Development of a reliable surgical quality assurance tool for gastrectomy in oncological trials.

BACKGROUND: Despite its recognized importance, there is currently no reliable tool for surgical quality assurance (SQA) of gastrectomy in surgical oncology. The aim of this study was to develop an SQA tool for gastrectomy and to apply this tool within the ADDICT Trial in order to assess the extent and completeness of lymphadenectomy. METHODS: The operative steps for D1+ and D2 gastrectomy have been previously described in the literature and ADDICT trial manual. Two researchers also performed fieldwork in the UK and Japan to document key operative steps through photographs and semi-structured interviews with expert surgeons. This provided the steps that were used as the framework for the SQA tool. Sixty-two photographic cases from the ADDICT Trial were rated by three independent surgeons. Generalizability (G) theory determined inter-rater reliability. D-studies examined the effect of varying the number of assessors and photographic series they rated. Chi-square assessed intra-rater reliability, comparing how the individual assessor's responses corresponded to their global rating for extent of lymphadenectomy. RESULTS: The tool comprised 20 items, including 19 anatomical landmarks and a global rating score. Overall reliability had G-coefficient of 0.557. Internal consistency was measured with a Cronbach's alpha score of 0.869 and Chi-square confirmed intra-rater reliability for each assessor as < 0.05. CONCLUSIONS: A photographic surgical quality assurance tool is presented for gastrectomy. Using this tool, the assessor can reliably determine not only the quality but also the extent of the lymphadenectomy performed based on remaining anatomy rather than the excised specimen.

Structure and Functional Differences of Cysteine and 3-Mercaptopropionate Dioxygenases: A Computational Study.

Thiol dioxygenases are important enzymes for human health; they are involved in the detoxification and catabolism of toxic thiol-containing natural products such as cysteine. As such, these enzymes have relevance to the development of Alzheimer's and Parkinson's diseases in the brain. Recent crystal structure coordinates of cysteine and 3-mercaptopropionate dioxygenase (CDO and MDO) showed major differences in the second-coordination spheres of the two enzymes. To understand the difference in activity between these two analogous enzymes, we created large, active-site cluster models. We show that CDO and MDO have different iron(III)-superoxo-bound structures due to differences in ligand coordination. Furthermore, our studies show that the differences in the second-coordination sphere and particularly the position of a positively charged Arg residue results in changes in substrate positioning, mobility and enzymatic turnover. Furthermore, the substrate scope of MDO is explored with cysteinate and 2-mercaptosuccinic acid and their reactivity is predicted.

Association of use of Chinese herbal medicines and the risk of fracture in patients with osteoporosis: a population-based cohort study.

After utilizing a large population-based claims database and the application of propensity score match approach to reduce the confounding effects, we found that the use of Chinese herbal medicines (CHMs) was related to the lower risk of sequent osteoporotic fracture by 27% among the individuals with osteoporosis. The predominant effect was observed in those receiving CHMs for more than two years. INTRODUCTION: Osteoporosis (OS) is a highly disabling condition that can lead to fragility fracture, thus posing greater burdens of functional limitations for the affected individuals. It is unclear if the use of Chinese herbal medicines (CHMs) could reduce the risk of fracture due to OS. This study aimed to investigate the association of CHMs and the subsequent osteoporotic fracture risk among OS patients. METHODS: This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 250,699 newly diagnosed OS patients aged 20 years or older between 1998 and 2010. We recruited 103,325 CHM users following the onset of OS (CHM users) and randomly selected 103,325 subjects without CHM usage as controls (non-CHM users) by propensity score matching according to the demographic characteristics and comorbidities at enrollment. All enrollees were followed until the end of 2012 to record the incidence of osteoporotic fracture. We applied the Cox proportional hazard regression model to compute the hazard ratio (HR) of the risk of osteoporotic fracture. RESULTS: During the 15-year follow-up period, 7208 CHM users and 11,453 non-CHM users sustained osteoporotic fracture, with an incidence rate of 9.26 and 12.96, respectively, per 1000 person-years. We found that CHM users had a significantly reduced risk of osteoporotic fracture compared to non-CHM users (adjusted HR 0.73; 95% confidence interval [CI] = 0.70-0.75). Those treated with CHMs for longer than 730 days had a lower fracture risk by 54%. Some commonly used CHMs, such as Yan hu suo (Rhizoma Corydalis), Huang Qin (Scutellaria Baicale), Jie Geng (Platycodon grandifloras), Xiang Fu (Cyperus rotundus), Hai Piao Xiao (Cuttlebone Sepium), Jia-Wei-Xiao-Yao-San, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, and Du-Huo-Ji-Sheng-Tang, are related to the lower risk of fracture. CONCLUSIONS: The use of CHMs was associated with lower risk of osteoporotic fracture for OS patients, suggesting that it could be integrated into conventional therapy to prevent subsequent bone fracture.

