completed over two separate weeks in two separate years with slightly different methods applied. The addition of patient experience questions was only included in the second year which meant that this valuable information was only obtained from 40% of the study population. Other limitations include our sample size of 246 patients, and heterogeneity of diagnoses.It is challenging to implement routine malnutrition screening in ambulatory cancer care settings. Resources tend to be stretched, therefore screening tools should be quick and simple. We found that the PG-SGA SF is a valid and suitable screening tool for cancer patients and is a good alternative to the MST. The addition of a handgrip strength test did not add value to screening or diagnosing malnutrition; it created extra work for clinicians and burden to patients and therefore has not been implemented as standard care in our cancer centre. The benefit of the PG-SGA SF in being patient-led aligns with core patient centred concepts and with engaging patients in the care process, and our data showed a good acceptance and patient experience. PG-SGA SF and the GLIM criteria both predict patient mortality, however, there needs to be more large-scale studies to validate the GLIM criteria and compare to reference assessment tools, and body composition techniques.The PG-SGA SF is an accurate, sensitive and specific malnutrition screening tool in the ambulatory cancer care setting. It is patient completed which aligns with patient-centred concepts, and it is well accepted by patients. The addition of a handgrip strength test did not add value, in fact, it reduced the sensitivity in screening or diagnosing malnutrition. The GLIM criteria diagnosed a greater percentage of malnutrition when compared to PG-SGA and the agreement of GLIM to this reference tool is fair. The GLIM criteria should not replace the use of a comprehensive nutrition assessment and should be used in parallel with established and validated tools such as PG-SGA.


P = 0.126). The implementation of hs-cTnI assay together with sex-specific 99th percentiles was associated with an increase in incidence of AMI regardless of sex, but had no major impact on clinical management and prognosis.Using high-sensitivity cardiac troponin (hs-cTn) assays with sex-specific 99th percentiles may improve management of patients with suspected acute myocardial infarction (AMI). We investigated the impact of transitioning from a conventional troponin I assay to a high-sensitivity assay with sex-specific thresholds, in patients with suspected acute coronary syndrome admitted to Swedish coronary care units. Based on data from SWEDEHEART registry , we compared periods before and after implementation of hs-cTnI assay (Abbott) using sex-specific 99th percentiles. We investigated differences on discharge diagnosis, in-hospital examinations, treatments, and clinical outcome. Upon implementation of the hs-cTnI assay, proportion of patients with troponin levels above diagnostic AMI threshold increased in women and men by 24.3% versus 14.8%, respectively. Similarly, incidence of AMI increased by 11.5% and 9.8%. Diagnostic interventions and treatments increased regardless of sex. However, these associations did not persist following multivariable adjustment, probably due to the effect of temporal management trends during the observation period. Overall, no risk reduction on major adverse cardiovascular events was observed (HR: 0.91 [95% CI 0.80–1.03],  Nowadays, these high-sensitivity cardiac troponin (hs-cTn) assays are recommended over conventional cardiac troponin (cTn) assays for AMI diagnosis5. The 99th percentiles of hs-cTn derived from a healthy reference population are the recommended threshold for AMI diagnosis. Although the use of 99th percentiles had been advocated already in 2000 ESC/ACC guidelines, this had not been feasible until the introduction of hs-cTn assays6. Overall, implementation of high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays revealed a higher proportion of patients being reclassified for myocardial injury and eligible for beneficial therapies8. Awareness has been raised that women are underdiagnosed for AMI and may receive less evidence-based treatment11. As female-specific 99th percentiles for troponins are lower than male-specific 99th percentiles, it is conceivable that implementation of a high-sensitivity assay with sex specific diagnostic thresholds will reduce underdiagnosis of AMI in women13. Studies that focus on the sex-specific clinical effect of implementing hs-cTn assays using sex-specific thresholds are scarce, and there is in particular limited data available from real-life studies14. During the changeover from cTn assays to hs-cTn