The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr  and plasma volume were higher in women than men . At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients.The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients . Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs,  Sex difference is a well-established issue in a heart failure (HF) setting ,2 as welCongestion is one of the main features of HF . The evaThe higher the number of signs and symptoms of congestion, the higher the risk of 30-day mortality rate in patients with AHF (up to 156% in cases of the presence of 6–7 symptoms/signs) . The litNevertheless, the literature is scant regarding the influence of sex on congestion markers in patients with HF, and conflicting data emerge from the analysis of the studies ,19,20,21The aim of this research was to investigate the influence of sex on congestion status of patients with AHF.This was a retrospective study. Patients with AHF admitted to the Cardiology Unit of Altamura Hospital, Bari , between January 2010 and November 2013, were enrolled. We collected data related to physical and clinical characteristics, comorbidities, laboratory evaluations, arterial blood gas parameters, and pharmacological treatments upon the admission to the intensive care unit.All patients underwent echocardiographic assessment in order to evaluate left ventricular ejection fraction (LVEF). Simpson’s method was adopted. Patients were defined in relation to LVEF into three groups according to international guidelines: “reduced LVEF” , “mildly reduced LVEF” , and “preserved LVEF”  .The laboratory and instrumental evaluations were performed as routine measurements upon admission to our intensive care unit.Patients younger than 18 years, with acute coronary syndrome, recent cardiac surgery intervention, and/or life-threatening malignancy were excluded.The study complied with the Declaration of Helsinki and was approved by the local Institutional Review Board. Written informed consent was obtained from each patient at inclusion .2 + 0.012 × TP3) + G/TP × (1.6 × TP + 0.15 × TP2 + 0.006 × TP3). COP normal values were 25 ± 2 mmHg  .Estimated plasma volume, as assessed by Kaplan–Hakim formula (KH-PVS), was calculated by comparing actual plasma volume (aPVS) to ideal plasma volume (iPVS) ,29. The BIVA was assessed at admission on the right side of the body using tetrapolar impedance plethysmography that emitted 50 kHz alternating sinusoidal current  ,31. The The HYDRA score is a simple score which we previously validated . Brieflyt-test and Chi-squared tests for continuous variables and categorical variables, respectively. A one-way ANOVA was used to analyse the differences between means. If we obtained significant ANOVA results, we adopted the post-hoc test of Student–Newman–Keuls in order to explore the mean differences among pairs of groups.Continuous variables were reported as means ± standard deviation. Categorical variables are expressed as counts (percentages) or medians with 95% confidence intervals. The comparisons between groups were performed using the Student’s p-values below 0.05 were defined as statistically significant. The analyses were performed using STATA software, version 12 .Multivariate analyses were performed by logistic regression to analyse the factors associated with sex at univariate analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were given. Four-hundred and ninety-four patients with AHF were included in this study: 252 women and 242 men. p = 0.001). Women demonstrated a higher prevalence in HFpEF as compared to men , while the prevalence of HFrEF was higher in men than women .No significant differences were found according to comorbidity prevalence, body mass index (BMI), serum electrolytes, creatinine levels, serum COP, serum osmolality, or arterial blood gas parameters. Men showed higher prevalence in pacemaker/implantable cardioverter defibrillator  on the congestion markers in relation to sex. Only BNP was different among the three groups as both men and women with HFrEF showed higher values in BNP as compared to those with HFmrEF and HFpEF. No differences were according to other congestion parameters .p = 0.005), and had higher plasma concentration in BUN  and lower eGFR values than men . Physical examination did not report any differences in terms of peripheral oedema, orthopnoea and jugular venous distention. BUN/Cr ratio and Duarte PVS were significantly higher in women than men  BUN/Cr ratio, and venous and intravascular congestion biomarkers. A sex-guided approach to the correct evaluation of patients with AHF might become a cornerstone for the correct management of these patients.


Vitamin D deficiency and insufficiency in older adults seems to be common, but the prevalence estimates are lacking in West China. Previous studies suggested that low vitamin D status was associated with obesity. However, most of them evaluated obesity based on body mass index (BMI) and there are no studies at present exploring the association between vitamin D status and different obesity markers. The present study aims to investigate the prevalence of low vitamin D status and evaluate the association between the vitamin D status and different obesity markers among older adults in West China.Data was based on the baseline of West China Health and Aging Trends study (WCHAT). All of the participants were older than 60 years old in the present study. Vitamin D status was based on laboratory data, and obesity markers were assessed by bioelectrical impedance analysis (BIA) using the InBody 770 analyzer. Multiple linear regression was performed to find the association between the vitamin D status and various obesity markers.P = 0.046 in males; β = -11.253, P < 0.001 in females). No significant association was found between vitamin D status and BMI in males.The study included 2661 individuals . The mean vitamin D level was 18.8 ± 6.3 ng/ml (range: 5 to 59 ng/ml); 5.2 % of participants had a sufficient level of vitamin D, 31.8 % had vitamin D insufficiency, and 63.0 % had vitamin D deficiency. Our results showed that vitamin D status was negatively associated with fat mass index (FMI), visceral fat area (VFA), and waist-hip ratio (WHR) in both sexes. Comparing to other obesity markers, WHR had the strongest correlation with vitamin D status in both sexes (β = -6.090, The prevalence of vitamin D insufficiency and deficiency among older adults in West China was high. Among the older adults in west China, WHR showed stronger association with vitamin D status and was better for the prediction of vitamin D insufficiency or deficiency in both sexes, compared to BMI.ChiCTR1800018895.Chinese Clinical Trial Registry:  With the steady increase in longevity over the past several decades, the number of individuals reaching old age is unprecedented and has been predicted to reach approximately 2 billion in 2050 . As sociVitamin D, including vitamin D2  and vitamin D3 , is a multifunctional hormone whose receptor is expressed in 36 types of tissues. Vitamin D is essential not only for musculoskeletal health but also to maintain the function of other systems . AlthougObesity, another global public health challenge in older adults, is associated with the risk of morbidities, such as cardiovascular disease, type 2 diabetes mellitus, and sleep apnea . MoreoveAlthough a relevant number of epidemiological investigations suggested that low vitamin D status was associated with obesity, only in few instances the associations between vitamin D status and distinct obesity markers were assessed in the same observational study , 17. As α2P(1-P)/δ2 was used. According to data literature [Data were based on the baseline of West China Health and Aging Trends study (WCHAT), a cohort study designed to assess the health status and its influencing factors in West China . The stuterature –21, the The following demographic information was collected by trained investigators in face-to-face interview: age, sex, ethnics , marital status , smoking history, drinking history, educational level , chronic disease and physical activity .Fasting blood samples were collected by trained nurses in the morning when the participants arrived at the study center. Blood handling and collection were carried out under strictly standardized conditions. Vitamin D was measured at baseline only, by assessing serum levels of 25(OH)D. Serum 25(OH)D was measured by using the ARCHITECT i2000SR Immunoassay system  and the intra-assay coefficient of variation (CV) was less than 5 %. Serum vitamin D levels were defined as “sufficient” (25(OH)D ≥ 30 ng/mL), “insufficient” (20 ≤ 25(OH)D < 30 ng/mL), or “deficient” (< 20 ng/mL) according to the Endocrinology Society .2). Fat mass index (FMI) and VFA were measured by bioelectrical impedance analysis (BIA) using an Inbody 770 , which was a convenient method for the measurement of body composition [Standing height and body weight was measured without shoes. BMI was calculated by dividing body weight by height squared . All continuous variables were checked for normality of distribution by using the Kolmogorov-Smirnov test. Means ± standard deviations (SD) were used to summarize the normally distributed variables, while medians and interquartile range (IQR) were used to summarize the non-normally distributed variables. Count and percentage were used to summarize all categorical variables. Difference of groups were tested by ANOVA/Kruskal-Wallis for continuous variables and the chi square test/Fisher’s exact test for categorical variables according to vitamin D status, respectively. Pearson’s/spearman correlation coefficients were computed between serum 25(OH)D concentrations and obesity markers adjusted by sex. Multiple linear regression was conducted to find the relationship between vitamin D status and obesity markers by adjusting socio-demographic variables, , number of chronic diseases and physical activity. β and 95 % confidence intervals (CI) were conducted and P < 0.05 was used to determine whether the effect was significant.Overall, 2661 participants  were included in our study  was observed in participants with shorter height, higher BMI and FMI, and larger VFA, WC and WHR.Table r = -0.102) and WC (r = -0.138), while in females, vitamin D status was negatively correlated with weight (r = -0.107), BMI (r = -0.124), FMI (r = -0.139), VFA (r = -0.155), AC (r = -0.009), WC (r = -0.122), HC (r = -0.093) and WHR (r = -0.122).Table P = 0.046), TSF , VFA , and WHR  were negatively correlated with the vitamin D status. In females, weight , BMI , FMI , VFA , MAC , WC , HC , WHR  were negatively correlated with vitamin D status.The relationships between vitamin D status and obesity in the two sexes was further analyzed using the multiple linear regression model Table . In maleIn this study, we found a high prevalence of vitamin D insufficiency (31.8 %) and deficiency (63.0 %) in West China older adults. The prevalence of vitamin D insufficiency and deficiency reported here was higher than most of previous studies performed in older adults in other countries. For example, in the United States, vitamin D insufficiency and deficiency were observed in 41.2 and 27.1 % older adults, respectively . In a EuOur results showed that low vitamin D status was associated with obesity in old individuals are consistent with previous studies , 29. TheBy providing more detailed information, FMI and VFA could better assess total fat mass. In this study, vitamin D status was found to be negatively associated with FMI and VFA in two sexes. Although there are many other methods for measuring FMI and VFA, such as computed tomography (CT), magnetic resonance imaging (MRI), and dual-energy X-ray absorptiometry (DXA), BIA has several advantages including ease of accessibility, no radiation exposure and relatively low cost , 32. EviOur study also found the correlations of WHR with vitamin D status were stronger than the other obesity markers in both sexes. Several studies demonstrated an inverse correlation between vitamin D status and the risk of abdominal obesity, but most of them included adults of all ages and determined abdominal obesity merely by WC . Few stuIn the current study, more obesity markers were found to be related to vitamin D status in females. Weight, BMI, MAC, WC and HC were associated with vitamin D status in females, while only TSF was found in males. The sex differences may reflect the fact that males are more prone to accumulate visceral adipose tissue, while females have greater fat accumulation in subcutaneous  depots than males , 40. Of The active form of vitamin D, 1,25-dihydroxyvitamin D, is thought to play a role in the production of testosterone . SupplemSeveral strengths and limitations of our study should be recognized. To our knowledge, this is the first report of the prevalence of vitamin D insufficiency and deficiency and assessed the association between the vitamin D status and several obesity markers in a relatively large sample size of older adults in West China. Second, we used sex-stratified analyses to identify these associations, which only few studies have done before . At the In summary, the results of this study suggest that the prevalence of low vitamin D status among older adults in West China is high. The inadequate vitamin D status should be a concern for the local government. Importantly, our study compared the associations between different obesity markers and the risk of low vitamin D status. WHR was more strongly associated with low vitamin D status in both sexes than other obesity markers. BMI was not associated with vitamin D status in males. Future studies related to vitamin D status should pay more attention to the older adults with high WHR.


