Since sarcopenia is an important risk factor for falls or cardiovascular disease, early detection and prevention of sarcopenia are being increasingly emphasized. Emerging evidence has indicated relationships between sarcopenia, insulin resistance, and inflammation. The triglyceride glucose (TyG) index, a novel surrogate marker of insulin resistance and systemic inflammation, has not yet been shown to be associated with sarcopenia. This study aimed to examine the relationship between the TyG index and muscle mass in Korean adults.This study included 15,741 non-diabetic adults over 19 years old using data from the 2008–2011 Korea National Health and Nutrition Examination Survey. Participants were divided into three groups according to tertiles of the TyG index. A low skeletal muscle mass index (LSMI) was defined by the Foundation for the National Institutes of Health Sarcopenia Project criteria. A weighted multivariate logistic regression model was used to analyze relationships between TyG index tertiles and LSMI.The ORs (95% CIs) for LSMI in the second and third TyG tertiles, compared to the first tertile, were 1.463 (1.131–1.892) and 1.816 (1.394–2.366), respectively, after adjusting for confounding factors. Higher TyG index values were also associated with increased odds of LSMI in adults under 65 years who did not exercise regularly, who consumed less than 30 g of alcohol per day, who did not currently smoke, and who ate less than 1.5 g of protein/kg/day.The TyG index was significantly and positively associated with LSMI in Korean adults.The online version contains supplementary material available at 10.1186/s12944-020-01414-4. Sarcopenia is defined as an unintentional decline in muscle mass, strength, and performance that arises with aging . HoweverSarcopenia is associated not only to increased risks of falls, fractures, and disabilities , 16, butThe triglyceride and glucose index (TyG index), a product of triglyceride levels and fasting plasma glucose concentration, has recently been recognized as a useful clinical surrogate marker of insulin resistance , 25 and All study data were obtained from the 2008–2011 Korea National Health and Nutrition Examination Survey (KNHANES), a nationwide representative survey conducted by the Korea Centers for Disease Control and Prevention to assess the health and nutritional status of Koreans. The KNHANES employs a cross-sectional, stratified, multistage, probability sampling design based on age, sex, and geographical area. Sample weights were assigned to subjects to capture a sample representing the general Korean population. Survey items in the KNHANES have been revised partially because of the availability of survey resources, and some questionnaires have been updated and changed over the years . Detailen = 9736), 2) those missing serum glucose level data (n = 2772), 3) those who did not report history of type 2 diabetes mellitus (n = 937), 4) those diagnosed type 2 diabetes mellitus by a doctor, treated with anti-diabetic medications, or treated with insulin (n = 917), 5) those who had fasting plasma glucose levels 126 mg/dL or more (n = 1551), 6) those missing body mass index (BMI) data (n = 89), 7) those missing serum triglyceride level data (n = 1), or 8) those missing whole-body dual-energy X-ray absorptiometry (DXA) data (n = 6369). Finally, a total of 15,741 participants (6646 men and 9095 women) were included in this analysis  those who were under 19 years old  cholesterol, and plasma glucose concentrations were measured using a Hitachi 7600 Analyzer. White blood cell (WBC) counts were analyzed using a XE-2100D blood cell counter. The TyG index was calculated as follows: log [serum triglycerides (mg/dL) × plasma glucose (mg/dL)/2]. At present, there is no reference value for the prediction of sarcopenia using the TyG index. Therefore, we divided participants into three groups according to tertiles of the TyG index: T1 (6.45–8.19), T2 (8.20–8.71), and T3 (8.72–11.29).2), fat mass (g), lean body mass (g), and total fat percentage . Skeletal muscle mass was calculated using the following equation: lean body mass (g) - bone mineral content (g). Appendicular skeletal muscle mass (ASM) was calculated as the summation of the skeletal muscle mass of both upper and lower extremities. We defined the skeletal muscle mass index (SMI) as ASM (kg) divided by body mass index (BMI) (kg/m2). Finally, the low skeletal muscle index (LSMI) was defined according to the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project criteria: SMI values less than 0.789 for men and less than 0.512 for women [DXA was performed from July 2008 to June 2011 to evaluate body composition . Body composition data were obtained from predefined anatomical areas as follows: head, arms, legs, trunk, pelvic region, and whole body. Participants were analyzed for bone mineral content (g), bone mineral density (g/cm2). Adults with a BMI greater than or equal to 25 kg/m2 were considered overweight and those with a BMI less than 18.5 kg/m2 were considered underweight according to the guidelines of the International Obesity Task Force of the World Health Organization [http://knhanes.cdc.go.kr).Height (cm) and body weight (kg) were estimated to the nearest 0.1 cm using a stadiometer without shoes in a standing posture or supine position and to the nearest 0.1 kg using digital scale in light clothing, respectively. BMI was calculated as body weight divided by height squared  serp less than 0.05.All data are presented as a mean or percentage (%) ± standard error (SE). For the analysis of clinical characteristics of the study population, a weighted analysis of variance (ANOVA) test was used for continuous variables, followed by post-hoc analysis with Bonferroni correction. For categorical variables, weighted chi-square tests were used to analyze differences among the three groups, followed by post-hoc analysis with Bonferroni correction. After adjusting for confounding variables, a weighted multivariate logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for LSMI according to the TyG index tertiles. We further analyzed subgroups according to age, alcohol drinking status, smoking status, amount of protein intake, and regular exercise through a weighted multivariate logistic regression analysis. All statistical analyses were conducted using SPSS statistical software . The significance level was set at Table p < 0.001).Table Table P was calculated by multivariate logistic regression analysis after adjusting for all confounders , except for the variable used in each subgroup analysis.Each The prevention of frailty is an important strategy through which to address related comorbidities, such as falls, cardiovascular events, cognitive impairment, and mortality , 39. TheIn this study, adults of both sexes who had higher TyG index values were more likely to have LSMI, even after adjusting for age and other confounding factors. These findings were based on data from a representative, nationwide, cross-sectional survey. The exact mechanism by which TyG index is positively associated with LSMI is not known, although we hypothesize that insulin resistance and chronic inflammation may be the major links between elevated TyG index and an increased risk of sarcopenia. The pathogenesis of sarcopenia has been suggested to be closely related to chronic inflammation , which cSarcopenia is accompanied by muscle fat accumulation and an increase in pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tissue necrosis factor alpha (TNF-α) within myocytes , 45, whiP = 0.087), compared to the non-regular exercise group. However, the ORs for LSMI showed consistent linearity with increases in TyG index tertile in both groups . Because the IPAQ does not provide information on the timing of exercise and or type/duration of physical activity, further research is needed with more detailed information on physical activity.In subgroup analysis, the TyG index was independently related to LSMI regardless of the presence of several risk factors for sarcopenia, such as sex, smoking status, and protein intake status –55. WhenThe relationship between the TyG index and LSMI was only significant in the normal alcohol consumption group (< 30 g/day). Prior evidence has suggested that heavy alcohol drinking may accelerate sarcopenia , and it Unlike aging, alcohol drinking, exercise, underweight, and obesity are modifiable risk factors. Therefore, reducing alcohol consumption, regular exercising, and maintaining normal weight could be priority strategies to preventing LSMI.This is the first study to confirm a relationship between the TyG index and muscle mass through the use of DXA and a representative, nationwide dataset from Korean adults. However, this study had several limitations. First, data on muscle mass information was only collected; this study could not obtain muscle strength or performance data, precluding a direct diagnosis of sarcopenia among the adults. Second, the study could not compare TyG index values with insulin resistance index values, such as homeostatic model assessment for insulin resistance. Finally, due to the cross-sectional study design, we could not assess causality between TyG index and LSMI.In conclusion, this study found that the TyG index is independently and negatively associated with LSMI in Korean adults over 19 years old. Because the TyG index can be easily measured in clinical settings through blood sampling, this may serve as a helpful method for the early detection of sarcopenia and related comorbidities, thus enabling timely initiation of treatment and reduced social, healthcare expenditures for treating sarcopenia. Longitudinal cohort studies and exploratory studies are needed to investigate the relationship between the TyG index and sarcopenia.Additional file 1. Table S1. Clinical characteristics of the study population without dual energy X-ray absorptiometry data. Table S2. Clinical characteristics of the study population with or without dual energy X-ray absorptiometry data.


