The COVID-19 outbreak was designated a global pandemic on March 11, 2020. The relationship between vaping and contracting COVID-19 is unclear, and information on the internet is conflicting. There is some scientific evidence that vaping cannabidiol (CBD), an active ingredient in cannabis that is obtained from the hemp plant, or other substances is associated with more severe manifestations of COVID-19. However, there is also inaccurate information that vaping can aid COVID-19 treatment, as well as expert opinion that CBD, possibly administered through vaping, can mitigate COVID-19 symptoms. Thus, it is necessary to study the spread of inaccurate information to better understand how to promote scientific knowledge and curb inaccurate information, which is critical to the health of vapers. Inaccurate information about vaping and COVID-19 may affect COVID-19 treatment outcomes.Using structural topic modeling, we aimed to map temporal trends in the web-based vaping narrative  to indicate how the narrative changed from before to during the COVID-19 pandemic.We obtained data using a textual query that scanned a data pool of approximately 200,000 different domains  such as public internet forums, blogs, and social media, from August 1, 2019, to April 21, 2020. We then used structural topic modeling to understand changes in word prevalence and semantic structures within topics around vaping before and after December 31, 2019, when COVID-19 was reported to the World Health Organization.Broadly, the web-based vaping narrative can be organized into the following groups or archetypes: harms from vaping; Vaping Regulation; Vaping as Harm Reduction or Treatment; and Vaping Lifestyle. Three archetypes were observed prior to the emergence of COVID-19; however, four archetypes were identified post–COVID-19 . A topic related to CBD product preference emerged after COVID-19 was first reported, which may be related to the use of CBD by vapers as a COVID-19 treatment.Our main finding is the emergence of a vape-administered CBD treatment narrative around COVID-19 when comparing the web-based vaping narratives before and during the COVID-19 pandemic. These results are key to understanding how vapers respond to inaccurate information about COVID-19, optimizing treatment of vapers who contract COVID-19, and possibly minimizing instances of inaccurate information. The findings have implications for the management of COVID-19 among vapers and the monitoring of web-based content pertinent to tobacco to develop targeted interventions to manage COVID-19 among vapers. COVID-19 is spreading rapidly and has been declared a global pandemic , and it There is some scientific knowledge that vaping cannabidiol (CBD) or other substances may be associated with more severe manifestations of COVID-19 ,6. Use oFor example, some Twitter posts around vaping indicated that e-cigarette devices may increase lung humidity and prevent COVID-19, and other posts stated that these devices can be used to administer COVID-19 medication to the lungs and possibly destroy the virus ,12. MuchA previous study analyzed Twitter content around COVID-19 and vaping [Using the novel computational technique of structural topic modeling (STM), we mapped temporal trends in the web-based vaping narrative  to show how discourse differed before versus during the COVID-19 pandemic. Topic modeling is a computer-aided content analysis technique where texts are organized into themes known as topics. These topics are not provided to the machine prior to modeling but emerge inductively as the algorithm learns patterns within the texts. The model assumes a relational theory of meaning by identifying structures of co-occurrence of words in individual texts and across all the texts. The model thus provides content analysis of text data sets that are too large to code by hand. Topic models use machine learning to uncover patterns and relationships that may be omitted by hand coding or traditional content analysis. Unsupervised machine learning methods have performed similarly to human coders on identical documents . UnsuperApproval and informed consent were not needed because the data were collected using publicly available textual query techniques. All data are publicly available and can be accessed by anyone. The data were provided to the research team with all identifiers removed.vape, vaping, and e-cigarette. The data that comprised vaping-related text fragments were collected from August 1, 2019, to April 21, 2020. As the data set represents a multitude of sources for web-based chatter related to vaping, our data set is likely representative of the web-based vaping narrative during the indicated period. The start date for the COVID-19 pandemic was denoted as December 31, 2019, when the Chinese government disclosed the existence of COVID-19 to the World Health Organization (WHO) [Data were obtained using a textual query that scanned a data pool of approximately 200,000 different domains, such as public forum posts, blogs, news articles, message boards, health care provider forums, and social media  for mentions of cannabis, COVID-19, tobacco, and vaping. References to cannabis were determined using these search terms: [We then used topic modeling to understand changes in word prevalence within topics around vaping and COVID-19. Topic modeling is a computer-aided content analysis technique in which texts are organized into themes known as topics ,26. In tWe used an approach to topic modeling known as STM ,20. STM Because STM is an unsupervised approach, the number of topics to estimate (k) is key to the analysis. We first estimated several models ranging from 5 to 200 topics. These models were then evaluated qualitatively by their ability to produce coherent topics and capture topics regarding vaping and COVID-19 . The numWe conducted qualitative analysis to determine the number of topics based on past social science studies in which topic modeling was used to extract meaning from large text samples. These studies ,31 deterTopic interpretation was influenced by prior knowledge about why texts were written and what they sought to accomplish. Most of the text was produced and consumed by people who engaged in vaping and other forms of tobacco use, and this lens was used to interpret the presence or absence of topics and words. Most of the topic labels were straightforward and did not require much interpretation. To characterize topics in the vaping narrative, we qualitatively coded each topic by investigating word clouds based on each topic and reviewing exemplar documents which detailed high proportions of each topic . The topcontrarian, polarized, and topic modeling. The 2016 paper by Farrell [Topic validation is key to assessing whether the substantive meaning of the topic and its words are parallel with the qualitative meaning of the text, and we used methodological guidance from past research for this purpose ,26. Past Farrell  was deteFinally, word clouds were again generated, this time to visualize topics with the top 100 words ranked by STM-generated weights per topic, for the models representing the full data set and the data sets from before and after COVID-19 was reported to the WHO. In these word clouds, a larger font size indicated a greater weight, with word clouds indicating the importance of a word within a topic. We then grouped topics and their associated word clouds into larger categories or archetypes based on shared concepts across topics . All anaWe collected 4,027,172 documents  comprised of text from blogs , news articles , forums , comments (<1%), professional reviews and Facebook posts (both <1%).The most frequently observed words in the data set were “ban” , “product” , and “make” .Topic modeling captured significant events in the vaping environment, such as the vaping health crisis and Walmart stopping e-cigarette sales. The vaping health crisis referred to the 2019 emergence of vaping-associated pulmonary injury (VAPI) in the United States . WalmartPot smoke is the best expectorant I’ve ever used and fresh cbd oil or weed brownies are verrrrrrry healing, promotes good sleep and good healing. If you are a non-smoker, tobacco smoke should help you clear out your lungs if you have nothing else.March 10, 2020COVID-19 deaths invariably involve a ”cytokine storm,” an excessive, un-checked immune system response. Cannabinoids from cannabis, cbd in particular, can lower cytokine production naturally. research needed asap!March 25, 2020Example text fragments regarding websites marketing CBD for COVID-19 prevention or treatment:Why hemp cbd flowers and a vaporizer are the best COVID-19 coronavirus prepping tools.February 18, 2020REDACTED COMPANY NAME applauds the use of cbd during the coronavirus outbreakMarch 30, 2020Toronto-based cannabis seller testing cbd’s effectiveness on reducing symptoms of coronavirus.April 1, 2020Our main finding was the emergence of discourse around vape-administered CBD treatment for COVID-19 when comparing web-based vaping narratives before and after the outbreak of COVID-19. Recent work suggested that CBD use may increase COVID-19 risks . Other sThere is limited empirical research on the intersection of the vaping narrative and COVID-19, especially around the emergence of CBD-related COVID-19 treatments and comparing the narratives before and during the COVID-19 pandemic. The role of web-based narratives in tobacco control, especially within social media, is a growing field of study . We expaIf health care professionals are aware that vapers with COVID-19 may use CBD as a treatment based on inaccurate information, these professionals may be better able to respond to vapers with COVID-19 who demonstrate CBD-related complications. Professionals can provide accurate information regarding COVID-19 to vapers who seek health care. Misinformation can also be combated with trusted information. Public health authorities can include COVID-19–specific information in targeted vaping-related messaging, perhaps mitigating consumption of inaccurate web-based information. Information-based campaigns can target inaccurate information in line with the topics identified by our results, such as vaping CBD as a COVID-19 treatment. There are several experimental interventions around reducing levels of inaccurate information ,50, withOur findings have several implications. From a policy standpoint, we suggest that vaping forums be mandated to provide accurate data around the interactions between vaping and COVID-19. These efforts may reduce levels of inaccurate information around COVID-19 and vaping and may minimize any COVID-19 complications associated with vaping. Future research can identify changes in the vaping narrative as the pandemic progresses further, allowing public health authorities to adjust treatment provision for vapers at risk of contracting COVID-19. Future work can also address how inaccurate information on the internet can be mitigated, especially as the pandemic progresses.Our results depended on the validity of the data collected through our textual query. We searched a wide range of web-based media and identified key themes that validated our results , and we are thus confident in the comprehensiveness of our data. We may have overlooked some slang terms for vaping and thus underestimated the web-based narrative. We did not obtain location data for individual text fragments; thus, we were not able to determine how COVID-19 cases in certain areas affected the narrative. Our data were drawn from August 1, 2019, to April 21, 2020, and we were not able to determine changes in the narrative after April. We were not able to collect all web-based vaping chatter and may have missed some themes. In future research, we will collect qualitative and survey data from vapers to enhance the current findings. We did not use interrater reliability for our qualitative analysis, and we will use such methods in future research.We demonstrated the advent of discourse around vape-administered CBD treatment for COVID-19 by comparing the web-based vaping narratives before and during the COVID-19 pandemic. The increase in CBD-related discussion within the vaping narrative may be due to the marketing of CBD products consumed through vaping as a COVID-19 treatment . Our fin


