In multivariate analysis predictors of PSM were a lower RENAL score (p = 0.001), longer warm ischemia time (WIT) (p = 0.003) and Chromophobe Renal Cell Carcinoma (chrRCC) (p = 0.043). This study found no impact of PSM on RFS, MFS or OS, and predictors of PSM were the RENAL score, WIT and chrRCC.The oncological impact of positive surgical margins (PSM) after robot-assisted partial nephrectomy (RAPN) is still under debate. We compared PSM and Negative Surgical Margins (NSM) in terms of recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) after RAPN, and we identified predictive factors of PSM. Multi-institutional study using the UroCCR database, which prospectively included 2166 RAPN between April 2010 and February 2021 . Two groups were retrospectively compared: PSM versus NSM. Prognostic factors were assessed using Kaplan–Meyer curves with log-Rank test, cox hazard proportional risk model and logistic regression after univariate comparison. 136 patients had PSM (6.3%) and 2030 (93.7%) had NSM. During a median follow-up of 19 (9–36) months after RAPN, 160 (7.4%) recurrences were reported. Kaplan–Meier curves and analysis suggested that RFS, MFS and OS were not affected by a PSM ( Partial nephrectomy (PN), whenever possible, is the reference treatment since 2010 to date4. The proliferation of robotic surgical platforms has resulted in an exponential increase in the number of patients undergoing robotic‐assisted partial nephrectomy (RAPN)5.Surgically resected tumors show a lower TNM stage than was the case 20 years ago, thanks to routine cross-section imaging6.The aim of this nephron-sparing surgery (NSS) is an optimal oncological control while preserving overall renal function, without any post-operative complication. However, its main pitfall remains the possibility of positive surgical margins, occurring in 0.1–10.7% of cases7. The majority of studies reported so far have indicated that positive surgical margins do not correlate with a higher risk of metastases or decreased cancer specific survival (CSS)9. On the other hand, large retrospective studies showed that PSM, are an independent predictor of recurrence11. Absence of PSM, such as in Trifecta12 achievement, has also shown a predictive role on long term outcomes after RAPN13.European guidelines recommend intensified follow-up after PSM encounter but there is no consensus for a particular strategy and the association between PSM and recurrence is still under debateThe objective of this study was to compare the oncological outcomes of patients undergoing RAPN for RCC according to the surgical margin status, and to identify factors associated with PSM.After institutional review board approval, the MARGINS study was conducted in the framework of the UroCCR project (NCT03293563). All patients were given oral and written information about the objectives and methodology of the UroCCR project, and data of those who provided written and informed consent were prospectively included in the UroCCR database. All experimental protocols were approved by the ethics committee of Commission Nationale de l'Informatique et des Libertés (CNIL authorization number DR-2013-206). We reviewed the medical records of all patients in this database, between April 2010 and February 2021 in 20 French centers.3 were followed. The following preoperative data were collected for each patient: age at RAPN, sex, BMI, ECOG and ASA score, Tumor characteristics, including the clinical TNM stage, clinical tumor size, tumor side and radiological RENAL nephrometry score. All patients had pre-operative CT scan including abdominal and pelvic sequences for evaluation of the tumor, most of the time with thoracic sequences for assessment of extension.Given the retrospective multicenter study design, the surgical techniques and preoperative work-up were not standardized across centers, but European GuidelinesThe following surgical data were recorded: indication of NSS , surgical approach , retroperitoneal (RP)), overall operative time, type of clamping, warm ischemia time (WIT), estimated blood loss, peri-operative complications and conversion to open surgery. The surgical approach was considered discordant when the tumor was anterior with an RP approach and inversely for posterior tumors with a TP approach.14 and graded according to the Clavien–Dindo classification15.Pathology characteristics included histologic subtype, pTNM, diameter and grade and UISS prognostic category. Post-operative complications were recorded according to current guidelinesFollow-up protocols were similar across centers. It involved a clinical interview, a physical examination, serum creatinine, a CT scan to assess local recurrence and metastasis progression. Median follow-up was calculated as the median time between surgery and the last consultation.The primary endpoint was PSM, which was defined as the presence of cancer cells at the margin of the surgical specimen reported for H&E stained tissues.p-value < 0.25 in univariate analysis were included in the multivariate model. Collinearities were included in the initial model, and the final model was built with factors restricted to those reported in the existing literature . R statistical software was used for the statistical analyses16. All tests were two-sided with a significance level at p < 0.05. All methods were performed in accordance with the relevant guidelines and regulations.Means and standard deviations were reported for continuous variables, and proportions for nominal variables. The exact Fisher test was used to compare nominal variables, the Kruskal–Wallis test for ordinal variables and the Student test to compare quantitative continuous variables. Non-parametric tests were used for small sample sizes. The probabilities of OS, RFS and MFS were estimated using the Kaplan–Meier method. Multivariable Cox regression analyses were used to seek predictors of OS, RFS and MFS. Only variables with a All patients were given oral and written information about the objectives and methodology of the UroCCR project, and data of those who provided written consent were prospectively included in the UroCCR database . The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.We reviewed the medical records of the 12,936 patients of the UroCCR network, including hereditary syndromes if known at baseline, and excluding patients with previous history of RCC. First, we excluded those who underwent open partial or radical nephrectomy , then those who had laparoscopic partial or radical nephrectomy . Of the 2922 patients who underwent RAPN over the study period, 2166 met the inclusion criteria. Exclusion criteria were cT3b-4, cN + or cM + (n = 332), conversion to OPN (n = 41), conversion to radical nephrectomy (n = 90), benign (n = 140) or multiple (n = 173) tumors. , ASA (p = 0.4), cTNM (p = 0.987) were similar in both groups. The RENAL Score was lower in the PSM group . The overall median follow-up was 1936 months; 160 (7.4%) recurrences  were reported: 9 (6.6%) in the PSM group and 151 (7.4%) in the NSM group.Of the 2166 patients included, 136 patients had PSM (6.3%) and 2030 (93.7%) had NSM. Patients’ characteristics are summarized in Table p = 0.001). Complications during surgery , retroperitoneal approach (n = 168) , discordant approaches  and on-clamp procedure  were not associated with PSM. Intraoperative data are shown in Table PSM was associated with a longer mean WIT  was significantly associated with PSM, whereas the ccRCC histology type  was associated with a lower likelihood of PSM.chrRCC . Survival analysis did not show any difference between the groups for RFS .The median follow-up was 21.5 mo [9–37] for PSM: versus 19 mo [9–36] for NSM (p = 0.001), a longer warm ischemia time (WIT) (p = 0.003) and chrRCC histology (p = 0.043) were predictors of PSM.Multivariate analysis Fig.  showed t17. Therefore, it had no impact on clinical practices over the years for the authors. In order to achieve its nephron-sparing potential, RAPN has to meet three main challenges: WIT < 25 min to prevent renal failure, oncological control, currently evaluated as NSM, and no perioperative complications.Early-stage diagnosis in RCC and the diagnosis of small renal masses have led to an evolution in surgical approaches. Since 2010 to date, for cT1-T2 renal mass, PN and then RAPN rather than OPN, when feasible, is the recommended surgical approach18, and an NSM is no guarantee that a recurrence will not occur7. Given the above, the prognostic value of PSM after RAPN is still a matter of debate.Although a PSM could be regarded as cancer cells remaining in the kidney, hemostasis may induce ischemia and necrosis in these cells. In addition, tumor cells in the surgical specimen may be in tangential contact with the margin, corresponding to a PSM, but with no cancer cells remaining in the resection bed. As for NSM, the analysis of frozen sections during tumor resection led to 5% of false-negative NSM6, but local recurrence occurred in only 5.9% (N = 8) of our PSM patients. Our median follow-up was 19 months, which is equivalent to the median time to recurrence after PN (19 mo) according to Takagi et al.19. In the literature, there is no consensus on the presence or absence of a statistical correlation between surgical margins and recurrence rates or specific survival. On one hand, Petros et al. showed a close association between PSM and disease progression after PN20 in a large single-center cohort of 2297 PN with 1863 (81%) RCC and 34 (1.48%) PSM. The 34 PSM patients were matched 1:3 with 100 NSM patients for tumor size, RENAL score, grade, and pathologic stage. They found that PSM had an impact on 5-year survival probability for OS (0.99 for NSM vs. 0.97 for PSM), local RFS (0.98 vs. 0.77), and MFS (0.95 vs. 0.84). Moreover, in another analysis, Wood et al.21 demonstrated a strong association between PSM at the time of PN and local tumor bed recurrence after a median time of 23mo: 15.9% of PSM in the recurrence group versus 3% in the control group. Khalifeh et al.22 evaluated the oncological outcomes of 21 PSM among 947 RAPN for malignant tumors with 13 months of median follow-up. Following the 947 procedures, there were nine recurrences and four cases of metastases. PSM were strongly linked to recurrence, with an HR of 18.4 after adjustment. The 3-year recurrence-free rate and metastasis-free survival rate were lower in the PSM group than in the NSM group (respectively 47% vs. 98.3% and 63% vs. 99.5%). In a retrospective study of 1240 PN for RCC with 97 PSM leading to 67 recurrences, Shah et al.23 demonstrated that PSM was an independent risk factor for recurrence. In their subgroup analysis, PSM was found to be a risk factor for recurrence in high-risk tumors (pT2-3a or grades III–IV) but not in low-risk tumors (pT1 or grades I–II). Moreover, Bernhard et al.24 evaluated the predictive factors for ipsilateral recurrence in 809 NSS procedures with 27 months of follow-up. They reported 26 local recurrences and 15.4% of PSM. Multivariate analysis showed a link between