Besides, the effects of baseline baPWV on either incident hypertension or SBP at revisit were interactively modified by the level of baseline SBP; the effect size increased as the SBP level decreased. baPWV independently predicted the risk of hypertension and BP progression, modified by the level of SBP at baseline in this Chinese community-based population. The combination of baPWV and SBP can help differentiate the potential high-risk candidates who will develop hypertension quickly and benefit from early diagnosis and treatment.Brachial-ankle pulse wave velocity (baPWV) was proven to be a prognostic indicator of cardiovascular events. However, the modifying effect of blood pressure (BP) on the longitudinal association between baPWV and new-onset hypertension is not well established. This study included 1849 non-hypertensive Chinese subjects from Shougang cohort study during December 2011 to July 2014. BaPWV was obtained using an Omron Colin BP-203RPE III device. Multivariate logistic regression models were used to evaluate associations of baPWV and outcomes. During a mean follow-up time of 2.36 years, 248 (13.41%) developed hypertension. BaPWV independently and gradably predicted the risk of incident hypertension and the SBP level at revisit (odds ratio or  High blood pressure (BP) was the leading risk factor for global disease burden among the 67 risk factors and risk factor clusters in 21 regions worldwide of the Global Burden of Disease study 2010 [As a maker of artery stiffening, pulse wave velocity (PWV)  or brachial-ankle PWV (baPWV)) can independently predict the risk of CVD morbidity and mortality in different populations –6 and isPrevious cohort studies have already elucidated that artery stiffness examined by different techniques like echocardiography , 14, cfPWe enrolled participants from the Shougang cohort study proposed to investigate the epidemiology and risk factors of atherosclerosis diseases. This study enrolled community-based participants aged ≥40 years in the Gucheng and Pingguoyuan communities of Shijingshan district in Beijing, China, during December 2011 to July 2014. Detailed study procedures  have beeThis study was approved by the ethics committee of both Peking University and Peking University First Hospital, and each participant provided written informed consent.All participants were interviewed by trained study coordinators. Standardized questionnaires were used including demographic characteristic, socioeconomic status, health behavior, and medical history. Current smoking was defined as smoking one cigarette per day for no less than half a year. Current drinking was defined as drinking once per week for no less than half a year.Anthropometric measurements such as height and weight were taken according to standard operating procedures. Body mass index (BMI) was calculated as weight (kilograms) divided by height (meters) squared.After a 5-minute rest, seated brachial BP of each participant was accessed using an Omron HEM-7117 electronic sphygmomanometer with standard calibrations. Triplicate consecutive measurements were acquired with ≥1 minute interval between each other. Peripheral systolic BP (SBP) and diastolic BP (DBP) were estimated using these three successive readings' average value.The baPWV measurement was performed using an oscillometry-based device  by a trained technician according to a standard protocol as previously described . The detAfter 12–15 hours of fasting, a venous blood sample was obtained from each participant. Serum or plasma samples were separated within 30 minutes of collection and were stored at −80°C. The Roche C8000 Automatic Analyzer was used for measurement of fasting blood glucose (FBG), the standard 75 g oral glucose tolerance test (OGTT), lipids profiles  cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides), and serum creatinine (Scr) concentrations.μmol/L) was measured using an enzymatic method, and then eGFR was estimated using the equation derived from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) [κ, 1)α × max −1.209 × 0.993Age × 1.018 , where Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is –0.329 for females and –0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.Scr (CKD-EPI) : eGFR = Hypertension was defined as any self-reported history of hypertension, SBP ≥140 mmHg, DBP ≥90 mmHg, or receiving antihypertensive medications. Diabetes mellitus was defined as any self-reported history of diabetes, FBG ≥7.0 mmol/L, OGTT ≥11.1 mmol/L, or receiving hypoglycemic drugs. Dyslipidemia was defined as any self-reported history of hyperlipidemia, triglyceride (TG) ≥1.70 mmol/L (150 mg/dL), total cholesterol (TC) ≥5.18 mmol/L (200 mg/dL), low-density lipoprotein cholesterol (LDL-C) >3.37 mmol/L (130 mg/dL), high-density lipoprotein cholesterol (HDL-C) <1.04 mmol/L (40 mg/dL), or receiving lipid-lowering medications. CVD was defined as any self-reported history of coronary heart disease, stroke, or transient ischemic attack.χ2 test.Quantitative data were expressed as mean  for normally distributed variables and median  for skewed distributed ones. One-way ANOVA was applied to compare normally distributed continuous variables, whereas the Kruskal–Wallis test for skewed distributed ones. Categorical variables were percentages (%) and compared using the Pearson β  were reported according to 1 m/s increase and quartiles of baPWV levels.Generalized linear regression models were used to investigate the effects of baseline baPWV on the risk of incident hypertension and SBP measured at follow-up. Odds ratios (OR) of incident hypertension and We also performed subgroup and interactive analysis to explore the modification effect of covariates, especially baseline SBP levels, on the relationships between baseline baPWV and BP progression and new-onset hypertension. baPWV ≥1400 m/s was adopted as the cut-off value of increased artery stiffness or arteriosclerosis as previously reported , 30.p value of <0.05 (two-sided) was considered statistically significant for all tests. All analyses were performed using Empower (R)  and R (http://www.R-project.org).A 2. The prevalence of diabetes mellitus, dyslipidemia, and CVD were 15.09%, 66.52%, and 5.57%, respectively. Mean (SD) baseline SBP and baPWV were 122.98 ± 9.76 mmHg and 1498.20 ± 276.69 cm/s. Among all participants, 663 (35.86%), 676 (36.56%), and 510 (27.58%) had optimal, normal, and high normal SBP levels, respectively. Participants with high SBP were more likely to be older and males; had higher BMI, DBP, baPWV, TG, FBG, and 2h-PG in OGTT levels, whereas lower HDL-cholesterol level; and had worse kidney function and higher prevalence of current smoking, current drinking, and diabetes mellitus.Baseline characteristics of all eligible participants are shown in P < 0.001).After a mean follow-up time of 2.36 years (median (IQR): 2.40 (2.30–2.40)), 248 (13.41%) developed incident hypertension. Of these, 21 (4.59%), 45 (9.74%), 72 (15.45%), and 110 (23.76%) had incident hypertension among participants with different baseline baPWV levels from quartile 1 (Q1) to quartile 4 (Q4); the risk of incident hypertension was higher among participants with baPWV in the higher quartiles than among those with levels in the lower quartiles (P for trend: <0.001).In P for trend: <0.001).The results of linear regressions for the effect of baseline baPWV on SBP measured at follow-up among 1771 participants without antihypertensive treatment in 2014 were similar as mentioned above . SBP at β and 95% CI: 1.25  for SBP at follow-up).Subgroup and interactive analyses between baseline SBP and baPWV were shown in No other significant heterogeneity was found among nearly all analyzed subgroups except for lipid-lowering drugs , and the main results remained statistically significant.In this study, we longitudinally examined the association of artery stiffness with future new-onset hypertension and the progression of BP in a Chinese community-based cohort. Two main findings were reached as follows: first, the incidence of hypertension and the SBP level at revisit gradually increased with the elevation of baseline baPWV, and this relation was independent of other traditional risk factors for CVD including baseline SBP. Second, interactive effect was found between baPWV and SBP on the risk of SBP progression and incident hypertension, that is to say, a more predominant effect on individuals with optimal SBP levels.Our finding of the relation between baPWV, as an indicator of artery stiffness, and an increased risk of hypertension or BP progression is consistent with previous studies –23. EarlThe mechanism for the artery stiffness and longitudinal BP progression is not completely clear and warrants further researches. Nevertheless, several plausible mechanisms may explain this relationship. The main pathophysiology of a stiffened vasculature is the disrupting elastin in the artery wall, which was proven to predate the subsequent development of hypertension both in mouse models  and patiAdding to prior reports on the existence of association between baPWV and BP increment or incident hypertension, our study is novel in showing that baseline SBP could modify this interrelationship. It is worth noting that there was obvious interactive effect between baPWV and SBP, and a stronger predicting value of baPWV existed in individuals with optimal SBP level, in accordance with the data in normotensive participants of a Korean genome and epidemiology study . One posActually, cfPWV is the most recognized and established index and considered as the “gold standard” for aortic stiffness assessment. However, its measurement requires a high level of skill and exposure of the inguinal region, which largely limit its applicability in clinical practice, especially in a large population research. BaPWV used in our study is an oscillometric technique for measuring arterial stiffness in large- and medium-sized arteries, which is automated and noninvasive and can be applied easily in general population studies. Previous studies have shown that baPWV showed a close correlation with cfPWV . What isSeveral limitations to our study should be acknowledged. First, this observational study does not provide a causal relation between baPWV and the development of hypertension, and this interrelationship should be further explored in intervention study to investigate the change of incident risk of hypertension by lowering artery stiffness. Second, this analysis is based on a short follow-up duration that was no more than 3 years. Consequently, whether the main results were also applied to a long-term examination will be doubted. Third, incident hypertension and BP change were identified by only two surveys (the baseline and the 2014 follow-up examination), so detailed BP information such as BP variations cannot be obtained in our analysis. Finally, our Chinese community-based population made the ability to generalize these results to other race-ethnic populations limited.In summary, our study has demonstrated that artery stiffness evaluated by baPWV independently and gradably predicted the risk of incident hypertension and the SBP level at revisit in this Chinese community-based population. Furthermore, the baseline value of SBP can modify the predicting effect of baPWV on the risk of incident hypertension and SBP progression. Consequently, the combination of the levels of baPWV and SBP can help differentiate the potential high-risk candidates who will develop new-onset hypertension quickly and benefit from early diagnosis and treatment. With regard to the large burden of hypertension worldwide, our study reinforces the importance of regular screening of baPWV in community-based populations and making effort to develop strategies to prevent new-onset hypertension as early as possible.


Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA  were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA. Rheumatoid arthritis (RA), a risk factor for osteoporosis, is accompanied by both periarticular and systemic osteoporosis. The mechanisms of osteoporosis associated with RA involve the influence of inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF); glucocorticoid treatment; and immobility.1. Previously we reported that serum FGF23 levels were related to inflammation and disease activity of RA, and matrix metalloprotease-3 (MMP-3), which is a bone destruction marker, and to bone absorption marker (serum type I collagen cross-linked N-telopeptide [NTx]) but not to bone mineral density (BMD)2. As the mechanism linking inflammation and FGF23 has been studied with regard to iron metabolism4, IL-15β, and IL-66, here we focused on hepcidin as a factor associated with RA inflammation, iron metabolism and systemic osteoporosis.Fibroblast growth factor 23 (FGF23) is bone-derived hormone for phosphorus diuresis that inhibits phosphate reabsorption and active vitamin D synthesis in the kidney. When kidney function decreases, the serum FGF23 level increases8. Hepcidin is synthesized in hepatocytes and secreted into the bloodstream, where it binds to the iron exporter ferroportin (FPN) in target cells, macrophages, and enterocytes and to some extent in hepatocytes. Hepcidin expression is modulated by iron, inflammation (IL-6), and erythropoiesis. Several recent reports have indicated that iron metabolism can affect bone metabolism10. Hemochromatosis and thalassemia cause iron overload and osteoporosis12. Iron overload is a risk factor for progressive bone loss in healthy postmenopausal women and middle-aged men13. Furthermore, in one study, lower serum hepcidin levels and higher serum iron levels were reported in patients with osteoporosis than healthy controls14.Hepcidin is a major regulator of iron metabolism and homeostasis and is related to anemia of inflammationThis study investigated whether iron metabolism and serum hepcidin are related to systemic osteoporosis in patients with RA.2). The mean disease duration was 13.6 ± 10.6 years and the mean disease activity scores in 28 joints (DAS28) based on serum CRP and erythrocyte sedimentation rate (ESR) were 2.2 ± 1.5 and 2.6 ± 1.0, respectively. Most patients were classified as being in remission or showing low disease activity, based on the DAS28-CRP and clinical disease activity index (CDAI) . Biological disease-modifying antirheumatic drugs (bDMARDs) including anti-TNF and tocilizumab (TCZ) treatment, were used by 33.6% of subjects, and TCZ was used by 8% of subjects. Active form of vitamin D preparation was prescribed in 14.1% of subjects. The mean eGFR was 73.3 ± 19.6 mL/min/1.73 m2, and 26% of the subjects showed an eGFR <60 mL/min/1.73 m2. Bisphosphonate or denosumab was used by 63% of subjects. Based on the T score of the femoral neck, osteoporosis and osteopenia were diagnosed in 18.7% and 57.3% of cases, respectively. Based on the T score of the lumbar spine, the respective rates were 22.1% and 36.6%. The T score was normal in the femur in 23.3% of cases, and in the lumbar spine in 41.2% of cases; this difference may have been due to the differential effects of osteoporosis treatment on trabecular and cortical bone. Another possible factor is the progression of vertebral compression and deformity. The mean hemoglobin (Hb) level was 12.5 ± 1.4 g/dL and only a patient showed Hb <9.0 g/dL (which was 8.9 g/dL). No patient was diagnosed with polycythemia. Only 3.4% of our patients used iron agent to treat iron deficiency anemia after being diagnosed by the attending physician.The characteristics of the study subjects are listed in Table The mean serum hepcidin concentration was 14.3 ± 19.7 ng/mL    and those showing low disease activity   but not in those showing in moderate to high disease activity (CDAI 10 < )  Table .With regard to osteoporosis and markers of bone metabolism, the serum iron level was positively related to femoral T and Z scores , and ferritin and hepcidin levels were positively related to the 25(OH)D level  , and serum ferritin and hepcidin levels were positively related to the serum 25(OH)D level . Annual change of lumbar T score, but not that of femoral T score, was positively related to serum hepcidin level . MMP-3 was also positively related to the serum ferritin level , whereas FGF23, bone alkaline phosphatase and TRACP-5b were not related to any of these three variables , and between serum hepcidin and the annual change in lumbar T score  in patients in remission  Table . Serum 2All subjects were divided into four groups according to serum hepcidin level D level D level, which is positively related to the femoral Z score. As to 231 patients re-examined BMD, annual change of lumbar T score was positively related to serum hepcidine level and higher 25(OH)D quartiles. The serum hepcidin level and iron metabolism indirectly and directly affected osteoporosis in patients with RA.16, which may be the result of inflammation due to RA. Iron deficiency, which often accompanies RA, is also an essential factor influencing serum hepcidin. In one study, patients with RA and iron deficiency had significantly decreased serum hepcidin levels compared to those with RA and anemia with chronic inflammation17. As hepcidin is influenced by inflammation and iron metabolism, results differ on the influence on Hb and disease activity associated with hepcidin on RA18. Furthermore, in the same study of patients with RA, iron metabolism was related to serum hepcidin levels cross-sectionally, but inflammation was related longitudinally19. Anti-IL-6 therapy decreases serum hepcidin and improves the Hb level22, and the effect is more marked with anti-IL-6 than anti-TNF therapy20. In our cross-sectional study, CRP and Hb were related to the serum hepcidin level, but stronger relationships were observed for iron metabolism . Moreover, positive relationships were found among serum hepcidin, ferritin, iron and Hb levels which seemed like iron deficiency anemia pattern. The reason for less influence from inflammation was considered because most patients in this study mainly showed low disease activity or were in remission. Also a high percentage of patients in the lower quartile of serum hepcidin level were treated with bDMARDs. Thus, the serum hepcidin level seemed to be closely reflected by iron metabolism, including in patients showing low disease activity or in remission.Researchers have reported serum hepcidin concentrations in patients with RA, focusing on anemia. In studies, the serum hepcidin level was higher in patients with RA compared to healthy subjects25. In one study, hepcidin knockout mice had a higher serum ferritin level and higher iron in the liver and femur than controls and showed low bone mass and changes in bone microarchitecture26. Hepcidin knockout mice also showed a marked reduction in bone load-bearing capacity with enhanced bone resorption23. A mouse model with overexpression of hepcidin showed higher levels of serum hepcidin and lower levels of serum ferritin, and bone loss and changes in markers of bone metabolism after ovariectomy were ameliorated24. In humans, genetic hemochromatosis and thalassemia cause iron overload, and osteoporosis is a major complication12. Iron overload (an elevated ferritin level) is a risk factor for progressive bone loss in healthy postmenopausal women and middle-aged men and a risk factor for radiological vertebral fracture in postmenopausal women13. Liu et al. compared serum hepcidin levels in 40 patients with osteoporosis and 40 healthy controls14. They identified lower serum hepcidin levels and higher iron levels in patients with osteoporosis compared to healthy controls, and the serum hepcidin level was negatively related to the serum iron level14. In this study, the serum hepcidin level was positively related to serum iron and ferritin levels, and serum iron levels were positively related to BMD, in contrast to the studies outlined above. Moreover, annual change of lumbar T score, not femoral, was positively related to serum hepcidin and 25(OH)D levels. No direct relations were found between markers of bone metabolism and the serum hepcidin level. Those findings were more apparent in patients who were in remission. The unexpected results about iron metabolism and osteoporosis in this study seemed because the relationships between serum iron and hepcidin levels and inflammation due to RA, bDMARD treatment, and iron deficiency in patients with RA are complicated. The disease activity of most patients in this study was low; the results may have been different in patients with higher RA activity.Iron accumulation is a risk factor for osteoporosis, and hepcidin is expected to be a useful therapeutic target27. Vitamin D affects bone mineralization and calcium regulation, and the serum level of 25(OH)D in RA is positively related to BMD28. A recent in vitro study suggested that binding of 1,25(OH)2D to the vitamin D receptor directly suppressed hepcidin gene transcription29. Furthermore, supplementation of vitamin D reduces serum hepcidin levels in healthy subjects30, patients with chronic kidney disease31, and pediatric patients with inflammatory bowel disease32. In this study, the serum 25(OH)D level was not related to disease activity but was negatively related to renal function and positively related to the serum adjusted Ca level, serum ferritin level, serum hepcidin level, serum FGF23 level, and femoral Z score. There are some possible explanations for the positive association between 25(OH)D and hepcidin. First, the results of cross-sectional studies of the relationship between hepcidin and 25(OH)D are inconsistent. One study of children with inflammatory bowel disease suggested that a higher 25(OH)D concentration was related to a lower hepcidin level33. Another study of older Mexican adults indicated that the serum hepcidin level did not differ between patients with 25(OH)D ≥ 50 nmol/L and <50 nmol/L34. The characteristics of subjects were markedly different in these two studies and the present study. Second, race may influence the association between vitamin D deficiency and anemia35. In one study, serum 25(OH)D < 50 nmol/L was significantly associated with anemia among black but not white subjects35. Further research is needed to reach definitive conclusions.Vitamin D deficiency is a risk factor for autoimmune disorders, including RA2, RA disease activity and MMP-3 are positively related to serum FGF23 levels. Meanwhile, this study showed that higher FGF23 levels are related to lower Hb levels and to higher 25(OH)D and adjusted Ca levels. This study and the previous study differed with regard to the subjects; the previous study included patients with higher disease activity  than patients in the present study.In this study, a higher FGF23 level was related to less kidney function and older age but not to serum hepcidin level. As we reported previously36. Hepcidin deficiency due to genetic hemochromatosis or severe liver dysfunction leads to higher iron levels, while higher hepcidin levels decrease iron levels, as seen in chronic inflammation and some cancers. When inflammation occurs due to RA, the production of hepcidin increases due to the expression of inflammatory cytokines, and affects to decreasing iron and increasing ferritin levels. In this study of RA patients in remission or showing low disease activity, the serum iron level was positively associated with serum hepcidin and ferritin levels, but was negatively associated with inflammation due to RA. Although iron overload and hepcidin may influence osteoporosis, the serum iron level was positively related to BMD in this study but serum hepcidin and ferritin levels were not. However, the serum 25(OH)D level was positively related to the serum hepcidin level and also positively related to femoral Z scores. Serum hepcidin level was also positively related to the annual change of lumbar T score. In contrast to previous reports, opposite effects of the serum iron level to BMD and the serum 25(OH)D level to the serum hepcidin level were indicated, and further research is needed to determine the mechanisms. However, the serum FGF23 level was not directly related to the serum hepcidin level, but the serum 25(OH)D level and inflammation were common factors related to both serum hepcidin and FGF23 levels.Finally, we investigated relationships among serum hepcidin, iron metabolism and osteoporosis in patients with RA Fig. . HepcidiThe major limitation of this study is single-center nature and the absence of healthy controls. Blood samples were not collected during fasting so an effect of diet cannot be ruled out. We could not analyze the patient background of smoking, alcohol intake, menopausal status and the use of hormone replacement therapy. Also, physical activity and body weight bearing activity were not included, but health assessment questionnaire without disability index (HAQ-DI) and BMI could replace them. We investigated only serum markers and BMD but not fracture data. Further studies are needed regarding to fragility fractures controlling patients’ background. The number of patients using iron agents was low and no significant effect was observed.In conclusion, the serum iron level was positively related to BMD in these patients with RA, and a higher iron level was not considered a risk factor for osteoporosis. The serum hepcidin level was not related to BMD and markers of bone metabolism but was positively related to the serum 25(OH)D level, which was positively related to the femoral Z score. And the serum hepcidin level was positively related to the annual change of lumbar T score. The serum FGF23 level was not associated with the serum hepcidin level. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in this study of patients with RA.37 and/or the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) RA criteria38. A total of 263 patients consented to participate in this study and 1 patient was excluded because of an elevated ferritin level . Blood samples were taken in either the morning or afternoon. RA activity and treatments were reviewed through medical records.The study population consisted of 262 patients with RA treated at the Niigata Rheumatic Center between December 2015 and October 2016. The inclusion criterion was meeting the 1987 American Rheumatism Association criteria for RAThe study protocol was approved by the ethics committee of the Niigata Rheumatic Center and performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.−1.094 × Age−0.287 × 0.739, which was developed using the inulin clearance of Japanese subjects as a standard39. Serum adjusted calcium levels were calculated if serum albumin levels were below 4 g/dL as follows: actual calcium level + 4 – serum albumin level40.Estimated glomerular filtration rates (eGFRs) were calculated using the standard formula for females, 194 × Cr41. 25(OH)D was quantified by electrochemiluminescence immunoassay .Hepcidin, FGF23, and 25-hydroxy vitamin D (25[OH]D) concentrations were determined using serum samples collected and stored at −80 °C. The serum hepcidin level using liquid chromatography-tandem mass spectrometry . The serum FGF23 level was measured using sandwich enzyme-linked immunosorbent assay , which detected full-length human FGF23Reference ranges of bone metabolic markers were follows; bone alkaline phosphatase, 3.7–20.9 μg/L for men, 2.9–14.5 μg/L for premenopausal women and 3.8–22.6 μg/L for postmenopausal women; tartrate-resistant acid phosphatase-5b (TRACP-5b), 170–590 mU/dL for men and 120–420 mU/dL for women; matrix metalloprotease 3 (MMP-3), 35.2–123.8 ng/mL for men and 16.1–56.8 ng/mL for women. The serum 25(OH)D levels were classified as follows: 30 ≤ ng/mL, sufficient; 20 ≤ and < 30 ng/mL, insufficient; <20 ng/mL, deficient.Bone mineral density (BMD) using dual-energy X-ray absorptiometry . Lumbar spine L1–4 and basically left, but if impossible right femoral neck, were evaluated at the recruitment in all patients. The T score represents the difference from the mean BMD of young healthy subjects (in terms of standard deviation), and the Z score is obtained based on comparison with age- and sex-matched controls. The BMD T scores were classified as follows: ≦−2.5, osteoporosis; −2.5< and < −1, osteopenia; −1≦, normal. Two hundred and thirty-one patients were re-examined BMD in about three years and annual change of T score was evaluated. The mean observational period was 2.0 ± 0.33 years (0.63–3.25).Most data are expressed as the mean ± standard deviation or number (%). As serum hepcidin levels were not normally distributed, the actual hepcidin level + 1 was logarithmically transformed. Correlation coefficients were obtained using Spearman’s rank method and also correlation coefficients adjusted for age, sex, body mass index (BMI), eGFR, C-reactive protein (CRP), and use of biological disease-modifying antirheumatic drugs (bDMARDs) were calculated. Two groups of categorical variables were compared using the Mann–Whitney U test. Multiple regression analyses were performed with adjustment for the following factors: age, sex, BMI, eGFR, CRP, and the use of bDMARD, PSL, anti-bone resorption drug, teriparatide, and iron agent. Serum hepcidin, FGF23, and 25(OH)D levels were divided into four groups as Q1–Q4 using SPSS software, and the associations between these quartiles and other parameters were analyzed with the Jonckheere-Terpstra trend test.p < 0.05 was taken to indicate statistical significance.All statistical analyses were performed with SPSS . In all analyses, Supplementary information.


To explore the clinical characteristics of reactivation of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The pathological correlation of prognosis and hepatitis B virus reactivation has been given detailed analyses in our research.  A total of 108 related TACE-treated HCC clinical data from January 2008 to January 2016 was gleaned and involved in this retrospective analysis. To lucubrate the nuance of survival rates between HBV reactivated group and HBV nonreactivated group, clinical data of each patient was analyzed in detail and refined the retrospective studies. 4 in patients showed a reactivation rate of 65.8% (25/38), which was significantly higher than the HBV DNA < 104 cases . Research data revealed a conspicuous lower cellular immunity (P < 0.01) and better 2-year survival rate (P=0.03) in the HBV-reactivated group when compared to the nonreactivated group.  HBV reactivation occurred in 42 patients with a proportion of 38.9%. The detected HBV DNA level ≥10 Some of the patients with primary hepatocellular carcinoma possibly had HBV reactivation at post-TACE-therapy. And the predominant risk factors of HBV reactivation are positive HBV test and immunosuppression. Our study suggested that HBV reactivation at post-TACE-therapy is an independent predictor of poor prognosis and low survival rate as well as a crucial reason for poor prognosis and lower survival rate, which indirectly proved that it is urgent to necessitate the antiviral therapy and immune enhancer in improving the curative effect and prognosis of HCC patients. Hepatocellular carcinoma (HCC) is a common malignant cancer that perils human health, which is a serious cause of mortality . RecentlFrom January 2008 to January 2016, patients with hepatitis B-related liver cancer who underwent TACE in the Department of Hepatobiliary Surgery, the second affiliated hospital of Jiaxing University, were collected. Patients were enrolled in this study when meeting the following criteria: age ≥20 years; histological or clinical diagnosis of HCC by early tumor staining, dynamic CT, and dynamic magnetic resonance imaging (MRI); the presence of unresectable HCC; absence of indications for liver transplantation and local ablation ; Child-Pugh A or B; PS 0-2; and a more than 60-day lifespan. Exclusion criteria were as follows: receiving liver cancer treatment within 28 days before TACE; frequent use of phenytoin, warfarin, or flucytosine; severe heart failure; uncontrollable diabetes mellitus; active infection; women of childbearing age who did not use effective contraceptives; pregnancy or lactation; severe drugs' allergic; mental disorders; watery diarrhea; moderate or obvious thoracic cavity Effusion or ascites; and other serious diseases. All patients received TACE for the first time and followed the principle of TACE.The study was approved by the institutional review committee of Jiaxing Second Hospital in Zhejiang Province. Written informed consent was obtained from each participant.Seldinger technology was utilized to conduct transcatheter arterial chemoembolization (TACE). The catheter was inserted into the common hepatic artery or the proper hepatic artery through the right inguinal femoral artery puncture. Splanchnic angiography was performed to assess tumor size, location, and arterial supply. The tip of the catheter was introduced into the tumor-supplying artery. Subsequently, 500–1000 mg of fluorouridine purchased from Zhejiang Haishun pharmaceutical, Zhejiang, China; 60 mg of epirubicin purchased from Pfizer, Bronx, New York, United States; 60 mg of cisplatin obtained from Qilu pharmaceutical, Shandong, China; and 10 ml of iodized oil obtained from GBE, Villepin, France, were injected into tumor blood vessels. Finally, we injected the gelatin sponge particles  to embolize the blood supply to the tumor.A retrospective analysis of all selected cases data was then performed using SPSS software. The levels of HBV DNA and alpha-fetoprotein (AFP) were measured before and 1 month after surgery. Flow cytometry was adapted to detect the preoperation and 1-week postoperation quantities of CD3+, CD4+, and CD8+ T cells. A patient was considered positive for HBV DNA when the HBV DNA level is over 1000 copies/mL. Serum HBV DNA levels 10 times higher than baseline are considered to be HBV reactivation . All patt-test and partly by the chi-square test. Kaplan-Meier analysis was used for survival analysis. A two-sided P value <0.05 was considered statistically significant.Data was analyzed using SPSS . Continuous variation was compared by the A retrospective analysis of 108 patients was done, including 69 males and 39 females, and the average age was 58.69 ± 10.23 years (33–83 years). We divided 71 cases of Child-Pugh A and 37 cases of Child-Pugh B into two groups, of which 81 cases were single nodules and 27 cases were multiple nodules. The average size of the nodules was 6.72 ± 2.08 cm (3–11 cm). And there were twenty-six cases of portal vein cancer thrombosis comorbidity (PVTT).4 copies/mL) after TACE, the HBV DNA levels of 73 HBV DNA positive patients before TACE (2.44 ± 3.19 × 105 copies/mL) were significantly increased (P < 0.01).Before TACE, patients with a proportion of 67.65% (73/108) were tested HBV DNA positive. One month after therapy of TACE, 42 patients had developed HBV reactivation (of which 24 cases of Child A and 18 cases of Child B), 3 patients who were tested HBV DNA negative subsequently turned into positive, and 39 patients had a 10-fold increase in HBV DNA levels. The reactivation of HBV has no distinct correlation with nodules number, the size of lesions, gender, age, HBeAg, liver cirrhosis, and PVTT. Compared with 76 HBV DNA positive patients (2.79 ± 2.68 × 10P < 0.01), which indicates that the patient's immune system is suppressed after TACE.In 4 copies/mL) were more likely to develop HBV reactivation (65.79% [25/38]) than patients with low HBV DNA levels (<104 copies/mL)  (P < 0.01). Nevertheless, other analytical results of related clinical features demonstrated that there were no statistical differences in age, gender, hepatitis B e antigen (HBeAg), child grade, cirrhosis comorbidity, and PVTT comorbidity between the two groups.Patients were allocated into two groups based on whether HBV reactivation occurred, and the clinical data of these two groups were compared to give an analysis. Patients with high HBV DNA levels (>10 < 0.01) . The immP > 0.05) in one-year survival rate between patients with HBV reactivation (69.2%) and patients without HBV reactivation .Patients' follow-up was conducted in outpatients or by telephone with an average of 17.8-month of follow-up time (range: 3–40 months). 9 cases were lost, which accounted for 8.3%. There was no significant difference . Our results and previous reports have proved that HBV reactivation can affect the efficacy of TACE therapy. Moreover, our follow-up data indicated that the two-year survival rate in patients with HBV reactivation was conspicuously lower than that in patients without HBV reactivation. This might be because HBV is highly replicated in patients with HBV reactivation, causing damage to liver function and suppressing the immune response. These events facilitate the development of HCC, resulting in a poor prognosis of HBV reactivation patients. From the analytical results of this study, we consider that the reactivation of HBV would thereby aggregate the course of HCC patients, and antiviral therapy against HBV is of great importance and is well recommended for the prognosis improvement of HCC patients who received TACE treatment, which is consistent with the consequence declared by Granito and Bolondi [In this study, we have found that the AFP level of HBV reactivation patients is conspicuously higher than that in patients without HBV reactivation. Previous reports have indicated that the serum AFP level affects the outcomes of TACE in HCC patients, so the serum AFP level is an independent factor affecting survival time , 19. Add Bolondi .In HCC patients who developed HBV, antiviral therapy is usually recommended by clinicians. A recent study shows that antiviral therapy can improve survival time for patients with HBV-related hepatocellular carcinomas . Nagamat4 copies/mL. Therefore, early prophylaxis should be provided by administering a combination of antiviral drugs and immunopotentiation therapy. Further studies are needed to confirm the efficacy of this combinatorial prophylaxis on the prognosis and survival time of patients with HBV-related HCC.In conclusion, not all HBV-related HCC patients experience HBV reactivation after TACE. HBV reactivation is more likely to happen in patients when HBV DNA level >10