assays, the Abbott assay was the only hs-cTnI method used in Sweden until the end of 2018. All Swedish hospitals who implemented hs-cTnI assay of Abbott, also applied sex-specific 99th percentiles for AMI diagnosis. The aims with the present study were therefore to (1) investigate differences between cTn period and hs-cTn period on proportion of AMI diagnosis in women and men, (2) assess the effect of implementation of hs-cTnI assay on in-hospital examinations and treatments in women and men, and (3) investigate whether this affected outcome in major adverse cardiac events and all-cause mortality as compared with cTn assays.Over the years, the improved sensitivity of cardiac troponin assays has allowed shorter time intervals between serial cardiac troponin measurements, from 6–9 to ≤ 3 h to establish diagnosis of AMIA total of 15,313 patients were admitted during respective observation periods at the nine hospitals . Stratified by sex, the proportion of females and males with troponin levels above the AMI threshold increased in hs-cTnI period by 24.3% and 14.9% as compared with cTn period, respectively . Proportion of patients with troponin levels below AMI threshold decreased significantly with 18.4% in the hs-cTnI period . Overall, proportion of patients diagnosed with ACS increased with 11.4% in hs-cTnI period as compared with cTn period  among women and 0.8% (P = 0.539) among men. Increased use of coronary angiography more often resulted in percutaneous coronary invention (PCI)/coronary artery bypass graft (CABG), particularly in men, regardless of hs-cTnI-status. The prescription of medications increased in the hs-cTnI period, with the exception of prescription of antiplatelets that decreased in the hs-cTnI period .Tables interaction = 0.082). Significant interactions between cTn period and sex were observed for use of intravenous/subcutaneous anticoagulants, echocardiography and prescription of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin-II receptor blockers (ARB) . In general, the use of these measures tended to increase in women and to decrease in men. In particular more women with troponin levels above the AMI threshold were discharged with ACEI/ARB in the hs-cTnI period as compared to men who had troponin levels above the AMI threshold in the same period (Pinteraction = 0.039).In analyses adjusted for hospital site and admission year, the overall difference between in-hospital examinations and treatments between the cTn period and hs-cTnI period was attenuated Table . NonetheAfter exclusion of readmitted patients, 10,226 patients were included for analysis. Information on major adverse cardiovascular events (MACE) was collected during 22,083 patient years  and on all-cause mortality during 27,876 patient years . Incidence rates tended to be higher in hs-cTnI period regardless of sex .interaction = 0.576; all-cause mortality, Pinteraction = 0.210, Supplementary Table After adjustment, no overall difference in MACE and all-cause mortality was noted in hs-cTnI group as compared with cTn group, respectively . For patients with troponin levels above the respective AMI threshold, no reduction in risk on MACE and all-cause mortality was noted after adjustment, without difference between sexes . This is expected since female-specific threshold in hs-cTnI period relatively decreased compared to overall threshold used in cTn-period11. As a consequence, incidence of AMI among women increased by 11.5%, while the incidence of AMI in men increased by 9.8%.Our study has three main findings. First, implementation of hs-cTnI assay using sex-specific thresholds was associated with an increase in admission of patients with troponin levels above diagnostic AMI threshold and those at increased risk, i.e. patients with higher age, cardiovascular risk factors or ischemic ECG changes. This is in line with previous studiesSecond, in-hospital examinations and treatments increased in hs-cTnI period as compared with cTn period. However, our adjusted analysis indicate that the divergence between cTn and hs-cTnI period seems particularly explained by temporal management trends irrespective of the implementation of hs-cTnI assay.11. For example, invasive assessment does not reduce risk unless hs-cTnT levels are three times above the 99th percentile18. This supports the hypothesis that 99th percentiles might not be the best benchmark to manage patients with suspected AMI7. Interestingly however, lower risk estimates were noted in patients with troponin levels below the AMI threshold. This indicates that true low-risk patients are identified more reliably by the hs-cTnI assay.Third, no overall difference in outcome was noted after changeover to hs-cTnI assay. This is in line