Plant-based polyphenol rich protein supplementation attenuated skeletal muscle loss and lowered the LDL level via gut microbiota remodeling in Taiwan's community-dwelling elderly.

Sarcopenia, characterized by muscle loss, negatively affects the elderly's physical activity and survival. Enhancing protein and polyphenol intake, possibly through the supplementation of fermented black soybean koji product (BSKP), may alleviate sarcopenia by addressing anabolic deficiencies and gut microbiota dysbiosis because of high contents of polyphenols and protein in BSKP. This study aimed to examine the effects of long-term supplementation with BSKP on mitigating sarcopenia in the elderly and the underlying mechanisms. BSKP was given to 46 participants over 65 years old with early sarcopenia daily for 10 weeks. The participants' physical condition, serum biochemistry, inflammatory cytokines, antioxidant activities, microbiota composition, and metabolites in feces were evaluated both before and after the intervention period. BSKP supplementation significantly increased the appendicular skeletal muscle mass index and decreased the low-density lipoprotein level. BSKP did not significantly alter the levels of inflammatory factors, but significantly increased the activity of antioxidant enzymes. BSKP changed the beta diversity of gut microbiota and enhanced the relative abundance of Ruminococcaceae_UCG_013, Lactobacillus_murinus, Algibacter, Bacillus, Gordonibacter, Porphyromonas, and Prevotella_6. Moreover, BSKP decreased the abundance of Akkermansia and increased the fecal levels of butyric acid. Positive correlations were observed between the relative abundance of BSKP-enriched bacteria and the levels of serum antioxidant enzymes and fecal short chain fatty acids (SCFAs), and Gordonibacter correlated negatively with serum low-density lipoprotein. In summary, BSKP attenuated age-related sarcopenia by inducing antioxidant enzymes and SCFAs via gut microbiota regulation. Therefore, BSKP holds potential as a high-quality nutrient source for Taiwan's elderly, especially in conditions such as sarcopenia.

Association between liver stiffness measurement by transient elastography and chronic kidney disease.

ABSTRACT: Transient elastography or elastometry (TE) is widely used for clinically cirrhosis and liver steatosis examination. Liver fibrosis and fatty liver had been known to share some co-morbidities that may result in chronic impairment in renal function. We conducted a study to analyze the association between scores of 2 TE parameters, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), with chronic kidney disease among health checkup population.This was a retrospective, cross-sectional study. Our study explored the data of the health checkup population between January 2009 and the end of June 2018 in a regional hospital. All patients were aged more than 18 year-old. Data from a total of 1940 persons were examined in the present study. The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD-simplify-GFR) equation. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 m2.The median of CAP and LSM score was 242, 265.5, and 4.3, 4.95 in non-CKD (eGFR > 60) and CKD (eGFR < 60) group, respectively. In stepwise regression model, we adjust for LSM, CAP, inflammatory markers, serum biochemistry markers of liver function, and metabolic risks factors. The P value of LSM score, ALT, AST, respectively is .005, <.001, and <.001 in this model.The LSM score is an independent factor that could be used to predict renal function impairment according to its correlation with eGFR. This result can further infer that hepatic fibrosis may be a risk factor for CKD.

Probiotic supplementation attenuates age-related sarcopenia via the gut-muscle axis in SAMP8 mice.