A series of evidence revealed that body mass index was an important confounding factor in the research of uric acid and ischemic heart disease/hypertension. The objective of this study was to investigate whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD, and the possible interactive effect of hyperuricemia and obesity.2. The adjusted OR values of hyperuricemia and obesity were analyzed by multivariate logistic regression analysis, and the additive model was used to investigate the possible interactive effect.We conducted a cross-sectional study in a total of 557 ultrasound diagnosed-NAFLD. The hepatic steatosis and liver fibrosis were quantitatively evaluated by transient elastography. Hyperuricemia was defined as serum uric acid > 420 μmol/L in men, > 360 μmol/L in women and obesity was defined as body mass index ≥ 25 kg/mMultivariate regression analysis showed that hyperuricemia was associated with serious hepatic steatosis (1.74[1.09–2.79]) and elevated ALT (2.17[1.38–3.41]), but not with advanced fibrosis (1.61[0.91–2.85]). The association was further investigated in different BMI group. Hyperuricemia was associated with higher odds of serious hepatic steatosis (2.02[1.14–3.57]) and elevated ALT (2.27[1.37–3.76]) only in obese NAFLD, not in non-obese subjects. Similarly, patients with hyperuricemia had higher odds of advanced fibrosis in obese subjects (2.17[1.13–4.18]), not in non-obese subjects (0.60[0.14–2.70]). Furthermore, there was an additive interaction between hyperuricemia and obesity on the odds of serious hepatic steatosis (AP: 0.39[0.01–0.77]) and advanced fibrosis. (AP: 0.60[0.26–0.95]).Hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Thus, management of uric acid may need to be targeted in obese NAFLD. Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing chronic liver disease and epidemiological data indicates that the prevalence of NAFLD is currently 25% globally . NowadayPrevious studies have revealed an independent link between hyperuricemia and the severity of liver damage in NAFLD. A biopsy-based study has demonstrated that hyperuricemia is associated with the severity of steatosis, lobular inflammation and nonalcoholic fatty liver disease activity score (NAS) . SimilarObesity is an established risk factor for the occurrence and development of NAFLD. Recently, a series of evidence reveal that body mass index (BMI) is an important confounding factor in the research of uric acid and metabolic diseases. Based on the data from two large prospective cohort study, Palmer shows that uric acid has no causal effect on the risk of ischemic heart disease and blood pressure. This conclusion is inconsistent with previous studies mainly due to the confounding role of BMI . The TroHence, we assume that it is of importance to take obesity status into account to investigate the association between hyperuricemia and the severity of NAFLD, particularly in the liver fibrosis. The objective of this study was to investigate whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD, and the possible interactive effect of hyperuricemia and obesity.2 and non-obesity was BMI < 25 kg/m2 [A total of 557 ultrasound diagnosed-NAFLD patients from the Second Affiliated Hospital of Xi'an Jiaotong University during March 2014 to January 2018 were included in this cross-sectional study. NAFLD was defined as hepatic steatosis detected by abdominal ultrasound, which was evaluated by two experienced sonographers independently. If there was an inconsistent diagnosis, the third sonographer was needed for evaluation. Exclusion criteria: (1) excessive alcohol consumption (> 20 g/day in man and 10 g/day in women) (2) use of steatogenic medications within the past 6 months (3) positive tests for hepatitis B surface antigen and hepatitis C antibody (4) drug-induced liver injury and autoimmune hepatitis (5) cirrhosis and other causes of liver disease  . Accordi25 kg/m2 . All patDemographic data was derived from the electronic medical record, including age, gender, height, weight, blood pressure, history of hypertension/diabetes/underlying liver disease/alcohol consumption . Biochemical markers were as follows: alanine transaminase (ALT), fasting plasma glucose (FPG), serum uric acid (SUA), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), platelets (PLT).Transient elastography (FibroTouch) was performed to assess hepatic steatosis  and fibrosis  quantitatively. It was conducted by a trained operator who had performed at least 500 operations. The available measurement needed to satisfy the following conditions: (1) At least 10 valid measurements were obtained, and the success rate > 60%. (2) IQR/M of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) < 30%.1/2).The severity of NAFLD was evaluated ranging from serious hepatic steatosis, elevated ALT to advanced fibrosis. Hepatic steatosis was divided into two groups according to CAP value: Mild steatosis ≤ 265 dB/m; Serious steatosis (moderate or severe steatosis) > 265 dB/m. Elevated ALT was defined as ALT level > 40 IU/L , 18. Con2 in both genders; (2) hypertriglyceridemia: triglycerides ≥ 1.7 mmol/L, or in therapy; (3) low HDL-C: HDL-C < 1.03 mmol/L in men and < 1.29 mmol/L in women; (4) elevated blood pressure: blood pressure ≥ 130/85 mmHg, or diagnosed hypertension; (5) elevated fasting glucose: FPG ≥ 5.6 mmol/L or diagnosed type 2 diabetes.Considering the close relationship between metabolic syndrome and NAFLD, the components of metabolic syndrome were adjusted in multivariate regression analysis. The diagnosis of metabolic syndrome needed to meet at least three of the following criteria : (1)centContinuous variables were shown as mean with standard deviation and compared using the t-test. Categorical variables were summarized as frequencies with percentages and compared by chi-square analysis. Multivariable logistic regression analysis was performed to determine the adjusted odds ratios (ORs) for serious hepatic steatosis, elevated ALT and advanced fibrosis. A method proposed by Rothman was used to test for additive interaction between hyperuricemia and obesity. The Excel software proposed by Andersson was used to quantify the amount of additive interaction, including the relative excess risk due to the interaction (RERI), the attributable proportion due to the interaction (AP) and the synergy index(S). Zero within the 95% confidence interval of RERI and AP indicated no additive interaction, and one within the 95% confidence interval of S indicated no additive interaction. SPSS 18.0 was used for statistical analysis, and P < 0.05 was considered to be significant.2, and 61.8% of NAFLD was male. The prevalence of metabolic syndrome and hyperuricemia was 72% and 23.9%, respectively. With regards to the incidence of components of metabolic syndrome, the highest incidence was 73.8% in central obesity, followed by low HDL-C, elevated fasting glucose and hypertriglyceridemia with an incidence of 64.1%, 61.4% and 61.2%, and the lowest was 46.7% in elevated blood pressure. In terms of the severity of NAFLD, the proportion of serious hepatic steatosis, elevated ALT and advanced fibrosis were 57.6%, 34.6% and 16.7%. Compared with normouricemia group, patients in the hyperuricemia group were younger and had higher BMI and triglyceride levels, but there was no difference in the distribution of other metabolic component. Moreover, hyperuricemia group had more serious hepatic steatosis and elevated ALT, but not advanced fibrosis.Characteristics of patients were shown in Table The adjusted ORs of hyperuricemia for the severity of NAFLD were shown in Table Furthermore, patients were categorized into four groups according to the level of SUA and BMI: Control group (normouricemia and non-obesity). Hyperuricemia group (hyperuricemia and non-obesity), Obese group (normouricemia and obesity), Obese-hyperuricemia group (hyperuricemia and obesity). Compared with the control group, the ORs for the severity of liver damage in NAFLD were shown in Table We further analyzed the additive interaction effect between hyperuricemia and obesity on the severity of NAFLD, and the results were shown in Table In the present study, we investigated whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD. There were three main findings. Firstly, hyperuricemia was associated with the severity of steatosis, liver inflammation in NAFLD, but not with liver fibrosis. Secondly, hyperuricemia was associated with higher odds of serious hepatic steatosis, elevated ALT and advanced fibrosis in obese NAFLD, whereas the significance was lost in non-obese individuals. Thirdly, there was an additive interaction between hyperuricemia and obesity on the odds of serious hepatic steatosis and advanced fibrosis.As mentioned previously, hyperuricemia was associated with the severity of steatosis, lobular inflammation in NAFLD, but not with liver fibrosis , 10.ThesWhen obesity and hyperuricemia were present together, there was a strikingly high odds of serious steatosis, elevated ALT and advanced fibrosis, compared with the effect of obesity alone. Whereas hyperuricemia alone was not related to the severity of liver damage. Furthermore, additive interaction analysis found that hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Specifically, when hyperuricemia and obesity were present together, 39% of the prevalence for serious hepatic steatosis and 60% of that for advanced fibrosis was due to the interaction effect. The classical ‘two hits thesis’, commonly accepted hypothesis of NAFLD pathogenesis, may explain the interaction effect. Obesity was the ‘first hit’ which promoted lipid accumulation in liver, and increased the susceptibility of the liver to injury. Hyperuricemia, as the ‘second hits’, contributed to inflammation with hepatocyte injury and further lead to NASH and hepatic fibrosis . Data inHere, we highlighted that uric acid may act as a pro-oxidant in the obese state, and hyperuricemia was synergistic with obesity to exacerbate the progression of NAFLD. Up to date, treatment of asymptomatic hyperuricemia was ambiguous, and optimal management of hyperuricemia was a matter of urgency in cardiovascular, metabolic, and renal comorbidities. Our study provided an idea for the targeted management of hyperuricemia in obese NAFLD. Several limitations should be noted in this study. Firstly, this was a cross-sectional study that could not determine the causal relationship between obesity, hyperuricemia and liver damage in NAFLD, only provide evidence of relevance. Thus, more large-scale prospective studies are demanded to verify results in this study. Secondly, liver biopsy was not available in this study, due to the low acceptability of liver biopsy in NAFLD. There were two main imaging techniques to non-invasively assess the degree of liver steatosis and fibrosis: ultrasound-based and magnetic resonance-based elastography techniques. MRE showed the highest diagnostic accuracy in the detection of advanced fibrosis in NAFLD. And diffusion-weighted MRI (DW-MRI) was the only functional imaging technology that can measure the motion of water in the extracellular space in living tissues, and the measured apparent diffusion coefficient (ADC) value can relatively accurately reflect the degree of liver fibrosis –31. TranOur results revealed that hyperuricemia was associated with the severity of liver damage in obese NAFLD, not in non-obese individuals. And hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Thus, management of uric acid may need to be targeted in obese NAFLD.