Overweight/obesity among adolescents is an emerging public health issue worldwide. However, the evidence on the determinants of body weight status and lifestyle behaviors among Nepalese adolescents is limited. This study aims to explore the sleep characteristics, dietary habits, and physical activity and its association with body mass index (BMI) among Nepalese adolescents.p-value < 0.05 and 95% confidence intervals (CIs).A cross-sectional study was conducted between July and November 2019 among 627 randomly selected adolescents from eight schools located in Kathmandu Metropolitan City, Nepal. A self-administrated structure questionnaire was used to collect the data. Anthropometric measurements (adolescent’s BMI), sleep characteristics, dietary habits, and physical activity were assessed using validated tools. Multinomial logistic regression analyses assessed the association between covariates and BMI categories. The statistical significance was considered at The overall prevalence of underweight and overweight/obesity among adolescents was 9.1% (95% CI: 7.1–11.6) and 23.7% (95% CI: 20.6–27.7) respectively. In multinomial logistic regression, adolescents who reported sleep problem compared to those with no such problem (Relative risk ratio (RRR) = 13.37, 95% CI: 7.14–25.05), adolescents who had obstructive sleep apnea (OSA) symptoms , who consumed soft drink ≥1 time/day in past 1 months , consumed high-fat dietary ≥2 times/day , and had a habit of junk food consumptions , adolescents who had 5–6 h/day sedentary behavior , adolescents from Terai/Madhesi castes  and adolescents whose father was employed  were at increased risk of being overweight/obesity. In contrast, adolescents aged 14–16 years had 71% lower , and adolescents who consumed less than five food groups had 45% lower  risk of being overweight/obesity compared to 12–14 years age groups and consumed more than five food groups respectively.The findings of this study warrant immediate interventions to improve the lifestyle to reduce overweight/obesity among Nepalese adolescents. Creating a conducive environment, both at school and home is essential to encourage adolescents for the adoption of healthy lifestyle behaviors. Overweight and obesity among adolescents aged 10–19 years are emerging public health issues worldwide . The gloAdolescence is a critical period of transition from childhood to adulthood, and therefore, both individual and environmental factors influence their health behaviors, dietary choices, and social activities . The oveAdequate sleep is a biological necessity of human life and a critical cycle of our daily life that helps to sustain the normal function of the brain and maintain homeostasis , 22. GooAlthough lifestyle factors have been considered as key determinants for overweight and obesity, such findings in the previous studies are mostly presented from developed countries . In mostIn the last few decades, Nepal has undergone a massive demographic shift in population, where it is expected that in 2021, adolescents will comprise of about 19% of the total Nepalese population  in NepalA cross-sectional study was conducted between July and November 2019, among adolescents aged 11–19 years in Kathmandu a Metropolitan City and capital of Nepal. Kathmandu Metropolitan City is a residence to 20% of Nepal’s urban population from a diverse ethnic and socio-cultural background and has a density of 13,225 population per square kilometers . The citN = Z2pq/d2, considering 95% confidence interval (CI), 50% assumed proportion (p) [The sample size was calculated using the single population proportion formula: tion (p) , and 5% A multistage cluster random sampling method was used to select the study sample. In the first stage, all 32 local administrative units  of Kathmandu Metropolitan City were considered as clusters for this study. There were a total of 91 public and 638 private schools within the Kathmandu Metropolitan City, with approximately a total of 165,000 adolescents; more than 90% of adolescents pursuing their education in private schools within the Kathmandu Metropolitan City . ConsideSelf-administrated questionnaires were distributed to a total of 635 eligible adolescents. The instructions about questionnaires were explained to the adolescents jointly by core study team members and health teachers of the respective schools before the adolescents filled up the questionnaires. Also, we collected the student’s information on the socio-demographic part from their parents by sending a questionnaire along with the consent form. The socio-demographic questionnaires completed by parents were collected at the respective schools of their children within the 4 days of the questionnaire distribution. Anthropometric measurements of children were taken at their respective schools. All tools were originally developed in English and then translated into Nepali language and back-translated to the English language to ensure that the originality of the questionnaire remains unchanged. Also, the tools were pretested among 50 adolescents from a school that was not included in the analytical samples. The data collectors were undergraduate nurses (BSc Nursing), and they were provided a four-day training. The training included an explanation of the objective of the study, data collection procedure, sampling method, ethical principles and guidelines, and data entry techniques. Approximately 20 min was required for adolescents to fill out the questionnaires.2 where kg was student’s weight in kilograms and m2 was their height in meters squared. The student’s height was measured to the nearest 0.1 cm using SECA ceo0123 portable Stadiometer. The participants were asked to take off their shoes and any object on the head before standing on the scale. Likewise, the weight of the participants with minimal clothes and without shoes was measured to the nearest 0.1 kg using calibrated digital bathroom weighing scales. The World Health Organization’s BMI-for-age guideline was used to classify the adolescents BMI scores into five categories: “very thin” (BMI for age between <5th percentile or < −3SD), “thin” (BMI for age between 5th -14th percentile or < − 2SD), “normal” (BMI for age between 15th -85th percentile or -2SD to +2SD), “overweight” (BMI for age between 85th -94th percentile or > +1SD to +2SD) and “obese” (BMI for the age ≥ 95th percentile or > +2SD) [Adolescent’s BMI was computed using the formula BMI = kg/m > +2SD) .Adolescents’ sleep habits and problems were assessed using the student version of the Child and Adolescents Sleep Checklist (CASC-s) , as thisLikewise, obstructive sleep apnea (OSA) symptoms, characterized by partial or complete obstruction of upper airways, were assessed by two-items related to individual snoring behavior and sleepiness feeling. Participants’ responses  to the statement “I snore (or someone else says I snore)” and “feeling sleepiness at least three days per week” were classified as having OSA symptoms. This operational definition of obstructive sleep apnea symptoms has been previously used in other epidemiological studies , 45.Self-administrated Nepalese version of Global School-Based Adolescents Health Survey (GSHS) core questionnaire modules developed by the World Health Organization  was usedPhysical activity questionnaires were adapted from the Nepalese version of Global School-Based Adolescents Health Survey (GSHS) core questionnaire modules developed by WHO . The tooThe socio-demographic information included: adolescents’ age, sex, grade, ethnicity , religip < 0.05) were applied to check the normal distribution of the data (z-score outliers). Pearson’s chi-square (χ2) and One-way analysis of variance (ANOVA) tests were applied to observe differences in socio-demographic characteristics, sleep measures, physical activity, and sedentary behaviors of participants by BMI categories. Multinomial logistic regression analyses were applied to observe the effects of the predictors on BMI categories considering “normal BMI” as a reference category. Multicollinearity amongst the predictor variables was checked using the Variance Inflation Factor (VIF). The mean value of VIF < 10 was the cut-off point [p-value < 0.05 and 95% confidence intervals (CIs).The collected data were entered into EpiData software 3.1v and transferred into StataMP version 14.1  for statistical analyses. WHO Anthro Plus Software V.1.0.4 was used for BMI scores. The descriptive results are presented in the form of mean, standard deviation, frequency, and percentage. Both histogram and Kolmogorov-Smirnov normality test (ff point . The stap < .05). Model-I was adjusted with the main predictor variables such as adolescents’ sleep characteristics and dietary habits. Model-II was adjusted for adolescents’ sleep characteristics, dietary habits, and socio-demographic characteristics of parents and adolescents. Model-III was adjusted with physical activity and socio-demographic characteristics of parents and adolescents. Model-IV adjusted for significant variables (p < 0.05) from Model- I, Model-II, and Model-III resulting in a parsimonious model in the multivariate analysis.Four models were created to adjust the association between different predictors such as socio-demographic variables of parents and adolescents, sleep characteristics, dietary habits, and physical activity with the outcome of interest as BMI among adolescents using multinomial logistic regression analyses. Backward stepwise processes were used to identify parsimonious models to explain the predictors of adolescent’s weight status . Permission was also taken from the participating schools. Written consent was obtained from the legal guardians or parents of eligible children aged 10–19 years. A separate questionnaire with an informed consent form and request letter from respective schools were sent to parents through their children. Written consent was also taken from the adolescents who participated in the study. Adolescents were also informed that they were allowed to leave any questions unanswered in the self-administered questionnaire. Participation was voluntary, and participants’ identity was kept confidential.Table The mean (± SD) age of adolescents was 14.4 (± 1.1) years. More than three fourth (77.9%) of the adolescents were aged between 14 and 16 years, attended private schools (75.1%), and followed the Hindu religion (78.6%). More than half were male (54.1%), had a nuclear family type (55.3%). Slightly more adolescents were from grade nine. More parents were from the Brahmin/Chhetri ethnic group (40.6%), and more mothers attended below high school education (58.2%), while approximately half (48.4%) of fathers had attended university-level education. The majority of mothers were unemployed (63.1%), and three fourth of fathers were employed (74.9%), and more (41.4%) of parents had a family monthly income between 15,000–30,000 Nepalese Rupees (130–260 USD) per month , males (54.1), private school attendant (54.3%), from Dalit and minority ethnicity (43.8%), and joint family (50.8%), whose mothers had less than high school education (50.8%) and unemployment (63.1%), unemployed fathers (63.1%), and having family monthly income between 15,000–30,000 NRs (33.3%) , males (51%), belonged to private school (75.1%), belonged to Brahmin/Chhetri ethnicity (44.9%), in a nuclear family (53%), amongst those whose mothers had below high school education (63.1%), in fathers university-level education (46.9%), in unemployment