with results of High-STEACS study and not unexpected since management changes in patients with cTn levels around the 99th percentile usually only have limited effect on hard outcomes8. Nonetheless, no overall increase in diagnostic examinations and treatment was noted in adjusted analyses. This indicates that changes over time19 to a greater degree affected patient management than the implementation of the hs-cTnI assay in itself. However, patients with hs-cTnI levels below the AMI threshold had apparently more often been perceived as having low risk, as reflected by significant decreases in the use of intravenous/subcutaneous anticoagulants, coronary angiography and revascularization procedures. At the same, the increase in the number of patients with hs-cTnI levels above the AMI threshold was not associated with an inappropriate inflation in the use of diagnostic examinations and treatments.The implementation of this assay was accompanied both with introduction of sex-specific thresholds and lowering of diagnostic threshold to 99th percentile at some hospitals. Accordingly, it is difficult to disentangle to which degree any of these components may have contributed to changes seen in our analysis. However, some assumptions are close at hand. The changeover to hs-cTnI assay was associated with an increase of at-risk patients being admitted to CCU, similar as seen in other investigationsThe use of sex-specific 99th percentiles appeared to affect management of women and men in several, partly unexpected aspects. Conceptually, lower female-specific 99th percentile would be expected to increase sensitivity while lowering specificity. This may have contributed to the increased prescription of ACEI/ARB in women. At the same time, the prescription of ACEI/ARB decreased in men, intriguingly in particular among those with troponin levels above the AMI threshold. This was accompanied by corresponding changes in the use of echocardiography, a finding that we are unable to explain on the basis of the present data. Clearly, further investigation is needed.What are the clinical implications of our study? The implementation of the hs-cTnI assay increased the proportion of AMI diagnosis significantly by approximately 10% in patients presenting at the CCU with suspected acute coronary syndrome, and this was similar for women and men. We only noted small changes in diagnostic examinations and treatment, mostly in women and men with troponin levels below the AMI threshold. These estimates however, should be acknowledged as rather conservative estimates given the possibility of collinearity between admission year and study period in the multivariable analyses. We feel that it is now of great importance to unravel what the most optimized ‘rule-in/rule-out’ algorithm is for hs-cTn assays to improve treatment and outcome in patients with suspected acute coronary syndrome. Intriguingly, we also noted that the proportion of women who presented at the CCU with suspected acute coronary syndrome did not change over time and was in both periods 39%, despite the use of sex-specific thresholds. This observation may suggest sex referral bias at cardiac emergency unit and requires further urgent attention.20. Accordingly, our results probably reflect the minimum effect on differences in diagnosis, management and outcome between women and men with suspected ACS admitted at CCU. (6) In the SWEDEHEART registry, only peak troponin levels are registered. We were therefore not able to investigate sex-differences regarding the relation between temporal cTn changes and in-hospital examinations and treatments. Greater temporal hs-cTn changes remaining below the AMI-threshold may for example, have led to more invasive diagnostic procedures in men compared to women. This hypothesis needs to be assessed in future research. (7) As the SWEDEHEART registry is based on real-world data, no standardized “rule-in/rule-out” algorithm for diagnosis of AMI was applied in hospitals. However, all hospitals introduced sex-specific thresholds during hs-cTnI period, and we were therefore able to investigate the impact of implementing a hs-cTnI assay using sex-specific thresholds in clinical practice.A number of limitations of this study should be mentioned. (1) Only hs-cTnI assay from Abbott is studied, and we cannot make firm conclusions on sex-specific impact of other hs-cTn assays. (2) The design of our study is observational, and our results reflect combined effects of changing to a high-sensitivity assay and using sex-specific thresholds. It is difficult to separate which aspect in assay change might have had greatest impact on the changes found in our analysis. Accordingly, inferences on causality should be made with