Parkinson's disease adversely affects function and quality of life, leading to increased mortality. The practice of Tai Chi has been associated with multifaceted improvements in health-related fitness. Considering the limited number of clinical studies included in previous reviews, inconsistent methodological quality, and inconclusive results, this meta-analysis aims to assess the effects of Tai Chi in patients with Parkinson's disease.  Four English language databases and four Chinese databases were systematically searched for existing randomized controlled trials (RCTs) of Tai Chi in Parkinson's disease from database inception through August 1, 2020. Methodological quality was appraised with the Cochrane Risk of Bias tool. A meta-analysis of comparative effects was performed using the Review Manager v.5.3 software.  Seventeen published RCTs totaling 951 subjects were included. Results showed that Tai Chi has a statistically significant effect on the outcomes of gait velocity, unified Parkinson's disease rating scale (UPDRS) motor score, activities-specific balance confidence (ABC) score, and Berg Balance Scale (BBS). The effects on the Timed Up and Go Test (TUGT) and Parkinson's Disease Questionnaire-39 (PDQ-39) were not statistically significant.  This systematic review and meta-analysis of Parkinson's disease and Tai Chi suggests Tai Chi is a relatively safe activity that can result in gains in general motor function and improve bradykinesia and balance. It has no statistically significant advantage for quality of life and functional mobility. Further randomized trials with larger sample sizes and of higher methodological quality are needed to confirm these results and to assess the feasibility of Tai Chi intervention for potential different clinical applications. Parkinson's disease (PD) is globally the second most common elderly neurodegenerative disease, characterized pathologically by degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies . ParkinsTai Chi is a popular exercise in Chinese society, consisting of slow, gentle, and flowing movements that involve strengthening, balance, postural alignment, mind concentration, relaxation, and breath control . Tai ChiHowever, considering the limited number of clinical studies included in previous reviews, inconsistent methodological quality of the published studies, and mixed and inconclusive results, this meta-analysis aims to assess the effects of Tai Chi in patients with Parkinson's disease.This study was designed following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systemic Review and Meta-Analyses (PRISMA) .The following electronic databases were searched from their inception until 1 August 2020: PubMed, Embase, Cochrane Library, and Web of Science (for relevant English literature) and China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal (VIP), and Chinese Biomedical Literature Database (CBM) (for relevant Chinese literature). Search strategies were combined as follows: for English databases, free text terms ((Tai Chi) OR (tai ji) OR (tai ji quan) AND (Parkinson's Disease OR Parkinson) were applied and for the Chinese databases, the terms were ((tai ji) OR (tai ji quan) AND pajinsen). Only Chinese and English articles were considered for this meta-analysis. The complete search strategy is shown in the Supplementary Material.The inclusion criteria for each study were as follows: (1) population consisting of participants with or without Parkinson's disease; (2) using any form of Tai Chi as an intervention; (3) having a control group, other treatments, or another exercise intervention as a comparison group; (4) reporting outcomes of symptoms related to Parkinson's disease or outcomes of exercise training; and (5) using a randomized controlled trial (RCT). Exclusion criteria were as follows: (1) not writing in English/Chinese; (2) having insufficient data or irrelevant outcomes; (3) and having no available full text.The data were extracted by two independent reviewers (Wu and Hou), who assessed all the studies based on the predesigned standards. Data were checked by a third investigator (Yu). Extracted data from the included studies contained the following information: author name, year of publication, sample size, mean age, interventions , and main outcome measures. We assessed the included studies' quality on the basis of Cochrane Collaboration's risk of bias tool. There were three scores for each item  according to the following criteria: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) incomplete outcome data, (5) selective reporting, and (6) other biases.I2 statistic [I2 ≤ 50% or Chi2test P < 0.10); otherwise, a random-effects model was employed. Potential sources of heterogeneity were identified using sensitivity analyses conducted by omitting one study in turn and investigating the influence of a single study on the overall pooled estimate. A P value <0.05 was considered statistically significant. Publication bias was detected by Egger's regression asymmetry test.All data and statistical analyses were combined and performed using Review Manager v.5.3 software . The mean difference (MD) with 95% confidence interval (CIs) was used to analyze continuous outcomes. We calculated the mean and standard deviation according to the calculation method mentioned in Cochrane Handbook version 5.1.0, chapter 16.1.3.2: imputing standard deviations for changes from baseline. Heterogeneity across studies was tested with the chi-square test and the Higgins tatistic . The fixDatabase searching retrieved a total of 711 studies (486 English literature studies and 225 Chinese literature studies). After removing duplicate entries, 385 studies were screened. 339 studies were excluded based on the abstract and title because of (1) being irrelevant to the theme; (2) no RCT; (3) no relevant outcomes; (4) meeting reports; and (5) no complete report. 46 potentially relevant studies were identified for full-text analysis. 29 were excluded due to (1) no available data; (2) incorrect random method; (3) subjects having other complications; and (4) intervention combined with other methods. After screening, a total of 17 studies were included , 15–28; Figures Sensitivity analyses were performed based on excluding studies with low quality, small sample sizes, and trials with different control groups to explore potential sources of heterogeneity. For each of these results with high heterogeneity, a separate sensitivity analysis was performed.P=0.009; P for heterogeneity = 0.0004; I2 = 74%) . Second, one study [P=0.01; P for heterogeneity = 0.0002; I2 = 85%). Finally, one study [P=0.005; P for heterogeneity = 0.04; I2 = 76%). A total of three sensitivity analyses reached similar results, reflecting that the results presented here are stable.Six studies , 23, 25 shown in . Sensitine study  with a sP=0.12; P for heterogeneity <0.001; I2 = 75%). First, two studies [P=0.002; P for heterogeneity = 0.03; I2 = 56%). Then, one study [P=0.003, P for heterogeneity = 0.05; I2 = 53%). Finally, three studies [P=0.001, P for heterogeneity = 0.89; I2 = 0%). Therefore, studies [Ten studies , 26, 27  studies , 27 with studies , 17, 26  studies , 27 withP=0.06; P for heterogeneity = 0.02; I2 = 69%)  or one study [P=0.06; P for heterogeneity = 0.05; I2 = 74%), the pooled results showed no change in statistical heterogeneity, but results for both changed.Four studies , 20, 28 2 = 69%) . After ene study  with a sP < 0.001; P for heterogeneity = 0.15; I2 = 48%)  .P=0.04; P for heterogeneity = 0.04; I2 = 59%) . Second, one study [P=0.24; P for heterogeneity = 0.04; I2 = 69%). Finally, one study [P=0.24; P for heterogeneity = 0.04; I2 = 76%).Five studies , 19, 25 2 = 59%) . First, ne study  with a sP < 0.001; P for heterogeneity = 0.09; I2 = 40%)  .Here, we presented a systematic review and meta-analysis that included 17 published RCTs totaling 951 subjects. This work aimed to address the effect of Tai Chi in the management of PD through the evaluation of Tai Chi on motor function, balance, and quality of life. The results provide a new level of evidence for clinical professionals.P < 0.002), which is consistent with previous work [P < 0.001), which surpasses the MCRD. This suggests there is stable evidence that Tai Chi is effective in improving motor function in patients with Parkinson's disease.The UPDRS motor scale is one of the most commonly used indicators of motor function for Parkinson's disease and was therefore chosen for our meta-analysis to determine the improvement of the general motor function after Tai Chi intervention . Previouous work ,10. AfteTai Chi is often classified as a low-to-moderate intensity physical activity and is a suitable exercise for individuals in the general population , 24 espeWith the progression of Parkinson's disease, patients have muscle stiffness, lose postural stability, and have gait dysfunction, leading to frequent falls, reduced quality of life, and increased mortality –5. We coP=0.009), and sensitivity analysis stability in the results. Tai Chi improves lower extremity muscle strength, a decisive factor of gait velocity [Many previous studies have reported that the abnormal walking pattern observed in people with PD is characterized by short, shuffling steps . Individvelocity . Thus, avelocity . Furthervelocity , 33; theP ≤ 0.001) and ABC  than in controls, consistent with previous work [Previous studies suggest that BBS and ABC are reliable indicators to measure generic balance performance . Our metous work . Sensitious work . These ious work . We augmous work , 36, to P=0.24). This is because the studies included in our meta-analysis have high heterogeneity and inconsistent results. The severity of Parkinson's disease may lead to a potential ceiling effect precluding larger magnitude improvements [TUGT is a functional mobility balance assessment tool that accurately predicts recurrent falls  and is rovements . TherefoPD-related quality of life reflects the overall influence of a disease on patients' physical mobility, daily activity, social functioning, psychological wellbeing, and cognition . Stable This meta-analysis has several limitations. First, the sample sizes of some included RCTs were quite small, and the relatively small number of eligible RCTs in the analysis may lead to limited power and the precision of the findings. Second, blinding of participants or care providers may be difficult in exercise interventions, and the high risk of performance and detection bias might weaken the strength of the evidence. Finally, the diversity of the type and parameters of Tai Chi in the included RCTs also limits the ability to make firm conclusions regarding the specific recommended Tai Chi exercise prescription for each chronic condition.In conclusion, this systematic review and meta-analysis article of Parkinson's patients suggests that there exists stable evidence to suggest Tai Chi is a relatively safe program resulting in gains in general motor function and improvements in bradykinesia and balance. However, no statistically significant advantage for quality of life and functional mobility was observed. These results provide new evidence for PD management. Further randomized trials with larger sample sizes and of higher methodological quality are needed to confirm these results and to assess the feasibility of Tai Chi intervention for different clinical application purposes.


