The main aim of the study was to assess the impact of individualized management of breakthrough cancer pain (BTcP) on quality of life (QoL) of patients with advanced cancer in clinical practice.A prospective, observational, multicenter study was conducted in patients with advanced cancer that were assisted by palliative care units. QoL was assessed with the EORTC QLQ-C30 questionnaire at baseline (V0) and after 28 days (V28) of individualized BTcP therapy. Data on background pain, BTcP, comorbidities, and frailty were also recorded.p < 0.001) at V28 with individualized therapy. Transmucosal fentanyl was used in 93.8% of patients, mainly by sublingual route. Fentanyl titration was initiated at low doses  according to physician evaluation. At V28, mean perception of global health status had increased from 31.1 to 53.1 (p < 0.001). All scales of EORTC QLQ-C30 significantly improved (p < 0.001) except physical functioning, diarrhea, and financial difficulties. Pain scale improved from 73.6 ± 22.6 to 35.7 ± 22.3 (p < 0.001). Moreover, 85.9% of patients reported pain improvement. Probability of no ≥ 25% improvement in QoL was significantly higher in patients ≥ 65 years old  and patients hospitalized at baseline .Ninety-three patients completed the study. Intensity, duration, and number of BTcP episodes were reduced  on July 19, 2016.This study was registered at The online version contains supplementary material available at 10.1007/s00520-021-06006-1. Breakthrough cancer pain (BTcP) is frequent in cancer patients and it significantly impairs their quality of life (QoL) –3. It isBTcP requires appropriate diagnosis and individualized management . An algoIndividualized BTcP management consists of an assessment process, from pain diagnosis to follow-up. First, physicians should assess patient characteristics and pain features . Adherence to background pain therapy should also be assessed. After BTcP diagnosis, strong opioid medication should be prescribed, considering the patient needs and preferences. Currently, specific guidelines support the use of rapid-onset opioids (ROOs) as rescue medication in unpredictable and rapid-onset BTcP, and the use of standard normal-release oral opioids in those cases with slow-onset pain episode or as pre-emptive administration before a predictable pain episode triggered by known events , 10. ROOPatients with advanced cancer assisted in palliative care units had multiple symptoms, chronic comorbidities, impaired functional and health status, and very limited life expectancy. Because of their frailty profile, these patients are usually excluded from clinical trials of BTcP management. Moreover, there are few data on QoL in these patients. Therefore, the main aim of the CAVIDIOPAL study was to assess QoL of patients with advanced cancer and BTcP treated with individualized pain therapy in palliative care units. Secondary aims included to examine BTcP features, global impression of improvement after individualized BTcP management, and frailty and its potential effect on QoL.A prospective, observational, multicenter study was conducted in patients with advanced cancer who were assisted by Spanish Palliative Care teams.Both hospitalized patients and outpatients were recruited from palliative care units at acute care hospitals in Spain. Inclusion criteria were age ≥ 18 years, diagnosis of advanced cancer, clinically estimated survival ≥3 months, attendance by palliative care units, background cancer pain controlled with opioids, diagnosis of BTcP using the Davies algorithm , and sigPatients were excluded if they had severe cognitive impairment or other condition or disease that hampered the study understanding or data collection according to the investigator judgment. Patients were also excluded if they fulfilled criteria of addiction to opioids, alcohol, or other recreational drugs.Pain intensity was measured with a visual analog scale (VAS) from 0 (no pain) to 11 (unbearable pain) points. Moderate pain intensity was defined as a value ≥ 4 in VAS.At baseline , after obtaining signed informed consent, BTcP treatment was individualized. This included a careful assessment of BTcP episodes; information on pain features; advisement on non-pharmacological therapy; onset or change of analgesia for BTcP episode according to the physician judgment; education on prescribed drug use; follow-up of BTcP therapy at each visit; alert measures; and adverse event prevention. An integral approach was also proposed, which included management of the rest of symptoms, and psychosocial and spiritual support, according to specific needs of patient.Primary outcome was QoL, measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30) version 3.0  at baselThe other study variables were measured at baseline visit (V0) and at the visits 8 (V8), 15 (V15), 28 (V28), and/or 90 (V90) days after inclusion in the study. An ad hoc questionnaire to assess the study variables was developed. In addition of the EORTC QLQ-C30, the questionnaire was composed of socio-demographic data (V0); type of cancer and its stage (V0); global health status measured with the Eastern Cooperative Group performance status scale (ECOG-PS)  (V0); nuA descriptive analysis of all the registered variables was performed. Global health status and EORTC QLQ-C30 scores at V0 and V28 were compared. In addition, the BTcP-related variables and BTcP treatment at each visit were analyzed. Moreover, EORTC QLQ-C30 results were stratified by frailty variables .t test or the Wilcoxon signed-rank test was used for analyzing differences between categorical variables, while the chi-squared test or the Fisher test was employed for differences between continuous variables. In addition, to identify variables of frailty related to changes in QoL, an analysis of covariance (ANCOVA) was performed; an increase ≥ 25% in the EORTC QLQ-C30 score between V0 and V28 was considered as an improvement in QoL. Then, the variables with differences with p value < 0.1 were included in a logistic regression analysis.Categorical variables were expressed with number and percentage, and continuous variables with mean (± standard deviation) and median . The Student p values <0.05 were considered statistically significant. However, all the statistical tests performed are explorative and descriptive since the sample size was not calculated. To our knowledge, there were no previous studies that identified the magnitude of variations in QoL parameters related to simple factors of frailty. Therefore, we were not able to estimate the sample size. A population of at least 100 patients was the sample objective, considering the recruitment ability and that the study was carried out in the clinical practice framework.All statistical analyses were conducted using IBM SPSS Statistics V22.0. n = 99). Five patients died before V28, one patient withdrawn consent, and 93 patients completed the study until V28.From June 2016 to December 2017, 100 patients were recruited from 8 out of the 10 planned palliative care units. One patient did not have advanced cancer and was excluded. Written informed consent was obtained from all individual participants in the study  were located more frequently in the bone, liver, lung, and lymph nodes. At baseline, most patients (77.7%) had an ECOG-PS score ≤ 2. Comorbidities were common, especially diabetes mellitus, chronic obstructive pulmonary disease, and chronic heart failure. Few patients presented mild cognitive impairment (7%) at baseline. Moreover, 24% met criteria of cachexia. Almost half of patients complained of dry mouth. Finally, no patient showed addictive behavior Table .Table 1BBackground pain had a mean intensity of 4 at baseline. Transdermal fentanyl was the main treatment, used in more than 45% of patients and with a mean dose of 81.1 μg/h. Oral morphine was employed in more than 15% of patients. Considering all opioids administered, mean oral morphine equivalent dose was 110.5 ± 46.7 mg/day. Other therapies for background pain were adjuvant drugs, mainly anticonvulsants and antidepressants Table .Table 2BAt baseline, BTcP was spontaneous in nearly 50% of patients and incident in the other 50% of patients. It had a mean intensity of 8 and it was located mainly in the abdomen (42% of patients) and chest (18% of patients). Patients suffered a mean of 3.6 episodes a day, with a mean duration of 27.5 min per episode. Therefore, the mean time with uncontrolled pain (number of episodes multiplied by its duration) per patient was 99 ± 20.2 min/day. Transmucosal fentanyl, especially by sublingual route, was the most used opioid , oral standard release morphine in 5 patients (5.1%), and standard release oxycodone in 1 patient (1.0%). Mean initial dose of transmucosal fentanyl prescribed at V0 was 116.7–± 86.2 μg, with a minimum dose of 67 μg in 39 patients and a maximum dose of 400 μg in 6 patients, according to the physician evaluation. Moreover, 17 patients also received non-pharmacological therapy, including physical therapy (5.1%), radiation therapy (4.0%), psychotherapy (4.0%), and nerve block (1.0%). Despite 35% of patients presented bone metastasis, only 4% were treated with radiotherapy, because in most of cases, this treatment was administered before inclusion in this study.p < 0.001 for each visit), both for background pain and BTcP. Mean intensity of background pain was reduced from 4 at V0 to 2 at V28 and 1.8 at V90 (p < 0.001). Mean intensity of BTcP was reduced from 8 ± 1.0 at V0 to 4.6 ± 2.4 at V28 and 4 ± 2.4 at V90 (p < 0.001).Intensity of pain (VAS scores) was reduced significantly at V8, V15, V28, and V90 compared with V0 (p < 0.001). Dose adjustments were the main cause of these changes in analgesia (74.5%), which was reduced during the study.Opioid therapy for background pain was changed in 45.9% of patients at V8, with successive reductions in the number of patients with opioid change. Most of these changes were dose adjustments . Opioid therapy for BTcP was also changed in 38.8% of patients at V8 and 12.6% at V15, but then 93 patients (97.9%) did not have therapies changes from V28 to V90  required hospitalization, including one case of non-predicted opioid side effect (acute urinary retention).p < 0.001 for each item), and constipation (p = 0.001). In particular, the pain rating changed from a mean of 73.6 ± 11.6 at V0 to a mean of 37.7 ± 22.3 at V28 (p < 0.001), indicating a significant reduction. No statistically significant differences were found for physical functioning, diarrhea, and financial difficulties , and pain characteristics .p < 0.211) was found between patients with and without high symptom burden. However, when adjusting by the symptom burden at baseline, difference was statistically significant (p = 0.008).Sixty patients (60.6%) presented a high symptom burden, defined as ≥ 5 symptoms according the ESAS instrument, with at least moderate intensity. After 28 days, no statistically significant difference in the EORTC QLQ-C30 score (p < 0.1) for use in the logistic regression model. However, the variable “number of BTcP episodes” was excluded because it was not significant in the model.Patients with ≥ 25% improvement in the EORTC QLQ-C30 questionnaire were compared according to a series of variables. For the variable “age,” patients were categorized as ≤ 65 years old (40.9% of patients) and > 65 years old (59.1% of patients). Only age, number of BTcP episodes during the previous 24 h, and hospitalization at study inclusion were identified as significant (p < 0.05) with age > 65 years and hospitalization. The risk of no improvement was 1.04-fold increased for each year of age above 65 and 4.06-fold increased with hospitalization at baseline , advice on non-pharmacological interventions, and education on the use of ROO medication. Transmucosal fentanyl was the drug most used for BTcP treatment. Sublingual low dosage  and cautious titration were a suitable option in frail and older patients, according to physician judgment. Therefore, these results could help to individualize BTcP management in patients with advanced cancer.From these results, it can be concluded that individualized BTcP therapy, in the context of a palliative comprehensive support, improves QoL of patients with advanced cancer in clinical practice. However, this improvement is less likely in patients older than 65 years or hospitalized.ESM 1(DOCX 19 kb)