BACKGROUND: Age-related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age-related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut-muscle axis. However, the effects and mechanisms of probiotics in age-related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. METHODS: We administered LcS (1 × 108 or 1 × 109  CFU/mouse/day) by oral gavage to senescence-accelerated mouse prone-8 mice for 12 weeks (16- to 28-week-old). Sixteen-week-old and 28-week-old SMAP8 mice were included as non-aged and aged controls, respectively. Muscle condition was evaluated using dual-energy X-ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. Gas chromatography-mass spectrometry was utilized to measure the short-chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. RESULTS: The LcS supplementation reduced age-related declines in muscle mass (>94.6%, P < 0.04), strength (>66% in holding impulse and >96.3% in grip strength, P < 0.05), and mitochondrial function (P < 0.05). The concentration of short-chain fatty acids (acetic, isobutyric, butyric, penic, and hexanoic acid) was recovered by LcS (>65.9% in the mice given high dose of LcS, P < 0.05) in the aged mice, and LcS attenuated age-related increases in inflammation (P < 0.05) and reactive oxygen species (>89.4%, P < 0.001). The high dose of LcS supplementation was also associated with distinct microbiota composition as indicated by the separation of groups in the beta-diversity analysis (P = 0.027). LcS supplementation altered predicted bacterial functions based on the gut microbiota. Apoptosis (P = 0.026), p53 signalling (P = 0.017), and non-homologous end-joining (P = 0.031) were significantly reduced, whereas DNA repair and recombination proteins (P = 0.043), RNA polymerase (P = 0.008), and aminoacyl-tRNA biosynthesis (P = 0.003) were increased. Finally, the genera enriched by high-dose LcS [linear discriminant analysis (LDA) score > 2.0] were positively correlated with healthy muscle and physiological condition (P < 0.05), while the genera enriched in aged control mice (LDA score > 2.0) were negatively associated with healthy muscle and physiological condition (P < 0.05). CONCLUSIONS: Lactobacillus casei Shirota represents an active modulator that regulates the onset and progression of age-related muscle impairment potentially via the gut-muscle axis.

Exploring and predicting mortality among patients with end-stage liver disease without cancer: a machine learning approach.

OBJECTIVE: End-stage liver disease is a global public health problem with a high mortality rate. Early identification of people at risk of poor prognosis is fundamental for decision-making in clinical settings. This study created a machine learning prediction system that provides several related models with visualized graphs, including decision trees, ensemble learning and clustering, to predict mortality in patients with end-stage liver disease. METHODS: A retrospective cohort study was conducted: the training data were from patients enrolled from January 2009 to December 2010 and followed up to December 2014; validation data were from patients enrolled from January 2015 to December 2016 and followed up to January 2019. Hospitalized patients with noncancer-related chronic liver disease were identified from the hospital's electrical medical records. RESULTS: In traditional multivariable logistic regression and Cox proportional hazard model, prothrombin time of international normalized ratio, which was significant with P value = 0.002, odds ratio = 2.790 and hazard ratio 1.363. Besides, blood urea nitrogen and C-reactive protein were also significant, with P value <0.001 and 0.026. The area under the curve was 0.771 in the receiver operating characteristic curve. In machine learning, blood urea nitrogen and age were regarded as the primary factors for predicting mortality. Creatinine, prothrombin time of international normalized ratio and bilirubin were also significant mortality predictors. The area under the curve of the random forest and AdaBoost was 0.838 and 0.792. CONCLUSION: The machine learning techniques provided a comprehensive assessment of patient conditions; it could help physicians make an accurate diagnosis of chronic liver disease and improve healthcare management.

Palliative medicine family conferences and caregiver psychological distress during prolonged mechanical ventilation.

OBJECTIVES: Little is known about the experience of family caregivers of patients who require prolonged mechanical ventilation (PMV). We examined the perspectives of caregivers of patients who died after PMV to explore the role of palliative care and the quality of dying and death (QODD) in patients and understand the psychological symptoms of these caregivers. METHODS: A longitudinal study was performed in five hospitals in Taipei, Taiwan. Routine palliative care family conferences and optional consultation with a palliative care specialist were provided, and family caregivers were asked to complete surveys. RESULTS: In total, 136 family caregivers of 136 patients receiving PMV were recruited and underwent face-to-face baseline interviews in 2016-2017. By 2018, 61 (45%) of 136 patients had died. We successfully interviewed 30 caregivers of patients' death to collect information on the QODD of patients and administer the Impact of Event Scale (IES), Hospital Anxiety and Depression Scale (HADS) and Center for Epidemiologic Studies Depression (CES-D) scale to caregivers. We observed that more frequent palliative care family conferences were associated with poorer QODD in patients (coefficients: -44.04% and 95% CIs -75.65 to -12.44), and more psychological symptoms among caregivers (coefficient: 9.77% and 95% CI 1.63 to 17.90 on CES-D and coefficient: 7.67% and 95% CI 0.78 to 14.55 on HADS). A higher caregiver burden at baseline correlated with lower psychological symptoms (coefficient: -0.35% and 95% CI -0.58 to -0.11 on IES and coefficient: -0.22% and 95% CI -0.40 to -0.05 on CES-D) among caregivers following the patients' death. Caregivers' who accepted the concept of palliative care had fewer psychological symptoms after patients' death (coefficient: -3.29% and 95% CI -6.32 to -0.25 on IES and coefficient: -3.22% and 95% CI -5.24 to -1.20 on CES-D). CONCLUSIONS: Palliative care conferences were more common among family members with increased distress. Higher caregiver burden and caregiver acceptance of palliative care at baseline both predicted lower levels of caregiver distress after death.