Risk of epilepsy in surgical patients undergoing general or neuraxial anaesthesia.

Limited information is available on the risks of epilepsy after surgery in patients receiving general or neuraxial anaesthesia. Using Taiwan's National Health Insurance Research Database, we identified 1,478,977 patients aged ≥ 20 years who underwent surgery (required general or neuraxial anaesthesia with hospitalisation for more than one day) between 2004 and 2011. We selected 235,066 patients with general anaesthesia and 235,066 patients with neuraxial anaesthesia using a frequency-matching procedure for age and sex. We did not study those with co-existing epilepsy-related risk factors. The adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of newly diagnosed epilepsy 1 year after surgery associated with general anaesthesia were analysed in the multivariate Poisson regression model. The one-year incidence of postoperative epilepsy for patients with general anaesthesia and neuraxial anaesthesia were 0.41 and 0.32 per 1000 persons, respectively, and the corresponding RR was 1.27 (95%CI 1.15-1.41). The association between general anaesthesia and postoperative epilepsy was significant in men (RR = 1.22; 95%CI 1.06-1.40), women (RR = 1.33; 95%CI 1.15-1.55) and 20-39-year-old patients. The risk of postoperative epilepsy increased in patients with general anaesthesia who had co-existing medical conditions and postoperative complications.

Risk and outcomes of fracture in peripheral arterial disease patients: two nationwide cohort studies.

Using national insurance claims data of Taiwan, we found that patients with peripheral arterial disease (PAD) had increased risk of fracture during the follow-up period of 2000-2013. History of PAD was also associated with adverse outcomes in hospitalized fracture patients. Prevention strategies were needed in this susceptible population. INTRODUCTION: Limited information was available on the association between PAD and fracture. The purpose of this study is to evaluate fracture risk and post-fracture outcomes in patients with PAD. METHODS: We identified 6647 adults aged ≥ 20 years with newly diagnosed PAD using the Taiwan National Health Insurance Research Database in 2000-2004. Comparison cohort consisted of 26,588 adults without PAD randomly selected with frequency matching in age and sex. Events of fracture were identified during the follow-up period from January 1, 2000 until December 31, 2013, to evaluate adjusted hazard ratios (HR) and 95% confidence interval (CI) of fracture associated with PAD. Another nested cohort study of 799,463 hospitalized fracture patients analyzed adjusted odds ratios (ORs) and 95% CIs of adverse events after fracture among patients with and without PAD in 2004-2013. RESULTS: Incidences of fracture in people with and without PAD were 22.1 and 15.5 per 1000 person-years, respectively (P < .0001). Compared with control, the adjusted HR of fracture was 1.59 (95% CI, 1.48-1.69) for PAD patients. In the nested cohort study, patients with PAD had higher post-fracture mortality (OR = 1.16; 95% CI, 1.09-1.25) and various complications. PAD patients also had comparatively higher medical expenditure (2691 vs. 2232 USD, P < .0001) and longer hospital stay (10.6 vs. 9.0 days, P < 0.0001) during fracture admission. CONCLUSIONS: Increased risk of fracture and post-fracture adverse outcomes were associated with PAD. This susceptible population needs care to prevent fracture and to minimize adverse outcomes after it occurs.

Birth month and risk of atopic dermatitis: a nationwide population-based study.