Although MRI is the gold-standard imaging method in the diagnosis of spondylodiscitis, role of follow-up imaging is debated and there can be discrepancies with regard to the significance of bony or soft tissue responses to treatment. Purpose of our study is to test whether the MRI changes on follow-up imaging correlate with laboratory findings of treatment response.A total of 48 patients with pyogenic spondylodiscitis who underwent baseline and follow-up MRI were retrospectively reviewed. The extent of bone marrow edema, paravertebral soft tissue inflammation, and disc height were compared on baseline and follow-up MRIs with the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels obtained from the medical records at baseline and on follow-up. Relationships between the MRI and laboratory changes were analyzed using the Spearmann correlation test.n = 19, resolving: n = 19, and aggravated: n = 10), there was significant correlation between the laboratory results and the changes in the bone and soft tissues . The correlation was best with soft tissue changes (rho: 0.48) followed by bony changes (rho: 0.41). Based on the ESR , the correlation was stronger with bone changes  than it was with soft tissue changes .The mean MRI follow-up period was 42.25 days. Based on the CRP (resolved: Follow-up MRI findings of pyogenic spondylodiscitis show variable tissue responses. CRP was best correlated with soft tissue changes, while ESR showed the best association with bony changes. MRI is the gold-standard imaging method in the diagnosis of spondylodiscitis, given its high sensitivity and specificity –4. The cThe management of spondylodiscitis is focused on eradicating the infection with antibiotic therapy. Clinical signs and symptoms, as well as laboratory data, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are typically used for disease monitoring. The appropriate discontinuation of antibiotic therapy depends on symptom improvement or resolution, as well as ESR or CRP normalization . The resThe current management algorithm for spondylodiscitis relies on a patient’s symptoms and laboratory findings as therapeutic response markers . HoweverThe purpose of this study was to test the hypothesis that MRI changes in the bone, soft tissue, and disc on follow-up imaging correlate with laboratory findings of treatment response.This retrospective study was approved by the institutional review board at our institution. Between September 2006 and December 2014, patients who were diagnosed with pyogenic spondylodiscitis who had undergone baseline and follow-up MRI were selected. At our hospital, the policy of when to follow up MRI is not strictly established. Some infection specialists performed follow up MRI before patient discharge after antibiotic treatment as a comparative study regardless of symptoms while others ordered only when clinically aggravation is suspected. Patients were excluded if they had a history of tuberculosis spondylitis, had undergone surgery, or had an infection after spine surgery. A total of 48 patients  were included.MRI was performed with 1.5-T  or 3.0-T  scanners. The imaging sequences included the T1-weighted and T2-weighted images for the axial and sagittal planes and contrast-enhanced T1-weighted fat suppressed axial and sagittal planes. Nine baseline MRIs were obtained from other institutions. Contrast enhancement was not performed in six baseline studies including four exams from other institution. Two musculoskeletal radiologists reviewed the pair of baseline and follow-up MRIs in consensus. The radiologists were blinded to other clinical information. The bone findings were assessed according to the volume of bone marrow enhancement or edema. The cases were separated into three subgroups  based on the baseline MRI. The follow-up MRIs were graded as improved, equivocal, or worse (from baseline). In case of multi-level involvement, most severely involved level was assessed. The disc height of the involved segment was compared between the baseline and follow-up MRIs, and graded as equivocal or worse. The soft tissue findings were determined as follows. Improved meant that there was decreased signal abnormality or abscess size in the paraspinal/psoas muscle, and/or epidural space compared with the baseline imaging findings. Equivocal results indicated that some areas improved while others worsened, or there was no substantial change. Worse findings reflected increased signal abnormality or abscess size in the paraspinal/psoas muscle, and/or epidural space or new levels involved, compared with the baseline imaging findings . CompariThe available medical records of the baseline and follow-up ESR and CRP levels were obtained. The values of the closest date with MRI examination were selected. Regarding our protocol of laboratory tests, ESR and CRP were routinely monitored after approximately 4 weeks of antimicrobial therapy. Three groups were established based on follow-up laboratory values: normalized (resolved); decreased but not normalized (resolving); and increased (worsened). Figure P values < 0.05 were considered statistically significant.The relationship between changes in the laboratory findings and changes in the MRI findings were analyzed using the Spearmann correlation test. Statistical analyses were performed using SPSS version 20.0 . n = 22), Staphylococcus aureus (n = 12), S. epidermidis (n = 7), methicillin-resistant S. epidermidis (n = 1), Klebsiella pneumoniae (n = 3), Escherichia coli (n = 2), and Corynebacterium striatum (n = 1). Eighteen cases were confirmed by blood culture and eight cases were confirmed by targeted biopsy or aspiration. The involved spinal levels included the cervical spine (n = 1), thoracic (n = 5), thoracolumbar (n = 4), lumbar (n = 34), and lumbosacral (n = 4). CRP resolved in 19 cases (1.9 ± 1.4 mg/L), and worsened in 10 cases (83.8 ± 76.7 mg/L). ESR improved in eight cases (8.0 ± 4.9 mm/hr), and worsened in 18 cases (57.5 ± 21.3 mm/hr). Eight cases showed improvement in both CRP and ESR, while five cases showed worsening of both CRP and ESR. The mean intervals between the laboratory examinations and MRI were 2.69 days for CRP and 2.73 days for ESR in the baseline studies, and 3.1 and 1.83 days on follow-up examinations, respectively.In our subject group, the mean period between the baseline and follow-up MRIs was 42.25 (± 22.25) days. The pathogens involved in the spondylodiscitis were identified as follows: culture-negative , but not with changes in disc height (p = 0.072). This correlation was best with soft tissue changes (rho: 0.482), followed by bony changes (rho: 0.408).Based on the CRP results, the number of subjects in the resolved, resolving, and worsened group were 19, 19, and 10, respectively. The bone findings worsened (6 of 19) or were equivocal (6 of 19) in the resolved group. In contrast, the soft tissue findings were improved (14 of 19) in many of the cases in the resolved group Figs.  and 3. Tp = 0.001 and 0.007, respectively), but not with the disc changes (p = 0.507). The correlation was better with the bony changes (rho: 0.447) than with the soft tissue changes (rho: 0.387).Based on the ESR results, the numbers of subjects in the resolved, resolving, and worsened group were 8, 22, and 18, respectively. The bone findings improved 3 of 8) or were equivocal 4 of 8) in the resolved subjects, while they were equivocal (7 of 22) or worse (11 of 22) in the resolving group . These changes may have changed the subgroups (e.g. resolving to resolved group) by even a few day intervals. Furthermore, we did not account for differences caused by the etiologic pathogens. Different pathogens and antibiotics may alter the clinical course; however, due to the small number of subjects, we could not consider the differences caused by the pathogens and antibiotics. Finally, we analyzed the MRI using a consensus manner without assessing inter-observer agreement.Follow-up MRI findings of pyogenic spondylodiscitis may show variable tissue responses. CRP was best correlated with soft tissue changes, while ESR had the greatest association with bony change. Knowledge regarding these relationships may be helpful in deciding or interpreting follow-up imaging. Like ESR normalizes more slowly than CRP, bone abnormalities on MRI takes more time to be normalized than soft tissue abnormalities. If ESR or CRP increases, follow-up MRI can be required to differentiate the condition is resulted from treatment failure or problem other than spondylodiscitis.


A retrospective and comparative study of transverse process strut  compared with titanium mesh cages  in the reconstruction of thoracic stability through the one-stage posterior approach to treat single-segment tuberculosis.Sixty patients from January 2013 to December 2016 were analyzed and divided into two groups. The following data of clinical and radiographical assessments were observed preoperatively, postoperatively and during follow-up (FU).P > 0.05). The bony fusion times were 5.85 ± 1.82 months and 8.4 ± 5.1 months with significant difference(P < 0.05). Comparing with the preoperative values, the kyphosis angle significantly improved, but at the final FU the significant difference was found between the groups (P < 0.05). The loss of the angular correction and the fused segmental height in group A was lower than that in group B (P < 0.05).The patients were followed up for an average of 50.20 ± 25.10 months (Group A) and 48.70 ± 27.30 months(Group B) without significant difference. No significant differences were found in the mean of operation time in minutes, blood loss, hospitalization time, drainage and follow-up duration between the groups. The VAS, ODI, ESR and CRP were reduced significantly at the final FU compared with the preoperation values and there was no significance between the groups. Neurological deficits were improved in all patients at the final FU without significant difference between the groups(TPS had a better osseous fusion rate, effective maintenance of fused segment stability which is a good bone graft for surgical management of single-segment thoracic spinal tuberculosis. Human tuberculosis (TB) is a chronic and ancient disease characterized by weight loss and it is a cause of death and most cases of tuberculosis occur in developing countries. According to the World Health Organization (WHO), TB causes 1.81 million deaths in Asia each year and China has 78% new cases every year . In receWhen severe bone destruction, kyphosis, or nerve deficit occurs, surgical management still plays a significant role in curing spine tuberculosis. After debridement and decompression, many interbody bone grafts are used for to reconstruct spinal stability, such as the iliac crest which is the gold standard or fibula grafts and titanium mesh cages (TMCs) , 10. AutThis study was approved by the Institutional Review Board of The First Affiliated Hospital of Chongqing Medical University. Two treatment plans were involved in the routine clinical care. When communicating with patients before surgery, the advantages and disadvantages of the two types of management were fully introduced, so the patients could choose the right treatment for themselves. All surgical procedures were performed by the same senior surgeon.From January 2013 to December 2016, 60 patients with single-segment thoracic spinal tuberculosis were treated and reviewed retrospectively in our department. In group A, 30 patients received TPS for the reconstruction and in group B, 30 patients underwent TMCs. Inclusion criteria: adult single-segment thoracic spinal tuberculosis who were indicated for surgery: increasing kyphosis, neurological deficits, bone destruction affecting the stability, the bone damage of the infected vertebral body did not exceed 1/2 the vertebral height, one-stage posterior approach for internal fixation, and reconstruction. Exclusion criteria: active tuberculosis of the lung and extrapulmonary organs, multiple-segment thoracic vertebral tuberculosis, cancer.Chemotherapy with an HREZ standard chemotherapy regimen comprising isoniazid(H)(5-10 mg/kg/day), rifampicin(R)(10 mg/kg/day), ethambutol(E)(15 mg/kg/day), and pyrazinamide(Z)(25 mg/kg/day) was administered 3-4 weeks before the operation. Surgery was performed when