SBRT) is an advanced technique of hypofractionated external beam radiotherapy (EBRT) that can be applied in patients with HCC. The current study showed that the area under the concentration–time curve of lenvatinib concentration (AUClenvatinib) increased by 148.8% with radiotherapy (RT)2Gy×3f’x (EBRT for the whole liver), and 68.9% with RT9Gy×3f’× (SBRT targeting a 1.5 × 1.5 cm region in the center of the liver) in the sequential regimen compared to the concurrent regimen in rats. Additionally, the AUClenvatinib was decreased by 50% in the concurrent regimen of both RT techniques with lenvatinib compared to the control group. The biodistribution of lenvatinib in the organs at risk was markedly decreased in the concurrent regimens. The radiation–drug interactions were between lenvatinib and RT, and showed sequential preferably.Lenvatinib is a systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Stereotactic body radiation therapy (lenvatinib) by 51.1% with three fractions of 2 Gy , and 48.9% with RT9Gy×3f’x (p = 0.03). The AUClenvatinib increased by 148.8% (p = 0.008) with RT2Gy×3f’x, and 68.9% (p = 0.009) with RT9Gy×3f’x in the sequential regimen compared to the concurrent regimen. There were no differences in the AUClenvatinib between RT2Gy×3f’x and RT9Gy×3f’x in the concurrent or sequential regimen. Both the RT2Gy×3f’x and RT9Gy×3f’x concurrent regimens markedly decreased the biodistribution of lenvatinib in the heart, liver, lung, spleen, and kidneys, which ranged from 31% to 100% for RT2Gy×3f’x, and 11% to 100% for RT9Gy×3f’x, compared to the sham regimen. The PK and biodistribution of lenvatinib can be modulated by simultaneous off-target irradiation and SBRT doses. The timing of lenvatinib administration with respect to RT, impacted the PK and biodistribution of the drug. Additionally, off-target and SBRT doses had a similar ability to modulate the effect of systemic therapy.Concurrent and sequential regimens involving radiotherapy (RT) and lenvatinib were designed with off-target or stereotactic body radiation therapy (SBRT) doses in a freely moving rat model to evaluate the effect of RT on the pharmacokinetics (PK) of lenvatinib. Liver RT concurrent with lenvatinib decreased the area under the concentration–time curve of lenvatinib concentration (AUC The oraStereotactic body radiation therapy (SBRT) is an advanced external beam radiotherapy (EBRT) technique, which can be considered as an alternative to ablation/embolization techniques, or used when these techniques fail or are contraindicated for HCC ,6. RecenNuclear factor kappa B (NF-κB) modulates the expression of cytochrome P450 (CYP) 3A4 , increasTaken together, these data suggest that there may be interactions between RT and lenvatinib. In the current study, the PK behavior of lenvatinib with different RT doses and schedules was evaluated. Furthermore, the biodistribution of lenvatinib with, and without, RT was evaluated to provide suggestions for clinical applications.Lenvatinib and cyclosporin A were purchased from Sigma-Aldrich . As an internal standard, biochanin A was purchased from Toronto Research Chemicals Inc. . Polyethylene glycol 400 (PEG 400) and heparin sodium were purchased from Sigma-Aldrich. Pentobarbital sodium was obtained from SCI Pharmtech . The solvents and reagents for chromatography were purchased from J.T. Baker  and Merck . Standard solutions of lenvatinib and biochanin A in methanol were stored at −20 °C. Triply deionized water from Millipore  was used for all preparations.v:v) at a flow rate of 1 mL/min. A wavelength of 251 nm was set for the optimal photodiode-array detection of lenvatinib. Lenvatinib had a retention time of 6.5 min, with good separation and no endogenous interference in the rat plasma samples, and the procedure exhibited good selectivity (The HPLC system consisted of a chromatographic pump (LC−20AT), an online injector (SIL−20C) equipped with a 10 μL sample loop to inject the sample, and an ultraviolet detector (SPD-M20A). Lenvatinib and samples were separated on an Agilent ZORBAX SB-phenyl column . The mobile phase for the lenvatinib group consisted of water and acetonitrile  for the calibration curve, which should be greater than 0.995. The limit of detection (LOD) was defined as the concentration that generated a signal-to-noise ratio of 3, and the lower limit of quantification (LLOQ) was defined as the lowest concentration within the linear regression that yielded a signal-to-noise ratio of 10. A 0.01 mg/mL limit of quantification was identified as the lowest concentration on the calibration curve that could be measured routinely with acceptable bias and relative SD. Calibration standards for plasma samples were prepared by adding known amounts of lenvatinib (10 μL) into rat plasma blanks (40 μL each) to yield a range of 0.05–50 μg/mL. These mixtures were supplemented with 150 μL of internal standard solution (10 μg/mL).The calibration curves covered a concentration range from 0.1 to 50 μg/mL. The linearity of the assay was determined using the coefficient of determination (Cnom) and the mean value of observed concentrations (Cobs) as follows: accuracy (% bias) = ((Cnom − Cobs)/Cnom) × 100. The relative standard deviation (RSD) was calculated from the observed concentrations as follows: precision (% RSD) = (standard deviation (SD)/Cobs) × 100. The same data were used to determine both accuracy and precision. The relative error and coefficient of variation were maintained within ± 15%, except for the LLOQ, which was not permitted to exceed ± 20%. Recovery was assessed at three different concentrations  by comparing the peak areas of the post-extraction spiked samples with those of the standard solution.The intra- and interassay variability for lenvatinib was determined by quantifying six replicates at concentrations of 0.05, 0.1, 0.5, 1, 5, and 10 μg/mL, using the above-described HPLC method on the same day, and on six consecutive days. The accuracy (% bias) was calculated from the nominal concentration . Adult male Sprague-Dawley rats (300 ± 20 g body weight) were provided by the Laboratory Animal Center at National Yang-Ming University . The animals had access to water and food ad libitum  and lived in a pathogen-free environment, with a 12/12 h light–dark cycle. All animal experiments followed the guidelines and procedures for the care of laboratory animals at National Yang-Ming University.2Gy, or RT9Gy, given concurrently or sequentially with lenvatinib. Data were collected from six rats per group.A freely moving rat model was designed for the current study . The rat0Gy (lenvatinib×3d); (B) whole-liver  RT2Gy×3f’x concurrent with 3 d of lenvatinib (3 mg/kg); (C) whole-liver RT2Gy×3f’x followed by 3 d of lenvatinib (3 mg/kg); (D) SBRT (9 Gy with 3 fractions) RT9Gy×3f’x concurrent with lenvatinib (3 mg/kg) for 3 d; and (E) RT9Gy×3f’x followed by 3 days of lenvatinib (3 mg/kg) for 3 d (n = 6 per group).A radiation dose of 2 Gy was considered the daily conventional EBRT dose or the off-target dose around the target that received an ablation RT dose. A dose of 9 Gy was used to simulate SBRT. The animals were divided into five groups, as follows: (A) sham group, lenvatinib (3 mg/kg) only for 3 days (d) with RT for 3 d . Rats weThe effects of ketoconazole (KZT), an inhibitor of CYP3A  and P-gpBlood samples were collected in a heparin-rinsed vial via polyethylene tubing (PE-50) implanted into the jugular vein of each rat. Aliquots of 100–120 µL blood were collected at time intervals of 0, 5, 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min following drug administration. At each time point, 200 μL of blood was drawn into heparin-rinsed Eppendorf tubes and then centrifuged at 13,000 rpm for 10 min at 4 °C to obtain plasma. Plasma was stored at −20 °C until analysis. Each collected blood sample was transferred to a heparinized microcentrifuge tube and centrifuged at 13,000 rpm for 10 min. The resulting plasma (50 μL) was then mixed with 150 μL of internal standard solution (10 μg/mL). The denatured protein precipitate was separated by vortexing for 20 s and centrifuged at 13,000 rpm for 10 min at 4 °C.×3d , blood samples were collected as mentioned above. The brain, liver, heart, spleen, lung, and kidney were collected and weighed. These collected samples were stored at −20 °C until analysis.Six hours after lenvatinib administrationg for 10 min at 4 °C. The supernatant was collected, placed in brown Eppendorf tubes, and stored at −20 °C until analysis. Briefly, each organ sample (50 μL) was combined with 150 μL of IS solution (diethylstilbestrol) for protein precipitation. Finally, 20 μL of filtrate was subjected to HPLC analysis.The thawed organ samples were homogenized in 50% aqueous acetonitrile (the ratio of sample weight and volume was 1:5), and the homogenate was centrifuged at 13,000× Glutamic-pyruvic transaminase (GPT) and creatine were measured to examine the influence of different modalities on hepatic function and renal function by a standard colorimetric method using a Synchron L × 20 spectrophotometer  and manufacturer-supplied reagents.t1/2), volume of distribution at steady state (Vss), and mean residence time (MRT), were calculated using the PK calculation software WinNonlin Standard Edition, Version 1.1  by a compartmental method.PK parameters, including the area under the concentration–time curve (AUC), clearance (CL), elimination half-life  for Windows, version 20.0 . All data are expressed as the mean ±SD. One-way analysis of variance (ANOVA) was used for comparisons between groups, and statistically significant differences were defined as * y = 1.6777 × −0.0751 (r2 = 1). The intraday accuracy (% bias) of lenvatinib ranged from 2.39 to 23.3%. The intraday precision (% RSD) ranged from 2.35 to 23.8%. The recovery rate of lenvatinib at 0.05 to 10 µg/mL ranged from 111.8% to 96.15%.In the current study, the LOD of lenvatinib in plasma was 0.5 μg/mL. The regression equation for lenvatinib in rat plasma was ×3d, the AUClenvatinib and Cmax decreased by 51.1% (p = 0.03) and 58.3% (p = 0.03), respectively, with RT2Gy×3f’x in the concurrent regimen. However, the AUClenvatinib increased by 21.6% with RT2Gy×3f’x in the sequential regimen (p = 0.44). Additionally, compared to the concurrent regimen, the AUClenvatinib and Cmax increased by 148.8% (p = 0.008) and 154.5% (p = 0.008), respectively, in the sequential RT2Gy×3f’x regimen. Moreover, the AUClenvatinib did not differ between the concurrent RT2Gy×3f’x and RT9Gy×3f’x regimens (p = 0.87). (Compared to lenvatinib= 0.87). Alenvatinib and Cmax decreased by 48.9% (p = 0.03) and 56.1% (p = 0.04), respectively, with the concurrent RT9Gy×3f’x regimen. There was no statistically significant difference in the AUClenvatinib between the lenvatinib x 3d and sequential RT9Gy×3f’x groups. Intriguingly, the AUClenvatinib and Cmax increased by 68.9% (p = 0.009) and 68.7% (p = 0.02), respectively, with the sequential RT9Gy×3f’x group compared to the concurrent regimen. Furthermore, there were no statistically significant differences in the AUClenvatinib between the sequential RT2Gy×3f’x and RT9Gy×3f’x groups (p = 0.12). . Blenvatinib in all groups except for the concurrent RT9 Gy group, which showed a nonsignificant 28% increase  Lenvatinib in Differentiated Cancer of the Thyroid (SELECT), patients treated with lenvatinib experienced cardiac dysfunction (7%), nausea and vomiting (20–40%), stomatitis (20–30%), diarrhea (60%), fatigue (more than 50%), palmar-plantar erythrodysesthesia syndrome (70%), hemorrhagic events (35%), thrombocytopenia (8.8%), fistula formation (1.5%), reversible posterior leukoencephalopathy syndrome (0.4%), and thromboembolic events (5.4%), and one-third of patients experienced