caution. Moreover, residual confounding may persist. (3) Patients with troponin levels above the AMI threshold determined with high-sensitivity assay are enriched with less sick patients that might have remained undetected when using conventional cTn assay. This introduces selection bias which could have affected our results. (4) We investigated patients with suspected ACS admitted at CCU. Accordingly, we are unable to comment to which extent men at risk but being “troponin-negative” by means of the relatively higher male-specific 99th percentile might not have been regarded being in need of CCU admission. This implies a residual risk of underdiagnosis and undertreatment in these individuals. In addition, generalization of our findings to emergency department patients should be done with caution. (5) The lower proportion of women as compared with men admitted to CCU may suggest sex referral bias at cardiac emergency unit. This is in line with recent data, showing a systematic sex-bias in the early management of patients with suspected ACSIn conclusion, implementation of a hs-cTnI assay using sex-specific thresholds was associated with an increase in the proportion of women and men with troponin levels above diagnostic AMI threshold, and has led to more AMI diagnosis at discharge. The increase of in-hospital examinations and treatments after hs-cTnI implementation seems particularly explained by temporal management trends irrespective of the implementation of hs-cTnI assay. Overall, implementation of hs-cTnI assay using sex-specific 99th percentiles had only limited effect on clinical outcome in both women and men.8. Patients included in the registry are informed about their participation which they have the right to decline. Written consent is not required according to Swedish law. In this study, only hospitals who implemented Abbott ARCHITECT STAT cardiac troponin I assay are included (n = 9). Based on the use of hs-cTnI assay, patients were divided into those admitted before implementation of hs-cTnI assay and those admitted thereafter. Patients diagnosed with ST-segment elevation myocardial infarction and those who lacked a troponin measurement were excluded from analyses. The present manuscript follows the Strengthening the Reporting of Observational Studies in Epidemiology guidelines21. The study was conducted according to principles of 1975 Declaration of Helsinki and approved by Regional Ethical Review Board in Stockholm (2012/60-31/2).We used data from Swedish Web based system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry recorded between time period from August, 2010 till the end of May, 2018. The SWEDEHEART registry includes all individuals with suspected ACS admitting at a CCU or other specialized facility at all Swedish acute cardiac care hospitalsThe cTn assays, applied decision limits for AMI diagnosis, and date of implementation of hs-cTnI assay are listed in Supplementary Table According to clinical primary discharge diagnoses, we categorized patients into cohorts with AMI, unstable angina (UA), heart failure, other cardiac conditions or non-cardiac conditions. In-hospital examinations contained echocardiography and coronary angiography. In-hospital treatment data on intravenous/subcutaneous anticoagulants , PCI and CABG were collected, and discharge medications included antiplatelets , ACEI, ARB, and statins.Information on patient outcome was obtained from mandatory Swedish Patient Registry  and Swedish population registry. Patients were followed for mortality until occurrence of death or May 28th, 2018, and for non-fatal events until December 31st, 2017. Outcomes were MACE and all-cause mortality. MACE was a composite endpoint of all-cause mortality, readmissions for non-fatal AMI (ICD-10-CM I21), heart failure (ICD-10-CM I50) and ischemic stroke (ICD-10-CM I63). During the first 30-days after index hospitalization, it is not possible to separate a new AMI from an index AMI in the Patient Registry. Therefore, only AMI occurring 30 days after index hospitalization were counted.22 and included admission year only. In addition, adjustment was made for hospital site. Multivariable cox proportional hazard regression analysis were conducted to quantify the relationship with hs-cTnI period  and outcome , adjusting for the same set of covariates as used for logistic regressions. Interaction was tested between sex and hs-cTnI assay, and was considered significant when P value < 0.1. Otherwise, statistical significance was reached when P value < 0.05. All statistical analysis are performed using SPSS for windows 23.0 .Differences of clinical characteristics between groups are assessed by Independent Student’s T test or Mann–Whitney-U test, as appropriate. For comparison of proportions, the Chi-squared test is used. The group of interest for management of AMI are patients with troponin levels above diagnostic AMI threshold (Supplementary Table Supplementary Information