Blockchain-Enabled iWellChain Framework Integration With the National Medical Referral System: Development and Usability Study.

BACKGROUND: Medical referral is the transfer of a patient's care from one physician to another upon request. This process involves multiple steps that require provider-to-provider and provider-to-patient communication. In Taiwan, the National Health Insurance Administration (NHIA) has implemented a national medical referral (NMR) system, which encourages physicians to refer their patients to different health care facilities to reduce unnecessary hospital visits and the financial stress on the national health insurance. However, the NHIA's NMR system is a government-based electronic medical referral service, and its referral data access and exchange are limited to authorized clinical professionals using their national health smart cards over the NHIA virtual private network. Therefore, this system lacks scalability and flexibility and cannot establish trusting relationships among patients, family doctors, and specialists. OBJECTIVE: To eliminate the existing restrictions of the NHIA's NMR system, this study developed a scalable, flexible, and blockchain-enabled framework that leverages the NHIA's NMR referral data to build an alliance-based medical referral service connecting health care facilities. METHODS: We developed a blockchain-enabled framework that can integrate patient referral data from the NHIA's NMR system with electronic medical record (EMR) and electronic health record (EHR) data of hospitals and community-based clinics to establish an alliance-based medical referral service serving patients, clinics, and hospitals and improve the trust in relationships and transaction security. We also developed a blockchain-enabled personal health record decentralized app (DApp) based on our blockchain-enabled framework for patients to acquire their EMR and EHR data; DApp access logs were collected to assess patients' behavior and investigate the acceptance of our personal authorization-controlled framework. RESULTS: The constructed iWellChain Framework was installed in an affiliated teaching hospital and four collaborative clinics. The framework renders all medical referral processes automatic and paperless and facilitates efficient NHIA reimbursements. In addition, the blockchain-enabled iWellChain DApp was distributed for patients to access and control their EMR and EHR data. Analysis of 3 months (September to December 2018) of access logs revealed that patients were highly interested in acquiring health data, especially those of laboratory test reports. CONCLUSIONS: This study is a pioneer of blockchain applications for medical referral services, and the constructed framework and DApp have been applied practically in clinical settings. The iWellChain Framework has the scalability to deploy a blockchain environment effectively for health care facilities; the iWellChain DApp has potential for use with more patient-centered applications to collaborate with the industry and facilitate its adoption.

Survival prediction among patients with non-cancer-related end-stage liver disease.

BACKGROUND: Predicting the survival of non-cancer related end-stage-liver-disease patients in general practice has been difficult for physicians because of the extremely variable trajectories due to multiple complex clinical factors, hence it remains a challenging issue to date. This study aimed to develop and validate a specific prognostic scoring system to early recognize the prognosis and improve the quality of end-of life care for non-cancer end-stage-liver-disease population. MATERIALS AND METHODS: A multicentre, retrospective cohort study was conducted during January 2010 ~ December 2012 and continued follow-up until December 2014. A cox proportional hazard regression analysis was used to derive and validate an optimized model. The main outcome measures were the 28-day, 3-month, 6-month, and 12-month mortality prediction. The performance of the novel model was evaluated, including discrimination and calibration. RESULTS: A total of 4,080 consecutive subjects were enrolled. The AUROCs for the 3-month survival discrimination in the MELD, MELD-Na and novel model were 0.787, 0.705 and 0.804 (P<0.001); the 6-month survival discrimination were 0.781, 0.702 and 0.797 (P<0.001); the overall survival discrimination were 0.771, 0.694 and 0.785 (P = 0.002) respectively, whereas the novel model showed a significantly higher discrimination power than did the MELD and MELD-Na for the 3-month, 6-month and overall survival prediction. In addition, calibration of external validation cohort showed no statistical difference in all 5 groups compared with the observed groups. CONCLUSION: This is a clinically relevant, validated scoring system that can be used sequentially to stratify the prognosis in non-cancer cirrhotic populations, which may help the patients along with medical team in decision making to improve the quality of end-of-life care.

Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.

BACKGROUND: Mycobacterium tuberculosis (TB) is one of the world's most devastating public health threats. Our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect the risk of new incident active TB disease. METHODS: We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan's national health insurance research database. Effects of NSAIDs on active TB were estimated by conditional logistic regression and adjusted using a TB-specific disease risk score (DRS). NSAIDs exposures were defined as having a prescription record of NSAIDs ≧ 7 days that ended between 31 and 90 days prior to the index date. RESULTS: A total of 123,419 users of traditional NSAIDs, 16,392 users of cyclooxygenase-2 selective inhibitor (Coxibs), and 4706 incident cases of active TB were identified. Compared with nonusers, use of traditional NSAIDs was associated with an increased risk of TB in the unadjusted analysis ([RR], 1.39; 95% [CI], 1.24 - 1.57 and DRS adjusted analysis ([ARR], 1.30; 95% [CI], 1.15- 1.47). However, use of Coxibs was not associated with a significant increase in the risk of TB after DRS adjustment ([ARR], 1.23; 95% [CI], 0.89 - 1.70). CONCLUSIONS: In this large population-based study, we found that subjects using traditional NSAIDs were associated with increased risk for active TB. We did not find evidence for a causative mechanism between traditional NSAIDs and TB, and more research is required to verify whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset.

Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling.

Toll-like receptor 4 (TLR4) plays a pivotal role in the host response to lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria. Here, we elucidated whether the endocytic adaptor protein Disabled-2 (Dab2), which is abundantly expressed in macrophages, plays a role in LPS-stimulated TLR4 signaling and trafficking. Molecular analysis and transcriptome profiling of RAW264.7 macrophage-like cells expressing short-hairpin RNA of Dab2 revealed that Dab2 regulated the TLR4/TRIF pathway upon LPS stimulation. Knockdown of Dab2 augmented TRIF-dependent interferon regulatory factor 3 activation and the expression of subsets of inflammatory cytokines and interferon-inducible genes. Dab2 acted as a clathrin sponge and sequestered clathrin from TLR4 in the resting stage of macrophages. Upon LPS stimulation, clathrin was released from Dab2 to facilitate endocytosis of TLR4 for triggering the TRIF-mediated pathway. Dab2 functions as a negative immune regulator of TLR4 endocytosis and signaling, supporting a novel role for a Dab2-associated regulatory circuit in controlling the inflammatory response of macrophages to endotoxin.

Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis.

PURPOSE: The study aims to determine the usefulness of procalcitonin (PCT) and other blood markers for identification of bacterial infection among patients with febrile neutropenia (FN). METHODS: The Medline, EMBASE, and Cochrane databases were searched for articles from 1966 to December 2012. We performed a search to identify articles that examined the diagnostic accuracy of PCT in patients with FN. Statistical analyses (fixed- or random-effect models) were conducted to summarize and calculate the sensitivity, specificity, likelihood ratios, and 95 % confidence intervals (CIs). RESULTS: Twenty-seven studies were included (1960 febrile episodes) for PCT analysis, 13 (1712 febrile episodes) for C-reactive protein (CRP) analysis, and five (314 febrile episodes) for interleukin (IL)-6 analysis. Increased PCT levels (odds ratio [OR] 11.5; 95 % CI 7.6 to 17.3), raised CRP levels (3.3; 2.7 to 4.2), and raised IL-6 levels (10.0; 5.5 to 18.0) were significantly associated with bacterial infection. Overall positive likelihood ratio was 5.49 (4.04-7.45) for PCT, 1.82 (1.42-2.33) for CRP, and 3.68 (2.41-5.60) for IL-6. Overall negative likelihood ratio was 0.40 (0.31-0.51) for PCT, 0.40 (0.26-0.61) for CRP, and 0.33 (0.23-0.46) for IL-6. CONCLUSIONS: Of the three potentially useful markers, PCT had the best positive likelihood ratio and can be used to confirm the diagnosis of bacterial infections in patients with FN. Due to unacceptably high negative likelihood ratio, medical decision for stopping antibiotics based on PCT alone in this high-risk population may not be possible.