mothers (67.1%), in employed fathers (82.5%), and had family monthly income between 15,000–30,000 NRs (38.9%) (Table The mean (± SD) sleep duration for weekdays and weekends was 8.9 (± 1.1) and 8 (± 1.1) hours, respectively. About one in four adolescents had sleep problems with a mean (± SD) CASC score of 24.7 (± 4.5), and one in ten had OSA symptoms  and history of OSA symptoms 92.9%). Conversely, overweight/obesity was most prevalent among adolescents who had sleep problems (56.3%) but no history of OSA symptoms (79.8%)  of adolescents never consumed fruits, one fourth (74.3%) of adolescents consumed vegetables more than two times a day, more (53.1%) of adolescents drank soft drinks, and one third 65.2%) of adolescents had consumed high-fat foods less than once a day in past 30 days. About nine in every ten children had consumed junk food, nearly half (46.1%) of adolescents have consumed junk food 1–3 times per week, more than half (53.4%) of adolescents took fast food 2–3 days per week, and more (55.8%) adolescents had consumed more than five food groups , consumed fruits ≥1 times/day (61.4%), consumed vegetables ≥2 times/day (71.9%), consumed soft drinks < 1 time/day (75.4%), consumed high-fat food ≤1 time/day (66.6%), consumed fast food 2–3 days per week (45.6%), had consumed junk food (77.1%), consumed junk food 1–3 times per week (61.4%), and consumed less than 5 food groups (68.4%). Similarly, overweight/obesity was most prevalent among those adolescents who never went hungry in school (61.1%), consumed fruits ≥1 times/day (57.7%), consumed vegetables ≥2 times/day (73.1%), consumed soft drinks ≥1 time/day (83.22%), consumed high-fat food ≥2 time/day (50.3%), consumed fast food 2–3/days per week (47.6%), consumed junk food (89.2%), consumed junk food ≥4 times per week (49.6%), and consumed ≥5 food groups (53%) (Table More adolescents (63.1%) were not physically active, and half of the adolescents (51.8%) didn’t walk or ride a bicycle in the past 7 days. The majority of the adolescents (56.3%) didn’t get any physical education/training during the past school year, and more adolescents 42.5%) spent 3–4 h per day in sedentary behaviors , didn’t walk or ride a bicycle (63.1%) in the past 7 days, who didn’t get any physical education during this school year (73.6%), and who had spent 3–4 h/day in sedentary behavior (40.5%). Likewise, overweight/obesity was most prevalent among those adolescents who weren’t physically active (66.4%), didn’t walk or ride a bicycle as their primary means of transport to and from school or around the home (41.6%) in the past 7 days, who didn’t get any physical education during this school year (68.4%), and who had spent 3–4 h/day in sedentary behavior (34.9%) , adolescents who had OSA symptoms compared to no OSA symptoms , who consumed soft drink ≥1 time/day compared to < 1 time/day in past 1 months , consumed high-fat food ≥2 times/day compared to ≤1 time/day , and adolescents who had consumed junk food compared to never consumed junk food . Parents who belonged to Terai/Madhesi castes had more than two times  increased risk of overweight/obese children compared to Brahmin/Chhetri castes. Adolescents whose fathers were employed also had more than two times  significantly higher risk of being overweight/obese. Adolescents who used bicycle or walked 1–3 days/week as their primary means of transport to and from school or around the home , and ≥ 4 days/week  as their primary means of transport to and from school or around the home were significantly higher risk of being overweight/obesity compared to those who didn’t. Adolescents who had spent 5–6 h/day in sedentary behavior were 3.21 times  increased risk of being overweight/obese than those who had spent < 1 h/day in sedentary behavior. In contrast, adolescents aged 14–16 years were 71% lower  and adolescents who had consumed less than five food groups had 45% lower  risk of being overweight/obesity compared to 12–14 years age groups and who had consumed more than five food groups respectively.The relative risk of underweight was found increased in adolescents who rarely/sometimes went hungry  compared to never went hungry, and Dalit and minority castes  compared to Brahmin/Chhetri castes. In contrast, those adolescents who consumed soft drink had 73%  than those who consumed < 1 time/day, physically active had 66%  compared to physically inactive, received 1–3 days physical education/training during this school year had 75%  compared to no physical education/training, and those who spent 3–4 h/ day in sedentary behavior had 43%  compared to those who spent < 1 h/day in sedentary behavior respectively were at lower risk of being underweight  were found to be overweight/obese, which is consistent with results from the previous studies conducted in Nepal (25–26% overweight/obesity) , 12. MosWe found nearly one in four adolescents (24.4%) had sleep problems and similar findings have been reported from several studies conducted in both developed and developing countries across the globe that showed sleep disorders as a common problem, particularly among the teenage population –56. In tLikewise, about one in every ten adolescents were found to have OSA symptoms, and those who had OSA symptoms were found to be at higher risks of overweight/obesity compared to those who did not have OSA symptoms. There is ample of evidence that suggests vice-versa associations of OSA and overweight/obesity among children and adolescents. The study conducted among Australian adolescents showed that with each standard deviation increase in BMI z-score, there is more than three times more risk of developing OSA, which supports the findings of our study . MitchelDue to “nutrition transition” in most of the low-income countries the food consumption patterns has shifted from locally available staple foods consumption towards the consumption of western diet pattern containing poor nutrients, foods high in fat, energy-dense foods, sugar-sweetened beverages, junk foods, fast foods and less consumption of vegetables and fruits . In thisOur study also revealed that adolescents who had consumed < five food groups within the last 24 h preceding to survey were found protective towards overweight/obesity as compared to those who consumed ≥ five food groups. These findings are supported by the results of the study conducted in the USA, where diversified food group consumption was positively associated with body fatness . HoweverOn the other hand, only a few food-related factors were associated with an increased risk of underweight. The relative risk of underweight was found increased in adolescents who rarely/sometimes went hungry. Similar findings are reported by Johnson et al. , where tOur study revealed that very low percentages of adolescents were found to be involved in physical activity and more than half of the adolescents were found to have more than 3 h of sedentary lifestyle per day. These results were found congruent with the findings from similar studies conducted in the past , 73. HowIn the current study, adolescents belonging to Terai/Madhesi castes were found more likely to be overweight/obese. There is a paucity of evidence demonstrating the association between ethnicity and overweight/obesity among adolescents; as a result, we couldn’t justify it anymore in this study. These findings recommend prospective researchers to explore the causal relationship between ethnic variations and BMI within the Nepalese context. However, the possible reason could be that the elite group or richest people in Nepal comes from Madhesi, Newar, Thakali, and Thakuri ethnic groups, alongside Bhramin and Chhetri. Those richest people who belonged to Terai/Madhesi caste were migrated from Terai to Kathmandu and are privileged to study in high-quality English-medium schools. Moreover, the richest peoples have access to energy-dense, fast foods in their family, and luxurious lifestyle and able to high daily expenses resulting in overweight/obese children. In contrast, adolescents who belonged to Dalit and minority caste were found to be underweight. Dalit castes, one of the most marginalized groups in Nepal, are still facing several forms of discrimination in all sectors, including the workplace. As a result, Dalits today stand at the bottom of most indicators of socio-economic development . PeoplesOur study has some limitations. First, due to the cross-sectional study design of the study, the directional cause and effect relationship between independent and dependent variables cannot be inferred. Generalizing the pattern of dietary habits, sleep characteristics, and physical activity throughout the entire calendar year would be misleading as the data were collected at a specific point of time. Second, the data collected were self-reported and it was retrospective, we could not completely ignore the recall bias. Third, calculating the actual amount of energy expenditure or sedentary behavior was not possible due to the use of self-reported information. Likewise, food consumption in terms of the nutrient amount was not calculated, which could result in overestimating or underestimating the actual extent of dietary habits influences on the BMI of adolescents. Fourth, since the participants were recruited from the schools located in urban settings, the results of this study cannot be generalized among adolescents living in rural areas of the country. Despite the mentioned limitations, our study has some strengths. This study is the first of its kind to explore the association of sleep characteristics with BMI of adolescents in the Nepalese context. Therefore, this study fills the gap of evidence regarding how sleep characteristics with dietary habits and physical activity influence the BMI status of Nepalese adolescents. Further, this study has attempted to bring the attention of researchers for the future in-depth study for the explicit understanding of the multifactor and the complexity of the overweight/obesity mechanism among Nepalese adolescents, which is one of the major current public health concerns in the country.The current study highlighted that overweight/obesity among Nepalese adolescents is at an alarming level and on par with many developing and developed countries. Sleep problem, OSA, consumption of carbonated /soft drinks, consumptions of fast foods and junk foods, physical education/training, sedentary behaviors, participant’s age, ethnicity, and father occupation status were major predictors for overweight/obesity among adolescents. The findings of this study warrant immediate interventions to improve lifestyle behavior and reduce overweight/obesity among adolescents. Creating a conducive environment both at school and home to encourage adolescents to adopt a healthy lifestyle and dietary choices are crucial in reducing overweight/obesity. It is also essential to regularly monitor the BMI status, sleep quality, and health behaviors of adolescents so that it would be possible to modify their dietary habits and other lifestyle behaviors timely. Adolescents and their parents need to be aware of the minimum sleep duration required for adolescents and also about the impact of inadequate sleeping on health, which could help to improve the sleep quality of adolescents. Finally, the concerned authorities are required to develop long-term practical health-promoting policies to reduce the risk of overweight/obesity as well as to improve the overall wellbeing of Nepalese adolescents.


