Interleukin-6, C-reactive protein, fibrinogen, and risk of recurrence after ischaemic stroke: Systematic review and meta-analysis.

BACKGROUND: Recent randomised trials showed benefit for anti-inflammatory therapies in coronary disease but excluded stroke. The prognostic value of blood inflammatory markers after stroke is uncertain and guidelines do not recommend their routine measurement for risk stratification. METHODS: We performed a systematic review and meta-analysis of studies investigating the association of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen and risk of recurrent stroke or major vascular events (MVEs). We searched EMBASE and Ovid Medline until 10/1/19. Random-effects meta-analysis was performed for studies reporting comparable effect measures. RESULTS: Of 2,515 reports identified, 39 met eligibility criteria (IL-6, n = 10; CRP, n = 33; fibrinogen, n = 16). An association with recurrent stroke was reported in 12/26 studies (CRP), 2/11 (fibrinogen) and 3/6 (IL-6). On random-effects meta-analysis of comparable studies, CRP was associated with an increased risk of recurrent stroke [pooled hazard ratio (HR) per 1 standard-deviation (SD) increase in loge-CRP (1.14, 95% CI 1.06-1.22, p < 0.01)] and MVEs (pooled HR 1.21, CI 1.10-1.34, p < 0.01). Fibrinogen was also associated with recurrent stroke (HR 1.26, CI 1.07-1.47, p < 0.01) and MVEs (HR 1.31, 95% CI 1.15-1.49, p < 0.01). Trends were identified for IL-6 for recurrent stroke (HR per 1-SD increase 1.17, CI 0.97-1.41, p = 0.10) and MVEs (HR 1.22, CI 0.96-1.55, p = 0.10). CONCLUSION: Despite evidence suggesting an association between inflammatory markers and post-stroke vascular recurrence, substantial methodological heterogeneity was apparent between studies. Individual-patient pooled analysis and standardisation of methods are needed to determine the prognostic role of blood inflammatory markers and to improve patient selection for randomised trials of inflammatory therapies.

High-flow Nasal Cannulae, Bronchopulmonary Dysplasia and Retinopathy of Prematurity

Aims To determine if HFNC use was associated with changes in incidence of BPD and ROP. Methods This retrospective study examined premature infants (<30 weeks GA or <1500g) in a tertiary neonatal unit from 2010- 2016. Patients were compared before and after introduction of HFNC. Further analysis of high-risk infants (<28 weeks GA or <750g or ventilated) compared those who received HFNC to those who did not across the whole period. Primary outcomes were incidence of BPD and ROP requiring surgery. Results Incidence of BPD rose following the introduction of HFNC (82/232 (35.3%) after vs 33/251 (13.1%) before, p<0.001). On multivariate analysis, the chance of developing BPD after HFNC introduction remained higher (OR 4.353, 95% CI 2.546-7.443). More infants received surgery for ROP following HFNC introduction (0/214 vs 11/205 (5.4%), p=<0.001). In the second analysis, the rate of BPD was higher in those who received HFNC (90/132 (68.1%) vs 33/153 (21.6%), p<0.001). Receiving HFNC demonstrated higher chance of BPD in multivariate analysis (OR 7.802, 95% CI 4.223-14.423). Rate of ROP surgery was higher in those who received HFNC (0/153 vs 13/134 (9.7%), p<0.001). Conclusions In this study, use of HFNC was associated with significantly increased risk of adverse outcomes.

Impact of supplemental home enteral feeding postesophagectomy on nutrition, body composition, quality of life, and patient satisfaction.