the patient’s erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and temperature recovered to normal or nearly normal. If the patient’s neurological condition deteriorated rapidly, an urgent salvage operation was performed.In group A, the patient was placed in prone position after the administration of conventional tracheal anaesthesia. The posterior elements, including the lamina, facet joint and transverse process, were exposed with a midline incision. Pedicle screws were fixed on the basis of imaging and C-arm X-rays to ensure their accuracy. After decompression and thorough debridement, the adjacent transverse process was cut off and trimmed to round cortical bone and double-sided cancellous bone Fig. . DependiThe drainage tube was removed when less 50 ml/day was drained from the surgical site. The patients received oral HREZ chemotherapy after surgery for 12 months, followed by 6-month regimens of HRE chemotherapy (12HREZ/12-18HRE). Rehabilitation training and nutritional support began the day after surgery. Ambulation with a brace was allowed the third day after surgery. All patients were evaluated clinically and radiologically at one week and 3, 6 and 12 months after surgery and once a year thereafter.For all patients, the following data were observed preoperatively, postoperatively, and during follow-up (FU): (1) the operation time, surgical blood loss, hospitalization time, drainage, bone fusion time  kyphAccording to the Cobb method, the kyphosis angle was defined as the angle formed between the superior endplate of the upper vertebral body and the inferior endplate of the lower vertebral body Fig. . Loss ofp value < 0.05.All statistic data were analysed with SPSS version 22.0 statistical soft ware . Quantitative data are presented as means and standard deviations. Repeated measures t-test was used for the statistical analysis of differences in mean values, and the chi-squared test was used for categorical data. Statistical significance was defined as a P > 0.05) (Table P > 0.05) (Table The patients were followed up for an average of 50.20 ± 25.10 months (group A) and 48.70 ± 27.30 months (group B) without significant difference. No significant differences were found in the mean of operation time in minutes, blood loss, hospitalization time,drainage and follow-up duration between the groups(P < 0.05). The loss of angular correction and fused segmental height in group A was lower than that in group B (P < 0.05) , fistula (one case in group A), water electrolyte imbalance , superficial infection (one case in group B) and mild intestinal obstruction . Implant subsidence occurred in five cases  and the difference between groups was not significant.The TB incidence is rising worldwide with 9 million new cases and 2 million deaths per year caused by the increased incidence of AIDS and resistance to anti-tuberculosis drugs [1–6]. Spinal TB remains a common spinal infection. Due to vertebral body collapse or severe deformity, surgical options may be considered appealing in conjunction with the more common conservative treatment options, such as anti-tuberculosis drugs, which are vital. Formal, appropriate and long-term anti-tuberculosis chemotherapy, strict bed rest, and supportive treatment are essential therapies –12. DespAfter debridement and decompression, many types of interbody bone grafts may be used to reconstruct the anterior and middle column. Autogenous bone graft, such as an iliac crest or fibula graft, can achieve good bony fusion, however, they can lead to complications at the donor site, such as pain, blood loss, hematoma and unhealed wounds. Allografts have been used to avoid donor site complications, but they are associate with decreased arthrodesis rates and increased graft collapse rates. Recently, a number of studies have reported that TMCs showed significant potential for reliable spinal reconstruction, offering excellent bone fusion, adequate sagittal profile maintenance and a low rate of implant-related complications. In our study, TMCs were filled with cancellous bone from excised vertebral lamina and articular processes, which allowed their design to be individualized according to different bone defects , 19. FurCui et al. reported that the thoracic transverse process was longer, thicker, higher and larger than the transverse processes of vertebrae at other spinal levels and could be used as a bone graft. Maria E. K.et al. and other studies demonstrated the quantitative three-dimensional anatomy of the thoracic vertebrae and the discs. Given these anatomical features, the transverse process satisfies the needs of grafts if the bone damage of the infected vertebral body did not exceed 1/2 the vertebral height , 22. TheThe results of this study showed that when used as a bone graft reconstruct the stability of single-segment thoracic tuberculosis, TPS has a better rate of osseous fusion than TMCs and can provide effective restoration and maintenance of fused segment height and alignment and a lower rate of complications. TPS is an ideal reconstructed bone graft for thoracic single segmental stability. However, we declare that there were a few limitations in the study. First, the study didn’t consider the intra and inter observer differences which was associated with bias. Second, the retrospective nature of the small-sample study may be associated with bias. Third, if the bone damage of the infected vertebral body did exceed 1/2 the vertebral height, TPS was not long and strong enough to stabilize which could be prone to subside, or even result in kyphosis and the TMCs or iliac bone graft could be more suitable. Fourth, we need to perform the biomechanical tests between the groups to know the difference of the strength, which could confirm that TPS meets the mechanics needs. In the future, the prospective, randomized studies with long-term follow-up periods are needed.


Multivariate analysis showed that age > 65 years, multiple tumors, RFA, albumin bilirubin grade > 1, and the occurrence of major peri-procedural morbidity were the independent risk factors that are predictive of poor OS. In conclusion, SR could be recommended as a first-line treatment modality for HCC patients with EGV if the patients are carefully selected and liver function is well preserved.There has been insufficient investigation of the differences in long-term outcomes between surgical resection (SR) and radiofrequency ablation (RFA) among patients with hepatocellular carcinoma (HCC) and esophagogastric varices (EGV). We retrospectively enrolled 251 patients with treatment-naïve HCC and EGV who underwent SR or RFA as a first-line treatment. Prognostic factors were analyzed using a Cox proportional hazards model. A total of 68 patients underwent SR, and the remaining 183 patients received RFA. Patients who underwent SR were younger, had better liver functional reserves, and had larger tumors. After a median follow-up duration of 45.1 months, 151 patients died. The cumulative 5-year overall survival (OS) rate was significantly higher among patients who underwent SR than those treated with RFA (66.7% vs. 36.8%,  Worldwide, it is estimated that around 745,000 patients die of HCC annually1. Vaccination programs for hepatitis B virus (HBV) have been successfully implemented for newborns, and antiviral therapy is widely prescribed for chronic HBV or hepatitis C virus (HCV) infection. Thus, the incidence and mortality of HCC have seemed to decline in several traditionally high-risk countries in East Asia3. Nevertheless, the prevalence rates of HCC are still rising in North America and Europe, especially among the elderly4. In the United States, the age-adjusted annual incidence rate of HCC increased from 4.4 to 6.7 per 100,000 individuals between 2000 and 20124. Moreover, the prevalence of HCC for patients on a waitlist for liver transplant increased from 6.4% in 2002 to 22.0% in 20175.Hepatocellular carcinoma (HCC) is the second leading cause of cancer death among males and the sixth among females6. For patients with HCC in stage 0 or A in the Barcelona Clinic Liver Cancer (BCLC) system, the recommended curative treatment modalities are liver transplantation, surgical resection (SR), and local ablation therapy according to the current guidelines for HCC management7. Among local ablation therapies, percutaneous radiofrequency ablation (RFA) could result in more reliable tumor ablation effects, fewer treatment sessions, lower rates of local recurrence, and higher overall survival (OS) rates than percutaneous ethanol injection therapy10. Moreover, due to the shortage of organs for liver transplantation, SR and RFA are the most commonly applied therapies for patients with early-stage HCC in daily practice11.With advances in surveillance programs for HCC, more and more patients are diagnosed of HCC at an early stage16. This might be due to differences in the etiologies, liver functional reserves, and tumor factors among the studies. These factors should be taken into consideration when choosing the optimal treatment modality for patients with early-stage HCC.Several studies have been conducted to compare the treatment efficacy and prognosis between SR and RFA for patients with early-stage HCC, but the results are inconsistent18. With the progression of liver injury and fibrosis, portal hypertension might develop over time. Esophagogastric varices (EGV) start to emerge when the hepatic venous pressure gradient (HVPG) level is greater than 10 mmHg, which is considered to indicate clinically significant portal hypertension (CSPH). This leads to the development of ascites, hepatic encephalopathy, and EGV bleeding with increases in HVPG levels. These conditions are recognized as hepatic decompensation20. Moreover, CSPH and EGV have been identified as poor prognostic factors for patients with cirrhosis or HCC22. However, the measurement of HVPG levels is costly and not applicable in most hospitals, so EGV has served as a surrogate for CSPH in clinical practice23.Most patients with HCC have an underlying advanced chronic liver disease, such as chronic HBV or HCV infection, alcoholism, or nonalcoholic steatohepatitis7. This is based on several studies that indicate that the presence of CPSH would increase the risk of postoperative liver failure and reduce the OS for HCC patients who undergo SR25.According to the current international guidelines for the management of HCC, SR is recommended for only patients with a single nodule of any size, good performance status, well-preserved liver function, and normal serum bilirubin levels, as well as a lack of tumor-related symptoms, CSPH, extra-hepatic spread, and major vascular invasion7. Nevertheless, thanks to the recent advances in perioperative management for patients with CSPH, the risk of surgery-associated death has been reduced26. Several studies have debated the role the SR in HCC patients with CSPH, and SR could yield acceptable long-term survival in this clinical setting29. Hence, for patients who have HCC concomitant with EGV, the benefits of SR in comparison to RFA have not been sufficiently investigated30. Therefore, we compared the outcomes of SR and RFA in HCC patients with EGV to elucidate this issue.Instead, local ablation therapy is recommended for HCC patients with CSPH or EGVp = 0.005). Liver functional reserves were better in the SR group, which had lower scores in the model for end-stage liver disease (MELD), more patients with Child–Pugh Grade A, more patients with albumin bilirubin (ALBI) grade 1, higher serum albumin levels, lower bilirubin levels, lower prothrombin time international normalized ratios (PT INRs), and higher platelet counts. Furthermore, tumor sizes were larger in the SR group than the RFA group .The baseline demographic data of the patients examined are shown in Table There were 251 patients who had EGV that was confirmed by an esophagogastroduodenoscopy (EGD). Regarding EGV status, 209 of these patients had esophageal varices (EV) alone at the time of HCC diagnosis, while 2 patients had gastric varices (GV) alone. The remaining 40 patients had both EV and GV. Moreover, 131 (52.2%) patients received prophylaxis therapy for EV bleeding, including 21 patients with non-selective beta-blockers (NSBB), 75 patients with esophageal variceal