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Evaluation of the optimal cuff volume and cuff pressure of the revised laryngeal tube \u201cLTS-D\u201d in surgical patients
Abstract
Background
Recent case reports have indicated significant cuff overinflation when using the standard filling volume based on the manufacturer\u2019s recommendations in older models of laryngeal tubes. The aim of this study was to determine the minimum cuff pressure needed to perform standardized ventilation without leakage in the new, revised model of the laryngeal tube \u201cLTS-D\u201d.
Methods
After ethical approval, LTS-D was placed for ventilation in 60 anesthetized patients. The cuff was inflated to the recommended volume (#3: 60\ua0ml, #4: 80\ua0ml, and #5: 90\ua0ml). After evaluation of the initial cuff pressure (CP), the CP was lowered in 10 cmH
2
O steps until a minimal cuff pressure of 30 cmH
2
O was achieved. The absence of an audible leak was required for a step-by-step reduction in the CP. Evacuated cuff volume, success rate, and airway injuries were documented. Data were expressed as medians (interquartile ranges [IQRs]). The comparison of CPs and cuff volumes was performed using the Mann-Whitney test.
Results
After initial inflation, the CP ranged from 105 cmH
2
O [90\u2013120; #5] to 120 cmH
2
O [110\u2013120; #3]. Lowering the CP to 60 cmH
2
O resulted in a reduced cuff volume ranging from 47\ua0ml [44\u201354; #3] to 77\ua0ml [75\u201382; #5] compared to the initial inflation ( p \u2009<\u20090.001). Leakage occurred more frequently when the CP was lowered to 40 cmH
2
O compared to the initial inflation (44/54 [81%]; p \u2009<\u20090.01). Using a CP between 50 cmH
2
O and 60 cmH
2
O, a leakage rate of 3/54 (5%) was observed, compared to a rate of 11/54 (21%) when using a CP lower than 50 cmH
2
O. The overall success rate was 90%, and airway injury occurred in 7% of patients (4/60).
Conclusion
We found significant overinflation of the revised LTS-D using the recommended volume for initial cuff inflation. A CP of 60 cmH
2
O was found to be sufficient for ventilation in the majority of patients evaluated. Checking and adjusting the CP in laryngeal tubes is mandatory to avoid overinflation.
Trial registration
..
Supplement of levosimendan to epinephrine improves initial resuscitation outcomes from asphyxial cardiac arrest
Abstract
Background
Levosimendan exerted favorable effects on the initial outcome in the treatment of ventricular fibrillation cardiac arrest. This study investigated the efficacy of levosimendan in the treatment of asphyxia-induced cardiac arrest in rats.
Methods
Animals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to three treatment groups: epinephrine (10\ua0\u3bcg/kg) supplemented with levosimendan (bolus 12\ua0\u3bcg/kg and infusion for 1\ua0h, EL group); epinephrine only (10\ua0\u3bcg/kg, E group), or levosimendan only (bolus 12\ua0\u3bcg/kg and infusion for 1\ua0h, L group). The resuscitation success rate, wet-to-dry ratio of lung, and rate of alveolar and blood gas analysis were recorded.
Results
10 rats in the EL group, 8 in the E group, and 2 in the L group showed an initial return of spontaneous circulation ( P \u2009<\u20090.001); among them, 10, 4, and 2 rats survived at the end of a 60-min observation period from each group, respectively ( P \u2009=\u20090.001). The coronary perfusion pressure in the EL group was higher than that of either the E or L group ( P \u2009<\u20090.05). The lung wet-to-dry weight ratio and rate of damaged alveoli were lower in the EL group than the E group ( P \u2009<\u20090.05).
Conclusions
In the early stage of resuscitation for asphyxia-induced cardiac arrest in rats, levosimendan supplemented with epinephrine can significantly increase coronary perfusion pressure, reduce lung injury, and ultimately enhance the survival rate
Quality of life and impact of bile reflux after retro colic retro gastric gastrojejunostomy in Whipple surgery
Abstract
Background
Delayed gastric emptying and bile reflux are common concerns in long-term survivors after Whipple surgery. The study was designed to assess modified retro colic retro gastric gastrojejunostomy in reducing macro and microscopic bile reflux and impact on dyspepsia related quality of life in long-term survivors.
Methods
Out of 43 patients operated, 23 long-term survivors were included. All underwent gastroscopy and bile reflux was grouped as normal, yellowish bile lakes and presence of greenish bile lakes. Six standard gastric biopsies were taken. Microscopic bile reflux index (BRI) was calculated and a score more than 14 was considered significant. Validated Nepean dyspepsia index-short form (NDI-SF) was used to assess the severity of dyspepsia-related quality of life and compared with age and gender-matched control.