proteinuria of any grade ,56. AddiThere were some limitations to our study. First, the current study did not use orthotopic or heterotopic models, but used a freely moving Sprague-Dawley rat model to confirm the interaction between RT and lenvatinib. However, the differences in the PK profile of lenvatinib between healthy subjects and patients are small . TherefoSecond, the current study did not include a disease model treated with lenvatinib and RT; therefore, we cannot report the treatment effects of the combination of RT and lenvatinib. However, the current analysis sheds light on the discrepancies of PK in the concurrent and sequential regimens of RT with lenvatinib, which may be useful for prospective clinical trial designs. Brade et al.  noted thThird, the possible mechanism was not examined in the current study, because the presence or absence of the RT-PK phenomenon in the context of lenvatinib plus RT could not be ensured before the study. However, we confirmed that the systemic PK of lenvatinib could be modulated by conventional EBRT and SBRT, as well as concurrent RT and sequential RT. The design of these combination regimens provides different scenarios in clinical practice. We realized that an in vitro study could not replicate or validate an in vivo study because the impacts of the local microenvironment and systemic modulators would be absent. Notably, the RT regimen affects P-gp activity, and the sequential RT regimen increases CYP3A4 activity to modulate the PK of sorafenib . Therefolenvatinib was decreased by 50% in multiple fractions of RT concurrent with lenvatinib. Additionally, off-target and SBRT doses had a similar ability to modulate systemic therapy. Furthermore, CYP3A4-related oxidative metabolism does not appear to be a major pathway involved in the action of lenvatinib alone or coadministration with RT. There is a pressing need to incorporate our current understanding of the systemic effects of localized irradiation into future treatment strategies, and the current findings can serve as a starting point for the scientific community to explore the effects of combined lenvatinib and RT as synergistic tools in HCC treatment strategies.Taken together, these data support the concept of the interplay between RT and lenvatinib by suggesting that the systemic PK of lenvatinib can be modulated by irradiation. The timing of lenvatinib and RT doses affected the AUC and biodistribution of the drug during treatment. The AUC


In the original article, the reference for The Bifrost pipeline was incorrectly written as ‘commitid 0f2ef57’. It should instead be written as ‘Lagesen, NorwegianVeterinaryInstitute/Bifrost: v1.1 (Version v1.1). Zenodo. doi: 10.5281/zenodo.4020511Lagesen, K. (2020). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


Two ipsilateral hemivertebrae is less common and presents severe growth imbalance caused by the vertebral anomalies. However, there is a paucity of reports regarding to two ipsilateral thoracolumbar hemivertebrae. The purpose of present study is to evaluate the long-term outcomes of the posterior surgical correction of thoraco-lumbar spine deformity caused by two ipsilateral hemivertebrae.From 2006 to 2014, a total of 14 consecutive pediatric patients with congenital thoraco-lumbar hemivertebrae were treated by posterior excision of hemivertebrae with short segment fusion. The following parameters were measured: coronal major curvature, cranial and caudal compensatory curvature, segmental kyphosis, lumbar lordosis, trunk shift, apical vertebra translation and sagittal vertical axis. These results were compared and evaluated in preoperatively, immediately postoperatively and at the final follow-up. All patients had a minimum of 5 years follow-up.The mean age at surgery was 11.1 ± 4.8 years (2yos to 17yos). The mean follow-up period was 80.2 ± 19.4 months (60mons to 117mons). There was a mean improvement of 74.2% in the coronal major curve from a mean angle of 64.1° before surgery to 15.8° at the final follow-up. The cranial and caudal curves improved of 69.8 and 69.0% from 25.6° to 7.7°, 26.9 to 8.2, respectively. The mean thoraco-lumbar kyphosis was 59.9° before and 13.6° after surgery, 20.8° at the final follow-up. Alignment in the coronal and sagittal plane was either maintained or improved within normal values in all patients.Good correction and spinal balance can be achieved by posterior-only hemivertebrectomy in patients with thoracolumbar kyphocsoliosis caused by two ipsilateral hemivertebra. The complication of neurological injury is low but a technically demanding procedure. More attention should be paid in residual curve progression after surgery. The natural history of congenital scoliosis has been well documented , 2. The Two ipsilateral HV are not common but have a much worse prognosis. The hemivertebrae are usually separated by normal vertebrae. Full segmented HV means the absence of four growth plates on concave side of the curvature, resulting in much greater growth imbalance. Prior study suggested that kyphoscoliosis due to anterolateral unsegmented bar combined with posterolateral quadrant HV progress at 5° per year until the age of 10 and 10° thereafter . TherefoThere are various types of surgical procedures in the treatment of congenital kyphoscoliosis. Combined anterior and posterior convex hemiepiphysiodesis, excision of HV via posterior or anterior-posterior fusion techniques have been used extensively , 8. HoweThere is a paucity of report regarding to congenital kyphoscoliosis caused by two ipsilateral HV. The aim of this study is to evaluate the long-term outcomes of the one-stage posterior-only surgical correction of thoraco-lumbar kyphoscoliosis caused by two ipsilateral HV.This retrospective study was approved by the Ethics Committee of our Hospital. From 2006 to 2014, we identified all patients with the diagnosis of congenital thoracolumbar kyphoscoliosis, among of these patients who had two ipsilateral HV were reviewed from our database. The thoracolumbar region was defined as range from T10 to L2. Of all, fourteen consecutive patients were included with a follow-up of at least 5 years.Demographic data were recorded including sex, age, height, body weight and Risser sign. In addition to the radiological data, inpatient and outpatient records were reviewed. Preoperative evaluation included a neurologic examination, full length radiographs in anterioposterior and lateral view. 3-D computer tomography in entire spine was performed to detect details of spine deformity, and MRI is for detecting intraspinal abnormalities and spinal cord malformation. To detect congenital heart and urogenital abnormalities, Cardiovascular and urogenital ultrasounds were also performed. No patient had undergone a prior surgery. No patient had a neurologic deficit.All patients underwent posterior hemivertebra resection in primary surgery. For patients needed revision surgery, PSO or Y-Shape osteotomy was performed depending on the status of spine deformity. The fusion level depends on severity of spine deformity, as well as scope and flexibility of curve. For very young children, one vertebra above and below after HV resection were fixated and fused. If the scoliotic curve was large or with focal kyphosis, two vertebrae above and below after HV resection were fused. Of course, for severe and rigid scoliosis or kyphoscoliosis, more fusion level may be needed. All radiographs were measured by two spine surgeons independently based on free standing posteroanterior and lateral X-ray taken in preoperatively, immediately after surgery and at the final follow-up. The location and number of the HV, relationship of the adjacent vertebrae (segmented status), coronal major curve, cranial and caudal compensatory curve, apex vertebra translation, trunk shift, segmental kyphosis, lumbar lordosis, thoracic kyphosis and SVA were record. The segmental scoliotic and kyphotic curves were measured according to Cobb’s method. The trunk shift (TS) was evaluated as the distance between a vertical line drawn from the center of C7 vertebral body to the middle of sacrum, which was related to the pelvis width  and expressed in percentage to avoid effects of radiographic enlargement . These pAfter surgery, all patients were required to a rigid brace for at least 3 months, aiming to protect the instrumentation. All patients were followed up at 1 week, 1 month, 3 month, 6 month, 1 year at postoperatively, and then every year. The method of fusion evaluation is bending film of X-ray and CT scan.P value less than 0.05 were considered as statistically significant.Pair t-test were used to analyze the difference of coronal major curve, cranial and caudal compensatory curve, segmental kyphosis, lumbar lordosis, apex vertebra translation, trunk shift and SVA at pre-operation, post-operation and final follow-up. The differences with a Of the all patients, there are seven girls and seven boys. The mean age at surgery was 11.1 ± 4.8 (3 to 17) years. The mean follow-up period was 80.2 ± 19.4 (60 to 117) months. One stage posterior hemivertebra resection with unilateral short fusion in patients less than 10 years old was performed  before operation, which improved to 17.1 ± 12.6° (4 to 45), 15.8 ± 11.0° (5 to 42) postoperatively and at the final follow-up, with a mean correction of 73.3 and 75.4%. The mean cranial compensatory curve was 25.6 ± 11.4° preoperatively and 7.7 ± 5.3° at the final follow-up, giving a correction of 69.9%. The mean caudal curve was 26.9 ± 9.3° preoperatively and 8.2 ± 6.1° at the final follow-up, giving a correction of 69.5%. The trunk shift was not significant difference between preoperatively and postoperatively, but had significant difference at the final follow-up. The apex vertebra translation (AVT) was improved significantly before and after operation, and kept stable during the follow-up period  before and 13.6 ± 9.5° (0 to 30) after surgery, 20.8 ± 13.8° (2 to 46) at the final follow-up. The mean thoracic kyphosis was 60.6 ± 15.7° (28 to 98) before surgery and 42.8 ± 12.5° (23 to 63) at the final follow-up. The mean lumbar lordosis was 65.3 ± 13.1° (46.8 to 96) before surgery and 45.8 ± 7.6° (31 to 59) at the final follow-up. Spinal alignment in the sagittal plane was either maintained or improved in all patients  translation and postoperative LIV disc angle were identified as two independent risk factors [Another concern is neurological complication after HV resection via posterior approach. Aydogan M, et al.  reportedSome cases presented residual curve progression after surgery, which may be attributed to a variety of factors, including multiple malformed vertebra, failure of segmentation, concave fused ribs, improper maneuver, shorter fusion level, incomplete HV resection and implants failure. Shi Z et al. investigate the causes of failure in the first operation and the revision procedure for patients with congenital scoliosis due to HV . They suIn terms of anterior column reconstruction (ACR), a titanium mesh cage was used for anterior column support and fusion in patients who had residual anterior gap after HV resection. Aydogan M et al.  reportedThis study has some limitations. First, it was a retrospective study with the inherent risk of data inaccuracy. Second, the wide range of the patients’ age makes this small series inhomogeneous and comparison is quite difficult. Finally, this study does not contain results about quality of life in the follow-up. Further study including quality of life and mental health status are needed in the future.Based on our experience, good correction and spinal balance can be achieved by one-stage posterior-only hemivertebra resection in patients with thoraco-lumbar kyphoscoliosis caused by two ipsilateral HV. Improvement of the segmental scoliosis and kyphosis curves is satisfactory and kept stable in long-term follow up. The complication of neurological injury is low but a technically demanding surgical procedure. More attention should be paid in residual curve progression after surgery.