ligation (EVL) therapy and 35 patients with NSBB and EVL combination therapy.p = 0.092), and more patients received prophylaxis therapy for EV bleeding . However, among those who had high-risk varices, 23 patients (60.5%) patients in the SR group received prophylaxis therapy, while 92 patients (73.6%) received it in the RFA group (p = 0.179).Compared to the SR group, the RFA group had more cases of high-risk EV , but the rates of major morbidity were comparable between both groups . The 90-day mortality rates were 2.9% and 1.1% in the SR group and RFA group, respectively (p = 0.371).No patients in our cohort died during the operations, both the SR group and the RFA group. As shown in Tables p = 0.025).Among the 68 patients in the SR group, 63 patients underwent conventional open liver resection (OLR), including 15 patients with major resection (defined as resection of three or more segments). Among the 5 patients who underwent laparoscopic liver resection (LLR), 2 patients had two segmentectomies, and the other 3 patients had one segmentectomy. The patients who underwent major resection had more major morbidity than those who received minor hepatectomy . As shown in Table p = 0.002), having multiple tumors , RFA , ALBI grade > 1 , and the development of major peri-procedure morbidity .After a median follow-up duration of 45.1 (months interquartile range (IQR): 19.6–69.8 months), 151 patients died. In the SR group vs. the RFA group, the cumulative OS rates at 1, 2, 3, 5, and 10 years were 91.0% vs. 92.2%, 81.5% vs. 73.3%, 78.2% vs. 61.0, 66.7% vs. 36.8%, and 57.4% vs. 15.9%, respectively  and RFA  were associated with higher recurrence rates after therapy.After therapy, 169 patients developed tumor recurrence, and the median recurrence time was 15.2 (IQR 7.3–31.5) months. In the SR group, 49 patients had tumor recurrence with a median development time of 20.8 (IQR 12.4–38.5) months. Among patients who underwent RFA, 120 of them developed tumor recurrence within a median time of 11.9 (IQR 5.4–27.2) months. Patients who underwent SR had a significantly higher rate of recurrence-free survival (RFS) than who received RFA , large tumor masses, and the ablation of tumors in close proximity to heat-sensitive organs41.However, the recurrence rate after RFA is still high. For example, the 10-year RFS rate after RFA was only 12.4% in our previous report42. Therefore, it could result in better local tumor control than RFA. However, the risk of liver decompensation and mortality after the operation are concerns when performing SR for HCC patients with a poorer liver functional reserve. Several studies compared the outcomes between SR and RFA for patients with early-stage HCC43. Most of these studies demonstrated that SR could reduce the risk of recurrence and might provide superior OS to RFA, although some studies observed that the OS rates were comparable between SR and RFA12.In contrast, SR could have a higher chance of complete excision of not only tumor tissue but also the hepatic parenchyma around the tumor, which might have microvascular invasion and micro-metastases30. However, the patients enrolled in that study were limited to those with HBV-related HCC, and the ablation therapies included both RFA (79 patients) and microwave ablation (57 patients).Nevertheless, the differences in prognosis between SR and RFA for HCC patients with CSPH have not yet been investigated sufficiently. Qiu et al. demonstrated that SR is safe and could provide a better OS and RFS than ablation therapy for patients with HBV-related HCC and CSPHIn the current study, we enrolled HCC patients from all etiologies and compared the prognoses between patients who underwent SR and RFA. In the SR group, no patient expired during the surgeries, and only one patient died within one month due to post-operative liver failure. The patients who underwent SR had a higher rate of post-procedure morbidity than those in the RFA group, but the rates of major morbidity and 90-day mortality were not statistically different between the two groups. Notably, our cohort revealed that SR could offer better long-term prognoses than RFA among HCC patients with EGV in terms of OS and recurrence. This was further validated by the multivariate analysis. The results could provide robust evidence for performing SR as a front-line treatment modality for patients with HCC and EGV if they have well-preserved liver function.44. This finding is similar to those of a nationwide cohort from Japan45. However, the survival benefit of SR over RFA was persistent after adjusting for the confounding factors for prognosis in the multivariate analysis.The patients in our cohort who underwent RFA as the primary treatment modality were older and had a poorer liver functional reserve than those who underwent SR. Older patients might choose RFA because of the greater chance of comorbidities than younger patients. RFA features less invasiveness, a lower complication rate, and lower costs, as well as higher repeatability in the event of recurrence48. Regarding the long-term outcomes, HCC patients who underwent LLR had similar OS and RFS rates to those who received OLR49. However, we could not compare the treatment efficacy and outcomes between LLR and OLR because the majority of patients in our cohort underwent OLR and only 5 patients received LLR. Further prospective studies are warranted to elucidate this issue. Lastly, this study enrolled HCC patients over a relatively long span of time, so the diagnoses, assessment of HCC patients, and SR and RFA techniques might not have been the same between different time periods.There were some limitations to our study. First, although EGD was recommended to screen for EGV among patients with a new diagnosis of HCC, the completion rate was only 48.6% in this cohort Fig. . SelectiDespite these limitations, this study provides robust evidence to reassure physicians that SR could serve as a first-line treatment option for HCC, in spite of evidence of CSPH and EGV. However, the patients should be selected carefully. Consequently, aggressive treatments beyond the current guidelines could be considered when clinically applicable to achieve the maximum survival benefit.SR could be recommended as the first-line treatment modality for HCC patients with EGV if the patients are carefully selected and liver function is well preserved.50. High-risk EV was defined by the F2 and F3 classifications or by F1 accompanied by red coloring51.This study retrospectively enrolled 251 treatment-naïve HCC patients who underwent SR or RFA as the first treatment modality for HCC. All of the patients had EGV diagnosed by EGD at the time of HCC diagnosis at Taipei Veterans General Hospital Fig. . EV was 52. Multidisciplinary expert meetings and an HCC registration system in Taipei Veterans General Hospital have been conducted since October 2007. The diagnosis and treatment strategy are discussed at weekly multidisciplinary meetings for all of the HCC patients at this hsopital53. The decision about the treatment modality is shared between the patient and the physician after discussing the risks, benefits, complications, and efficacies of the available treatments, as well as the recommendations from the multidisciplinary expert meetings.The diagnosis of HCC was established based on the criteria from the American Association for the Study of Liver Disease consensus17. RFA was performed in cases of (1) a single tumor with size < 5 cm or 2‒3 tumors < 3 cm; (2) no extra-hepatic metastasis or major vascular invasion; (3) Child–Pugh grade A or B; (4) platelet count > 50,000 /mm3; (5) the absence of ascites; and (6) no other comorbid diseases that might complicate RFA40. Liver transplantation was indicated for patients with end-stage liver disease, HCC, or acute liver failure according to the criteria of United Network for Organ Sharing (UNOS)54. For patients with HCC, the tumor size criterion for liver transplantation was based on the criteria of the University of California San Francisco (UCSF)55.In our center, the indications for SR are as follows: (1) Child–Pugh grade of liver function of A or B, with an indocyanine-green 15-min retention rate (ICG-15R) of ≤ 30%; (2) tumor involving no more than two Healey’s segments without involvement of the main portal vein trunk; and (3) the absence of extra-hepatic tumor dissemination3; (5) absence of ascites; and (6) no other comorbid diseases that might complicate SR or RFA .The indications for SR and RFA were not the same, so we selected HCC patients using the Milan criteria for this study. Consequently, the inclusion criteria were as follows: (1) solitary tumor with size < 5 cm, in which anatomic resection could be achieved after through evaluation or 2‒3 tumors < 3 cm; (2) no extra-hepatic metastasis or major vascular invasion; (3) grade A or B Child–Pugh classification of liver function; (4) platelet count > 50,000 /mmThere were 2958 consecutive patients who were enrolled in the HCC registration system database from 2008 to 2017. As shown in Fig. 56. Grade III-V complications were defined as major morbidities. Postoperative liver failure was defined according to the International Study Group of Liver Surgery (ISGLS)57. All of the patients were followed up regularly every 3 months after SR or RFA until their last visit to our hospital or death.After SR or RFA, the peri-procedural morbidities were recorded and graded by the Clavien-Dindo classificationThis study was conducted in accordance with the Declaration of Helsinki and current ethical guidelines. Approval was obtained from the Institutional Review Board (IRB) of Taipei Veterans General Hospital (VGHIRB No. 2018-07-029BC). Informed consent was obtained before the patients underwent SR or RFA.58. The ALBI grades were defined as grade 1 (score ≤ – 2.60), grade 2 (score >  − 2.60 and ≤ – 1.39), or grade 3 (score > – 1.39).Serum biochemistry was measured using a Roche/Hitachi Modular Analytics System . Serum alpha-fetoprotein (AFP) levels were tested using a radioimmunoassay kit . The ALBI score was calculated using the following equation:  + (0.66 × log10 bilirubin in μmol/L)The primary endpoint of the study was OS, which was calculated from the date of HCC diagnosis until death, the last visit, or loss to follow-up. Pearson’s chi-squared analysis or Fisher’s exact test was used to compare categorical variables. The medians with IQRs were used to express continuous variables and compared using the Mann–Whitney U test.p < 0.05) or were proximate to it (p < 0.1) in the univariate analysis were included in a multivariate analysis, which was conducted using a forward stepwise Cox regression model. The ALBI scores were derived from serum albumin and bilirubin levels, so we used the ALBI grade but not the serum albumin and bilirubin levels in the multivariate analysis.Cumulative rates of OS and RFS were estimated by the Kaplan–Meier method, and the results were compared using a Cox proportional hazards model. Variables that had statistical significance .A two-tailed