PSM and local recurrence with an HR of 11.5 (p < 0.01).We found 6.3% of PSM, which is in line with the 0.1–10.7% reported in the literature.8 conducted a matched-pair study that included 101 PSM and 102 NSM matched for surgical indication, tumor size, and tumor grade. PSM had no influence on 5-year RFS, 5-year cancer specific survival (CSS) or 5-year OS. Yossepowitch et al.25 studied 77 PSM in 1390 PN with a median follow-up of 40.8 months and found that PSM were not associated with worse RFS or MFS. In addition, Rothberg et al.26 compared 797 NSM with 42 PSM after RAPN and reported that oncological outcomes in PSM patients were no worse than those in NSM patients after a median follow-up of 18.8 months. The outcomes in our study are in line with those of the Rothberg study in that we found no statistical association between PSM and RFS, MFS or OS.In contrast, Bensallah et al27, who founded that smaller tumors cT1a versus cT2, laparoscopic technique rather than open and volume center < 60 RAPN/year are risk factors of PSM. Another hypothesis is that easier procedures may have been left to young surgeons, since most of the centers in the study are academic.Multivariable analysis showed that higher RENAL scores were associated with NSM. This paradoxical finding could be because smaller masses within the renal parenchyma may be harder to find, and the surgeon might feel overconfident during such a PN procedure, which in theory should be technically easier given the small size of the tumor. This hypothesis is supported by Schiavana et al.As for more complex tumors, surgeons performing RAPN may cut more deeply into healthy parenchyma to reduce the risk of PSM. Whatever the reason, this result is robust even in multivariable analysis, after the inclusion of tumor size, overall operative time, blood loss and histology..28, we found that the RP approach (n = 168) was not a risk factor for PSM. They specifically compared RP with TP, though in a smaller sample size (48 RP vs. 290 TP) and found no significant difference between the two groups for PSM. Arora et al.29 also compared 99 RP-RAPN with 394 TP-RAPN and found no difference between the arms for margin status. Both of these studies suffered from the same limitations: retrospective design with a small sample size, and the absence of precise data about the surgeon’s experience and surgical technique for the tumorectomy.Like Takagi et al30. A longer WIT also reflects the occurrence of surgical difficulties during the procedure.As expected, a longer WIT is also a risk factor for PSM. WIT is a proxy for surgical experience and falls steeply in the early part of the learning curve, as described by Larcher et al.31.The fibrous stromal tumoral reaction and the presence, size and density of the tumor fibrous capsule vary according to histological sub-type. The reduced nature of these elements in chrRCCs may explain the higher frequency of PSMs in this sub-typeFinally, we set out to determine the impact of margins on oncological outcomes in this large, prospective, multicenter cohort of patients. To this end, further analyses are ongoing and will be published in due course.. (40.8mo)25. However, according to part of the literature, the median time to recurrence after RAPN ranges from 13.1 to 20 months33 and median time between partial nephrectomy and detection of local bed tumor recurrence was 23 months21. Experience is also an important factor to include. The number of RAPN already performed at the time of the first procedure recorded in UroCCR was not available for all surgeons, neither was the involvement of trainees. It was therefore impossible to assess the impact of experience on PSM. However, Larcher et al.30 highlighted that although surgeon experience was associated with a shorter warm ischemia time (WIT) and a lower probability of Clavien–Dindo complications (CD) ≥ 2, but it was not associated with a lower rate of PSM. We believe this cohort shows routine practice in university centers, where juniors are operating patients under seniors’ supervision so that EXP is a shallow concept. Finally, like numerous studies about RAPN, we lacked data concerning the length of the margin, the tumorectomy technique and the presence of adherent perinephric fat (APF), but these two last factors do not seem to be predictive of PSM in the literature36. We also lacked data for the treatment of the recurrence, and this treatment may have generated a selection bias by changing the results for MFS and OS. However, Brassier et al.37 showed that 40% of patients treated for local recurrence after PN by percutaneous ablation or surgical resection experienced disease recurrence within a median follow-up of 23 mo, which also means that only 60% of patients presented controlled disease after retreatment.Our study has several limitations that should be acknowledged. First, we deliberately excluded advanced tumors , benign or multiple tumors and metastatic disease in order to establish a homogenous model of RAPN. Secondly, the follow-up was relatively short. Other series had a longer follow-up, especially that of Yossepowitch et alBased on this large, French multicenter, retrospective series, PSM rates remained low after RAPN and had no impact on short-term oncological prognosis. PSM was associated with a longer WIT, chrRCC and surprisingly with a lower RENAL score.


Resting energy expenditure (REE) comprises 60% of total energy expenditure and variations may be associated with gestational weight gain (GWG). This study aims to explore the usability and feasibility of REE guided intervention for GWG in obese and overweight women. We conducted a prospective cohort study in LuHe Hospital of Capital Medical University in Beijing, China between May 1, 2017 and May 31, 2018. Obese/overweight women who had routine prenatal care visit at 10 to 13 weeks of gestation, were recruited after written informed consent was obtained. The intervention group  used REE calculated daily total energy to manage GWG, while the control group  used prepregnancy body mass index calculated daily total energy to manage GWG. GWG and daily total energy between the 2 groups were recorded from 10 to 13 weeks of gestation to delivery. A total of 68 eligible women (35 in intervention group and 33 in control group) were included in the final analysis. Daily total energy in the intervention group increased less than the control group, especially from 2nd trimester to 3rd trimester . The variation of daily total energy from 1st trimester to 3rd trimester in the intervention group was lower than the control group . Overall GWG of the intervention group (13.45 kg) was significantly lower than the control group (18.20 kg). The percentage of excess-GWG in the intervention group (31.42%) was also significantly lower than the control (57.57%). Findings from our pilot study suggest that diet recommendation basting on REE may improve management of GWG in obese/overweight women. The Institute of Medicine weight gain guidelines have been widely accepted. Yet a systematic review in 2017, the authors found that about 47% of women gained excess weight than the recommended weight. Excessive GWG is associated with a multitude of complications that impact both maternal and neonatal health. These adverse short- and long-term health consequences include preeclampsia, gestational diabetes mellitus (GDM), postpartum weight retention, macrosomia, neonatal hypoglycemia, and admittance to the neonatal intensive care unit.–7 A recent review of about 15,581 women in Beijing, China showed that 67.8% of prepregnant obese women had excess weight gain during pregnancy.Obesity/overweight is a major public health problem worldwide. In 2015, rates of obesity and overweight in Chinese adults were 11.9% and 30.1%, respectively, and about 50% women were obese or overweight at the beginning of their pregnancy.,10 The most widely used method is based on pre-pregnant body mass index (BMI), although this method often leads to an overestimation of the caloric needs in obesity/overweight women. An excess of caloric intake leads to hyperglycemia with increased CO2, free fatty acid, and excess GWG. Alves et al suggested that indirect calorimetry should be performed preferentially in pregnant women with obesity/overweight to determine TEE adequately, to adjust for over- or under-energy intake.GWG is closely related to total energy expenditure (TEE), and TEE of pregnant women with obesity/overweight varied greatly. It remains controversial regarding the ideal method to monitor/manage total energy during pregnancy.,13 It is well known that pregnant women usually reduce their physical activities and expend less energy, especially for obese/overweight women. Therefore, physical activity is not the main contributor of TEE in pregnant women. Increased basal metabolic rate (BMR) is instead one of the major components of TEE during pregnancy. Resting energy expenditure (REE) and BMR are interchangeable terms, and REE is frequently used in clinical practice due to difficulties in the measurement of BMR. An important concept in energy balance is that TEE is composed primarily of REE, which accounts for approximately 60% to 70% of TEE. REE shows a significant correlation with energy intake (EI).,19 Weight and body fat are important factors contributing to variability of REE during pregnancy and are correlated to cumulative REE in pregnancy. Recently, studies have found that changes of REE reflect increase in calorie needs and weight gain.,20 Some investigators hypothesized that interventions could be developed to tailor recommendations for EI for women’s needs based on REE measured in clinical setting, especially for obese/overweight women.,21,22 We hypothesized that REE could be improve the management of GWG. We therefore explored the usability and feasibility of using REE guided diet recommendations to manage GWG for pregnant women with obesity/overweight in a small-scale study in China.Previous recommendations for obese women consist of assessment and counseling, which includes the provision of information on the increased health risks of obesity in pregnancy and encouragement to make lifestyle changes to support weight management. Unfortunately, to date, lifestyle intervention trial had limited success at mitigating excess-GWG.This was a prospective cohort study, and was conducted in accordance with the Strengthening the reporting of cohort Study in STROBE guidelines. This study complies with the Declaration of Helsinki, for ethical considerations. We obtained approval from the Research Ethics Committee of LuHe Hospital of Capital Medical University in Beijing (2018-LHKY-027-02), China, before the commencement of this study, and obtained written informed consent from all participating patients.2 ≥ 30) or overweight (30 > BMI ≥ 25) who visited LuHe Hospital, Capital Medical University in Beijing, China, for their routine prenatal care at 10-13 weeks of gestation between May 1, 2017 and May 31, 2018. High-risk pregnancies with the following diseases were