While emergent pancreatic resection for trauma has been previously described, no large contemporary investigations into the frequency, indications, and outcomes of emergent pancreatectomy (EP) secondary to complications of neoplastic disease exist. Modern perioperative outcomes data are currently unknown.ACS-NSQIP was reviewed for all non-traumatic pancreatic resections  in patients with pancreatico-biliary or duodenal-ampullary neoplasms from 2005 to 2013. Patients treated for complications of pancreatitis were specifically excluded. Emergent operation was defined as NSQIP criteria for emergent case and one of the following: ASA Class 5, preoperative ventilator dependency, preoperative SIRS, sepsis, or septic shock, or requirement of > 4 units RBCs in 72 h prior to resection. Chi-square tests, Fisher’s exact tests were performed to compare postoperative outcomes between emergent and elective cases as well as between pancreatectomy types.p < 0.001) for emergent vs. elective operations. Emergent operations resulted in increased transfusion rates , return to OR , organ-space infection , unplanned intubation , pneumonia , length of stay , and discharge to skilled facility (31.1% vs. 13.9%). These differences persisted when stratified by pancreatic resection type. The 30-day operative mortality was higher in the emergent group  and highest for emergent TP (20%).Of 21,452 patients who underwent pancreatectomy for neoplastic indications, we identified 534 (2.5%) patients who underwent emergent resection. Preoperative systemic sepsis (66.3%) and bleeding (17.9%) were most common indications for emergent operation. PD was performed in 409 (77%) patients, DP in 115 (21%), and TP in 10 (2%) patients. Overall major morbidity was significantly higher (46.1% vs. 25.6%, Emergent pancreatic resection is markedly uncommon in the setting of neoplastic disease. Although these operations result in increased morbidity and mortality compared to elective resections, they can be life-saving in specific circumstances. The results of this large series of modern era national data may assist surgeons as well as patients and their families in making critical decisions in select cases of acutely complicated neoplastic disease. Emergency pancreatic surgery is a rare event that is most commonly performed in the setting of blunt or penetrating abdominal trauma resulting in severe pancreatico-duodenal injury  . EmergenIn the elective setting, pancreas resections are being more commonly performed at high-volume centers with well-defined outcomes with anticipated perioperative morbidity and mortality, 32–38% and 0–5%, respectively , 5. UtilData was queried from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2013. ACS-NSQIP collects data on 305 variables including 30-day morbidity and mortality for patients undergoing surgical procedures. All patients with a Current Procedural Terminology (CPT) code for Pancreaticoduodenectomy , Distal Pancreatectomy , or Total Pancreatectomy  were queried. Only patients with an International Classification of Diseases 9th Revision (ICD-9) code for pancreas cancer , duodenal neoplasm , neuroendocrine tumor , and bile duct and ampullary neoplasm  were included in the analysis. Patients with an ICD-9 code for pancreatitis (577.0–577.9) or a procedure code for resection or debridement of the pancreas for acute necrotizing pancreatitis (48105) were excluded to minimize confounding ambiguity. We specifically excluded patients that underwent emergent re-operation after recent previous pancreatectomy. Three patients had both a DP and PD and were excluded from the analysis. Operations were considered to be emergent if the case was coded as emergent per ACS-NSQIP or any of the following: American Society of Anesthesiologists (ASA) Class 5, preoperative ventilator dependency, preoperative Systemic Inflammatory Response Syndrome (SIRS), sepsis, or septic shock, or requirement of > 4 units RBCs in 72 h prior to resection. Pre-operative mechanical ventilation was utilized as a surrogate indicator for EP given the ICU status of patient and obvious contraindication to elective oncologic resection. SIRS, sepsis and septic shock were defined according to the 2001 international sepsis definitions conference [p < 0.05 being considered significant. The Cochran-Armitage test for trend p-values (two-sided) was used to compare annual outcomes over the course of the study period. Only 5 covariates could be utilized in the multivariable modeling as there were only 50 patients with the outcome of interest . Given the changes in transfusion data and limited availability of preoperative chemotherapy and radiation therapy at all participating NSQIP centers in the later years of our study, these were excluded from multivariate modeling. All statistical analysis was performed using SAS Version 9.3 .The primary end points of this study were 30-day morbidity and mortality. Major postoperative morbidity was defined as: cardiac arrest, myocardial infarction, stroke/CVA with deficits, wound disruption, deep incisional surgical site infection (SSI), organ space SSI, sepsis or septic shock, unplanned intubation, postoperative ventilator requirement exceeding 48 h, pneumonia, acute renal failure, progressive renal insufficiency, DVT/thrombophlebitis, pulmonary embolism, and unplanned return to OR. While there exists no ACS-NSQIP code for postoperative pancreatic fistula (POPF), organ-space surgical infection is often utilized as a proxy for this development and was thus included . Of noten = 409, 76.6%), DP , and TP . Mean age of all patients undergoing an EP was 64.7 ± 12.7 years. The median age in the PD and TP groups  was greater than those who underwent a DP (60 years) (p < 0.001). Overall, 48.7% of the EP cases were male gender with similar distributions between the different types of pancreatectomy . Median BMI was similar across all groups, 26.4 in PD, 26.8 in DP, and 22.9 in TP (p = 0.22). Patients undergoing emergent TP or PD had a higher preoperative bilirubin levels (median 1.8 mg/dl and 1.5 mg/dl) compared to those undergoing DP (0.5 mg/dl), (p < 0.001). There were no differences in preoperative functional status, transfusion requirements, delivery of chemotherapy and/or radiotherapy in the preceding 30 days between pancreatectomy types.During the study period 21,452 patients underwent pancreatectomy for non-traumatic, non-pancreatitis, neoplastic disease indications. Of these, 534 patients (2.5%) underwent an EP based upon our defined parameters. Preoperative systemic sepsis (66.3%) and transfusion-dependent hemorrhage (17.9%) were the most common indications for emergent pancreatectomy (Table p < 0.001). Furthermore, major complications were experienced in 46.1% of emergent cases compared to 25.6% elective patients (p < 0.001). No difference was demonstrated in the SSI rate between the emergent and elective cohorts . However, when stratified by SSI subtype, organ-space infection rates were greater in those undergoing an EP versus elective pancreatectomy . Unplanned intubation and return to the OR rates were also greater (p < 0.001). With the increased morbidity associated with EP, median LOS was prolonged by 6 days  and more patients required discharge to a skilled nursing facility for rehabilitation . Lastly, 30-day mortality for the EP cohort was significantly increased at 9.4% compared to 2.7% in the elective cohort (p < 0.001).Table p < 0.001). No difference for perioperative transfusion in the emergency TP (ETP) group was seen . The major complication rate was greater in emergent vs elective PD . The same held true for emergent vs elective DP , while no difference existed between patients undergoing emergent vs elective TP . For the EPD group, organ-space infection rates were higher than those in the elective cohort . For both DP and TP, no difference was demonstrated for organ space infection rate . Mean LOS was prolonged for all pancreatectomy subgroups, but this only reached statistical significance for PD  and DP . Furthermore, EPD and EDP patients required transfer to a skilled nursing facility at rates greater than those in the elective groups . Lastly, 30-day mortality was 10.3% in the EPD group vs. 3.2% in the elective cohort (p < 0.001). For the DP group, mortality was also higher in the emergent vs elective group . While there was no statistical difference in the 30-day mortality rate between the TP cohorts, a trend towards increased mortality was seen (20% vs. 5.6% p = 0.11).The comparative outcomes between emergent and elective cases stratified by pancreatectomy type are demonstrated in Table p = 0.08 across all groups, DP vs. PD p = 0.12). SSIs of any type were the highest in the PD group (27.1%) compared to DP (19.1%) and TP (10.0%) . No difference in organ-space infection rates in the PD (15.6%) and DP groups (11.3%) groups compared that experienced in the TP group (10%) . Perioperative blood transfusion requirements were the highest in the TP group (66.7%) compared to 49.8% in PD and 38.8% in DP (p < 0.001). Median LOS was similar for the TP group (15 days) and PD group (15 days) compared to the DP group (9 days) . Thirty-day mortality was greatest in the TP group (20%) compared to 10.3% in PD and 5.2% in DP .Differences in perioperative outcomes within the EP cohort by pancreatectomy type are shown in Table p = 0.02, OR 2.60, 95% CI 1.16–5.84).On univariate analysis, predictors of 30-day mortality included; age, BMI, jaundice, sepsis, preoperative transfusion > 4 units in the 72 h prior to surgery, impaired functional status and delivery of systemic chemotherapy or radiation therapy within preceding 30 days. Gender as well as weight loss exceeding 10% in the 6 months prior to EP did not influence mortality Table . Multivap = 0.47) and 30-day mortality (p = 0.93) over the study period (Table p < 