Comparing to Wide Midfielders, Centre Backs showed lower total , high-intensity , and sprint  distances. Sprint distance was also lower in Centre Backs vs. Strikers , and in Central Midfielders vs. both Strikers  and Wide Midfielders . The present findings highlight the physical match performance of elite Scottish players and provide useful information within the context of understanding how methods of physical development of youth soccer are implemented in different countries.The present study aimed to assess the physical match performance among senior and youth soccer players from an elite Scottish Premiership club during the 2021/2022 season. Twenty-two first team  and 16 youth players  were examined. A selection of physical match performance variables were measured using a global positioning system. Linear mixed-effect regressions revealed for all examined variables no significant differences between first team and U-18 players and no significant differences between playing level by position interaction. Across both teams, Centre Backs compared to Wing Backs, showed a 295 m ( Soccer is a physically demanding sport that is played throughout the world by a broad range of individuals . The occThe most intense periods during match-play have recently been referred to as ‘worst case scenarios’ ,7,8. ProAt the elite level, soccer is played at various age groups ranging from developing academy youth players through to senior first team players (~>18 years old). The demands of soccer may vary significantly in relation to a number of factors, such as the players’ age, the players’ competitive level, and the playing style of any given team ,15. In sAn important part of developing soccer players for elite-level competition is ensuring they are able to cope with the physical demands of senior elite-level soccer. With this in mind, it is important to fully understand the differences in required physical outputs between late-stage academy soccer U-18) and senior soccer, as suggested by a recent systematic review on training intensity in young male soccer players . This ma and seniTo date, no study has examined and compared the mean and peak physical performance characteristics in match-play of youth and senior soccer players from the same Scottish Premiership (SP) club. Historically, the SP league is known for physically challenging match-play and there has been an increasing competitive level over recent years. Examining data from different countries and leagues is vital to improve our understanding of various methods of physical development . Albeit Several physical variables have previously been reported to be critical moments in successful performance and often differentiate between high- and low-level adult players . As an eTherefore, the aim of this study was to analyze a selection of physical performance indicators in match-play of elite youth and senior soccer players from an SP club. Besides comparing the physical performance between competition levels (youth versus senior), differences between playing positions were also examined. Our hypothesis was that senior, first team players will produce higher physical match performance when compared to their U-18 counterparts. Furthermore, more attacking players will demonstrate greater high-intensity and sprint actions regardless of competitive level.p < 0.01) and mean height (p = 0.02), with higher values in first team when compared to U-18 players for both variables. The study was conducted according to the requirements of the Declaration of Helsinki and was approved by the local Ethics Committee of Sechenov University (N 22-21 dated 12 December 2021) and the SP club from which the participants volunteered [Thirty-eight professional senior and U-18 outfield soccer players from a SP club formed the sample for this study. Data from the complete 2021–2022 season highlighted 22 senior outfield players (first team squad) and 16 youth outfield players (U-18 youth squad). Data from the first and U-18 youth teams from the same SP club were analyzed for comparison between senior and youth players, and the influence of playing position between the levels was also examined. The following playing positions were examined: Centre Backs (CB), Wing Backs (WB), Centre Midfielders (CM), Wide Midfielders (WM), and Strikers (ST). Goalkeepers were excluded from the investigation due to the specific nature of their match activity and their low running demands ,28. Tablunteered . To ensun = 38) and CAS (n = 28) youth league matches for the 2021/2022 season were used in the present study, and individual players’ data were included only when that player completed a whole match. For both the first team and U-18 squads, only players having played during the 2021/2022 season at least two whole official matches, respectively in the SP and CAS youth league, were included. The total number of examined individual match performances was n = 275 and n = 217 for first team and U-18 team, respectively. All data collected resulted from normal analytical procedures regarding player monitoring over the competitive season, nevertheless, approval for the study from the club was obtained [The SP league is typically split into two distinct periods. The first phase can be subdivided into pre-season (average 4-weeks) starting mid-June and competition (25-weeks) concluding in end-December, fulfilling on average 20 official league fixtures. The second phase commences after a 3-week winter break (end-December to mid-January) and also has two definite periods consisting of pre-season (2-weeks) commencing early-January and competition (17-weeks) finishing in mid-May, completing the remaining 18 league fixtures. The Club Academy Scotland (CAS) youth league follows a similar structure to the SP, and is also divided into two phases, before and after a 5-week mid-season break (mid-December to mid-January). The youth pre-season commences mid-June (average 4-weeks) and completes 14 matches until mid-December. The second period re-starts in mid-January and finalizes at end-May completing the remaining 14 league matches. All SP , that has been previously validated . All dev2), number of very high-intensity accelerations (>+3 m/s2 with minimum duration of 0.5 s), number of very high-intensity decelerations distance (<−3 m/s2 with minimum duration of 0.5 s) [The total distance covered (m), high-intensity distance , and sprint distance  were examined based on previous studies ,38,39. Tf 0.5 s) .p < 0.05.All data are presented as the mean ± standard deviation. The analysis was carried out with the software R, version 4.2.0 . Linear mixed-effect models with random intercepts for individual players were used to assess the effects of team (first team/U-18), position, and their interaction on physical match performance data. When there was a significant effect of playing position, post-hoc Tukey comparisons were performed to check which positions were different. The differences between teams and positions were standardized by the between-subject standard deviation of each outcome variable to determine the effect size (ES). Standardized differences were evaluated as trivial (<0.2), small (0.2–0.6), moderate (0.6–1.2), large (1.2–2.0), and very large (2.0–4.0) . The staThe mean ± standard deviation values of all examined physical performance variables in first team and U-18 players divided by playing position are shown in p > 0.05) (p > 0.05) of team by position interaction. There was also no significant effect of position for explosive distance and the number of accelerations (both p > 0.05). Conversely, there was a significant effect of playing position for total distance, high-intensity distance, sprint distance, and number of decelerations. On average, total distance was lower in CB compared to WM, with an estimated difference of 1297 m , while high-intensity distance was lower in CB compared to both WM  and WB . Moreover, sprint distance was lower in CB compared to both ST  and WM , and was lower in CM compared to both ST  and WM . Finally, the number of decelerations was 36 accelerations  lower in CB compared to WB.When compared to first team players, U-18 players showed trivially to moderately higher mean values for total distance covered, high-intensity distance, explosive distance, and number of decelerations, and lower mean values for sprint distance and number of accelerations, with small differences. The estimated differences between U-18 and first team players were not statistically significant  . The linThe aim of this study was to analyze a selection of physical match performance indicators of elite senior and youth soccer players from an SP club and compare the physical match performance between competition levels (senior versus youth), and identify any differences between playing positions. There were no actual differences found between first team and U-18 players for the examined physical performance variables, while some differences were reported between playing positions.The lack of differences between both teams is the main novel finding of the present study, and to the best of the author’s knowledge, only one other study with a similar approach was found . SpecifiIn addition, the U-18 players in the present study covered higher total distance than U-18 international players , U-18 EnOn the one hand, previous information highlighted that U-18 players from the present study showed higher levels of intensity. Although, the first team showed lower levels of total distance and high-intensity speed thresholds in matches than other studies conducted in first teams during training sessions, as highlighted by a recent systematic review . This coRegarding positional differences, the results for both teams showed an overall tendency of lower values for CB for total distance, sprint distance, and number of decelerations. In addition, WM showed a tendency for higher values in total distance, high-intensity distance, and sprint distance, while WB showed a tendency for higher values in accelerations and decelerations. Considering total distance, the present results are in contrast with previous studies that showed higher values for CM for adult professional, semi-professional, and amateur teams ,57,58,59Indeed, this study ,59,60 alOnly two teams from the same SP club were examined, which limited the total sample size and that of each position and thus may affect the generalization of results related to positions. Moreover, and despite not being an aim of the present study, internal load variables  may provide more insights into the findings of the present study if applied. This variable was not included in the present study as it is not well documented in U-18 players. Therefore, it was not included to ensure it did not affect its validity.The fact that U-18 players were compared with the first team may also be a limitation, previous studies have included other age brackets, such as U-19 or U-20 , which iThe highlights of this study support the analysis of positional match demands, which may provide useful information for training program design and tactical strategy. For example, the differences observed between playing positions in match-play suggest that the position specificity approach should be taken in consideration for training periodization. Furthermore, this study is relevant by showing similar external load values of two teams from the same club at different levels. This may also be used as a strategy when deciding when to include young soccer players into the first team.This study confirmed that playing position influenced the external load performance in soccer match-play. However, it failed to support the hypothesis that suggested the competitive level could also influence the external load, which, in this case, was not evident when comparing first team and U-18 players.