Clin Transl Immunol, 8: e01081. https://doi.org/10.1002/cti2.1081. The above article published online on 27 September 2019 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal's Editor‐in‐Chief, Rajiv Khanna, the Australian and New Zealand Society for Immunology Inc., and John Wiley and Sons Australia, Ltd. The retraction has been agreed following an investigation by the QIMR Berghofer Medical Research Institute into research published by the senior author, Professor Mark J Smyth. The investigation concluded that at least two figures (3b and 4b) generated by the senior author Professor Mark Smyth are likely fabricated. As a result, the conclusions are considered unreliable, and the article has been retracted.Dougall WC, Roman Aguilera A, Smyth MJ (2019), Dual targeting of RANKL and PD‐1 with a bispecific antibody improves anti‐tumor immunity.


Open resection of small bowel neuroendocrine neoplasms (SB-NEN) is still considered standard-of-care, mainly because of frequently encountered multifocality and central mesenteric masses. The aim of this study was to evaluate surgical approach for SB-NEN at a national level and determine predictors for overall survival.Patients with SB-NEN who underwent resection between 2005 and 2015 were included from the Netherlands Cancer Registry. Patient and tumor characteristics were compared between laparoscopic and open approach. Overall survival was assessed by Kaplan–Meier and compared with the Log-rank test. Independent predictors were determined by Cox proportional hazards model.p = 0.004). In multivariable analysis, age above 60-years ; > 75 years, HR 7.63 (95% CI 3.86–15.07)), stage IV disease (HR 1.86 (95% CI 1.18–2.94)) and a laparoscopic approach (HR 0.51 (95% CI 0.28–0.94)) were independently associated with overall survival, whereas multifocal primary tumor, grade and resection margin status were not.In total, 482 patients were included, of whom 342 (71%) underwent open and 140 (29%) laparoscopic resection. The open resection group had significantly more multifocal tumors resected (24% vs. 14%), pN2 lymph nodes (18% vs. 7%) and stage IV disease (36% vs. 22%). Overall survival after open resection was significantly shorter compared to laparoscopic resection (3-year: 81% vs. 89%, 5-year: 71% vs. 84%, Laparoscopic resection was the approach in 29% of SB-NEN at a national level with selection of the more favorable patients. Laparoscopic resection remained independently associated with better overall survival besides age and stage, but residual confounding cannot be excluded. Small bowel neuroendocrine neoplasms (SB-NEN) are a rare type of gastrointestinal cancer and constitute 15% of all neoplasms of the jejunum and approximately 60% of the ileum, making it the most common gastroenteropancreatic NEN . PatientThe majority of patients with SB-NEN already present with mesenteric lymph node metastases, and multifocal primary tumors can be found in up to 25–44% , 5.Considering the evolution in the application of advanced laparoscopic resection for more complex oncological disease, and more specifically the experience with D3 mesenteric lymphadenectomy , applicaThe primary aim of this study was to evaluate surgical approach for SB-NEN at a national level considering selection based on patient and tumor characteristics. Secondarily, the aim was to identify independent predictors of overall survival.Data from all patients with SB-NEN diagnosed between 2010 and 2015 were extracted from the Netherlands Cancer Registry (NCR). The NCR contains all cases of cancer in The Netherlands , mainly based on notification by the digital pathology archive and the national registry of hospital discharge diagnoses. Independent data-managers collect data on baseline and tumor characteristics as well as treatment and survival data in each Dutch hospital based on hospital records. Full histopathology reports were requested from The Nationwide Network and Registry of Histo- and Cytopathology in The Netherlands (PALGA) .Patients with histopathologically proven SB-NEN of any stage and differentiation grade were included. The diagnosis was based on the International Classification of Disease-Oncology (ICD-O-3) topography and morphology codes . SurgicaPrimary tumor location was classified as jejunum (C17.1), ileum (C17.2) or small bowel not otherwise specified (C17.9), according to the ICD-O-3 codes. Missing TNM stage was assessed using supplementary data on “extend of disease” present in the NCR database.Data in both NCR and PALGA databases correspond based on unique NCR-codes. This feature was used to couple both datasets. Data regarding topography, differentiation grade, resection margins, TNM staging and tumor positive lymph nodes were extracted from the full histopathology reports provided by PALGA. Morphology codes were used in case of a mismatch in differentiation grade . Data frIn case of multiple histopathology reports , the first date was used as ‘date of diagnosis’. Time to treatment analyses could not be performed because the diagnosis was based on pathology data, which was often the date of surgery. Overall survival was defined as the time between date of diagnosis and date of death or censored at the end of follow-up.Categorical data are presented as number of cases and percentages, whilst continuous data are presented as either mean with standard deviation (SD) or median with interquartile range (IQR), depending on the data distribution. Overall survival analyses were performed using the Kaplan–Meier method and compared with the Log-Rank test. Univariable and multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) to identify factors associated with overall survival. Factors with a p value < 0.2 in univariable analyses were added to multivariable analyses in a forward stepwise fashion. The study period was divided into two time periods (2010–2012 and 2013–2015), and added to the Cox proportional hazards regression model to correct for historical improvements in outcomes. A two sided p value ≤ 0.05 was considered statistically significant. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 26 .p = 0.012). Patients undergoing open resection were more often male  and older  compared to patients undergoing laparoscopic resection. Emergency procedures constituted a minority of patients, with a slightly skewed distribution toward more emergencies in the open group: 5% versus 3% obstruction (p = 0.36) and 2% vs. 0% perforation (p = 0.07), respectively.In total, 482 patients were included over a period of six years 2010–2015), of whom 342 (71%) underwent open and 140 (29%) laparoscopic resection .Patients in the open resection group had a significantly higher clinical stage of NEN with higher proportions of cN1-2 and cM1 stage. Also pathological outcomes were significantly different between the two surgical approaches, with higher pT, pN and pM stages in the open group, as well as a higher percentage of multifocal tumors and larger size of the (largest) primary tumor. A trend toward more positive resection margins in the open resection group was observed .Conversion rate was only available for the year 2015, in which 8 of 30 (27%) laparoscopic procedures were converted. Although no strict reasons for conversion were documented, the following outcomes were observed: pT4 tumors were present in 5/8 (63%) patients, multifocal tumors in 3/8 (38%), pN2 lymph node metastases in 2/8 (25%) and R1/2 resection margin in 1/8 (13%) patients. Mean (SD) tumor size was 27 (9) in the converted cases and 21 (9) mm in the non-converted cases (p = 0.19). Estimated 5-year overall survival of the entire cohort  was 74%. Without correction for confounders, patients undergoing laparoscopic resection had significantly higher 5-year overall survival rates compared to open resection: 84% versus 71% (p = 0.004), respectively , while there was no significant difference between the two surgical approaches for stage IV .Within 30 days postoperatively, 16 patients (5%) died in the open group and 3 patients 2%) after laparoscopic resection (% after lp < 0.001) and ≥ 75 years , stage IV disease , and laparoscopic resection  remained significantly associated with overall survival. The results of univariable and multivariable analyses for overall survival are shown in Table In univariable analysis, age above 60 years, multifocal tumors, stage IV disease and laparoscopic resection showed an association with overall survival Table . In mult95% CI 1.0–2.99, pThe main finding of this nationwide study was that 29% of the patients with SB-NEN were planned for a laparoscopic approach. There was a slight but non-significant increase in laparoscopic resection rate over time. Case selection was clearly seen, with less favorable tumors in patients who underwent open resection, as reflected by significantly higher stage, larger size, and more multifocal tumors. Academic centers performed less laparoscopic resections as compared to regional hospitals, likely reflecting tertiary referral of more advanced cases. With the available variables in the dataset, the association between surgical approach and overall survival was corrected for confounding as much as possible. The multivariable model revealed better overall survival after a laparoscopic approach, with age and stage as the other independent predictors. Potential prognostic factors such as margin status, grade and multifocal tumor location were not found to be associated with overall survival in this patient cohort.The application of a laparoscopic approach for resection of SB-NEN is mainly determined by the extensiveness of mesenteric lymph node metastases. Ohrvall et al. proposed a classification of these metastases, ranging from resectable stage I (close to the intestine) to irresectable stage IV  . In thisThe recent European Society of Medical Oncology guideline states that patients with SB-NEN often present in the emergency setting . An emerA common misunderstanding of laparoscopic resection is the inability of palpating the small bowel. However, after completion of the lymph node dissection, almost the entire small bowel can be exteriorized through an umbilical extraction site, enabling meticulous palpation . IdentifThe conversion rate (36%) was only reported in the last registration year 2015) and was higher compared to previous studies (25–30%)  and was . In contPedrazzani et al. described a case series of nine patients undergoing laparoscopic right hemicolectomy with complete mesocolic excision for terminal ileum/right colon/appendix NEN . AlthougLong-term nationwide population-based data were used for this study, making it more representative than cohort studies. However, the findings of this study should be seen in light of some limitations. The NCR database is primarily focused on oncologic characteristics, which limits analysis of (peri-) operative characteristics  and imaging data such as postoperative CT or PET scanning to assess the completeness of mesenteric lymphadenectomy. Time to recurrence, which is a relevant marker of “surgical success” in regard to lymphadenectomies, could not be reported, as recurrent disease is often not diagnosed with biopsies. The most important missing data concern the reasons for choosing an open or laparoscopic approach and whether surgery was performed in the emergency setting.We propose that guidelines should adapt their recommendations regarding selection criteria for laparoscopic resection, for example using the classification as proposed by Ohrvall et al. . It seemFurther work is required to establish the role of laparoscopic resection for SB-NEN. Ideally, this would be a multicenter international randomized clinical trial with stratification for extent of lymph node metastases. However, such a trial would be challenging because of the rarity of the disease and potential lack of equipoise. To overcome this issue, a prospective international cohort study with clearly documented inter-hospital variability in surgical practice could also provide relevant data. To really be of added value, such a study should include variables that reflect “surgical success”, which are part of standard follow-up protocols  .In conclusion, this study showed that laparoscopic resection of SB-NENs was performed in 29% of patients in the Netherlands. Current data do not raise major concern regarding oncologic adequacy of laparoscopic resection in selected cases.