Undernutrition among preschool children in Northern region is the highest in Ghana. However, there is scarcity of data on the factors that determine undernutrition in these children. This study investigated the effect of maternal and child factors on undernutrition among preschool children in Northern Ghana.This study was a community based analytical cross-sectional survey on a sample of 425 mother- child pairs drawn from 25 clusters. A semi- structured questionnaire was used to collect data on maternal and child socio-demographic characteristics, feeding practices and anthropometry. Anthropometric indices of Height-for-age Z-scores (HAZ), Weight-for-height Z-scores (WHZ) and Weight-for – age Z-scores (WAZ) were used to classify child stunting, wasting and underweight respectively. Bivariate and multivariate analyses were performed to determine associations between explanatory variables and undernutrition.p = 0.003], children of mothers less than 150 cm in height , mothers 155–159 cm tall , and older children aged 12–23 months . Wasting was significantly higher among male children , consumption of less than four food groups  and among children of underweight mothers . Male children  and having low birth weight  were associated with higher odds of underweight in children.The prevalence of stunting, wasting and underweight were 28.2, 9.9 and 19.3% respectively. Multiple logistic regression analysis showed that, the odds of stunting was higher among male children [AOR = 1.99; 95% CI (1.26–3.13); Maternal height associated negatively with stunting but not wasting. Factors that affect low height –for-age z-score (HAZ) may not necessarily be the same as stunting. Infant and child feeding practices as measured by dietary diversity score associated positively with weight-for-height Z-scores than length-for-age Z-scores of young children. Surprisingly, consumption of some specific food groups including, animal source foods, legumes, staples and eggs were associated with lower HAZ but with increased likelihood of higher WHZ among children 6–59 months.The online version of this article (doi:10.1186/s40795-017-0154-2) contains supplementary material, which is available to authorized users. Malnutrition is of public health importance in developing countries and is responsible for over half of child deaths each year from preventable causes . StuntinAlthough over the past decades child stunting has decreased worldwide, it has remained high in Sub-Saharan Africa and Asia and afflicts an estimated 165 million children globally  to 19% iDespite the high prevalence of stunting among children, its determinants are poorly established and understood  and limi2 land area which represent 11.0% of the total land area of the region and shares boundary with the southern parts of Ghana. The district is divided into five sub- districts for administrative purposes with a total population of 87,877 with 49.9% as males and 50.1% as females. The population of the district is largely youthful with children aged 0–4 years forming the largest part representing 17.6% of the total population. The main economic activity of the people is agriculture (74.2%) involving crop production, livestock and fish farming. Some of the crops cultivated are maize, sorghum, millet, groundnut, cowpea, soy beans, yam, rice, as well as cassava. Fishing and livestock are considered supplementary activities to crop farming  were the main dietary intake indicators for children. These indicators were measured by recall of food and liquid consumption during the previous day or night preceding survey as per WHO/UNICEF food frequency questionnaire (FFQ) . MinimumA household wealth index based on household assets and housing quality was used as a proxy indicator for socio-economic status (SES) of households.Absolute household wealth index was calculated from information collected on housing quality , source of drinking water, type of toilet facility, the presence of electricity, type of cooking fuel, and ownership of modern household durable goods and livestock  –21. ThesA number of measures were used to ensure that accurate and reliable data were collected and analyzed. These included extensive practical training of data enumerators, pre-testing of data collection tools and extensive monitoring of the field teams. Field supervisors provided on-the-spot assistance to interviewers. Data were checked for completeness and consistency by field supervisors in the field and during data entry in order to ensure good quality.Data analyses was performed with PASW/SPSS, version 21.0 for Windows using procedures in SPSS complex samples module for Windows. Design weights were added to perform weighted analysis. This module of SPSS takes into account the complex nature of the cluster sample design.The Z- scores for weight-for-age (WAZ), weight-for- height (WHZ), height-for-age (HAZ) and prevalence underweight, wasting and stunting were calculated using the 2006 World Health Organization (WHO) growth standards.WHO Anthro software was used to convert height, weight and age measurements to Height- for- age Z- scores (HAZ), weight- for –height Z- scores (WHZ) and weight-for – age (WAZ) which were used to classify stunting, wasting and underweight respectively. Child undernutrition was defined as Z- scores below −2 standard deviations below the median of the reference population.χ2) tests were performed to identify the predictors of stunting, wasting and underweight significant at p < 0.05. ANOVA was used to compare mean anthropometric Z-scores and selected predictors.Bivariate and multivariate analyses were both performed to identify the determinants of stunting, wasting and underweight. Chi-square  tests were included in the regression modeling.The association between undernutrition and the independent variables was determined using binary logistic regression modeling. This test statistic was used because stunting, wasting and underweight were coded into two categories . All of the potential predictors of stunting, wasting and underweight that were significant at The association between selected factors and HAZ was determined using multiple linear regression modeling. This test statistic was used because the dependent factor (HAZ) is a continuous variable.Before testing for associations between independent variables and the dependent outcomes, the data were cleaned and outliers removed. Z-scores which were outside the WHO flags: WHZ −5 to 5; HAZ −6 to 6; and WAZ −6 to 5 were excluded from the data set.Permission to carry out this study was sought from the district health directorate and the study protocol was approved by the School of Allied Health Sciences, University for Development Studies, Ghana. Informed consent was verbally obtained from participant mothers after needed information and procedures were explained. Participation was voluntary and participants signed or thumb printed a statement of an informed consent before being interviewed.The mean age ± SD of mothers was 30.3 ± 6.0 years with the majority (75.3%) in the 18–34 age groups. The majorities of the respondents had no formal education (78.1%), were married (91.3%), practiced Islamic religion (93.4%) and mostly from the Gonja ethnic group (53.6%). Sixty-three percent of mothers were from low wealth households.Children had mean age ± SD of 25.14 ± 13.6 months; male children (50.8%) were slightly more than the female children (49.2%) with most of the children found in the age group 12–23 months (32.5%). Majority of the children had adequate birth weight ≥ 2.5 and a mean birth weight of 2.97 ± 0.49  and weight-for-height Z-scores (WHZ) are shown in Tables Whereas, HAZ associated negatively with minimum dietary diversity as well as the consumption of some specific food groups including, animal source foods and legumes, WHZ associated positively with these variables. Other variables that were tested but were not in any way associated with HAZ and WHZ were the educational level of the mother, initiation and frequency of ANC attendance.A host of explanatory variables were tested for their association with child stunting. The variables tested included age and sex of child, type of residence, current breast feeding status, diarrhoeal infection, utilization of antenatal care services, birth interval, parity, birth weight, maternal height, maternal educational level, household wealth index, source of drinking water, type of toilet facility, bottle feeding, minimum dietary diversity score and number of under five children in household.Bivariate analysis revealed that, stunting was significantly higher among male children than their female counterparts. Stunting was less prevalent among children whose mothers attended antenatal care (ANC) services for at least 4 times during pregnancy. In addition, stunting was significantly higher among children who were born low birth weight <2.5 kg) compared to children with adequate birth weight. The prevalence of stunting decreased as maternal height increased, and children who lived in households without a toilet facility were also more likely to be stunted (Table  kg compaFactors that affect low height –for-age z-score (HAZ) may not necessarily be the same as stunting Tables  and 7.TaMultiple logistic regression analysis showed that, age of child, low maternal height and gender of the child were the three significant consistent predictors of stunting. This set of variables accounted for 13.8% of the variability of stunting (Nagelkerke R Square = 0.138).p = 0.003] of being stunted compared to female children.Male children were 1.9 times more likely  and mothers 155–159 cm tall also had significantly higher odds of having a stunted child . Older children aged 12–23 months were 9.8 times greater odds  of being stunted, compared to children aged 6–8 months.Compared to mothers with heights at least 160 cm, others who were less than 150 cm in height were about 3.9 times more likely to have a stunted child . The odds of child wasting was significantly higher among underweight mothers  compared to mothers who had normal body mass index  in wasting. Compared to female children, male children were 2.4 times more likely to experience wasting  compared to female children. The odds of underweight was significantly higher among children who were born low birth weight than those born of adequate birth weight. Compared to children born of adequate birth weight, children born low birth weight were 3.8 times more likely to be underweight . Table Only two of the predictors of underweight significant in bivariate analysis were able to reach significance in multivariate analysis. Sex of child and birth weight were associated with child underweight in multivariate analysis. These factors accounted for 10.9% of the variability (Nagelkerke R Square = 0.109) in underweight in children. Implying that other factors not in the equation, probably not measured in this study also explain underweight in children. Male children were 2.7 times more likely to be underweight [AOR = 2.685; 95% CI (1.205–5.98); 1.440–9.9; p < 0.0This study sought to investigate the maternal and child factors that determine child stunting, wasting and underweight among children aged 6–59 months in Northern Ghana. The main findings were that maternal height associated negatively with stunting but not wasting. The factors that are associated with low height- for-age z-score may not necessarily be the same as stunting. In addition, infant and child feeding practices as measured by dietary diversity score associated positively with weight-for-height Z-scores than length-for-age Z-scores of young children and the consumption of some specific food groups including, animal source foods and legumes and eggs were associated with lower HAZ but with increased likelihood of higher WHZ among children. Stunting was associated with sex, maternal height and age of child, whereas wasting was associated with dietary diversity, sex and body mass index of mother. Child underweight was associated with sex and birth weight of children.The prevalence of child malnutrition indicators measured in present study were lower than the regional prevalence of 33.1, 20.0 and 6.3% for stunting, underweight and wasting respectively in the recent Ghana demographic and health survey report , except A higher proportion of children in the study sample consumed a diversified diet from at least four food groups. Nearly sixty- four percent of the children met the minimum dietary diversity recommendation with an average dietary diversity score of 3.6. A study among children under five years in the Central region of Ghana however reported lower minimum dietary diversity scores . DietaryThe association between older age and stunting is consistent with data from Ethiopia  and BangWasting was associated with sex of child, minimum dietary diversity and maternal body mass index. Male children had higher odds of acute malnutrition. This finding is consistent with earlier studies among preschool children , 36. ChiUnderweight was high in the study sample, however only two factors were associated with it in multivariate analysis. These factors however explained an appreciable amount (10.9%) of the variance in underweight among children in the study sample. Obviously no single study can identify all the factors related to malnutrition considering the different contexts within which children find themselves. Sex and birth weight of child were associated with underweight in children. Male children were as well more likely to experience underweight than their female counterparts. The high likelihood of underweight among male children has been reported earlier . ChildreThis study is limited by the cross-sectional nature of the data, therefore causal conclusions were not possible. Our study has however, thrown more light on the maternal and child factors that determine undernutrition in children.Maternal height associated negatively with stunting but not wasting. Factors that affect low height –for-age z-score (HAZ) may not necessarily be the same as stunting. Infant and child feeding practices as measured by dietary diversity score associated positively with weight-for-height Z-scores than length-for-age Z-scores of young children in rural Northern Ghana. Surprisingly, consumption of some specific food groups including, animal source foods, legumes, staples and eggs were associated with lower HAZ but with increased likelihood of higher WHZ among children 6–59 months.Additional file 1:Study questionnaire. (DOCX 28 kb)