A. lividus genotypes. The color parameters, such as the yellowness/blueness (b*) and the chroma (C*); the antioxidant components, such as the polyphenols and flavonoids; and the antioxidant capacities of the leaves were remarkably increased by 39, 1, 5, 10 and 43%, respectively, at 50 mM of NaCl, and by 55, 5, 60, 34, 58 and 82%, respectively, at 100 mM NaCl concentrations. The green tower and SA6 genotypes were identified as tolerant varieties. The total phenolic content (TPC) and the total flavonoid content (TFC) played vital roles in scavenging reactive oxygen species (ROS), and they would be beneficial for the human diet and would serve as good antioxidants for the prevention of aging, and they are also essential to human health. A correlation study revealed the strong antioxidant capacities of the pigments and antioxidant components that were studied. It was revealed that A. lividus could tolerate a certain level of salinity stress without compromising the antioxidant quality of the final product. Taken together, our results suggest that A. lividus could be a promising alternative crop for farmers, especially in saline-prone areas in the tropical and subtropical regions.This is the first attempt to evaluate the impact of four salinity levels on the color parameters, pigments, polyphenols, flavonoids, and antioxidant capacities of four promising  A. lividus) is a C4 dicotyledonous plant that belongs to the family, Amaranthaceae. Vegetable amaranth is a rich source of nutrients, such as vitamin A, vitamin B , vitamin C, calcium, magnesium, potassium, phosphorus, iron, zinc, copper, and manganese [Vegetable amaranth  with excellent antioxidant activity.Amaranth is a leafy vegetable that is well acclimatized to different abiotic stresses ,22,23,24Cichorium spinosum [A. tricolor genotypes under drought and salinity stress and found augmentations of the leaf color parameters, the antioxidant leaf pigments, the polyphenols, the flavonoid contents, and the antioxidant capacities. It is the first report of the effect of salinity stress on color parameters, antioxidant leaf pigmentation, polyphenols, flavonoids content, and antioxidant capacity of A. lividus leafy vegetable. Therefore, the present investigation aimed to study A. lividus genotypes in response to salinity stress in terms of color parameters, antioxidant leaf pigmentation, polyphenols, flavonoids content, and antioxidant activity Salt stress elevated the phenolics, flavonoids, antioxidant activity, and chlorophyll pigments in spinosum . Alam etspinosum  observedspinosum  report tThe experimental site is located at the center of the Madhupur tract (24.09° N latitude and 90.26° E longitudes), which is 8.4 m above sea level.A. lividus) genotypes , and SA3 and SA6 genotypes ) were selected for the study. The experiment was conducted as a factorial design of the salinity treatments and varieties in a randomized complete block design (RCBD) with three replications.Four vegetable amaranth .The trays (38 cm × 24 cm × 10 cm) were filled with 5.5 kg of sandy loam soil. The upper portion of the tray (1–1.5 cm) was kept empty to hold the irrigation water. The fertilizers, N, PA. lividus were harvested. All of the parameters were measured in three replicates.The trays were well irrigated every day using fresh water, up to 9 DAS the seeds for the proper establishment and vigorous growth of the seedlings. The salinity stress treatment was started at 11 DAS, and it was continued up to 35 DAS (the edible stage). The salinity stress was applied by irrigating the respective trays with concentrations of 0 mM of NaCl (Control); 50 mM of NaCl, or medium salinity stress (MSS); 100 mM of NaCl, or severe salinity stress (SSS); and 150 mM of NaCl, or very severe salinity stress (VSSS), at 24 h intervals, from sowing to harvesting. The control plants received irrigation with normal water (without NaCl or freshwater). At 35 days after sowing (DAS), the leaves of The chemicals that were used in the study are acetone, methanol, ascorbic acid, the Folin–Ciocalteu reagent, sodium carbonate, aluminum chloride, potassium acetate, DPPH , gallic acid, and quercetin.2 + b2)1/2.The color parameters  were measured by a color meter  following Sarker and Oba ,30,31. Ta, chlorophyll b, chlorophyll a/b, total chlorophyll, and total carotene analyses, following the method prescribed by Sarker and Oba [a, chlorophyll b, total chlorophyll, and total carotene were calculated by using the following formulas:Fresh leaves of each genotype were used for the chlorophyll  and Oba ,33,34. A−1 of the fresh leaf weight, and the total carotene was calculated as μg of the total carotene per g of the fresh leaf weight.Finally, the chlorophylls were calculated as μg·g−1), ε = Extinction coefficients of betacyanin (62 × 106 cm2 mol−1), L = Path length is the 1 cm cuvette”); and Betaxanthin (μg·g−1) = [(A × DF × MW)/ε × L × leaf weight (g).From each genotype, the fresh leaf was used for the betacyanin analysis, and their average values were obtained according to the method that is prescribed by Sarker and Oba ,36. A to−1); ε is the extinction coefficients of the betaxanthin (48 × 106 cm2 mol−1); and L is the path length, which is the 1 cm cuvette.Here, A is the absorption at 475 nm; DF is the dilution factor (the extraction amount); MW is the molecular weight of the betaxanthin  with shaking. After 1 h, the extract was filtered for further analytical assays of the polyphenols, the flavonoid content, and the antioxidant activity.2CO3 (10%) was added after 3 min, and the mixture was allowed to stand for 1 h in the dark. The optical density was taken at 760 nm by using a spectrophotometer . The concentration of the total phenolic compounds in the leaf extracts was determined as the μg·g−1 of gallic acid equivalent by using an equation (Y = 0.009X + 0.019) that was obtained from a standard gallic acid graph and the following formula: C = (c × v)/m, where C is the total phenolic content; c is the concentration of the gallic acid; v is the volume of the extract; and m is the weight of the crude extract in g. The results are expressed as the μg·g−1 gallic acid equivalent of the dry weight (dw).The phenolic content was determined by the Folin–Ciocalteu reagent ,38. A to−1 quercetin equivalent of the dry weight (dw).The aluminum chloride colorimetric method was followed to estimate the total flavonoid content ,40. For blank is the absorbance of the control reaction, and A sample is the absorbance of the test compound in the sample.The TAC was measured by the DPPH  radical degradation method ,42. A top ≤ 0.05) to identify the differences between the means.The recorded data were arranged according to a randomized complete block design, with three replications for the statistical analysis . The crop performances were subjected to an analysis of variation (ANOVA) with Statistix 8 software ,44,45. TThe analysis of variance (ANOVA) provided significant variations among the treatments for all of the considered traits. A wide range of variations was also reported in the agronomic traits of maize ,47,48, rA. lividus at different levels of salinity stress (A. tricolor and A. hypochondriacus) and they observed significant differences between the cultivars. Khandaker et al. [A. tricolor). The highest C* value was observed in the green tower (32.30), while the lowest value was noticed in the SA6 (9.25), followed by the SA3 (9.77). These results agree with the results of Sarker and Oba [A. tricolor genotypes under salinity stress.Significant variations in the leaf color attributes were observed among the four genotypes of y stress . Among ty stress . Khanam r et al.  also rep and Oba , who repA. tricolor genotypes with the increments of salinity stress. The extreme NaCl concentration under VSSS interrupted the physiology of A. lividus, which enhanced the drastic reductions in the L*, a*, b*, and C* values.In terms of the salinity treatments, the highest L* value was obtained under the control treatment, followed by the MSS (43.38) and SSS (39.89) treatments, and the lowest value was obtained from the VSSS treatment (21.46). Increases in the salinity resulted in a significant reduction in the L* value from the control condition to the VSSS condition, following the order: Control > MSS > SSS > VSSS. In the case of the a* value, the highest value was found for VSSS (−2.35), followed by SSS (−3.01), and MSS (−4.92), and the lowest value was found in the control (−8.62). In contrast, the highest b* value was obtained under SSS (10.33), followed by MSS (10.31), and the control (8.64), and the lowest value was found under VSSS (7.51), as the red tower and SA3 genotypes failed to germinate under VSSS . The higA. tricolor genotypes, with the increments of light intensity and salinity stress, respectively.In the case of the interaction effect, the L*, a*, b*, and C* values ranged from 34.03 to 59.01, from 15.57 to 26.65, from −4.46 to 23.94, and from 8.82 to −34.48, respectively. The red tower genotype exhibited the highest L* value under the control condition, followed by the green tower under the control and MSS conditions. In contrast, the lowest L* value was reported in the SA6 genotype under the control condition. The highest a* value was found in the SA3 genotype under SSS conditions, followed by the SA3 genotype under MSS conditions, which indicates higher redness. In contrast, the lowest a* value was observed in the green tower genotype under the control condition, followed by the green tower genotype under MSS and SSS conditions, which indicates greenness. In the case of the b* value, the highest value was obtained from the green tower genotype under VSSS, followed by the green tower genotype under MSS and SSS conditions, which indicates yellowness. In contrast, under the control condition, the SA3 genotype exhibited the lowest b* value, which indicates blueness . The leaa, chlorophyll b, chlorophyll a/b, and the total chlorophyll content differed significantly among the four cultivars by a Tukey’s test at a 5% level of significance (a content was obtained from the green tower genotype (355.07 μg·g−1), followed by the SA6 (346.14 μg·g−1) and SA3 (245.53 μg·g−1) genotypes. In contrast, the lowest chlorophyll a was found in the red tower genotype (221.99 μg·g−1). The SA6 genotype exhibited the highest chlorophyll b content (190.10 μg·g−1), followed by the green tower genotype (182.59 μg·g−1), whereas the lowest chlorophyll b content was recorded in the SA3 genotype (117.73 μg·g−1). The highest chlorophyll a/b value was exhibited in the SA3 genotype (2.09), which was followed by the green tower genotype (1.94) and the SA6 genotype (1.82), whereas the