While a minority of inflammatory bowel disease (IBD) patients receives biologics in Germany, little is known about therapeutic needs of patients receiving non-biologic therapies. This study aimed to identify indicators of active disease/steroid dependency in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC) treated with conventional therapies and to describe health care resource use (HCRU)/cost.CD/UC patients treated with immunosuppressants (IS) and/or systemic or locally acting oral corticosteroids (CS) were identified in German claims data (2013–2017) and followed for 12 months post-therapy start. Indicators of active disease/steroid dependency during follow-up period were (i) ≥ 2 prescriptions of CS (sensitivity ≥ 4) or (ii) ≥ 1 IBD-related surgery or (iii) > 7 days IBD-related hospitalization(s).Of 9871 included IBD patients , 25.7%/19.9% (CD/UC) received ≥ 2 prescriptions of CS  (i), 3.2% experienced IBD-related surgeries (ii), and 2.5% > 7 days of hospitalizations (iii). Altogether, 44.4% had indicators of active disease/steroid dependency . Among patients with active disease/steroid dependency, 78.0% received CS monotherapy at baseline. Of these, 89.6% received a CS monotherapy in the follow-up period, too. Proportionally, fewer patients with CS monotherapy (57.4%) than IS therapy (91.0%) visited a specialist. HCRU/cost per patient year was significantly higher in patients with than without active disease/steroid dependency.A substantial percentage of biologic-naïve IBD patients suffers from active disease/steroid dependency. The majority receives a monotherapy with systemic CS. Referral to gastroenterologists for treatment optimization is recommended, also because active disease/steroid dependency is associated with increased HCRU/cost.The online version of this article (10.1007/s00384-020-03588-w) contains supplementary material, which is available to authorized users. Crohn’s disease (CD) and ulcerative colitis (UC) are the most common forms of inflammatory bowel diseases (IBD) and can be characterized by chronic intestinal inflammation with mucosal lesions. The prevalence of IBD is estimated to surpass 0.4% in western countries, with substantial burden for modern health care systems , 2. In GThe primary IBD treatment goal is long-lasting corticosteroid (CS)-free disease remission with a good HRQoL , 7. To r. Treatment with non-biologic drugs has not been studied in detail over the recent years. That is why our study aimed to describe the treatment of IBD patients with at least moderate disease severity in Germany treated with conventional therapies only, but not with biologics. Specifically, in these patients, we assessed whether there were still indicators of active disease and/or steroid dependency as observed by specific drug prescriptions and/or IBD-related surgeries or hospitalizations. Assessment of indicators of active disease/steroid dependency in this patient population is important from a clinical point of view as any observed active disease/steroid dependency might implicate a need for a therapy change or intensification. Furthermore, active disease/steroid dependency might be associated with increased health care resource use (HCRU) and cost. Therefore, we additionally compared HCRU and cost between these biologic-naïve patients with and without indicators for active disease/steroid dependency.Several previous studies addressed the real-world treatment of moderate-to-severe IBD patients receiving biologic therapies –16. HoweWe conducted a retrospective claims data analysis using data provided by several statutory health insurance funds geographically distributed in Germany (AOK PLUS and insurance funds represented by service provider GWQ ServicePlus AG). As these data include diagnoses and services across all health care sectors with no study-related selection bias, they are therefore representative of the German health care context. The database included about 8.5 million insured lives, which reflects 11.8% of the German population insured by statutory health insurance funds.The dataset provided information on patient demographics , outpatient treatment , inpatient treatment , and claims filed for prescription medications. Clinical information, such as instruments to assess the severity of disease or disease activity  was not available in the dataset. Our data covered four consecutive years from 1 July 2013 to 30 June 2017 . All continuously insured patients with an age of at least 18 years and a confirmed diagnosis of CD or UC  were included. Patients with one inpatient or two outpatient diagnoses of both CD and UC were excluded as well as patients with a double diagnosis of CD or UC and indeterminate colitis (ICD-10 K52.3).As patients with moderate to severe IBD disease severity were addressed, we included patients who received at least one prescription of a non-biologic IS (azathioprine (ATC L04AX01), mercaptopurine (ATC L01BB02), methotrexate (ATC L01BA01 and L04AX03)) and/or a systemic corticosteroid (ATC H02) or oral budesonide ,≥ 2 prescriptions of locally-acting oral budesonide ,at least one inpatient stay for IBD-related surgery (operation and procedure (OPS) codes 5-45 – incision, excision, resection and anastomosis of small intestine/colon, 5-46 – other surgery of the small intestine/colon, 5-48 – surgery of the rectum, 5-49 – surgery of the anus),IBD-related hospitalizations (ICD10: K50.-/K51.-) of more than 7 days in total in the follow-up period.Active IBD disease and/or steroid dependency was assumed to exist if at least one of the following criteria during the 12 months follow-up period was met:We reported CS drug therapy including CS dosages in prednisolone equivalents, IBD-related hospitalizations  were calculated. Direct cost calculation was based on list prices for drugs as documented in the database , outpatient costs of services based on coded physicians’ uniform rating scale (EBM) numbers, and hospitalizations based on DRG-based reimbursement. Indirect costs associated with sick leave days were estimated based on official statistics on the average gross real salaries in Germany by gender, age, and year . As the t test, chi-square, Mann-Whitney U) and, additionally, based on a multivariate logistic regression model. To account for early death of some patients, drug dosages, HCRU, and cost were reported per observed patient year. Analyses were performed using SAS (Version 9.4), SPSS (Version 24), STATA (Version 14.1), and MySQL (Version 8.0).All reported variables for patient characteristics, treatment and dosage patterns, HCRU, and costs were analyzed using descriptive statistics, including mean, median, ranges, and standard deviation. Patient characteristics as well as HCRU and cost were compared between CD and UC patients with and without indicators for active disease/steroid dependency by means of suitable parametric and non-parametric tests . The study was evaluated by a scientific steering committee to which all the authors belonged and was based on a study protocol approved before start of data analysis.Among 59,908 identified IBD patients in the database, 39,716 patients  were excluded due to the fact that they did not receive any non-biologic IS or systemic CS in the inclusion period  and ≥ 4 oral budesonide prescriptions (16.1%)  received at least two prescriptions of systemic CS, whereas less patients received at least two prescriptions of oral budesonide 12.2%), experienced at least one IBD-associated surgery (2.2%), and spent more than 7 days in total in hospital (1.9%). Overall, 41.3% of UC patients had an indicator of active disease/steroid dependency , and experienced more IBD-associated surgeries and/or hospitalizations in the baseline period compared to patients without indicators of active disease/steroid dependency Table . This waIn CD patients, the following baseline characteristics were associated with a higher risk for indicators of active disease/steroid dependency in the follow-up period: age of at least 60 years, male gender, higher rate of comorbidities (Charlson Comorbidity Index (CCI)), no prescription of conventional IS in the baseline period, at least one CS prescription in the baseline period, and at least one CD-related hospitalization as well as at least one hospitalization due to IBD-related complications. An inpatient IBD-related surgery in the baseline period  was associated with a lower risk of being classified as having active disease/steroid dependency in the CD patient sample.Factors found to be significantly associated with the risk to be classified as having active disease/steroid dependency in UC were the same as for CD patients, with exception of IBD-related surgery and hospitalizations due to IBD-related complications at baseline as well as gender Table .Baseline and follow-up treatments of patients with indicators of active disease/steroid dependency are shown in Fig. Among 1940 UC patients with indicators of active disease/steroid dependency, 1599 patients (82.4%) received a systemic CS/oral budesonide and no non-biologic IS in the 24 months baseline period (including index date), whereas 341 patients (17.6%) received at least one prescription of an IS  whereas this was 10.9%  in those without indicators. Outpatient visit and sick leave day differences were also similar to the CD patient sample.p < 0.001), respectively, with CD-hospitalization cost as the most important cost driver . Similarly, among UC patients, the difference in UC-associated cost between the two patient groups was 8655€ versus 5708 € (p < 0.001), with UC hospitalization cost again as the most important cost driver  were higher than those for patients without active disease (6353€ and 4811€). Among CD patients, the difference in CD-associated cost between patients with indicators for active disease/steroid dependency and patients without such indicators was 9047€ versus 4049€  were finally excluded from our main sample since they did not receive any biologic or non-biologic IS or systemic CS in the inclusion period. Frequently prescribed medications in this group were antibacterial agents for systemic use, aminosalicylates, and locally acting CS for topical use. Due to these treatment patterns, we interpret above excluded patients to be patients who were responsive to 5-ASA and/or suffered from mild disease only. In addition, we excluded patients who received a biologic either in the baseline or follow-up period. The main reason was that this study aimed to address non-biologic treatments only. Data about effectiveness and safety of biologic treatments as well as persistence and switch rates have already been explored in an earlier study based on the same dataset . In thisThree main conclusions can be drawn from our analysis. First, in our cohort of IBD patients with at least moderate disease, we observed a substantial percentage of patients with indicators of remaining active IBD disease and/or steroid dependency. Second, over a period of at least 3 years, most of these patients received a CS monotherapy, which deviates from guideline recommendations , 7. ThirThe assessment of active disease/steroid dependency was, due to the nature of the study, based on hospital and prescription data. However, as we chose conservative thresholds, we believe that our approach identifies IBD active disease and steroid dependency with good validity. The majority of the patients with indicators of active disease/steroid dependency was assigned to this group because of CS use. Based on guidelines and clinical practice, at least two systemic CS prescriptions and/or two prescriptions of oral budesonide were interpreted as a strong signal for IBD active disease/steroid dependency. Average daily doses of 7.3 mg (in CD) and 7.4 mg (in UC) over a period of 12 months and the fact that 10.9% of CD and 17.8% of UC patients received a dosage of at least 10 mg prednisolone equivalents per day  are a stWithin the group of IBD patients with indicators for active disease/steroid dependency, we observed a substantial percentage receiving a CS monotherapy over a period of 3 years. 