Higher flexible and rigid CR were associated with higher CR overall, emotional eating (TFEQ-R21) and eating disorders (SCOFF), and lower intuitive eating (IES-2). In addition, higher flexible CR was associated with lower impulsivity (BIS-11) while higher rigid CR was associated with higher uncontrolled eating (TFEQ-R21) and lower self-esteem (RSES), satisfaction with life (SWLS), and optimism (LOT-R). Flexible and rigid CR internal consistency was satisfactory  and test–retest reliability was good . This study validated a flexible and rigid CR tool in a French population and confirmed that these two types of CR represent distinct eating behaviors.Distinguishing between flexible and rigid cognitive restraint (CR) may be useful for understanding the role of CR in dietary behavior and weight status. This study aimed to translate and adapt the flexible and rigid CR scales to the French context and test their psychometric properties. Construct validity, internal consistency, and test–retest reliability were examined in a sample of 620 individuals. Confirmatory factor analysis of the scales found a two-factor structure  that provided a good fit and supported the initial solution ( Many individuals display a chronic tendency to limit food intake in order to control their body weight. The social context where thinness is perceived as an ideal might be one of the predisposing factors leading to this behavior. The term “restrained eating” was first introduced in the mid-1970s by Herman and Mack to describe this tendency . For decThe potentially deleterious effect of restraint has been attributed to the co-occurrence of restriction and disinhibition, the latter describing the occasional hyperphagia that occurs as a result of a breakdown of inhibition in individuals who diet rigidly and then suddenly lose control and overeat in response to different types of stimuli ,15. The Subsequent studies have confirmed that rigid CR was positively associated with disinhibition, whereas flexible CR typically showed a negative or null association ,19. In aThe aims of the present study were therefore to adapt the flexible and the rigid CR scales to the French context and examine their psychometric properties in a sample derived from the general population. Specifically, we evaluated the construct validity of the translated instrument, i.e., studying its factor structure, comparing scores between subgroups with “a priori” differences in flexible and rigid CR, and testing its correlation with other scales assessing eating behaviors and psychological well-being. We also examined the instrument’s internal consistency and test–retest reliability.This study was conducted within the NutriNet-Santé study, which is a large, ongoing web-based prospective cohort started in France in May 2009. The rationale, design and methods of the study have been described elsewhere . Its oveThe original flexible and rigid CR scales were developed and validated by Westenhoefer et al.  as an exThe flexible and rigid CR dimensions were cross-culturally adapted from English to French following the guidelines by Beaton et al. . ForwardParticipants completed the French version of the revised 21-item Three-Factor Eating Questionnaire (TFEQ-R21)  approximIntuitive eating is defined as generally eating in response to physiological hunger and satiety signals rather than external and/or emotional cues, along with giving oneself unconditional permission to eat desired food when hungry ,35. It wImpulsivity was assessed with the French version  of the BThe French version  of the SThe French version  of the RParticipants completed the French version  of the SThe French version  of the L2) was calculated as the ratio of the self-reported weight in kg to the squared height in m.Socio-demographic, anthropometric and lifestyle data were self-reported each year, using online tools that were pilot-tested and validated against traditional assessment methods ,50 and aχ2/df), the comparative fit index (CFI), the Tucker-Lewis index (TLI), and the root mean square error of approximation (RMSEA). The standardized root mean square residual (SRMR) was not reported because this index was found to perform poorly with binary outcomes [χ2/df < 5; CFI > 0.95; TLI > 0.95; and RMSEA < 0.06.A CFA seldom yield a robust model in the first try . Indeed,outcomes . Estimatχ2 would decrease if fixed parameters were freely estimated), expected parameter change values , and theoretical considerations were explored [Inter-item tetrachoric correlations were calculated to identify items with too weak (r < 0.30) (suggesting lack of association) or too strong (r > 0.80) correlations (suggesting redundancy), leading to the suppression of one of these items. Furthermore, to identify potential sources of misspecification, standardized coefficients (standardized regression slopes), standardized residuals (standardized difference between observed and model-implied variance for each item), modification indices  and anthropometric characteristics (BMI) were evaluated with ANOVA to estimate convergent and discriminant validity. Convergent and discriminant validity was further assessed by calculating Pearson’s correlations, with the original subscales of the TFEQ-R21 assessing CR, emotional eating and uncontrolled eating, the IES-2  measuring intuitive eating, the BIS-11 measuring impulsivity, the SCOFF measuring eating disorders, the RSES measuring self-esteem, the SWLS measuring satisfaction with life and the LOT-R measuring optimism. Since interactions between gender and each scale were not significant, analyses were not stratified.Scale reliability was assessed with the McDonald’s ω . Test-reHypotheses were specified before the data were collected and the analytic plan was pre-specified. All tests of statistical significance were 2-sided and the significance level was set at 5%. Statistical analyses were performed using R software . CFA were performed with the lavaan package for latent variable modelling   and reli2 (SD = 4.8). A total of 337 participants (54% of those who received it) completed the questionnaire the second time, with a mean test–retest interval of 45 days .Among the original 1000 randomly drawn participants, 620 (296 men and 324 women) completed the CR questionnaire in 2017 (62% of those who received it). Mean age was 52.4 years (SD = 15.2), 19.7% had postgraduate education, 16.9%-undergraduate education, 56.5%-secondary education, and 6.9%-primary education. Mean BMI was 24.9 kg/mp = 0.67). In addition, inter-item correlations indicated collinearity between items FC8  and FC11  (modification indice = 105.69) suggesting that they measured the same concept. Thus, a respecified model, where item RC10 was dropped and the covariance between items FC8 and FC11 was considered, was tested. Covariances do not modify the use of the scales but allow taking into account common errors in the item residual variances, which could be due to similarity in wording. The respecified two-factor model exhibited a good fit  and rigid CR scales The test-retest over a 45-day period revealed good ICC for the flexible  and the rigid  subscales.The flexible and rigid CR scales were translated and validated in a randomly selected subsample of the NutriNet-Santé cohort. The final model included 27 items: 12 for the flexible CR scale and 15 for the rigid CR scale. The construct validity of the respecified two-factor model was good as seen in CFA, hypotheses testing with a comparison of scores between subgroups with “a priori” differences in flexible and rigid CR, and correlation measures of eating behaviors and psychological well-being. Measures of scale reliability showed satisfactory internal consistency and good test-retest reliability.The original flexible and rigid CR scales, developed by Westenhoefer , were coAccording to the initial definition, flexible CR behavior is characterized by a graduated approach to eating, dieting, and weight, in which “fattening” foods are eaten in limited quantities without feelings of guilt . The fleBivariate analyses supported prior evidence indicating that women have higher levels of flexible and rigid CR compared with men ,12,17. SBivariate analyses showed no correlation between flexible CR and weight status. Cross-sectional data in the literature are contrasted, showing null ,19,20,22In the present study, flexible and rigid CR were positively correlated with CR overall, which was expected due to their conceptualization. In addition, both scales were associated with eating disorders, the association with rigid CR being stronger than the one with flexible CR. The literature in this domain mostly focused on bulimia or binge eating, and showed contrasting results with either positive associations for both scales  or for tn = 2513) of the NutriNet-Santé cohort showed convergence with self-reported data [The present validation study has several strengths and limitations. First, it included a general-population-derived sample of both men and women of diverse age and education backgrounds. Moreover, we used a random subsample of the NutriNet-Santé cohort, selected for the purpose of being representative of the French population in terms of age, gender, and level of education . HoweverIn the present study, we translated, adapted, and validated the flexible and rigid CR scales, originally developed by Westenhoefer and colleagues, in a French population-based sample. This 27-item instrument demonstrated good psychometric properties, confirming that flexible and rigid CR are independent constructs. Our data suggested that rigid CR was associated with more underweight or overweight/obesity. In addition, both rigid and flexible CR were associated with rather unfavorable eating behavior and well-being characteristics. The distinct flexible and rigid CR scales may prove useful tools to better understand the role of CR in weight control in the general population as well as in clinical samples. Longitudinal population-based studies, taking into account pertinent confounders, are needed to determine if causal relationships exist between flexible and rigid CR, dietary intake, weight status and eating disorders, and what the direction of causality might be.