COVID-19 is a new human-infecting coronavirus for which the World Health Organization declared a global pandemic. The first Italian cases occurred in February 2020: since then, there has been an exponential increase in new cases, hospitalizations and intensive care assistance demand. This new and sudden scenario led to a forced National Health System reorganization and review of welfare priorities. The aim of this study is to evaluate the effects of this pandemic on ordinary activities in two plastic surgery divisions in Rome, hosted in a COVID-19 and a non-COVID-19 hospital.The data of this comparative retrospective study was collected between 9 March and 9 April 2019 and the same period of 2020 from two plastic surgery units, one in a COVID-19 hospital and second in a non-COVID-19 hospital in Rome, Italy. The 2019–2020 data of the two hospitals was compared regarding the number of surgeries, post-operative dressings and first consultations performed.p value = 0.0047) and first consultations  were found between the COVID-19 and non-COVID-19 institutes, with a drastic trend limiting non-urgent access to COVID-19 hospitals.Both units sustained a decrease in workload due to lockdown effects. Statistically significant differences for day surgery procedures (The long-term effects of healthcare reshuffling in the “COVID-19 era” imply a delay in the diagnosis and treatment of skin cancer and cancellation of many reconstructive procedures. These findings pose a question on the future consequences of a long-term limitation in plastic surgery healthcare.Level of evidence: Level III, risk/prognostic study. Betacoronavirus, first reported in Wuhan (China) in December 2019 and rapidly spreading to all continents, causing a pandemic and a public health emergency. This virus is highly contagious with a human-to-human transmission and may present a benign course showing flu-like symptomatology  or a serious health hazard with severe acute respiratory syndrome (SARS), acute cardiac injury and acute kidney injury [COVID-19 is a new human-infecting R0) of COVID-19, a mathematical term that indicates how contagious a disease is, indicating the average number of people who will catch COVID-19 from one single infected patient as 3.8 [Contact frequency among individuals is known as one of the major elements affecting the spread of the disease. Liu et al. estimate the basic reproduction number  was set as a COVID-19 hospital and San Gallicano (ISG) as a non-COVID-19 hospital. PU1 Plastic Surgery Department serves the Faculty of Medicine and Dentistry at Rome’s Sapienza University, Italy, with a staff consisting of six consultants and eleven trainees. In 2019, the in-hospital ward had ten beds and five weekly theatres treating 500 patients; the day surgery ward had three beds and five weekly theatres treating 750 patients; 1610 outpatient clinic surgery operations were performed and 10. 500 outpatient consultations were carried out, of which 3.360 were referrals and 7.140 were dressing changes.ISG Plastic Surgery Department is located in a Roman IRCSS, a biomedical institution of relevant national interest, which drives clinical assistance in strong relation to research activities. The staff is made up of nine consultants and one trainee. In 2019, the in-hospital ward had seven beds and five weekly theatres treating 341 patients; the day surgery ward had four beds and five weekly theatres treating 981 patients; 1.655 ambulatory surgery operations were performed and 9.151 outpatients received a consultation, of which 3.635 were referrals and 5.516 were dressing changes.The total number of patients treated in both hospitals and in each hospitalization regimenThe pathologies operated on in-patients and day surgery regimens of careThe total monthly number of theatre hours for DS patients and for in-patientsThe total monthly ward beds given to each unit in DS and in IP regimen of careThe number of staff members on dutyThe pre-hospitalization screening tests and the admittance criteria to the plastic surgery departmentThe study analysed the data collected between 09 March  and 09 April 2020 and the same period of 2019. Outpatient, day surgery (DS) and in-patient (IP) medical charts were retrieved from both plastic surgery departments and the following data compared:p < 0,05) using SPSS statistics version 18 .Statistical analysis on retrieved data was conducted with the chi-squar test , taken at least 48 h before scheduled surgery. All non-oncologic surgery was curtailed in both hospitals.When compared with the same period of 2019, 2020 witnessed a percentage decrease with regard to in-patient and outpatient procedures in both hospitals.In detail, PU1 faced a total in-patient surgery decrease of 62.90%, while at ISG it amounted to 51.28%. Figure Ambulatory surgery decreased by 90% at PU1 and by 80% at ISG when compared with the same period in 2019.Day surgery procedures decreased by 87.65% at PU1 and by 70.87% at ISG.The average number of in-patient hospitalization days between 2019 and 2020 remained almost unchanged for PU1 (from 6.4 to 6.8 days) and for ISG (from 2.8 to 2.5 days)..Overall, there is a clear decrease in welfare procedures in both hospitals, with statistically significant differences at chi-square test between the two institutes for day surgery procedures and first consultations Table .Table 2CThe primary objective of this study was to ascertain if there was a qualitative and quantitative modification in the activities of plastic surgery departments caused by the COVID-19 pandemic. The secondary end-point was to ascertain whether the nature of COVID-19 hospital or non-COVID-19 hospital hosting plastic surgery division had any influence on such result.The pandemic-based guidelines of state authorities in many countries stipulate that all elective procedures that could be safely delayed must be cancelled , 12 untiDespite the national government decree, plastic surgery activities show different managements depending on the COVID-19 or non-COVID-19 nature of the host hospital.After this work, it is possible to ascertain that both plastic surgery departments enrolled in this study are facing an overall decrease in activities, with a substantial cut in plastic surgery cares, which normally include a wide spectrum of diseases.Study data shows the effects of the consequence of cancellation of plastic surgery elective surgeries in both hospitals during the lockdown, when the operating theatre was available only for such urgent procedures as melanoma or melanoma and SLNB removal or for post-traumatic reconstruction in PU1. These non-delayable procedures were unaffected in both hospitals, and this fact caused a relative increase in trauma surgeries and oncological figures compared with 2019. That is not due to a surge of patient population affected by these pathologies but reflects the drop in elective procedures.Due to the reduced availability of operating theatres and the restricted hospital policy admission criteria, the limited numbers of staff on duty were sufficient in both hospital to cover all the activities.The data qualitative analysis showed a similar decrease in both units about in-patient and day surgery cases and a statistically significant difference in workload between the units concerning the outpatient surgery and the referrals.This reduction in health services had a higher impact in PU1, where some of the anaesthetist staff and intensive care beds were recruited for COVID-19 patients. Another reason for this difference is that patients requiring referrals or outpatient surgery are more apt to avoid COVID-19 hospital for fear of nosocomial transmission and, accordingly, ISG endured a lesser drop in these activities.Procedures that are delayed until elective surgery because deemed safe include basal cell carcinoma removal, secondary breast reconstruction, post-bariatric surgery, regenerative medicine, hand surgery and electrochemotherapy for the treatment of cutaneous and non-cutaneous cancer.Fuertes described the impact of COVID-19 pandemic in Spanish plastic surgery units on twelve plastic surgery unit across Spain, investigating on different effects of the pandemic: team members schedule reduction, variation in type and number of surgical procedure, etc. Fuertes results are comparable to ours in respect to the drastic reduction in overall surgical procedures (in-patient and outpatient) and consults, with a prevalence of oncologic case and a postponement of elective surgical activity. In this report, one hospital only, geographically located in a mildly affected pandemic area, declared to have maintained its usual activities. Staff policy reductions were applied also in Spain, with effects on increase of shifts numbers per consultants.At present, 6 weeks after the lockdown began, there is no scheduled date yet to plan the return to full activities in both COVID-19 and non-COVID-19 hospitals, with the next national government guidelines expected on 19 May. As a result, some patients could be damaged because of an undetected worsening of a long-standing lesion while in waiting list for planned elective surgery. Other surgical specialties are facing the same problem, due to the restriction in elective surgery procedures , 16. EmeThis is a preliminary study that evaluates the current situation in Italian plastic surgery units amid the COVID-19 outbreak. The decrease in procedures has relevant economic implications not to be underestimated. We are now working on guidelines in the event of similar future scenarios since, to date, we are not able to predict the foreseeable events.