66.4% of CD patients and 74.2% of UC patients with indicators of disease activity received a CS therapy in the 24 months baseline and 12 months follow-up period only, i.e., for three consecutive years. Long-term CS use is associated with serious risks, including osteoporosis, cardiovascular disease, alterations in glucose, and psychiatric disturbances , 21. PatTreatment of patients with indicators of active disease/steroid dependency was associated with a substantially higher HCRU and cost in our study, including indirect cost due to IBD-associated sick days. We conclude from these numbers that a revision of the treatment of these patients might increase medication cost due to added non-biologic IS or biologics, but has the potential to lead to HCRU and/or cost savings especially around hospitalization and sick days cost.Due to the lack of recent publications addressing a similar IBD population, we were not able to compare our findings to previous literature. Older publications analyzed real-world effectiveness and safety of non-biologic treatments in CD and UC patients –25, but,Despite the strengths of our study, we also acknowledge limitations. First, we were able to assess the non-biologic treatment history of our patients for a baseline period of 24 months only. If patients received a non-biologic IS or biologic earlier than that, they were wrongly assigned to the CS monotherapy group. Second, clinical information concerning disease severity and activity as well as laboratory values were not available. Proxy codes were used to account for this. Also, documentation on the reasons why physicians prescribed specific treatments and dosages of IS/CS were not available. Third, our conclusions about the prescribed CS dosage were based on prescription patterns only. Finally, we might have over-estimated the percentage of patients receiving a CS monotherapy as we required at least one prescription of CS or a non-biologic IS as inclusion criterion, to address patients with at least moderate IBD severity. So, as CS use was one of the inclusion criteria and, at the same time, an indicator of active disease/steroid dependency, this might have led to a pre-selection of patients with active disease. On the other hand, active disease/steroid dependency was only assumed if a patient received ≥ 2  CS prescriptions.According to our data, in clinical practice, a substantial percentage of at least 24 to 44% (depending on thresholds used for CS use) of moderate to severe IBD patients without a biologic therapy show indicators of active disease. Most of these patients (66.4% of CD and 74.2% of UC patients) receive a therapy with systemic CS and/or oral budesonide without immunosuppressants over a period of at least 3 years. Referral of these patients to gastroenterologists or specialized IBD-centers is strongly recommended to optimize treatment, also because active disease is associated with substantial HCRU and cost increases.ESM 1(DOCX 13 kb)ESM 2(DOCX 16 kb)ESM 3(DOCX 14 kb)ESM 4(DOCX 14 kb)


Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) characterized by hyperglycemia and metabolic acidosis. Hypophosphatemia in DKA often occurs during hospital admittance for DKA. Literature on the magnitude, determinants and consequences of hypophosphatemia in DKA is scarce. Primary aim of this study was to investigate the incidence and consequences of hypophosphatemia during hospitalisation for DKA.Cohort study among individuals with T1DM who were admitted for DKA between 2005 and 2020 in an academic and a non-academic hospital. Multivariate regression models were performed to investigate determinants of the lowest phosphate during the treatment of DKA.s reported during the treatment phase were 0.54 (0.32–0.83) mmol/L and hypophosphatemia was present in 74% (62/84). The time to lowest phosphate was 16 (8–23) hours. In multivariate analysis, baseline bicarbonate and hemoglobin at admission were significantly associated with the lowest phosphate level reported. No adverse effects of hypophosphatemia on hospital stay duration, morbidity or mortality were found, even if left untreated.A total of 127 episodes of DKA among 80 individuals were identified. Age at DKA presentation was 28 (22–46) years, 45% of the cases was female, diabetes duration was 13.2 (8.9–25.5) years with glycosylated hemoglobin levels of 91.9±26.2 mmol/mol. In 9% of all cases, DKA was the first presentation of T1DM. Lowest phosphate levelsHypophosphatemia during DKA is common and increases with severe acidosis. However, in this study it was not related to adverse outcomes. Although limitations of this retrospective study should be taken into account, the routine and repeated measurement of phosphate levels in DKA could be reconsidered, provided that possible symptoms related to hypophosphatemia are monitored. In diabetic ketoacidosis (DKA), net (urinary) loss of phosphate occurs because of a transcellular shift, osmotic diuresis and reduced renal phosphate reabsorption.In this study, the incidence of hypophosphatemia during the treatment phase of DKA is 74%.The main determinant of hypophosphatemia is the severity of acidosis.We observed no negative clinical outcomes related to hypophosphatemia.The routine assessment and treatment of hypophosphatemia during a DKA may be reconsidered.Diabetic ketoacidosis (DKA) is an acute and life-threatening complication of type 1 diabetes mellitus (T1DM), with an estimated mortality rate of DKA of 2%–14%. The incidence of DKA is 46–80 per 10 000 persons‐years.3Phosphate is the most abundant intracellular anion in the body and is among others involved in bone mineralization and energy metabolism.Studies investigating the incidence, determinants and consequences of hypophosphatemia in DKA are scarce.13 14Given scarce literature on the prevalence of hypophosphatemia during DKA on one hand and the lack of evidence concerning outcomes on the other hand, we aimed to investigate the prevalence and clinical outcomes of hypophosphatemia during DKA.This is a cohort study among individuals with T1DM admitted because of DKA. This study was executed at two hospitals in the Netherlands: Isala  and the University Medical Center Groningen .Primary outcome was the prevalence of hypophosphatemia in DKA (defined as concentrations <0.80 mmol/L) during the treatment phase of DKA. As secondary outcomes, we investigated the determinants of hypophosphatemia on clinical outcomes, such as length of hospital stay. Furthermore, we investigated the compliance with current guidelines (stating phosphate measurement in the first 24 hours of DKA and phosphate therapy should be given at levels <0.32 mmol/L).Patients were included in the present analysis if they were aged between 18 and 70 years and diagnosed with T1DM (defined as presence of autoantibodies and/or c-peptide concentrations).Both patients with known T1DM as well as patients with new-onset T1DM presenting with a DKA were included. DKA was defined according to current guidelines,Patients with a known pre-existing condition that could have led to the presence of low phosphate concentrations, including hyperparathyroidism, Fanconi syndrome and chronic diarrhoea were per protocol excluded from the present analysis, but no patients fulfilling this were identified. Patients who were transferred from another hospital were excluded from this study. In addition, patients who left the hospital within 24 hours while the DKA had not yet been controlled were excluded from analyses.Treatment of DKA is based on Dutch guidelines.Intravenous therapy of potassium is considered if plasma potassium is <5.5 mmol/L.Phosphate therapy should be considered in severe hypophosphatemia (<0.32 mmol/L).For this study, data were collected using standardized forms. Due to the retrospective study design, blood samples and vital sign monitoring were not performed according to strict study protocols. Collection of data was executed by investigating medical records of patients admitted to hospital in the years 2005–2020. Specific tools, embedded in the electronic health records (EHR) software, that is, slicer dicerUsing this strategy, we analysed all UMCG cases (104) and we blindly and randomly selected a part of the Isala cases (28) that brought us to a total of 132 analysed cases.Baseline data, including laboratory measurements or prehospital insulin use, were collected on hospital entry. Blood samples at arrival at the emergency department were defined as initial measurements. The assumed lowest phosphate was determined on the basis of all phosphate measurements during the treatment phase of DKA. This treatment phase was defined as 1.5 hours from admission to the end of the treatment, based on the fact that treatment usually starts after 30–60 min of arrival and that the effects of treatment can be determined after at least 3060 min.We assessed whether there was a complication of hypophosphatemia according to hospitalization notes in the EHR. Additionally, length of hospitalization was determined by the number of hours from hospital admission until actual discharge. Length of DKA was calculated as the number of hours from the first blood test confirming DKA until the blood glucose was <15 mmol/L, and at least two of the following criteria: pH >7.30, plasma bicarbonate >15 mmol/L, anion gap within the normal ranges (8–12 mmol/L), beta-hydroxybutyrate <0.5 mmol/L.Q-Q plots and detrended histograms were used to define whether data are normally or not normally distributed. Descriptive summaries included the mean with SD for normally distributed variables and the median with the IQR 25th–75th percentile for non-normally distributed variables. For categorical variables, absolute number of patients (%) for phosphate is shown. The Student’s t-test was used for normally distributed variables and the Mann-Whitney U test was used for non-normally distributed variables.Univariable analysis for correlation, using the Pearson’s product-moment correlation coefficient for continuous data and point-biserial correlation coefficient for categorical data, was performed to investigate the association between serum phosphate and other variables.−) or in case the p value was ≤0.1 in the univariable analysis. The model was checked for collinearity (variable with variance inflation factor (VIF) >10 was determined as collinear2 value. Normality and homoscedasticity of residuals were checked with normality plots and scatter plot. For all analyses, a (two-sided) p value of <0.05 was considered statistically significant. All analyses were performed using SPSS V.25.0 .Linearity was checked on a scatter plot. Extreme outliers defined as 3× IQR from the 25th or 75th percentile were identified on a box-whisker plot were excluded. Next, multivariable linear regression analysis (method: backward-entry) was performed to investigate associations between serum phosphate as dependent variable and multiple independent variables. Variables were used in the multivariable model based on previous literature  or Isala (n=28), were eligible for analyses and are presented in Median age at DKA presentation was 28 (22–46) years, 45% (36/80) were female. The diabetes duration, not including new-onset T1DM DKA, was 13.2 (8.9–25.5) years with glycosylated hemoglobin levels of 93 (26.2) mmol/mol. At admission, phosphate levels were determined in 58 cases, 2 (3%) had a hypophosphatemia (<0.80 mmol/L), 18 (31%) had a normophosphatemia and 38 (66%) had a hyperphosphatemia (>1.50 mmol/L). Median phosphate concentrations at admission were 1.70 (1.35–2.70) mmol/L.Phosphate levels were measured during the treatment phase in 66% (84/127) of all cases. Hypophosphatemia was present in 74% (62/84) and severe hypophosphatemia (<0.32 mmol/L) in 23% (19/84). The median lowest phosphate level during the treatment phase of DKA was 0.54 (0.32–0.83) mmol/L. When measured, the median number of measurements were 2 (1–4) times in the first 24 hours of admission. When hypophosphatemia occurred, the phosphate levels were measured until within normal values in 53% of all cases. The time to lowest phosphate was 16 (8–23) hours.Nadir phosphate levels were significantly lower in patients suffering from new-onset T1DM DKA: 0.26 (0.19–0.31) mmol/L vs 0.57 (0.45–0.88) mmol/L. The time to nadir phosphate was not significantly different between these groups. Also, pH levels were significantly lower in new-onset T1DM DKA compared with DKA among persons with known T1DM: 7.15 (7.04–7.21) kPa vs 7.03 (6.94–7.11) kPa.Among the cases with severe hypophosphatemia during DKA therapy, 79% (15/19) received phosphate therapy, in 11% (2/19) it was unknown whether therapy was given and 11% (2/19) did not receive phosphate therapy. Thirty per cent (13/43) received phosphate therapy with phosphate levels between 0.32 and 0.80 mmol/L. One patient received phosphate therapy but did not develop hypophosphatemia (lowest phosphate 1.03 mmol/L). In 86% (25/29) of the cases that received phosphate therapy, phosphate levels were measured until levels >0.80 mmol/L.In addition, 24% (6/25) of this group subsequently developed hyperphosphatemia.In univariate regression analyses, hypertension, new-onset T1DM DKA, hemoglobin (Hb) and sodium were negatively associated with lowest phosphate levels. On the other hand, creatinine, potassium, pH, bicarbonate and pCO2 were positively associated with lowest phosphate levels .