excluded: multiple gestations, fetal growth problems, gastrointestinal disorders, malabsorptive diseases, hyper- or hypo-parathyroid conditions, diabetes mellitus, cardiac diseases and conditions, and intellectual disabilities.We recruited pregnant women with obese  and then again at 2nd trimester (24–28 weeks of gestation) and 3rd trimester (32–36 Weeks of gestation). For this group, TEE was obtained by measuring REE and physical activity index (PAI). TEE recommendation was adjusted, depending on REE from 2nd trimester to 3rd trimester.Below is the formula for TEE calculation for the 2 groups:Intervention group:TEE = REE × PAIPAI was assessed using the International Physical Activity Questionnaire (IPAQ) before measuring REE. IPAQ reported as Metabolic Equivalent-Minutes per week (MET-minutes/week). PAI was obtained at recruitment (1st trimester 10–13 weeks of gestation) and then again at 2nd trimester (24–28 weeks of gestation) and 3rd trimester (32–36 weeks of gestation).Exercise level was defined as the following:Low level (PAI = 1.2): total physical activity of MET-minutes/week < 600.Moderate level (PAI = 1.5): total physical activity of MET-minutes/week between 600 and 3000..High level (PAI = 1.7): total physical activity of MET-minutes/week > 3000O2) and carbon dioxide production (VCO2) were monitored continuously for 30 minutes while the participant remained awake, silent, and motionless. Minute by minute values of VO2, VCO2, respiratory quotient, and energy expenditure were monitored over the 30-minute collection period to obtain the REE. REE and body composition were measured at recruitment , 2nd trimester (24–28 weeks of gestation), and 3rd trimester (32–36 weeks of gestation).We used Vmax Encore 29n (product of CareFusion company USA) to measure REE. The measurement was conducted by a professional technician, at LuHe Hospital Adult Nutrition Research Center. Participants were asked to arrive at the nutrition center in the morning after a 12-hour overnight fast. They were instructed to have a 30-minute rest in a semi-recumbent position, remaining calm during this time. They were then escorted to a comfortable (temperature maintained at 21–22°C) room and asked to lie down quietly for 30 minutes. An instrument with a transparent plastic hood was positioned to cover the area from head to neck, with fresh air free flowing through the instrument. After the equilibration period, oxygen consumption (VO2 + 1.106 × VCO2) × 4.18(Weir’s)REE = (3.941 × VFor the control group:Kg × ECTEE = (Height-105)EC: energy coefficient according to the level of Pre-pregnant BMI.Overweight: 25–30 Cal/kg·dayObese: 20–25 Cal/kg·dayIdeal Weight (Kg) = Height-105Nutritional recommendation,25 GWG of 2 groups were monitored and recorded each week. Dietary recommendations for the 2 groups were based on guidelines of GDM. GDM guidelines were used because no dietary guideline existed specifically for pregnant women who were obese/overweight. Daily total energy was generally provided by approximately 50% to 60% of energy from carbohydrate, 25% to 30% from fat, and 15% to 20% from protein, divided into 3 meals and 3 snacks. Food diary was recorded on daily basis by the participants themselves, including carbohydrate, meat, vegetables, and oil. Food was weighted with an electronic scale with a precision to 1 g. Study staff frequently contacted participants by telephone, text messages or WeChat to check compliance every week. Food diary provided a basis for estimating total EI to nutritionist. It was considered satisfactory if total EI was not less or more than 10% to 15% of the calculated TEE; otherwise, the nutritionist would give them dietary instruction.The hospital nutritionist made dietary recommendations based on TEE by the way of Food Exchange Share. For the intervention group, daily total energy recommendations were adjusted, depending on REE measured at 2nd trimester and 3rd trimester. For the control group, daily total energy was calculated at recruitment by the standard method involving ideal weight and pre-pregnant BMI only. An extra 300 Kcal was added to the daily total energy at 2nd trimester, and an extra 450 Kcal was added at 3rd trimester as recommended by guideline for the control group.2. During the duration of the study, maternal weight was measured with an electronic scale with precision to 0.1 kg at each study visit. Participant was asked to wear a gown of known weight and with no shoes or jewelry on. Rate of weight gain was calculated as the total weight gain in kilograms divided by the number of weeks the participant was followed.Anthropometrics data were collected at every study visit for both groups except for prepregnancy weight which was obtained by participants recall at first study visit. Research staff collected height using an anthropometer with a precision of 1 mm for height. These measurements were used to calculate BMI as kg/mVenous blood was drawn from study participants after a 12-hour fast, as well as plasma and serum samples. The plasma and serum samples were stored at ≥80°C before testing. Analyses of triglycerides (TG), total cholesterol (TC), high-density lipoproteins cholesterol (HDL-C), and low-density lipoproteins cholesterol (LDL-C) were conducted at the Biochemistry Laboratory of LuHe Hospital. TG was detected by phosphor glycerol oxidase method. TC was measured with bile Sterol oxidase method. HDL-C and LDL-C was detected by direct one-step method. Reagent from North Provided by Beijing Jiuqiang company, Olympus AU400 automatic biochemical analyzer  was used for testing. When TG more than 1.7 mmol/L or/and TC higher than 5.17 mmol/L or/and HDL-C lower than 0.77 mmol/L or/and LDL-C higher than 4.13 mmol/L were abnormal.Demographic and clinical data including occupation, age, education, family income, family history, past history, gravidity, gestational age, and pregnancy complications were collected by study staff using an ad hoc questionnaire developed by the research team. Gestational age was based on last date of normal menstrual period and validated by ultrasound examination in early gestation. Study staff assessed exercise condition by the IPAQ to estimate PAI.P-value of the Kolmogorov–Smirnov’s test was higher than .05, the data was considered normally distributed and 2 independent samples Student’s t-test (2-tailed) was used to compare the mean differences between the 2 study groups. For categorical data, the differences between the 2 groups were compared by using the Pearson χ2 or Fisher’s exact test. All test statistical tests were 2-sided, with significance evaluated at P < .05.Statistical analysis was performed using the SPSS 18.0  for Windows. Distribution of data was assessed by Kolmogorov–Smirnov’s test. If the A total of 109 obesity/overweight women were recruited into this study. They were divided into 2 groups according to the study periods. The intervention group (n = 55) were recruited between January 1 and May 31, 2018. The control group (n = 54) were recruited between May 1 and December 31, 2017. Forty-one participates were excluded the study for the following reasons: diagnosed GDM , thyroid disease , miscarriage (2 in the control group), drop out trail , lost to follow , or with incomplete study data . A total of 68 eligible women (35 in the intervention group n = 35 and the control group n = 33) were included in the final analysis  in the whole pregnancy. Obviously, it is inappropriate to adopt a “one size fits all” energy recommendation for women, leads to excess- or under- weight gain in pregnancy. Our study suggested that in order to get appropriate weight gain for obesity/overweight women, individual EI recommendation is needed for women who have more risks of excessive GWG.Excess EI during pregnancy may have a negative impact on health outcomes for pregnant women and their infants. REE rises ranging from 13% to 35% in pregnancy, because of increased maternal body mass.,29 Rasmussen hypothesized that nutritional intervention should be developed to tailor recommendations for EI for obese/overweight women’s needs based on REE measured in clinical setting. Our pilot study, basing on REE to guide diet to manage GWG, aims to test this hypothesis. Considering increased REE or BMR, we chose the formula combine REE and PAI, to calculate TEE. Our study suggested that individual EI recommendation is needed for obesity/overweight women to get appropriate weight gain. Whether this formula fits other categories pre-pregnancy BMI, requires conformation by additional studies.Physical activity is not the main contributor of TEE in pregnant women, while REE is one of the major components (about 60%–70%) of energy expenditures during pregnancy.To the best of our knowledge, this is the first study in China and one of the few studies in the world that has assessed the effect of REE calculated TEE on managing GWG. The study generated results that could be useful in the management of GWG for obese/overweight women. However, this study has several limitations. First, because of resources and other logistic difficulties in our hospital, a before-after design instead of a parallel randomized controlled trial conducted, making it difficult to make a direct estimation of the effect of REE based management of GWG with routine care. On the other hand, before-after comparison avoided communication among patients in the intervention group and the control group with reduced risk of cross-contamination. There is no change in maternity care team and hospital facilities, and the distribution of baseline characteristics of the 2 groups was essentially the same. As a result, the risk of bias/confounding from non-randomized design may be small. Second, this study was based on a sample size recruited in a single center. Replication of the study findings by future large-scale studies is needed. Third, some of the data such as pre-pregnancy weight was collected based on women’s recall, which may introduce certain amount of bias.Our pilot study suggests that diet recommendation based on REE may improve management of GWG for obese/overweight women. Large-scale randomized controlled trials are needed to confirm the findings from our pilot study.X.Z. and J.G. designed the study, conducted the statistical analysis of the data, and drafted the manuscript. W.M and P.X. conducted the lab tests and collected the clinical data. C.Z and S.J performed nutritional and lab analysis. L.G. reviewed the interpretation of the result and the manuscript. S.W.W supervised the study implementation and statistical analysis, and critically revised the manuscript. All authors participated in the review and critical revisions of the final manuscript. The correspondence authors attest that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.Data curation: Xiuling Zhao, Shan Jiang.Formal analysis: Xiuling Zhao, Shi Wu Wen, Wei Ma, Jie Gao.Investigation: Xiuling Zhao, Pili Xu, Chunmei Zhang.Methodology: Shi Wu Wen, Laura M. Gaudet.Writing—original draft: Xiuling Zhao.Writing—review and editing: Wei Ma.


Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats. Taxus. These compounds are used to treat various cancers and are preliminary therapies for earlier stages of cancer [Taxanes are natural compounds produced by members of the genus f cancer –4. Paclif cancer . The Foof cancer . Subsequf cancer –10. Howef cancer . Furtherf cancer –14. Paclf cancer , and mayf cancer . Furtherf cancer , 18. Accf cancer –21.Citrus species are an important biological resource from an economic perspective; these plants produce a diversity of phytonutrients and phytochemicals with promising therapeutic properties [viaanti-inflammatory, antioxidant, antimicrobial, antiproliferative, proapoptotic, and hormone regulatory properties [via antioxidant activity [operties . Flavonooperties –25. Comboperties . Rutin eoperties . Also, ioperties –31. Hespoperties . The comactivity . Furtheractivity .Chemotherapeutic drugs such as paclitaxel have several deleterious side effects, including kidney and heart damage, and we intend to reduce these effects by employing plant constituents with antioxidant and anti-inflammatory properties. Thus, this study assessed the renal and cardiac protection by rutin and hesperidin against the toxicity caused by paclitaxel in male Wistar rats. The study also focused on evaluating the functions of the heart and kidneys as well as the histological integrity, architecture, and defenses against oxidative stress and antioxidants.∗ (CrEL) contains paclitaxel, often known as Taxol or paclitaxel by trade (polyoxyethylated castor oil) (batch number: 7E05628), was obtained from Bristol–Myers Squibb global biopharmaceutical company . Rutin (batch number: 501) was obtained from Oxford Laboratory Company . From the Sigma-Aldrich Company, hesperidin (lot number: # SLBT3541) was obtained . Creatinine reagent kit  and urea reagent kit  were bought from Biosystem S.A. (Spain), respectively. Uric acid, creatine kinase-MB (CKMB), and lactate dehydrogenase (LDH) reagent kits were purchased from Spin React (Spain); these kits have catalog numbers: MD41001, MD41254, and MX41214, respectively. Chemicals of oxidative stress including trichloroacetic acid (TCA) (batch number: 5O011689) was obtained from PanReac AppliChem ITW Companies (Spain); thiobarbituric acid (TBA) (batch number: L 16A/1916/1212/13) was obtained from Sd Fine Chem Limited (SDFCL) Company (India); 1,1,3,3-tetramethoxypropane or malondialdehyde (MDA)  was obtained from Sigma-Aldrich ; metaphosphoric acid (batch number: M 21519) was obtained from ALPHA CHEMIKA Company (India); 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB or Ellman's reagent) (batch number: 40K3652) was obtained from Sigma-Aldrich ; GSH (batch number: 3W010085) was obtained from PanReac AppliChem ITW Companies (Spain); pyrogallol (batch number: 1280B251114) was obtained from ResearchLab Company (India). The highest purity and analytical grade reagents were used throughout the investigations.The formulation vehicle of Cremophor® ELRutin has a molecular weight of 610.5 and the empirical formula C27H30O16. It is a light-yellow crystalline powder that tastes slightly bitter. It has low solubility in water (125 mg/L), while highly soluble in polar solvents, and melts at around 176–178°C.Hesperidin is a light yellow crystalline powder with the empirical formula C28H34O15 and a molecular weight of 610.6; it is odorless and tasteless. It demonstrated poor pH-independent aqueous solubility; however, it is soluble in formamide and dimethyl formamide at 60°C, slightly dissolve in other polar solvents, and melts at around 258–262°C.ad libitum on a daily basis. The Faculty of Science at the University of Beni-Suf in Egypt followed all guidelines and directions issued by the Experimental Animal Ethics Committee . All efforts have been made to mitigate animal suffering, anxiety, and discomfort.Thirty mature male Wistar rats weighing 130–150 g and aging 8–9 weeks were provided as the experimental rats. Rats were taken from the animal house of the National Research Center in Dokki, Giza, Egypt. For avoiding intercompetitive infection, the animals were observed for 15 days prior to the experiment. Rats were maintained in stainless steel-covered, ventilated polypropylene cages that were kept at room temperature (25 ± 5°C) and subjected to 12-hour light/dark cycles every day. Animals received unrestricted water availability but were also nourished with a well-balanced meal via the intraperitoneal (i.p.) route for 6 weeks.Negative control group: this group of rats received 5 mL of 1% carboxymethylcellulose orally (CMC) (vehicle used to dissolve rutin and hesperidin)/kg body weight (b. wt) on an alternate day and 2 mL of isotonic saline (0.9% NaCl) (vehicle in which paclitaxel is dissolved)/kg b. wt twice per week nd and 5th days of each week for 6 weeks; every other day an oral equivalent dose from 1% CMC (5 mL/kg body weight) was also administered.Paclitaxel-administered control group: paclitaxel was given to this group of rats at a dose of 2 mg/kg body weight (in 2 mL 0.9% NaCl) by i.p. injection  twice a Paclitaxel-administered group treated with rutin: this group of rats received paclitaxel as in the paclitaxel-administered control group, as well as rutin at a dose of 10 mg/kg b. wt   on an alternate day for six weeks.Male adult Wistar rats had been subdivided into 5 groups in this study (6 rats per group) Negative Rats were slaughtered under diethyl ether anesthesia  after reUrea and creatinine levels were detected as previously described, respectively, by Fabiny and Ertingshausen  and TabaSo according to the respective methods belonging to Young  and Pescμl of Tris buffer (pH 7.6), 50 μl of GSH solution (2 mM), and 50 μl of hydrogen peroxide (H2O2) (3.38 mM) were combined with 50 μl of homogenate supernatant (3.38 mM). The remaining GSH content was then evaluated using the aforementioned procedure for GSH measurement at 430 nm following a 10-minute incubation period. Standard tests were prepared by substituting 50 μl of distilled water for 50 μl of the sample, and a blank test tube was prepared by substituting 100 μl of distilled water for 50 μl each of the sample and GSH solution. The sample's residual GSH concentration may then be detected, and GSH can then be transformed to GSSG to measure the activity of the enzyme. Using the Marklund and Marklund [Utilizing chemical reagents made in the lab, the heart and kidney oxidative stress and antioxidant defense parameters were evaluated. Lipid peroxidation (LPO) was determined as stated earlier by Preuss et al. . In brieMarklund  method, All animals were immediately decapitated by cervical dislocation and dissection, and their kidneys and hearts were removed. They were subsequently transferred to the pathology department of the faculty of veterinary medicine at Beni-Suef University in Egypt for additional processing, wax blocking, sectioning, and staining with hematoxylin and eosin after being stored in 10% neutral buffered formalin for 24 hours (H&E) . Five rap < 0.05 [The mean and standard error of the mean were used to reveal all the data SEM ± Mean. The statistical analyses were carried out using the IBM software, USA, Statistical Package for the Social Sciences (SPSS) computer software (version 22). To determine the significance of group means, a one-way analysis of variance (ANOVA) test was conducted. Tukey's posthoc test was then used to compare pair averaged results. Differences were deemed significant at p < 0.05 :(1)% chap < 0.05) in their serum levels of urea, uric acid, and creatinine with respective percentage changes +111.90, +68.94, and + 361.67%, compared with corresponding normal controls. Rutin and its combination with hesperidin significantly restored increased creatinine, urea, and uric acid levels to normal in paclitaxel-induced rat models. Treatment with hesperidin indicated a nonsignificant decrease (p ≥ 0.05) in serum creatinine and urea levels but significant improvement in serum uric acid levels. The combination of rutin and hesperidin treatment of paclitaxel-administered rats was the most efficacious in lowering high creatinine, urea, and uric acid levels, with respective percentage decreases −43.82, −38.03, and −60.65%  concentration, and enzymatic antioxidant (GPx and SOD) activities are all related to detrimental biochemical and histological alterations in the current investigation. Similarly, Ren et al.  reportedvia lowering production of ROS and MDA and by augmenting antioxidant status through increasing SOD, GSH, and GPx in several models of cardiovascular disease. An article of Qu et al. [Paclitaxel-induced oxidative stress in the kidney or heart was remarkably suppressed by rutin and hesperidin treatment with reduced LPO and elevated GSH content and activities of antioxidant enzymes. Both compounds enhance endogenous antioxidant activity beyond their ability to scavenge free radicals and reduce the formation of lipid peroxide radicals. Remarkably similar results were mentioned by Geetha et al. , Huang eu et al.  showed tu et al. .By alleviating the oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy-induced by valproic acid, rutin administration ameliorated liver and kidney damage . It was Coadministration of rutin, hesperidin, or their combination with paclitaxel in male Wistar rats might diminish the incidence and severity of detrimental effects of paclitaxel (Taxol)-induced toxicity in the kidney and heart. These protective effects are likely mediated by suppressing oxidative stress and enhancing antioxidant defenses. Moreover, a combination of rutin and hesperidin treatment of paclitaxel-administered rats was most efficacious in preventing renal and cardiac dysfunction and adverse histological impacts. Before using rutin and hesperidin in patients and receiving FDA approval, more clinical trials are required to evaluate their effectiveness and safety.