BACKGROUND: An individual's birth month has been associated with allergic diseases, but little is known about the association between birth month and atopic dermatitis (AD). OBJECTIVE: The aim of this study was to investigate the risk of AD in children born in various months. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a case-control study that included 31 237 AD cases and 124 948 age- and gender-matched controls without AD. Data regarding sociodemographic factors and coexisting medical conditions were collected and controlled in the multivariate logistic regression to determine the adjusted odds ratios and 95% confidence intervals for AD associated with the participant's birth month. RESULTS: Compared with people born in May, people born in December had the highest risk of AD (OR 1.17, 95% CI 1.10-1.25), followed by people born in October (OR 1.15, 95% CI 1.08-1.22) and November (OR 1.13, 95% CI 1.06-1.20). Low income (OR 1.28), asthma (OR 1.88), allergic rhinitis (OR 1.70), psoriasis (OR 2.36), vitiligo (OR 1.99), urticaria (OR 2.14), and systemic lupus erythematosus (OR 1.91) were significant coexisting medical conditions associated with AD. CONCLUSION: Being born in December, October, or November may be associated with an increased risk of AD. Future investigations are needed to evaluate the possible mechanism behind the association between birth month and AD.

Risk and adverse outcomes of fractures in patients with Parkinson's disease: two nationwide studies.

UNLABELLED: The association between Parkinson's disease and fracture was not completely understood. This nationwide study investigated increased risk of fracture in patients with Parkinson's disease. In the nested cohort study, Parkinson's disease was associated with pneumonia, septicemia, stroke, urinary tract infection, and mortality after fracture admission. INTRODUCTION: Falls are a common complication in people with Parkinson's disease (PD). This study evaluated fracture risk and post-fracture outcomes in patients with PD. METHODS: We identified 1,423 adults aged 40 years and older newly diagnosed with PD using the Taiwan National Health Insurance Research Database from 2000 to 2003. Comparison cohort consisted of 5,692 adults without PD randomly selected from the same dataset, frequency matched in age and sex. Followed-up events of fracture from January 1, 2000, until December 31, 2008, were ascertained from medical claims. Adjusted hazard ratios (HR) and 95 % confidence interval (CI) of fracture associated with PD were evaluated. Another nested cohort study of 397,766 hospitalized fracture patients analyzed for adjusted odds ratios (ORs) and 95 % CIs of adverse events after fracture among patients with and without PD between 2004 and 2010. RESULTS: The incidences of fracture for people with and without PD were 39.5 and 23.9 per 1,000 person-years, respectively (p < 0.0001). Compared with control, the adjusted HR of fracture was 2.25 (95 % CI 1.97-2.58) for PD patients. Previous PD was associated with risks of pneumonia (OR 1.44, 95 % CI 1.36-1.52), septicemia (OR 1.41, 95 % CI 1.33-1.49), stroke (OR 1.40, 95 % CI 1.32-1.50), urinary tract infection (OR 1.53, 95 % CI 1.46-1.61), and mortality (OR 1.25, 95 % CI 1.15-1.35) after fracture. CONCLUSIONS: PD was associated with higher risk of fracture. Patients with PD had more complications and mortality after fracture. Fracture prevention and attention to post-fracture adverse events are needed for this susceptible population.

Outcomes after surgery in patients with previous stroke.