The aim of this prospective cohort study is to analyze the impact of supplemental home enteral nutrition (HEN) post-esophageal cancer surgery on nutritional parameters, quality of life (QL), and patient satisfaction. A systematic review reported that over 60% of patients lose >10% of both body weight and BMI by 6 months after esophagectomy. Enteral feeding (EF) is increasingly a modern standard postoperatively; however, the impact of extended HEN postdischarge has not been systematically studied. One hundred forty-nine consecutive patients [mean age 62 ± 9, 80% male,76% adenocarcinoma, 66% on multimodal protocols, and 69% with BMI ≥ 25 kg/m2] were studied. Jejunal EF commenced day 1 postoperatively, and supplemental overnight HEN (764 kcal; 32g protein) continued on discharge for a planned further 4 weeks. Weight, BMI, and body composition analysis (bioimpedance analysis) were measured at baseline, preoperatively and at 1, 3, and 6 months, along with the EORTC QLQ-C30/OES18 QL measures. A patient satisfaction questionnaire addressed eight key items in relation to HEN (max score 100/item). Median (range) total duration of EF was 49 days (28-96). Overall compliance was 96%. At 6 months, compared with preoperatively, 58 (39%) patients lost >10% weight, with median (IQR) loss of 6.8 (4-9) kg, and 62 (41%) patients lost >10% BMI. Lean body mass and body fat were significantly (p < 0.001) decreased. Mean global QL decreased (p < 0.01) from 82 to 72. A high mean satisfaction score (>70 ± 11/100) was reported, >80 for practical training, activities of daily living, pain, anxiety, recovery and impact on caregivers, with lower scores for appetite (33 ± 24) and sleep (63 ± 30). Supplemental HEN for a minimum of one month postdischarge is associated with high compliance and patient satisfaction. Weight and BMI loss may still be substantial, however this may be less than published literature, in addition the impact on HR-QL may be attenuated. HEN has both subjective and objective rationale and merits further validation toward optimizing nutritional recovery and overall wellbeing.

Leptin and adiponectin receptor expression in oesophageal cancer.

BACKGROUND: Oesophageal adenocarcinoma is an exemplar model of an obesity-associated adenocarcinoma. Altered secretion of adipokines by visceral fat is believed to play a key role in tumorigenesis. This study examined leptin receptor (ObR) and adiponectin receptor (AdipoR1 and AdipoR2) expression in oesophageal cancer, and its relationship with patient obesity status, clinicopathological data and patient survival. METHODS: Tissue microarrays were constructed from paraffin-embedded oesophagectomy specimens. ObR, AdipoR1 and AdipoR2 expression was quantified by immunohistochemistry. Anthropometric data were measured at the time of diagnosis, and obesity status was assessed using visceral fat area determined by computed tomography and body mass index. Receptor expression was correlated with various clinicopathological and anthropometric variables. Patient survival was estimated using the Kaplan-Meier method, and results compared between those with low versus high receptor expression. A Cox multivariable regression model was used to assess the relationship between survival and a number of co-variables. RESULTS: All 125 tumours analysed expressed AdipoR1 and AdipoR2, whereas 96·8 per cent expressed ObR. There was no significant difference in tumour pathological features or patient obesity status between tumours with low versus high ObR expression. A high level of AdipoR1 expression was significantly associated with increased patient age, obesity and less advanced tumour (T) category. Expression of AdipoR2 was inversely associated with T category (P = 0.043). Low AdipoR1 expression was an independent predictor of improved overall survival (hazard ratio 0.56, 95 per cent confidence interval 0.35 to 0.90; P = 0.017). CONCLUSION: The association between adiponectin receptor expression, obesity status and tumour category and survival suggests a potential mechanism linking obesity and oesophageal cancer.

The potential lost hospital income from miscoded emergency department boarders in Ireland.

BACKGROUND: Emergency department (ED) boarders, namely patients who have been admitted under an in-patient service but remain on a trolley in the ED, have long been a problem in the Irish healthcare system. METHODS: We conducted a retrospective analysis of all ED boarders in Cork University Hospital (CUH) for a 6-month period from January to July 2011. Data were obtained from the Hospital In-Patient Enquiry Office (HIPE). The income generated by the hospital for a subset of these patients (January and February attendances) was obtained from the Finance Office in the hospital, based on diagnoses as recorded on the HIPE system. A convenience sample of two-thirds of the 39 acute hospitals nationally was surveyed to ascertain whether ED boarders were coded by individual HIPE offices as hospital in-patients or as ED attendees. RESULTS: A total of 806 patients were admitted to an in-patient service from January to July 2011 in CUH and subsequently discharged, having completed their entire stay in the ED. The income generated by a sub-sample of 228 patients (January and February ED boarders) was determined. The hospital was remunerated by 685,111 for these patients, i.e. an average income of 3,098 per patient. Only 8 hospitals of the 27 surveyed hospitals coded overnight ED Boarders as in-patients and were thus able to request income for these patients appropriately. CONCLUSION: Discrepancies in coding of ED boarders may result in significant revenue losses for certain hospitals.