To understand the awareness of COVID-19 vaccine, the willingness to vaccinate and the influencing factors of willingness to vaccinate in inflammatory bowel disease (IBD) patients.The online questionnaire was distributed to conduct a survey to analyze and evaluate the willingness, awareness and trust in vaccines of IBD patients. Bivariate analyses and logistic regression models were used to analysis influencing factors.We sent the questionnaire to the WeChat group for patient management and 304 patients responded, out of which 16 respondents had to be excluded and 288 respondents were included for the analysis. Among them, 209 patients vaccinated with COVID-19 vaccine. Among the non-vaccinated 79 patients, the main reasons for their concerns were afraid of vaccination aggravating IBD and fear of adverse effects. Our results showed that IBD patients with long disease duration were more willing to receive COVID-19 vaccination (P<0.05). We also observed that a high perception of benefits and cues to action to receive the vaccine were the two most important constructs affecting a definite intention for COVID-19 vaccination (P<0.05).Patients with IBD have a more cautious attitude towards COVID-19 vaccination, which may lead to a higher rate of vaccine hesitancy. Further efforts should be made to protect patients with IBD from COVID-19 infections and achieve adequate vaccination coverage. By the middle of March 2022, the coronavirus-19 disease (COVID-19) had infected more than 450 million people and caused nearly 6 million death worldwide  from September 1, 2021 to December 31, 2021. All adult IBD patients from the SAHZU Crohn’s and Colitis Center, with a confirmed diagnosis of IBD were eligible to participate in the study. Inclusion criteria included age greater than or equal to 18 years and diagnosed with Crohn’s disease or ulcerative colitis. Participants were invited to complete an online questionnaire. Patients were excluded if they had difficulty in understanding the content. As shown in The COVID-19 vaccine hesitancy rate was reported to be 18% (12–24%) among patients with IBD in different countries. This study was a cross-sectional study to evaluate the acceptance rate of COVID-19 vaccination among patients with IBD in China, requiring bilateral tests, α was 0.05. The allowable error was 0.04. Using PASS 15 software to calculate the sample size N=288 cases. Considering the 20% loss rate, at least 360 cases needed to be included in this case as the study object. The social demographic profile included current age, gender, marital status , working condition , education level  and level of income per month (under ¥2000 (US $315), ¥2000-¥5000 (US $315-$786), ¥5000-¥10000 (US $786-$1572), ¥10000-¥20000 (US $1572- $3144) and above ¥20000 (US $3144). The clinical disease profile consisted of a type of disease and disease activity, which were reported by patients with IBD themselves using the validated patient-based Harvey-Bradshaw Index (HBI) items for patients with CD and the Patient-based Simple Clinical Colitis Activity Index (P-SSCAI) for patients with UC , 18. HBIData analyses were performed using IBM SPSS software . For quantitative variables, mean and standard deviation or inter-quartile range [IQR] were calculated, and comparisons of differences between groups were compared using t-tests if normally distributed, or with the Wilcoxon test if non-normally distributed. Categorical variables were expressed as frequency or percentages, and differences in frequencies between groups were calculated using χ2 test or Fisher’s exact test. Furthermore, univariate analysis was used to determine characteristics associated with the definite intention to take the COVID-19 vaccine. Multivariate logistic regression was used to assess whether these individual variables were related to outcomes. Odds ratios (OR), 95% confidence intervals (95% CI) and p-values were calculated for each independent variable. For all tests, 2-sided p-value of 0.05 will be used for defining the level of significance.As shown in Among 288 IBD patients, 209 patients vaccinated with COVID-19 vaccine, which were defined as vaccinated population. In addition, 79 patients did not vaccinate with COVID-19 vaccine were defined as non-vaccinated population. In addition, 81.1% (30/37) patients with UC and 71.3% (179/251) patients with CD vaccinated with COVID-19 vaccine. Furthermore, almost half of patients 149 (52%) inoculated hepatitis B vaccine, less than one third (28%) patients inoculated varicella vaccine, 14% patients inoculated flu vaccine. There were 81 patients who received COVID-19 vaccine but had never been inoculated with other vaccines before, which is much more than those who had cross-vaccination Figure 2Among the non-vaccinated patients, the main reasons for their concerns were as follows: afraid of vaccination aggravating IBD (39%), fear of adverse effects (22%), worry about the current use of drugs affecting the efficacy of vaccination (14%), unknow the most appropriate time to vaccinate (8%), other reasons (17%) Table 2.The crude OR analysis of sociodemographic, clinical disease profile and perception about COVID-19 vaccine in general were shown in In the univariate analysis, most of the constructs in the HBM model  were obvThe present study examined the vaccinated and non-vaccinated patients with IBD, and investigated various sociodemographic, health-related and behavioral predictors for these patients based on the HBM model. The acceptance of the COVID-19 vaccine in patients with IBD has not been adequately evaluated, and the reasons for the hesitancy of patients with IBD about the COVID-19 vaccine are unknown. A total of 288 IBD patients were finally included in this study, of which 72.6% had received the COVID-19 vaccine, which was consistent with other findings in Italy and United States , 24. We It was reasonable to find higher intention of vaccination among respondents in the long disease duration, as their more stable condition, a better understanding of the vaccination, or a greater willingness to follow gastroenterologist advice . With rePrevious studies have shown that inactivated vaccines such as hepatitis B vaccine, varicella vaccine and flu vaccine are well tolerated and safety , 27. MeaWhether patients with IBD should be vaccinated against COVID-19, D’Amico et al. suggested that they should receive COVID-19 vaccines, regardless of medication or comorbidities . AccordiIn our study, multivariable analysis found that HBM constructs were associated with vaccination intention, which was in concordance with other studies . EspeciaThere were several limitations to our study. Firstly, the present study was self-reported from patients and certainly related to the retrospective nature which might have been recalling bias and selection bias. Secondly, our study focused on the IBD patients, we just compared the factors among IBD patients and didn’t compare the factors with non-IBD controls. Thirdly, detailed characteristics of individual patients were not available. Other limitations to mention were that the survey respondents represented only a small proportion of all Chinese IBD patients and thus may not be generalizable to all Chinese IBD patients or other countries, especially considering differences in rates of both COVID-19 and IBD. The strength of our study was that we did a comprehensive survey on sociodemographic, clinical disease profile and health belief in IBD patients.COVID-19 vaccination for the general population has been proceeding in China. Meanwhile, IBD specialists are still called upon in conducting a campaign to convince their patients to get vaccinated. Our study suggests that patients with IBD are more cautious about vaccinating against COVID-19, resulting in a higher rate of vaccine hesitancy. It is necessary to explain to patients that the benefits of vaccines outweigh the risks, especially in patients without immune disease. Further efforts should be made to protect patients with IBD from COVID-19 infections and achieve adequate vaccination coverage. Healthy education and advice from government and IBD experts may facilitate COVID-19 vaccination.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Institutional Review Board of the Ethics Committee of the Second Affiliated Hospital, School of Medicine, Zhejiang University in China (IR2021001361). The patients/participants provided their written informed consent to participate in this study.YC, SH and JL participated in study design and study conception. SL collected the questionnaire data. SH, JL, performed statistical analysis. QW, XW, and DX performed the check of results. SH and JL drafted the manuscript. All authors provided critical review of the manuscript and approved the final draft for publication. All authors contributed to the article and approved the submitted version.


Background: Heavily calcified lesions in acute coronary syndrome (ACS) still represent a challenging subset for percutaneous coronary intervention (PCI). Rota-lithotripsy—a marriage of rotational atherectomy and intravascular lithotripsy—has recently been introduced to clinical practice as a novel therapeutic option. Methods: This study is among the to present the 6-month clinical outcomes of rota-lithotripsy when performed in the ACS setting. The study cohort consisted of 15 consecutive ACS patients who underwent a rota-lithotripsy-PCI due to the presence of a highly calcified, undilatable lesion. Results: The procedural success ratio reached 100%. During the 6-month follow-up, in two of the patients, instances of MACE (major adverse cardiac events) occurred, including one fatal event. Additionally, during the observation period, one target lesion failure, due to subacute stent thrombosis, was identified. Conclusions: Rotational atherectomy with the subsequent use of shockwave intravascular lithotripsy appears to be a safe and effective therapeutic bail-out option for the management of highly calcified coronary artery lesions. Despite, these initial favorable outcomes, carrying out a large number of studies with long-term observations is still necessary in order to establish the potential benefits and shortcomings of rota-lithotripsy. Calcifications in the coronary vessels imply the presence of coronary artery disease (CAD) and are a well-established risk factor for unfavorable clinical events . DespiteRota-lithotripsy, also known as rota-tripsy, is a combination of rotational atherectomy with subsequent intravascular lithotripsy ,8,9,10. An investigation into a total of 15 consecutive ACS patients who underwent a series of PCI treatments  was conducted. The procedures were performed at two cooperative high-volume  cardiology departments in the Lower Silesia Region in Poland. All the PCI procedures were performed from May 2019 to February 2022. During this period, in both cardiac centers, no other alternative methods  of management with undilatable lesions had been used.The main inclusion criteria were the presence of a culprit calcified lesion treated with a rotational atherectomy (RA) device due to initially unsuccessful pretreatment with a non-compliant (NC) balloon. Additionally, the lesion had to be defined by the operator as impracticable for primary S-IVL (mainly long lesions with high-grade stenosis). In all involved cases—despite the successful passage of a rotational atherectomy burr still—a significant (over 20% in diameter) under-expansion of the NC balloon (sized 1:1 to vessel references) was observed. A flow chart of the study design is presented in The decision to perform the PCI was based either on the cardiology team’s judgment or on clinical indication . All patients were thoroughly informed regarding the available therapeutic options and the PCI-related risks before written informed consent was provided. There were no vessel-related exclusion criteria regarding lesion anatomy, length, tortuosity, severity, or prior stent placement. All the clinical features regarding the PCI procedure including vascular access point; guiding catheter size; intravascular imaging guidance (OCT/IVUS); burr or shockwave balloon size ; rotablation speed; number of ultrasonic pulses applied; and periprocedural pharmacotherapy, along with stenting technique, were left to the operators’ discretion.The primary endpoint of the study was in the investigation of occurrences of major adverse cardiac events (MACE) during the hospitalization period, as well as during the 1- and the 6-month post-discharge observation periods. MACE was defined as: death, myocardial infarction, need for second target vessel revascularization, and probable or diagnosed in-stent thrombosis. The secondary endpoints included cerebrovascular episodes, target lesion failure, all kinds of revascularization procedures, major bleeding, and scaffold restenosis. The myocardial infarction definition was based on the fourth universal definition of myocardial infarction . In addiThe R language was used for analyses. Continuous variables were characterized by their mean and standard deviation. They were also characterized by median, and first and third quartiles (dependent on their distribution), whereas the frequencies were used for the purposes of categorical variables. The Shapiro–Wilk test was used to verify the normality of continuous variables. Further, the significance level was set to <0.05.The study population consisted of 15 patients, mainly males (86.7%), with a mean age of 70.9 ± 9.1 years. Most of the subjects had suffered from NSTEMI (73.4%) and were characterized by a high prevalence of cardiovascular risk factors such as hyperlipidemia (100%), hypertension (86.6%), diabetes (66.6%), and a previous history of MI (53.3%). All basal clinical data regarding the study cohort are pooled in Despite the initial high advancement of coronary artery disease (the mean Syntax I score reached 21.1 ± 10.9) and mild impairment of the left ventricular ejection fraction (44.8 ± 16.2), radial access was used in 80.0% of cases. However, most of the procedures were performed using a 7F (73.3%) catheter. The data regarding periprocedural features are presented in During the hospitalization period, one MACE related to a subacute stent  thrombosis of the target lesion was observed. Additionally, one patient underwent a scheduled PCI for a non-culprit lesion. In the study cohort, we observed two major occurrences of bleeding: one was related to the femoral access site (the patient required a blood transfusion and urgent surgery); the second was not directly related to the procedure  implanted stent-graft to the abdominal aorta). There were no additional MACEs in the 30-day follow-up period. In one subject, a scheduled PCI of another vessel was performed. During the 6-month follow-up period, an additional episode of MACE was observed. Approximately 5 months after discharge, one death occurred. A patient with a high number of comorbidities and a low left ventricular ejection fraction (LVEF) (15–20%) with a previously implanted cardioverter–defibrillator (ICD) and newly diagnosed COVID-19 was admitted to the emergency department and died a few hours later with symptoms of acute heart failure. All data regarding clinical outcomes were collected in Coronary artery lesions with a high calcium burden still represent a challenging task for interventional cardiologists. Further, these lesions are connected with a greater risk of periprocedural complications, as well as with a late failure due to the stent underexpansion and malapposition, consequently resulting in poor clinical outcomes ,21,22. HTo tackle these highly demanding lesions, several debulking modalities  have become a part of contemporary clinical practice. Despite the well-established safety and efficiency of the atherectomy devices, utilization in the ACS subset is burdened with worse outcomes compared to stable patients ,27. Due Different mechanisms may be responsible for suboptimal lesion preparation in the context of calcified lesions. Atherectomy devices are mainly dedicated to long, tight lesions modifying calcium plaques, due to their high-speed  rotating burrs, which perform atheroablation leading to the pulverization of calcified deposits. For that reason, atherectomy devices’ field of action is mainly limited to superficial plaques with a lack of impact on profound calcium deposits ,34. On tIn response to the shortcomings of listed plaque-modification methods, a novel technique of highly calcified lesion preparation rota-lithotripsy, also known as rota-tripsy or rota-shock, has been recently introduced. The initial low-number and short-term ,27,28,38Even though the need for additional S-IVL may be reduced by an escalation of burr size, when the burr-to-artery ratio exceeds over 0.5/0.6, this leads to an increased rate of complications  ,40,41,42To the best of our knowledge, this is the first description of a mid-term follow-up on the outcomes of the simultaneous use of rotational atherectomy and shockwave intravascular lithotripsy in terms of ACS subjects. The results obtained in our cohort indicate the safety and efficacy of the rota-lithotripsy treatment to high-risk subjects where the single-burr RA strategy is revealed to be insufficient for adequate lesion preparation.A relatively high Syntax Score I (21.1 ± 10.9) along with a high Syntax II PCI score (39.0 ± 14.9) confirm the complexity and advancement of CAD in the study group. Despite an unfavorable clinical subset—i.e., in the ACS setting, the high lesion complexity as well as the considerable comorbidities observed in the study group—the mid-term MACE rate was comparable to the one observed in the ACS cohorts undergoing only rotational  or orbitAlthough only one non-fatal subacute stent thrombosis occurred in our study cohort, and we did not observe any other rota-lithotripsy-related periprocedural complications, further studies are required in order to address the safety concerns. The use of RA increases the rate of thrombotic events, particularly slow flow phenomena , and somThis is a non-randomized observational pilot study with a relatively small number of participants. Nevertheless, the procedures have scarcely been introduced in clinical practice and have still managed to obtain bail-out life-saving status in extremely high-risk patients. Moreover, for the same reason, the rate of intravascular guidance has been comparatively low .To the best of our knowledge, this is the first description of mid-term follow-up outcomes of the simultaneous use of rotational atherectomy and shockwave intravascular lithotripsy in ACS subjects. Rotational atherectomy with the subsequent use of shockwave intravascular lithotripsy appears to be a safe and effective therapeutic bail-out option for the management of highly calcified coronary artery lesions. Further studies with a higher number of participants, a longer observation period, and broader support for intravascular imaging are necessary in order to fully establish the potential benefits and shortcomings of rota-lithotripsy, before its wider implementation into clinical practice can be achieved.


Recent US blood pressure (BP) guidelines recommend using ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) to screen adults for masked hypertension. However, limited evidence exists of the expected long-term effects of screening for and treating masked hypertension.We estimated the lifetime health and economic outcomes of screening for and treating masked hypertension using the Cardiovascular Disease (CVD) Policy Model, a validated microsimulation model. We simulated a cohort of 100,000 US adults aged ≥20 years with suspected masked hypertension . We compared usual care only , usual care plus ABPM, and usual care plus HBPM. We projected total direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs were discounted 3% annually. Secondary outcomes included CVD events and serious adverse events.Relative to usual care, adding masked hypertension screening and treatment with ABPM and HBPM was projected to prevent 14.3 and 20.5 CVD events per 100,000 person-years, increase the proportion experiencing any treatment-related serious adverse events by 2.7 and 5.1 percentage points, and increase mean total costs by $1,076 and $1,046, respectively. Compared with usual care, adding ABPM was estimated to cost $85,164/QALY gained. HBPM resulted in lower QALYs than usual care due to increased treatment-related adverse events and pill-taking disutility.The results from our simulation study suggest screening with ABPM and treating masked hypertension is cost-effective in US adults with suspected masked hypertension.  HBPM requires an individual to measure their BP in the morning and at night over a minimum of 3 days. ABPM is often considered the reference standard for hypertension diagnosis, but BP guidelines also support the use of HBPM, which is less expensive, and more readily accessible than ABPM.13Out-of-office BP can be measured using ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM).Despite recommendations from BP guidelines to screen for masked hypertension using out-of-office BP monitoring, the expected long-term impact of screening for and treating masked hypertension on the risk of incident CVD events, risk of medication-related serious adverse events, and healthcare costs are currently unknown. This study seeks to estimate the lifetime cost-effectiveness of masked hypertension screening and treatment compared with usual care.14–17 In the simulation, individuals started with no history of CVD and each year were at risk of experiencing CHD, stroke, both CHD and stroke, and dying from CVD or non-CVD-related causes  and stroke incidence and prevalence in US adults.d causes  online. The simulation model and key inputs used to conduct this research are available upon reasonable request and approval by the model team. Interested researchers can submit a research proposal and collaboration plan to Dr. Bellows and will be required to sign a Creative Commons agreement.18–21 Of these, individuals aged 20 years or older with suspected masked hypertension  with no history of CVD and no self-reported use of antihypertensive medications were included .1 To achieve stable cost-effectiveness estimates, nationally representative cohorts of 100,000 US adults were simulated.The model was populated with individuals from National Health and Nutrition Examination Survey (NHANES) 1999–2014 cycles who were matched to participants from the National Heart, Lung and Blood Institute Pooled Cohorts Study (NHLBI-PCS) for whom lifetime CVD risk factor trajectories  have been developed.1 The second and third were “usual care plus ABPM” and “usual care plus HBPM,” in which patients received usual care plus screening for masked hypertension using either ABPM or