The purpose of this study was to investigate the effects of acute repeated hypoxia–hyperoxia preconditioning on resistance exercise (RE)-induced muscle damage in male athletes.2 = 0.21), or alternating hypoxic/hyperoxic air  for 60 min. Thirty minutes after preconditioning, subjects performed acute bouts of RE consisting of bench press, deadlift, and squats. Each exercise included 6 sets of 10 repetitions at 75% one-repetition maximum (1RM) with 2 min rest between sets. After a 2-week washout period, subjects changed trials and completed the same study procedure after the alternate preconditioning. Muscle soreness, maximal voluntary contraction (MVC), and circulating biochemical markers were tested before preconditioning (baseline) and during recovery at 0, 24, and 48 h after exercise.Eleven young male athletes participated in this randomized double-blind counter-balanced crossover study, and were divided into Normoxia (N) and Hypoxia–Hyperoxia (HH) trials. Subjects of the respective trials were supplied with normoxic  and myoglobin (Mb), and decreased levels of peak knee extension torque in the N trial. Muscle soreness, CK, and Mb levels of the HH trial were significantly lower than that of the N trial after exercise. Interestingly, interleukin-6 (IL-6) levels of the HH trial increased significantly 0 h after exercise compared to baseline and were significantly higher than that of the N trial 0 and 24 h after exercise. However, no significant differences of thiobarbituric acid reactive substances (TBARS), cortisol, testosterone, peak torque, and average power levels were found between N and HH trials during recovery.Our data suggest that pre-exercise treatment of alternating hypoxic/hyperoxic air could attenuate muscle damage and pain after acute RE, but has no effect on muscle strength recovery in young male athletes. In athletic training, resistance exercise (RE) effects are derived by controlling the loading, sets, repetitions, rest duration, and movement velocity of exercise, these stimulations result in physiological response and adaptation . Heavy R2) followed by oxygen-enriched air (>20.9% inspired O2). Intermittent hypoxia–hyperoxia training (IHHT), resulting from chronic or prolonged hypoxia–hyperoxia exposure, has recently been found to positively impact a number of medical conditions. These include improving cardiorespiratory fitness , and musculoskeletal injury. In order to reduce the metabolic effects associated with these substances, subjects were asked to avoid use of tobacco, alcohol, or sports supplements  from 1 month before to the end of the experiment. In addition, subjects maintained moderate physical activity and avoided high intensity or RE during the experiment. Subjects were informed of the purpose and experimental protocol of the study before experiments began, and they were informed of potential risks of participation and then signed their consent. The procedure of this study was ethically approved by the Institutional Review Board of University of Taipei, Taipei, Republic of China . Prior to the beginning of the study, demographic and anthropometric information including age, height, and weight was collected or measured by the research staff. Based on relevant investigations , a prior2 = 0.21) or alternated between hypoxic (FiO2 = 0.10) and hyperoxic (FiO2 = 0.99) air for 60 min according to their trial. Thirty minutes after N or HH preconditioning, subjects performed an acute bout of heavy RE to induce muscle damage. Muscle soreness and isokinetic muscle strength were determined before preconditioning and at 0, 24, and 48 h after exercise. Blood samples were collected at the same time points and used to assess the levels of muscle damage [creatine kinase (CK) and myoglobin (Mb)], inflammation , oxidative damage , and catabolism/anabolism (cortisol and testosterone). After the first trial, subjects switched preconditioning trials and completed the same study procedure. The trials were separated by a 2 weeks washout period. The study procedure was completed during off-season.In this randomized, double-blind, counter-balanced crossover study design, participants were randomly divided into Normoxia (N) or Hypoxia–Hyperoxia (HH) preconditioning trials. On the experiment day, subjects were supplied either normoxic air  measurements [mean height 172.5 ± 1.4 cm; median weight 70.3 (62.0–71.9); 2 = 0.21), hypoxic (FiO2 = 0.10), or hyperoxic (FiO2 = 0.99) air was produced by mixing 100% oxygen and nitrogen gas, each resulting gas was then checked using Model GB300 Percent Portable Oxygen Analyzer  before treatment. The HH preconditioning protocol consisted of 6 cycles of alternating hypoxia/hyperoxia (5 min each) for a total 60 min. In the HH trial, hypoxic and hyperoxic air were supplied, respectively, via Y tube and switched every 5 min using a switching valve. Normoxic air was continuously supplied in a blind manner to subjects of the N trial for 60 min also using the same type of Y tube in order to reduce the placebo effect.PVC balloons were filled with normoxic, hypoxic, or hyperoxic air, and supplied to subjects by mask and two-way non-rebreathing valves . Oxygen concentration of normoxic . After standardized dynamic stretches, participants performed the squat, deadlift, and bench press for 10 repetitions at 50% of their 1RM to warm up before the acute RE protocol. This protocol was modified from a previous study  and consThe maximum voluntary contraction (MCV) of knee extensor was assessed using a Biodex System 4 isokinetic dynamometer . Before testing, subjects performed a 5 min walking warm up on a treadmill. The right leg of each subject was investigated. Subjects were fixed in a rigid chair with 90° hip to knee angle, then performed 20 repetitions of knee extension and flexion between 90° and 0°. The angular velocity was fixed at 180° per second. Subjects exerted maximum power against the mechanism during extension and flexion. Knee extension peak torque  and average power  were calculated as muscle strength and endurance, respectively.Muscle soreness was scored using ratings of perceived muscle soreness (RPMS), a verbal rating scale (VRS) ranging from 0 to 6. The numbers corresponded with no soreness (0), dull feeling of soreness (1), light continuous soreness (2), more than light soreness (3), annoying soreness (4), severe soreness (5), and intolerable soreness 6; .g and 4°C, supernatant (serum) was obtained and stored at −80°C until biochemical analysis was performed. A bench top DT-60II analyzer  was used to enzymatically analyze CK levels. Mb, IL-6, cortisol, and testosterone levels were tested using commercially available enzyme-linked immunosorbent assay (ELISA) kits. These kits were the Human Myoglobin ELISA Kit , IL-6 ELISA Kit , Cortisol ELISA  and Testosterone (Free) ELISA , respectively, and were used following the manufacturers’ protocols. The lipid peroxidation marker  was measured using a TBARS assay kit .Blood samples were taken using vacutainer tubes and needles (22-gauge) from the median antebrachial vein of the left forearm. After centrifugation at 3000 p < 0.05.All statistical analyses were performed using the SPSS 22.0 software . The data in figures and tables were expressed as changes from baseline. The Shapiro–Wilk normality test was used to analyze the normal distribution of all indicators. The normally and non-normally distributed variables are presented as mean ± standard error and 1st quartile median–3rd quartile, respectively. For non-normally distributed variables , the Friedman non-parametric statistical test was used to analyze the results at different time points within groups. The Wilcoxon signed rank test was used to determine the difference between N and HH trial results at the same time point. For normally distributed variables (TBARS and cortisol), two-way ANOVA with repeated measure was used to analyze mean differences. The results were considered to be significant when p < 0.05) 0 to 48 h after RE compared to baseline. The muscle soreness levels of the HH trial were significantly lower than those of the N trial at 24 h after RE.Muscle soreness is shown in The circulating biochemical markers are shown in The peak torque and average power of knee extension are shown in The biochemical and mechanical stresses caused by RE included inflammatory response, free radical generation, and muscle cell damage. These stresses temporarily cause reduced skeletal muscle function. To examine the potential of acute HH preconditioning to impact recovery from RE, we measured a number of markers including muscle soreness, cell damage, inflammation, oxidative damage, and isokinetic muscle function. The major findings of this study are as follows: (1) Acute HH preconditioning showed a protective effect resulting in reduced muscle damage after RE when compared to the N trial. This was evidenced by decreased circulating levels of CK and Mb, and reduced muscle soreness. (2) Interestingly, inflammatory cytokine levels after RE were increased with HH preconditioning, evidenced by elevation of IL-6 levels. (3) Catabolic, anabolic signal, and isokinetic muscle function response to RE were not affected by HH preconditioning. Taken together, our data suggest that the RE-induced muscle damage is partly blunted by HH preconditioning in young male athletes.Levels of CK and Mb are important circulating indirect indicators of muscle damage response to strenuous or unaccustomed exercise . In agre2)–hyperoxia (30% O2) treatment can reduce acute hypoxia (2+/ascorbate (p = 0.071 by t-test) in the HH trial immediately after exercise, evidenced by increased TBARS levels after exercise  in healthy humans  decreased 24 h after exercise .P-WC contributed by recruiting subjects, collecting data, and analyzing statistics. C-CH, L-FL, and C-PC contributed by recruiting subjects and collecting data. S-HY contributed by conceiving the study, interpreting the results, and writing the manuscript. All authors contributed to the article and approved the submitted version.The authors acknowledge financial support from the Ministry of Science and Technology (Grant number: 106-2410-H-197-003-), Republic of China (Taiwan).The authors declare that this study does not present them with any conflict of interest resulting from their commercial or financial relationships.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Pulmonary artery hypertension (PAH) is a common complication of congenital heart disease (CHD) and is associated with worse outcomes and increased mortality. The Doppler echocardiography (DE) is a commonly used imaging tool for both diagnosis and follow-up examination of PAH. Here is to evaluate the diagnostic performance of DE combined with NTproBNP/BNP as screening strategy in PAH patients with CHD.  A retrospective study in 64 patients with CHD has been carried out to compare estimate pulmonary artery systolic pressure (PASP) measured with DE to that measured with right heart catheterization (RHC). The Pearson correlation analyses were used to calculate the correlation coefficients between RHC and DE. The Bland-Altman analyses were carried out to assess the agreement between the two methods. ROC analyses were used to evaluate the diagnostic performance of DE, NTproBNP/BNP, and DE combined with NTproBNP/BNP. r = 0.4401, P < 0.01) was observed between PASP (78.1 ± 29.0 mmHg) measured during RHC and PASP (74.9 ± 19.7 mmHg) as estimated using DE. The Bland-Altman analysis demonstrated that the bias for DE PASP estimates was 3.2 mmHg with 95% limits of agreement ranging from -49.53 to 55.90 mmHg. The results of DE showed an AUC of 0.848 , the sensitivity of which was 98.3% and the specificity was 77.8%. The AUC of NTproBNP/BNP for the identification of PAH was 0.804 , the sensitivity of which was 81.4% and the specificity was 87.5%. The AUC of DE combined with NTproBNP/BNP was 0.857 , of which sensitivity was 100% and specificity was 77.8%. The positive predictive value (PPV) and negative predictive value (NPV) were 96.6% and 100%, respectively.  