To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma.t testing were used to make parametric comparisons, and Fisher’s exact test or the Mann–Whitney U test were used to make nonparametric comparisons.A total of 23 patients with clinical stage II-III low-lying  rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student’s Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS.TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT. Laparoscopic colon resection has been considered as an alternative procedure to open colon resection after a series of randomized controlled trials (RCTs) from 2004 to 2005, with short-term advantages, like less morbidity and hospital stay, but similar long-term survival –3. HowevTransanal total mesorectal excision (TaTME) was a new surgical procedure first introduced in 2010 , which hIn the current study, we investigated the feasibility and short-term clinical outcomes of neoadjuvant CCRT followed by TaTME-SPLS in Asian patients with middle to lower third rectal adenocarcinoma. We also estimated the differences of TaTME-SPLS in Western and Eastern patients with middle to lower third rectal adenocarcinoma.According to our previous studies, patients were proven to have rectal adenocarcinoma histologically if they had the middle to lower third tumor margin within 8 cm from anal verge pre-operatively as measured by rigid sigmoidoscopy; and those diagnosed with rectal adenocarcinoma between December 2015 and December 2018, at Taipei Medical University-Wan Fang Hospital were included in this study –22. The Surgery was usually performed 6-10 weeks after the completion of neoadjuvant CCRT. Patients were given information regarding the expected benefits and potential risks of the procedures and an informed consent was obtained from all participants included in the study. Approval for this study was obtained from the Institutional Review Board of Taipei University-Wan Fang Hospital (JIRB N201906057).The patient was placed in the lithotomy position. A Lone Star Retractor®  was placed to expose the anal canal. A transanal single-port device, the Gelpoint path® , was positioned. Three trocars were inserted via the Gelpoint path®, and a flexible endoscope was inserted via a trocar. Under endoscopic guidance, the tumor was identified and the rectum was closed circumferentially at least 10 mm distal to the lower margin of the tumor by purse-string suture to avoid tumor spillage. Then, the rectum was divided circumferentially.2 with a low flow (1.5 L/min) and a maximal pressure of 12 mmHg. According to the principle of TME, “bottom-to-up” dissection was performed under endoscopic guidance to achieve the rectum mobilization circumferentially [If a tumor is located near the dentate line of the anus, an inter-sphincter resection (ISR) is necessary . Convententially . Then, t2 to a pressure of 12 mmHg. The operation table was rotated toward the right side. The sigmoid colon and rectum were mobilized using the medial to lateral approach, and the inferior mesenteric pedicle isolation was performed. The roots of the inferior mesenteric artery and vein were ligated with laparoscopic clips, and then, were divided. Extensive mobilization of the splenic flexure and transverse colon was performed in selective patients. For this step, an additional 5-mm trocar was inserted at the site of the future pelvic drain in the left iliac fossa. Finally, the total mobilization of the rectum was performed to meet the plane created by transanal dissection, and the specimen was completely freed. Extraction of all specimens was performed through the abdominal single-port. The sigmoid colon was clamped and divided. TaTME was performed. In selective patients, a transverse coloplasty pouch (TCP) was created for colon-anal anastomosis using the sigmoid colon [All the patients were placed in the lithotomy position. A 4-cm transverse incision was performed at the right lower quadrant of the abdomen, the site of the future ileostomy. The wound was deepened to enter the peritoneal cavity and an abdominal Gelpoint system® , was inserted into the peritoneal cavity. A flexible laparoscope, 10 mm in diameter, and only standard straight laparoscopic instruments were used. The abdomen was insufflated with COid colon . The rect test for continuous numerical variables. Statistical significance was defined as a value of P < 0.05. We compared all study data with Statistical Package for the Social Sciences (SPSS) version 13.0 for Windows .Frequency tables were used for