HBPM, respectively. For masked hypertension screening, patients were rescreened every 3 years when aged <40 years and annually when aged ≥40 years.22 Other screening intervals were evaluated in sensitivity analyses.We evaluated 3 strategies to diagnose and treat masked hypertension . The firuntreated “true” office BP represents an individual’s underlying office BP, without measurement error, had they not been treated with antihypertensive medication at any time in their life. It is derived from the NHLBI-PCS lifetime CVD risk factor trajectories.18–21 The “true” office BP is the treatment-adjusted office BP of an individual that applies the estimated BP reduction based on number of half- and full-standard dose medications used and adherence . The diagnostic accuracy of HBPM was obtained from a meta-analysis comparing HBPM measurements with daytime ABPM measurements at a 130/80 mm Hg threshold (sensitivity 91.8% and specificity 41.4%) and accounted for typical use by patients at home.27 Similar to prior analyses, failure to obtain a complete ABP reading was set at 5% and required rescreening.29As NHANES does not include out-of-office BP measurements, the validated Predicting Out-of-OFfice BP (PROOF-BP) algorithm, which uses office BP readings and patient characteristics, was used to estimate 21 The probability of an incident CVD event each year was calculated using the untreated “true” office BP  and stroke (RR = 0.73) when using antihypertensive treatment.9 The probabilities for nonincident CVD events were stratified by age and sex , or serious .ons used  online.128 The cost of an HBPM device was estimated by averaging the costs of the top 3 rated HBPM devices on Amazon at the time of the analysis. In the primary analysis, patients were assumed to purchase their own HBPM devices , but this was explored in a scenario analysis. The Centers for Medicare and Medicaid Services Physician fee schedule was used to define costs of physician visits associated with ABPM (CPT code 93784) and HBPM (CPT codes 99473 and 99474). Based on prior analyses and warranty information from manufacturers, ABPM and HBPM devices were assumed to be replaced every 5 years in the primary analysis but this was varied in sensitivity analysis.34 Antihypertensive medication, acute and chronic CVD event, medication-related adverse event, and background healthcare costs were derived from prior cost-effectiveness analyses , which range from one, indicating a year of full health, to zero, indicating death. history  online.114–17As in prior analyses, the model was calibrated to match contemporary incidence and total event rates of CHD and stroke, and CVD and all-cause mortality from the Centers for Disease Control and Prevention, National Hospital Discharge Survey, National Inpatient Sample, and National Vital Statistics System, and cross-validated against the original, dynamic population version of the CVD Policy Model  online.136 The simulation model was developed and performed using TreeAge Pro  and other analyses were performed in R . The primary outcome was the incremental cost-effectiveness ratio (ICER), defined as the additional cost per QALY gained. Costs (2021 USD) were from a US healthcare sector perspective, which includes all direct medical costs regardless of the payer.36 All future costs and QALYs were discounted 3% annually.36 We used the cost-effectiveness thresholds recommended by the ACC/AHA, considering an ICER <$50,000/QALY gained highly cost-effective and an ICER ≥$50,000/QALY to <$150,000/QALY gained intermediately cost-effective.37 For the primary analysis, 200 probabilistic iterations in which model inputs were randomly sampled from prespecified distributions were used to obtain the mean and 95% uncertainty interval (UI) for costs, QALYs, and the probability of being cost-effective. The rates of CVD events, CVD mortality, and serious adverse events were also projected.Our analysis adhered to recommendations from the Second Panel on Cost-effectiveness in Health and Medicine  online.329 Finally, scenario analyses were performed in which (i) HBPM devices were purchased by physician offices and used by an average of 52 patients per year , (ii) HBPM had 100% sensitivity and specificity to detect masked hypertension, and (iii) ABPM had the same accuracy as HBPM .15One-way sensitivity analyses were performed by systematically varying model inputs related to masked hypertension across plausible ranges while holding all other parameters constant. The lower and upper bounds for the 1-way sensitivity analyses were derived from 95% confidence intervals or ranges reported in the literature. As the potential benefits and harms of treating masked hypertension are unknown, a 2-way sensitivity analysis assessed the joint impact of the probability of serious adverse events and the relative risk of CVD events per 10-mm Hg reduction in office BP with antihypertensive treatment on cost-effectiveness outcomes. Several scenario analyses were conducted to compare our approach to calculating the expected reduction in CVD event risk and quality of life to those used in prior cost-effectiveness studies  online.22, office SBP was 123.9 (2.6) mm Hg, and office DBP was 72.1 (5.5) mm Hg.The simulated cohort was 43.3% female; 47.8% were non-Hispanic White and 19.5% non-Hispanic Black. The mean (SD) baseline age was 42.2 (14.8) years, body mass index was 25.4 (4.3) kg/mDue to decreased specificity, screening for masked hypertension with HBPM was projected to result in more antihypertensive medications being started within the first year (68.3%) than usual care alone (0.0%) or usual care plus ABPM (28.5%). Screening for masked hypertension was projected to reduce the cumulative incidence of CVD events  online. Compared with usual care alone, usual care plus ABPM screening increased costs by an average $1,076  per person over a lifetime and usual care plus HBPM by an average of $1,046  per person  online. The cost-effectiveness of masked hypertension screening was most sensitive to changes in the specificity of ABPM, frequency of masked hypertension screening, and pill-taking disutility . The impIn the scenario analyses that used approaches from prior studies to calculate the expected reduction in CVD event risk and quality of life, a greater number of CVD events were prevented with masked hypertension screening using ABPM  and HBPM  than in the primary analysis  online. In this simulation study, we evaluated the cost-effectiveness of screening for and treating masked hypertension using either ABPM or HBPM in US adults with suspected masked hypertension. Both usual care plus ABPM and usual care plus HBPM screening strategies were projected to decrease CVD events and CVD-related mortality compared with usual care at lifetime incremental costs of screening near $1,000. Adding screening with ABPM to usual care was estimated to cost an average of $85,164/QALY gained over an individual’s lifetime compared with usual care. However, usual care plus HBPM resulted in lower QALYs than usual care due to increased treatment-related adverse events and pill-taking disutility and was not cost-effective. The cost-effectiveness of masked hypertension screening was most sensitive to the specificity of the screening strategy and the screening frequency.29 However, these prior studies examined different populations and uses of ABPM compared with our study. Beyhaghi and Viera22 examined the use of ABPM for adults aged 21 years and older in a US representative population, including those with high office BP.1 Lovibond et al.28 focused on use of ABPM in those with an office BP ≥140/90 mm Hg, and Monahan et al.29 on those with an office BP ≥130/80 mm Hg, aged 40 years and older. In contrast, we examined US adults aged 20 years and older without high office BP and with suspected masked hypertension , many of whom may have a much lower risk of CVD than the populations studied in prior studies. Additionally, the prior studies used a different approach to estimating QALY reductions with CVD that generally results in a greater quality of life benefit from CVD event prevention than our approach and used a greater CVD event-specific relative risk for individuals on antihypertensive medications than in our analysis.29 When we adopted a similar approach, usual care plus ABPM became highly cost-effective .28The economic impact of out-of-office BP monitoring has been explored in previous studies, which have shown screening with ABPM to cost less and be more effective than not screening.29 These assumptions resulted in a modest CVD benefit in our model because office BP is lower in those with masked hypertension than those with sustained hypertension, and meta-analyses show higher starting BPs are associated with greater BP reductions with treatment.38 Additionally, our analysis did not include the reduction in risk of heart failure associated with antihypertensive treatment.9 Heart failure is associated with substantial morbidity, mortality, and healthcare costs; therefore, the benefits of antihypertensive treatment are likely underestimated in our analysis.40 Another potential limitation of our study is the assumption that ABPM is the reference standard (100% sensitivity and specificity) for diagnosing masked hypertension. Recent literature suggests that, compared with 24-hour ABPM, mean BP measured by 1 week of HBPM is more reliable and strongly associated with left ventricular mass index, a reliable measure of end-organ damage.41 When HBPM was assumed to have 100% sensitivity and specificity, usual care plus HBPM was projected to be the most cost-effective option . Given this, and that the 2017 ACC/AHA BP guidelines state that HBPM or ABPM may be used to screen for masked hypertension, additional research is needed to better understand the ability of out-of-office screening to detect masked hypertension. Additionally, our analysis did not examine the impact of screening for masked hypertension within specific racial or ethnic groups. Future work is needed to ensure that screening for masked hypertension is equitable and reaches those at highest risk. Finally, while the PROOF-BP algorithm has been shown to accurately predict out-of-office BP, it may lead to some misclassification of participants.The results of our study need to be considered in the context of the following potential limitations. While the CVD Policy Model was calibrated to reproduce contemporary CVD event rates and mortality, it is a simulation model with a fixed set of assumptions about the underlying data and real-world clinical practice. Our primary analysis assumed the treatment benefits of antihypertensive medications were based on changes to office SBP and that individuals with masked hypertension receive the same treatment benefit per 10-mm Hg office SBP reduction as individuals with sustained hypertension. This assumption was based on the results from prior studies, but the treatment effect of antihypertensives on out-of-office BP and CVD risk in masked hypertension has not been assessed in any published randomized control trials.In this simulation analysis, the addition of ABPM to usual care is estimated to reduce CVD morbidity and mortality and be an intermediately cost-effective way to screen for and treat masked hypertension in US adults suspected to have masked hypertension.hpac071_suppl_Supplementary_MaterialClick here for additional data file.