Results
The median age was 48 (21\u201370) years. Median survival of the group was 37\ua0months (6\u201340). Endoscopically, 20/23 (87%) had macroscopic bile reflux (74% yellowish bile lakes, 13% greenish bile lakes). None had stomal ulcers or macroscopic inflammation. Mean bile reflux index score was 9.7 (range 1.77\u201334). Mean NDI\u2013SF score of Whipple group was 23.1 (SD 8.88). In controls, mean score was 19.9 (SD 8.23), showing no significant difference ( p \u2009=\u20090.245).
Conclusions
Though there was macroscopic bile reflux, clinical symptoms and microscopic changes were minimal. The modified technique had good long-term results
Long-term mortality in older patients discharged after acute decompensated heart failure: a prospective cohort study
Abstract
Background
Data are available on short- and intermediate-term mortality rates after discharge for acutely decompensated heart failure (ADHF). However, few studies specifically addressed ADHF outcomes in patients aged 75\ua0years or over, who contribute more than half of all ADHF admissions. Our objectives here were to estimate the long-term mortality of patients aged 75\ua0years or over who were discharged after admission for ADHF and to identify factors, especially geriatric findings, independently associated with 2-year mortality.
Methods
This prospective cohort study in five French hospitals included consecutive patients aged 75\ua0years or older and discharged after emergency-department admission for ADHF meeting Framingham criteria ( N\u2009= \u2009478; median age, 85\ua0years; 68% female). Kaplan-Meier 1-year and 2-year survival curves were plotted. Admission characteristics independently associated with overall 2-year mortality were identified using multivariable Cox proportional-hazards regression.
Results
Mortality was 41.7% (95% confidence interval [95% CI], 37.2%\u201353.5%) after 1\ua0year and 56.0% (95% CI, 51.5%\u201360.7%) after 2\ua0years. By multivariable analysis, independent predictors of 2-year mortality were male sex (hazard ratio [HR], 1.36; 95% CI, 1.00\u20131.82), age >85\ua0years (HR, 1.57; 95% CI, 1.19\u20132.07), higher number of impaired activities of daily living (HR, 1.11 per impaired item; 95% CI, 1.05\u20131.17), recent weight loss (HR, 1.61; 95% CI, 1.14\u20132.28), and lower systolic blood pressure (HR, 0.86 per standard deviation increase; 95% CI, 0.74\u20130.99). Creatinine clearance \u226430\ua0mL/min showed a trend toward an association with 2-year mortality (HR, 1.36; 95% CI, 0.97\u20132.00).
Conclusion
Functional impairment before admission is associated with higher long-term mortality in patients \u226575\ua0years admitted for ADHF. This study focused on geriatric markers not traditionally collected in heart-failure patients but did not analyse all cardiologic parameters associated with outcomes in other studies. Nevertheless, our findings may contribute to identify those patients admitted for ADHF who have the worst prognosis
Lung cells support osteosarcoma cell migration and survival
Abstract
Background
Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined.
Methods
Three human OS cell lines (SJSA-1, Saos-2, U-2) and two human lung cell lines (HULEC-5a, MRC-5) were cultured according to American Type Culture Collection recommendations. Human lung cell lines were cultured in growth medium for 72\ua0h to create conditioned media. OS proliferation was evaluated in lung co-culture and conditioned media microenvironment, with a murine fibroblast cell line (NIH-3\ua0T3) in fresh growth medium as controls. Migration and invasion were measured using a real-time cell analysis system. Real-time PCR was utilized to probe for Aldehyde Dehydrogenase (ALDH1) expression. Osteosarcoma cells were also transduced with a lentivirus encoding for GFP to permit morphologic analysis with fluorescence microscopy. The anti-OS efficacy of Disulfiram, an ALDH-inhibitor previously shown to inhibit OS cell proliferation and metastasis in vitro, was evaluated in each microenvironment.
Results
Lung-cell conditioned medium promoted osteosarcoma cell migration, with a significantly higher attractive effect on all three osteosarcoma cell lines compared to basic growth medium, 10% serum containing medium, and NIH-3\ua0T3 conditioned medium ( p <0.05). Lung cell conditioned medium induced cell morphologic changes, as demonstrated with GFP-labeled cells. OS cells cultured in lung cell conditioned medium had increased alkaline phosphatase staining.
Conclusions
Lung endothelial HULEC-5a cells are attractants for OS cell migration, proliferation, and survival. The SJSA-1 osteosarcoma cell line demonstrated greater metastatic potential than Saos-2 and U-2 cells. ALDH appears to be involved in the interaction between lung and OS cells, and ALP may be a valuable biomarker for monitoring functional OS changes during metastasis
Nomogram prediction of individual prognosis of patients with hepatocellular carcinoma
Abstract
Background
The purpose of this study was to develop an effective nomogram capable of estimating the individual survival outcomes of patients with hepatocellular carcinoma (HCC), and compare the predictive accuracy and discriminative ability with other staging systems.