Coronavirus disease 2019 (COVID-19) is a respiratory viral illness caused by the novel severe acute respiratory syndrome coronavirus 2. It is known to cause severe illness in certain patients, who develop acute respiratory distress syndrome (ARDS) often requiring intubation and mechanical ventilation adding to significant morbidity and mortality. Tocilizumab is an interleukin-6 inhibitor that has shown promise in improving outcomes in patients with COVID-19. It is usually administered to patients with severe COVID-19 who develop ARDS. We present three cases of COVID-19 where the patients were admitted to the hospital for observation and were found to be worsening clinically. They were believed to be developing ARDS, and intubation and mechanical ventilation were anticipated. Tocilizumab was administered in the early phase of the disease before intubation. Patients improved clinically and ultimately did not require intubation. Our findings suggest that early use of tocilizumab might be beneficial in preventing clinical deterioration and intubation in select COVID-19 patients. We present three cases of COVID-19 where the patients were worsening based on clinical as well as laboratory parameters and were given TCZ early in the disease course. They were believed to be heading towards the development of acute respiratory distress syndrome (ARDS) but ultimately did not require intubation and mechanical ventilation.The world is currently experiencing a coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A recent Chinese report suggested that of the multitude of COVID-19 cases, about 14% are severe and 5% are critical [Case 12) was 93% on room air. Laboratory results were as shown in Table A 55-year-old male presented to the emergency room with complaints of worsening shortness of breath. He had contacted his physician 11 days ago complaining of low-grade fever and nasal congestion and was tested for COVID-19. On arrival to the emergency room, he was hemodynamically stable and his oxygen saturation , and certain patients who clinically stabilized after TCZ had pre-TCZ IL-6 levels similar to those who died . However, the study reported that the three patients who died were critically ill at the time of administration of TCZ . The finIn our study, the three patients were aged 53 to 64 years. All three of them were deemed mild-moderately ill initially and received full doses of hydroxychloroquine  and azithromycin (standard dosing of 500 mg once a day for five days) except the first case. They were relatively doing well on admission but began to quickly deteriorate clinically, with inflammatory markers uptrending. The IL-6 levels were low on admission for cases 1 and 2, while for case 3 it had begun to downtrend. After the administration of TCZ, there was laboratory and clinical improvement in the patients’ conditions. The need for intubation and mechanical ventilation was avoided and they were soon discharged from the hospital.Limitations of our study include small sample size, lack of control group, and publication bias. Further studies might help confirm our observation, in which case early TCZ administration might help improve patient morbidity and mortality and healthcare costs associated with ICU admission, mechanical ventilation, and prolonged hospital stay.Our experience with these patients suggests that early intervention is useful in COVID-19 patients. Patients who are found to be worsening based on clinical and/or laboratory parameters might benefit from the early administration of TCZ. Further studies are needed to shed more light on this area.


Previous studies have postulated a causal role of patent foramen ovale (PFO) in the aetiology of embolic stroke in the general population. We hypothesised that the presence of concomitant PFO and atrial fibrillation (AF) will add incremental risk of ischaemic stroke to that linked to AF alone.We analysed data on 3069 consecutive patients  undergoing transoesophageal echocardiography-guided electrical cardioversion (ECV) for AF between May 2000 and March 2012. PFO was identified by colour Doppler and agitated saline contrast study. All patients were followed up after ECV for first documentation of ischaemic stroke. Outcomes were compared using Cox regression models.The prevalence of PFO was 20.0% and the shunt direction was left-to-right in the majority of patients (71.4%). Patients with PFO had a higher frequency of obstructive sleep apnoea  and higher mean peak left atrial appendage emptying velocity  compared with those without PFO. Otherwise, baseline characteristics were similar between groups. During a mean follow-up period of 7.3±4.6 years, 214 patients (7.0%) had ischaemic stroke. Multivariable analysis showed no significant association between PFO and ischaemic stroke ). PFO shunt direction was strongly associated with stroke: HR, 1.91 (95% CI 1.16 to 3.16) for right-to-left shunt and HR, 0.58 (95% CI 0.36 to 0.93) for left-to-right shunt.The presence of concurrent PFO in this largely anticoagulated group of patients with AF was not associated with increased risk of ischaemic stroke. The literature suggests that the presence of a patent foramen ovale (PFO) may have a role in the pathogenesis of cerebral and systemic embolism ostensibly because of paradoxical embolisation from sources within the venous circulation across the atrial right-to-left shunt.Atrial fibrillation (AF) is also a condition that is linked to ischaemic stroke. Yet, it is not known whether the coexistence of PFO and AF has incremental impact on the risk of ischaemic stroke compared with either condition alone.Although previous studies have postulated a causal role of PFO in the aetiology of embolic stroke in the general population, in the present study, the presence of PFO in patients with AF was not associated with embolic risk beyond those with right-to-left shunt and other established risk factors in this predominantly anticoagulated AF population. Large-scale studies are needed to further examine the impact of PFO and shunt flow direction on clinical outcomes in AF patients.The presence of concurrent PFO does not increase the risk of ischaemic stroke in patients with AF, mainly due to shunt flow at baseline (unprovoked) being directed from left-to-right in the majority of patients with AF.This study’s finding of no association of PFO with stroke in patients with AF suggests that in patients with no competitive stroke risks, adequate oral anticoagulation with or without concurrent antiplatelet therapy may suffice to mitigate the purported PFO-stroke association.Patent foramen ovale (PFO) is a common remnant of the foetal circulation that is found in about 25% to 30% of the general population.6–8Similarly, atrial fibrillation (AF) is a condition that is also linked to ischaemic stroke.We analysed prospectively collected data on all patients who underwent their first transoesophageal echocardiography (TEE)-guided electrical cardioversion for persistent AF at the Mayo Clinic between May 2000 and March 2012 (n=3329). Patients were excluded if they had a history of congenital heart disease, moderate or greater mitral stenosis, mitral valve surgery or no documented assessment of interatrial shunting (n=260). A total of 3069 patients comprised the study population.We did not directly include patient and public involvement (PPI) in this study, but the database used in the study was developed with PPI and is updated by a committee that includes patient representatives.All patients underwent TEE immediately before electrical cardioversion to exclude atrial thrombus, according to a previously described protocol.interatrial septum seen on colour flow Doppler and/or the appearance of microbubbles in the LA or LV within three cardiac cycles after opacification of the right atrium with intravenous injection of agitated saline either at rest or after cough, and/or Valsalva release.A PFO was defined as shunting of blood across the The primary outcome was ischaemic stroke, determined on the basis of results of radiographic examination, including MRI or CT scan or by physician decision after thorough chart reviews. Stroke outcomes were verified from the health records by cross reference with available administrative databases and outside records, when possible.2DS2-VASc score , diabetes mellitus, prior stroke or transient ischaemic attack (doubled), vascular disease, age 65 to 74, female), mean left atrial appendage (LAA) emptying velocity, LAA thrombus, mitral regurgitation (≥moderate) and patent foramen ovale. For assessment of the impact of PFO shunt directionality on the risk of stroke, in lieu of patent foramen ovale, the variables ‘PFO with right-to-left shunt’ and ‘PFO with left-to-right shunt’ were tested separately versus no PFO. For each variable, HR and 95% CI were computed. For proportional hazards models, assumptions were tested by analysing main effects and product terms of covariates and time factor transformed to logarithmic scale. Data for ties were approximated using the Efron method. All tests of significance were two-tailed, and an α level of 0.05 was considered the threshold for statistical significance. All statistical analyses were performed using SAS software V.9.4 .Continuous variables are presented as means±SD and median (IQR), as appropriate and categorical variables as counts and percentages. Comparisons between groups with and without PFO were performed using the t-test for continuous variables and χ2 test for categorical variables. Kaplan-Meier survival analyses with log-rank tests were used to estimate cumulative probabilities of ischaemic stroke on the basis of all available follow-up data among PFO and non-PFO groups. Patients who did not experience the event of interest (ischaemic stroke) during follow-up were censored on the follow-up end date or death. A time-dependent Cox proportional hazard regression model was used to estimate the independent association of PFO and other predictors with ischaemic stroke based on clinical variables at the time of TEE-guided cardioversion. Assessment of prognostic variables was first performed by univariate analysis and baseline covariates with a p value ≤0.10 were included in the multivariable model. The potential confounding variables included in the multivariable regression model were CHA2, p=0.09). Otherwise, baseline characteristics including age, sex, prior history of stroke , CHA2DS2-VASc score, left ventricular ejection fraction, duration of AF, oral anticoagulation (OAC) therapy and antiplatelet therapy were similar between the two groups.Baseline characteristics of the patient population are presented in Cardioversion success rate was not different between patients with PFO and those without .2DS2-VASc score ), and LAA thrombus )  patients had ischaemic strokes. In the approximately 10% of patients who were not discharged on oral anticoagulation, there were 3/28 strokes in the PFO group versus 21/186 strokes in the no-PFO group, p=0.10. Kaplan-Meier survival analysis showed no significant difference in the probability of stroke-free survival between patients with and without PFO (log-rank p=0.24) . Multivao 4.45)) .Since the PFO shunt flow direction was observed to be left-to-right in the majority of this AF cohort, we also performed multivariate Cox regression analysis to examine the impact of PFO directionality on the risk of stroke. After adjusting for variables that were significant in univariate analysis, PFO shunt direction had an independent impact on the risk of stroke: ; left-to-right, HR: 0.58 (0.36 to 0.93) . Kaplan-2DS2-VASc score, LAA thrombus, in addition to shunt flow direction were independently associated with ischaemic stroke, (3) unprovoked left-to-right shunting at the atrial level predominated at baseline and had a protective effect against stroke in patients with AF while right-to-left shunting was associated with an increased risk of stroke in patients with AF.To our knowledge, this is the first study to date to assess the incremental effect of PFO on the risk of adverse cerebrovascular events in patients with AF. In this study of patients with AF referred for TEE-guided electrical cardioversion, the principal findings are (1) that the presence of a concurrent PFO does not increase the risk of ischaemic stroke in patients with AF, (2) only traditional risk factors such as CHAThe prevalence of PFO in the general population has been estimated to be 25% to 33%.et alet alThe scientific literature is discordant on the relationship between PFO and ischaemic stroke. Although prior studies have shown an association of PFO with stroke in young patients without identifiable cause,et alBy contrast, Homma It must be emphasised that PFO-related shunt directionality may play a major role in the risk of stroke. Prior studies have shown that patients with cryptogenic stroke have larger PFO and more extensive right-to-left shunt flow than patients with stroke of determined cause.10 11 19After birth, the foramen ovale closes functionally as pulmonary vascular resistance decreases and allows pressure in the LA to exceed that in the right atrium. A similar process appears to manifest in the elderly due to changes in loading conditions.21Previous studies have shown that treatment of PFO with OAC therapy may mitigate the PFO-stroke association.27 28In the current study, the finding of no association of PFO with stroke in patients with AF suggests that adequate OAC with or without concurrent antiplatelet therapy may suffice to mitigate the purported PFO-stroke association. Although OAC is a physiologically attractive medical therapy to prevent recurrent stroke in patients with a PFO, it is not clear whether PFOs detected incidentally in patients without prior history of embolic events comprise an indication for preventive treatment. The more interesting question of whether a PFO may increase the stroke risk in AF patients who are not on anticoagulation could not be addressed by this study.2DS2-VASC score and were therefore equally likely to continue OAC therapy during follow-up.Our data are based on a single-centre experience, and a number of limitations should be taken into consideration for a correct interpretation of results. The study was non-randomised and therefore we cannot preclude the presence of unidentified confounders. However, the study data were collected prospectively from both groups, and all the TEE-guided electrical cardioversions were performed in the same time period, therefore, confounding factors such as advances in technology and operator experience were eliminated. Although both groups were similarly studied by TEE with the use of colour Doppler and saline contrast imaging, clinical risk factors that could potentially enhance the effect of PFO on the risk of paradoxical embolism, such as PFO size,The presence of PFO in patients with AF was not associated with embolic risk beyond those with right-to-left shunt and other established risk factors in this predominantly anticoagulated AF population. Large-scale studies are needed to further examine the impact of PFO and shunt flow direction on clinical outcomes in AF patients.