To report two cases of oocyte retrieval performed in asymptomatic SARS-CoV-2-positive patients. Setting. Outpatient private practice infertility center. Patients. A 28-year-old woman at risk for OHSS who took her trigger injection prior to testing positive for SARS-CoV-2 and a 19-year-old oncofertility patient who tested positive prior to retrieval due to a family exposure. Both patients were asymptomatic. Main Outcome Measures. Cycle outcomes, patient safety, and staff safety.  Case report.  Both patients underwent successful oocyte retrieval procedures without developing symptoms or complications from COVID-19. No staff members that cared for these patients developed symptoms of COVID-19.  Worsening fertility outcomes and potential for psychological and financial burdens to the patient must be balanced with risk of perioperative complications in patients testing positive for SARS-CoV-2. As we continue to provide fertility care in a world with COVID-19, appropriate risk mitigation strategies should be implemented to minimize exposure to SARS-CoV-2. Amid the ever-changing COVID-19 pandemic, many fertility clinics have fully resumed patient care, however with necessary adjustments to reduce the spread of COVID-19 and optimize patient safety. At the beginning of the pandemic, there were many ovulation induction, intrauterine insemination (IUI), and in vitro fertilization (IVF) cycles cancelled after the American Society for Reproductive Medicine (ASRM) released practice recommendations to suspend initiation of all new treatment cycles on March 17, 2020 [Most medical institutions have implemented universal preoperative SARS-CoV-2 testing prior to performing elective, outpatient surgeries. The goal is to identify patients who may be in the early incubation period of COVID-19 infection and may have increased morbidity if undergoing intubation during this time . SpecifiThe impact of COVID-19 on treatment cancellations has lasting ramifications. In a recent survey of patients who had a cycle cancelled due to the COVID-19 pandemic, 85% of respondents found it to be moderately to extremely upsetting with 22% rating it to be equivalent to the loss of a child . COVID-1Our infertility clinic has not implemented universal testing for patients. Rather, we have implemented a triage and screening approach for COVID-19 symptoms as well as universal precautions for COVID-19. All patients are required to wear masks and must undergo screening with a temperature scan and completion of a questionnaire prior to being admitted to the clinic. If there is a positive screen or elevated temperature, then the case is discussed with the patient's physician, and COVID-19 testing is recommended prior to patient care. Recently, we had two cases where patients who voluntarily sought out COVID-19 testing a few days prior to oocyte retrieval tested positive although they were asymptomatic for COVID-19. Both underwent oocyte retrieval. To our knowledge, there have been no case reports in the literature describing outcomes of retrieval in COVID-19-positive patients. Informed consent was obtained from both patients for this case report. We will discuss these challenging cases as well as the decision-making process that can be employed when caring for these patients.A 28-year-old G0 female with primary infertility, dysmenorrhea, and obesity (BMI 36) presented to our Reproductive Endocrinology and Infertility practice desiring to conceive. On infertility evaluation, she was found to have bilateral endometriomas (3.0 cm and 1.3 cm) and recurrent endometrial polyps which were removed by hysteroscopic polypectomy. Ovarian reserve testing revealed an antral follicle count (AFC) of 12 and anti-müllerian hormone (AMH) of 4.55. Semen analysis of the male partner revealed teratozoospermia . The couple elected to proceed with IVF including preimplantation genetic testing for aneuploidy (PGT-A). After pretreatment with oral contraceptive pills, an antagonist protocol was utilized. After eleven days of stimulation, the patient had a peak estradiol of 5,801 pg/ml, a progesterone level of 1.18 ng/ml, 32 follicles imaged on ultrasound, and 19 follicles > 14 mm diameter in size. She was triggered with a single dose of Lupron 4 mg. On the evening she took her trigger injection, the patient's partner became symptomatic and tested positive for COVID-19. Both the patient and her partner were unvaccinated against COVID-19. The day after her trigger, the patient underwent rapid testing for SARS-CoV-2 and tested positive. She was asymptomatic. The patient was instructed not to present to the clinic the morning after Lupron administration for posttrigger labs in the setting of positive SARS-CoV-2 testing, and the option of cycle cancellation was reviewed. She was counseled on the risks of COVID-19 infection in the setting of a surgical procedure. The decision was made to proceed with oocyte retrieval 36 hours after trigger, with additional precautions taken to minimize risk of infection to staff and other patients. Based on the timing of her trigger, the patient's retrieval occurred as the last retrieval of the day. The patient was asked to wait in her car until specifically instructed to enter the facility so that all other patients could be discharged from the PACU prior to her entering the building. Her partner was instructed to produce his semen specimen at home rather than in the practice collection room. Only fully vaccinated, essential staff necessary for patient care were present in the preoperative, operating room (OR), and PACU area. All staff and the patient each wore an N95 mask. During the oocyte retrieval, total IV anesthesia was utilized (TIVA) in our ambulatory surgical center outpatient OR without complications. During the retrieval, 19 oocytes were retrieved, 17 of which were mature and underwent ICSI, resulting in 10 blastocysts. PGT-A testing revealed 8 euploid blastocysts. The patient remained on the GnRH antagonist (Cetrotide) 0.25 mg daily for 7 days postoocyte retrieval as a precautionary measure. The patient did well postoperatively with no evidence of OHSS and no symptoms of COVID-19 infection. No additional SARS-CoV-2 testing was performed as per the September 2021 CDC guidance recommending that patients who remain asymptomatic should not be retested within 90 days [A 19-year-old G0 female presented for fertility preservation via oocyte cryopreservation in the setting of a recent diagnosis of acute promyelocytic leukemia, having completed one round of chemotherapy treatment  with plans for further consolidation chemotherapy using the same ATO/ATRA regimen. The patient had no other significant past medical history. She had a hormonal IUD in place for the past 10 months. A random start antagonist protocol was initiated. On day 10 of stimulation, the patient did not present to the clinic for her scheduled appointment. When contacted by phone, she reported that she had multiple family members who had tested positive for COVID-19; therefore, she obtained rapid testing, which was positive for SARS-CoV-2. The patient was asymptomatic. She continued her scheduled dose of stimulation medications, and the following day, she underwent confirmatory SARS-CoV-2 PCR testing which also returned positive. She was counseled on the risks of proceeding with oocyte retrieval, and she desired to proceed. The patient was then triggered that evening (day 11 of stimulation) with hCG 5,000 IU. The decision to use an hCG trigger instead of a GnRH agonist trigger was to reduce the risk of a failed trigger, especially as a failed GnRH agonist trigger would not be identified until day of retrieval due to not obtaining posttrigger labs. Oocyte retrieval was performed 36 hours later. Due to the patient not presenting to clinic, the last estradiol level and ultrasound data we have was on stimulation day 9, with a peak estradiol level of 3,067 pg/ml, progesterone of 0.77 ng/ml, and 37 follicles imaged sonographically, with 16 follicles > 14 mm in diameter. She underwent an uncomplicated oocyte retrieval obtaining 35 oocytes. Twenty-two mature oocytes were vitrified. The same infectious disease precautions were used as for case 1. The patient did well postoperatively without symptoms and was able to continue with her planned chemotherapy treatment five days after oocyte retrieval.vs. the risk of thromboembolism in our asymptomatic, ambulatory patient. While knowledge of outcomes in patients with COVID-19 infection and OHSS is limited, current data suggests that physiologic changes seen with fertility treatment may be exacerbated by common pathophysiological aspects of COVID-19 viral infection. In our case, we believed that without retrieval, this patient would have been at risk for developing OHSS that would have been further complicated and potentially worsened by her COVID-19 infection.In the first case, the patient had a known COVID-19 exposure, and she subsequently tested positive for SARS-CoV-2 the day after taking her Lupron trigger. She was asymptomatic. The risks of cancelling the cycle versus proceeding with retrieval were thoroughly considered by several physicians in the practice, as well as with risk management. This patient had a high peak estradiol of 5,801 pg/ml and had already taken the Lupron trigger when testing positive. As such, she was at risk for developing OHSS. Current literature describing the risks of OHSS in COVID-19-positive patients is limited but describes more severe outcomes. A case report described a patient with mild COVID-19 infection who developed significant bilateral pleural effusions requiring bilateral thoracentesis with only minimal abdominal ascites . IsolateDespite the dangers associated with cancelling the patient's cycle, proceeding with retrieval was not without risk to both the patient and medical staff who cared for her. In one international, multicenter cohort study, postoperative pulmonary complications occurred in half of patients with perioperative COVID-19 infection and were associated with high mortality . HoweverThe ASA recommendations for timing of elective surgery after recovery from COVID-19 prompt the question of what truly constitutes “elective” procedures. During the pandemic, elective procedures have typically been defined based on implications for physical health and survival . HoweverAnother consideration for this patient's care concerns her male partner who not only tested positive for SARS-CoV-2 but was also symptomatic. COVID-19 infection can have a negative impact on semen analysis parameters, with potential long-term implications such as germ cell depletion and hypogonadism . We chosACE2 and TMPRSS2, both of which are critical in SARS-CoV-2 entry into cells, are expressed in some trophoblast, syncytiotrophoblast, and hypoblast cells, suggesting that embryos may be susceptible to COVID-19 infection [The implication of potential SARS-CoV-2 infection on embryo development and risk during trophectoderm biopsy for PGT-A was also considered. Studies suggest that nfection –23. Hongnfection . In sixtnfection . While fIt is important to highlight that this patient was young, a good responder, and, cost aside, would likely be able to undergo another cycle later without diminished changes of future pregnancies. In patients with diminished ovarian reserve, a delay in initiating IVF treatment up to 180 days from the initial visit does not affect pregnancy outcomes, and our patient would also likely have similar pregnancy outcomes should her cycle have been cancelled . HoweverIn the second case, the patient tested positive for COVID-19 on day 10 of stimulation. She also was asymptomatic. The risks of proceeding with retrieval were again compared to the benefits of cancelling the cycle. In contrast to the first case, this patient who would be proceeding with gonadotoxic chemotherapy would likely not have similar fertility outcomes should her cycle be cancelled. Patients who have a cancer diagnosis and desire future fertility are a unique and vulnerable population that must receive special consideration, especially during the COVID-19 pandemic. Leukemia, breast cancer, endometrial cancer, and cervical cancer are just a few malignancies that impact reproductive age women, highlighting the importance of counseling and offering timely fertility preservation options for those who have not yet completed childbearing , 27. TheInfertility is a well-known consequence of combination chemotherapy given for leukemia, although the reported rates differ based on various factors including chemotherapeutic protocol and age at treatment . Not proIn the setting of COVID-19 infection, this patient had similar risks of perioperative complications compared to the first case. While some studies show that surgery for malignant disease was associated with worsening perioperative outcomes in the setting of COVID-19 infection, it is unclear whether this patient's leukemia itself was an independent risk factor for complications in the setting of COVID-19 infection and surgery . FurtherAs the pandemic continues, new practice guidelines will be necessary to optimize ART care for patients with or exposed to COVID-19. Our practice was able to safely perform oocyte retrieval on two asymptomatic patients who tested positive for COVID-19 by minimizing in-person exposure prior to retrieval, reducing staff to essential, vaccinated personnel, and utilizing appropriate PPE including N95 masks for all staff involved with direct patient care based on the ASA recommendations for COVID-19 precautions . These aThese cases demonstrate the challenges in determining whether to proceed with fertility treatment in COVID-19-positive patients. More discussion is necessary on how to proceed should a patient test positive for COVID-19 and is asymptomatic during ART. Clinicians must weigh the risks of OHSS and potential for decreasing fertility with perioperative complications associated with COVID-19 infection. Additionally, the psychological and financial burdens associated with cycle cancellation and patient autonomy must also be factored into the decision. As we continue to provide fertility care in a world with COVID-19, an algorithm may be necessary to help clinicians proceed with these difficult decisions.We recommend cycle cancellation, per ASA guidelines, when COVID-19 infection is diagnosed in the early days of stimulation. However, we believe that cases must be individualized to balance risk/benefit ratios for each patient. If it is necessary to proceed with a procedure, appropriate risk mitigation strategies should be implemented to minimize COVID-19 exposure.