Prognostic determinants of community-acquired bloodstream infection in type 2 diabetic patients in ED.

OBJECTIVES: The objective of the study is to describe the epidemiology and outcome of community-acquired bloodstream infection (BSI) in type 2 diabetic patients in emergency department (ED). METHODS: All patients admitted to the ED of the university hospital from June 2010 to June 2011 with a history of type 2 diabetes mellitus and microbiologically documented BSI were retrospectively enrolled. Demographic characteristics, Charlson comorbidity index, antibiotic therapy, clinical severity, microbiological etiology, and diabetes-related complications were recorded in a standardized form. The major outcome measure was 30-day survival. χ2 Or Student t test was used for univariate analysis, and Cox proportional hazards models were used for multivariate analysis. RESULTS: Among 250 enrolled emergency patients with BSI, the overall 30-day mortality rate was 15.5%. Twenty-seven patients (10.7%) developed diabetic ketoacidosis (DKA), and 22 patients (8.8%) developed hyperosmolar hyperglycemic state. On univariate analysis, DKA rather than hyperosmolar hyperglycemic state was associated with adverse outcome. Other risk factors include higher mean glycated hemoglobin level, presence of underlying malignancy, long-term use of steroids, lower respiratory tract infection, and higher Charlson scores. Multivariate analysis identified 3 independent risk factors for early mortality when severity, comorbidity, age, and sex were under control: DKA (hazard ratio, 3.89; 95% confidence interval, 1.6-8.9), inappropriate antibiotics (2.25, 1.05-4.82), and chronic use of steroid (3.89, 1.1-13.2). CONCLUSION: In type 2 diabetic patients with BSI, a substantial proportion of patients developed DKA. This condition was probably underrecognized by clinicians and constituted an independent risk factor for short-term mortality. Other identified risk factors are potentially correctable and may allow preventive efforts to individuals at greatest potential benefit.

Distinct effects of Disabled-2 on transferrin uptake in different cell types and culture conditions.

Iron uptake by the transferrin (Tf)-transferrin receptor (TfR) complex is critical for erythroid differentiation. The mechanisms of TfR trafficking have been examined, but the adaptor proteins involved in this process are not fully elucidated. We have investigated the role of the adaptor protein, Disabled-2 (Dab2), in erythroid differentiation and Tf uptake in the cells of hematopoietic lineage. Dab2 was upregulated in a time-dependent manner during erythroid differentiation of mouse embryonic stem cells and human K562 erythroleukemic cells. Attenuating Dab2 expression in K562 cells diminished TfR internalization and increased surface levels of TfR concomitantly with a decrease in Tf uptake and erythroid differentiation. Dab2 regulated Tf uptake of the suspended, but not adherent, cultures of K562 cells. In contrast, Dab2 is not involved in TfR trafficking in the HeLa cells with epithelial origin. These differential effects are Dab2-specific because attenuating the expression of adaptor protein 2 µ subunit inhibited the uptake of Tf regardless of culture condition. We offer novel insight of Dab2 function in iron uptake and TfR internalization for the suspended culture of hematopoietic lineage cells.

Predictive value of plasma brain natriuretic peptide for postoperative cardiac complications--a systemic review and meta-analysis.