Background and objectiveSurgical site infections (SSI) are the most common healthcare-associated infections in low- and middle-income countries associated with substantial morbidity and mortality and impose heavy demands on healthcare resources. We aimed to study the microbiological profile of SSI pathogens and their antibiotic-resistant patterns in a tertiary care teaching hospital serving mostly rural populationMethodsA prospective, hospital-based cross-sectional study on pathogen profile and drug resistance was conducted from January 2015 to December 2016. Study subjects were the patients who developed signs of SSI after undergoing surgical procedures at three surgical wards . The selection of the patients was based on CDC Module. Standard bacteriological methods were applied for isolation of pathogens and antibiotic-susceptibility testing based on CLSI  guidelines.ResultsEscherichia coli (22.4%) and Klebsiella species (20.6%) were the predominant isolated bacteria followed by Staphylococcus species (18.4%), Pseudomonas species (12.3%), and Enterococcus species (6.6%). Gram-negative bacteria (GNB) were highly resistant to ampicillin (90.1%) and cefazolin (85.9%). High resistance was also observed to mainstay drugs like ceftriaxone (48.4%), cefepime (61%), amoxycillin-clavulanic acid (43.4%), and ciprofloxacin/levofloxacin (37.7%). Among the Gram-positive cocci, Staphylococcus aureus showed 85-96% resistance to penicillin and 65-74% to ampicillin. But GPCs were relatively less resistant to quinolones (16-18%) and macrolides (21.5%). S. aureus was 100% sensitive to vancomycin and clindamycin but vancomycin-resistant Enterococci was encountered in 3/15 (20%) isolates.Out of 518 enrolled subjects, 197 showed growth after aerobic culture yielding 228 pathogen isolates; 12.2% of samples showed polymicrobial growth. ConclusionGNBs were responsible for more than two-thirds of aerobic-culture positive SSI and showed high resistance to the commonly used antibiotics thus leaving clinicians with few choices. This necessitates periodic surveillance of causative organisms and their antibiotic-susceptibility pattern to help in formulating hospital antibiotic policy. The antibiotic stewardship program is yet to be adopted in our hospital. Modern surgery has proved to be a great boon to mankind which took its roots in the nineteenth century after Lister introduced the aseptic treatment of wounds. Following the discovery of antibiotics in the twentieth century, it was further revolutionized, when complicated, life-saving, and reconstructive surgeries became possible. But following the emergence of drug-resistant organisms, surgical site infections (SSI) posed a major challenge to the advancement in the surgical field.An SSI is an infection that occurs after surgery, in the part of the body where the surgery took place, within 30 days of operation or after one year if an implant is placed ,2. It caSSIs are the most frequent of all healthcare-associated infections (HCAI) in low- and middle-income countries (LMICs) and second most frequent in Europe and the USA and are a major contributor to morbidity and mortality due to HCAI ,4. The pThe objectives of the study were to show the distribution of SSI in a tertiary care center of northeast India serving mostly rural population of lower Assam, over a two years period; and to study the microbiological profile of SSI pathogens and their antibiotic-resistant patterns, isolated from three surgical wards.This is a hospital-based cross-sectional study, conducted over a period of two years from January 2015 to December 2016 at a tertiary care teaching hospital. The study was approved after it was ethically reviewed by the Institutional Ethics committee of our institute . All surgical patients admitted in the Department of General Surgery, Obstetrics & Gynecology, and Orthopedics department, who had been operated on during the study period and had developed any signs of SSI during the period of hospitalization was considered to be eligible for the study. Any patients who had presented the clinical signs of SSI like purulent drainage from the superficial incision, developed localized pain or tenderness, localized swelling, erythema, malodor or heat, or had developed fever within 30 days of surgery were included in the study  study evaluating the determinants and predictors that leads to the development of antibiotic resistance and strategies to control them is necessary to determine their impact on patient outcomes.Despite the increased use of minimally invasive surgery and enhancement of infection control practices in surgery, SSI contributes to a substantial burden of morbidity and mortality. The emergence of gut bacilli as the predominant causative agent of SSI is indicative of the need for effective infection-control practices. A paradigm shift of bacteriological profile from Gram-positive bacteria to multidrug-resistant Gram-negative bacilli is a great threat to patient outcome and a major hindrance to progress in the field of surgery. Knowledge of the microbiology of surgical infections and regular surveillance with the feedback of appropriate data to surgeons can be an important component of strategies to reduce SSI risk.