Clinicians should be aware that the number of recommended doses may differ between immunocompromised and immunocompetent patients. For immunocompromised children, including cardiac transplant patients, there are additional doses recommending in the primary series for most ages. In addition, guidance surrounding administration of booster vaccines is evolving and clinicians should check the ACIP website for the most updated recommendations (ACIP COVID-19 Vaccine Recommendations | CDC). As of January 2022, only the Pfizer/BioNTech mRNA vaccine is available for children in the United State, but there are ongoing clinical trials evaluating other pediatric vaccine candidates. Pediatric vaccine trials and observational studies have consistently demonstrated the COVID-19 vaccine is both safe and effective, with >90% effectiveness against severe disease.35 Children with underlying comorbidities, such as congenital heart disease, are at higher risk for severe disease, highlighting the importance of vaccination in this vulnerable group.The COVID-19 pandemic continues to change the world. The healthcare industry must adapt and respond as we understand more about the detection, transmissibility, severity of illness, vaccination, quarantine and isolation duration, effects on children, and treatment options for SARS-CoV-2, including variants of concern. While pediatric heart surgery  is running at or near normal capacity without significant restrictions, important issues in pediatrics continue to evolve. Since our original publications (below), several variants of concern have appeared, vaccinations have been authorized for children ≥ 5 years old, advances in diagnosis and treatment have occurred, and Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as an important entity. In light of these developments, an updated document is needed to ensure clarity of understanding and to facilitate optimal clinical decision-making.https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html2. Are there any specific considerations related to vaccine timing in cardiac surgery patients?As above, all eligible congenital heart disease patients should receive the COVID-19 vaccination. Ideally, the vaccine series should be completed at least two weeks prior to major surgery to reduce the chance of a child acquiring severe COVID-19 in the peri-operative period, but surgery should not be delayed in order to complete the vaccine series. In particular, patients who are candidates for heart or lung transplants should receive the COVID-19 vaccination series at least 2 weeks prior to transplant whenever possible to optimize protection both pre- and post-transplant (see question 7). This highlights the important role of cardiac surgeons in advocating for vaccination during pre-transplant evaluations. Cardiopulmonary bypass and transfusions may dilute or suppress the patient's intrinsic immunologic vaccine response. For these reasons, we often suggest vaccination immediately prior to discharge.Unvaccinated patients hospitalized for cardiac surgery or other illness should be strongly considered for vaccination prior to hospital discharge. Neither of these scenarios are themselves contraindications to vaccination; however, it is prudent to wait until after recovery from major surgery and critical illness to optimize immunogenicity from the vaccine.https://ishlt.org/ishlt/media/documents/ISHLT-AST-ASTS_Joint-Statement_COVID19-Vaccination_30-December.pdf3. What are the contraindications to pediatric COVID-19 vaccination?There are very few absolute contraindications to pediatric COVID-19 vaccination. Contraindications include a severe allergic reaction  to a prior dose of COVID-19 vaccine or vaccine component and/or history of COVID-19 vaccine-related myopericarditis (discussed below in question 4).https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html#Contraindications). Allergic reactions (including anaphylaxis) that are unrelated to the vaccine  are no contraindications or precautions. Some patients may experience a significant local reaction including erythema and induration after vaccination; this is not a contraindication to subsequent COVID-19 vaccines.Nonsevere reactions or allergies to the COVID-19 vaccine components, other vaccines, or injectable therapies, are precautions for COVID-19 vaccines; a detailed discussion of these is available on the CDC website . There are approximately 2000 cases reported to date in the United States, an estimated 5 to 10 cases per 1 million second doses overall and 40 cases per 1 million second doses in males 12 to 29. Fortunately, almost all affected teens with vaccine-associated myocarditis responded well to medical therapy. Population studies have demonstrated that the risk of COVID-19-related myocarditis is approximately 4 times higher than the risk of vaccine-associated myocarditis in all age groups.810Collectively, these data support that the benefit of COVID-19 vaccination outweighs the small risk of myocarditis in all age groups. Patients, particularly adolescent males, should be counseled on the potential and symptoms of myocarditis. For patients who develop myocarditis or pericarditis after a dose of an mRNA COVID-19 vaccine, administration of the subsequent dose of the mRNA vaccine is not recommended.There are no data related to vaccination during or after nonvaccine-related myocarditis or pericarditis . A prior history of myocarditis or pericarditis is not an absolute contraindication to vaccination, but it is recommended that vaccination be deferred until cardiac inflammation resolves. Based on expert consensus, a recent episode of multisystem inflammatory syndrome in children (MIS-C) is also not a contraindication to vaccination. Current recommendations are to wait approximately 90 days after MIS-C before administering COVID-19 vaccination because mild heart inflammation can be associated with MIS-C.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-11-2-3/04-COVID-Oster-508.pdfhttps://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html#Contraindications5. What is the role for testing asymptomatic patients prior to cardiac surgery?Asymptomatic screening has two potential benefits: (1) detection of early or mild disease in patients who could be at risk for worsening peri-operatively and (2) identification of patients who are infectious to facilitate appropriate transmission-based precautions or case delay to limit healthcare worker exposures.11,12 Given the current incubation period of the predominant Omicron variant circulating, screening tests are most beneficial when obtained within 2 to 3 days prior to surgery and less useful more than 5 days prior.6. What type of test is most appropriate?PCR tests detect any amount of viral genetic material and are the most sensitive test for detecting SARS-CoV-2. However, a PCR test may stay positive for weeks to months after an active infection, particularly in younger children or immunocompromised patients. PCRs may continue to be positive long after active infection has resolved, and the patient is no longer contagious. Thus, PCR tests are less useful when a patient has had a recent COVID-19 infection. Experts generally recommend against re-testing with a PCR test within 90 days unless new symptoms  have developed. They are less sensitive than PCR tests, meaning that they have a higher chance of a false negative or missing a current infection. However, they generally work well when combined with a high pre-test probability for detecting active infection—for example, when collected in a symptomatic individual. A positive antigen test is thought to correlate with viral transmissibility. Symptom and time-based strategies to end isolation are favored, but antigen tests may also have utility because patients no longer antigen positive are less likely to be infectious.Antigen tests, including most home COVID-19 tests, detect proteins from the SARS-CoV-2 virus, so are more likely to detect living “active” virus.Serologic or antibody testing is effective for detecting prior infection (nucleocapsid serology) as well as prior vaccination or infection (spike protein serology). It does not detect active infection, so has little role in preprocedural testing.https://www.cdc.gov/coronavirus/2019-ncov/hcp/testing-overview.html7. Are there special considerations for COVID-19 in cardiac transplant patients or other immunocompromised cardiac surgery patients?Patients who are immunosuppressed may be at higher risk of severe COVID-19. This includes solid organ transplant patients, particularly those who are more severely immunocompromised , as well as cardiac surgery patients with syndromes or postoperative complications that affect the immune system . Vaccine recommendations may differ for these immunocompromised individuals and the most updated CDC guidance should be followed regarding additional doses in the primary series and/or booster doses. Additionally, recent data supports completing COVID-19 vaccination pretransplant, when possible, because immunogenicity of vaccines may not be as robust posttransplant due to immunosuppression.8. What are the considerations for newborns born to mothers with COVID-19?Perinatal transmission of SARS-CoV-2 is rare, estimated to occur in 2% to 4% of neonates born to an infected mother. When perinatal transmission occurs, it generally occurs in the postnatal period via infectious respiratory droplets. Transplacental or intrapartum transmission of SARS-CoV-2 is exceedingly rare but has been reported. The most common symptom among infected neonates remains respiratory distress.Even if a patient has received all recommended vaccines, it is still possible that they will be infected with SARS-CoV-2, and this may occur more often in solid organ transplant recipients compared to the general population. In this case, cardiac transplant patients may be candidates for several treatments which target high-risk individuals, including monoclonal antibody therapy (see treatment options below in question 8).Most infants born to SARS-CoV-2 positive mothers do not need to be separated from the infected mother/family. However, it may be reasonable to separate infants with congenital heart disease who are expected to require repair within the first 1 to 2 weeks of life to avoid the risk of them acquiring COVID-19. The choice regarding separation of infant–mother dyads should be an individualized decision made by the local surgical and medical teams, in collaboration with the affected families. If not separated, the American Academy of Pediatrics recommends that infectious mothers mask and perform hand hygiene when providing hands-on care to the newborn. Breastfeeding (masked) or