The aim of this study was to investigate albumin, nutritional status, and inflammation in the perioperative course of patients undergoing elective intestinal surgery.  A retrospective analysis of patients with preoperative measurements of nutritional parameters who underwent intestinal surgery between April 2017 and August 2018 at our institution was performed. Preoperatively, the correlation of albumin levels with markers for inflammation and nutritional status was investigated. Postoperatively, albumin levels were assessed with regard to high-grade morbidity and inflammation. p=0.004) and C-reactive protein (CRP) (p < 0.001) as independent factors predicting the albumin levels in multivariable analysis. Postoperatively, the reduction in serum albumin  on postoperative day (POD) 1/2 (p=0.025) and POD 4/5 (p=0.003) was significantly associated with Clavien–Dindo complications ≥grade III. A cut-off value of 27.3% for ∆-albumin on POD 1/2 predicted postoperative high-grade morbidity (sensitivity 75% and specificity 69%). The product of ∆-albumin and CRP on POD 4/5 identified patients with major complications more reliably than ∆-albumin or CRP alone (sensitivity 91% and specificity 72%).  A total of 105 patients were included. Preoperatively, albumin levels were correlated with both markers for nutritional status and inflammation, with phase angle (PA) ( Preoperatively, albumin was a marker for nutritional status even if an inflammatory component was present. Postoperatively, ∆-albumin on POD 1/2 predicted high-grade morbidity. A new marker to identify patients with major complications on POD 4/5 is presented. Hypoalbuminemia is a powerful predictor of postoperative morbidity in patients undergoing gastrointestinal surgery for malignancies or inflammatory bowel diseases (IBD) , 2. Low The aim of this study was twofold. First, we aimed to investigate whether albumin is a useful nutritional marker in patients scheduled for elective intestinal surgery. Second, we intended to further investigate albumin levels in the postoperative phase with regard to major complications and inflammation.Ethical board approval was obtained from the Medical Ethics Commission II of the Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (2017-554N-MA). Written informed consent was obtained from all patients included in this study. All investigations were performed according to the Declaration of Helsinki.Between April 2017 and August 2018, elective patients undergoing intestinal surgery at our institution were offered a preoperative nutritional risk screening (NRS 2002) and measurements of handgrip strength (HGS), body mass index (BMI), and phase angle (PA) in addition to the routine measurements of serum albumin and C-reactive protein (CRP). Exclusion criteria were patients who were not willing or able to provide written informed consent, patients under 18 years of age, and patients undergoing nonelective procedures. All patients who took part in these measurements were eligible for this study.Further patient characteristics and data on surgery were collected from medical records. Concerning NRS, patients were regarded as nutritionally at risk when a score ≥3 was obtained . PreoperHandgrip strength (HGS) was determined using a Saehan Hydraulic Hand Dynamometer SH5001 . For measurements, patients sat in a comfortable position with a 90° angle at the elbow joint and were asked to squeeze the dynamometer using their maximum strength, and the test was repeated after a break of 30 seconds. In total, three measurements of the dominant hand were obtained and averaged.Bioelectrical impedance analysis (BIA) measurements were conducted to obtain PA values. In brief, after physical rest for 30 minutes, four gel electrodes were applied, with two detecting electrodes placed at the ulnar aspect of the wrist and the medial malleolus of the dominant body side of the patients. Measurements were conducted and recorded by a multiple frequency BIA instrument following standard protocols . Body composition values were calculated using Nutriguard Plus software .2) at the third lumbar vertebra (L3) was determined and averaged for each patient. The following muscles were selected using aycan workstation pro software : rectus abdominis, abdominal , psoas, and paraspinal muscles (quadratus lumborum and erector spinae). The muscle area in centimeters squared (cm2) was calculated and then normalized by patient height in meters squared (m2) and reported as lumbar SMI (cm2/m2).The skeletal muscle mass index (SMI) was derived from the muscle mass determined by computed tomography (CT) or magnetic resonance imaging (MRI) studies conducted for routine diagnostic purposes up to 8 weeks before surgery. Two adjacent axial images within the same series were selected, and the total muscle cross-sectional area , Spearman's correlation (rs), or the point biserial correlation (rpb) were used, as appropriate. Furthermore, a receiver-operator characteristic (ROC) analysis was performed to determine optimal cut-off values for parameters separating patients with major postoperative complications from patients without major postoperative complications. Statistical analyses were performed using IBM SPSS Statistics  and GraphPad Prism version 8.1.0 .Mean and standard deviation (SD) were calculated for each quantitative variable. Qualitative variables are expressed as absolute and relative frequencies. Student's Between April 2017 and August 2018, 111 patients scheduled for intestinal surgery gave informed consent to preoperative measurements of nutritional parameters. In three patients, preoperative measurements were not possible due to technical reasons, and in another three patients, no intestinal procedure was performed. The data of the remaining 105 individuals were used in the analysis. The patients' characteristics are summarized in rs = −0.563; p < 0.001) and NRS scores ≥3  and were positively correlated with PA , HGS , BMI , and SMI . Dispersion graphs of correlations between preoperative albumin levels and nutritional parameters are shown in p < 0.001) and PA (p=0.004) were the independent factors influencing albumin levels  = 44.177, and p < 0.001). In addition, a subgroup analysis of the patients for whom SMI was available was performed (n = 36). For these patients, CRP (p < 0.001) and PA (p=0.004) remained the two independent parameters predicting albumin values  = 19.510, and p < 0.001). Postoperatively, an increase in correlation strength between albumin and CRP was observed from POD 1/2 (r = −0.351) to POD 4/5 (r = −0.555) (Preoperative measurements are listed in  −0.555) .p < 0.001) for patients with major postoperative complications (16 ± 8.7 days) compared with patients without major postoperative complications (8 ± 2.5 days). Neither preoperative albumin (p=0.843) nor preoperative CRP (p=0.342) showed a statistically significant association with the occurrence of major postoperative complications. However, the ∆-albumin from the preoperative to the first  and second postoperative measurement  was significantly greater in patients with major postoperative complications as compared with patients without major postoperative complications. A ROC analysis was performed and a cut-off value for ∆Alb1 of 27.3% was calculated to separate patients with high-grade morbidity from patients without high-grade morbidity . For ∆Alb2, this cut-off value was 24.3% . At POD 4/5, the CRP values of patients with major complications were significantly higher as compared with patients without major complications (p=0.003) with a cut-off value of 67.3 mg/L . When the product of ∆Alb2 and CRP on POD 4/5 was calculated, a more reliable identification of patients with high-grade morbidity than with ∆Alb2 or CRP alone was achieved . The corresponding ROC curve is shown in Postoperative complications and the length of hospital stay are reported in In this study, we investigated albumin, nutritional parameters, and inflammation in the perioperative course of 105 patients undergoing elective intestinal surgery between April 2017 and August 2018. Preoperatively, serum albumin was a marker of nutritional status even if an inflammatory component was present. However, when inflammation increased during the early postoperative course, albumin levels were increasingly correlated with CRP, thus no longer suitable as a nutritional marker. A significant association with surgical outcomes was found for the reduction of albumin levels from the preoperative day to POD 1/2 and POD 4/5, and a new surrogate marker for postoperative morbidity was calculated.The correlation of preoperative albumin levels with several different established nutritional biomarkers  indicated that preoperative albumin was a marker of nutritional status in patients scheduled for elective intestinal surgery. This is an important finding as the suitability of albumin as a nutritional parameter was questioned in several previous publications –15. MoreConcerning nutritional status, a gold standard for its evaluation does not exist . We measDuring the acute phase of the postoperative course, we observed an increase in the strength of the negative correlation of albumin with CRP, reflecting the role of albumin as an acute-phase protein . In the We report an overall rate of Clavien–Dindo complications ≥ grade III of 12.4%. Most probably, because of the small number of major complications, we did not find a significant association of preoperative albumin levels with postoperative major complications, which has been reported in a number of larger studies . The proSome limitations of our study must be mentioned. Although preoperative data on nutritional parameters were prospectively collected, the study was retrospective in nature and not all consecutive patients during the study period could be included. Perioperative treatment was not controlled but followed standard operating procedures. The cohort was inhomogeneous regarding diagnoses and surgical procedures. However, the patients in this study represent the spectrum of elective intestinal surgery at a tertiary referral center, with the majority of patients operated for CRC, IBD, and diverticular disease. Therefore, we investigated albumin levels in a cohort in which its prognostic value has been demonstrated in previous studies , 2, 5, 6First, our study demonstrates that albumin may be regarded as a surrogate marker for nutritional status prior to elective intestinal surgery despite contradictory reports in the past. This also seems to be true when a certain chronic inflammatory component is present, which is common in surgical patients diagnosed with CRC or IBD. We also show that, in the acute postoperative phase, albumin should not be used as a nutritional parameter due to an increasing correlation with inflammation. Therefore, assessment of the patients' inflammatory state is essential before using albumin as a nutritional marker. Second, even in a cohort where preoperative albumin did not predict postoperative complications, ∆-albumin identified patients at risk for major morbidity, underlining the importance of albumin as a prognostic tool. The product of ∆-albumin and CRP on POD 4/5 could be a useful parameter to reliably identify patients with high-grade morbidity.