Background: Sepsis is a life-threatening condition associated with an exacerbated production of both pro- and anti-inflammatory cytokines that can promote a hyperactive response to infection or induce immunoparalysis. Data regarding the immune response to sepsis in cats are scarce. Establishing the profiles of cytokines and chemokines in feline sepsis to characterize the nature of the immune responses to sepsis might enable individualized treatments to be developed and targeted.Objective: To evaluate the cytokine and chemokine network in cats with sepsis and septic shock, and to investigate the associations of these analytes with disease severity and outcome.Methods: Blood samples prospectively collected at presentation of cats with sepsis and septic shock to two veterinary teaching hospitals were analyzed. Forty healthy cats were included as controls. A 19-plex feline cytokine/chemokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Dunn's post-hoc correction for multiple comparisons. Cytokine concentrations were compared between survivors and non-survivors with the Mann-Whitney U test. Odds ratios were calculated using logistic regression. A multivariable logistic regression model for prediction of septic shock was constructed.Results: The study enrolled 35 septic cats. Many cytokines were undetectable in both sick and healthy control cats and were excluded from subsequent analyses. Comparisons of cytokine concentrations among healthy controls, cats with sepsis (n = 12) and cats with septic shock (n = 23) revealed that sick cats (sepsis or septic shock) had significantly higher plasma concentrations of IL-6, IL-8, KC-like, and RANTES compared to healthy controls. The combination of MCP-1, Flt-3L, and IL-12 was predictive of septic shock. None of the cytokines analyzed was predictive of outcome in this study population.Conclusion: Plasma concentrations of IL-6, IL-8, KC-like, and RANTES are increased in cats with sepsis and may play important roles in pathogenesis. Multivariable modeling suggested that analysis of cytokines might aid differentiation of septic shock from sepsis. None of the cytokines analyzed was predictive of outcome. Measurement of these cytokines might enable future studies to better diagnose and characterize feline sepsis and septic shock. The inflammatory response in sepsis involves leukocyte activation through the recognition of pathogen and damage associated molecular patterns by Toll-like receptors and the subsequent production of pro- and anti-inflammatory cytokines . These sRecently the importance of sepsis-induced immunoparalysis in the morbidity and mortality of sepsis has been recognized . In humaImmunophenotyping data characterizing sepsis are scarce in veterinary medicine and are predominantly available for dogs –13. RecoRecently, the advent of multiplex technology has increased the ability to screen for multiple biomarkers of systemic conditions. Multiplex assays are able to simultaneously and rapidly measure a wide variety of immunologically active proteins in small volumes of biological samples. Feline-specific multiplex assays have recently been used to measure cytokines in serum and plasma samples from cats affected by heterogeneous diseases, idiopathic cystitis and degenerative joint disease –22, and The evaluation of cytokines and chemokines profiles in cats with sepsis and with septic shock may offer novel insights into the immune pathways of this syndrome and identify potential non-invasive biomarkers to diagnose, prognosticate and predict the therapeutic response of the disease. The aims of the current study were to describe the cytokine and chemokine network in cats with sepsis and septic shock using a commercially available multiplex magnetic bead assay and to investigate the associations of these analytes with disease severity and outcome. It was hypothesized that concentrations of pro- and anti-inflammatory cytokines in cats with sepsis and septic shock would differ from those of healthy cats, and that these concentrations would correlate with sepsis severity and prognosis.Data for the current analysis are a subset of the data collected for studies on the characterization of sepsis and septic shock in cats prospectively enrolled between 2016 and 2019 at the veterinary teaching hospitals at the University of Bologna, Italy and Cornell University, Ithaca NY. These studies were approved by the respective local Institutional Animal Care and Use Committees. Respective primary clinicians determined all aspects of patient management. The study population of 35 cats  represents 17% (9/54) of the cats with sepsis hospitalized at Cornell University during the study period and 15% (26/176) of the cats with SIRS or sepsis hospitalized at the University of Bologna during the study period.Cats were diagnosed with sepsis if at least 2/4 SIRS criteria were satisfied , and if Forty healthy privately-owned cats were enrolled as controls with informed owner consent. These cats were eligible if they had no history or evidence of recent or chronic medical conditions, and were classified as healthy based on history, physical examination, complete blood count and serum chemistry results.full and APPLEfast) scores as previously described . Blood gas and electrolyte analyses and blood lactate measurement were performed using point-of-care analyzers . Complete blood count and serum chemistry analyses including serum amyloid-A (SAA) evaluation were performed using automated analyzers . Patient data were used to calculate the feline Acute Patient Physiologic and Laboratory Evaluation  was used to measure 19 cytokines as previously described . AnalyteU test, Kruskal Wallis test with Dunn's correction for multiple comparisons) were used to compare cytokines between different groups . Logistic regression and construction of receiver operating characteristic (ROC) curves was performed to calculate odds ratios and confidence intervals for prediction of disease status. Multivariable logistic regression was performed to identify combinations of cytokines that could differentiate septic shock from sepsis. Potential predictor variables were chosen based on univariate analyses. All potential predictors were simultaneously entered into the model to maximize predictive ability. Classification tables were used to assess model accuracy. Calibration of the final model was determined using the Hosmer–Lemeshow goodness-of-fit (model rejected if P < 0.05) and model utility assessed by calculation of the Nagelkerke R2 value. Multicollinearity was assessed by calculation of the variation inflation factor (VIF), with values <2.5 determined to be acceptable. The ability of the final model to discriminate the outcome was determined by calculating area under receiver-operating characteristic curves (AUROC). Statistical analyses were performed with commercial software . Alpha was set at P < 0.05.Prior to test selection, data were assessed for normality with the D'Agostino Pearson test. Descriptive statistics were calculated and expressed as median (min-max) or mean ± standard deviation. Non-parametric statistics (Mann-Whitney-n = 7), septic peritonitis (n = 7), bite wounds (n = 6), feline panleukopenia (n = 4), pyelonephritis (n = 4), pyometra (n = 4), bacterial cholangitis (n = 2), abdominal abscess (n = 1). Twenty-one cats survived to hospital discharge, while 14/35 cats died or were euthanized, equivalent to an overall case fatality rate of 40%. Descriptive statistics for selected clinical and clinicopathological variables in the study population are summarized in The study enrolled 35 septic cats and 40 controls. Among the septic cats, there were 33 domestic shorthaired cats, 1 Bengal and 1 Siamese. There were 12 male neutered cats, 5 male intact cats, 10 spayed female cats, 8 intact female cats. The median age was 3 years (0.3–16), and the median body weight was 3.9 kg (0.7–7.3). The median number of SIRS criteria identified upon admission was 3  were undetectable in all samples  and were excluded from subsequent analyses.Comparisons of analyte concentrations among healthy controls, cats with sepsis and cats with septic shock revealed that sick cats (both with sepsis and septic shock) had significantly higher plasma concentrations of IL-6, IL-8, KC-like, and RANTES compared to healthy controls . No otheP = 0.370, suggesting the model was well-fitted. The Nagelkerke R2 value was 0.612, suggesting the model explained most of the variation in the data.Calculation of odds ratios  and consComparisons between survivors and non-survivors were only performed for IL-6, IL-8, KC-like, and RANTES because a significant difference between healthy and sick cats was documented only for these four analytes. No significant relationships between outcome and any of these cytokine concentrations were observed .Cytokines directly or indirectly affect every tissue in the body and play multiple roles integral to host defense against infection. The present study aimed to describe the cytokine and chemokine network in cats with sepsis and septic shock and to investigate the associations of these analytes with disease severity and outcome. Various proinflammatory cytokine concentrations were significantly different between healthy cats and those with sepsis and septic shock, but none of these cytokines was predictive of outcome in these patients. Specifically, IL-6, IL-8, KC-like, and RANTES were the biomarkers that were most discriminating for sepsis in cats.IL-6 is a multifunctional cytokine produced by various cells, that has both pro- and anti-inflammatory activity and is involved in a multitude of immune responses. In the early phase of sepsis, IL-6 is rapidly expressed and its concentration remains increased for a prolonged period compared to other inflammatory mediators. This makes it a potentially useful biomarker of systemic inflammation , 18, 26.The chemokine IL-8, also called chemokine (C-X-C motif) ligand 8 (CXCL8), is a major chemotactic factor in acute inflammation . It is rThe chemokine RANTES, also known as chemokine (C-C motif) ligand 5 (CCL5), is involved in leukocyte migration. Inverse correlations have been reported between its circulating concentrations and mortality in sepsis in humans, suggesting it has a beneficial proinflammatory role in infection states . KeratinAlthough IL-6, IL-8, KC-like, and RANTES acted as inflammatory mediators in our population of septic cats, they had no prognostic value, and they were not reflective of sepsis severity. Whether the lack of prognostic significance is true in feline sepsis, or it has been biased by the heterogeneity of underlying causes for sepsis and different immune status and immune phenotypes of enrolled patients, remains a question to be addressed in future studies. It is possible that the lack of correlation between cytokine concentrations and disease severity may reflect limitations of the SIRS criteria and may question the validity of feline SIRS criteria to for identification and characterization of sepsis in cats. The present study used the presence of at least 2/4 SIRS criteria to identify eligible cats for this study because they enabled swift, simple and objective identification of the potential presence of systemic inflammation. The choice to enroll cats using less stringent criteria in the present study [2/4 rather than 3/4 as proposed by Brady et al. ], was baThe present study defined septic shock based on the presence of persistent hyperlactatemia or the need for vasopressors to support blood pressure. The vasopressor requirement is consistent with the prevailing definitions of septic shock in veterinary and human medicine , 23, whiIndividually, the concentrations of Flt-3L, IL-12 and MCP-1 were moderately discriminant for septic shock in the present population. In a multivariable model, the combination of these three cytokines differentiated sepsis from septic shock in over 91% of cases. These three cytokines have distinct but linked physiologic roles. MCP-1 is a member of the chemotactic cytokine family that functions to recruit monocytes and modulate T-cell function ; Flt-3L Interestingly, >50% of cats had one or more measured concentration that was lower than the LLD for 15 of the 19 cytokines for healthy controls, and for 11 cytokines for cats with sepsis and septic shock. This inevitably limited our evaluation of the utility of these markers and may warrant reassessment of the utility of the full 19-plex assay in cats. As the present study involved an exploratory analysis of cytokines in feline sepsis it was desirable to measure the maximum number of cytokines, similar to other exploratory studies in related fields , 48. AddThis study has some limitations that should be acknowledged. The sample size was large for feline sepsis studies, but remains relatively small and was heterogeneous in terms of sepsis etiologies. Although euthanasia was performed only after clinical perception of moribund condition or end-stage disease  the potential impact of euthanasia should be considered a possible source of bias, particularly with regards to the outcome analyses. Additionally, although the sampling was performed prospectively using standardized procedures for sample collection and storage, minor variations in sample processing  could have negatively affected analytes concentrations. The intrinsic limitations of the multiplex assay should be considered, as it is conceivable that concentrations of other analytes could have been significantly different between groups, but remained undetected because of the limited assay sensitivity. In this regard, the substitution of out-of-range concentrations with the respective LLD reported by the assay could have biased statistical outcomes , 51. SimTo conclude, this is the first study describing the cytokine and chemokine network in cats with both sepsis and septic shock. The cytokines IL-6, IL-8, KC-like, and RANTES appear to be important for the pathogenesis of both sepsis and septic shock in cats, but these biomarkers are not discriminating for sepsis severity or outcome. Concentrations of the other cytokines investigated suggest they may not be useful for the assessment or investigation of sepsis in cats. Immune paralysis and leukocyte hyporeactivity could have been responsible for the low concentrations of these inflammatory mediators in our study population, but assay-related problems cannot be ruled out. Further prospective studies are needed to evaluate cytokine profiling in specific subsets of feline sepsis, and could contribute to immunophenotyping of septic individuals according to sepsis severity and underlying disease.All datasets generated for this study are included in the article/supplementary material.All samples analyzed in this study were collected from cats managed at the two participating veterinary teaching hospitals  as part of studies approved by the local Institutional Animal Care and Use Committees (IACUC), and undertaken under written informed client consent . Healthy privately owned cats were enrolled as controls with local Institutional Animal Care and Use Committees approval and written informed client consent (Cornell IACUC 2014-0052).RT assisted with the study design, collected and analyzed the data, and co-wrote the manuscript. GM, CA, DL-P, and MG collected and analyzed the data, and edited the manuscript. RG designed the study, collected and analyzed the data, and co-wrote the manuscript. All authors contributed to read and approved the final 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.