− and Hb were independently associated with lowest phosphate levels in first 24 hours of admission.In multivariate linear regression analysis, only baseline HCO3The hospital charts did not reveal that any patient suffered from symptoms related to hypophosphatemia. Two patients died during or shortly after admission, they had three and eight previous episodes of DKA. One patient died due to DKA, after leaving the hospital prematurely against medical advice (lowest phosphate 0.54 mmol/L). One patient died during hospitalization for DKA after being admitted with a cardiac arrest (lowest phosphate 1.03 mmol/L). Seizures and confusion, without a clear cause, was reported in another case (lowest phosphate 0.26 mmol/L).Hypophosphatemia was not associated with intensive care unit admission, prolonged duration of DKA or hospitalization in univariate analysis. Twenty-nine cases left the hospital with hypophosphatemia, none returned to the hospital with signs of hypophosphatemia.This study provides insight in the course and determinants of phosphate concentrations in DKA among adults. On admission to the hospital for DKA, 66%of all cases in which phosphate levels were measured at baseline present with hyperphosphatemia. However, during the treatment phase of DKA, hypophosphatemia occurred in 74% and a severe hypophosphatemia even in 23%. Nadir lowest phosphate level during the DKA treatment was 0.54 mmol/L, with a median duration of 16 hours to reach this phosphate level. Baseline bicarbonate and Hb levels, and thus severity of DKA, are determinants for nadir lowest phosphate levels during the treatment phase of DKA.et al,It has long been known that serum phosphate levels decrease during the treatment phase of DKA.Furthermore, reduced tubular reabsorption of phosphate, as a direct effect of acidosis, and subsequent increased urinary phosphate excretion, contribute to low phosphate levels.3et alDuring the treatment of DKA, rising pH levels and reversal of insulinopenia, increase intracellular glycolysis, which uses phosphate to form ATP.An important finding of the current study is that in 66% of the cases phosphate levels were determined, according to current international guideline. In 53% of the cases who developed hypophosphatemia during DKA therapy, confirmation of restoration of normal phosphate concentrations was checked. Among the patients who developed hypophosphatemia, there were no adverse events recorded in the hospital charts which were likely associated with low phosphate levels or lack of therapy. Although the limitations of this retrospective study do not allow firm conclusions, it may suggest that hypophosphatemia during DKA does not lead to serious clinical consequences. Furthermore, as previous guidelines also recommend repeated phosphate levels, it could also be concluded that guidelines are not well complied.22As such, our findings question the relevance of current guidelines.assumed lowest. As phosphate determinations were snapshots, there is a considerable chance that we missed the actual lowest phosphate and we overestimated or underestimated the time until the lowest phosphate occurred. As phosphate was no longer determined after 24 hours in almost half of the patients, the actual time to lowest phosphate could well be even later than described. It should be noted that the population studied consisted of adults. As such, the role of phosphate in DKA among children with T1DM remains to be studied. As hypertension was a significant factor in the univariate analysis, a future study may focus on the potential association between medication for hypertension and hypophosphatemia, as many of these drugs target the kidney and therefore could have an effect of renal phosphate losses.To our knowledge, this is the first two-center study that investigated the role of phosphate in DKA among a large (>100) population. Nevertheless, limitations of the present study should be acknowledged. There may be selection bias: only a minority (n=17) of the included cases were treated in the period 2005–2010. As we expect that the actual incidence of DKA in both hospitals is higher, this may indicate that we missed data in that period. A possible explanation for this omission is the introduction of electronic patient charts in this period in both hospitals. In addition, with the use of electronic searching tools we potentially miss cases. Furthermore, in this study data were collected from two centers. As presented in 10.1136/bmjdrc-2020-002018.supp1Supplementary dataHypophosphatemia during the treatment phase of DKA occurs in 74% and its main determinant is the severity of acidosis. Although limitations of the retrospective nature of this study should be taken into account, it seems that no clinical symptoms or adverse effects of hypophosphatemia were present in this study. However, more studies should be performed on this topic before firm conclusions can be drawn.


Solanum nigrum is a wild non-tuber-bearing species belonging to Solanaceae family. The complete chloroplast genome of S. nigrum was constituted by de novo assembly using a small amount of whole genome sequencing data. The chloroplast genome of S. nigrum was 155,432 bp in length and consisted of 25,289 bp of a pair of inverted repeats, 18,402 bp of small single copy, and 85,852 bp of large single copy regions. A total of 139 genes were annotated including 96 protein-coding genes, 39 tRNA genes, and four rRNA genes. Maximum likelihood phylogenetic analysis with 25 Solanaceae species revealed that S. nigrum is grouped with S. melongena. Solanum nigrum, a wild hexaploid species, is a relative to potato (S. tuberosum) and widely grows in South Korea. It has several desirable characteristics such as various resistances against biotic and abiotic stresses, especially late blight resistance  was collected in Gyeongsan, South Korea, and has been stored at Daegu University, South Korea. An Illumina paired-end (PE) genomic library was constructed with total genomic DNA according to the PE standard protocol  and sequenced using an Illumina HiSeq2000 at Macrogen (http://www.macrogen.com/kor/), South Korea. Low-quality bases with raw scores of 20 or less were removed and then ∼1.9 Gbp of high-quality of PE reads were assembled by a CLC genome assembler  with the parameters of minimum (300–1000 bp) autonomously controlled overlap size as described by Kim et al. (S. bulbocastanum (NC007943) as the reference sequence  was 155,432 bp in length including 25,589 bp inverted repeats (IRa and IRb) regions separated by small single copy (SSC) region of 18,402 bp and large single copy (LSC) region of 85,852 bp with the typical quadripartite structure of most plastids, and the structure and gene features were typically identical to those of higher plants. A total of 139 genes with an average size of 571 bp were annotated including 96 protein-coding genes with an average size of 754 bp, 39 tRNA genes, and four rRNA genes. An overall GC content was 38%.The complete chloroplast genome of S. nigrum and 24 published species in Solanaceae family by a maximum likelihood method in MEGA 6.0 (Tamura et al. S. nigrum belonged to the same clade in Solanum species. However, interestingly it was close to S. melongena and separated with six other Solanum species including S. tuberosum (Phylogenetic analysis was performed using chloroplast coding sequences of uberosum .


Dalbergia tonkinensis is a critically vulnerable tree species that is distributed in Vietnam and Hainan Island of China. The complete chloroplast genome sequence of D. tonkinensis was characterized using Illumina pair-end sequencing. The cpDNA is 156,086 bp in length and contains a pair of 25,720 bp inverted repeats, one large single copy region of 85,761 bp, and one small single copy region of 18,885 bp. It contains 131 genes including 86 protein-coding genes, 36 tRNAs, eight rRNAs, and one pseudogene. The overall G + C content of the whole genome is 36.1%. Phylogenetic analysis based on 35 chloroplast genomes of Papilionoideae including Cercis glabra (as an outgroup) indicates that all the species of the Dalbergioids sensu lato formed a monophyletic clade and D. tonkinensis formed a sister relationship with the D. hainanensis and D. odorifera group. Dalbergia tonkinensis is a 5–13 m tall floral tree species belonging to Papilionoideae de Candolle (Fabaceae) and is distributed in Vietnam and Hainan Island of China  via comparison with chloroplast genomes of D. odorifera T. Chen (MF668133) and D. hainanensis Merr. et Chun (MF926268). The annotated chloroplast genome sequence was submitted to the GenBank (MK599470).The plant material was sampled at Bac Huong Hoa nature reserve (Vietnam). The voucher specimen (KRIB0077649) was deposited in herbarium of KRIB. The total genomic DNA was sequenced using the Illumina Hiseq 2500 platform. The pair-end library was comprised 43,285,230 reads (length 2 × 101 bp). The Geneious D. tonkinensis has a total length of 156,086 bp, with a pair of inverted repeats of 25,720 bp that separate a large single copy region of 85,761 bp and a small single copy region of 18,885 bp. The chloroplast genome contained 131 genes including 86 protein-coding genes, 36 tRNA genes and 8 ribosomal RNA genes. Among these genes, 15 genes  have one intron and three genes  have two introns. The ycf1 gene was inferred to be pseudogenes. Most of the genes occurred as a single copy; however, six protein-coding genes , seven tRNA genes  and four rRNA genes  in the IR regions were duplicated. The overall G + C content of chloroplast genome is 36.1%,. respectivelyThe complete chloroplast genome of D. tonkinensis and those of 35 related species of Papilionoideae including Cercis glabra Pamp, as an outgroup. These chloroplast genomes were aligned by using MAFFT (Katoh and Standley sensu lato formed a monophyletic clade and D. tonkinensis formed a sister relationship with the D. hainanensis and D. odorifera group.Phylogenetic analysis was performed using chloroplast coding sequences of