0.001), in that the rate of unplanned return to the OR decreased from 2005 to 2013.The rates of morbidity , return to OR during index hospital stay and 30-day mortality were categorized by year during the period of data analysis (2005–2013). Specifically, no difference was appreciated for total morbidity p = 0.4 and 30-dp = 0.011) and a greater duration of median length of stay .Forty-four patients underwent emergent pancreatic resection in the setting of benign disease . While total morbidity and 30-day mortality rates were similar when compared to those with underlying invasive disease, two differences emerged. Patients with malignant disease experienced a higher rate of postoperative transfusion  were significantly higher than the non-emergent/elective cases. This correlates with previously published perioperative elective outcomes –11. WhenRegarding complications specific to pancreatectomy, organ-space surgical infection was queried as this served as a surrogate for the rate of POPF. In an ACS-NSQIP study by Tseng et al. , the ratThe data presented here are unique as very few previous publications on emergent pancreatic resection exist and are solely single institution reviews. In an earlier series of over 400 pancreatic head resections, the prevalence of emergency non-traumatic pancreatoduodenectomy was 1% . This unOf note, patients undergoing EP experienced an increased length of hospital stay of 6 days and nearly one-in-four were transferred to an alternate care facility to facilitate rehabilitation. This has important implications on health care expenditure and resource allocation. Additionally, if a decision is made to undergo emergent pancreatectomy in the setting of cancer, the patient must fully understand the long-term effects on quality of life and the ability to return to preoperative or acceptable levels of functioning. In the elective setting, postoperative PD patients have a quality of life and independent functioning that is equivalent to, or approaches, that in the general population , 20. It Functional status emerged as the sole predictor of 30-day mortality on multivariate modeling in the setting of emergent pancreatectomy. This finding is congruent with growing surgical literature highlighting the clinical significance and prognostic performance of this specific patient metric –24. HoweThe significant influence of both surgeon and hospital volume on patient outcome is unaccounted for in this analysis. The true indications for EP in the setting of neoplastic disease are rare and should ideally be only considered and performed in high volume referral centers. It is also unclear if any patients could have been temporized utilizing interventional endoscopic or radiologic procedures. Notably, the rate of unplanned return to the OR decreased from 2005 to 2013. Unfortunately, the factors contributing to this finding cannot be accurately determined with the available dataset, but may reflect continued improvements in critical care and advancements in interventional and endoscopic procedures.The present study has several limitations. First and foremost is the lack of detailed case data available from the NSQIP database. This included the absence of pancreas-specific outcomes in the database, namely POPF. In addition, the rarity of TP in the emergent setting also leaves the study underpowered to better compare outcomes of this cohort to those undergoing emergent DP or TP. The emergent nature of the pancreatectomy was inferred if coded as such within the database or if the patient was labelled an ASA class 5, mechanically ventilated, experienced preoperative systemic sepsis , or was transfused greater than 4 units in the preceding 72 h. Data was unavailable for the specific indications for emergent pancreatic resection such as bleeding tumor, duodenal perforation, etc. Although preoperative systemic sepsis was the primary indication for emergent pancreatectomy, the specific cause of this sepsis was uncertain. NSQIP does not code for type of hospital setting , or type of surgeon , so it is impossible to tell by who and in which setting these operations were performed. The strengths of this study include a large national dataset with straightforward and sound statistical comparisons.Emergent, non-traumatic, non-pancreatitis, pancreatic resection in the setting of neoplastic disease results in significantly higher mortality and morbidity compared to elective pancreatic resections. Although emergent surgery carries substantial risk, in selected cases operative intervention should be strongly considered. The results of this large series of modern national data will inform the challenging clinical decision making that surrounds these rare and unanticipated patient presentations.


Recently, the endothelial Activation and Stress Index (EASIX) score has been reported to predict overall survival (OS) after allogeneic stem cell transplantation. This study evaluated the prognostic role of EASIX score in patients with newly diagnosed multiple myeloma (MM).9/L) and were evaluated based on log2 transformed values.This retrospective study analyzed the records of 1177 patients with newly diagnosed MM between February 2003 and December 2017 from three institutions in the Republic of Korea. Serum lactate dehydrogenase (LDH), creatinine, and platelet count at diagnosis were measured in all included patients. EASIX scores were calculated using the formula-LDH (U/L) × Creatinine (mg/dL) / platelet count (10p < 0.001). After median follow-up for 50.0 months , the median OS was 58.2 months (95% CI 53.644–62.674). Overall, 372 patients (31.6%) showed high EASIX scores at diagnosis, and had significantly inferior OS compared to those with low EASIX (log2 EASIX ≤1.87) . In multivariate Cox analysis, high EASIX was significantly associated with poor OS . In the subgroup analysis of patients who underwent ASCT, patients with high EASIX showed significantly inferior OS compared to those with low EASIX . In addition, in each group of ISS I, II, and III, high EASIX was associated with significantly inferior OS .The median age of patients was 63 years , and 495 patients (42.1%) underwent autologous stem cell transplantation (ASCT). The median log2 EASIX score at diagnosis was 1.1 (IQR 0.3–2.3). Using maximally selected log-rank statistics, the optimal EASIX cutoff value for OS was 1.87 on the log2 scale (95% CI 0.562–0.619, EASIX score at diagnosis is a simple and strong predictor for OS in patients with newly diagnosed MM. Multiple myeloma (MM) is a monoclonal plasma cell proliferation disorder with various symptoms and signs caused by monoclonal proteins . Recent 9/L) as a reliable factor to predict the prognosis of acute graft-versus-host disease after allogeneic stem cell transplantation , but was not different in R-ISS I or R-ISS III   with high EASIX showed significantly inferior OS compared to other patients with low EASIX [45.2 months (95% CI 12.8–77.5) vs. 76.0 months (95% CI 54.7–97.3), This study showed that EASIX is a simple and powerful predictor of survival outcome in patients with newly diagnosed MM. Although fewer patients with high EASIX received ASCT than those with low EASIX, EASIX showed a prognostic value independent of ASCT. EASIX is a simple formula that can be calculated using platelet counts, serum creatinine, and LDH. These three variables as EASIX have been reported as a prognostic factor in MM. Elevated levels of serum LDH are associated with advanced disease and inferior survival outcomes in patients with MM who were treated with effective new agents such as thalidomide, lenalidomide, or bortezomib , 12. RenEASIX was originally developed as an endothelial damage-related biomarker in patients with acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Luft et al.  first evThis study showed that EASIX is useful to predict the survival in each group of ISS. ISS is a simple risk stratification system based on serum β2-microglobulin and albumin ; howeverThis study has some limitations. First, we do not have any data regarding progression-free survival (PFS). The clinical significance of PFS is growing in MM as many effective salvage treatment regimens including novel drugs are developed and affect OS prolongation. Further analysis about the association between EASIX and PFS could strengthen the prognostic role of EASIX. Second, we only evaluated EASIX score at the time of initial diagnosis. Assessment of EASIX at ASCT, disease progression, or recurrence might also be useful to analyze the prognostic value of EASIX. Third, there might be some limitations in the assessment of EASIX because platelet counts, creatinine, and LDH levels could be affected by several other conditions like heart problems, liver disease, or infection. Although the frequency of cardiovascular and liver disease was similar between the high EASIX and low EASIX group, we did not accurately analyze the effect of underlying disease on EASIX. Finally, this study cohort is heterogeneous because the diagnosis year is widely distributed and patients received variable induction and salvage treatment. Also, there is a possibility of over-fitting because of the lack of validation cohorts, and therefore the prognostic role of EASIX needs to be validated in further researches.This study firstly evaluated the prognostic impact of EASIX in patients with newly diagnosed MM. Patients with high EASIX at diagnosis had unfavorable characteristics, advanced disease stages, and showed significantly inferior survival outcomes compared to those with low EASIX. In addition, EASIX was useful to predict survival in each group of ISS or R-ISS II. Therefore, EASIX is a simple and powerful predictor of survival outcome in patients with newly diagnosed MM.Additional file 1: Supplementary Table 1. Univariate and multivariate Cox analysis for overall survival .