lowest chlorophyll a/b value was observed in the red tower genotype (1.77). In the case of the total chlorophyll, the highest total value was obtained by the green tower genotype (537.32 μg·g−1), followed by the SA6 genotype (535.80 μg·g−1), while the lowest total chlorophyll content was observed in the red tower genotype (347.22 μg·g−1) (A. tricolor.Chlorophyll was found to be one of the most abundant pigments among the genotypes studied. The chlorophyll ificance . Among t μg·g−1) . Sarker a content was observed in the control treatment (438.65 μg·g−1), followed by the MSS (328.97 μg·g−1) and SSS (262.37 μg·g−1) treatments. In contrast, the VSSS (138.74 μg·g−1) condition showed the lowest chlorophyll a content. Similarly, the highest chlorophyll b content was observed in the control treatment (233.78 μg·g−1), followed by the MSS (183.96 μg·g−1) and SSS (136.33 μg·g−1) conditions, while the lowest chlorophyll b content was observed under VSSS (61.76 μg·g−1). The highest chlorophyll a/b value was observed under VSSS conditions (2.25), followed by the SSS (1.92) and MSS (136.33 μg·g−1) conditions, whereas the lowest chlorophyll a/b value was obtained under MSS conditions (1.79), followed by the control condition (1.88). In the case of the total chlorophyll, the highest total chlorophyll was observed in the control condition (672.29 μg·g−1), followed by the MSS (512.57 μg·g−1) SSS (398.92 μg·g−1) conditions, and the lowest total chlorophyll was obtained under VSSS conditions (200.57 μg·g−1). With the increase in the salinity, the chlorophyll a, chlorophyll b, and total chlorophyll contents were drastically and significantly reduced, from the control condition to the VSSS condition, following the order: Control > MSS > SSS > VSSS, while chlorophyll a/b was increased, following the order: MSS < Control < SSS < VSSS, which indicates that the severity of the salinity stress enhanced a drastic reduction in chlorophyll b, rather than in chlorophyll a. Under MSS, SSS, and VSSS conditions, the chlorophyll a, chlorophyll b, and the total chlorophyll content were decreased by 25, 40, and 68%, by 21, 42, and 78%, and by 24, 41, and 70%, respectively , followed by the SA3 genotype under the control conditions (456.13 μg·g−1), and the green tower genotype under the control conditions (442.22 μg·g−1). In contrast, the lowest chlorophyll a content was observed in the SA3 genotype under SSS conditions (202.67 μg·g−1), followed by the SA6 under VSSS (238.29 μg·g−1), and the red tower under SSS (241.14 μg·g−1). The SA6 genotype showed the highest chlorophyll b content under the control condition (323.91 μg·g−1), followed by the green tower under the control condition (236.30 μg·g−1), and the green tower under the MSS condition (208.11 μg·g−1). In contrast, the lowest chlorophyll b content was observed in the SA3 genotype under SSS (95.06 μg·g−1), followed by the SA6 genotype under VSSS (111.01 μg·g−1), and the green tower genotype under VSSS (136.02 μg·g−1). The SA3 genotype showed the highest chlorophyll a/b content under the control condition (2.41), followed by the green tower under VSSS (236.30 μg·g−1). In contrast, the lowest chlorophyll a/b content was observed in the SA6 genotype under control conditions (1.61), followed by the red tower genotype under SSS (1.63), and the green tower genotype under MSS (1.65). The SA6 genotype exhibited the highest total chlorophyll content under the control condition (843.43 μg·g−1), which was followed by the green tower genotype under the control condition (676.03 μg·g−1), and the SA3 genotype under the control condition (646.21 μg·g−1). The SA3 genotype exhibited the lowest total chlorophyll content under SSS (298.34 μg·g−1) conditions, followed by the SA6 genotype under VSSS (348.86 μg·g−1) conditions, and the red tower genotype under SSS (388.14 μg·g−1) conditions . Among the varieties, the highest betacyanin content was reported in the SA6 genotype (128.20 ng·g−1), followed by the red tower (68.51 ng·g−1) and SA3 (68.39 ng·g−1) genotypes, whereas the betacyanin content was the lowest in the green tower genotype (64.83 ng·g−1)  which was followed by the SA3 genotype , and the green tower genotype . On the other hand, the lowest betaxanthin and betalain contents were reported in the red tower genotype  (−1), followed by the SA3 (41.35 μg·g−1) and SA6 (41.27 μg·g−1) genotypes. The lowest total carotene content was noticed in the red tower genotype (27.15 μg·g−1). Khanam and Oba [A. tricolor cultivars.Pronounced and significant variations were observed for the betacyanin, betaxanthin, betalain, and the total carotene content across the four cultivars that were studied ( ng·g−1) . Ali et ctively) . In cont SA3 68.3 ng·g−1 g−1, and 64.79 μg·g−1, respectively) followed by the MSS treatment , whereas the VSSS treatment  exhibited the lowest betacyanin, betaxanthin, betalain, and total carotene contents. There was a drastic reduction in the betacyanin, betaxanthin, betalain, and total carotene with the increase in the salinity levels from the control condition to the VSSS condition in the following order: Control > MSS > SSS > VSSS , followed by the genotype SA6 under SSS (156.38 ng·g−1), and the red tower genotype under the control condition (136.77 ng·g−1). In contrast, the lowest betacyanin content was recorded in the green tower genotype under VSSS (38.74 ng·g−1), followed by the green tower genotype under SSS (40.87 ng·g−1), and the red tower genotype under SSS (63.83 ng·g−1) (−1) exhibited the highest betaxanthin content, followed by the SA6 genotype under the MSS (368.26 ng·g−1) and SSS (340.99 ng·g−1) conditions. The green tower genotype showed the lowest betaxanthin content under VSSS (148.73 ng·g−1), followed by the green tower under SSS (163.53 ng·g−1) and MSS (214.80 ng·g−1) (−1), followed by the SA6 genotype under MSS (524.64 ng·g−1) and MSS (454.82 ng·g−1). Conversely, the green tower genotype exhibited the lowest betalain content under VSSS (187.47 ng·g−1), followed by the green tower under SSS (204.40 ng·g−1) and MSS (277.42 ng·g−1) (−1), followed by the SA3 under the control condition (70.80 μg·g−1), and the SA6 under MSS (66.20 μg·g−1). In contrast, the lowest carotene content was found in the red tower genotype under SSS (20.64 μg·g−1), followed by the red tower under MSS (24.80 μg·g−1), and the SA6 under VSSS (29.13 μg·g−1)  . The SA6 ng·g−1) . The SA6 ng·g−1) . The hig μg·g−1) . Alam ettion 136. ng·g−1. p < 0.05) (−1 GAE dw), followed by the red tower genotype (207.68 µg g−1 GAE dw) and the SA3 genotype (193.36 µg g−1 GAE dw). In contrast, the green tower genotype (96.78 µg g−1 GAE dw) exhibited the lowest total polyphenol content among the varieties (−1 QE dw), followed by the SA3 genotype (64.50 µg g−1 QE dw), and the red tower genotype (49.00 µg g−1 QE dw). In contrast, the lowest value was found in the green tower genotype (46.51 µg g−1 QE dw) (A. tricolor). Moreover, Khandaker et al. [A. tricolor.The studied cultivars differed significantly for the total polyphenols, the total flavonoid content, and the antioxidant activity in response to the salinity stress ( < 0.05) . Across arieties . Gins et1 QE dw) . Gins etr et al.  observed−1 GAE dw and 89.95 µg g−1 QE dw, respectively), followed by MSS (219.44 µg g−1 GAE dw and 76.45 µg g−1 QE dw), while the lowest total polyphenol and total flavonoid contents were observed under VSSS   . Increasctively) . Neverthctively) . Even thctively) . In contctively) . Under tctively) . Yarnia nditions ,81.−1 GAE dw; from 38.50 to 137.85 µg g−1 QE dw; and from 4.47 to 29.95%, respectively (−1 GAE dw) under VSSS, followed by the red tower genotype under SSS (319.75 µg g−1 GAE dw), and the SA3 genotype under SSS (293.21 µg g−1 GAE dw). The lowest polyphenol content was found in the green tower genotype under the control condition (48.46 µg g−1 GAE dw). The highest total flavonoid content was detected in the SA6 genotype under VSSS (137.85 µg g−1 QE dw), followed by the SA3 genotype under SSS (122.69 µg g−1 QE dw), and the SA6 genotype under SSS (114.99 µg g−1 QE dw) (−1 QE dw), followed by the green tower genotype under MSS (44.76 µg g−1 QE dw) and SSS (50.28 µg g−1 QE dw)  . In cont1 QE dw) . The hig1 QE dw) . Sarker or. They  also shoe stress ,81.b, the total chlorophyll, the total carotene content (TCC), the betacyanin, betaxanthin, and betalain, and the total polyphenol content (TPC). Chlorophyll b also showed a higher significant association with the total chlorophyll and the total carotene, and with the betacyanin, betaxanthin, and betalain contents  demonstrated significant correlations with the total flavonoid content (TFC) and the total antioxidant activity (TAA).The chlorophyll exhibited highly significant correlations with chlorophyll contents . The totcontents . This inA. tricolor. Sarker and Oba [A. tricolor under salinity stress. Moreover, Khandaker et al. [A significant association between the total flavonoid content (TFC) and the total antioxidant activity (TAA) was observed . This in and Oba ,23,24 alr et al.  observeda/b, the total polyphenol and flavonoid contents, and the total antioxidant activity of the leaf of an A. lividus leafy vegetable. Among the four varieties, the green tower and SA6 genotypes may be considered to be the best salinity-stress-tolerant varieties, as they survived up to very severe salinity stress (150 mM NaCl). The red tower and SA3 genotypes also showed salinity tolerance and survived up to extreme salinity stress. Under MSS and SSS conditions, the leaf color parameters, such as the b*, the c*, the total polyphenol and flavonoid contents, and the total antioxidant activity of A. lividus leaves were very high in comparison to the control conditions, which allows for the assignment of A. lividus as a valuable food source for human diets and health benefits. The interrelationships of salt-stressed amaranth reveal the potent antioxidant activity for the leaf pigments, the TPC, and the TFC. The leaf pigments, the TPC, and the TFC played vital roles in scavenging ROS, and they would be beneficial for human nutrition by serving as a good antioxidant and antiaging source for human health benefits. Furthermore, A. lividus, which is cultivated under salinity stress, could contribute to the high quality of the final product in terms of polyphenols, flavonoids, and antioxidants. It could be a promising alternative crop for farmers, especially in saline-prone areas and in the coastal belts of the world, and it could be recommended to the farmers of salt-affected areas.Salinity stress significantly enhanced the b*, the chroma, chlorophyll