BACKGROUND: Limited information is available on the association between a medical history of stroke and postoperative outcomes. This study investigated the outcomes following non-neurological surgery in patients with previous stroke. METHODS: Using Taiwan's National Health Insurance Research Database, a nationwide cohort study was conducted of patients who underwent non-neurological surgery between 2008 and 2010 with a medical history of stroke in the 24-month period before operation. Patients who had non-neurological surgeries without previous stroke were selected as controls by the propensity score-matched pair method. Thirty-day postoperative complications and in-hospital mortality were compared between the two groups. RESULTS: Some 1 426 795 adults underwent major inpatient non-neurological surgery, of whom 45 420 had a medical history of previous stroke. Patients with previous stroke who underwent surgery had an increased risk of postoperative pneumonia, septicaemia, acute renal failure, acute myocardial infarction, pulmonary embolism and 30-day in-hospital mortality (adjusted rate ratio (RR) 1·79, 95 per cent c.i. 1·61 to 1·99). Compared with controls, patients with previous stroke due to intracerebral haemorrhage (RR 3·41, 2·97 to 3·91), and those who were treated in intensive care (RR 2·55, 2·24 to 2·90) or underwent neurosurgery (RR 2·49, 2·12 to 2·92), had an increased 30-day in-hospital mortality rate. Postoperative mortality also increased with stroke-related co-morbidities, and with stroke 1-6 months before surgery (RR 3·31, 2·91 to 3·75). CONCLUSION: Patients with previous stroke had a higher risk of adverse postoperative outcomes; their 30-day in-hospital mortality rate was nearly twice that of patients without previous stroke.

Effects of sheng hua tang on uterine involution and ovarian activity in postpartum dairy cows.

The effects of Sheng Hua Tang (SHT) on uterine involution and ovarian activity were investigated in postpartum dairy cows. SHT (70 g) was given to dairy cows (n = 10) to evaluate its effects for five days from the first postpartum day. Postpartum cows fed with a basal diet without SHT were used as the control group (n = 10). Ultrasounds and blood tests were recorded for four weeks from postpartum day seven with a 3-d interval. The results showed that the areas and diameters of endometria were significantly (p<0.01) reduced in the group that received SHT compared to the control group on the seventh postpartum day. The group that received SHT had an intrauterine fluid volume mean of 1.2±0.6 cm(3), which was significantly lower than that of the control group, 2.3±0.8 cm(3) (p<0.01) on the 13th postpartum day. In addition, the uterine tension score was a mean of 1.0±0.0 in the group that received SHT, which was also significantly lower than that of the control group, 1.5±0.5 (p<0.01) on the 19th postpartum day. Taken together, the Chinese herbal medicine remedy, SHT, promoted uterine involution and ovarian activity in postpartum dairy cows.

Effects of red yeast rice prescription (LipoCol Forte) on adverse outcomes of surgery.

BACKGROUND: The influence of red yeast rice (RYR) on perioperative outcome remains unknown. AIM: We aimed to compare the complications and mortality after surgery between patients treated with and without RYR prescription. DESIGN: In this surgical cohort study of 3.6 million surgical patients who underwent major inpatient surgeries, 2581 patients who used RYR prescription pre-operatively were compared with 25 810 non-RYR patients selected by matching for age and sex. METHODS: Patients' demographics and medical conditions were collected from the claims data of the National Health Insurance in Taiwan. Complications and mortality after major surgeries in association with RYR prescription were investigated by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) by multiple logistic regression. RESULTS: Compared with patients without RYR prescription, patients prescribed RYR had lower risks of post-operative bleeding (OR 0.36, 95% CI 0.15-0.89), pneumonia (OR 0.54, 95% CI 0.36-0.83), stroke (OR 0.66, 95% CI 0.47-0.92) and 30-day in-hospital mortality (OR 0.37, 95% CI 0.15-0.92). Decreased risk of intensive care (OR 0.64, 95% CI 0.54-0.77), shorter length of hospital stay (P < 0.001) and lower medical expenditures (P = 0.0008) during the index surgical admission were also noted for patients with RYR prescription compared to those for patients without RYR prescription. CONCLUSIONS: This study showed a potentially positive effect of RYR on outcomes after major surgeries. However, patient non-compliance for taking medication should be noted. Our findings require future prospective studies to validate RYR prescription for improving perioperative outcomes.

Reduced use of emergency care and hospitalization in patients with post-stroke cognitive impairment treated with traditional Chinese medicine.