patients’ presentations and tumor characteristics. We used the two-tailed chi-square test for differences in proportions and the Student’s A total of 23 patients underwent neoadjuvant CCRT followed by TaTME-SPLS, and one patient underwent open TME. The demographic and tumor characteristics are presented in Table The pathological findings after neoadjuvant CCRT followed by TaTME-SPLS are presented in Table Comparing with the 2 leading studies based on Western and Eastern country patients with middle to lower third rectal adenocarcinoma, receiving TaTME-SPLS, higher rates of neoadjuvant CCRT, mobilization of the splenic flexure, ISR, and stapled types of anastomosis were found in our study Table . In our In 2011, Tuech et al. described the first case of TaTME-SPLS in the world . Then, DAfter the first single-port laparoscopic right hemi-colectomy had been described in 2008 , severalLAR involves removal of the sigmoid colon and rectum to a level, where the distal margin is free of cancer, followed by a primary anastomosis between the descending colon and the rectum  or the anal sphincter  , 37. ThePatients with low-lying rectal adenocarcinoma , receiving TaTME-SPLS had better pathologic complete response rate and more downstaging of pathologic T and N stages, compared with the Meillat et al. study Tables  and 3. IThis study had some strengths. Prior to this study, no clinical data had proven that neoadjuvant CCRT followed by TaTME-SPLS in patients with low-lying rectal adenocarcinoma leads to excellent organ preservation, clean distal margin, acceptable toxicities, and good pathologic complete response; this study provides novel data. Our definition of low-lying rectal adenocarcinoma was clear , and measuring tools were consistent, that is, rigid sigmoidoscopy. Our regiments of neoadjuvant CCRT, the interval from completion of CCRT to surgery, and procedures of TaTME-SPLS were consistent and without discrepancy treatments. Our study was the first study to evaluate the effect of neoadjuvant CCRT followed by TaTME-SPLS in patients with low-lying rectal adenocarcinoma. Additionally, this is also the first study that presents neoadjuvant CCRT followed by TaTME-SPLS as safe and effective for organ preservation without inadequate margin in Asian patients with low-lying rectal adenocarcinoma.This study had some limitations. First, in this study, the sample size of patients with low-lying rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS was small. Second, all patients with low-lying rectal adenocarcinoma were enrolled from an Asian population, and so, the corresponding ethnic susceptibility remains unclear. Therefore, our results must be cautiously extrapolated to non-Asian populations. Third, surgeons not familiar with this technique needed standardized training, including observations, cadaveric labs or hands-on courses, and proctorship or mentorship, with early case experiences , 45. PatTaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.


The effects of PDI blockade in vivo were examined by treating mice with the irreversible PDI inhibitor, PACMA-31, in an ovalbumin-induced model of food allergy. The role of dietary PDI modulators was investigated using various dietary compounds including curcumin and quercetin-3-rutinoside (rutin). PDI expression was observed on resting mast cell surfaces, intracellularly, and in the intestines of allergic mice. Furthermore, enhanced secretion of extracellular PDI was observed on mast cell membranes during IgE and antigen activation. Insulin turbidimetric assays demonstrated that curcumin is a potent PDI inhibitor and pre-treatment of mast cells with curcumin or established PDI inhibitors such as bacitracin, rutin or PACMA-31, resulted in the suppression of IgE-mediated activation and the secretion of various cytokines. This was accompanied by decreased mast cell proliferation, FcεRI expression, and mast cell degranulation. Similarly, treatment of allergic BALB/c mice with PACMA-31 attenuated the development of food allergy resulting in decreased allergic diarrhea, mast cell activation, and fewer intestinal mast cells. The production of TH2-specific cytokines was also suppressed. Our observations suggest that PDI catalytic activity is essential in the regulation of mast cell activation, and that its blockade may benefit patients with allergic inflammation.The thiol isomerase, protein disulfide isomerase (PDI), plays important intracellular roles during protein folding, maintaining cellular function and viability. Recent studies suggest novel roles for extracellular cell surface PDI in enhancing cellular activation and promoting their function. Moreover, a number of food-derived substances have been shown to regulate cellular PDI