Impact of a third stage of labor oxytocin protocol on cesarean delivery outcomes.

BACKGROUND: There are currently no standard recommendations regarding the dose, rate, or duration of intravenous oxytocin administration for the active management of the third stage of labor in the USA. In 2008, we initiated a standardized postpartum oxytocin protocol for active management of the third stage of labor. In cesarean deliveries, upon clamping of the umbilical cord, an oxytocin infusion of 18 U/h was started and adjusted upward if there was ongoing uterine atony. The aim of this study was to compare intraoperative data on oxytocin dose, estimated blood loss, supplemental uterotonic use and vasopressor use before and after the implementation of this protocol. We hypothesized that implementation of the protocol would result in lower intraoperative oxytocin doses without increasing estimated blood loss. METHODS: In this retrospective study, patient characteristics, estimated blood loss, vasopressor administration, and supplemental uterotonic use during two time periods were compared: the two-month interval before initiation of the oxytocin protocol and the two-month interval after initiation. Data were compared using the chi-squared test, t-test, or Mann-Whitney U test as appropriate. P < 0.05 was considered significant. RESULTS: Data for 901 deliveries were analyzed. The amount of intraoperative oxytocin administered decreased after implementation of the protocol (median difference 8.4 U, 95% CI 7.4 to 9.4). Although there was an increase in estimated blood loss, there were no differences in the percentage of patients experiencing intraoperative blood loss >1000 mL or the need for additional uterotonic mediations between the two time periods. CONCLUSIONS: We found that the use of an oxytocin management protocol reduced the amount of intraoperative oxytocin administered without increasing the rate of postpartum hemorrhage or the need for additional uterotonics. Clinicians may consider using a rate of 18 U/h as a starting point for administration of oxytocin to achieve adequate uterine tone in healthy parturients for prevention of postpartum hemorrhage.

The Appropriateness Evaluation Protocol is a poor predictor of in-hospital mortality.

BACKGROUND: The Appropriateness Evaluation Protocol (AEP) proposes admission criteria based only on physiological and laboratory parameters and has recently informed an Irish national bed utilisation review. Severity of illness tools can be poorly predictive of outcomes, particularly in older patients. AIMS: To assess the clinical utility of the AEP in moribund older and younger patients. METHODS: The study was conducted in four acute hospitals in South Munster, Ireland, and was of retrospective analytical cohort study design. The Hospital In-Patient Enquiry Scheme was used to ascertain patients who died within 10 days of hospital admission, over a 2-year period. Proximate death was used as a robust measure of validity of admission. Emergency department (ED) records were screened retrospectively to allocate the AEP criteria. RESULTS: There were 803 eligible in-hospital deaths. Establishment of AEP criteria was available in 72.9 % (585 patients, 50.8 % female). The median length of stay until death was 4 days. Just over 30 % (179/585) of patients did not meet AEP criteria, two-fifths (72/179) of whom had been coded as severely unwell on arrival to the ED. There was no significant difference in AEP identification rates between older and younger age groups. CONCLUSIONS: Our study illustrates that the AEP is a poor predictor of mortality in all age groups, having failed to identify approximately one-third of our cohort. Based on our findings, we feel that this tool should not be used to assess the appropriateness of admission.

Metabolic syndrome and leptin are associated with adverse pathological features in male colorectal cancer patients.