The COVID-19 pandemic has rapidly spread across the world and now affects more people within the United States than any other country. New York City has emerged as the epicenter of the outbreak in the United States. Both locally and across the country, there is great concern in our ability to deliver appropriate medical care during this time. Radiation therapy is another essential clinical service that cannot afford to suffer prolonged delays without compromising patient outcomes. Early action and guidance are therefore critical to minimize transmission events and ensure safe and timely delivery of radiation therapy. The New York Proton Center (NYPC) is a high-volume free-standing multi-institutional proton center located in Manhattan. The purpose of this report is to describe the institutional patient experience and quantify the impact of treatment delays and interruptions over the first month of the COVID-19 outbreak. We also quantify the incidence of COVID-19 positive patients on census and provide guidance on proactive institutional policies to mitigate patient risk.  We commend Dinh et al. for their early and informative work describing the radiation therapy policy and procedural changes of the University of Washington (UW) in the Seattle-Puget Sound region during the initial stages of the U.S. COVID-19 outbreak [The New York Proton Center (NYPC) is a freestanding facility located in Manhattan. Currently, five NYPC-employed radiation oncologists and 19 partner radiation oncologists from three consortium institutions  treat 80-85 patients/day. Since the first reported COVID-19 case in New York on March 1, 2020, the center has faced many challenges maintaining safe delivery of patient care. As the impact on radiation oncology patients of the COVID-19 pandemic is yet to be quantified, we describe some of our challenges and institutional policies aimed at mitigating the spread of COVID-19 amongst our patients and detail the proportion of patients affected during the initial one-month interval.Similar to the UW, we instituted policies to minimize risks to patients, including providing patient education materials; completing daily symptom screenings of patients and close contacts; implementing rigorous sanitization measures; deferring treatment of indolent diseases; instituting telemedicine appointments, virtual meetings, restricting visitors, spacing-out treatment times, and closing patient waiting rooms. Patients in subacute care or nursing facilities were no longer eligible for treatment until discharged and we utilized hypofractionation to shorten treatment schedules per expert-consensus, when feasible -5. LastlBased on increasing personnel losses due to illness and the need to optimize safety for all of our patients and staff, we deferred treatment of COVID-19-positive patients. By March 19, 2020, we instituted a new patient policy requiring symptomatic patients to obtain a negative COVID-19 test before treatment could resume/initiate, and COVID-19-positive patients must be serologically cleared prior to resuming. Patients with high-risk exposure are immediately quarantined and must either remain asymptomatic for a minimum of 10 days prior to treatment  and/or obtain a negative COVID-19 test, if available. Treatment starts are delayed to accommodate these requirements unless urgent circumstances are present, determined on a case-by-case basis.Institutional Review Board approval was obtained for the evaluation of the following patient-level data. From March 1, 2020 to March 31, 2020, 137 patients received, or underwent simulation to receive, radiotherapy at NYPC. Of these 137 patients, 15 (11%) were monitored for concerning symptoms or high-risk exposures . The most common scenario was the development of new symptoms prior to simulation. Of these patients, all but one has since been cleared and rescheduled, resulting in a median delay of 4.5 days (range 0-32 days). The one patient not yet cleared was confirmed COVID-19 positive and treatment remains on hold. Of the six patients on-treatment requiring further evaluation (40%), five suffered treatment interruptions, three of whom are now rescheduled to resume after a median delay of four days (range 0-5 days). Three remain indefinitely delayed, including two who were confirmed COVID-19 positive and one who terminated treatment early with two fractions remaining.Given the proportion of patients who developed symptoms prior to initiating treatment, our experience supports the recommendation for rigorous screening in advance of treatment initiation as well as between appointments . In addition, with increasing reports of asymptomatic transmission, routine inspection of lung imaging on simulation and cone-beam CT images is strongly encouraged -7. PatieWe also have an average of five to seven pediatric patients on-treatment requiring daily sedation with anesthesia. UW’s anesthesia policy included airborne precautions due to reports of aerosol transmission . NYPC inLastly, we assessed the utilization and sanitization procedure of our respiratory motion management system, SDX . Similar to UW and Thomas Jefferson University, we developed a new and stringent disinfecting protocol and encouraged the use of abdominal compression and proton repainting techniques over breath-hold whenever clinically possible -10. NYPCDespite the early implementation of measures described by the UW radiation oncology department as well as our own highly conservative policies, NYPC still had 11% of patients affected, including 3% confirmed positive for COVID-19 within the first month and one patient death. All of the delays at NYPC occurred in the second half of the month, suggesting other cities should expect and prepare for an acceleration of patient events near their projected regional pandemic peak. While most interruptions were of short duration and did not appear clinically meaningful, implementation of these strict policies likely mitigated further patient exposure and more significant treatment delays. We plan to continue to enforce and reassess our policies throughout the pandemic to balance patient safety and optimal treatment delivery.


The higher DQI-P score was associated with increased weight gain DP of 3.3 kg  after adjusting for the mother's age and household income. The DQI-P score was not associated with an increased risk of chronic energy deficiency DP and overweight–obesity at 3YPP. Thus, the diet adequacy was associated with weight gain DP but did not affect the MUAC DP and BMI at 3YPP. The DQI-P score DP was slightly better than the diet at 3YPP; however, the overall diet quality was inadequate. In conclusion, a higher DQI-P score was associated with increased weight gain DP of 3.3 kg but was not associated with other nutritional status indices in DP and 3YPP. Innovative dietary quality improvement programs are required to reduce malnutrition risk in pregnant and reproductive-age women.Dietary changes during pregnancy (DP) and post-partum are essential for women’s nutrition status and the health of their offspring. We compared the diet quality DP and at 3-year post-partum (3YPP) and assessed the relationship between maternal diet quality and nutritional status using a prospective cohort design among women in East Jakarta. In total, 107 women were recruited from the study in 2014 and followed up at 3YPP in 2018. The mid-upper arm circumference (MUAC), weight, and height were evaluated. Food consumption data were collected from repeated 24-h recalls. The validated US Diet Quality Index-Pregnancy (DQI-P) scores with eight components were calculated using the food consumption data and compared between DP and 3YPP. Associations of the DQI-P score with the MUAC and weight gain DP and body mass index (BMI) at 3YPP were analyzed using multivariable linear and logistic regression. The median of the DQI-P score DP was significantly higher than at 3YPP [35  versus 27 ;  Indonesia is among the low-middle-income countries (LMICs) suffering from a double burden of malnutrition. According to the Indonesian national health research conducted in 2018, the prevalence of child stunting is high, which is about 30.8% among under-5-year-old and 29.9% among below-2-year-old children  and having sufficient-excessive weight gain DP . Moreover, DQI-P also did not exhibit an association with the mothers not being overweight-obesity of the mothers at 3YPP , even after being adjusted for age and household income for all the associations tested. Table 6 demonstrates that the DQI-P score positively correlates with the weight gain DP . The higher DQI-P score was associated with an increase in 3.3 kg of weight gain DP but not with other nutritional status indices in those two periods. However, DQI-P was not associated with MUAC, and the risk of being overweight and obese at 3YPP , respectively.The current study found that a higher DQI-P score was associated with increased weight gain during pregnancy of 3.3 kg but was not associated with other nutritional status indices during pregnancy and at 3-year postpartum. The overall diet quality of women during pregnancy and at 3-year postpartum based on the DQI-P score calculation was insufficient to meet the recommended dietary requirement. The grain (most were white rice and flour-based food) and meal patterns were two variables that encountered the maximum score of 10 in the DQI-P calculation for the two periods, indicating adequate serving consumption of grain and frequency of meals and snacks. Diet quality during pregnancy was not associated with sufficient–excessive weight gain during pregnancy, either before or after adjustment by the age of the mothers and household income; moreover, it did not affect MUAC during pregnancy and BMI at 3-year postpartum. Although the prevalence of overweight and obesity was slightly higher at 3-year postpartum than pre-pregnancy, this study did not find a significant association between CED DP or being overweight–obese at 3-year postpartum. The higher DQI-P score will increase the weight by 3.3 kg during pregnancy after adjusting for the mother's age and household income. Indonesia's healthy and balanced diet guidelines have provided a practical recommendation for daily intake; however, the consumption was low either during pregnancy or at 3-year postpartum.The PIN study developed the DQI-P score calculation  and yiel–obesity at 3YPP. The inability to associate with overweight–obesity at 3YPP may be related to the scope of DQI-P, which fails to identify some nutrients that may contribute to positive