activity and alter disease progression. We hypothesized that PDI may have similar roles during mast cell-mediated allergic responses and examined its effects on IgE-induced mast cell activity during cell culture and food allergy. Mast cells were activated  These events are tightly orchestrated involving several phosphorylative reactions that culminate in the activation of transcription factors which regulate gene expression.IgE-mediated mast cell activation is a critical component in the induction of allergic responses to food-derived antigens –3. The cWe have previously shown that food-derived components such as curcumin can attenuate the development of mast cell responses during food allergy , 5. CurcWe hypothesized that dietary components such as curcumin may modulate the mast cell response during food allergy by inhibiting the direct activation of circulating proteins and enzymes and explored likely targets. One common mechanism of protein activation is through an allosteric disulfide bond, where a disulfide will rearrange to alter the intra- or intermolecular structure of the protein to activate or inactivate it . The reaThiol isomerases such as PDI catalyze the breakage, formation and rearrangement of disulfide bonds, regulating protein folding within the endoplasmic reticulum (ER) , 15. HowIn this study, we verify the PDI inhibitory activity of curcumin and explore the role that PDI plays in the development of mast cell-mediated responses during food allergy using known PDI inhibitors. To date, with the exception of a postulation that PDI catalyzes the formation of IgG4 under conditions of chronic antigen exposure , there hBALB/c mice were purchased from Taconic Farms and Envigo. All mice were bred in our facility and all animal research was approved by the IACUC of Western New England University.via PDI-catalyzed reduction of insulin in the insulin turbidity assay as previously described by us and others (compound + PDI + DTT] – OD[DTT])/(OD[PDI + DTT] – OD[DTT]) × 100%. Enzyme inhibition was determined by the following formula: enzyme inhibition = (1 – [ODmax{compound + enzyme}/ODmax{buffer control + enzyme}]).PDI activity was measured d others –22. BrieBMMCs were generated from naïve BALB/c mice and cultured with 10 ng/ml of rIL-3 (Shenandoah) and rSCF (Shenandoah) for >4 weeks as we have previously described . Harvest6 BMMCs/ml were cultured in triplicates with 10 ng/ml IL-3 and SCF. Cells were activated by pre-sensitizing with 1 µg/ml DNP-IgE  or vehicle (medium), followed by treatment with 200 ng/ml DNP-BSA  to unactivated BMMCs or cells activated with IgE and antigen as described above. The effects of PDI inhibition were examined by treating with PDI inhibitors such as curcumin or PACMA-31. Six hours after activation with IgE/Ag, cells were stained for surface antigens such as c-Kit or FcεRI with fluorescently-labeled mAbs. Intracellular cytokine staining was then performed using a kit from Biolegend . Cells were fixed, then permeabilized and stained for various cytokines using mAbs. Cytokine-producing cells were enumerated by flow cytometry.Quantitative RT-PCR was performed as previously described using Taqman probes , 24. ExpBMMCs were activated with DNP-IgE and DNP-BSA in the presence or absence of various PDI inhibitors. β-hex activity in cell culture supernatants was assessed as previously described by us , 24. PerBMMCs were cultured with rIL-3 and rSCF as described above. Some groups of cells were treated with various concentrations of bacitracin, rutin or PACMA-31. Cells were counted daily for 4 to 5 days, and live cells were enumerated on the basis of trypan blue exclusion.BMMCs and MC/9 cells (a murine mast cell line) were incubated with mAbs against mouse c-Kit (Biolegend), FcεRI (Biolegend), PDI (Life Technologies), and isotype controls for PDI (IgG2a/Life Technologies). Expression of cell surface PDI was assessed at various times in cells after activation with IgE and antigen and in unactivated controls. Intracellular PDI expression was assessed 30 min later in fixed and permeabilized cells. Flow cytometric analysis was performed using an Accuri C6 flow cytometer and Flow jo software.BMMCs and MC/9 cells were activated with DNP-IgE and DNP-BSA and total protein extracts were harvested after 4 h. Western blot was performed as previously described  was determined by the unpaired Student’s t-test, whenever applicable. In experiments comparing multiple experimental groups or time points, one or two-way analysis of variance was performed followed by the Dunnett test for multiple comparisons.in vitro and in mice  inhibiting disulfide bond formation , in hume assays , 33, 34.e assays . Quercete assays , suggestOur observations above demonstrating