Brazil is a violent society and police officers play a fundamental role in this scenario. Police work is a stressful occupation. Dealing with routine violence, police officers must have high standards of physical and mental health. Patrolling the streets involves several risks and stressful situations that may hamper military policemen's quality of life. The identification of factors associated with health-related quality of life may help in planning and providing adequate care to military policemen. This study aimed to identify factors associated with health-related quality of life of military policemen in Salvador, Brazil.A cross-sectional design study investigated a random sample of 329 male military police officers, engaged in patrolling the streets of Salvador, Brazil. A structured questionnaire applied to the policemen collected information about age, education, marital status, income, house ownership, car ownership, police rank, working day, alcohol consumption, smoking, frequency of vigorous physical activity, obesity (body mass index ≥ 30.0), and work ability. Health-related quality of life was evaluated through the 36-Item Short Form Health Survey Questionnaire (SF-36). Work ability was assessed through the Work Ability Index questionnaire. Poor work ability was defined by a 7–27 points score. Multiple linear regression models were used to measure the impact of police officers characteristics on the variation in the Physical Component and Mental Component Summary scores.P < 0.05) associated with poor work ability, while the Mental Component Summary was associated with poor work ability, excessive alcohol consumption, and younger age (24–34 years). Multivariate analysis estimated that the Physical Component Summary was 7.386 units (%) lower among policemen with poor work ability compared to those with moderate/good/excellent work ability. The Mental Component Summary was 12.755 units lower among those with poor work ability, 5.354 units lower among those with excessive alcohol consumption, and 5.532 units higher among those with younger age.Normalised scores were below 50.0% for seven out of the eight SF-36 domains and for the two component summaries. The SF-36 Physical Component Summary was significantly (The military police officers investigated presented low health-related quality of life, associated with younger age, excessive alcohol consumption, and poor work ability. During the Vietnam War, between 1955 and 1975, 47,406 American soldiers were killed in action or captivity .As other Latin American countries, Brazil is a violent society and police officers play a fundamental role in this scenario. Police work is a stressful occupation. Dealing with routine violence, police officers must have high standards of physical and mental health, which usually deteriorate over time . PatrollInformation obtained after identification of factors associated with health-related quality of life may be useful to propose adequate policies and to implement effective care to military policemen. This study aimed to identify factors associated with the health-related quality of life (HRQoL) of military policemen in the city of Salvador, in the state of Bahia, Brazil.A cross-sectional study of factors associated with health-related quality of life was carried out in a representative sample of military policemen from Salvador, Bahia, Brazil.Salvador city had estimated 2.9 million inhabitants in 2016; in 2014, its per capita Domestic Gross Product was R$ 19.5050,84 , ranking 26 among the 5565 Brazilian municipalities . SalvadoThe accessible population was composed of all the 3500 military police officers from 27 battalions. The study included only males, engaged in visible patrolling in public spaces in the city, and excluded those who were on medical leave, engaged in administrative functions, or in specific situations not related to their core-activity. This study is part of a larger study that evaluated other health aspects in military police officers from Salvador .Between February and April 2014, a trained researcher applied an individual, structured questionnaire to the policemen during their working hours. The policemen were individually interviewed, in a reserved consultation office of the batallion. All randomly selected policemen participated voluntarily in the survey. Information was collected about age , education , marital status , income  house ownership , car ownership , police rank , working day , excessive alcohol consumption , smoking , vigorous physical activity  and obesity, defined as body mass index ≥ 30.0 .The policeman’s own perception of their work ability was measured by the Work Ability Index—WAI . The WorHealth-related quality of life was evaluated using the 36-Item Short Form Health Survey questionnaire (SF-36) , cross-cA random sample, proportionally stratified by the 27 battalions, was selected. As recommended by the SF-36 manual , Cohen'sBased on answers to the SF-36 questionnaire, eight multi-item scales  were constructed and subsequently aggregated into two Component Summaries: the Physical Component Summary and the Mental Component Summary. The eight scales were scored using raw data , while the respective normalized scores and the scores for the two summary measures was performed using QualityMetric Health Outcomes™ Scoring Software 4.0 . The stuThe internal consistency of the SF-36 and WAI domains was evaluated using Cronbach's alpha. Values should exceed 0.70, but values ≥ 0.60 are acceptable in exploratory research .Literature discuss whether the WAI questionnaire presents one or two dimensions . In ordet-tests to compare means from the independent samples. Multivariable linear regression models were used to measure the impact of police officer characteristics on variation in the Physical Component and Mental Component Summary scores. All prediction variables  were inserted as a block in each equation, using the default selection method ‘Enter’. Cases presenting studentized residual analysis varying around ± 3.000 standard deviations were identified as outliers. Data were analysed using SPSS version 20.0 .Bivariate analyses used After explanation of the study objectives, participants signed a free informed consent form. All information related to the participants was confidential. The study was approved by the Ethics Committee in Research on Human Beings of the Medical School of Bahia for opinion number 554,724.Normalised scores were below 50.0 for the eight SF-36 domains and the two component summaries, except for vitality 51.8 ± 10.7). Scores for general health (44.6 ± 7.8) and social functioning (43.9 ± 11.1) were particularly low. The internal reliability indices for each domain, measured by Cronbach's alpha coefficient, varied from 0.624  to 0.896  .P < 0.05 or less) associated with working day (P = 0.023), vigorous physical activity (P = 0.045), obesity (P = 0.041), and poor work ability (P < 0.001). The Mental Component Summary was significantly lower among military policemen from age group 24–34 years (P = 0.005), with excessive alcohol consumption (P = 0.002) and poor work ability (P < 0.001) (Table The policemen in the study were predominantly married (61.1%), presented low levels of education (64.4%), were soldiers 92.4%), owned a car (70.2%), and worked > 8 h/day (79.6%). They did not practice vigorous physical activity frequently (47.7%), and some were obese (14.3%), smokers (5.8%), heavy drinkers (7.3%), and presented poor work ability (10.3%). Bivariate analyses revealed that the Physical Component Summary was strongly . Equation 1 estimates that the mean Physical Component Summary was 7.368 units (%) lower among those with poor work ability. Equation 2 revealed that the Mental Component Summary was associated with poor work ability (P < 0.001), excessive alcohol consumption (P = 0.028), and age (P = 0.011). Equation 2 estimates that the mean Mental Component Summary was 3.532 units (%) lower (P < 0.006) among those aged 35–54 years, 5.354% lower (P < 0.028) among those with excessive alcohol consumption, and 12.755%% lower (P < 0.001) among those with poor work ability  regression coefficients enable comparisons of the relative effect of each independent variable on the model’s dependent variables. Compared to the other twelve variables in the models, poor work ability presented the highest betas in both Equation 1 (− 0.275) and Equation 2 − 0.334) (Table 34 (Table2) were always high for both equations, ranging from 0.502 to 0.957. Tolerance statistics close to zero indicates that a variable is almost a linear combination of the other predictors in the model. Adjusted R2 was 0.093 in Equation 1 and 0.135 in Equation 2. The Durbin-Watson statistics fell within the acceptable range (1.5–2.5) in Equation 1 (1.972) and in Equation 2 (1.925) , and two outliers in Equation 2 (with MCS as the dependent variable). Excluding these outliers did not substantially change the results in either equation. Collinearity among the predictors did not provide important limitations to the analyses. Tolerance collinearity statistics  for most of the SF-36 domains ; good (0.743) for the SF domain, and acceptable (0.642) for the GH domain.P < 0.001) and Mental (P < 0.001) Component Summaries of the health-related quality of life of the study population presented strong associations with poor work ability. The Work Ability Index is a complex construct that represents interaction between the individual’s resources and their physical, mental and social work demands, the work environment, organizational culture and management. The WAI may be affected by various aspects of a worker's health-related quality of life [The Physical  lower was estimated for mean PCS among policemen with poor work ability, compared with policemen with moderate/good/excellent work ability. For mean MCS, the estimated value was 12.755% lower among policemen with poor work ability.Minimal Clinically Important Difference (MCID) can be defined as the smallest difference in score in the domain of interest which is perceived to be beneficial or harmful, and that would imply in a change in patient´s management. Ideally, the MCID should be ascertained to each particular study population . The MCIIt is unacceptable for 10.3% of these military policemen to present poor work ability. Policemen should be physically fit in order to undertake patrols. Difficulty in patrolling the street may be harder to policemen with poor work ability, since they also present lower mental health component of their health-related quality of life.Policemen who were heavy drinkers presented MCS scores 5.354 lower than those who did not drink alcohol or were light drinkers. The inherently stressful work in the police service may be an important contributor to alcohol use. Excessive alcohol consumption is a frequent problem among a number of occupational groups in the USA, such as miners (17.5%) and construction workers (16.5%), aged between 18 and 64 . In a laP = 0.006) association between age and the mental component of health-related quality of life (MCS). This association probably reflects a healthy worker survivor effect [Multiple regression analysis revealed a positive, statistically significant  can be due to: (1) relevant predictors were not included in the model; and/or (2) a great proportion of the relationship among the outcomes and the predictor variables investigated was not linear.Some limitations of this study need to be addressed. Its cross-sectional design precludes the possibility of establishing causality among our key variables, mainly because of a lack of knowledge about their temporal sequence. Bi-directional cause-effect relationships between HRQoL component summaries (PCS and MCS) and poor work ability cannot be ruled out. Low values of adjusted RDespite these limitations, this pioneering study was the first to evaluate the HRQoL of military policemen in a representative sample from a large city in Brazil. The physical and mental components of HRQoL were strongly associated with poor work ability. The mental component of HRQoL was lower among heavy drinkers and those who were younger. Given the key role military policemen play in community safety, these results are worrisome and deserve the attention of military police corporate managers in order to take preventive measures to protect these workers’ health. Indeed, the results of this study provided valuable information to the military corporation health department to plan and establish its first Medical Control Program .In conclusion, military police officers from Salvador city presented low health-related quality of life, associated with excessive alcohol consumption and poor work ability, which may hamper their professional activities. The association between younger age and lower mental component of their health-related quality of life (MCS) is probably due to a healthy worker survivor effect. These findings were important in planning the activities of a health care program for this particularly vulnerable occupational group.