AIM: Metabolic syndrome (MetS) describes a clustering of factors including central obesity, hypertension and raised plasma glucose, triglycerides and high-density lipoprotein (HDL) cholesterol. Central obesity is associated with a risk for colorectal cancer, but the impact of MetS on colorectal cancer biology and outcomes is unclear. METHOD: A prospective observational study of colorectal cancer patients was carried out in an Irish population. Patients underwent metabolic and anthropometric assessment before treatment, including measurement of serum hormones and adipokines and CT measurement of visceral fat. MetS was defined according to the International Diabetes Federation definition(3) . RESULTS: One-hundred and thirty consecutive colorectal cancer patients (66 men and 64 women) were recruited. MetS was diagnosed in 38% patients compared with the population norms reported at 21%(21) . Male patients had a significantly greater visceral fat area compared with female patients. MetS was associated with node-positive disease (P = 0.026), percentage nodal involvement (P = 0.033) and extramural vascular invasion (P = 0.049) in male patients but no significant association was observed in female patients. HDL cholesterol was also significantly associated with a more advanced pathological stage (P = 0.014) and node-positive disease (P = 0.028). Leptin was associated with nodal status (P = 0.036), microvascular invasion (P = 0.054), advanced pathological stage (P = 0.046) and more advanced Dukes stage (P = 0.042). CONCLUSION: We report a high prevalence of MetS and visceral obesity in a colorectal cancer population. MetS and plasma leptin are associated with a more aggressive tumour phenotype in male patients only.

Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease.

Obesity is an established risk factor for esophageal adenocarcinoma, although the mechanism is unclear. A pathway from reflux to inflammation through metaplasia is the dominant hypothesis, and an added role relating to visceral adiposity and the metabolic syndrome has been mooted in Barrett's esophagus (BE) patients. Whether BE differs from gastroesophageal reflux disease (GERD) in obesity and metabolic syndrome profiles is unclear, and this was the focus of this study. Patients with proven BE or GERD were randomly selected from the unit data registry and invited to attend for metabolic syndrome screening, anthropometry studies including segmental body composition analysis, and laboratory tests including fasting lipids, insulin, and C-reactive protein. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. One hundred and eighteen BE patients and 113 age- and sex-matched GERD controls were studied. The incidence of obesity (body mass index >30 kg/m(2)) was 36% and 38%, respectively, with the pattern of fat deposition predominantly central and an estimated trunk fat mass of 13 and 14 kg, respectively. Using the NCEP criteria, metabolic syndrome was significantly more common in the BE cohort (30% vs 20%, P < 0.05), but there was no significant difference using IDF criteria (42% vs 37%, P= 0.340). Central obesity and the metabolic syndrome are common in both Barrett's and GERD cohorts, but not significantly different, suggesting that central obesity and the metabolic syndrome does not per se impact on the development of BE in a reflux population. In BE, the importance of obesity and the metabolic syndrome in disease progression merits further study.

Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer.

AIMS: Obesity is associated with both an increased risk of postmenopausal breast cancer and increased mortality rates. The mechanism is unclear, and central (visceral) obesity, insulin resistance, altered sex steroids and altered adipokines are mooted as possible factors. These features may cluster in the so-called metabolic syndrome. The relevance of metabolic syndrome to the biology of breast cancer is unknown, and this was the focus of the present study. MATERIALS AND METHODS: All postmenopausal women with newly diagnosed breast cancer (n=105) were recruited. A detailed clinical history was carried out, as well as a body composition analysis, metabolic screen and measurement of adipokines and inflammatory markers. RESULTS: The median age was 68 years (40-94 years) and the mean body mass index was 28.3+/-5.2 kg/m2, with 87% of patients centrally obese. Metabolic syndrome was diagnosed in 39% of patients, and was significantly associated with central obesity (P<0.005) and increased inflammation, with C-reactive protein levels doubling in metabolic syndrome patients compared with non-metabolic syndrome patients (10.3 vs 5.8 mg/l; P=0.084). Patients with a later pathological stage (II-IV) were significantly more likely to be obese (P=0.007), centrally obese (P=0.009), hyperglycaemic (P=0.047) and hyperinsulinaemic (P=0.026); 51% had metabolic syndrome compared with 12% for early stage disease. Patients with node-positive disease were significantly more likely to be hyperinsulaemic (P=0.030) and have metabolic syndrome (P=0.028) than patients with node-negative disease. DISCUSSION: The data suggest that metabolic syndrome and central obesity are common in postmenopausal breast cancer patients, and that metabolic syndrome may be associated with a more aggressive tumour biology.