Our data have demonstrated that a mild correlation ( Our study shows that the Doppler echocardiography combined with NTproBNP/BNP has better diagnostic performance in pulmonary artery hypertension associated with congenital heart disease, especially when DE negative screening in PAH patients. Congenital heart disease, referred to as CHD, is an abnormality of cardiovascular morphology, structure, and function caused by developmental disorders of the heart and blood vessels, with an incidence of about 7‰ to 10‰ in live births, and is the primary birth defect disease in humans. In adults, approximately 6.5%-10% of CHD patients will develop into pulmonary artery hypertension (PAH) .NTproBNP or BNP are secreted by cardiomyocytes due to excessive stretching of the ventricles, which remain the most promising blood biomarkers for risk prediction of patients with PAH .Here, we investigate the accuracy of DE and, further, DE combined with NTproBNP/BNP in estimating the pulmonary arterial pressure of patients with CHD by comparing with RHC.A total of 64 patients diagnosed as CHD or PAH associated with congenital heart disease (PAH-CHD) by the Doppler echocardiography (DE) and RHC who were hospitalized in the Department of Cardiovascular Surgery, Tianjin Chest Hospital, between March 2017 and March 2022 were collected. All patients had no right ventricular outflow tract obstruction and tricuspid valve prolapse and no family history of pulmonary hypertension. The RHC examination was performed within 72 h after the DE examination, and the relevant parameters were recorded. This study was approved by the Ethics Committee of Tianjin Chest Hospital, and all patients and their families signed informed consent.The 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for the diagnosis and treatment of pulmonary hypertension was used: mean pulmonary arterial pressure ≥ 25 mmHg by right heart catheterization at sea level and at rest . FurtherVmax2 + right atrial pressure (RAP), where V is the maximum velocity of tricuspid valve) was estimated with the tricuspid valve method (hereinafter referred to as the three-back method), and for PDA and VSD cases, PASP  was also estimated with the left-to-right shunt differential pressure method .Philips IE 33 Doppler ultrasonic diagnostic apparatus was applied with a probe frequency of 1 ~ 5 MHz. Supine position was placed before testing; the tricuspid valve area, tricuspid pressure gradient, left-to-right shunt pressure gradient, right atrial and right ventricular diameters, main pulmonary artery, tricuspid annular systolic excursion, and ejection fraction were measured under two-dimensional ultrasound at the end of expiration. Under the condition of excluding right ventricular outflow tract obstruction, according to the simplified Bernoulli equation, pulmonary artery systolic pressure , pulmonary arterial pressure (PAP), pulmonary arteriolar wedge pressure (PCWP), and aortic pressure; the saturation of each cardiac chamber and great vessels was measured. Hemodynamic parameters such as pulmonary blood flow (Qp), systemic blood flow (Qs), pulmonary circulation resistance (RP), systemic vascular resistance (Rs), and pulmonary vascular resistance (PVR) were calculated by the Fick method.Blood was collected after admission and transferred immediately to the Department of Laboratory. The samples were processed and analyzed using CLIA assay for plasma BNP  and ECLIA assay for serum NTproBNP concentrations . The normal reference range of NTproBNP was 0-300 pg/ml and also 0-100 pg/ml for BNP in our laboratory.P < 0.05 was defined as statistically significant difference. Mean ± SD was calculated to present continuous data, while the percent and frequency were used to present categorical data. Chi-square test and Student's t-test were used to analyze data when appropriate. Statistical significance was defined as a two-side value of P < 0.05. The Pearson correlation analyses were used to calculate the correlation coefficients between RHC and DE.SPSS 22.0 was used for statistical analysis, and A total of 64 CHD patients were prospectively enrolled in this study. All of the patients estimated PASP using both DE and RHC. Patients' baseline characteristics are presented in r = 0.4401, P < 0.01) (A wide range of PASP (33-160 mmHg by RHC and 25-110 mmHg by DE) was measured. A mild correlation was observed between PASP (78.1 ± 29.0 mmHg) by RHC and PASP (74.9 ± 19.7 mmHg) by DE ( < 0.01) . Using t < 0.01) .2 by RHC. And also, PAH was identified when PASP > 40 mmHg or mean PAP ≥ 25 mmHg at rest either by DE. ROC curve analyses were constructed to evaluate the predictive values of DE with/or NTproBNP/BNP levels for the identification of PAH (P < 0.001), the sensitivity of which was 98.3% and the specificity was 77.8%. The AUC of NTproBNP/BNP for the identification of PAH was 0.804 , the sensitivity of which was 81.4% and the specificity was 87.5%. The AUC of DE combined with NTproBNP/BNP was 0.857 , of which sensitivity was 100% and specificity was 77.8%. The positive predictive value (PPV) and negative predictive value (NPV) are listed in Here, PAH was defined as a PASP ≥ 30 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and PVR index > 3 wood units·mn of PAH . The resr = 0.31 to r = 0.99 [The blood flow of left-to-right shunt in CHD continuously impacts the pulmonary artery, causing vascular remodeling, which in turn leads to the progressive increase of pulmonary arterial pressure and resistance, and finally reverses the blood flow direction to right-to-left and develops into Eisenmenger's syndrome (ES). Therefore, accurate diagnosis, follow-up, and timely intervention of PAH are of great clinical significance. Although the Doppler echocardiography is an excellent noninvasive screening tool for PAH, it has limited accuracy in estimating the right ventricular systolic pressure in PAH and is typically used for assessing the risk of PAH rather than for diagnosis . Many huAccording to Tsujimoto et al.'s review , a fixedOur study is a retrospective study assessing the value of DE in estimating pulmonary arterial pressure and diagnosing pulmonary hypertension and has a sample size of 64 subjects. We controlled for the time interval between the two examination methods within 72 hours, as well as the parameters measured and the examination conditions. These control measures will greatly reduce the limitations of the study and improve the credibility of the research. In our study, PASP estimated by DE showed a relatively mild correlation in linear regression analysis with PASP by RHC measurements in patients with CHD, and these results were consistent with previous studies –13.β1 and VEGF165b [Since pathological changes in the pulmonary arteries occur prior to cardiac affection in PAH, pulmonary derived biomarkers would be optimal to detect early PAH. However, although such biomarkers are promising results that have recently been reported as TGF-VEGF165b , 15, theVEGF165b . AnalysiThe NPV is higher than the single detection, suggesting that, when the Doppler echocardiography fails to detect while PAH is suspected by clinicians, BNP or NT-proBNP are useful as subsequent screening tests.In summary, our study also showed that the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of NTproBNP/BNP combined with the Doppler echocardiography for the prognosis prediction of pulmonary hypertension in CHD-PAH patients were higher than those of single detection. The results are consistent with the research of Yin et al. , and theNevertheless, there are several limitations regarding this study. First of all, there is noticeable heterogeneity across studies both in terms of the spectrum of the underlying congenital heart disease and the age of the patients. Secondly, two essays used for NTproBNP/BNP measurement and we used cut-off values for PAH diagnosis respectively here. Finally, both invasive and noninvasive measurements were carried out within 72 h in our study; however, PASP can fluctuate widely within a single day due to the variability of pulmonary vascular resistance.Our study shows that the Doppler echocardiography combined with NTproBNP/BNP has better diagnostic performance in pulmonary artery hypertension associated with congenital heart disease, especially when DE negative screening in PAH patients.


There is paucity of data regarding effects of guided meditation (Yoganidra) on quality of life among patients of chronic kidney disease on maintenance hemodialysis. Our objective was to study effects of guided meditation on physical, emotional, and cognitive dimensions of well-being and quality of life in patients undergoing maintenance hemodialysis.We collected baseline and post intervention data in control and intervention groups on hemodialysis and studied the effect of Guided mediation provided for 6 weeks.Eighty patients (forty in control and intervention group each) were studied. Mean age was 51 years. Hypertension and Diabetes were the most common etiological condition (28.75%) followed by undermined aetiology (25.00%). 8.75% of the patients had dialysis vintage of less than 1 year. There was statistically significant difference in qualities of happiness and all measures of physical general wellbeing. There was statistically significant difference in burden and effect of kidney disease as well as symptoms of kidney disease post intervention in Kidney Disease Quality of Life score. We carried out Qualitative analysis in our study by maintaining a diary of their subjective experiences related to listening music/guided meditation during the study period in which the feeling of peace and feeling inspired to manage the illness/ do regular work were the most common experiences (97.5%) reported by participants. Guided meditation resulted in statistically significant improvement in happiness, enthusiasm, inspiration, activeness, alertness, awareness, degree of stability, self-confidence, clarity of thoughts, control over anger, self-reflection intervention in the intervention group. It reduced perceived stress. It improved burden and effect of kidney disease, symptoms of kidney disease and total Kidney Disease Quality of Life score. In qualitative dimensions of wellbeing , feeling of peace and feeling inspired to manage the illness/ continue regular work, clarity of thoughts, happiness, concentration, reduction of laziness, improved sleep pattern, reduction in anger among other psychological components.This trial has been registered under clinical trial registry of India. (CTRI number-CTRI/2020/02/023438) (Date: 19/02/2020).The online version contains supplementary material available at 10.1186/s12906-022-03717-8. The pattern of disease burden in the twenty-first century has significantly shifted towards chronic diseases (CDs) . PopulatHealth-related quality of life (HRQOL) is a critically important outcome for patients with end-stage renal disease (ESRD) . The Nat1. To study physical, psychological, and biochemical parameters of patients of CKD undergoing maintenance dialysis.2. To study Health related quality of life in CKD patients. (KDQOL).3. To document effects of dynamic meditation (Yoganidra) on KDQOL and psychological wellbeing through quantitative and qualitative observations.After an informed written consent as attached in Annexure for 80 patients undergoing hemodialysis were enrolled in the study  using balanced double-blinded (participants and care provider) randomisation method as suggested by statistician.: CTRI/2020/02/023438).Patients of CKD on hemodialysis attending Shree Krishna Hospital, Karamsad.1. Age between 18–70 years.2 (KDIGO definition) and on maintenance hemodialysis 3 times a week.2. CKD with eGFR (by CKD-EPI equation) < 15 ML/MIN/1.73 m3. Patients who are clinically stable (not having suffered from any acute illness) for last 3 months.1. Any solid organ or bone marrow transplant recipient.2. Active malignancy in last 2 years.3. Palpitation or dyspnoea at rest or asymptomatic only when resting.4. Ethnicity: Non-Indian.5. Pregnancy .6. Current immunosuppressive drug therapy.7. Expected life expectancy < 1 year Group 1: Intervention group.Group 2: Control group.Clinical and Laboratory Evaluation: Symptoms, General and systemic examination, Type and detail Of Hemodialysis received, Assessment of Quality/ Effectiveness Of hemodialysis, Baseline and End of study biochemical parameters KDQOL, Experimental Record (Diary)Perceived stress scale Faces scale of Happiness (Andrews) VAS Scale for Stress Investigator designed scale for assessment of positive wellbeing1.Pre and post intervention Evaluation:Consent, Randomization: An informed consent was obtained from all participants.Intervention group: Guided Meditation session of 30 min during each dialysis (three days /week)Control group: Standard quality careClinical and biochemical record of patients were maintained during the study period as per standard practices as advised by Nephrologist .All forty participants in the intervention group were asked to write whatever they experienced so far as effects of Yoganidra on physical and emotional wellbeing were concerned.Duration of intervention: 6 weeks (21/02/2020 to 03/04/2020)An audio recording of guided dynamic meditation session: was prepared by the principle /co-investigator having experience of conducting similar sessions in diverse populations.This study was approved by the Institutional ethical committee-2, H M Patel centre for medical care and education, Karamsad, Anand (IEC/HMPCMCE/114/Faculty/246/19) approved on 18/12/2019 and also registered under clinical trial registry of India. CTRI number-CTRI/2020/02/023438. (Date:19/02/2020).