Zhibai Dihuang Wan (ZDW) has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients' morality rate. However, the active substances in ZDW and the molecular mechanisms of ZDW in SLE remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of ZDW by using a network biology approach. First, we collected putative targets of ZDW based on TCMSP, GeneCards, and STITCH databases and built a network containing the interactions between the putative targets of ZDW and known therapeutic targets of SLE. Then, the key hubs were imported to DAVID Bioinformatics Resources 6.7 to perform gene ontology biological process (GOBP) and pathway enrichment analysis. A total of 95 nodes including 73 putative targets of ZDW were determined as major hubs in terms of their node degree. The results of GOBP and pathway enrichment analysis indicated that putative targets of ZDW mostly were involved in various pathways associated with inflammatory response and apoptosis. More importantly, eleven putative targets of ZDW  were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZDW acting on SLE. This study provides novel insights into the mechanisms of ZDW in SLE, from the molecular level to the pathway level.Systemic lupus erythematosus (SLE) is a refractory autoimmune disease.  Zhibai Dihuang Wan  has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients' morality rate [zhī mŭ), Phellodendri Chinensis Cortex , Rehmanniae Radix Praeparata , Rhizoma Dioscoreae , Cornus officinalis , poria cocos , Alisma orientale , and Cortex Moutan . ZDW exerts many effects, such as enriching yin, subduing fire, and returning fire to its source. Meanwhile, patterns of yin deficiency and fire exuberant are the most typical in TCM's view on SLE [Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component, characterized by hyperactive T and B cells, autoantibody production, immune complex deposition, and multiorgan damage . Given tity rate –8. ZDW iw on SLE . Due to w on SLE .In the present study, we, respectively, collected the information of targets from active ingredients in ZDW and related targets of SLE from several databases for the first time. Network construction and topological structural analysis were established, which may provide a basis for a more comprehensive understanding of the action mechanisms of ZDW in the treatment of SLE.http://ibts.hkbu.edu.hk/LSP/tcmsp.php) [The entire compound data of ZDW were retrieved from the TCM Systems Pharmacology Database and Analysis Platform  . The acthttps://www.genecards.org, v4.10.0) and the STITCH database  with the species limited as “Homo sapiens” and the condition of high confidence (0.700) [The integrative efficacy of the compounds in ZDW was determined by analyzing the compounds and target interactions obtained from the GeneCards database ( (0.700) , 13. Genhttp://www.omim.org/, updated in May, 2019), which provides over 1,500 relevant genes assigned to the known diseases [There are 3 sources used for predicting SLE-associated targets. The first batch of genes associated with SLE were collected from the Online Mendelian Inheritance in Man (OMIM) database  [The gene ontology (GO) biological process (BP) was analyzed with the limitation of “rf.gov/) . The terhttp://www.kegg.jp). Then, we analyzed the top 10 significant pathways and their related targets to elucidate the molecular mechanisms.To comprehensively understand the molecular mechanisms of ZDW, the dominating target-pathway network was constructed using Cytoscape 3.7.1. The significant pathways were identified by performing enrichment analysis of the proteins by using DAVID Bioinformatics Resources 6.7 and were extracted from KEGG  network was built  first. TAmong 73 hub targets, ZDW exhibited great action on CASP3 (degree = 16), which has been identified as the executioner of apoptosis and the key enzyme of the apoptosis cascade. Similarly, ZDW also strongly affected CASP9 (degree = 11) and CASP8 (degree = 10), suggestive of its contribution to apoptosis. Beyond that ZDW could influence BCL2 (degree = 12) and BAX (degree = 12) to regulate apoptosis. Meanwhile, ZDW also has the potential to act on the MAP kinase family, which participates in the cellular processes like proliferation, differentiation, and development, such as MAPK1 (degree = 12), MAPK14 (degree = 11), and MAPK8 (degree = 9).The top 5 of the 22 central compounds in ZDW are quercetin (degree = 228), ethyl oleate (degree = 134), (+)-catechin (degree = 129), berberine (degree = 96), and kaempferol (degree = 76).p ≤ 0.05). The results revealed that numerous targets are involved in the regulation of apoptotic process, lipopolysaccharide (LPS), and inflammation.A GO enrichment analysis was performed using DAVID Bioinformatics Resources 6.7 to clarify the mechanism of ZDW's main action in SLE. 73 hub targets obtained from the CT network were included in the GO enrichment analysis. P value ≤ 0.05 are presented in The KEGG pathway enrichment analysis was performed with the 73 hub targets by using the functional annotation tool of DAVID Bioinformatics Resources 6.7. The pathways with κB pathway, the hypoxia inducible factor (HIF)-1 signaling pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway. The medium module is related to apoptosis, including the TNF signaling pathway, apoptosis, and the Forkhead Box O (FoxO) signaling pathway. The minimum module concerned prolactin (PRL).Modularity is a critical measurement for analyzing a network. Nodes highly interconnected within a network usually participate in the same biological modules. In terms of functional distribution, the interaction network of the top 10 significant signaling pathways and corresponding targets was divided into 3 modules. The groups of the main pathways and modules are shown in κB and MAPK signaling pathway. Suppression of the NF-κB and MAPK signaling pathway in SLE could reduce proinflammatory cytokine production [κB pathway. The HIF pathway has been identified as a possible therapeutic target for diseases including chronic inflammation, infection, and autoimmunity [According to oduction , 21. Hypimmunity .κB and MAPK signaling pathway and induce apoptosis and necroptosis [TNF signaling pathway, which has a leading position among the 10 pathways, plays a crucial role in SLE immunopathogenesis, as it can activate the prosurvival NF-roptosis . Apoptosroptosis .The minimum module is centered on the PRL signaling pathway. PRL has an antiapoptotic effect, enhances proliferative response to antigens and mitogens, and enhances the production of immunoglobulins and autoantibodies . It has κB, NFKBIA , IL(interleukin)-6, TLR4, IL-1β, PTGS2 (prostaglandin-endoperoxide synthase 2), CCL2(C-C motif chemokine ligand 2), and TNF-α . The main biological processes related with certain ZDW regulation are shown in SLE is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes . TherapeκB signaling way [κB expressions. This suggests that the TLR4/NF-κB signaling pathway could regulate apoptosis [Patients with SLE often display a deficiency in clearing apoptotic cells. The accumulation of postapoptotic remnants and fragments derived from secondary necrotic cells in the presence of autoantibodies against apoptotic cells or adaptor molecules obliges their pathological elimination and maintains autoinflammation, which is responsible for the initiation of SLE . Thus, aling way . Extractling way . Extractling way . More impoptosis . Interespoptosis . HoweverκB, as a key transcription factor involved in the regulation of immune responses and apoptosis, could promote the inflammatory responses in the body. NFKBIA, known as I-kappa-B-alpha (I-κBα), which inhibits the activity of dimeric NF-kappa-B/REL complexes, has been reported as a target for glucocorticoid-mediated immunosuppression [κB signaling pathway [κB activation, we found that ZDW might be more sensitive to an LPS-induced TLR4/NF-κB signaling pathway. LPS could bind the CD14/TLR4/MD2 receptor complex in many cell types, especially in monocytes, dendritic cells, macrophages, and B cells, so as to promote the secretion of proinflammatory cytokines [κB signaling pathway is activated during the progression of a direct autoantibody-mediated tissue injury and the deposition of complement-fixing immune complexes, inducing chronic inflammatory response. Importantly, the activation of NF-κB is critically responsible for the secretion of cytokines including, IL-6, IL-1β, PTGS2, CCL2, and TNF-α [κB signaling pathway [κBα and the activation of NF-κB [α, can not only be activated by canonical NF-κB and MAPK signaling playing a role in inflammation, but can also participate in the derivation of inflammatory responses [α-induced NF-κB p65 translocation and suppress the expression levels of MCP-1 induced by TNF-α [κB signaling pathway and decreasing proinflammatory cytokines in SLE.NF-pression . It has  pathway . Althougytokines . As a reytokines , 48. Theytokines . Cytokinnd TNF-α , 51. IL-nd TNF-α . Extract pathway . Furtherof NF-κB . CCL2, kof NF-κB . The comof NF-κB . TNFα, cesponses . The extby TNF-α . In summTCM, one of the most important parts of complementary and alternative medicine, markedly contributes to the therapeutic action of autoimmune diseases. This study uses a scientific approach to holistically elucidate that the pharmacological mechanisms of ZDW in the treatment of SLE may be associated with its involvement in apoptosis suppression and anti-inflammation. Among these crucial biological functions, eleven targets were identified as key active factors involved in the main biological processes with validated evidence. However, to comprehensively understand the mechanism of ZDW, further experimental research needs to be undertaken to validate if ZDW treats SLE through this mechanism as a formula.