a dose-dependent suppression of cytokine expression and secretion by PDI inhibitors are consistent with well-described roles of PDIs as molecular chaperones during the intracellular generation of various proteins. To further determine whether PDI is also involved during mast cell degranulation and the release of pre-formed mediators, we examined cell culture supernatants immediately after activation with DNP-BSA, and assessed the secretion of the enzyme β-hexosaminidase (β-hex) as previously described . As obseTo further investigate the effects of PDI inhibition on mast cells, we also examined the effects of bacitracin and rutin exposure on BMMC proliferation and survival as previously described . BMMCs w50 of 10µM in animal studies  was shown to have broad-spectrum activity against various cancer cell lines , 35. Of extracellular secreted PDI in various cells  that catalyzes the formation of 4-hydroxyproline in collagen (reviewed in ). We thevia its enzymatic activity. The secretion of extracellular PDI is further enhanced soon after IgE activation has occurred. Next, to examine the levels of intracellular PDI protein in mast cells, we evaluated its presence in unactivated and IgE-activated mast cells six h after IgE-activation had occurred. As observed in The secretion and extracellular activity of PDI in endothelial cells and platelets is well-established , 42, 43,εRI, on resting and activated BMMCs. As observed in εRI. In contrast, pre-incubation with PACMA-31 significantly decreased the expression of the receptor in BMMCs. In activated mast cells, the overall intensity of unbound FcεRI expression was decreased as would be expected as a consequence of saturation by IgE molecules. However, this was further reduced in PACMA-31-exposed and IgE-activated BMMCs.The data above suggest that PDI can be secreted by mast cells after activation, with the potential to modulate downstream events such as the transcription of cytokine genes. To further assess the role of PDI inhibition on mast cell activation, we examined the effects of PACMA-31 pre-treatment on the expression of the high affinity receptor for IgE, Fcvia inhibition of constitutively present cell surface PDI. To further investigate the effects of PDI inhibition during mast cell activation and to determine whether activation-associated PDI activity can modulate downstream cellular events, BMMCs were incubated with PACMA-31 starting 30 min prior to activation with DNP-BSA. Six h post-challenge with antigen, the levels of cytokines in supernatants were assessed. As observed in in vivo. Furthermore, inhibition of PDI was sufficient to attenuate the suppression of both pre-formed mediators such as TNF-α as well as de novo synthesized cytokines such as IL-13. To further confirm the effects of inhibition of cell surface PDI, BMMCs were treated with an anti-PDI mAb (Abcam), followed by activation via IgE and antigen  during mast cell activation may modulate downstream cellular events, contributing to changes in molecular and cellular function. In this context, cell-surface specific PDI has been found to be important for the functions of hepatocytes, endothelial cells, and platelets , 53. Furvia inhibition of NF-κB activation , activation (mMCP-1 levels), and mast cell-mediated effects such as allergic diarrhea in the IgE and mast cell-dependent model of OVA-induced food allergy. However, although we have not examined other immune cell types in this study, it is likely that the activity of PDI family members is also altered in other cells during allergic responses. Particularly, our data in in vivo blockade of their activity may prove to be of therapeutic benefit in patients with mast cell-mediated disorders.Taken together, our data suggest that PDI and its related family members may play vital roles in the regulation of mast cell activation during the allergic response, and that The original contributions presented in the study are included in the article/The animal study was reviewed and approved by The Institutional Animal Care and Use Committee at Western New England University.CBM and DRK conceived and directed the project. DK, SP, JG, JR, EK, CG, MP, NS, DRK, and CBM performed experiments and analyzed data. DK, SP, JG, DRK, SSS and CBM prepared figures for the manuscript. CBM, DK and DRK wrote the paper. All authors contributed to the article and approved the submitted version.This project was supported by funds from the National Institutes of Health grants: NIAID R15AI107668 (CM) and NCI R21CA231000 (DRK).CBM and DRK are authors on a patent application submitted by Western New England University regarding the role of thiol isomerases in mast cell activation.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.