We aimed to test which life course model best described the association between leisure-time physical activity (LTPA) and multimorbidity at age 55. We analyzed data from birth to age 55 using the database from the 1958 National Child Development Survey.Multimorbidity was considered as the presence of more than one chronic condition. LTPA was measured through questionnaires from 1965 (age 7) to 2013 (age 55), which were applied in eight different occasions. We compared the fit of a series of nested adjusted logistic regression models  with a fully saturated model. Data were reported as odds ratio (OR) and 95% confidence interval (CI).p < 0.001). LTPA every day in the week was more frequent in women than men in ages 33, 42, and 50 (p < 0.001). The prevalence of multimorbidity at age 55 was 33.0% (n = 2778). The sensitive analysis revealed that LTPA during adolescence  and mid adult life  have a stronger effect on the risk for multimorbidity at age 55 considering all other life stages in the model. Also, adolescence showed a critical independent effect on the risk for multimorbidity . No difference was found between those models.From an eligible sample of 15,613 cohort members, 9137 were interviewed in the latest sweep (58.5%). Men were more physically active than women at ages 11, 16, and 23 (These data support the notion of a protective physical activity “legacy” at early ages of childhood against multimorbidity at older ages. We highlight the need for LTPA promotion through intervention tailored especially on schooling and older ages in order to reduce the burden of multimorbidity.The online version contains supplementary material available at 10.1186/s12889-021-10719-7. Multimorbidity, defined as the co-occurrence of two or more chronic conditions in the same individual , affectsMoreover, multimorbidity is associated with increased risk of all-cause mortality in a dose-response effect  regardlePhysical activity can be divided into four domains: leisure-time, occupational, commuting, and household activities. Leisure-time physical activity (LTPA) is related to physical activities performed during spare hours or leisure periods, based on individual or collective preferences. LTPDA has been shown an inverse relationship with all-cause, specific-cause mortality , and unhThus, the present study aimed to assess whether there is an association of LTPA at different stages of life with multimorbidity at age 55 and evaluate its cumulative effect during the early life stages on multimorbidity in middle-to-older adults.https://www.ukdataservice.ac.uk/deposit-data/). Full description of sampling design and methods can be found elsewhere [N = 17,638) of all births between 3rd and 9th March 1958 in England, Wales, and Scotland. Sociodemographic and behavioral information from both parents besides data regarding to pregnancy and the child were assessed. Further, any child born in the Great Britain in that specific week were identified by school registers and added to cohort sample during second through fourth sweeps , reaching a final sample of 18,558 cohort members. Flow diagram about sample composition is shown in Figure SWe analyzed data from the 1958 National Child Development Survey (NCDS). The dataset is freely available upon request at the UK Data Service  (https:/lsewhere . Brieflyn = 1659) and emigrants (n = 1286) through cohort summed 2945. Thus, from an eligible sample of 15,613, 9137 participants were interviewed (response rate: 58.5%) [https://cls.ucl.ac.uk/cls-studies/1958-national-child-development-study-2/).Fifty-five years after baseline assessments, this cohort remains largely representative of the sample that it was drawn. In the latest sweep (2013) cumulative deaths (: 58.5%) . After bWe considered multimorbidity as the co-occurrence of more than one of the following morbidities at age 55 : asthma LTPA was assessed from 1965 to 2013. Data collected in 2002 (age 44 sweep) and 2004 (age 46 sweep) regarding to LTPA were not used in this study because they were assessed by different interview methods , which may decrease significantly both reliability and comparability of measurements . All incAll multivariate analyses were adjusted for the following variables: gender, marital status, education level, income, country of birth, ethnicity, smoking, alcohol intake, hours of sleep, and LTPA. We considered sex, country of birth, and ethnicity collected at birth sweep. We used LTPA as a possible confounder in analysis where the main exposure was a time-specific sweep and it was adjusted for previous and future LTPA practice. All remaining used variables were assessed in the latest sweep (2013).Descriptive analysis is reported as absolute and relative frequencies. The difference between groups was assessed using chi-square tests. To evaluate the PA effect during earlier life, we stratified the variable in childhood (age 7 and 11 sweeps), adolescence (age 16 sweep), young (age 23 sweep), middle (age 33 sweep), and middle-to-old age (age 50 and 55 sweeps) adults.Logistic regression was performed as crude analysis model 1) and using hierarchical model adjusting for gender, marital status, education level, income, country of birth, ethnicity (model 2), as well as smoking, alcohol intake, and hours of sleep (model 3). For regression analyses, PA was categorized as either “inactive” or “active” for each individual. Such categorization was conducted for each life stage considered in the analysis and was based on the daily or weekly frequency of PA. The criteria used for PA categorization for each life stage are presented in Supplementary Table S and usinThen, a structured modeling approach developed by Mishra et al.  was usedAccumulation model was tested in two versions. First, a strict model (continuous) was assessed by adding the number of times an individual reported being physically active across their life course to form an overall score, which was then used as the exposure. This model assumes that the effect of LTPA at each life period  period is the same. Second, a relaxed model  was examined in which all time periods are contributing to multimorbidity at age 55 but not necessarily in an equal way.The critical period model assumes that only LTPA in a certain age influences multimorbidity at age 55 regardless of any other time period. Similarly, sensitive model was tested to allow the examination of the varied effect of LTPA across the life course, which can be modelled by simultaneously including all LTPA variables in the model. Finally, a null model was tested with only our outcome at the model .p > 0.05), the one with the lowest Akaike’s information criterion (AIC) was selected. When more than one model presented p-value higher than 0.05 and there is not a large difference in p-values, the simpler model was selected [To identify the most appropriate life course model to explain multimorbidity at age 55, likelihood ratio test was conducted comparing each life course model to the saturated model. When nested life course models  provided similar fit to the fully saturated model , alcohol intake were higher among women (p < 0.001).From the initial sample of 18,558 cohort members, 9137 49.2%) were interviewed in the latest sweep. Excluded participants were more likely to be male (54.8%), have no academic qualification (36.8%), be divorced/separated (24.7%), unemployed (16.5%), and smoker at age 50 (35.9%), as shown in Supplementary Table S% were inp = 0.087), however, men reported higher work-related physical activity than women (p < 0.001). In addition, 80% of sample self-rated their health as good to excellent with no detectable difference between gender (p = 0.071).Our analysis did not detect difference in LTPA between gender .Men were more physically active than women in age 11, 16, and 23  were classified as having multimorbidity. Multimorbidity was more likely among participants with low educational achievement, at lowest quintile interval of income, who were not regular drinkers of alcoholic beverages, and with worse general health perception, as shown in Supplementary Table S3.0% werep < 0.001). However, critical period model for LTPA during adolescence (p > 0.99) and sensitive model (p > 0.99) provided a fit not worse than saturated model with no clear difference between models based on p-value, log-likelihood, and AIC. Accumulation models provided similar fit compared to saturated model (p > 0.99); however, AIC values were higher than observed in adolescence as a critical period and the sensitive model, as shown in Table Table As shown in Table Our findings confirmed our hypothesis that engage in LTPA through life would reduce the risk for multimorbidity in older ages. Both sensitive and critical periods best explained the association between LTPA through life course and multimorbidity. We revealed that being physically active at adolescence and middle-to-late adult life reduced in about 17 and 18% the odds of multimorbidity at age 55, respectively, even when controlled for LTPA at all other analyzed ages. Similarly, engage in LTPA early in life was revealed as a critical period for decreasing the odds of multimorbidity at age 55.Adolescence is an important life period where healthy lifestyle promotion (e.g. LTPA) could reduce the risk for some conditions such as obesity , 24, diaIn a retrospective study conducted by Fernandes and Zanesco , physicaPhysical activity engagement in practice adulthood has been associated with reduced risk for chronic diseases and all-cause mortality . Based oDregan et al.  reportedSome limitations of this present study must be acknowledged. First, LTPA was measured by questionnaires. In order to reduce the bias from that measurement, we chose to use in our study only those sweeps with face-to-face interview administrated questionnaire. The 1958 National Child Development Survey is one of the oldest national-based cohort studies, so although the level of LTPA was not examined by devices-based measurements, the information from those sweeps are reliable, comparable, and relevant . Also, aIn conclusion, we identified LTPA during adolescence as a critical period associated with reduced risk for multimorbidity in late adult life. Similar protective status was found in the sensitive model for LTPA during the same period and in middle-to-late adulthood (ages 50 and 55). Although analysis of factors associated with the outcome along lifetime is complex and should be carefully interpreted, our results support the need for LTPA promotion through intervention tailored especially on schooling age and older ages to reduce the burden of multimorbidity.Additional file 1: Figure S1. Flow diagram about sampling process through sweeps. 1958 National Child Development Study. United Kingdom.Additional file 2: Table S1. Operationalization of physical activity since age 7 sweep and in the present study.Additional file 3: Table S2. Sociodemographic, behavioral, and clinical characteristics from the included and excluded sample. N = 18.558. United Kingdom, 2013.Additional file 4: Table S3. Sociodemographic, behavioral, and clinical characteristics from the sample. N = 8414. United Kingdom, 2013.