• The quantitative variables are expressed as Mean ± SD. Qualitative variables are expressed as frequencies/ percentages and compared between groups using Fisher Exact test.P-value < 0.05 was considered statistically significant. STATA version 14.2 and Microsoft Excel software were used for tabulation of data and statistical analysis. Pre and post intervention comparison of clinical, QOL parameters, qualitative analysis .1. Change in Quality of Life as measured by KDQOL.2. Psychological general wellbeing as measured by quantitative and qualitative methodsThe mean age of study population was 51 years with SD of 16.49 as shown in Table p = 0.0027 and p =  < 0.001 respectively). There was no significant reduction in degree of stress measured by VAS scale. There was statistically significant improvement in the qualities of enthusiasm, happiness, feeling inspired, activeness, alertness, awareness, stability, self-confidence, clarity of thoughts, control over anger, soul inspection except Quietness in intervention group in pre and post study as shown in Table p =  < 0.001) and Effect of Kidney disease (p = 0.0001) as well as Symptoms of kidney disease (p = 0.01461) in the KDQOL score post intervention. There was significant improvement in total KDQOL score in pre and post study in intervention group as shown in Table Baseline degree of psychological measures studied were comparable in control and intervention groups. There was significant difference in the degree of happiness measured by Faces scale and perceived stress post-intervention  were seen after 6 months .In a study of 175 patients, Sapna Kothari et al. have reported that meditation results in significant decrease in depression, anxiety and stress in hemodialysis patients practicing Arham Purushakar meditation, and also improvement in other physical and medical conditions .Masina et al., (2016) have reported that overall health related quality of life was low  with the lowest scores recorded for physical health component summary score (50.4 ± 22.8) compared to mental health component summary (61.3 ± 23.0) and kidney disease component summary (67.9 ± 13.2) and also reported that low household income (< $4000 per year) was associated with lower mental health component scores .We have studied happiness, stress, positive wellbeing parameters, psychological wellbeing, and KDQOL-36 questionnaire. The Uniqueness of our study is that we have done qualitative analysis- Experiential effects of Guided meditation” . Attributes measured were feelings of enthusiasm, being active, alert, and inspired, experiencing quietude, experiencing a state of self‑awareness, stability and self‑confidence, having clarity of thoughts and control over anger.Thus, in a small set of study participants all parameters of general wellbeing in CKD patients were taken into consideration and results were analysed accordingly giving us an insight on effect Yoganidra. Summing up the effect of Yoganidra on patients having CKD with MHD, it had positive impact on various factors studied in our study like happiness, stress, positive wellbeing, laboratory parameters as well in experimental effects.Longer duration of intervention (> 6 weeks), larger sample size and long-term follow-up, and external validation of Investigator designed tool can enhance strength of the intervention. Implementation of Yoganidra for longer period may result in better control of blood pressure. The scientific pursuit can be further enhanced by studying effects of guided meditation on physiological and biochemical parameters such as heart rate variability and markers of inflammation.Guided meditation resulted in statistically significant improvement in qualitative dimensions of wellbeing such as degree of happiness, enthusiasm, inspiration, activeness, alertness, awareness, degree of stability, self-confidence, clarity of thoughts, control over anger, self-reflection in the intervention group as measured by quantitative and qualitative methods. There was significant improvement in stress level as measured by perceived stress scale, KDQOL related to burden and effect of kidney disease, symptoms of kidney disease and total KDQOL score. Guided meditation is easy to implement, and effective in enhancing several components of quality of life and wellbeing; it has high acceptability and compliance. It can be easily incorporated in standard of care of patients of CKD on MHD. It can be recommended for inclusion in standard of care for enhancement of quality of life of patients on maintenance hemodialysis.Additional file 1.


Birth weight was positively associated with shuttle run performance . BMI was positively associated with handgrip strength  and shuttle run performance , but negatively associated with standing long jump performance . GMC was positively associated (p < 0.001) with all three MSF tests, while PA was associated with standing long jump  and shuttle run  performance only. No school environment effects were found, and SES was not related to any MSF tests. Children’s MSF development showed a curvilinear shape with increasing age, with boys outperforming girls. Weight status and physical behavior characteristics predicted MSF development, while environmental variables did not. Examining potential longitudinal predictors of MSF across multiple dimensions is important to gain a more holistic understanding of children’s physical development as well as to future interventions.This study models children’s musculoskeletal fitness (MSF) developmental trajectories and identifies individual differences related to effects of time-invariant, as well as time-varying covariates. A total of 348 Portuguese children (177 girls) from six age cohorts were followed for three years. MSF tests , age, body mass index (BMI), socioeconomic status (SES), gross motor coordination (GMC) and physical activity (PA) were assessed. Data were analyzed using multilevel models. Between 5 and 11 years of age, boys outperformed girls in all three MSF tests ( Musculoskeletal fitness (MSF), a multidimensional construct comprising muscle strength, muscle endurance, and muscle power, is an important marker of health status . DiffereLongitudinal studies of human growth indicate the pattern of curvilinear growth is consistent, but the timing and magnitude of growth is highly individualized ,7. This A longitudinal study by Ruedl et al.  reportedThe growth, motor development and cognition study (GMDC)  was initn = 24) were excluded from the analysis as were 4-year-old’s (n = 88) whose GMC was not assessed. Written informed consent was obtained from parents or legal guardians, and the project was approved by local authorities and the ethics committee of the Faculty of Sport, University of Porto (CEFADE 01.2016).The GMDC was carried out in Vouzela, a central region of Portugal, between 2013 and 2016. The mixed-longitudinal design has been described in detail elsewhere . Birth weight (kg) was obtained retrospectively from children’s health booklets.Height (cm) was measured, without shoes, using a portable stadiometer  holding the child’s head in the Frankfurt plane, (accuracy = 0.1 cm). Body mass (kg) was measured with a portable bioelectrical impedance scale  with children wearing light clothing and without shoes (precision = 0.1 kg). Body mass index (BMI) was calculated using the standard formula [BMI = body weight (kg)/height (m)MSF (isometric strength and explosive strength/agility)  was asseKöperkoordinationstest für Kinder (KTK) test battery [TS) [The  battery  was usedery [TS) . The KTK® software 6.5.4 was used to process the recorded data immediately upon retrieval of each accelerometer. Children’s data, to be considered valid, had to have a minimum of at least 4 days (with at least one weekend day) and a minimum of 10 h of daily wear time. Any sequence of at least 20 consecutive minutes of zero activity counts was considered non-wear time [−1.PA was objectively measured using an Actigraph GT3X+ accelerometer  over 7 consecutive days (5 weekdays and 2 week-end days). Children were instructed to only remove the device during water activities and while sleeping at night. The accelerometer was placed on the iliac crest and held in place by an elastic belt with an adjustable clip. Each child received individual instructions and all parents received written instructions. ActiLifeear time . Moderatear time , definedAll measures were taken by trained team members of the Kinanthropometry and Motor Learning Labs . Each year, a sample of ~60 children was randomly selected from each cohort and retested. Technical error of measurement (TEM) and ANOVA-based intraclass correlation (R) were used for reliability estimates: TEM = 0.17 cm in height, and 0.10 kg in weight; R-values ranged from 0.71 to 0.97 for PF tests, and from 0.78 to 0.91 in GMC tests. Finally, a systematic check was performed regarding errors in data entry and normality of variables’ distributions. 2, sex, age-by-sex and age-by-sex2 interactions as predictors; parameters were dropped from the final models if they were non-significant (p > 0.05); Model 2 included the cohort effect, non-varying , and time-varying  covariates. Individual models were developed for each of the three MSF markers . The significance level was set at p < 0.05.Descriptive statistics by sex across age were calculated. A multilevel modeling approach was used . As advoTS increased with increasing age. No differences in birth weights were found between sexes. Girls’ MVPA decreased until 9 years and increased thereafter; in boys this decrease was seen until 10 years and then increased. SES level C (≥ EUR 5.870 per year−1) was the most frequent category noted. Boys’ and girls’ descriptive statistics (mean ± SD or percentages) are shown in 2. Only five schools had a sport center, three of them with more than 50 m2. All schools had equipment for PA; however, fifteen schools had only one infrastructure space for PA. The duration of PE classes ranged from 45 to 60 min and the time children spent active varied from 30 to 50 min. The same PE opportunities were offered to all children since schools employed PE specialists.The number of students per school varied, from a minimum of 5 to a maximum of 87 . Most sc2-by-sex, or for the school random effects. These factors were not included in the second model (2) was also statistically significant . A similar trend was observed for SLJ , and SR . Cohort effects were all significant (p < 0.05) in all MSF markers. Birth weight was only significantly related to SR, i.e., children born with higher birth weight demonstrated, on average, better agility during childhood , i.e., faster SR test time. Further, SES was not significantly linked to any PF developmental trajectory. In contrast, children with higher BMI were stronger in HG ; less agile , i.e., slower SR test time, and showed lower explosive strength . Children with higher GMCTS demonstrated better PF developmental trajectories . In model 1, no significant effects were identified for the interactions of age-by-sex or agend model . Regardiσ2) in the longitudinal age-related trends across individuals , meaning that children’s MSF developmental trajectories were significantly heterogeneous.Additionally, more physically active children displayed a higher rate of increase in SLJ and SR, but not in the rate of HG development. Finally, children’s MSF developmental trajectories showed significant inter-individual differences, i.e., there was significant variation (2 was significant) during childhood, which are analogous to other longitudinal studies [TS, and MVPA), boys outperformed girls in all PF developmental trajectories, corroborating other studies’ results [The results show that isometric and explosive strength, as well as explosive agility, exhibit a curvilinear developmental trajectory  the GMDC-Vouzela study does not cover all Portuguese regions, and generalizability is questioned; (ii) a pure longitudinal study would have provided a more robust design. However, comprehensive testing of multiple intra-individual and environmental factors linked to physical development has never been conducted and the mixed-longitudinal approach is a highly viable and reliable design.In conclusion, children’s MSF development exhibited a curvilinear trend with boys outperforming girls. The complex nature of interactions among MSF attributes, GMC and bodyweight status are difficult to untangle, specifically with the additional influence of biological growth and maturation variables. However, the unique nature of this investigation provides new novel insight on the overall physical development of children, supplying parents, physical education teachers and coaches with a more holistic view of children´s MSF development for future interventions.