To evaluate the effect of breast MRI on overall survival (OS) and disease-free survival (DFS) of patients with invasive breast cancer in the Netherlands.We selected all women from the Netherlands Cancer Registry diagnosed with invasive breast cancer (a) between 2011 and 2013 for the OS-cohort and (b) in the first quarter of 2012 for the DFS-cohort. The study population was subdivided into an MRI and non-MRI group. In addition, subgroups were created according to breast cancer subtype: invasive carcinoma of no special type (NST) versus invasive lobular carcinoma (ILC). OS and DFS were compared between the MRI and non-MRI group using the Kaplan–Meier method and the log-rank test. Cox proportional hazard regression analysis was performed to estimate hazard ratios (HR) with a 95% confidence interval (CI). To account for missing data, multiple imputation was performed.p = 0.35), nor in the different histological subtypes. Multivariable Cox regression analysis showed that breast MRI was also not significantly associated with DFS , nor in the different histological subtypes.Of the 31,756 patients included in the OS-cohort (70% non-MRI and 30% MRI), 27,752 (87%) were diagnosed with invasive carcinoma NST and 4004 (13%) with ILC. Of the 2464 patients included in the DFS-cohort (72% non-MRI and 28% MRI), 2161 (88%) were diagnosed with invasive carcinoma NST and 303 (12%) with ILC. The distribution of breast MRI use was significantly lower over different age categories, from 49.0% aged < 50 to 16.5% aged > 70. Multivariable Cox regression showed that breast MRI was not significantly associated with OS overall  contains supplementary material, which is available to authorized users. Breast cancer is the second most common cancer-type in the world (2.09 million cases) and for women it is the most common cancer-type . AnnuallConventional imaging techniques for early detection and diagnosis of breast cancer are full-field digital mammography (FFDM) and ultrasound, in combination with tissue sampling of suspicious lesions . In the Regarding short-term effects of the use of breast MRI, previous studies have shown that mastectomy rates increased, and that the risk of positive surgical margins and re-excision rates showed no or only a slight improvement , 4, 8. HThis retrospective study included all female patients treated with surgery for invasive breast carcinoma of no special type (NST) or ILC, diagnosed in the period of 2011–2013 in the Netherlands. The OS had a maximum follow-up of 7 years. Data on recurrent disease for the DFS-cohort were available for patients diagnosed and treated in the first three months of 2012, and had a maximum follow-up of 5 years. No age-limits were applied and patients treated with adjuvant radiotherapy, chemotherapy, hormonal and/or target therapies were included. Patients who did not undergo surgical treatment, who had distant metastases at baseline, and/or who had received neo-adjuvant therapy were excluded.Data were obtained from the Netherlands Cancer Registry (NCR), and were registered by trained registrars based on notification by the automated pathology laboratory archive (PALGA). The 7th edition of the TNM-classification was used . AccordiThe following variables were selected for the present study: age at diagnosis , tumour status , nodal status , molecular subtypes (ER/PR + HER2−: estrogen receptor (ER) and/or progesterone receptor (PR) positive, HER2 negative; ER/PR + HER2 + : ER and/or PR positive, HER2 positive; HER2 enriched: ER and PR negative, HER2 positive; and triple negative: ER, PR, and HER2 negative), histological grade , multifocality (yes or no), tumour location , breast MRI use (yes or no), surgical margin status after surgery (negative margin (NM) < 0 mm, focal positive margin (FPM) < 4 mm, or more than focal positive margin (MFPM) > 4 mm), type of final surgery (mastectomy or breast conserving surgery), adjuvant therapy , and vital status (date of death). For patients diagnosed and treated in the first quarter of 2012, active follow-up was conducted whereby information on the date of local recurrence (yes or no), regional recurrence (yes or no), and distant metastases (yes or no) was collected. Time period until death or last contact was linked with the database of the municipality, and was updated until February 1st, 2018.U test for continuous variables. OS and DFS were calculated with the Kaplan–Meier method and its survivor function, which predicts the chance of survival after a given period of time. Kaplan–Meier survival curves were compared with the log-rank test. For the DFS an event was defined as any local recurrence (LR), regional recurrence (RR), or distant metastasis (DM) within 5 years after the primary diagnosis. Possible confounders were examined using univariable and multivariable Cox proportional hazard regression analysis, with hazard ratio (HR) and corresponding 95% confidence interval (CI). In the multivariable model of the OS analysis, the interaction term MRI and age per category was included to test whether the effect of MRI differs between age category. Multiple imputation by the chained equations, with 50 iterations and 20 imputations, was used to account for missing data [P-Values (two-sided) less than 0.05 were considered statistically significant.The study population was divided into an MRI and non-MRI group, according to the use of breast MRI. Subsequently, the study population was stratified into one of the following histological subgroups: invasive carcinoma NST or ILC. General characteristics between the groups were tested using the Chi-square test for categorical variables and the Mann–Whitney ing data . The poon = 80), unknown surgery (n = 20), or an unknown adjuvant treatment (n = 21) were excluded. After exclusion of these patients 31,756 (99.6%) patients composed the OS-cohort for the analysis of the OS. Of these patients 22,124 (70%) did not undergo breast MRI, 27,752 (87%) had invasive carcinoma NST (73% non-MRI and 27% MRI) and 4004 (13%) had ILC (44% non-MRI and 56% MRI). The final study cohort for the DFS (DFS-cohort) included 2464 patients, of whom 1767 (72%) did not undergo breast MRI. Of these patients, 2161 (88%) had invasive carcinoma NST (75% non-MRI and 25% MRI) and 303 (12%) had ILC (46% non-MRI and 54% MRI).In the period 2011–2013 31,877 patients were treated with surgery for invasive carcinoma NST or ILC. Patients with no follow-up data (p = 0.08) and the invasive carcinoma NST (p = 0.39). For the ILC subgroup a statistically significant difference was observed (p = 0.002); here the MRI group was more likely to have negative margins (79% versus 73%), and less likely to have more than focal positive margins (8% versus 12%), compared to the non-MRI group.Table There were 2939 (9%) incomplete cases in the OS-cohort ) and 231 (9.0%) in the DFS-cohort ) for which multiple imputation was used, assuming that the data were missing at random. The imputed data were compared with the original data, which showed an overall comparable distribution of the data , 2938 (13.0%) of the 22,124 patients in the non-MRI group died, compared to 743 (8.0%) of the 9632 patients in the MRI group, after a mean follow-up of 5.3 years . The Kaplan–Meier analysis and the log-rank test showed that patients in the MRI group had a significantly better OS than the patients in the non-MRI group (p < 0.0001); the 7-year survival rates were 0.89 (95%-CI 0.87–0.90) and 0.83 (95%-CI 0.82–0.83), respectively (Online Appendix 3). However, after age stratification in the total study population, this difference in OS proved to be only statistically significant for the age groups 60–69 (p = 0.036) and > 70 (p < 0.0001). In Figs. In the total OS-cohort n = 3,756, 293p = 0.06; invasive carcinoma NST: p = 0.07; ILC: p = 0.23) , 114 (7.0%) of 1767 patients in the non-MRI group had an event compared to 48 (7.0%) of 697 in the MRI group, after a mean follow-up of 4.6 years. Table p = 0.84). The 5-year DFS rates was 0.93 (95%-CI 0.91–0.95) for the MRI group vs 0.93 (95%-CI 0.92–0.94) in the non-MRI group . In both the invasive carcinoma NST and ILC subgroups, breast MRI use was also not significantly associated with DFS. In the invasive carcinoma NST group the 5-year survival rate was 0.93 (95%-CI 0.90–0.94) for the MRI group and 0.93 (95%-CI 0.92–0.95) for the non-MRI group (p = 0.54). In the ILC subgroup these figures were 0.94 (95%-CI 0.89–0.97) and 0.92 (95%-CI 0.86–0.95), respectively (p = 0.36).Within the DFS-cohort n = 464, 114 p = 0.42; invasive carcinoma NST: p = 0.32; ILC: p = 0.96) , neither in the overall OS-cohort, nor in the histological subgroups. Yet, the use of breast MRI decreased dramatically from 49.0% in patients aged < 50 to 16.5% in patients aged > 70. Regarding the DFS-cohort, Multivariable Cox regression showed also no statistically significant difference in DFS between patients with or without breast MRI.p = 0.51), however many patients underwent breast MRI after surgery within this study cohort [p = 0.24) [p = 0.362) [p = 0.231) [In contrast to our study, which demonstrated no significant effect of breast MRI use with regard to overall survival, a tendency towards positive correlation of breast MRI use on OS was observed in previous studies, but this association was not statistically significant , 11–14. y cohort . In a no = 0.24) . Choi etAlthough previously mentioned studies observed similar results when compared to our study, these studies were limited by heterogeneous data and several impairments. For instance multivariable analyses without including breast MRI , unequalp = 0.002), but not in the subgroup of invasive carcinoma NST (p = 0.39). In contrast to our results, Lai et al. showed an overall increased risk of surgical margin involvement when breast MRI was omitted [Surgical margin in patients treated with breast conservative surgery is an important prognostic factor as it is known to affect DFS in women who did not undergo breast MRI . Accordi omitted . This co omitted  versus 8This study has several strengths and limitations. One strength is the use of a nationwide population-based cancer registry, which increases the generalizability of the results. This also led to a large sample size, which made stratification on the subgroups invasive carcinoma NST and ILC, and the age categories possible. However, since the sample size was large, the confidence intervals were relatively small which might lead to statistically significant results, yet not clinically relevant. It is important to take this in consideration while interpreting the results. Another strength of this study is that it includes several other prospective factors which may influence and adjust the HR of breast MRI, such as the tumour location, type of operation and surgical margins.A limitation of this study is the retrospective and observational design. This reflects daily practice which leads to a large difference in distribution of breast MRI use among the different age categories in our study. The use of breast MRI decreased with increasing age, especially in patients 60–70 and > 70. The use of MRI might be affected by factors which we did not have any information on in the NCR, such as the presence of comorbid conditions in patients. Another important limitation is that the reason to perform an MRI and whether the MRI findings changed the original surgical treatment plan or not were unknown, which leaves room for confounding by indication. Besides, the number of surgical excisions to achieve negative margins per patient in the current study was unknown. Next, for this study patients treated with neo-adjuvant systemic therapy were excluded. Yet, this subgroup of patients is considered to be an important subgroup of patients with regard to potential change in treatment decision based on breast MRI findings .In addition, the patient characteristics and treatment characteristics within our observational study were not well balanced. After further examination of the treatment characteristics of the OS study population, it was somewhat noticeable that patients in the total study population and in the age categories > 60 treated with mastectomy, were slightly more treated with adjuvant radiotherapy in the MRI group, compared to the non-MRI group. Patients in the age category of > 70 and treated with breast conserving surgery, were slightly less treated with adjuvant radiotherapy in the non-MRI group, compared to the MRI group. In both the invasive carcinoma NST subgroup and the ILC subgroup the same results applied, however in the invasive carcinoma NST subgroup this was less noticeable. In addition, in the ILC subgroup patients in the age category of < 50 and treated with breast conserving surgery, were slightly less treated with adjuvant radiotherapy in the non-MRI group, compared to the MRI group. Although we corrected for the unbalanced patient and treatment characteristics in our multivariable analysis, we still cannot exclude residual confounding.Another limitation is the maximum follow-up of 7 years, which resulted in a mean follow-up of 5.3 years. A longer follow-up would have given more insight into the possible long-term impact of breast MRI on the OS, especially with regard to hormone receptor positive patients, and would have increased the statistical power to detect clinically relevant differences. In addition, the cause of death was unknown in the current study, consequently breast cancer related mortality cannot be evaluated in the current cohort. In order to provide a better recommendation for breast MRI in general use, it is recommended that a next study should focus on a longer follow-up period, including a breast cancer related mortality analysis.Finally, our DFS-cohort consisted only of a relatively small proportion of the patients out of the OS-cohort. Due to limited resources active follow-up performed by the registrars of the NCR could only be accomplished for the patients diagnosed in the first quartile of 2012.Future studies should investigate the effect on prognosis by comparing patients in whom MRI findings led to a change in treatment plan with those without treatment change and/or patients without MRI. For instance, the currently recruiting European wide MIPA trial could identify this specific subgroup of patients allowing to investigate prognosis in these patients into detail .In summary, use of breast MRI showed no statistically significant effect regarding DFS nor OS for different age categories in patients treated with primary surgery.Supplementary file1 (DOCX 67 kb)Below is the link to the electronic supplementary material.