BACKGROUND: The effect of traditional Chinese medicine (TCM) on the outcomes of dementia remains unclear. Our purpose is to compare the use of emergency care and hospitalization in patients with post-stroke cognitive impairment (PSCI) with or without treatment of TCM. METHODS: In a stroke cohort of 67 521 patients with PSCI aged over 40 years obtained from the 23 million people in Taiwan's national health insurance between 2000 and 2007, we identified 6661 newly diagnosed PSCI patients who were treated with TCM and 6661 propensity score-matched PSCI patients who were not treated with TCM. Under the control of immortal time bias, we calculated the adjusted rate ratios (RRs) and 95% CIs of the 1-year use of emergency care and hospitalization associated with TCM. RESULTS: The means of the emergency care medical visits (0.40 ± 0.98 vs. 0.47 ± 1.01, P = 0.0001) and hospitalization (0.72 ± 1.29 vs. 0.96 ± 1.49, P < 0.0001) were lower in the PSCI patients treated with TCM than in those without the TCM treatment. The RRs of emergency care and hospitalization associated with TCM were 0.87 (95% CI = 0.82-0.92) and 0.81 (95% CI = 0.78-0.84), respectively. The PSCI patients treated with a combination of acupuncture and herbal medicine had the lowest risk of emergency care visits and hospitalization. CONCLUSIONS: Our study raises the possibility that TCM use was associated with reduced use of emergency care and hospitalization after PSCI. However, further randomized clinical trials are needed to provide solid evidence of this benefit and identify the underlying mechanism.

Stroke in Parkinson's disease.

BACKGROUND: The association between Parkinson's disease (PD) and stroke remains completely understood. AIM: We aimed to investigate stroke risk and post-stroke outcomes in patients with PD. DESIGN: The retrospective cohort study included 1303 patients aged ≥ 40 years with new-diagnosed PD and 5212 non-PD adults were selected by frequency matching with age and sex in 2000-05. Both two groups were followed up until the end of 2013. Another nested stroke cohort study of 17 678 patients with stroke hospitalization in 2002-09 was conducted to compare the admission outcome in patients with and without PD history. METHODS: We collected patients' characteristics and medical conditions in the present two studies from claims data of Taiwan's National Health Insurance. Incidences and risks of stroke in people with and without PD during the follow-up period were calculated by adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in the Cox proportional hazard model. Complications and mortality during the stroke admission associated with PD were analysed by calculating adjusted odds ratios (ORs) and 95% CIs in the logistic regressions. RESULTS: Incidences of stroke for people with and without PD were 19.8 and 9.93 per 1000 person-years, respectively, with corresponding HR of 1.96 (95% CI 1.67-2.30). History of PD was associated with post-stroke gastrointestinal bleeding (OR 1.25, 95% CI 1.05-1.49), epilepsy (OR 1.64, 95% CI 1.32-2.04), pneumonia (OR 1.34, 95% CI 1.20-1.49), urinary tract infection (OR 1.33, 95% CI 1.21-1.45) and mortality (OR 1.35, 95% CI 1.13-1.62). CONCLUSION: PD increases stroke risk and influences post-stroke outcomes.

ALFRED: the ALelle FREquency Database. Update.

Elaboration of ALFRED (http://alfred.med.yale.edu) is being continued in two directions. One of which is developing tools for efficiently annotating the entries and checking the integrity of the data already in the database while the other is to increase the quantity and accessibility of data. Information contained in ALFRED such as, polymorphic sites, number of populations and frequency tables (one sample typed for one site) has significantly increased.

Adenovirus-mediated p14(ARF) gene transfer in human mesothelioma cells.

BACKGROUND: The p14(ARF) protein encoded by the INK4a/ARF locus promotes degradation of the MDM2 protein and thus prevents the MDM2-mediated inhibition of p53. Homozygous deletion of the INK4a/ARF locus is common in human mesothelioma and may result in the loss of p14(ARF) and the inactivation of p53. We designed this study to evaluate the biologic and potential therapeutic roles of p14(ARF) expression in mesothelioma cells. METHODS AND RESULTS: We constructed Adp14, an adenoviral vector carrying human p14(ARF) complementary DNA, and used it to transfect human mesothelioma cell lines H28, H513, H2052, and MSTO-211H. Overexpression of p14(ARF) led to increased amounts of p53 and the p21(WAF) proteins and dephosphorylation of the retinoblastoma protein. The growth rate of mesothelioma cells was inhibited markedly by infection with Adp14 compared with mock infection or infection with a control adenovirus vector, AdCtrl. Overexpression of p14(ARF) induced G(1)-phase cell cycle arrest and apoptotic cell death. Cytotoxicity assays showed that Adp14 had a statistically significantly (P =.002) greater effect on colon cancer (HCT116) cell lines containing two copies of the wild-type p53 gene than on p53-null cells, suggesting that functional p53 is a critical determinant of p14(ARF)-mediated cytotoxicity. CONCLUSIONS: The transfection of p14(ARF) into mesothelioma cells led to the overexpression of p14(ARF), which resulted in G(1)-phase arrest and apoptotic cell death. These results suggest that this gene therapy-based approach may be of use in the treatment of mesothelioma.