Osteoporosis and Parkinson’s disease (PD) are age-related diseases, and surgery for osteoporotic vertebral collapse (OVC) in PD patients become more common. OVC commonly affects the thoracolumbar spine, but low lumbar OVC is frequent in patients with lower bone mineral density (BMD). The aim of this study was to identify differences in clinical and imaging features of low lumbar OVC with or without PD and to discuss the appropriate treatment. The subjects were 43 patients with low lumbar OVC below L3 who were treated surgically, including 11 patients with PD. The main clinical symptoms were radicular pain in non-PD cases and a cauda equina sign in PD cases. Rapid progression and destructive changes of OVC were seen in patients with PD. The morphological features of OVC were flat-type in non-PD cases with old compression fracture, and destruction-type in PD cases without old compression fracture. Progression of PD was associated with decreased lumbar lordosis, lower lumbar BMD, and severe sarcopenia. High postoperative complication rates were associated with vertebral fragility and longer fusion surgery. Progression of postural instability as a natural course of PD may lead to mechanical stress and instrumentation failure. Invasive long-fusion surgery should be avoided for single low lumbar OVC. Clinical and imaging features in low lumbar OVC may differ from those in thoracolumbar OVC, based on our previous findings2.The incidence of osteoporotic vertebral collapse (OVC) is likely to increase with aging of the population. Conservative management is effective in most cases, but OVC with back pain, neurological complications or a concern of paralysis requires surgery to permit a return to activities of daily life (ADL). In a multicenter cohort of 403 patients in Japan who underwent fusion surgery for OVC with neurological deficits, a thoracolumbar junction lesion at T12 and L1 was most frequent, but 18.9% of cases had low lumbar OVC below L33. Complications after surgery for OVC occurred in 14.1% of cases in a multicenter cohort study, with age, liver disease, and Parkinson’s disease (PD) found to be independent risk factors for postoperative complications4. In the same series, a comparison of patients with thoracolumbar spine (T10-L2) with and without PD found higher rates of perioperative complications and lower walking ability at follow-up in the PD group5.Low lumbar OVC is also frequently found in patients with lower bone mineral density (BMD) and a higher mechanical failure rate, compared with thoracolumbar junction collapse6. Thus, both OVC and PD are age-related diseases with low bone quality. Higher rates of postoperative complications and revision surgeries have been reported after spine surgery for patients with PD, such as fusion surgery for degenerative diseases and thoracolumbar OVC. However, clinical status, neurological symptoms, radiological findings, and surgical strategies for patients with low lumbar OVC with PD have not been described.PD is a common neurodegenerative disease with features of locomotor dysfunction, including resting tremors, rigidity, and bradykinesia. Patients with PD also often have low bone quality, loss of muscle mass (sarcopenia), and an abnormal posture. PD affects 1% of the population over age 60 and up to 4% over age 80, and the prevalence generally increases with ageWe hypothesized that the different clinical and imaging features in patients with low lumbar OVC with and without PD may be related to neurological symptoms. In this study, we examined these relationships, with the goal of proposing appropriate surgical treatments.2, p = 0.17). The mean follow-up period was 3.7 ± 1.0 (range 1–5) and 3.5 ± 2.0 (1–8.5) years in PD and non-PD cases, respectively. The Hoehn & Yahr stage before surgery was stage II in 5 patients and stage III in 6. Progression of severity of PD occurred in 4 of 11 patients (36.4%): 3 of 5 (60.0%) in stage II reached stage III, and 1 of 6 (16.7%) in stage III reached stage IV.Demographic data for patients who underwent surgery for low lumbar OVC below L3 are shown in Table p = 0.016), whereas a cauda equina sign, such as motor and/or sensory disturbance, was most common in PD cases (p = 0.0047). Importantly, rapid progression of OVC was much clearer in PD cases compared with non-PD cases .Symptoms and durations from diagnosis of compression fracture to that of burst fracture with neurological symptoms are summarized in Table p = 0.0003). No patients had type 1 OVC (wedge-type), as often found in thoracolumbar OVC. There was a higher rate of cases with type 2 OVC (flat-type) in non-PD cases and of type 4 (destruction-type) in PD cases (p = 0.0073). Twelve of 23 type 2 cases (52.2%) had intervertebral cleft formation at the affected vertebra, but with no significant difference between the two groups. Preoperative lumbar BMD (p = 0.043) and L3 total psoas area/vertebral body area ratio (p = 0.044) were significantly lower in PD cases. There was no significant difference in preoperative lumbar lordosis and local lumbar lordosis before and after surgery, but PD cases had decreased lumbar lordosis at follow-up (p = 0.02).Differences in imaging findings between patients with and without PD are shown in Table p = 0.14) (Table p = 0.015). In addition, change of lumbar lordosis (p = 0.047), and longer fused vertebrae (p = 0.041) were also significant. No significant differences in BMI (p = 0.60), presence of PD (p = 0.51), type of OVC (p = 0.92), change of local lumbar lordosis (p = 0.84), L3 total psoas area/vertebral body area (p = 0.75), and surgical procedures (p = 0.87) were observed.Postoperative complications occurred in 5 PD 45.5%) and 11 non-PD (34.4%) patients, including loosening and migration of pedicle screws (PS), progression of vertebral collapse, infection and delirium. In addition, exacerbation of dyskinesia was observed in one PD patient. The rate of revision surgery was higher in PD cases, but with no significant difference compared with non-PD cases  and surgery for OVC (hazard ratio 2.69) in PD patients compared to non-PD subjects10. Weight loss and sarcopenia are common in PD patients and correlate with greater motor changes, a higher rate of fall, and disease progression11. In a cross-sectional study, 55.8% of PD cases had sarcopenia compared to only 8.2% of controls12. There is also a strong negative correlation of BMD with the severity of PD, particularly for the lumbar spine14. Similarly, lower BMI, lumbar BMD, and sarcopenia were present in PD cases in the current study.This study showed important differences in low lumbar OVC in patients with or without PD. Rapid progression and destructive changes of low lumbar OVC in patients with PD, and significantly more PD cases with a cauda equina sign requiring urgent surgery were important findings in this study. Fragility fractures are more likely to occur in patients with PD than in similarly aged non-PD subjects because of a higher risk of falls and lower BMD due to weight loss and lower mobility2. In contrast, rapidly progressive OVC in type 4 could lead to cauda equina symptoms due to rapid and severe spinal canal stenosis. In addition, old compression fracture at the thoracolumbar level was found in most non-PD cases, but in few PD cases. Spinal alignment changes may increase middle and/or posterior low lumbar spine loading, and lower bone quality and severe sarcopenia in PD might cause rapid progression and destructive changes of OVC  low lumbar OVC was dominant in non-PD cases, whereas destructive-type (type 4) was found in most PD cases. The main clinical symptom in type 2 low lumbar OVC is radicular pain resulting from retropulsed bony fragments causing foraminal stenosis and/or canal stenosis low lumb15. Another large-scale matched-pair cohort study using an inpatient database in Japan also suggested that PD was a significant predictor of postoperative complications (odds ratio 1.74) following spine surgery, with delirium being most frequent16. In our study, postoperative complications were associated with lower preoperative lumbar BMD, decreased lumbar lordosis, and longer fusion surgery. In a multicenter study of lumbar spine surgery, surgical failure was more frequent in PD cases in fusion (45.8%) and corrective (67.7%) surgeries than in laminectomy only (33.3%). Thus, lower preoperative lumbar lordosis may be associated with failure of initial surgery, which suggests that use of rigid fixation to achieve and maintain proper lumbar lordosis may be effective in PD cases17. We agree with the necessity of long-segment corrective fusion surgery to maintain spinopelvic harmony for global sagittal malalignment, especially such as camptocormia in patients with a stooped posture due to PD progression. However, poorer outcomes and lower fusion rates in multi-level fusion surgery have also been reported for PD cases19, and PD patients treated with long instrumentation, surgery including the thoracic spine, and with less effective spinopelvic realignment tend to require earlier revision20.We found relatively high rates of postoperative complications of 45.5% in PD cases and 34.4% in non-PD cases, mainly related to instrumentation. The rate of revision surgery was particularly high in PD cases (27.3%). In