Epidemiological studies have shown inverse association between intelligence and coronary artery disease (CAD) risk, but the underlying mechanisms remain unclear.n = 34,083) and UK Biobank . From UK Biobank, we extracted phenotypes including body mass index (BMI), type 2 diabetes (T2D), smoking, hypertension, HDL cholesterol, LDL cholesterol, measured intelligence score, and education attainment. To estimate the effects of gIQ on CAD and its related risk factors, regression analyses was applied. Next, we studied the mediatory roles of measured intelligence and educational attainment. Lastly, Mendelian randomization was performed to validate the findings.Based on 242 SNPs independently associated with intelligence, we calculated the genetic intelligence score (gIQ) for participants from 10 CAD case–control studies (P = 4.93e–5), which was validated in UK Biobank . In UK Biobank, we also found significant inverse correlations between gIQ and risk factors of CAD including smoking, BMI, T2D, hypertension, and a positive correlation with HDL cholesterol. The association signals between gIQ and CAD as well as its risk factors got largely attenuated after the adjustment of measured intelligence and educational attainment. The causal role of intelligence in mediating CAD risk was confirmed by Mendelian randomization analyses.In CAD case–control studies, one standard deviation (SD) increase of gIQ was related to a 5% decrease of CAD risk  contains supplementary material, which is available to authorized users. Epidemiological studies have shown an inverse association between intelligence score and risk of coronary artery disease (CAD) , 2. HighGenome wide association studies (GWAS) have identified large numbers of genetic variants, typically single nucleotide polymorphisms (SNPs), associated with a wide range of complex traits providing opportunities of exploring the relationships between traits. Polygenic risk scores defined as sum of trait-associated SNPs weighted by effect size derived from large-scale GWAS measure the liability of individuals developing such traits , 10. TheSavage et al. performed genome-wide association meta-analysis in 269,867 individuals and identified 242 SNPs independently associated with intelligence . We usedIndividual level genotype data were collected from ten case–control studies of CAD as discovery set –21. All The data of UK Biobank were also applied to characterize interplay between intelligence and risk factors of CAD including body mass index (BMI), type 2 diabetes (T2D), HDL cholesterol, LDL cholesterol, hypertension, and smoking behavior. These traits were either self-reported or extracted from hospital episodes or death registries as reported by UK Biobank . IntelliP < 5e–8) to intelligence scores [Savage et al. performed GWAS meta-analysis of 14 independent epidemiological cohorts of European descent and reported 242 independent SNPs with genome-wide significant association (e scores . We estie scores . Detailsz-scores with mean of 0 and standard deviation (SD) of 1. By logistic regression analyses, we estimated effects of gIQ on CAD risk for each study separately. To control the bias due to population stratification or different genotyping platforms, the first two principle components for 10 CAD studies were added as adjustments of the regression model. In UK Biobank, because of more complex population structure, we employed top five principle components and array platforms for this data set. Lastly, the fixed-effect size meta-analysis was performed to estimate the combined effects across all CAD studies. Based on gIQ, all individuals were evenly separated into low, medium and high groups to study the distribution of cases and controls along with increasing gIQ.The summary statistics of 242 independent SNPs of intelligence were applied to calculate the individual-level weighted genetic score of intelligence for each study. Firstly, each variant was given a value from 0 to 2 according to the presence of the intelligence allele in the imputed genotype data of each participant, which was then multiplied with the effect size of the variant on intelligence. For variants with missing genotypes in the imputed data, the reference allele frequency was applied. Then we summed these values of 242 variants for each participant as the polygenic score of intelligence, namely the genetic intelligence score (gIQ). Afterwards, the continuous gIQ was standardized into Albeit the gIQ reflects intelligence at first place, the SNPs utilized in this score may be pleiotropic and thus affects other traits –26. SeveIn UK Biobank, we estimated effects of gIQ on measured intelligence, educational attainment, risk factors of CAD including BMI, T2D, smoking, HDL cholesterol, LDL cholesterol and hypertension. Definitions of these traits are shown at Supplementary Notes and Table S3. Logistic regression was applied to binary traits like T2D, smoking, hypertension; and linear regression was for continuous traits like measured intelligence, educational attainment, BMI, HDL cholesterol, and LDL cholesterol. Top five principle components and array platforms were used as adjustment of regression models. We also studied phenotypical association of measured intelligence with educational attainment and CAD incidence in UK Biobank. Additionally, to avoid the genetic influence of education derived from genetic overlaps between intelligence and education, we re-estimated the effects of intelligence on CAD and its risk factors by eliminating seven overlapping SNPs .Mendelian randomization (MR) is a method using genetic variants as instruments to study causal relationships between exposures and outcomes . We intrP < 0.05) in at least two of three methods were identified to be reliable and shown by IVW results. Lastly, sensitivity analysis of effects of intelligence and educational attainment on CAD were performed by excluding SNPs that were moderately associated with risk factors of CAD (P < 0.001) from intelligence SNPs and education SNPs respectively. Details are shown at Supplementary Notes.To address the influence of genetic overlaps between education and intelligence, we eliminated seven SNPs that are both associated with intelligence and educational attainment in MR analysis. Three MR methods including inverse-variance-weighted average (IVW) , MR-eggeTen case–control studies of CAD with 16,144 CAD cases and 17,939 controls were included in this study. Majority of participants were from the Germany and UK. Individual-level genotype data and elaborate phenotype data from UK Biobank were used as validating set containing 20,310 CAD cases which were defined by either self-reported, or hospital episode and death registry data, and 406,996 controls. (Supplementary Notes and Table S1). For each cohort, we generated gIQ based on 242 SNPs reported to be genome-wide significantly associated with intelligence .P = 4.93e–5) along with per 1-SD increase in gIQ . Meta-analysis using fixed-effect size model indicated relative decrease of CAD risk by 5%  in UK Biobank. As expected, the association between gIQ and CAD risk was abolished after adjustment for measured intelligence defining measured intelligence as an intermediary trait between gIQ and CAD risk  and prolonged years spent in school by 0.45 year. In addition, one more year spent in school increased the measured intelligence score by 0.16 unit (P < 1e–10). Vice versa, one unit increase in measured intelligence prolonged years spent in school by 0.98 year (P < 1e–10). Both the measured intelligence and educational attainment had inverse effects on CAD risk. See results in Table S5.In UK Biobank, we found that 1-SD increase of gIQ increased measured intelligence score by 0.29 unit , indicating these risk factors were involved in mediating the association between gIQ and CAD risk.P < 1e–10), decrease of BMI by 0.1 kg/m2 , decrease of T2D risk by 15% . A SD increase in the education years resulted in decrease of risk of CAD by 38% , decrease of BMI by 0.32 kg/m2 , increase of HDL cholesterol by 0.19 mmol/L , decrease of the risk of smoking by 43% , and decrease of T2D risk by 47% . The effects of educational attainment on CAD and its risk factors displayed the same direction as intelligence but were stronger in magnitude. See details at supplementary notes and Table S7.To substantiate our observations, we performed multivariable two-sample MR analysis taking intelligence or educational attainment as exposures, CAD and its risk factors as outcomes. The estimates of the direct effects on outcomes for intelligence and education were generally in a consistent direction Fig. . 1-SD inP < 0.001) with CAD (n = 5), BMI (n = 45), and HDL cholesterol (n = 5) were removed from intelligence SNPs. The sensitivity analysis showed 1-SD increase in intelligence to decrease the risk of CAD by 22% . Same as intelligence, SNPs moderately associated (P < 0.001) with CAD (n = 13), BMI (n = 155), HDL cholesterol (n = 6), LDL cholesterol (n = 5), and smoking (n = 2) were removed from education SNPs. The sensitivity analysis showed 1-SD increase in education years to decrease the risk of CAD by 34% . Results are shown at Table S8.Lastly, MR sensitivity analysis were performed for intelligence and educational attainment respectively. For intelligence, SNPs moderately associated Below is the link to the electronic supplementary material.