In addition, the clinical data of epileptic children who were newly diagnosed in the same period without antiepileptic drug (AED) treatment  and normal children who received physical examination in our hospital  were selected as controls. We analyzed the efficacy and safety of different AEDs, used blood ammonia and homocysteine levels as the observation indicators, and calculated the incidence of hyperammonemia (VAH) and hyperhomocysteinemia (HHcy) treated with different AEDs. And, based on the effect of epilepsy status on the cognitive function of patients, we also analyzed the effect of different AED treatments on children's cognitive function. Our results show that sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels, so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.In this study, we performed a study on 106 children with epilepsy who were treated with sodium valproate (the VPA group,  Pediatric epilepsy is a chronic paroxysmal disease in which multiple factors cause repeated abnormal discharges of brain neurons in children, causing sudden and transient disorders of the brain function, which is one of the most destructive and common neurological diseases in pediatrics that seriously affects the physical and mental health and intellectual development of children and poses a great threat to their healthy growth . For theOxcarbazepine is currently the first-line drug used to treat partial epilepsy in children with good efficacy and safety and so it has been recognized by clinicians and children's families. However, in recent years, its effect on the improvement of patients' cognitive function is still controversial . Levetir2, and a course of the disease of (3.87 ± 1.02) years. According to different types of medication, they were divided into the sodium valproate group , the oxcarbazepine group , and the levetiracetam group . Comparison of baseline information in P > 0.05), and they were comparable. In addition, the epileptic children who were newly diagnosed in the same period without AED treatment and normal children who received physical examination in our hospital were selected as controls and they were recorded as the untreated group (n = 35) and the healthy group (n = 35), respectively. Among them, in the untreated group, there were 18 boys and 17 girls, with an age of (7.08 ± 3.76) years, a body mass index of (18.10 ± 2.69) kg/m2, and a course of the disease of (3.09 ± 0.98) years. In the healthy group, there were 17 boys and 18 girls, with an age of (6.90 ± 3.82) years and a body mass index of (18.10 ± 2.69) kg/m2. There was no statistical difference in baseline information between the treated group, untreated group, and healthy group (P > 0.05), and they were comparable.A total of 106 children with epilepsy who were diagnosed and treated in our hospital from January 2019 to June 2020 and treated with a single AED were collected and recorded as the treatment group. Among them, there were 57 boys and 49 girls, with an age of (6.98 ± 3.84) years, a body mass index of (18.06 ± 2.71) kg/mThe inclusion criteria were as follows: children aged 6∼12 years; children meeting the International Anti-Epilepsy League's diagnostic criteria for epilepsy and epilepsy syndrome [The exclusion criteria were as follows: children treated with other AEDs or a combination of two or more AEDs; children with mental illness, gastrointestinal disease, severe anemia, thyroid dysfunction, or other metabolic diseases; children with hepatic encephalopathy and other diseases that could cause abnormally elevated blood ammonia; children who took methotrexate, vitamin B6, vitamin B12, folic acid tablets, and other drugs that affected blood Hcy levels during the same period; children with cancer; children with hematological diseases or urea cycle disorders; children with progressive intracranial space-occupying lesions.The VPA group was given sodium valproate solution (Sanofi (Hangzhou) Pharmaceutical Co., Ltd.; approval number H20041435; specification: 40 mg/ml) orally , 2 times/d; maintenance dose 20∼40 mg/(kg·d)). The OXC group was given oxcarbazepine tablets  orally , 2 times/d; maintenance dose 20∼40 mg/(kg·d)). The LEV group was given levetiracetam tablets  orally , 2 times/d; maintenance dose 20∼50 mg/(kg·d)). All children in the 3 groups received 12 months of treatment.μmol/L) and HHcy (>15 μmol/L) in different AED treatments was compared. The neurocognitive function of children in the VPA group, OXC group, and LEV group was compared ). The item factor includes three parts: full-scale intelligence quotient (FIQ), performance intelligence quotient (PIQ), and verbal intelligence quotient (VIQ). The score is proportional to the level of intelligence. The specific intelligence level distribution is shown in The efficacy and safety of the treatment in the VPA group, OXC group, and LEV group were compared. The criterion of efficacy was based on the revised scoring standard of the International Anti-Epilepsy League : ① no aut test. The count data were expressed in (%), and the χ2 test was implemented. P < 0.05 indicated that there was a statistical difference.Data analysis was carried out by SPSS 22.0 software. The measurement data conforming to the normal distribution were expressed as   > OXC group (79.41%) > VPA group (70.27%)), but there was no statistical difference between the three groups (P=0.160) .χ2 = 8.884,P=0.012). There were statistical differences between the VPA group and the LEV group, and the VPA group and the OXC group (P < 0.05)  < OXC group (11.76%) < VPA group (27.03%)) ( < 0.05) .μmol/L, respectively, and Hcy levels were (12.04 ± 2.49), (7.31 ± 2.18), (7.03 ± 2.13), (6.75 ± 2.02), and (6.36 ± 1.77) μmol/L respectively. The blood ammonia and Hcy levels of the VPA group were higher than those of the OXC group, LEV group, untreated group, and healthy group (P < 0.05), and the blood ammonia levels of the OXC group, LEV group, and untreated group were higher than those of the healthy group (P < 0.05); there was no statistical difference between the other groups (P > 0.05) , (31.15 ± 12.04), (30.03 ± 11.69), (27.36 ± 10.41), and (22.50 ± 9.82)  > 0.05) .P < 0.05); the incidence of HHcy in the VPA group (10.81%) was higher than that in the OXC group (0.00%) and the LEV group (0.00%) (P < 0.05).After medication, the number of VAH occurrences in the VPA group, OXC group, and LEV group was 4, 0, and 0, respectively, and the number of HHcy occurrences was 4, 0, and 0, respectively. The incidence of VAH in the VPA group (10.81%) was higher than that in the OXC group (0.00%) and the LEV group (0.00%) (P > 0.05). After medication, the comparison of FIQ, PIQ, and VIQ scores of the OXC group and LEV group was higher than that of the same group before medication and the VPA group after medication (P < 0.05). There was no statistical difference within the VPA group (P > 0.05) , (97.22 ± 2.58), and (97.39 ± 2.83), respectively; PIQ scores were (99.52 ± 2.42), (99.33 ± 2.68), and (99.17 ± 2.56), respectively; and VIQ scores were (95.25 ± 3.43), (94.94 ± 2.89), and (95.02 ± 3.19), respectively. After medication, the FIQ scores of the VPA group, OXC group, and LEV group were (98.01 ± 3.09), (99.53 ± 2.40), and (99.81 ± 2.11), respectively; PIQ scores were (99.84 ± 2.60), (102.46 ± 2.98), and (103.37 ± 2.96), respectively; and VIQ scores were (96.47 ± 2.61), (97.63 ± 2.20), and (97.92 ± 2.87), respectively. Before medication, the comparison of FIQ, PIQ, and VIQ scores among the 3 groups was not statistically significant ( > 0.05) .Epilepsy has the characteristics of short-term seizures and stereotyped repetitions, which is a common neurological syndrome in childhood, with a prevalence of about 68∼83% , 15. Theγ-aminobutyric acid to reduce neuronal excitability and inhibit epileptic seizures but it also has the risk of causing adverse reactions such as tremor, hair loss, vomiting, and constipation [+ channels in brain cells, thereby inhibiting abnormal discharge of brain neurons and inhibiting epileptic seizures [Sodium valproate, oxcarbazepine, levetiracetam, etc. are currently widely recognized broad-spectrum AEDs, which are effective for most epileptic seizures. In this study, three AEDs  were applied to the clinical treatment of children with epilepsy. The results showed that, after treatment, the total effective rate in the LEV group was the highest (LEV group (88.57%) > OXC group (79.41%) > VPA group (70.27%)), and the adverse drug reaction rate of the LEV group was the lowest (LEV group (2.86%) < OXC group (11.76%) < VPA group (27.03%)). In terms of effective rate, there was no statistical difference between the three groups; in terms of adverse drug reaction rates, there were statistical differences between the VPA group and the LEV group, and the VPA group and the OXC group. This suggests that the above three AEDs are effective and can be used as first-line options for antiepileptic treatment in children with epilepsy. However, levetiracetam and oxcarbazepine have higher drug treatment safety than sodium valproate. Analyzing the reasons, the seizures of epilepsy are related to the impaired balance of excitability and inhibition of the central nervous system. As a classic AED, sodium valproate can interfere with the synthesis (promotion) and degradation (inhibition) of the inhibitory neurotransmitter tipation , 20. Oxcseizures . The latseizures . And, coAccording to previous studies, the application of AEDs in patients with epilepsy is an important cause of abnormal blood ammonia and Hcy metabolism, which induces VAH and HHcy; VAH is associated with fatal encephalopathy, and HHcy is associated with increased risk of cardiovascular and cerebrovascular events –26. AftePatients with epilepsy usually have varying degrees of cognitive impairment. After medication in this study, the FIQ, PIQ, and VIQ scores of the OXC group and LEV group were higher than those of the same group before medication and the VPA group after medication. There was no statistical difference within the VPA group. This shows that compared with sodium valproate, the treatment of levetiracetam and oxcarbazepine has a better effect on the recovery of neurocognitive function in children with epilepsy and it is worthy of clinical promotion. Studies have shown that ammonia, as a protein-degradation product, can interfere with the energy metabolism of brain cells, affect the conduction activities of nerves, and impair the cognitive function of patients. It can also induce the production of neuroinflammatory factors, cause strong neurotoxicity, and ultimately lead to a series of neuropsychiatric symptoms in patients . HoweverIn summary, sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels and so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.