energy balance such as red meat and sugar. The Norwegian study indicated that red meat, sugar, and sodium should be consumed in a limited amount [A Norwegian mother and child cohort study revealed that low adherence to healthy and balanced diet guidelines and recommended nutrient would increase the risk of excess weight gain, which tends to remain after pregnancy . Contrard amount . A studyd amount .The highest score achieved within this study population was from meal grain consumed and eating frequency. Conversely, insufficient intake of fruits, vegetables, and micronutrients was observed within two periods. The women in this study consumed fruits, vegetables, and iron less than 30% of the recommended amount. A possible explanation for the slightly better diet quality DP compared with that at 3YPP is the impact from the existing program of the government, family support, and special attention given DP, which resulted in better compliance with Indonesia's dietary guidelines DP. Six serving portions of grain and four portions for vegetables and fruits for pregnant women are recommended to meet the macro- and micronutrient requirements for fetal development . FurtherTo our knowledge, our study is among the limited studies examining the diet quality of women between the DP and 3YPP periods in the low socioeconomic group of developing countries. The subjects recruited in this study are representatives of the population in the low and middle socioeconomic levels in the urban setting of LMICs . This DQOverall, poor diet quality DP may increase the risk of weight gain DP. Obesity-related DP may be related to adverse birth outcomes  as well Poor diet quality is consistent in almost all components, except for the total fat that makes up ≤30% of the total energy and meal patterns. This data emphasizes the fact that serious problems existed in the adult dietary pattern, which needs to be solved with comprehensive actions. The pre-pregnancy and gestational periods need to be highlighted as modifiable factors for the mother and the children for long-term effects.Further study should include more subjects with diversed socioeconomic levels and geographical areas from urban-rural settings. Enhancement in the socioeconomic status and eating behavior of the women at reproductive age would lead to better food intake and quality of life as well as reduce risk of weight retention after pregnancy in the future.A higher DQI-P score was associated with increased weight gain during pregnancy of 3.3 kg but was not associated with other nutritional status indices in during pregnancy and 3-year postpartum. Although the overall dietary quality of women was impoverished based on the DQI-P score during pregnancy and three-year post-partum, the diet quality during pregnancy was slightly better with that at three-year post-partum. The adequacy of DQI-P components contributed to a higher score of the diet quality index in terms of grain consumption food-based and frequency of meals and snacks and was associated with weight gain DP. The DQI-P score was not related to the risk of being overweight and obese at 3YPP. Further research and actions should be conducted and taken, respectively, to spread awareness of the meal pattern that helps combat the high prevalence of overweight and obesity, which would lead to a lower incidence of NCDs in Indonesia.S1 Data(XLS)Click here for additional data file.


The review analyzes the potential advantages and problems associated with using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19. HIF prolyl hydroxylase inhibitors are known to boost endogenous erythropoietin (Epo) and activate erythropoiesis by stabilizing and activating the hypoxia inducible factor (HIF). Recombinant Epo treatment has anti-inflammatory and healing properties, and thus, very likely, will be beneficial for moderate to severe cases of COVID-19. However, HIF PHD inhibition may have a significantly broader effect, in addition to stimulating the endogenous Epo production. The analysis of HIF target genes reveals that some HIF-targets, such as furin, could play a negative role with respect to viral entry. On the other hand, HIF prolyl hydroxylase inhibitors counteract ferroptosis, the process recently implicated in vessel damage during the later stages of COVID-19. Therefore, HIF prolyl hydroxylase inhibitors may serve as a promising treatment of COVID-19 complications, but they are unlikely to aid in the prevention of the initial stages of infection. In 2019, a spike in the cases of lethal pneumonia caused by the global spread of the SARS-CoV-2 virus led to an urgent need to develop effective therapies, especially vaccines . The vir.The history of ischemic stroke treatment with drugs is discouraging because no drug can enter a lesion deprived of blood supply. The biggest difference between ischemia and hypoxia is that the former involves both oxygen and glucose (and other nutrient) deprivation, so no energy is available to activate the pro-survival genetic programs, whereas hypoxia only involves low oxygen levels. The latter case can be potentially treated with drugs activating the anti-hypoxic response at the cellular level, as the nutrients are still available. Hypoxia without glucose deprivation is exactly what happens with COVID-19. When the virus infects the body, the lung damage results in low oxygen tension/insufficient oxygen in the blood, but as long as the heart is functioning, the blood’s access to the tissues is uncompromized. This peculiar characteristic of COVID-19 leads to a hypothesis stating that activation of the intrinsic anti-hypoxic program non-pharmacologically, with ischemic preconditioning, , or pharLow oxygen levels trigger a general organismal response due to the inhibition of various oxygen-dependent enzymes. It took more than 2 decades of intense research to fully appreciate the role that these enzymes play in cell fate. These oxygenases are either iron or FAD dependent, and they control the stability of various transcription factors and key proteins relevant to cell division, demethylate DNA and histones, and result in many other effects. During the early 1990’s, the stabilization of a transcription factor, a hypoxia inducible factor (HIF) that switched the cell from aerobic to anaerobic glycolysis, was documented in hypoxia . However2) and a stable β-subunit . Hydroxylation of HIF-1α, Pro564 and/or 402 is required for its interaction with the von Hippel-Lindau (VHL) tumor suppressor, leading to the formation of a complex that ubiquitinates HIFα and sentences it to subsequent proteosomal degradation , a bacterial siderophore and multidentate iron chelator used to treat iron poisoning, stabilizes HIF-1  and help effects , and DFO effects . It is i effects . Similar effects . Linden  effects . BesidesIn addition to HIF PHD inhibition, the compounds of the first two groups can also indirectly affect the replication apparatus of the SARS-CoV-2 virus, as supposed in the review on the use of iron chelators . SpecifiThe third group of inhibitors exploits the fact that HIF PHD belongs to the family of α-ketoglutarate-dependent non-heme iron dioxygenases. Therefore, structural analogs of α-ketoglutarate will work as enzyme inhibitors. The substitution of α-ketoglutarate as a way to inhibit HIF PHD is more specific than iron substitution or chelation since iron is involved in many cellular processes, and the side effects from its displacement or chelation could be deleterious. The human genome contains more than 60 α-ketoglutarate dependent oxygenases, with only some of those being well characterized. Currently, the other best known members of this family include enzymes directly engaged in epigenetic modifications, histone demethylase and cytosine demethylase (TET-enzyme). The inhibition of HIF PHD by substituting α-ketoglutarate might also lead to many off-target effects. The most studied representatives of this group of inhibitors are dimethyloxalylglycine (DMOG) and the compounds developed by FibroGen  and Akebia (“Vadadustat” ) for theDimethyl oxalylglycine (DMOG) is one of the most widely used HIF PHD inhibitors in laboratory research. DMOG easily enters the cell, where it is converted to N-oxalyl glycine by the action of carboxyl esterases . The incRoxadustat (FG-4592) belongs to the group of compounds mimicking the binding mode and therefore, competing with α-ketoglutarate for the HIF-PHD active site. This drug is undergoing clinical trials for the treatment of anemia in patients with chronic kidney insufficiency . RoxadusVadadustat, like Roxadustat, successfully passed clinical trials. However, the drug is significantly less characterized with respect to potential applications other than the treatment of anemia. The structural class of Vadadustat and Roxadustat is the same as for collagen prolyl-4-hydroxylase (CP4H) inhibitors which were patented more than 20 years ago . The simA number of HIF PHD inhibitors of the same class were developed by the other companies. The mode of binding remained essentially the same as for Roxadustat and Vadadustat, but it had a different scaffold for the active site iron binding. Daprodustat (GSK1278863) was developed by GlaxoSmithKline and passed clinical trials . Desidusin vivo hemorrhagic stroke models, likely working by suppressing the pro-death functions of ATF4  to overcome the competition from 1 to 2 mM intracellular α-ketoglutarate . The fou of ATF4 , a plaus of ATF4 . 