Recurrent esophageal cancer is associated with dismal prognosis. There is no consensus about the role of surgical treatments in patients with limited recurrences. This study aimed to evaluate the role of surgical resection in patients with resectable recurrences after curative esophagectomy and to identify their prognostic factors.We retrospectively reviewed patients with recurrent esophageal cancer after curative esophagectomy between 2004 and 2017 and included those with oligo-recurrence that was amenable for surgical intent. The prognostic factors of overall survival (OS) and post-recurrence survival (PRS), as well as the survival impact of surgical resection, were analyzed.p = 0.108), while the 3-year PRS rates were 42.9 and 23.5% (p = 0.100). In the subgroup analysis, surgery for resectable recurrence, compared with non-surgery, could achieve better PRS for patients without any comorbidities .Among 654 patients after curative esophagectomies reviewed, 284 (43.4%) had disease recurrences. The recurrences were found resectable in 63 (9.6%) patients, and 30 (4.6%) patients received surgery. The significant prognostic factors of PRS with poor outcome included mediastinum lymph node (LN) recurrence and pathologic T3 stage. In patients with and without surgical resection for recurrence cancer, the 3-year OS rates were 65.6 and 47.6% (Mediastinum LN recurrence or pathologic T3 was associated with worse OS and PRS in patients with oligo-recurrences after curative esophagectomies. No definite survival benefit was noted in patients undergoing surgery for resectable recurrence, except in those without comorbidities. Esophageal cancer is an aggressive gastrointestinal cancer with high rates of recurrence even after curative treatments. Although multimodality treatments combining (neo)adjuvant therapy and radical surgical resection have improved the prognosis for esophageal malignancy , 2, postThe concept of oligometastases was first proposed by Hellman in 1995 . It is dPrior studies –10 have We retrospectively reviewed patients receiving esophagectomy for cancer at Taipei Veteran General Hospital between January 2004 and December 2017. To identify patients with resectable recurrences after esophagectomy, we excluded the patients who were (1) at M1 stage, (2) operated on R2 resection, (3) lost from follow-up, (4) without evidence of disease recurrence during follow-up period, and (5) with unresectable recurrences.The preoperative staging examinations in our protocol included physical examination, laboratory tests, esophagogastroduodenoscopy, flexible bronchoscopy (for upper third and middle third tumors), computed tomography (CT) scans from neck to upper abdomen, and radionuclide bone scans. Endoscopic ultrasound and positron emission tomography/CT (PET/CT) scan became a routine preoperative staging examination for esophageal cancer from 2007. From 2010, multidisciplinary team meetings were held regularly for discussion of examination results and treatment plans. For patients receiving upfront surgery, adjuvant therapy was suggested in patients with pT3/T4 stage and N+ stage. Since the publication of Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) study, neoadjuvant chemoradiotherapy followed by surgery has become the popular treatment combination for patients with locally advanced tumors. The study protocol was approved by the Institutional Review Board of Taipei Veterans General Hospital and, because of the retrospective nature of the study, informed consent from included patients was waived .Clinicopathological stage was determined according to the eighth edition American Joint Committee on Cancer (AJCC) TNM staging system. After curative treatments, all patients were followed routinely every 3 months in the first 2 years, and every 6–12 months after then. Routine follow-up examinations included serum tumor marker, chest radiography, and CT scan from the neck to the upper abdomen. Endoscopy, abdominal sonogram, brain magnetic resonance imaging (MRI), radionuclide bone scans, and PET/CT scan were obtained as clinically indicated.Diagnosis of recurrence or metastasis was based on histological, cytological or radiological evidences. Recurrences at the anastomotic site or within the area of previous resection and nodal clearance in the mediastinum or upper abdomen were classified as locoregional recurrence. Distant recurrence was defined as hematogenous metastasis to solid organs or recurrence in the pleura or peritoneal cavity. Resectable lesion was defined as (1) oligo-recurrence, i.e. limited number (≤5) or single site of recurrence, (2) Eastern Cooperative Oncology Group (ECOG) performance status < 2, and (3) surgical approachability based on image studies and determined by two surgeons, PC Tsai and PK Hsu. For example, recurrence in two solid-organ sites or combined failure  was considered as disseminated disease that was unresectable. Patient with limited number of lesions in same lobe of liver but judged as not suitable for partial hepatectomy by a multidisciplinary team meeting was defined as unresectable.p < 0.05 was defined as indicative of statistical significance. All calculations were performed using IBM SPSS 25.0 software, and picture design was finished based on R version 4.1.1  using the Survival, ggplot2, survminer packages.Chi-square test was used to compare between categorical variables and independent t test was used to compare between continuous variables. In the survival analysis, overall survival (OS) was defined as the period of time from the curative esophagectomy to death or the last follow-up. Disease free interval (DFI) was defined as the period of time from the curative esophagectomy to the detection of recurrence. The duration between the detection of initial recurrence and either death or the last follow-up was defined as post-recurrence survival (PRS). Survival curves were plotted by Kaplan-Meier method and compared by log-rank test. Cox’s proportional hazards model was used for univariate and multivariate survival analysis. A n = 30) and non-operation group (n = 33) , and had more with locoregional oligo-recurrence . Otherwise, we found no substantial differences between both groups in parameters such as gender, performance status, Charlson Comorbidity Index (CCI), tumor characteristics, or initial treatment modality of the primary esophageal cancer.A total of 654 patients who underwent esophagectomy between 2004 and 2017 were included, and 284 of them (43.4%) had disease recurrence. After exclusionary screening, 63 patients were deemed with oligo-recurrence amenable for surgical intent. Based on definitive treatments for “resectable” recurrences, these patients were divided into operation group  patients, and locoregional only in 27  patients (Table p = 0.003) and mediastinum recurrence  were the independent prognostic factors of PRS.The overall 1- and 3-year PRS rates were 62.7 and 31.6%. Median survival for all patients after recurrence was 18 months (interquartile range (IQR): 8 to 64 months). The prognostic factors of PRS are shown in Table p = 0.001) and mediastinum recurrence  were also the poor prognostic factors of OS. Additionally, we found brain metastasis  as an independent prognostic factor of worse OS.In the univariate analysis Table , patholop = 0.108 in PRS and p = 0.100 in OS), and between any types of local treatments and systemic treatments (median OS: 39.5 months (IQR:19–60.8) vs. 23 (IQR:13–51), p = 0.171; median PRS: 16.5 vs 8 months, p = 0.145). Further subgroup analysis of patient who underwent surgery (with adjuvant therapy or not) or alternative treatment (chemo-radiotherapy/chemotherapy only/ radiotherapy only) were demonstrated in Fig. p = 0.284; median PRS: 17.5 (IQR:9–25.3) vs 18 months (IQR:9–29), p = 0.497). Between chemo-radiotherapy /chemotherapy only/ radiotherapy only treatment groups  were no statistical significance in each group comparison.Figure p = 0.038).To identify who might benefit from surgical resection for resectable recurrence, survival analysis was undertaken to compare between operation and non-operation groups Fig. . AlthougEsophageal cancer is one of the deadliest cancers with rapidly rising incidence. In our previous report , tumor rIn general, patients with multiple recurrent sites had a worse survival compared with those with less involved sites . CombineIn Ghaly et al’s study , no pronCervical and mediastinal lymph node failures have been reported to be one of the most common types of recurrence after esophagectomy in patients with thoracic esophageal squamous cell carcinoma , 13. In Limited reports on oligo-recurrence to distant solid organ have made it difficult to collect sufficient cases for analysis. The role of surgery in these patients thus remains unknown. For example, only 30% of the patients with oligo-recurrence had surgery in Nobel’s study . Howeverp = 0.031) compared with patients with oligo-recurrences in other sites, which are compatible with the findings in Nobel’s cohort. Whether patients with esophageal cancer should be screened or surveyed for brain metastases remains unclear [On the other hand, Nobel et al. have reported significantly worse outcome in patients with liver and brain oligo-recurrence from esophageal cancer when compared with lung oligo-recurrence, which showed a more indolent course . In our  unclear –24. Alth unclear  has repo unclear .There are several limitations in our study. First, this is a single-institution study. The inherent bias of retrospective nature and relatively small sample size may limit the power of statistical significance. Second, due to the lack of strict definition for “resectable” and guidelines for therapeutic approach in each recurrence site, selection bias for treatment modalities and surgical intervention are inevitable. Third, routine surveillance for bone and brain was not performed in our practice, which might miss early diagnosis of oligo-recurrences in these sites. Finally, since only patients with single site of recurrence were selected, the role of surgery in combination with other aggressive local control or systemic therapy in patients with limited or multiple sites of recurrence was beyond the scope of our study. External validation study with more cases is needed to confirm our observations.Patients with oligo-recurrence represent a small subgroup of patients with recurrence, surgical resection may offer a survival benefit for properly selected patients. We demonstrated that patients with mediastinum LN recurrence or pathologic T3/4 stage were independent factors of OS and PRS for those who had oligo-recurrences after esophagectomy. In patients without comorbidities (CCI = 0), surgical resection was associated with better PRS. Further studies are warranted to define the role of surgical resection in the management of resectable oligo-recurrence.