BACKGROUND: We aimed to undertake a systematic review and meta-analysis of studies addressing perioperative natriuretic peptide (NP) levels to predict postoperative major adverse cardiac events (MACE) after major surgery. METHODS: We searched MEDLINE and Embase with no language restrictions up to May 2013. The end points were major cardiac complications. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. RESULTS: Of the 662 retrieved articles, 24 studies satisfied the predefined eligibility criteria, including 5438 patients along with 712 (13.1%) events. After major surgery, the diagnostic odds ratio (DOR) of NP in predicting postoperative MACE was 14.3 (95% confidence interval [CI], 9.87-20.7) for overall population, 13.9 (8.43-22.8) for patients undergoing cardiac surgery, and 15.0 (8.84-25.5) for patients undergoing noncardiac surgery. The pooled sensitivity was 0.84 (95% CI, 0.79-0.88) and specificity was 0.76 (95% CI, 0.71-0.81). Postoperative measurement (DOR, 18.9; 7.68-46.3) was associated with higher predictive value than preoperative measurement (DOR, 13.6; 7.68-46.3). Results were similar for a subgroup with the composite outcome including mortality (DOR, 16.4; 10.6-25.5). B-type natriuretic peptide was associated with higher predictive accuracy (area under the summary receiver operating characteristic, 0.84; 0.81-0.87) than N-terminal pro-b-type natriuretic peptide (area under the summary receiver operating characteristic, 0.90; 0.87-0.92). CONCLUSIONS: The existing literature suggests that perioperative NP testing have reasonable accuracy and can be useful in perioperative risk stratification. Natriuretic peptide testing has high rule-out value and low rule-in value for predicting postoperative MACE. Medical decisions should be made in the context of these characteristics.

Use of bisphosphonates and the risk of osteonecrosis among cancer patients: a systemic review and meta-analysis of the observational studies.

PURPOSE: This study aims to systematically review observational studies evaluating the use of bisphosphonates (BPs) and risk of osteonecrosis of the jaw (ONJ) among cancer patients. METHODS: PubMed, Embase, and Cochrane Library were screened from database inception to Aug 2012. Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals were derived by random effects meta-analysis. Subgroup analyses were carried out according to patients' characteristics and route of BP use. RESULTS: We identified eight studies, including 1,389 cases and 569,620 controls. Use of BPs was associated with a significantly increased risk of ONJ (odds ratio (OR) 4.25; 95 % confidence interval (CI) 3.67-5.36; I (2) = 0 %). The summary OR was 4.22 (95 % CI 3.21-5.54; I (2) = 0 %) for adjusted studies. IV BPs were associated with higher risk (OR 4.27; 95 % CI 3.38-5.40; I (2) = 0 %) than oral BPs (OR 1.18; 95 % CI 0.89-1.56; I (2) = 0 %). Hospital-based studies were associated with higher risk estimates than population-based studies. CONCLUSION: The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at the highest risk. It is important to assess oral health before initiating therapy and to avoid dental procedures during the active phase of intravenous BP therapy.

Diagnostic role of procalcitonin in patients with suspected appendicitis.

BACKGROUND: The aim of this study was to assess the diagnostic value of procalcitonin (PCT) in emergency department (ED) patients with suspected appendicitis. METHODS: A prospective observational study was carried out in the emergency department of a university hospital between July 2007 and June 2008. Adult patients who presented to the ED with clinically suspected appendicitis were enrolled. Each patient underwent serum PCT, C-reactive protein (CRP), and Alvarado score evaluation on admission. The results of these three measurements were analyzed in relation to the final diagnosis determined by histopathological findings or compatible computed tomography findings. RESULTS: Of the 214 study patients, 113 (52.8 %) had a confirmed diagnosis of appendicitis and 58 had complicated appendicitis (phlegmon, perforation, or gangrene). For the diagnosis of appendicitis, the area under the receiving operating characteristic (ROC) curve is 0.74 for Alvarado score, 0.69 for PCT, and 0.61 for CRP. Overall, the Alvarado score has the best discriminative capability among the three tested markers. We adopted two cutoff point approaches to harness both ends of the diagnostic value of a biomarker. PCT levels were significantly higher in patients with complicated appendicitis. For diagnosis of complicated appendicitis, a cutoff value of 0.5 ng/mL had a sensitivity of 29 % and a specificity of 95 %, while a cutoff value of 0.05 ng/ml had a sensitivity of 85 % and a specificity of 30 % in diagnosing complicated appendicitis. For those with a PCT value in the gray zone, clinical findings may play a more important role. CONCLUSION: The study does not support the hypothesis that the PCT test may be useful for screening ED patients for appendicitis. However, determination of the PCT level may be useful for risk assessment of ED patients with suspected complicated appendicitis.