p14(ARF) modulates the cytolytic effect of ONYX-015 in mesothelioma cells with wild-type p53.

ONYX-015 has been reported to kill selectively tumor cells lacking functional p53. Genetic alterations of INK4a/ARF locus, which is a predominant event in malignant pleural mesothelioma, may result in loss of p14(ARF) and subsequent disruption of p53 pathway in cancer cells. In the present study, ONYX-015 was able to kill three mesothelioma cell lines (H28, H513, and 211H) with wild-type p53 but lacking p14(ARF). In contrast, MS-1 mesothelioma cells, which expressed both p53 and p14(ARF), were resistant to ONYX-015. Introducing p14(ARF) gene into the H28 cell, a mesothelioma cell without p14(ARF) expression, significantly increased the resistance of this cell line to the cytolytic effect of ONYX-015. Our results suggest that human mesotheliomas with wild-type p53 yet lacking p14(ARF) are potential candidates for ONYX-015 therapy.

Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells.

Manganese superoxide dismutase (MnSOD) has been shown to play an important role in preventing the development of cancer. MnSOD activity is reduced in many transformed cells and tumor tissues. We previously showed that the reduced level of MnSOD activity in cancer cells was not due to a defect in the primary structure of MnSOD protein, but rather was due to defects in gene expression. To elucidate the cause for the reduced expression of human MnSOD in cancer, we investigated the nucleotide sequence in the regulatory region of the MnSOD gene in a normal human cell line and various human tumor cell lines. A DNA fragment spanning 3.4 kb 5' flanking region of the MnSOD gene isolated from a normal human genomic DNA library was used to determine the DNA sequence of MnSOD promoter. PCR primers were used for amplification of the 3.4 kb 5' flanking region of the human MnSOD gene in cancer cells. Sequence analysis identified three heterozygous mutations in the proximal region of the promoter in five human tumor cell lines. These mutations, clustered around the GC-rich region of the human MnSOD promoter, change the binding pattern of AP-2 and lead to a reduction in transcription activity using a luciferase reporter assay system. These results suggest that the reduced level of MnSOD expression in some tumor cells is, at least in part, due to a defect in the DNA sequence of the promoter region.

Adsorption and thermal reactions of alkanethiols on pt(111): Dependence on the length of the alkyl chain.

The adsorption and thermal decomposition of alkanethiols (R-SH, where R = CH3, C2H5, and C4H9) on Pt(111) were studied with temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS) with synchrotron radiation. Dissociation of sulfhydryl hydrogen (RS-H) of alkanethiol results in the formation of alkanethiolate; the extent of dissociation at an adsorption temperature of 110 K depends on the length of the alkyl chain. At small exposure, all chemisorbed CH3SH, C2H5SH, and C4H9SH decompose to desorb hydrogen below 370 K and yield carbon and sulfur on the surface. Desorption of products containing carbon is observed only at large exposure. In thermal decomposition, alkanethiolate is proposed to undergo a stepwise dehydrogenation: R'-CH2S --> R'-CHS --> R'-CS, R' = H, CH3, and C3H7. Further decomposition of the R'-CS intermediate results in desorption of H2 at 400-500 K and leaves carbon and sulfur on the surface. On the basis of TPD and XPS data, we conclude that the density of adsorption of alkanethiol decreases with increasing length of the alkyl chain. C4H9SH is proposed to adsorb mainly with a configuration in which its alkyl group interacts with the surface; this interaction diminishes the density of adsorption of alkanethiols but facilitates dehydrogenation of the alkyl group.