Health-related quality of life assessment at presentation may predict complications and early relapse in patients with localized cancer of the esophagus.

SUMMARY: Health-related quality of life (HR-QOL) assessment in esophageal cancer is increasingly performed. However, the association of baseline HR-QOL in predicting outcome is unclear. This study aimed to assess the impact of HR-QOL scores at diagnosis with major morbidity, mortality, failure to progress to surgery, recurrence within 1 year, and survival in patients with localized esophageal cancer. The European Organization for Research and Treatment of Cancer's quality of life questionnaire was completed at diagnosis. Univariate and multivariate logistic regression were used to investigate the relationship between baseline HR-QOL and outcomes adjusting for confounding variables. A total of 185 patients with localized esophageal cancer were included, 89 undergoing multimodal therapy and 96 surgery alone. Global QOL scores were significantly associated with in-hospital mortality (P = 0.020) but not with major morbidity (P = 0.709) or 1-year survival (P = 0.247). Symptoms of fatigue and dyspnea at baseline were significantly (P < 0.05) associated with major morbidity, in-hospital mortality, and survival in univariate analysis. After adjusting for known confounding variables in multivariate analysis, only worse dyspnea score remained predictive of in-hospital mortality and a worse fatigue score remained predictive of 1-year survival. HR-QOL was of no benefit in predicting survival in multivariate analysis that identified pathological nodal status as the most significant factor. HR-QOL questionnaires may be helpful in preoperative assessment of risk. It is possible that patients with unrecognized micrometastatic disease at the time of surgery may report worse systemic symptoms at diagnosis, in particular fatigue and dyspnea, and these and global QOL scores may also identify poorer reserves that may increase in-hospital morbidity and mortality postoperatively.

Analysis of silica hydride and surface hydrosilation reactions by solid-state NMR in the preparation of p-chlorobenzamide bonded silica phase.

29Si and (13)C CP-MAS NMR spectroscopy was used to follow the conversion of native silica to a p-chlorobenzamide bonded silica material. The benzamide bonded phase was prepared via a hydrosilation reaction of a hydride silica intermediate with p-chloro- N-allylbenzamide. Solid-state NMR was used to show the disappearance of reactive surface hydride species (M(H)) and to identify newly formed bonded chemical species on the silica surface. DRIFT spectroscopy, elemental analysis, and specific surface-area determinations (BET) of the prepared phases are also reported.

Enantiomeric separation of R,S-naproxen by conventional and nano-liquid chromatography with methyl-beta-cyclodextrin as a mobile phase additive.

Chiral separations of R,S-naproxen mixtures were obtained on an achiral column (ODS) with methyl-beta-cyclodextrin as a mobile phase additive using conventional and nano-LC. The optimised mobile phase composition was 20 mmol l(-1) methyl-beta-cyclodextrin, 20% (v/v) acetonitrile, and 50 mmol l(-1) sodium acetate buffer at pH 3 using hydrochloric acid for pH adjustment. In addition to UV detection at 232 nm, amperometric detection was also investigated. Without using any internal standard, the reproducibility of amperometric detection (+1.05 V vs. Ag/AgCl) over a long analysis cycle in LC was greatly improved by choosing the peak area ratio between R- and S-naproxen as the analytical readout (the relative standard deviation was 2.11%) and enantiomeric purity could be assessed directly. This method was successfully employed for enantiomeric purity assessment in commercial naproxen tablets. Finally, successful transfer from conventional LC to nano-LC was realised, resulting in over 1000-fold reduction in reagent consumption.

Structural and functional features of the CD34 antigen: an update.