Tumor micro-angiogenesis and lymphangiogenesis are effective prognostic predictors in many solid malignancies. However, its role on Xp11.2 translocation RCC has not been fully elucidated. Herein, we purposed to explore the correlation between quantitative parameters of tumor-related micro-angiogenesis or lymphangiogenesis and the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 translocation RCC).Tissue samples were obtained from 34 Xp11.2 translocation RCC and 77 clear cell renal cell carcinoma (ccRCC) between January 2007 and December 2018. Micro-angiogenesis was detected using CD34 antibody and quantified with microvessel density (MVD) and microvessel area (MVA), while the lymphangiogenesis in RCC was immunostained with D2–40 antibody and assessed using lymphatic vessel density (LVD) and lymphatic vessel area (LVA). The Kaplan-Meier method of survival analysis was used to estimate prognosis, and both univariate and multivariate analysis was performing using the Cox proportional hazards.P > 0.05). Notably, D2–40-positive lymphatic vessels of Xp11.2 translocation RCC were highly detected in the peritumoral area compared to the intratumoral area. Interestingly, the peritumoral LVD and LVA of Xp11.2 translocation RCC were higher than that of ccRCC . Furthermore, both intratumoral MVD or MVA and peritumoral LVD or LVA were significantly associated with pT stage, pN stage, cM stage, AJCC stage, and WHO/ISUP grade . Univariate analysis of Cancer-specific survival (CSS) revealed that CSS was substantially longer in patients with low intratumoral MVD or MVA than in patients with high intratumoral MVD or MVA . Lastly, the Cox proportional hazards model in CSS demonstrated that both intratumoral MVD or MVA and peritumoral LVD or LVA were not independent prognostic parameters .The MVD and MVA of Xp11.2 translocation RCC in two detected areas  were not significantly different from that of ccRCC (all This study outlines that Xp11.2 translocation RCC is a highly vascularized solid RCC, characterized by rich lymph vessels in the peritumoral area. Quantitative parameters of micro-angiogenesis and lymphangiogenesis could not be considered as novel prognostic factors for patients with xp11.2 translocation RCC. In primary tumors, distant metastasis is the most important predictive factor of prognosis in many malignant tumors. The common route of tumor metastasis involves tumor cell invasion and penetration lymphatics and/or blood vessels, subsequently disseminating to distant organs. Furthermore, angiogenesis within the tumor is crucial for tumor growth and metastasis, whereas lymphangiogenesis is a critical factor for tumor progression –3. GrowtXp11.2 translocation renal cell carcinoma (Xp11.2 translocation RCC) is a rare subtype of renal cell carcinoma (RCC), characterized by several different chromosomal translocations involving Xp11.2 and the formation of TFE3 fusion genes, followed by overexpression of TFE3 protein . PatientHerein, we purposed to explore the correlation between tumor-related microvascular or lymphatic quantitative parameters and the prognosis of Xp11.2 translocation RCC. Based on quantitatively analyzing the distribution of microvessels and lymphatics of Xp11.2 translocation RCC histologically, and comparing it with ccRCC.This study was reviewed and approved by the institutional ethics committees of Nanjing Drum Tower Hospital. We reviewed the data of 34 patients diagnosed with Xp11.2 translocation RCC from January 2007 to December 2018, while 77 patients with ccRCC were grouped as the control using the statistic method of propensity score matching (PSM) to keep the homogeneity of the clinicopathological data. The Xp11.2 translocation RCC was diagnosed using both TFE3 immunohistochemistry staining and self-designed break-apart TFE3 fluorescence in situ hybridization probes . All enrFormalin-fixed paraffin-embedded tissue sections (thickness 4 μm) were deparaffinized in xylene and rehydrated in graded ethanol series. Next, the deparaffinized slides were placed in boiling saline sodium citrate to repair antigen for 10 min. Then, the specimens were incubated in 3% hydrogen peroxide for 10 min to block endogenous peroxidase activity and also washed with phosphate-buffered saline (PBS) three times. Afterward, all dried sections were incubated in 10% bull serum albumin for 30 min, followed by incubation overnight at 4 °C with primary CD34 monoclonal antibody (Dako) at 1:100 dilution or D2–40 monoclonal antibody (Dako) at 1:100 dilution. The biotinylated secondary antibodies were labeled using the streptomycin avidin-peroxidase solution (Dako) at 1:500 dilution. Lastly, they were stained using Simple DAB Stain Kit (Dako) as per the manufacturer’s instructions, and the sections were counterstained with hematoxylin. The sections from each specimen (processed with nonimmunized mouse serum instead of the primary antibody) were used as negative controls.2). Then, 5 consecutive fields within the “hot spots” at × 400 magnification were captured using a digital image capture device  for the estimation of MVA. The images resolution is 2592 Pixel Per Inch at width and 1944 Pixel Per Inch at height, and it is unchanged during image processing. Additionally, the MVA was calculated using image analysis software  and depicted as the mean lumen area of the microvessels within the five 0.20 mm2 fields. The evaluation protocol of LVA and LVD was similar to that of quantifying the microvessels. Finally, intratumoral microvessels and lymphatics were described as those located within the tumor mass, while peritumoral microvessels and lymphatics were outlined as those located within 2 mm outside of the tumor border.To quantify the MVD, tumor sections stained with CD34 antibody were screened to select the maximum staining area (hot spot) by two experienced pathologists based on the criteria  at × 100P < 0.05. All statistical analysis was implemented using SPSS software version 23.0 . The survival curves were drawn using GraphPad Prism software version 7.0.Quantitative data were expressed as mean ± standard deviation and compared using Student′s t-test, whereas qualitative data were presented as counts and percentages, and assessed using either Chi-Square test or Fisher′s exact test. To control the homogeneity of the clinicopathological data between the two groups, the PSM was applied to balance the clinicopathological covariates including laterality, pathological T or N stage, clinical M stage, AJCC stage, WHO/ISUP grade and tumor size. Moreover, we excluded the age and gender of patients between subgroups when performing PSM since they are different naturally . The KapP < 0.001). However, after performing PSM there was no significant difference between the two groups in terms of laterality, pathological T or N stage, clinical M stage, AJCC stage, WHO/ISUP grade and tumor size .The clinicopathological features of the two groups (Xp11.2 translocation RCC and ccRCC groups) are shown in Table P > 0.05). Furthermore, in particular, the MVD and MVA of the intratumoral area in Xp11.2 translocation RCC were significantly different compared to those of the peritumoral area (both P < 0.05). On the other hand, D2–40-positive lymphatic vessels were assessed microscopically throughout the two detected areas of Xp11.2 translocation RCC and ccRCC . Nonetheless, the intratumoral LVD and LVA of Xp11.2 translocation RCC were not statistically different compared to that of ccRCC (both P > 0.05). Lastly, the peritumoral LVD and LVA in Xp11.2 translocation RCC were significantly higher than those of the intratumoral area (both P < 0.05) , pN stage (both P < 0.001), cM stage , AJCC stage (both P < 0.001), and WHO/ISUP grade . Although we also analyzed the correlation of pathological variables with MVD or MVA in the peritumoral area, no correlation was noted  , pN stage , cM stage , AJCC stage , and WHO/ISUP grade .As shown in Table 5) Table . ConversP = 0.001 and P = 0.005, respectively). On the other hand, peritumoral LVD or LVA was not associated with CSS in patients with both low peritumoral LVD or LVA and high peritumoral LVD or LVA in the Fig. P = 0.352 and P = 0.264, respectively). Lastly, multivariate analysis using the Cox proportional hazards model for CSS in Table P > 0.05).The threshold level of MVD, MVA, LVD, or LVA was characterized according to the median. The median cut-off values for intratumoral MVD and MVA were 157 and 44,259, while for peritumoral LVD and LVA were 10 and 3326, respectively. High and low group values were defined based on the median cut-off value. Kaplan–Meier analysis of CSS in patients with intratumoral MVD or MVA (Fig. Angiogenesis and lymphangiogenesis within malignant tumors are crucial for tumor growth and metastasis , 2. NumeThe tumor micro-angiogenesis has been measured in several ways including MVD, MVA, quantifying tumor angiogenic molecules, microvessel invasion and assessing the presence of tumor-associated angiogenic receptors, while the lymphangiogenesis has been quantified using various methods such as LVD, LVA, lymphatic vessel invasion, and vascular endothelial growth factors family members , 21–23. Here, the prognostic value of MVD and MVA indicating the microvessels in RCC remained inconsistent and unclear. In another study by Sharma et al. reported that the MVD within RCC was not significantly correlated with tumor grade and stage, and thereby MVA appeared to be a good prognostic factor for RCC . ElsewheTo avoid the selection bias of different areas of the tumor examined under the microscope, we analyzed the intratumoral and peritumoral areas of Xp11.2 translocation RCC. The results revealed that MVD or MVA in the intratumoral area was significantly higher compared to that of the peritumoral area, which was inconsistent with the findings of Cao et al. . In partThere are some limitations in the study. The sample size was not enough large due to the low incidence of this rare disease, and the follow-up time for patients was relatively short. In addition, the criteria for defining microvessels need to be further clarified, whereas the counting method should be more objective, accurate, convenient and efficient.Overall, findings from this study indicate that Xp11.2 translocation RCC is a highly vascularized solid RCC, characterized by rich lymph vessels in the peritumoral area. Inhibiting tumor lymphangiogenesis and micro-angiogenesis would delay tumor growth and metastasis, which may provide novel strategies for treating Xp11.2 translocation RCC. Although MVD, MVA, LVD, or LVA cannot be used as novel risk factors predicting prognosis for Xp11.2 translocation RCC patients, high intratumoral MVA and MVD indicated poor prognosis and thereby they may be important to clinicians.


Alcidodes juglans Chao (Coleoptera: Curculionidae), is an important agricultural pest and distributed widely in China. The complete mitochondrial genome of A. juglans is 15,638 bp long, and consists of 13 protein-coding genes (PCGs), two ribosomal RNA genes, 21 transfer RNA (tRNA) genes and a putative control region (GenBank accession No. MH819192). The trnI gene has not been observed in the A. juglans mitogenome. The nucleotide composition is significantly biased  with A + T contents of 75.02%. All of the 21 tRNAs have the typical cloverleaf structure, with an exception for 1trnS(AGN). All PCGs are initiated by ATN codons, except for cox1 with AAT instead. Ten PCGs use a common stop codon of TAA or TAG, whereas the remaining three were terminated with a single T. The phylogenetic relationships based on neighbour-joining method showed that A. juglans is closely related to Naupactus xanthographus, which is in accordance with the traditional morphological classification.The walnut weevil,  Alcidodes juglans Chao (Coleoptera: Curculionidae), is an important agricultural pest and distributed widely in China. The larvae of A. juglans bore tunnels into the centre of fruits, and spend their larval stage inside host plants. It causes great economic losses in walnut cultivated areas , and deposited in the insect specimen room of Guiyang University with an accession number GYU-Col-20180001.The walnut weevil, A. juglans is a closed-circular molecule of 15,638 bp in length (GenBank accession No. MH819192), and containing the typical set of 13 protein-coding genes (PCGs), two ribosomal RNA genes (rrnL and rrnS), 21 transfer RNA genes (tRNAs), and a putative control region. The gene order and organization of A. juglans are consistent with those of putative ancestor of insects  with A + T contents of 75.02%. The AT-skew and GC-skew of this genome were 0.022 and −0.330, respectively. Fourteen genes were oriented on the N-strand, whereas the others were transcribed on the J-strand.The complete mitogenome of ts Boore . The trnA. juglans mitogenome harbours a total of 16 bp overlapping sequences in six regions. The longest overlap is 7 bp in length, and located between atp8 and atp6. This mitogenome has a total of 182 bp intergenic spacer sequences, which is made up of 14 regions in the range from 1 to 67 bp. The largest intergenic spacer sequence of 67 bp is located between 2trnS and nad1. The control region was located between rrnS and trnQ genes with a length of 803 bp, and the A + T content was 83.44%. With an exception for 1trnS(AGN), all tRNAs have the typical cloverleaf structure, which are similar to those reported in most animal mitogenomes (Wolstenholme trnT and trnE) to 71 bp (trnK), A + T content ranged from 59.42% (trnR) to 90.91% (trnD). Two rRNAs (rrnL and rrnS) are located between 1trnL and trnV, and between trnV and the control region, respectively. The rrnL was 1323 bp in length with A + T content of 77.63%, and the rrnS was 789 bp in length with A + T content of 73.26%.The A. juglans were the canonical putative start codons ATN . However, cox1 used AAT as start codon, as observed in Tribolium castanum (Liu et al. cox1, cox2, and nad5 were terminated with a single T. Based on the concatenated amino acid sequences of 13 PCGs, the neighbour-joining method was used to construct the phylogenetic relationship of A. juglans with 14 other bettles. The result showed that A. juglans is closely related to Naupactus xanthographus (The initial codons for 12 PCGs of ographus , which i