a large-scale cohort study of thoracolumbar spine fusion surgery using a national insurance database in the US, PD was significantly associated with an increased risk for medical complications (odds ratio 1.22) and revision surgery (odds ratio 1.70)21, and adjacent disc stress in longer fusion and fusions involving lower lumbar segments is higher than that in upper lumbar segments22. These results suggest that progression of postural instability in the natural course of PD could lead to mechanical stress and instrumentation failure, especially at an upper adjacent level. In the current study, the presence of PD alone was not correlated with instrumentation failure, but significantly lower lumbar BMD and decreased lumbar lordosis in PD patients might contribute to a higher rate of instrumentation failure compared to that in non-PD patients. An epidemiological study revealed camptocormia in 4.1% of PD patients23, and we found that sagittal spinopelvic alignment did not differ in low lumbar OVC cases with and without postoperative complications2. Long-fusion surgery should be avoided for patients with single-vertebra OVC because poor sagittal alignment is less common in such cases, but short fusion from a posterior approach cannot correct a spinopelvic mismatch and instrumentation should not be ended in a kyphotic segment.In the present study, lumbar lordosis at follow-up was significantly lower in PD patients, although there was no significant difference in local lumbar lordosis at follow-up between PD and non-PD cases. A biomechanical study showed that a flexion loading condition increased stress by 39.5%-42.7% in the suprajacent disc24. In assessing long-term outcomes of PD patients, it should also be recognized that the rates of reaching stages III and IV by 5, 10, and 15 years after onset are 30.2% and 6.5%, 57.2% and 27.9%, and 83.5% and 41.2%, respectively25. In addition, the rates of dyskinesia, which increases the risk of instrumentation failure, at these time points are 8.4%, 35.1%, and 62.8%, respectively. Appearance of depression decreasing the motivation for rehabilitation after surgery and deterioration of ADL associated with progression of PD is also important in treatment of OVC. Depression can have a significant impact on severity of PD based on health-related quality of life26. In our study, 4 of 11 cases (36.4%) had progression of severity of PD at follow-up. Thus, medical management as well as surgical strategy are important to improve the outcomes of spinal surgery in patients with PD.The surgical indication and strategy should be considered based on the high possibility of deterioration of ADL in the natural course of PD, even if no postoperative complications occur. PD severity of stage III or above has been found to be a significant risk factor for further lumbar spine surgery2. In PD cases, the surgical procedure is chosen based on severity of PD, type of OVC, neurological signs, endplate destruction, and kyphotic changes in the lumbar spine. For most patients with PD, additional reconstruction of the anterior column should be considered, especially for type 4 OVC. Anterior reconstruction using an expandable cage from a lateral lumbar approach and 1-above 1-below fixation as shown in case 2 in Fig. In surgery for type 2 or 3 low lumbar OVC in non-PD cases, short fusion from a posterior approach is ideal due to easier decompression for the lumbar canal and intervertebral foramen stenosis for fractured vertebraThis study has certain limitations. First, the study was retrospective, single-center design, and small number of patients without inclusion of cases receiving conservative treatment. Some results lack statistical power, and the results may change as the number of samples increases for some parameters that did not show a significant difference in the current study. Second, it had lack of use of minimally invasive surgeries, including anterior reconstruction and percutaneous pedicle screw fixation, which have been developed in recent years. In addition, the samples, including those examined in various types of surgery that may affect spinal alignment more than PD itself, might be too small for generalizability of the results to discuss surgical outcomes and strategies. Larger prospective and multicenter clinical studies are needed to provide further evidence in support of our results. Despite these limitations, we believe that our findings provide key insights on management of surgery for low lumbar OVC in patients with PD, since there are few reports on this condition in this patient population.Between 2005 and 2018, 43 patients underwent surgeries for symptomatic low lumbar OVC at vertebral levels below L3 at our hospital and had a minimum follow-up period of 2 years. Eleven of these patients had PD, and clinical features and imaging findings in these patients were compared with those for non-PD cases (n = 32). No patients had comorbidities that caused lower extremity sensory or motor deficits directly, including symptomatic lumbar spinal canal stenosis. All patients underwent plain radiography, computed tomography (CT), high-resolution magnetic resonance imaging (MRI), and a BMD scan before surgery. Before surgery, written informed consent was obtained from each patient. The study protocol was approved by the Human Ethics Review Committee of Fukui University Medical Faculty  and strictly followed the Clinical Research Guidelines of the Ministry of Health, Labor, and Welfare of the Japanese Government.Data for age, gender, body mass index (BMI), disease duration from diagnosis of compression fracture to that of burst fracture and/or appearance of neurological symptoms, surgical procedures, and postoperative complications were acquired from medical charts. In patients with PD, the Hoehn & Yahr stage before surgery and at follow-up was assessed by senior neurologists. Clinical symptoms, low back pain, radicular leg pain, and cauda equine sign were also stratified based on cleft formation. Radicular leg pain was defined as lower extremity pain consistent with a neurological dominant region. Cauda equina syndrome was diagnosed based on symptoms of neurogenic intermittent claudication or motor and/or sensory disturbance, including bladder dysfunction. The Japanese Orthopaedic Association (JOA) score for neurological status was obtained before surgery and at follow-up, with all neurological evaluations performed by senior spine surgeons. Neurological improvement rate at follow-up was calculated using the following formula: (postoperative follow-up JOA score—preoperative JOA score) × 100/(29-preoperative JOA score). Plain standing radiographs were used to identify other vertebral collapses, the type of vertebral collapse, lumbar lordosis and local lumbar lordosis before surgery and at follow-up.2: type 1 is a wedge-type collapse defined as a ratio of the anterior to posterior height of the vertebral body of < 60%; type 2 is a flat or vertebra plana-like fracture with uniform compression; type 3 is a concave or H-shaped fracture with anterior spur formation or sclerotic change; and type 4 is a burst fracture with severe destruction of the anterior vertebral body. Type 2 collapse often appears as intervertebral cleft formation on radiographs or MRI. Dual-energy X-ray absorptiometry  was used to measure mean BMD of the lumbar spine (L1-L4) in the posteroanterior projection excluding fractured vertebra. To assess the degree of sarcopenia, the sum of the left and right psoas area on the axial image in the middle of the L3 vertebral body divided by the area of the L3 vertebral body was calculated using a Picture Archiving and Communication System27. All measurements were performed in triplicate by each of two observers blinded to data related to surgery, and the average value was used.Each OVC was classified as one of four types based on its appearance on a lateral projection in a neutral position Fig. 2: type 1Vertebroplasty (VP) (n = 5) and a combination of decompression, VP, pedicle screw fixation, and posterolateral fusion (VP + PSF) (n = 13) were performed for cases with clefts at affected vertebra; whereas decompression, PSF, and posterolateral fusion (PSF) (n = 7), and posterior lumbar interbody fusion (PLIF) (n = 6) were used for cases without cleft formation. Other surgeries included correction osteotomy, including pedicle subtraction osteotomy (PSO) and vertebral column resection (VCR) (n = 2); anterior spinal fusion (ASF) using a plate system with iliac bone or a metal cage (n = 2); combined ASF with PSF (APSF) (n = 4); and laminotomy (LM) without fusion (n = 4).p < 0.05 denoting significance. Inter- and intraobserver reliabilities were assessed using intraclass correlation coefficients (ICC). All calculations were performed using SPSS software . Power analysis were performed with EZR , which is a graphical user interface for R .Data are shown as mean ± SD. Differences between groups were examined by Wilcoxon signed rank test, Mann–Whitney U-test or chi-square test, with The study protocol was approved by the Human Ethics Review Committee of our University Medical Faculty  and strictly followed the Clinical Research Guidelines of the Ministry of Health, Labor, and Welfare of the Japanese Government.