CD34 is a heavily glycosylated type I transmembrane molecule, that can be phoshorylated by a variety of kinases including Protein kinase C and Tyrosine kinases. The classification of epitopes detected by different CD34 MAbs has aided the selection of appropriate antibodies for use in specific clinical and research laboratory settings. Detailed structural analyses and cloning studies have confirmed that CD34 is a sialomucin, and have suggested that the fine composition of the carbohydrate moieties contained in its extended N-terminal region is important in determining its interactions with a variety of different ligands. For high endothelial venules (HEV) CD34 to serve as a ligand for L-selectin, the O-linked glycans of HEV CD34 are modified in an exquisitely specific manner with a variety of sialyl- and sulfo-transferases. In contrast, CD34 is not the ligand for L-selectin in hematopoietic stem/progenitor cells (HSPCs) and despite much endeavour, ligands for hematopoietic CD34 remain to be identified.

Induction and time-dependent accumulation of micronuclei in peripheral blood of transgenic p53+/- mice, Tg.AC (v-Ha-ras) and parental wild-type (C57BL/6 and FVB/N) mice exposed to benzene by inhalation.

In this study, we determined the induction and time-dependent accumulation of micronuclei in the peripheral blood of transgenic C57BL/6 p53+/- mice (p53+/- mice), FVB/N Tg.AC v-Ha-ras mice (Tg.AC mice) and their isogenic parental strains, FVB/N and C57BL/6 following inhalation exposure to benzene. Our objective was to determine the impact of p53 heterozygosity in p53+/- mice and the v-Ha-ras transgene in Tg.AC mice on micronuclei induction following exposure to inhaled benzene. A flow cytometric technique that distinguishes micronucleated red blood cells (MN-RBC) from micronucleated reticulocytes (MN-RET) was used. Mice were exposed to 0, 100 or 200 p.p.m. benzene using three different exposure regimens that resulted in an equal weekly cumulative exposure (3000 p.p.m.x hours) to benezene: 100 p.p.m. for 6 h/day, 5 days/week, Monday to Friday (M-F); 100 p.p.m. for 10 h/day, 3 days/week, Monday, Wednesday, Friday (MWF); and 200 p.p.m. for 5 h/day, 3 days/week MWF. Significant elevations of MN-RBC and MN-RET were observed from 1 week exposure in all of the benzene-exposed groups that increased in a time-dependent manner for up to 13 weeks exposure. Fewer MN-RBC and MN-RET were induced in the 200 p.p.m. benzene exposure group than in mice exposed to 100 p.p.m. The reduction in the frequency of MN-RBC in the 200 p.p.m.x5 h benzene exposure group is probably due to metabolic saturation resulting in a lower bone marrow dose (concentration x time) than in the 100 p.p.m. exposure groups. No differences were observed in the frequency of MN-RBC or MN-RET in Tg.AC compared with the FVB/N isogenic controls. At certain time points the frequency of micronuclei was less in the heterozygous p53+/- mice than determined in the wild-type C57BL/6 isogenic parental strain. These results indicate that the heterozygous state in p53+/- mice, but not the v-Ha-ras transgene in Tg.AC mice can influence the induction of micronuclei by benzene.

Expression and distribution of cytochrome P450 2E1 in B6C3F1 mouse liver and testes.

Cytochrome P450 2E1 (CYP2E1) is believed to have a significant role in the bioactivation of 1,3-butadiene (BD) to DNA reactive epoxide metabolites that induce somatic and germ cell genotoxicity in mice. To assess the potential role of in situ bioactivation of BD by mouse testes for inducing germ cell genotoxicity, the presence of CYP2E1 in testes has been demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoprecipitation-Western blotting methods (IP-Western) and immunohistochemistry of tissue sections. Detection of CYP2E1 in the testes was limited to interstitial cells. In liver a known site of BD bioactivation and a positive control tissue used for these studies, a discrete, zonal staining pattern of liver CYP2E1 expression detected by immunohistochemical staining was shown. These results suggest that in situ bioactivation of BD in testes by CYP2E1 may contribute to BD-induced germ cell genotoxicity.