Similarly, PJP with maltodextrin and gum arabic had higher total soluble solids (10.3 and 10.4 °Brix), respectively. Total anthocyanin content was 54% more in PJP with maltodextrin than waxy starch PJP. Similarly, the powder produced with maltodextrin had higher radical scavenging activity  compared to gum arabic (28.45 mM TE/g DM) and waxy starch (26.96 mM TE/g DM). Overall, maltodextrin reflected the most suitable carrier agent to produce PJP.The physicochemical and technofunctional properties and antioxidant capacity of freeze-dried “Wonderful” pomegranate juice powder (PJP), produced with different carrier agents, were investigated. Powders were produced using maltodextrin, gum Arabic, and waxy starch as carrier agents and characterised by scanning electron microscopy (SEM) and particle size distribution. Results showed that PJP produced with maltodextrin had the highest yield (46.6%), followed by gum arabic (40.6%), while waxy starch had the least yield (35.4%). Powders produced with maltodextrin (96.5%) and gum arabic (96.1%) were highly soluble, which indicates better reconstitution properties. Waxy starch-added PJP had the lowest hygroscopicity (4.7%), which offers good stability during storage and a lower degree of caking compared to maltodextrin (10.2%) and gum arabic (12.6%) powders. Powders obtained from maltodextrin and gum arabic exhibited larger particle diameters ranging between 12 to 120 µm while the lowest particle diameter range was with powders formed from waxy starch (8–40 µm). Freeze-dried pomegranate powder produced with maltodextrin retained more redness ( Punica granatum L.) belongs to the Punicaceae family and is widely grown in many parts of the world, such as Europe, Asia, North Africa, the Mediterranean basin and, in recent times, South Africa [Pomegranate  were harvested at commercial maturity from Blydeverwacht orchard, Wellington, South Africa. The fruit were sorted for uniformity of size, shape, and colour and transported in an air-conditioned vehicle to the Postharvest Technology Laboratory at Stellenbosch University. Fruits were washed, and the juice was extracted using a hand-operated domestic press and frozen at −20 °C for about 24 h.The fresh juice was thawed and clarified using a centrifuge system  at 10,000 rpm for 20 min. The cold, sterile single strength clarified juice with 16.2 °Brix  was diluted and standardised with distilled water to 12 °Brix and rapidly frozen at −80 °C until experiments were carried out.In order to obtain a flowable powder from pomegranate juice, a preliminary study was conducted to investigate the amount of carrier that would be added to the pomegranate juice. Each of the carriers  was incorporated in 100 mL pomegranate juice at a range between 10 to 40 g to select a suitable concentration of carrier agent. A 30 g concentration of /100 mL pomegranate juice was observed to produce a flowable powder, which was added after standardisation. The mixture was homogenised using a laboratory homogeniser for 5 min .The pomegranate juice was placed in a 90-mL specimen jar and frozen in a static-air freezer at −80 °C. Freeze-drying of frozen samples was carried out in triplicates. A specimen jar containing the samples was carefully taken to a laboratory-scale freeze-dryer  operating at condenser temperature −85 °C and pressure 18 mTorr and drying continued for 72 h. Dried samples were removed from the freeze-dryer and ground by electrical blender into free-flowing powder . The pomThe percentage yield of powder was calculated based on the fresh weight (1)Yieldaw) of PJP was determined with an electronic dew point water activity meter . The final moisture content of the PJP was measured using a moisture analyser  at 120 °C.The water activity (L* (brightness/darkness), a* (redness/greenness), and b* (yellowness/blueness). The measurements were taken at three different times from a colourless petri dish and averaged. The maximum for ‘L*’ value is 100 (white), and the minimum is zero (black). The colour attributes chroma C*, hue angle h° and total colour difference (TCD) were calculated [Colour of PJP was determined by direct reading using a chromometer  to obtain the colour values: lculated .(2)ho=tL*, a* and b* represent the value after drying at each treatment level and results were expressed as means ± SE of the determinations obtained.Five grams of PJP were extracted in 50 mL distilled water. For 5 min, the mixture was vortexed with the use of a vortex and sonicated for 15 min in an ultrasonic bath . This was followed by centrifugation at 10,000 rpm for 25 min and recovery of the supernatant for TSS, TA and pH measurements. TSS measurement was determined with the use of a digital hand refractometer  blanked with distilled water. For TA, 2 mL of supernatant was diluted in 70 mL of distilled water and titrated against 0.2 N of sodium hydroxide (NaOH) to a pH of 8.2 with the use of a Metrohm 862 compact titrosampler .2O of 50 mL and distilled in a vortex for 30 s. At 3000 rpm for 5 min under 25 °C, the solution was carefully placed in a tube and centrifuged. A 25 mL aliquot of the supernatant was transferred to preweighed Petri dishes and the sample was immediately dried at 105 °C for 5 h. Solubility (%) was determined by subtracting the initial weight from the final weight divided by the initial weight.Solubility (%) was determined using the Eastman and Moore method  and modiHygroscopicity was calculated according to , with slIn a 100 mL graduated cylinder, PJP (20 g) was weighed and carefully dropped 10 times from a height of 15 cm using a rubber mat. The bulk density was determined by the division of the mass of powder and the volume estimated from the cylinder .According to Jalal et al. , the watThe particle size of the powder was determined with the use of a laser light diffraction instrument . Under magnetic agitation, a small amount of PJP was homogenised in 99% isopropanol, following careful monitoring of the distributed particle size, which was taken in three successive measurements. De Brouckere’s mean diameter was used to express the particle size and the mean diameter over the volume distribution. This is mostly used to characterise a particle .The microstructure of PJP was examined with the use of a scanning electron microscope . SEM images of powder were obtained from uniformly mixed powder samples. Under a high vacuum condition, the samples were coated with a very thin layer of gold. This is often used to provide a reflective surface for the electron beam. The gold coating was carried out in a sputter coater  under a low vacuum condition while inert argon gas was present. Subsequent viewing of the gold-coated samples was carried out under the microscope.2CO3 and further incubation for 40 min in the dark. The absorbance of each sample was read at 520 nm in a UV-vis spectrophotometer  against a blank containing 50% methanol. Absorbance was compared with a standard curve , and results were expressed as mg gallic acid equivalent per gram dry matter (mg GAE/g DM).TPC was determined by the Folin-Ciocalteu method using a methanolic extract of PJP . In a teA = absorbance, ε = cyd-3-glucoside molar absorbance , MW = anthocyanin molecular weight (449.2), DF = dilution factor, and L = cell path length (1 cm). Final results are expressed as equivalent per gram dry matter (mg C3gE/g DM).Total anthocyanin content (TAC) was quantified differentially by using the pH method . In tripIn triplicate, the RSA assay was carried out according to Fawole and Opara . Briefly3+-TPTZ complex to a coloured Fe2+-TPTZ complex at low pH by PJP extracts. Trolox (0–10 mM) was used for the calibration curve, and the results were expressed as Trolox (mM) equivalents per gram dry matter (mM TE/g DM).The antioxidant power of PJP was measured using the calorimetric method, according to ,37. The Data were analysed using STATISTICA  and presented as means ± standard error. All analyses were done in triplicates. Data were subjected to analysis of variance (ANOVA), and means were separated according to Fisher’s LSD test at a level of significance of 95%. The graphical presentations were processed by using GraphPad Prism software 4.03 . Principal component analysis (PCA) was carried out using XLSTAT software version 2012.04.1 .L*, a*, C* and h°), the investigated pomegranate juice could be considered as slightly red in colour. Properties of colour are quality indicators that are necessary to reflect sensory attractiveness; thus, the production of phenolic-rich coloured PJP was of high priority in this study.The effect of carrier agents on the yield of freeze-dried PJP is presented in aw) of freeze-dried PJP were significantly (p < 0.05) different among carriers (The moisture content (MC) and water activity (carriers . Gum-arap < 0.05) and water activity and was strongly and positively correlated (r = 0.947). This was expected as the decrease in moisture content could directly be linked to reduced water activity and, therefore, the powder produced with waxy starch could perform better in storage stability than powders obtained with other drying agents. Decreased water activity prevents the growth of most bacteria, yeasts, and moulds, which are not capable of growing below water activity values of 0.87, 0.88, and 0.80, respectively [In dried food materials, moisture content is one of the factors related to drying efficiency . From thectively . Furtherectively  noted thectively  also repectively , who repectively . Lower md r = 0.9. This waectively .L*) of freeze-dried PJP was significantly (p < 0.05) different among carrier agents  different among carrier agents (p < 0.05) difference was observed between carrier agents for chroma (C*) of freeze-dried pomegranate powder  of PJP was significantly (p < 0.05) different among carrier agents. PJP produced with maltodextrin had the least colour purity , closer to 0°, which suggests a higher degree of redness compared to PJP produced with gum Arabic, with highest hue angle (11.9). This suggests that changes observed in the red colour of PJP depend on the type of carrier agent [The characteristic red colouration of pomegranate powder measured as r agents . Juice pe powder . PJP proer agent ,50. The er agent .p < 0.05) difference among carrier agents in the titratable acidity (TA) of PJP  than those produced with waxy starch  of PJP . PJP prop < 0.05) among the juice powders , while waxy starch had the least solubility (35.4%). Higher values observed in the powders produced with maltodextrin and gum arabic could be related to the crystalline nature of the powder. Cano-Chauca et al. , in theip < 0.05) differences among carrier agents in the hygroscopic nature of freeze-dried PJP. The powder produced with gum arabic had the highest hygroscopicity (12.6%), followed by maltodextrin (10.2%), while samples produced with waxy starch showed the lowest hygroscopicity (4.7%). Differences in hygroscopic values could be due to the nature of the powders and the rate at which the powders produced hold molecules of water from the surrounding air. The result from this study was similar to the study by Tonon et al. [n et al. , who repFurthermore, a higher number of hydrophilic groups are present in maltodextrin and gum arabic, which relates to the easy absorption of moisture from the atmosphere . The aut−3), followed by gum arabic (0.74 g cm−3), while waxy starch had the least bulk density (0.64 g cm−3). Bulk density is the “addition of the mass of solid particles and moisture per total volume occupied by the particles, surface moisture and all pores, closed or open, in the surrounding atmosphere and is generally used to characterise the final product obtained by milling or drying” [The results of the bulk density of freeze-dried PJP produced with different carrier agents are also shown in  drying” ,62. Furt drying”  reported drying” , who relp < 0.05) difference among carrier agents in the water-holding capacity (WHC) of freeze-dried PJP (There was a significant (ried PJP . Resultsp < 0.05) difference among carrier agents in the oil-holding capacity (OHC) of freeze-dried PJP  different among carrier agents  of freeze-dried PJP was significantly  difference among carrier agents (3gE/g DM), whereas waxy starch had the lowest TAC (35.01 mg C3gE/g DM). Furthermore, an approximate 54% higher in total anthocyanin content was observed for maltodextrin compared to waxy starch. Yousefi et al. [Similarly, for the total anthocyanin content (TAC), there was a significant  different among carrier agents  of PJP was significantly (r agents a. The pop < 0.05) different among carrier agents  of PJP was significantly  explain 100.0% of the total data variance .aw), total soluble solids (TSSs), titratable acidity (TA), pH, yield, total phenolic content (TPC), radical scavenging activity (RSA), total anthocyanin content (TAC), solubility, hygroscopicity, bulk density and oil-holding capacity (OHC)  .a*), chroma (C*), hue (h°) and ferric-reducing antioxidant power (FRAP) of freeze-dried powder produced with maltodextrin and gum arabic. Likewise, high positive scores along F2 (h°), moisture content (MC), pH and oil-holding capacity (OHC) of the freeze-dried powder produced with gum arabic (a*), chroma (C*), total phenolic content (TPC), radical scavenging activity (RSA) and ferric-reducing antioxidant power (FRAP). However, lower positive scores along F2 were from freeze-dried powder from gum arabic (associated with water activity (aw), total soluble solids (TSSs) and hygroscopicity). The lower negative scores (L*), TCD, titratable acidity (TA), solubility, total anthocyanin content (TAC), bulk density and water-holding capacity (WHC). The results from the PCA showed that powders produced with carrier agents  resulted in significantly different properties.In addition, higher negative scores along F1  correspoalong F2  is assocm arabic . Additiom arabic  for malte scores  along F2e scores  were froThe use of three carrier agents  in the production of freeze-dried PJP was investigated. The results indicated that maltodextrin was more effective in enhancing the yield as well as the physicochemical properties of the PJP, such as colour, TSSs and TA. Similarly, maltodextrin and gum arabic performed better as carriers agents in enhancing the solubility of freeze-dried PJP compared to waxy starch. Maltodextrin was better in the preservation of phenolic content and antioxidant capacity of PJP. Therefore, it could be inferred that maltodextrin resulted in the best carrier agent that retained biochemical activities and maintained the technofunctional properties in the production of freeze-dried pomegranate powder. This study has shown that maltodextrin is the most suitable carrier agent for the formulation or fortification of pomegranate-based food products for baking, candies and ice-cream. This study reports the results of powder produced in a laboratory-scale freeze-dryer. However, a scale-up can be investigated in order to produce, on an industrial scale, powders with similar characteristics. Moreover, further research is required to investigate the storability and optimisation of PJP.