Chinese herbal medicine for miscarriage affects decidual micro-environment and fetal growth.

INTRODUCTION: Intrauterine growth restriction complicates 5-10% of pregnancies. This study aims to test the hypothesis that Chinese herbal formula, JLFC01, affects pregnancy and fetal development by modulating the pro-inflammatory decidual micro-environment. METHODS: Human decidua from gestational age-matched elective terminations or incomplete/missed abortion was immunostained using anti-CD68 + anti-CD86 or anti-CD163 antibodies. qRT-PCR and Luminex assay measured the effects of JLFC01 on IL-1ß- or TNF-α-induced cytokine expression in first trimester decidual cells and on an established spontaneous abortion/intrauterine growth restriction (SA/IUGR)-prone mouse placentae. The effect of JLFC01 on human endometrial endothelial cell angiogenesis was evaluated by average area, length and numbers of branching points of tube formation. Food intake, litter size, fetal weight, placental weight and resorption rate were recorded in SA/IUGR-prone mouse treated with JLFC01. qRT-PCR, Western blot and immunohistochemistry assessed the expression of mouse placental IGF-I and IGF-IR. RESULTS: In spontaneous abortion, numbers of decidual macrophages expressing CD86 and CD163 are increased and decreased, respectively. JLFC01 reduces IL-1ß- or TNF-α-induced GM-CSF, M-CSF, C-C motif ligand 2 (CCL2), interferon-γ-inducible protein-10 (IP-10), CCL5 and IL-8 production in first trimester decidual cells. JLFC01 suppresses the activity of IL-1ß- or TNF-α-treated first trimester decidual cells in enhancing macrophage-inhibited angiogenesis. In SA/IUGR-prone mice, JLFC01 increases maternal food intake, litter size, fetal and placental weight, and reduces fetal resorption rate. JLFC01 induces IGF-I and IGF-IR expression and inhibits M-CSF, CCL2, CCL5, CCL11, CCL3 and G-CSF expression in the placentae. DISCUSSION: JLFC01 improves gestation by inhibiting decidual inflammation, enhancing angiogenesis and promoting fetal growth.

Carotid interventions (CEA and CAS) in acute stroke patients: which procedure on which patient.

Treatment of carotid bifurcation disease in patients presenting with acute stroke has been a controversial issue over the past four decades. Classically, patients were asked to wait four to six weeks before intervention was entertained in order for the brain to stabilize and the risks of intervention to be minimized. Unfortunately, up to 20% of patients will have a secondary event after their index event and the window of opportunity to save, potentially salvageable ischemic tissue will be missed. Early reports had demonstrated poor results with intervention. However, more recently, institutions such as ours have demonstrated excellent result in early intervention in patients who present with stable mild to moderate stroke with an NIH stroke scale less than 15 and preferably less than 10, present with stroke and ipsilateral carotid artery lesion of 50% or greater. Also more recently, we have been aggressively treating patients with larger ulcerative plaques even if the stenosis approaches 50%. In our and others experiences, patients who are treated at institutions that have comprehensive stroke centers (CSCs) where they have a multidisciplinary system that consists of vascular surgeons, neuro interventionalists, stroke neurologists, specifically trained stroke nursing staff and a neuro intensive ICU have had optimal results. Early assessment, diagnosis of stroke with recognition of cause of embolization is mandatory but patient selection is extremely important; finding those patients who will benefit the most from urgent intervention. Most studies have demonstrated the benefit of carotid endarterectomy in these patients. More recent studies have demonstrated acceptable results with carotid stenting, especially in smaller lesions, those less than 1.2 centimeters. Early intervention should be avoided in most patients who are obtunded or with an NIH stroke scale greater than 15 or who do not have any "brain at risk" to salvage. These patients may be better served by being treated medically than those small group of patients that do have some improvement may benefit from interval intervention.