Autocrine signaling of platelet-derived growth factor regulates disabled-2 expression during megakaryocytic differentiation of K562 cells.

Platelet-derived growth factor (PDGF) is involved in megakaryocytopoiesis and is secreted into the culture medium during megakaryocytic differentiation of human leukemic cells. We investigate whether PDGF plays a role in the regulation of the adapter protein Disabled-2 (DAB2) that expresses abundantly in platelets and megakaryocytes. Western blot analysis revealed that conditioned medium from 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated, megakaryocytic differentiating K562 cells upregulated DAB2 expression. DAB2 induction and megakaryocytic differentiation was abrogated when cells were co-treated with the PDGF receptor inhibitor STI571 or when the conditioned medium was derived from TPA-plus STI571-treated cells. Although the level of PDGF mRNA was not altered by STI571, an approximate 44% decrease in PDGF in the conditioned medium was observed. Consistent with these findings, interfering PDGF signaling by PDGF neutralization antibody or dominant negative PDGF receptors attenuated DAB2 expression. Accordingly, transfection of an expression plasmid encoding secreted PDGF upregulated DAB2. This study shows for the first time that PDGF autocrine signaling regulates DAB2 expression during megakaryocytic differentiation.

Acute Cycas seed poisoning in Taiwan.

OBJECTIVE: The seeds of cycads contain cycasin and neocycasin, which belong to the family of cyanogenic glycosides. These glycosides of cycads are considered pseudocyanogenic with little potential to liberate hydrogen cyanide as other cyanogenic glycosides do. This study investigated the clinical spectrum of Cycas seed poisoning and its cyanogenic potential. METHODS: This was a retrospective chart review conducted at the Poison Control Center in Taiwan (PCC-Taiwan) from 1990 to 2001. RESULTS: Twenty-one cases of Cycas seed poisoning were identified. The reasons for seed ingestion were misuse as an edible food (70%), health promotion (10%), cancer prevention (10%), cosmetic use (5%), and gastrointestinal discomfort (5%). All patients had eaten the seeds after washing and cooking them. The time from ingestion to the onset of symptoms ranged from 30 min to 7 h (mean 2.8 h); patients had ingested between 1 to 30 seeds. Respiratory depression did not occur. Severe vomiting was the most striking symptom. All patients except one presented with gastrointestinal disturbance, and 90% sought medical care at the emergency department. Within 24 h, all patients had recovered. Six patients had blood cyanide or thiocyanate levels measured. Although the levels were higher than normal, they did not reach the toxic range. CONCLUSIONS: The cyanogenic potential of Cycas seeds is documented in our cases. The gastrointestinal symptoms were severe enough that most patients sought medical attention but recovery was quick and complete.

Priapism--a rare presentation in chronic myeloid leukemia: case report and review of the literature.

Priapism is a complication rarely seen in leukemia. We report a 21-year-old man presented with persistent painful erection of penis for 19 hours at home. The patient had undergone immediate irrigation and decompression of priapism by urologist at emergency department. This approach resulted in a flaccid penis later. During hospitalization, peripheral blood smear and bone marrow aspiration was confirmatory of chronic myeloid leukemia. No impotency nor other sequela was noted after his discharge. This case illustrates the importance of all physicians in the diagnosis and management of patients with priapism.

Secondary aortoduodenal fistula.

Secondary aortoenteric fistula (SAF) is now recognized as an uncommon but exceedingly important complication of abdominal aortic reconstruction. The complication often occurs months to years after the original surgery. The main clinical manifestation of the disease is always upper gastrointestinal bleeding. Treatment of the disease is early surgical intervention. The mortality is high if no prompt operation. We present a case of secondary aortoduodenal fistula (SADF) found 20 days after aortic reconstructive surgery, with the clinical presentation of upper gastrointestinal bleeding. Even immediate exploratory laparotomy was performed, the patient died 48 hrs after the surgical management. Because of the increasing number of elective aortic aneurysm repairs in the aging population, it is likely that more patients with SAF will present to the clinical physicians in the future. So, a high index of suspicion is necessary for prompt diagnosis and treatment of this actually life-threatening event.