The United States Census Bureau recommends distinguishing between “Asians” vs. “Native Hawaiians or Other Pacific Islanders” (NHOPI). We tested for prognostic differences according to this stratification in patients with prostate cancer (PCa) of all stages.Descriptive statistics, time-trend analyses, Kaplan–Meier plots and multivariate Cox regression models were used to test for differences at diagnosis, as well as for cancer specific mortality (CSM) according to the Census Bureau’s definition in either non-metastatic or metastatic patients vs. 1:4 propensity score (PS)-matched Caucasian controls, identified within the Surveillance, Epidemiology and End Results database (2004–2016).Of all 380,705 PCa patients, NHOPI accounted for 1877 (0.5%) vs. 23,343 (6.1%) remaining Asians vs. 93.4% Caucasians. NHOPI invariably harbored worse PCa characteristics at diagnosis. The rates of PSA ≥ 20 ng/ml, Gleason ≥ 8, T3/T4, N1- and M1 stages were highest for NHOPI, followed by Asians, followed by Caucasians . Despite the worst PCa characteristics at diagnosis, NHOPI did not exhibit worse CSM than Caucasians. Moreover, despite worse PCa characteristics, Asians exhibited more favorable CSM than Caucasians in comparisons that focussed on non-metastatic and on metastatic patients.Our observations corroborate the validity of the distinction between NHOPI and Asian patients according to the Census Bureau’s recommendation, since these two groups show differences in PSA, grade and stage characteristics at diagnosis in addition to exhibiting differences in CSM even after PS matching and multivariate adjustment. According to the official recommendation of the United States (US) Census Bureau, Asian American and Pacific Islander (AAPI) race should be referred to as either being “Native Hawaiian or Other Pacific Islander” (NHOPI) or being “Asian” –3. DespiIn consequence, we tested for differences in pathological characteristics at diagnosis (prostatic-specific antigen (PSA), grade and stage) as well as for cancer specific mortality (CSM) when the Census Bureau’s definition is applied and comparisons are made with Caucasian patients as a control group. We hypothesized that NHOPI exhibit clinically and statistically meaningful differences in PSA, grade and stage at diagnosis as well as in CSM relative to Asians using Caucasians as control. For purpose of all analyses, we relied on the most contemporary Surveillance, Epidemiology and End Results database (SEER database) between 2004 and 2016.n = 1), with known racial/ethnical information not other than Asian or Caucasian , with histologically confirmed PCa diagnosis  and with PSA value . Patients with clinical stage T0 (n = 524) or unknown metastatic status , as well as death certificate only and autopsy cases (n = 306) were excluded. According to the official Census Bureau of the United States, NHOPI are defined as persons having origins in any of the original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. Conversely, persons having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent are defined as Asians [n = 380,705) across all disease stages of 355,485 Caucasian, 23,343 Asians and 1877 NHOPI eligible patients according to the Census Bureau’s recommendation.The SEER database samples 34.6% of the United States and approximates the United States in terms of demographic composition, as well as of cancer incidence . Within anyN0M0)  and patients with lymph node and/ or distant metastases  .Subgroups consisted of patients without lymph node or distant metastases  were reported for continuously coded variables. The Chi-square tested the statistical significance in proportions’ differences. The anyN0M0 and in the TanyN1 and/or M1 subgroup.To maximally reduce the differences between the racial groups, 1:4 propensity score (PS) was performed matching each AAPI category to their Caucasian counterparts for age at diagnosis, PSA, biopsy Gleason Grade Groups , clinicaThe endpoint consisted of CSM within Kaplan–Meier Survival plots and multivariate Cox regression analyses. CSM was defined as death attributable to PCa. In all analyses, the predictor of interest consisted of NHOPI vs. Asian vs. Caucasian race. In all statistical analyses, R software environment for statistical computing and graphics (version 3.6.1) was used. All tests were two sided with a level of significance set at p < 0.05.Within the SEER database, 380,705 eligible PCa patients across all disease stages were identified. Of all, NHOPI accounted for 1877 (0.5%) vs. 23,343 (6.1%) remaining Asians vs. 355,485 (93.4%) Caucasians. The overall patient and cancer characteristics are displayed in Table As graphically depicted in Fig. In three out of five annual trend analyses, NHOPI exhibited highest rates of, respectively, PSA greater than 20 ng/ml, Gleason greater than 8 and M1 stage. Conversely, in the two remaining time trend analyses, T3/T4 stage and N1 stage, annual proportions indicated a tendency towards higher rates in NHOPI followed by Asians and followed by Caucasians in that order, at least in the most contemporary years  patients, 10-year CSM-free rates were 91.0 in NHOPI vs. 93.3% in Caucasians (p = 0.4). In multivariate Cox regression analyses predicting CSM after adjustment for stage at presentation, NHOPI race did not reach independent predictor status  for CSM relative to Caucasians  patients, 10-year CSM-free rates were 38.3% in NHOPI vs. 21.2% in Caucasians (p = 0.03). In multivariate Cox regression analyses predicting CSM after adjustment for stage at presentation, NHOPI race did not reach independent predictor status  relative to Caucasians  patients, 10-year CSM-free rates were 95.3 in Asians vs. 93.2% in Caucasians (p < 0.01). In multivariate Cox regression analyses predicting CSM after adjustment for stage at presentation, Asian race remained a significant predictor  for favorable CSM relative to Caucasians  patients, 10-year CSM-free rates were 41.9 in Asians vs. 30.6% in Caucasians (p < 0.01). In multivariate Cox regression analyses predicting CSM after adjustment for stage at presentation, Asian race remained a significant predictor  for favorable CSM relative to Caucasians , highest rates of Gleason score ≥ 8 , highest rates of stage-T3/T4 at diagnosis (5.5 vs. 4.2 vs. 3.5%), highest rates of stage N1 at diagnosis  and highest rates of stage M1 at diagnosis (8.3 vs. 4.9 vs. 3.9%). To the best of our knowledge, we are the first to apply the Census Bureau’s definition of NHOPI and Asians within PCa patients. The recorded differences between these two groups validate the pertinence of the Census Bureau’s definition in the context of PSA, grade and stage at diagnosis. Previous investigators have not used the Census Bureau recommended definition, but instead relied on other stratifications of AAPI patients. With one exception .Second, we examined the annual proportions of patients with high PSA, high Gleason grade, T3/T4 stage, N1 or M1 stage within NHOPI, Asian and Caucasian race over time. Our analyses showed highest rates of unfavorable tumor characteristics in NHOPI that were followed in absolute rates by Asians and Caucasians, in that order. To the best of our knowledge, we are the first to perform annual rates’ analyses of PCa characteristics at diagnosis according to Census Bureau’s definitions of NHOPI vs. Asian race groups. In consequence, we cannot compare these results with any other study. Nonetheless, it should be noted that the rates of unfavorable grade and stage distribution have also risen over time in Caucasian patients, at a relatively similar pace to their NHOPI and Asian counterparts. This finding is in agreement with two recently published studies that also found rising incidence of primary metastatic PCa in population-based analyses , 15.anyN0M0 patients and 0.62 in TanyN1 and/or M1 patients). These findings suggest that after accounting for important PSA, grade and stage differences at diagnosis, NHOPI race does not exert a prognostic effect on CSM. Conversely, the presence of Asian race exerts a prognostically favorable effect on CSM, relative to Caucasians. These observations are in accordance with several reports that focused on Asian Americans as a whole, without applying the Census Bureaus’ definition of either NHOPI or other Asian race [Third, to account for important differences in PSA, grade and stage between NHOPI, Asians, and Caucasians, we relied on 1:4 PS matching to compare CSM between these racial groups. First, we found no statistically significant CSM differences between NHOPI and Caucasians in either non-metastatic or metastatic PCa stage. Second, we found more favorable CSM in Asians, relative to Caucasians in both non-metastatic and metastatic PCa stage  may provide a similar perspective regarding AAPI patients. In consequence, even a more limited patient cohort is of great value and the worth of its contribution should not be underestimated. Furthermore, despite best efforts aimed at PS matching, retrospective analyses and PS matching for known and available variables may still suffer from remaining differences related to unmeasured or unavailable confounding variables. As in all SEER-based analyses, comorbidities were not available and could lead to residual confounding effects in CSM analyses. Finally, the SEER database only includes North American patients and our findings are only applicable to Asians from the United States and may not be generalizable to Asians from other parts of the world. These, as well as all other limitations related to the retrospective, population-based nature of the SEER database, apply to this, as well as to other similar analyses that were based on the SEER database or other similar large-scale data repositories, such as NCDB, NIS  or NSQIP .Our observations corroborate the validity of the distinction between NHOPI and Asian patients according to the Census Bureau’s recommendation, since these two groups show differences in PSA, grade and stage characteristics at diagnosis in addition to exhibiting differences in CSM even after PS matching and multivariate adjustment. Specifically, NHOPI and Asians exhibit more unfavorable stage and grade at presentation than Caucasians. Moreover, Asians exhibit a CSM advantage; whereas, NHOPI exhibit no differences in CSM after PS matching and multivariate adjustment. In consequence, given the different cancer profiles, our results show that there is a need for disaggregation of AAPI data according to the official recommendation of the United States Census Bureau.