Duodenal perforation is a common surgical emergency and carries mortality ranging from 4% to 30% reported in Western countries, but there is a paucity of reports from India. We aimed to determine the factors which influence the surgical outcomes in patients with duodenal perforation.  We retrospectively analyzed prospectively collected data from January 2010 to December 2018. n = 25, 45.5%), followed by post-ERCP complications , surgery , and blunt trauma  with perforations localized at D2  and at D1 . Patients underwent primary repair with an additional diversion procedure  and repair only in 18 (32.8%). There were 21 (38%) deaths. Patients with ERCP-associated duodenal perforation had longer hospital stay (P ≤ 0.001), ICU stay (P=0.049), duration of drainage (P ≤ 0.001), and higher leak rate (P=0.001) and re-exploration rate (P=0.037). A high mortality rate was seen in patients with preoperative organ failure , postoperative leak , and longer duration from onset of symptoms to surgery (≥4 days) (P=0.045).  A total of 55 patients were included in the study of which 69% (38) were males and 31% (17) were females (M : F = 4.5 : 2). The mean age was 52.3 years. The cause for duodenal perforation was duodenal ulcer ( Perforation of the duodenum is associated with high morbidity and mortality regardless of its cause and is higher in those who have a longer interval to surgery, preoperative organ failure, and a postoperative leak. Duodenal perforation is a common surgical emergency. It can be secondary to an ulcer, endoscopic procedure, trauma, or surgery for a non-gastroduodenal condition and carries a mortality rate ranging from 4% to 30% reported in Western countries. However, there are few reports comparing its outcome depending on the cause of the perforation.It was previously a major complication of peptic ulcer (DU) disease; although it is now becoming progressively rarer with the increasing use of acid-lowering drugs, it still affects 2%–10% of such patients. Different authors have reported mortality rates in this condition ranging from 1.3% to 20% –6.Trauma and abdominal surgery are other causes of duodenal perforation in 0.2%–3.7% of all trauma-related laparotomies, and the associated mortality of duodenal injuries was in the range of 11.2%–26% .Advanced age, preoperative shock, coexisting medical illness, and delay in treatment are common risk factors associated with poor outcomes in patients with duodenal perforation . We reviFrom a retrospective analysis of prospectively maintained data, we identified all patients who were operated for duodenal perforation admitted to our department at Sir Ganga Ram Hospital, New Delhi, between January 2010 and December 2018. Their demographic details, cause of perforation, preoperative variables such as organ failure, and the interval before surgery were collected. We used the Boey score to predict morbidity and mortality. For each patient, a score was assigned which was obtained by the total of three risk factors . Intraoperative findings such as the site of the perforation and type of surgery were collected. Postoperative variables recorded included the total length of hospital stay, time in the intensive care unit (ICU), postoperative leak rate, need for re-exploration, postoperative complications (according to the Clavien–Dindo grades), duration of drainage, and in-hospital mortality.P < 0.05. The study has been reported in line with the STROCSS criteria [For statistical analysis, we used the SPSS software (version 24) for Windows. The mean, median, and ranges were calculated for continuous variables. The chi-square test and Fisher's exact test were used to test the significance of the association between predictors of outcomes. Receiver-operating characteristic (ROC) curve analysis was used to estimate the predictive ability of the Boey score. The area under the ROC curve (AUC) indicates the probability of postoperative morbidity or mortality and actual postoperative condition and is considered perfect (1), good (>0.8), moderate (0.6–0.8), and poor (<0.6) for AUC. The level of significance was set as criteria .A total of 214 patients underwent surgery for duodenal diseases during this period, of which 55 patients underwent surgery for duodenal perforation.P=0.016). Their ages ranged from 16 to 81 (mean 52) years.Of 55 patients with duodenal perforation, there were 38 males (69%) and 17 females (31%). Duodenal perforation was found to be significantly higher in males as compared to females , followed by ERCP-associated perforations , inadvertent injury during surgery for adjacent organs , and trauma . Of the 15 ERCP-associated perforations, two patients had come from elsewhere with perforation and two patients underwent delayed surgery due to failed conservative management. Of the eleven patients with duodenal perforations due to inadvertent duodenal injury, four (36%) were due to laparoscopic cholecystectomy, with missed intraoperative diagnosis and were referred from elsewhere to this institute. In the remaining six patients, duodenal perforation was only recognized at operation. Of the six patients, two (18%) perforations each occurred during open right hemicolectomy , right nephrectomy (for emphysematous pyelonephritis and xanthogranulomatous pyelonephritis), and pancreatic necrosectomy. One (9.1%) patient sustained duodenal perforation during the surgery for a jejunal enterocutaneous fistula. Blunt trauma was the cause of duodenal injury in four patients  followed by D1 . All patients had broad-spectrum antibiotics before surgical intervention, along with supportive measures. The most commonly performed procedure was a primary repair of the duodenal perforation with diversion, e.g., a gastrojejunostomy , followed by primary repair of perforation only , diversion only , and a resectional procedure . In all patients, wide-bore abdominal drains were placed. The decision to extubate or ventilate in the immediate postoperative period was taken in consultation with the critical care team (23 patients (42%) had preoperative organ failure, thirteen had acute kidney injury (AKI) alone, six patients had AKI with respiratory insufficiency requiring respiratory support, and four patients had circulatory failure requiring inotropic support. However, none of the patients needed dialysis preoperatively. The mean duration between the onset of symptoms and surgery was 4.6 days (range 0–20), and the majority of perforations found were in the second part of the duodenum, i.e., D2 , and the mean ICU stay was 5.9 days (0–28). Abdominal drains placed during the surgery drained for a mean duration of 12 days (0–70). Eleven patients (20%) developed a duodenal leak in the postoperative period, of which 6 (40%) were in the post-ERCP group, followed by 3 (27%) in the surgery group and one (8%) in the ulcer group. Of the 11 patients who developed a leak, five (45%) underwent re-exploration with lavage, drain placement, and a feeding jejunostomy, and we managed the remaining six patients conservatively. 22 (40%) patients had minor complications (Clavien grades I and II), and 12 (22%) had major complications (Clavien grades III and IV). Of the 55 patients, 21 patients (38%) died.P < 0.001)  in those having duodenal perforation secondary to ERCP  and with inadvertent duodenal perforation  compared to patients with ulcer perforation. In this last group, there was no mortality (n = 0) (< 0.001) .n = 6, 40%) patients had a prolonged ICU stay (>10 days) as compared to those after ulcer  and inadvertent injury group  (P=0.049). Postoperative leaks were also significantly more common after ERCP  as compared to ulcer perforations  (P=0.001), and they also had a higher re-exploration rate  compared to duodenal ulcer perforations (n = 0) (P=0.037). Post-ERCP perforation patients  needed abdominal drains for longer periods (>10 days) compared to ulcer perforation , postsurgery perforation , and traumatic perforation  (P < 0.001). However, no significant difference was observed among various aetiological variables for preoperative organ failure rate and mortality  had higher mortality as compared to patients of ≤50 years of age  (P=0.001). We found patients who underwent surgery ≥4 days  had high mortality as compared to <4 days group  (P=0.045). A higher mortality rate was observed in patients with preoperative organ failure  compared to those without preoperative organ failure  (P < 0.001). Similarly, mortality was higher in patients who had postoperative leaks  as compared to those who did not have leaks  (P=0.05). There was no significant association between mortality and gender, cause or location of the perforation, and type of surgery. On multivariate analysis, only preoperative organ failure positively correlated with mortality (P=0.002) , presence of preoperative organ failure, and postoperative leak to be significantly associated with mortality. Patients with age >50 years (P=0.002) .n = 6) and 80% (n = 4) mortality rates with scores of 2 and 3, respectively. However, in patients with ERCP-associated perforation, majority  had a score of 1, and mortality was at 40% (n = 2) in patients with a score of 2  and 2 (41%). Patients of peptic ulcer perforation had 50% , higher re-exploration rate, and prolonged requirement of keeping drain in situ as compared to other aetiological factors. It is explained with the fact that this group of patients required the addressal of the primary disease and additional procedures were done apart from addressing perforation. The findings are consistent with these studies [Post-ERCP perforations were associated with a significantly prolonged hospital stay with a mean (±SD) of 26.9 (±21.4) days, ICU stay of 9.8 ±16.7) days, higher leak rate  occurred in the course of laparoscopic cholecystectomy, and none were recognized intraoperatively and were identified at a mean duration of 6.75 days (range 4–8) after the surgery. It is a well-recognized entity, and common duodenal perforation is secondary to a thermal injury with delayed manifestation. In a review of literature, the incidence of duodenal injury reported was 0.04% (range: 0.001%–4%) [n = 2).In the inadvertent duodenal injury group, the majority (001%–4%)  and was 001%–4%) . The ass001%–4%) , and in n = 21) of the patients, but it climbed to 75% (n = 8) in patients with a Boey score of 3, and it was 39% (n = 23) in patients with a Boey score of 2. Although Boey et al. [The Boey score is a well-validated scoring system for predicting morbidity and mortality and is used in patients with peptic ulcer perforation. In this study, patients with higher Boey score had higher mortality rate in all the groups of patients except the trauma group. Mortality occurred in 38% n =  of the py et al. –25.Boey et al. and Khan and Aziz, in their study, reported that delay in diagnosis and initiation of surgical treatment is associated with high morbidity and mortality after surgery , 26. AltOutcomes are generally poor when there is a delay in the diagnosis of perforation .Delay in treatment, location of the perforation, advanced age, female gender, coexisting medical problems, failed primary surgery, and gastrectomy are the poor prognostic factors reported in the literature –32. In tKim et al. found that age >60 years and female sex were associated with a high mortality rate , and in Studies have reported that delayed treatment, preoperative shock, and concurrent severe medical illness were the risk factors affecting prognosis , 35. EarIn the present study, mortality for duodenal perforation of all aetiologies was 38.2%. A significant proportion of patients presenting late (≥4 days) and with preoperative organ failure because of delayed referral could be the reason for such high mortality in our study.Limitation: sample size.Perforation of the duodenum is a common surgical emergency with a varied aetiology. We found that older age, the presence of preoperative organ failure, delayed presentation, and postoperative leak were factors associated with poor outcomes. Patients with higher Boey scores fare badly with high mortality rates across the aetiologies. Patients with ERCP-associated perforation, the second part of duodenum perforation, and those treated with repair and diversion, ICU stay, and longer duration of drains in situ had a significantly extended hospital stay but were not associated with higher mortality rates.