COVID‐19 pneumonia causes several complications that include pneumothorax, hydropneumothorax, empyema, and rarely leads to bronchopleural fistula (BPF). BPF is a communication between the pleural space and the bronchial tree. We report a case of 24 years man with pneumothorax, hydropneumothorax, and BPF that appeared after COVID‐19 infection. Bronchopleural fistula may develop in a patient with COVID‐19 along with pneumothorax and hydropneumothorax. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that is known to cause severe respiratory dysfunction including pneumonia, acute respiratory distress syndrome (ARDS), and sepsis. The complications of COVID‐19 pneumonia include pneumothorax, hydropneumothorax, empyema, and rarely lead to bronchopleural fistula (BPF). BPF is a communication between the pleural space and the bronchial tree . BPF commonly occurs after pulmonary resection  and is less common after infection. It has been estimated that BPF has a significant morbidity rate ranging from 25% to 71% following pneumonectomy or other pulmonary resection.2A 24‐year‐old man was brought to our center with chief complaints of shortness of breath and cough for 6 days. He had shortness of breath even on walking on the level ground. The cough was copious and productive while sputum was yellowish. He had chest pain on right side that aggravated with coughing. He had no history of palpitation, loss of consciousness, lower limb swelling, and fever. He had COVID‐19 one month back that was resolved after 25 days of treatment. He had no known comorbidities. He neither smoked nor consumed alcohol.On examination, patient was ill looking, conscious, and was well oriented to time, place, and person. He had pulse rate 110 beats/minute, respiratory rate 25/min, blood pressure 124/80 mm of Hg, and temperature was 98°F. He had no pallor, icterus, lymphadenopathy, cyanosis, or clubbing. There was bilateral decrease in air entry on chest auscultation over 4th and 5th intercostal spaces which was more on the left side. He had bronchial breath sounds bilaterally.3, neutrophils 82%, lymphocytes 11%, and platelet count 508,000/mm3. Prothrombin time (PT) and international normalized ratio (INR) were 16 s and 1.22, respectively. His random blood sugar level was 3.7 mmol/L. The level of urea (10.7 mmol/L) and creatinine (215 µmol/L) was raised in the blood. He had elevated level of AST (86 U/L), ALT (221 U/L), and LDH (960 U/L) but decreased level of albumin (23 gm/L) and total protein (44 gm/L) in the blood.His laboratory investigations revealed hemoglobin 11.8 gm %, total leucocyte count 23,000/mmChest X‐ray showed bilateral consolidation of lungs in the middle zone Figure . High‐reAcinetobacter lwoffi. He was treated with  for 14 days. Repeat chest X‐ray was normal following which, chest tube was removed. He improved clinically and was discharged on oral medications . His follow‐up was not eventful.Based on the radiological findings, diagnosis of left‐sided hydropneumothorax, right‐sided pneumothorax, and bronchopleural fistula (BPF) on left side was made. Following this, bilateral chest tube was inserted to treat left side hydropneumothorax and right side pneumothorax. He developed fever after 5 days of hospital stay for which culture of the pleural fluid was done that revealed the growth of 3Necrotizing lung infections, post‐lung resection, and chemoradiation therapy are the common causes of BPF.The radiological investigation of choice for diagnosing BPF is contrast‐enhanced chest computed tomography.Endobronchial occlusion is a less invasive alternative to thoracic surgery for treating BPFs.4Bronchopulmonary fistula is one of the rare complications of COVID‐19. Clinicians should be aware of this scenario, which can be treated with bronchoscopy procedures like EBV or sealing the fistula with glues or blood patch or even surgery for severe cases. In our patient, chest tube was sufficient for the treatment without the complications.None.SS conceptualized the study, reviewed, edited the manuscript, and charged the case. PM and SS wrote the original, reviewed and edited the manuscript. SS, PM, RC, RY, YP, SKS, BSP, and MG charged the case and reviewed the manuscript.Written informed consent was obtained from the patient.


This study aimed to determine the prevalence and correlates of successful ageing in older community-dwelling adults in India. The cross-sectional sample included 21,343 individuals (≥ 65 years) from the Longitudinal Ageing Study in India (LASI) Wave 1 in 2017–2018. Successful ageing was assessed utilizing a multidimensional concept, including five components: (1) absence of major illness, (2) free of disability, (3) no major depressive disorder, (4) social engagement and (5) life satisfaction. Overall, 27.2% had successful ageing, including 83.3% had no major diseases, 51.0% free from disability, 91.8% had no major depressive disorder, 73.6% were socially engaged and 74.6% had high life satisfaction. In the adjusted logistic regression analysis, male sex , married , having formal education , high subjective socioeconomic status , urban residence , Sikhs , high physical activity , and daily Yoga practice  increased the odds of successful ageing, while increasing age , poor childhood health , and underweight  decreased the odds of successful ageing. Almost one in three older adults in India were successfully ageing. Factors associated with successful ageing included, male sex, married, having formal education, high subjective socioeconomic status, urban residence, Sikhs, physical activity, Yoga practice, younger age, good childhood health, and not having underweight. The share of population over the age of 60 is projected to increase from 8 percent in 2015 to 19 percent in 2050. By the end of the century, the elderly will constitute nearly 34 percent of the total population in the countryThere has been a shift in focus from “how long” to “how healthy” or “how successful” older adults live3. The “National Policy on Older Persons” (NPOP) in India has been instituted for improving quality of life of elderly in India2. One means to be used for evaluating quality of life of older adults in India is by assessing and monitoring successful ageing (SA). Definitions of SA or healthy ageing include “survival to a specific age, being free of chronic diseases, autonomy in activities of daily living, well-being, good quality of life, high social participation, only mild cognitive or functional impairment, and little or no disability”4. Common domains assessed in SA include “physical capability, cognitive function, metabolic and physiological health, psychological well-being, and social well-being,” which significantly predict morbidity and mortality5. Commonly used models of successful ageing include the biomedical model of successful ageing (BMSA) and a multidimensional concept of successful ageing (MMSA)7. The BMSA may include five components: “no major disease, high cognitive functioning, high physical functioning, no disability and active engagement with life”7, and MMSA may include five components, such as no major disease, no disability, mental well-being, social engagement, and life satisfaction8.“India is projected to become the world's most populous nation by 2028, with a population of some 1.45 billion”8, in South Korea (≥ 65 years) 25.2%8, and in 15 European countries (≥ 50 years) 23.5%9. Using the BMSA, the prevalence of SA was among older adults (≥ 60 years) in China 13.2%10, in Singapore (≥ 60 years) 25.4%7, in three East Asian countries  (65 and 75 years) 17.6%11. The proportion of five components of MMSA was, for example in China (≥ 65 years) “no major illness 75.1%, no disability 86.0%, no depression symptom 75.2%, active social/productive engagement 51.2%, and life satisfaction 57.1%”8, and the prevalence of five components of BMSA was, for example in China (≥ 60 years) no major diseases 41.7%, no disability 92.1%, high cognitive functioning 54.2%, high physical functioning 70.2%, and active engagement with life 46.0%10. To our knowledge, we could not find any study on SA among older adults in India, which prompted this study. Such data could give us a better understanding on successful ageing at a national level and make cross-cultural comparisons.Using the MMSA, the prevalence of SA was among older adults (≥ 65 years) 18.6% in China12, male sex12, married12, spouse accompany8, higher education15, higher income/wealth14, higher childhood wealth15, ethnicity7, region10, and urban residence16. In addition, various health behaviours have been found associated with SA, including not smoking17, alcohol drinking8, physical activity19, healthy diet20, cognitive activity12, and a normal body mass index17. Studies on SA among older adults have largely been conducted in high-income countries, except for China. Considering differences in socioeconomic contexts, culture, retirement and leisure in low resourced countries, such as in India, an understanding of SA among older adults in India is important. Therefore, this study aimed to determine SA in older community-dwelling adults in India in 2017–2018.Sociodemographic factors associated with SA may include younger age21. In a household survey, “interview, physical measurement and biomarker data were collected from individuals aged 45 and above and their spouses, regardless of age”21. We restricted our sample to those 65 years and older in this analysis. The study was approved by the “Indian Council of Medical Research (ICMR) Ethics Committee and written informed consent was obtained from the participants”21. All methods were carried out in accordance with relevant guidelines and regulations.This secondary data analysis utilized data from the cross-sectional and nationally representative “Longitudinal Ageing Study in India (LASI) Wave 1, 2017–2018”; “the overall household response rate is 96%, and the overall individual response rate is 87%”8.SA was assessed utilizing a MMSA, including five components: (1) absence of major illness, (2) free of disability, (3) no major depressive disorder, (4) social engagement and (5) life satisfactionAbsence of major illnesses were sourced from the questions, “Has any health professional ever told you that you have…?”: (1) “chronic lung disease such as asthma, chronic obstructive pulmonary disease/chronic bronchitis or other chronic lung problems; (2) cancer or malignant tumor; (3) chronic heart diseases such as coronary heart disease , congestive heart failure, or other chronic heart problems; and (4) stroke”21.Free of disability was measured based on “Activities of Daily Living (ADL) (6 items) and Instrumental Activities of Daily Living (IADL) (7 items)”23,  and defined as 0 ADL and 0 or 1 IADL difficulty.Major depressive disorder was assessed with the Composite International Diagnostic Interview short form (CIDI-SF)24. Study respondents were required to “endorse either anhedonia or depressed mood for most of the day for most of a 2-week period or more,” and those who fulfilled this criterion “completed an additional seven symptoms: lost interest, feeling tired, change in weight, trouble with sleep, trouble concentrating, feeling down, and thoughts of death”25. “Those with a score ≥ 3 was considered to meet the criteria for having MDD in the previous 12 months; MDD symptomology scores ranged from 0 to 7”25.21. Responses were coded 1 = daily to at least once a month and 0 = rarely/once a year or never . Social engagement was defined as any positive response to any of the 6 items.Social engagement was measured with 6 items, e.g., “Eat-out-of-house (restaurant/hotel)”Life satisfaction was sourced from the 5-item Satisfaction With Life Scale (SWLS)26. Higher scores (20–35) (range 5–35) indicated higher life satisfaction. .High cognitive functioning was defined as an above median total score on tests involving immediate and delayed word recall, serial 7 s, and backward counting (0–27)15. High physical function was defined as 0–1 difficulty with the following five activities: “(1) waking 100 yards; (2) climbing one flight of stairs without resting; (3) stooping, kneeling or crouching; (4) pulling or pushing large objects; (5) lifting or carrying weights over 5 kilos like a heavy bag of groceries”21.SA was further assessed utilizing BMSA, including five components: (1) absence of major illness , (2) free of disability (0 difficulty with ADL), (3) high cognitive functioning, (4) high physical function, and (5) social engagement. Sociodemographic variables consisted of level of education , age in years, sex , residential status, religion, and marital status . Subjective socioeconomic status was assessed with the question, “Please imagine a ten-step ladder, where at the bottom are the people who are the worst off—who have the least money, least education, and the worst jobs or no jobs, and at the top of the ladder are the people who are the best off—those who have the most money, most education, and best jobs. Please indicate the number (1–10) on the rung on the ladder where you would place yourself”21. Steps 1 to 3 on the socioeconomic ladder were defined as low, 4–5 as medium, and 6–10 as high socioeconomic status.Poor childhood health was assessed with the question, “Would you say your childhood health was very good, good, fair, poor or very poor on the basis of what you remember, or what you heard or perceived from your parents?”) (Coded poor or very poor = 1)21.Childhood poverty was sourced from the item, “Now think about your family when you were growing up, from birth to age 16. Compared to other families in your community, would you say your family during that time was pretty well off financially, about average, or poor?”21, and defined as “poor” .Current tobacco use was assessed from (1) “Do you currently smoke any tobacco products ?” and/or (2) “Do you use smokeless tobacco ?” 