feeding with maternal breastmilk is permitted and encouraged in all scenarios. Breastmilk from infectious individuals does not transmit SARS-CoV-2 and has been shown to have anti-SARS-CoV-2 antibodies.https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/faqs-management-of-infants-born-to-covid-19-mothers/9. What are the current treatment options for COVID-19? (updated)The majority of children infected with SARS-CoV-2 experience a mild illness and recover uneventfully with supportive care only. However, some cardiac surgery patients may be at sufficiently high risk that even mild illness warrants consideration of treatment to slow potential progression. Others may develop illness severe enough to warrant hospitalization, in which case therapy is often indicated. There are several different categories of treatments for children with COVID-19 including (1) passive immunization , (2) antivirals, and (3) immunomodulatory therapies. While these data are promising, direct extrapolation to children is challenging. Sotrovimab is currently authorized only for patients ≥12 years old and ≥40 kg who are at high risk for progression to severe illness. Sotrovimab supply is extremely limited in the United States, so available drug is often allocated preferentially to older adults at the highest risk.For patients with mild illness able to be managed in the outpatient setting, administration of monoclonal antibodies can be considered in select high-risk patients. There are several monoclonal antibodies that bind to distinct but overlapping regions of the SARS-CoV-2 spike protein, preventing the virus from attaching to human cells. Clinical trials have demonstrated consistent reductions in hospitalization with monoclonal antibody therapy. Because of this mechanism, they are most effective when given very early in the course of illness, when viral replication is highest. Multiple monoclonal antibodies are authorized under FDA Emergency Use Authorization (EUA). However, as of January 2022, only one monoclonal antibody, called sotrovimab, has activity against the Omicron variant. Sotrovimab was studied in a randomized trial including unvaccinated adults with comorbid medical conditions  and was administered to participants within 5 days of symptom onset. Treatment with sotrovimab was associated with an approximately 85% relative risk reduction in hospitalization or death.Convalescent plasma from recovered patients is also available under EUA for children of all ages but there is limited evidence to date of improved outcomes, with the most promising data supporting use very early after infection in severely immunocompromised adults. Very few blood banks are supplying convalescent plasma as of January 2022.https://www.fda.gov/media/155050/download). Notably, the ritonavir component is a strong CYP3A inhibitor and has potentially life-threatening drug interactions with several cardiac medications, including many anti-arrhythmics, amiodarone, tacrolimus, or warfarin. Molnupiravir is a nucleoside analog that inhibits viral replication, and it is authorized under an FDA EUA for outpatients  ≥18 years old at risk of severe disease progression in situations where no alternative treatment  is available. Molnupiravir is substantially less efficacious in preventing severe disease than other available therapies and has significant toxicities including teratogenicity; it is not available for children due to potential bone and cartilage toxicity.Nirmatrelvir/ritonavir is an oral protease inhibitor combination antiviral with EUA for outpatient children (≥12 yo and >40 kg) at high risk of progression to severe COVID-19; initiation is recommended within 5 days of COVID-19 symptom onset. This drug had reported efficacy for decreasing severity in pharmaceutical-sponsored adult trials but this data has not yet been published with peer review  and has now also been granted EUA for younger children (≤12 yo and ≥3.5 kg). Remdesivir seems to shorten the duration of illness among hospitalized patients with hypoxia and may slow progression to respiratory failure. It is the most commonly used inpatient COVID-19 antiviral at this time, including in hospitalized children, though to date there remains limited pediatric evidence.Dexamethasone continues to be the first-line immunomodulatory therapy for hospitalized children with severe COVID-19 with significant hypoxia and/or invasive or noninvasive mechanical ventilation, including patients on high-flow nasal cannula. This practice is based on data from the RECOVERY trial, which demonstrated a reduction in mortality with dexamethasone therapy in adults requiring supplemental oxygen or respiratory support.23 Prior to these studies, multiple trials conducted in hospitalized patients who were less severely ill demonstrated no benefit from tocilizumab, suggesting that efficacy is limited to a subset of critically ill patients. Despite a lack of pediatric evidence, some experts use tocilizumab in critically ill children with COVID-19, particularly those with evidence of inflammation despite dexamethasone. In part this is because tocilizumab is commonly used for several non-COVID-19 pediatric inflammatory conditions, so adverse effects and toxicity are understood. Baricitinib was studied in combination with remdesivir initially; the combination of baricitinib and remdesivir reduced time to clinical recovery in hypoxic adults compared to the use of remdesivir alone. Subsequently, baricitinib was compared to standard care in hypoxic adults and demonstrated a reduction in mortality in the baricitinib group. Baricitinib received EUA status for children ≥2 years of age with COVID-19, and may be considered in critically ill children with escalating respiratory support needs.Two other immunomodulatory therapies may be considered for hospitalized children with severe COVID-19: tocilizumab  and barcitinib (a JAK inhibitor). Consultation with pediatric subspecialists comfortable with the use of immunomodulatory medications is suggested. Two randomized trials have demonstrated that tocilizumab may reduce both mortality and severity of disease in critically ill adults, particularly those with significant inflammation.IDSA Guidelines on the Treatment and Management of Patients with COVID-19 (idsociety.org)https://www.covid19treatmentguidelines.nih.gov/special-populations/children/https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/outpatient-covid-19-management-strategies-in-children-and-adolescents/10. Are the Delta and Omicron variants worse or more severe in pediatric populations than prior SARS-CoV-2 variants?Although there have been more children hospitalized during the Delta and Omicron surges both globally and in the United States, expert consensus is that disease caused by these variants is not necessarily more severe in children than prior variants. Prevalence of infection of any severity has been higher during these variant surges, so it is not surprising that the absolute number of pediatric hospitalizations is also higher, including children requiring critical care. This increase may be in part due to increasing transmission and contagiousness of Delta and Omicron variants. Further, children are less likely than adults to be vaccinated and therefore remain more vulnerable to infection. In many adult vaccinated populations, omicron has had a milder disease course than prior waves. This is encouraging and likely to also be true in children, though we have less evidence to date; it is another reason to encourage pediatric vaccination.https://publications.aap.org/11. What PPE is needed for COVID-19, and is it different for different variants? (updated)Our knowledge of respiratory disease transmission continues to grow throughout the pandemic, including understanding of appropriate PPE . SARS-CoV-2 is transmitted via a combination of larger infectious droplets and smaller infectious aerosols, which exist on a spectrum. Transmission generally occurs within 6 feet of an individual, though aerosolization can occur beyond that distance, particularly during certain procedures  often termed “aerosol-generating procedures.” General PPE advice during the first year of the pandemic included surgical masks and eye protection with N95 or respirators are recommended for aerosol-generating procedures. This worked well to prevent transmission in most healthcare settings and the community. During 2021, we have seen variants emerge with higher transmissibility, and, in response, many healthcare systems have expanded the indications for N95/respirator protection. Currently, the CDC recommends the use of either N95s or well-fitted surgical masks while caring for known COVID-positive patients or persons under investigation (PUIs) for COVID-19. Choice of a mask may in part be based on the types of care being performed , patient or healthcare worker specifics (such as vaccination status), and facility parameters like ventilation. Eye protection should be worn at all times during COVID-19 care. While cloth masks may be more comfortable and are often worn in a nonhospital setting, they are less effective than medical-grade masks and should not be used for clinical care. Guidance continues to evolve, and we recommend following local infection control guidelines which may be based, in part, upon local COVID-19 prevalence.In terms of patient and community protection, the best way to prevent respiratory disease transmission is to employ a “layering” approach. Layers of protection may include vaccination, ventilation, distancing, and masking in certain settings.https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.htmlThe dreadful SARS-CoV-2 virus continues to create exceptional challenges at all levels—public sector, hospitals, and the entire healthcare industry. We are now more adept at evaluating and prioritizing (COVID-19 and non-COVID-19) patient problems and have established standardized management algorithms. Collaboration between the surgical and medical specialties has been exemplary. Leadership in our specialty is about bringing order to chaos and fighting uncertainty…and that is what our specialty is doing collectively. As the virus and pandemic evolve, the medical profession evolves. We are living in unprecedented times which have presented often difficult dilemmas. Who gets surgery and who should be delayed? Can family members visit their ailing child or sibling? When and how best to test? How long to quarantine? Some of these questions have been answered and some will continue to change. Regardless, we will adapt and make decisions based on the accumulation of scientific evidence to provide the best possible care to our patients during this inimitable time.