Congenital cataract (CC) and congenital heart disease (CHD) are significant birth defects. In clinical practice, the concurrence of CC and CHD is frequently observed in patients. Additionally, some monogenic diseases, copy number variation (CNV) syndromes, and diseases associated with intrauterine infection involve both cataract and heart defects. However, little is known about the association between CC and CHD. Here, we characterised the demographic, clinical, and genetic features of patients with CC and heart defects.Medical records for 334 hospitalised patients diagnosed with CC were reviewed. Demographic and clinical features of patients with CC with and without CHD were compared. Clinical and genomic information for patients with ‘cataract’ and ‘cardiac defects’ were reviewed from Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER). Microarray-based comparative genomic hybridisation and whole-exome sequencing were performed in 10 trio families with CC and CHD to detect de novo genomic alterations, including copy number variants and single nucleotide changes.GJA8 responsible for CC.In a retrospective analysis of 334 patients with CC over the past 10 years at our hospital, we observed a high proportion of patients (41.13%) with CHD . The CC with CHD group had higher incidences of preterm birth and Down’s syndrome than the CC without CHD group. Atrial septal defect was the most frequent heart defect. A total of 44 cases with cataracts and heart diseases were retrieved from Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER). In total, 52 genomic alterations were reported, 44% of which were de novo germline variants. In the 10 trio families with CC and CHD, we found de novo CNVs responsible for two well-known chromosomal disorders and identified a novel pathogenic mutation in We observed significant associations between CHD and CC in our 10-year patient cohort. Based on the cohort and data from DECIPHER, developmental syndromes in some patients were due to genetic defects, thus explaining the concurrence of CC and CHD. Additionally, we detected de novo mutations as an independent cause of cataracts. Our findings suggest that developmental syndromes in patients with CC deserve more attention in clinical practice by ophthalmologists.The online version contains supplementary material available at 10.1186/s13023-021-01873-7. Congenital cataract (CC) is one of the main causes of visual impairment and blindness in children. Opacity of the lens prevents light from entering the eye, thereby stunting the retinas and optic nerves and leading to amblyopia or blindness. About a quarter of CC cases are caused by genetic factors , 2, and Furthermore, among patients with CHD who visit cardiology departments, a portion also show ocular abnormalities involving CC . HoweverBCOR mutations [FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome by FBXL4 mutations [AGK mutations [NHS mutations [Some aetiological bases, including genetic mutations, underlying CC and CHD have been revealed respectively. More than 100 genes and nearly 200 loci have been identified in monogenic forms of CC . Copy nuutations , Sengersutations , Nance-Hutations , Down’s utations , and conutations . The freIn the present study, we characterised the demographic and clinical features of patients with CC and heart defects by reviewing the 10-year patient cohort at our hospital. We also attempted to identify the individual and/or common causes underlying these two defects based on genetic findings for reported patients and newly recruited trio-families.P = 0.002). Additionally, 2.94% of patients in the CC with CHD group had pregnancy with rubella, diabetes, rash, or cold, which were not reported in the CC without CHD group; however, there were no statistically significant differences in these conditions. Cataracts could be inherited from parents or occur de novo. There was no difference in the family history of CC between CC with CHD and without CHD groups. However, cataracts typically occurred de novo in both groups, with frequencies of 95.1% (N = 97) and 90.41% (N = 132) in CC with CHD and without CHD, respectively. For patients who had affected parents, maternal inheritance was more common. As for ophthalmic manifestations, most patients had bilateral cataracts and presented pure lens opacity, and there was no difference between the two groups. We also observed other ophthalmic manifestations in both groups, such as vitreous opacity, strabismus, and nystagmus; however, the frequencies of these phenotypes did not differ between the two groups. Developmental abnormalities were found in some patients, including brain CT abnormalities, diagnosed Down’s syndrome, developmental retardation, deafness, limb malformation, mental retardation, external auditory canal atresia, and anal atresia. It is noteworthy that four patients were diagnosed with Down’s syndrome in the CC with CHD group, and the frequency differed between the two groups (P = 0.028). Some other extraocular and extracardiac diseases/symptoms were occasionally identified in each group, but the differences in frequencies between groups were not significant.Based on early observations that CHD is frequently associated with CC, echocardiography for evaluating heart defects has become a routine preoperative examination for patients with CC in the past 10 years. In total, 334 patients with CC referred to our hospital in 2010–2020, including 248 who underwent echocardiography examination. We found that 41.13% of patients with CC (102/248) also had CHD. For the reason that left-to-right shunt in echocardiography also represent innocent CHD, such as small ASD or PFO , the observed CHD in this study include major heart structural defect and innocent CHD which cannot be classified as either physiologic or pathologic –22. AccoWhen focusing on cardiac phenotypes in the CC with CHD group, atrial septal defect (ASD) 73, 71.57%)  was the most common type of heart disease, followed by patent ductus arteriosus  and ventricular septal defect (VSD) . Most patients had a single type of heart defect , and a few patients had complex heart defects    in patient 3  indicated that it was deleterious, with a D: A algorithm score of 22:23 and a damaging score of 0.96, and the mutation was extremely rare in public datasets, with no reported allele frequency. Mutations in POLG are responsible for progressive external ophthalmoplegia, which includes cataracts as an additional symptom. However, patient 8 with a POLG mutation did not present weakness of the external eye muscles or exercise intolerance. Biallelic mutations of YIF1B could lead to an autosomal recessive neurodevelopmental disorder, Kara-Barakat-Masson syndrome (KABAMAS), characterized by global developmental delay, motor delay, ocular abnormalities, and nervous system change [YIF1B, and present no typical KABAMAS clinical manifestations. Other genes with detected pathogenic or likely pathogenic mutations were either not associated with any diseases  or associated with unrelated phenotypes (LIPC)  and/or whole-exome sequencing (WES). Since the patients were born to healthy parents and no pregnancy complications were reported, we focused on de novo genomic alterations that were large in size or had potential deleterious effects. These alterations were only detected in patients but not in their unaffected parents. De novo CNVs larger than 100 kb and de novo SNPs or insertions/deletions (InDels) interpreted as pathogenic or likely pathogenic are listed in Table m change . The vism change . PatientOver 20 years of experience in ophthalmology has revealed that CC is frequently associated with CHD. However, barely any study was performed to describe and explain this observation , 9. As oBCOR mutations [BCOR acts as a pivotal multisystem transcriptional regulator during early embryogenesis. Recurrent rearrangements of chromosome 1q21.1 and Down's syndrome are both caused by chromosomal mutations involving many different genes, and congenital rubella syndrome is caused by multisystem interference by infection in early development. Accordingly, we reasoned that early in embryonic development, the eye and heart might be regulated by a set of reciprocally regulated genes, genes that function independently in these organs might be located in close proximity on the chromosome, or the foetus might be susceptible to infection.CC with CHD is often reported in rare syndromes with well-defined genetic or chromosomal mutations or in syndromes resulting from intrauterine infection, such as OFCD syndrome caused by utations , recurreutations , Down's utations , and conutations . BCOR acBCOR mutations for OFCD syndrome , and the 11q21.1 deletion for 1q21.1 rearrangements of chromosome 1q21.1 (DECIPHER ID 323303).We also reviewed genomic findings for 44 cases with CC and CHD in DECIPHER. We found no significant difference in sex ratio, the type, and proportion of heart disease, or clinical features between these cases and our patient cohort. The main types of heart disease were ASD and VSD. Genomic changes, including structural and nucleotide changes, were distributed across different chromosomes, showing no obvious enrichment . GJA8 encodes a gap junction protein, which is crucial for maintaining ionic and water balance and for the transparency and optical properties of the lens [GJA8 and heart defects, although other gap junction protein-coding genes, GJA1 and GJA5, play crucial roles in heart development and function [We also identified a novel pathogenic mutation in the the lens . It is afunction –44. It iIn this study, we observed significant associations between CHD and CCs in our 10-year patient cohort. Detailed clinical and genomic findings for both the patient cohort and cases in DECIPHER were evaluated. We found some patients had developmental syndromes due to genetic defects, especially CNVs affecting contiguous or reciprocally regulated genes involved in eye and heart development. Our findings suggest that developmental syndromes in patients with CC are underestimated in clinical practice by ophthalmologists. We also detected several de novo mutations in trios; however, we could not determine whether the de novo mutations detected in our trios are common or independent causes of heart and ocular anomalies. Comprehensive genetic analyses based on larger sample sizes and functional studies could provide further insight into the association between CC and CHD.The medical records for 334 hospitalised patients diagnosed with CC in the Department of Ophthalmology of Shengjing Hospital, Shenyang, China, from 2010 to 2020 were reviewed. Gender, age, family history, past medical history, birth status, ocular and systemic physical examination, and imaging data were collected. In total, 248 patients completed echocardiography and were included in statistical analyses and the collation of medical records. In addition, 10 trio families we recruited in 2018–2019. In these trio families, patients with CC and CHD were born to their healthy parents and no other family history or pregnancy complications were reported. Peripheral blood from patients and parents was collected for genetic analysis after obtaining informed consent. The study was approved by the institutional review board of China Medical University.P < 0.05 were considered statistically significant. Statistical analyses were performed using IBM® SPSS® Statistics version 24 .Clinical data for 248 patients who underwent echocardiography were reviewed. General information, including date of birth, gender, and family history were collected. Cataracts in one or both eyes and other ocular abnormalities were identified based on the two-dimensional or three-dimensional ocular ultrasound and ophthalmic examinations. CHD was diagnosed by echocardiography and relevant systemic examinations. All 248 patients were divided into two groups, CC with or without CHD. Categorical variables were compared between the two groups by a chi-squared test or Fisher's exact test, and values of Reported clinical and genomic information for patients with ‘cataract’ and ‘cardiac defects’ were reviewed from the Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER). The term ‘cataract’ was used for the search and patients with cardiac defects were manually selected according to the documented phenotypes. Clinical information  and genomic findings  for 44 patients were reviewed and analysed.http://dgv.tcag.ca) and DECIPHER (https://decipher.sanger.ac.uk/) were used to determine the pathogenicity of candidate CNVs as follows. (1) A full CNV region reported in the general population in DGV n ≥ 3 times or a CNV region without genes was defined as a benign CNV. (2) A full CNV region reported in the general population in DGV n < 3 times and including genes overlapping with CNV syndromes reported in DECIPHER or reported as causes of a similar phenotype in PubMed and OMIM was defined as a pathogenic CNV. (3) The remaining were defined as uncertain pathogenic [http://varcards.biols.ac.cn/). Sanger sequencings were used to verify candidate SNPs/InDels.De novo genomic alterations were detected in 10 CC with CHD trios at a genome-wide scale. CNVs were detected by microarray-based comparative genomic hybridisation (aCGH), and whole-exome sequencing (WES) was used to detect SNPs and InDels. When DNA was not sufficient to detect CNVs using aCGH, WES results were used to detect CNVs using the CoNIFER tool based on read depth . Geneticthogenic –48. For Additional file 1: Figure 1. aCGH results for CNVs of uncertain pathogenicity using the Agilent Cytogenomics tool and Sanger sequencing results for other pathogenic/likely pathogenic de novo SNPs. A–E show the 10q11.21 deletion in patient 4, 17q21.2 duplication in patient 5, 13q12.13 duplication in patient 6, 7q22.3 deletion in patient 7, 4q34.3-q35.1 duplication in patient 8, in order. F–J represent Sanger sequence results for mutations in PRAMEF12 (c.1372C>G p.R458G) and LIPC (c.317C>T p.A106V) in patient 5, POLG (c.2669A>C p.D890A) in patient 8, MDN1 (c.16697A>G p.Y5566C) in patient 9, and YIF1B (NM_001039672 c.709G>A p.V237I) in patient 10Additional file 2: Table 1. Genomic findings in patients with cataract and heart diseases in DECIPHER databaseAdditional file 3: Table 2. Genomic location of CNVs in patients with congenital cataract and congenital heart diseases in trio families