21.Heavy alcohol use was assessed with the question, “In the last 3 months, how frequently on average, have you had at least 5 or more drinks on one occasion?”21 and defined as “one to three days per month, one to four days per week, five or more days per week, or daily.”Physical activity (PA) was assessed with the questions (1) “How often do you take part in sports or vigorous activities, such as …: everyday, more than once a week, once a week, one to three times a month, or hardly ever or never?” (2) “On the days you did vigorous activity, how much time did you usually spend doing any vigorous activity? (___minutes)”, (3) “How often do you take part in sports or activities that are moderately energetic such as…?” and (4) “How much time did you usually spend doing any moderate activity on an average in a day?”21. The participants were classified into 4 levels of PA according to their waking duration throughout the week: a) no PA (0 min/week), b) low- PA , c) moderate PA , and high PA 28.Frequency of Yoga practice was assessed with the question, “How often do you engage in any of the following activities like yoga, meditation, asana, pranayama or similar?” Responses were trichotomized into “1 = hardly ever or never, 2 = One to three times a month, once a week, or more than once a week, and 3 = every day”21.Anthropometry “Height and weight of adults were measured using the Seca 803 digital scale”21. “Body Mass Index = BMI was calculated according to Asian criteria: underweight (< 18.5 kg/m2), normal weight (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2), class I obesity (25.0–29.9 kg/m2), and class II obesity (≥ 30.0 kg/m2)”29.P < 0.05 was accepted as significant, missing values were excluded, and no multi-collinearity was found. Statistical analyses were conducted using “STATA software version 15.0 ”, taking the complex study design into account.Descriptive statistics were applied to describe sociodemographic information, health indicators and SA. Pearson Correlation was used to calculate correlations between SA components. Unadjusted and adjusted logistic regression was utilized to assess associations between sociodemographic, health behaviour and MMSA and BMSA. The sample included 21,343 older adults , 52.2% were female and 47.8% male. Majority (69.9%) of the participants were rural dwellers, 58.4% had no schooling, 55.2% were married, 82.0% were Hindus, and 39.6% had low subjective socioeconomic status. Few of participants (1.7%) had poor childhood health, and 42.2% had childhood poverty. One third of the older adults (33.0%) were currently using tobacco, 2.3% in heavy alcohol use, 38.1% in no physical activity, 9.2% engaged in daily Yoga practice, and 28.4% were underweight. Overall, 27.2% had successful ageing, including 83.3% had no major diseases, 51.0% free from disability, 91.8% had no major depressive disorder, 73.6% were socially engaged and 74.6% had high life satisfaction , followed by Nagaland (52.7%), Gujarat 44.0%), and Puducherry (45.3%), and the lowest was in Karnataka (18.7%), followed by Telangana (20.9%), and West Bengal (19.7%), while using the BMSA the highest prevalence of SA was in Puducherry (27.8%), Mizoram (25.3%), and Chandigarh (23.4%), and the lowest in Odisha (6.9%), West Bengal (7.1%), and Arunachal Pradesh (7.9%) , married , having formal education , high subjective socioeconomic status , urban residence , Sikhs , high physical activity , and daily Yoga practice  were positively associated with MMSA, while increasing age , poor childhood health , and underweight  were negatively associated with associated with MMSA. The correlates for BMSA were for the most part (8 variables) like MMSA. In addition, childhood poverty and overweight/obesity were negatively associated with BMSA and urban residence was not associated with BMSA 8, and in 15 European countries (≥ 50 years) 23.5%9. Possible reasons for the higher MMSA in India than in China may be related to the use of different indicators, e.g., in China depressive symptoms were measured that have a higher prevalence than in India measuring major depressive disorder, and lower awareness of chronic diseases in India than in China. Using the BMSA, we found that more than one in ten (11.0%) older adults in India were successfully ageing, which is similar to China 10, and lower than in Singapore 7, and in three East Asian countries  11. Comparing the assessment of SA with MMSA and BMSA, this study found in line with previous research9 that the rates of MMSA were higher than BMSA. The more flexible MMSA may be more useful for targeting identified deficiencies in public health interventions9.To our knowledge, this study is the first to assess the prevalence and factors associated with SA among older adults (≥ 65 years) in a national community-based sample in India in 2017–2018. Using the MMSA, we found that almost one in three older adults (27.2%) in India were successfully ageing, which is higher than in China  in China8. No disability was in this study lower than in the China (≥ 65 years) study, and social engagement and life satisfaction was higher in this study than in the China (≥ 65 years) study8. Using the BMSA, we found in this study that 71.0% had no disease, 72.9 no disability, 73.6% social engagement, 31.3% high physical functioning, and 55.4% high cognitive functioning, which compares with the China (≥ 60 years) study of active engagement with life 46.0%, high physical function 70.2%, high cognitive functioning 54.2%, no disability 92.1%, and no major diseases 41.7%10. The proportion of older adults with no disease and social engagement were higher in this study than in the China (≥ 60 years) study10, while high physical function and no disability were higher in the China (≥ 60 years) study10 than in this study. Analysing the different components of SA by age groups, we found that the decline with age was stronger for social engagement, high cognitive functioning, high physical function, and no disability, while this was less pronounced for no disease, no major depressive disorder and life satisfaction. Similar findings were identified in an investigation among older adults in Germany12.Using the MMSA, 83.3% had no disease, 51.0% no disability, 91.8% no major depressive disorder, 73.6% social engagement, and 74.6% life satisfaction in this study, which compares to the China (≥ 65 years) study, as follows, no major illness 75.1%, no disability 86.0%, no depression symptom 75.2%, active social/productive engagement 51.2%, and life satisfaction 57.1%12, male sex was found to be associated with SA, which may be related to gender paradox in health 8. These gender differences seem to be mainly attributed to men having higher no disability and social engagement than women. The found gender differences are consistent with research showing lower functional health among older women than men in India30. In addition, it may be possible that women experience greater barriers to access health care services than men in India31. In addition, younger age and being married was associated with SA in this study, which concurs with previous findings12. The negative association between age and SA is expected due to the biological, functional and cognitive decline with ageing7.We found that male sex, married, having formal education, high subjective socioeconomic status, no childhood poverty, urban residence, Sikhs, physical activity, Yoga practice, younger age, good childhood health, not having underweight and overweight/obesity were associated with MMSA and/or BMSA. Consistent with previous research15, higher socioeconomic status (in childhood and adulthood), higher education and urban residence were associated with SA in this study. Higher education may increase health behaviour, health care seeking, and cognitive functioning, and thus increase SA7. Likewise, higher economic status shows better access to economic resources, which may help in enabling to engage in better health and dietary behaviour32. Urban residence may be associated with higher educational and economic status and better access to health care, all of which could increase SA16. No disability and social engagement were lower among older adults residing rural compared to urban areas in this study. Social participation should be promoted among older adults in rural areas in India. Furthermore, we found ethnic and regional differences in the prevalence of SA, as found in previous research10. Compared to Hindus, Sikhs were likely to have a higher prevalence of SA in this study. Sikhs had the highest rates of no major diseases, no disability and life satisfaction, which contributed to their overall SA. The highest prevalence of SA was in the Indian states of Mizoram, Nagaland, Gujarat, Puducherry and Chandigarh, and the lowest was in Karnataka, Telangana, West Bengal, Arunachal Pradesh, and Odisha. Some of these state differences may be attributed to differences in the level of economic development and health outcomes. For example, life expectancy ranged from 56 years in Madhya Pradesh to 74 years in Kerala33, and in this vain, states with a higher life expectancy, such as Delhi (74.7 years), and Punjab (72.4 years) had also higher rates of SA, Delhi 33.6% MMSA and 15.4% BMSA, and Punjab 38.6% MMSA and 18.4% BMSA, while states with a lower life expectancy, such as Madhya Pradesh (66.0 years) and Karnataka (69.2 years) had also lower rates of SA, Madhya Pradesh 24.7% MMSA and 12.3% BMSA, and Karnataka 18.7% MMSA and 10.6% BMSA34.In line with various studies19, this study showed a positive association between physical activity, daily Yoga practice and SA. In a systematic review Yoga practice was found to be associated with better subjective health and health behaviours35. Research has provided evidence that physical activity improves health36, prevents several chronic conditions19, is beneficial to mental health38, and increases life satisfaction39, cognitive functioning41, and functional ability40, all of which may contribute to better SA. While some previous research17 found an association between not smoking, alcohol drinking and SA, we did not find a significant association. Furthermore, a body mass index not in the normal range ” in India addresses: “many health concerns of elderly (such as increasing incidence of non-communicable disease) which demand the strengthening and reorientation of the primary health care system to the special needs of the elderly, improving geriatric care at all levels, and promoting the concept of healthy ageing”2.Consistent with studies20, that have been shown to influence SA were not assessed and should be included in future research. The statistical models were adjusted for various confounding variables, but findings may still have been confounded by other variables, such as psychological coping resources, not included in the analyses. Furthermore, the study focused on community-dwelling older adults and excluded institutionalised persons.Study limitations include the cross-sectional design, the assessment of some variables by self-report. A bias may be less for diagnosed chronic conditions than for self-reported health. Some variables, such as dietary behaviour and mental or cognitive activityAlmost one in three older adults in India were successfully ageing. Factors associated with successful ageing included, male sex, married, having formal education, high subjective socioeconomic status, urban residence, Sikhs, physical activity, Yoga practice, younger age, good childhood health, and not having underweight. Since LASI was designed as a longitudinal study, future research may want to evaluate and monitor the predictive value of MMSA and BMSA in the older adult population in India.