8-Oxyqu of ATF4 . This fi hypoxia . The tes hypoxia . However hypoxia , and the hypoxia . Later oThe general analyses of the existing investigational drugs targeting HIF PHD allow one to conclude that these drugs are worth trying in COVID-19 patients at the disease stages associated with hypoxia. These drugs launch a number of pro-survival pathways in addition to the classical HIF-pathway, since, as written above, there are multiple client substrates of HIF PHD. However, an integral effect of HIF PHD inhibitors for COVID-19 treatment is difficult to predict. First, there is some uncertainty in the pro-survival mediators stabilized or triggered by the enzyme inhibition, and second, it is due to a great variation of COVID-19 manifestations and post-infection effects. If we focus on the HIF-pathway only, as it is the best studied program launched by a HIF PHD inhibitor, some concerns will arise with respect to the initial steps of viral infection. A hypothesis on HIF activation to treat COVID-19 has been recently put forward , howeverThe first step of viral invasion is the interaction of SARS-CoV-2 with the ACE2 (angiotensin converting enzyme 2) receptor on the cell surface .Despite the fact that the data on the role of ACE2 in health and disease are growing, relatively little is known about the factors controlling its expression, and the available information is often contradictory. Correlations between clinical outcomes and the enzyme expression level on the target cell surfaces of patients from various age groups are of big interest . It is aThis fact supports the hypothesis on a plausible regulation of ACE2 expression through the mechanism of cellular response to hypoxia: an increased expression of HIF PHD leads to a down-regulation of HIF expression in the cell and, subsequently, to an increased expression of ACE2. Another piece of indirect evidence for the role of hypoxia and, accordingly, the role of HIF in ACE2 regulation, is the recently published data that showed people who live at higher altitudes had less serious complications from COVID-19 . TherefoThe next step of viral entry is the proteolytic cleavage of the SARS-CoV-2 spike protein, which contains sites for transmembrane serine protease 2 (TMPRSS2)  and furiTMPRSS2 is a target of the androgen receptor (AR), and this may explain the higher male susceptibility toward this viral infection . HIF1 isThere is no consensus on the role of HIF in the modulation of immune response and in counteracting inflammation in severe cases of COVID-19 induced injury. In the recent review, , the autRecent findings on the urokinase plasminogen activator (uPA)/uPA receptor (uPAR)system suggest its potential role as a main orchestrator of the fatal progression to pulmonary, kidney, and heart failure in coronavirus patients . PatientOne of the “bad” players in viral and autoimmune diseases is the macrophage migration inhibitory factor (MIF), a pleiotropic proinﬂammatory cytokine that mediates diverse immune responses. MIF counteracts the anti-inﬂammatory effects of glucocorticoids and plays a role in the progress of septic shock. This factor is a well-known HIF target gene and, moreover, MIF and HIF are bound into an autoamplifying feedback loop that can be interrupted by glucocorticoids (dexamethasone in particular) . The serErythropoietin (Epo), the final target of HIF PHD inhibitors that are aimed at replacing Epo IV administration with a tablet, is more than an anti-anemic drug. Epo is known to suppress proinflammatory cytokines, protect cells from apoptosis and promote wound healing. Epo receptors are expressed on a variety of immune cells, enabling Epo to directly modulate their activation, differentiation and function. Right now, researchers are investigating Epo’s ability to ease severe cases of Covid-19 and to protect patients from neurological side effects once the SARS Cov-2 virus attacks the brain. Already, the initial case studies were very positive, and researchers are currently starting a randomized clinical trial to systematically investigate the effects of Epo treatment in COVID-19 patients .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.


Since the beginning of the coronavirus disease (COVID-19) pandemic, in March 2020, the number of people infected with COVID-19 worldwide increases continuously. Brazil is being followed with great concern in the international media, as it can, very soon, be the epicenter of the pandemic. Initial surgical data suggest that patients who acquire COVID-19 in the perioperative period are prone to a higher morbidity and mortality, however, evidence in cardiac surgery is still scarce.This article aims to aggregate to the growing evidence suggesting that perioperative infection with severe acute respiratory syndrome coronavirus 2 contributes to a more morbid evolution of the case. As of May 19th, 2020, there have been 4,731,458 confirmed cases and 316,169 deaths worldwide. In Brazil, the first case was confirmed in February 26th, 2020. Currently, Brazil is being considered the future epicenter of the pandemic, with 241,080 confirmed cases and 16,118 deaths until May 19th, 2020.Since December 2019, the world is facing a unique situation: the coronavirus disease (COVID-19). COVID-19 is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), considered a pandemic since March 11As physicians are passing through real-time learning process on the management of COVID-19, patients continue to present with other medical conditions. Unstable cardiovascular disease is one of these conditions, sometimes requiring urgent treatment.-against the risk of patients being infected with SARS-CoV-2 during the perioperative period and its consequences.Physicians will have to balance the risk of delaying medical  treatment for patients with significant cardiovascular disease-associated with high mortality in COVID-19 patientsThere are few case reports of patients who underwent cardiac surgery and were diagnosed with COVID-19. The aim of this article is to draw the attention of adult cardiac surgeons and cardiologists regarding the management of patients considered for surgical procedures in the context of the current COVID-19 pandemic.A 63-year-old male patient with hypertension was admitted to the emergency room with non-ST-segment elevation myocardial infarction. Coronary angiogram showed severe multivessel coronary disease with a high syntax score (35.5). Transthoracic echocardiography showed preserved left ventricle ejection fraction and no other abnormalities. The calculated values of risk scores were: EuroSCORE II 1.62% and STS score 0.97%. Based on the recommendations of the Brazilian health government organizations at the time, preoperative screening for COVID-19 was not performed.Surgical procedure was performed 4 days after the patient’s admission. The patient underwent CABG via full sternotomy, with cardiopulmonary bypass (CPB) and myocardial protection with intermittent cold blood cardioplegia. The targeted grafts were: left internal mammary artery to the left anterior descending artery and saphenous veins grafts to two diagonal branches and an obtuse marginal branch. The right coronary territory was not grafted due to poor targets. The patient was weaned from CPB without difficulty. After completion of the procedure, the patient was transferred to the intensive care unit (ICU)-timeline in  with lymphopenia-516 lymphocytes/mm. On POD 9, he had shortness of breath and oxygen saturation of 78%. A chest computed tomography scan revealed multiple peripheral ground-glass opacities in both lungs  4, the patient developed cough and atrial fibrillation with rapid ventricular response, which was controlled with amiodarone. Laboratory tests disclosed an increase in C-reactive protein of 147.50 mg/L and 5730 leukocytes/mmth lungs . QuantitIn the COVID-ICU, he had difficulty breathing and multiple complications. The sternum became unstable and a small dehiscence of the lower segment of the sternal wound was evident, but without local signs of infection. Debridement of sternal and subcutaneous tissues plus sternal refixation and installation of negative pressure wound therapy system were performed. Concerning his sternal wound, the patient showed a remarkable evolution and, 6 days after the first procedure, he underwent reconstruction of the sternal wound with a pectoralis muscle flap. The patient presented a favorable evolution with weaning from inotropic drugs and extubation. However, a new worsening, requiring a new intubation, occurred due to secondary pulmonary infection.The patient persisted in the ICU with prolonged use of inotropes and mechanical ventilation, as well as multiple clinical complications until POD 40, when he died due to pulmonary infection and multiple organ failure.. Surgeons and cardiologists are facing a series of difficult decisions to be made, since it is necessary to balance the risk between postponing surgery in patients with significant cardiovascular disease and the risk of operating a patient in latent period of COVID-19 or acquiring nosocomial COVID-19 infection.Cardiac surgery has been particularly affected by the coronavirus outbreak since elective surgeries were cancelled and ward and ICU beds dedicated to cardiac surgery were reassigned to COVID-19 patients reported data from 34 patients who underwent different surgeries during the incubation period of COVID-19 and suggested that surgery may exacerbate disease progression, since the mortality rate in his cohort-20.6%-is higher than in surgical patients without COVID-19 as well as in COVID-19 patients without surgery. This may be related to impaired immune function and early systemic inflammatory response due to surgery.Data on surgical outcomes of patients with COVID-19 are rare. Lei et al.. It is also suggested that these patients may be more susceptible to myocardial disfunction-a possible complication of COVID-19-after surgery, especially if cardioplegic arrest is used.Patients who need cardiac surgery are likely to have a more severe presentation of COVID-19, due to their underlying cardiovascular disease, which is associated with high mortality in COVID-19. Despite the same outcome occurred in both cases, the death of our patient was due to indirect consequences-nosocomial infections-from prolonged hospital length of stay in COVID-19.Currently, data on COVID-19 and cardiac surgery results are almost inexistent; there is only one report of in-hospital infection of a patient submitted to a CABG who died in POD 9 with COVID-19 pneumonia as a presumed cause of death. Aiming to reduce perioperative morbidity, all patients should be tested preoperatively, and a positive result should elicit a Heart Team evaluation about the urgency of the case. Patients should be operated as soon as possible to reduce possible SARS-CoV-2 nosocomial infection. In this situation, some patients could be operated before the end of the period of discontinuation of antiplatelet medications.Due to the current situation, many scientific societies have published guidance statements for cardiac surgery institutions. Recommendations are based on inpatient COVID-19 load and operative capacityThis article adds evidence of a poor outcome in a lowrisk urgent CABG patient infected with SARS-CoV-2 in the perioperative period. Unfortunately, the patient was not tested preoperatively, and hence we cannot affirm that he was already infected when operated on. During COVID-19 pandemic, patients are liable to a more morbid postoperative course, reinforcing the importance of Heart Team evaluation for choosing the best treatment option, even in low-risk patients.