Methods
The nomogram was established based on a retrospective study of 661 patients newly diagnosed with HCC at the Beijing Ditan Hospital (Beijing, China), Capital Medical University, between October 2008 and July 2012. The predictive accuracy and discriminative ability of the previously developed nomogram were assessed by C-index and calibration curves, and were compared to seven current commonly used staging systems. The results were validated, using a bootstrap approach to correct for bias, in a prospective study of 220 patients consecutively enrolled between August 2012 and March 2013.
Results
Multivariate analysis of the primary cohort for survival analysis identified the independent factors to be aspartate aminotransferase, \u263-glutamyl transpeptidase, white blood cell count, neutrophil-to-lymphocyte ratio, prothrombin activity, \u3b1-fetoprotein, tumor number and size, lymph node metastasis, and portal vein involvement, which were all included to build the nomogram. The calibration curve for predicting the probability of survival showed consistency between the nomogram and the actual observation. The C-index of the nomogram was 0.81 (95% confidence interval, 0.79\u20130.82), which was statistically better than that of the Tumor, Node, Metastasis staging (0.71), Barcelona Clinic Liver Cancer staging (0.77), Okuda (0.62), Japan Integrated Staging (0.73), Cancer of the Liver Italian Program score (0.76), Chinese University Prognostic Index (0.68), and the Groupe d\u2019 Etude et de Traitement du Carcinome Hepatocellulaire Prognostic classification (0.65) ( p \u2009<\u20090.001 for all). The results were validated in the prospective validation cohort.
Conclusions
The prognostic nomogram resulted in more accurate individualized risk estimates for overall survival in HCC patients
An increase in physical activity after colorectal cancer surgery is associated with improved recovery of physical functioning: a prospective cohort study
Abstract
Background
The influence of physical activity on patient-reported recovery of physical functioning after colorectal cancer (CRC) surgery is unknown. Therefore, we studied recovery of physical functioning after hospital discharge by (a) a relative increase in physical activity level and (b) absolute activity levels before and after surgery.
Methods
We included 327 incident CRC patients (stages I\u2013III) from a prospective observational study. Patients completed questionnaires that assessed physical functioning and moderate-to-vigorous physical activity shortly after diagnosis and 6\ua0months later. Cox regression models were used to calculate prevalence ratios (PRs) of no recovery of physical functioning. All PRs were adjusted for age, sex, physical functioning before surgery, stage of disease, ostomy and body mass index.
Results
At 6 months post-diagnosis 54% of CRC patients had not recovered to pre-operative physical functioning. Patients who increased their activity by at least 60\ua0min/week were 43% more likely to recover physical function (adjusted PR 0.57 95%CI 0.39\u20130.82), compared with those with stable activity levels. Higher post-surgery levels of physical activity were also positively associated with recovery (P for trend\u2009=\u20090.01). In contrast, activity level before surgery was not associated with recovery (P for trend\u2009=\u20090.24).
Conclusions
At 6 month post-diagnosis, about half of CRC patients had not recovered to preoperative functioning. An increase in moderate-to-vigorous physical activity after CRC surgery was associated with enhanced recovery of physical functioning. This benefit was seen regardless of physical activity level before surgery. These associations provide evidence to further explore connections between physical activity and recovery from CRC surgery after discharge from the hospital
Higher IGFBP-1 to IGF-1 serum ratio predicts unfavourable survival in patients with nasopharyngeal carcinoma
Abstract
Background
The insulin-like growth factor (IGF) system plays an important role in the development and progression of cancer. However, little is known about the expression of the IGF system components and their clinicopathological significance and prognostic value in nasopharyngeal carcinoma (NPC).
Methods
IGF system components (IGF-1, IGF-2, IGF-1SR, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-6) were quantified from the plasma of NPC patients and healthy individuals using the RayBio Human Cytokine Antibody Array. IGFBP-1 and IGF-1 mRNA levels were quantified by real-time qPCR, and protein expression was detected by western blot in nine NPC cell lines and four immortalized nasopharyngeal epithelial (NPE) cell lines. Tissue-specific expression of IGFBP-1 and IGF-1 was detected by immunohistochemistry in paraffin-embedded NPC tissues. ELISA analysis was used to measure the serum levels of IGFBP-1 and IGF-1 in 142 NPC patients and 128 healthy controls and determine potential correlation with clinicopathological parameters.
Results
Significantly higher levels of circulating IGFBP-1 and lower levels of IGF-1 and IGF-2 were detected in NPC patients compared to healthy controls by Cytokine Antibody Array analyses ( P\u2009= \u20090.034 , 0.012, 0.046 , respectively). IGFBP-1 expression was detected in the majority of NPC cell lines, but not in NPE cell lines, and was shown to localize to the nucleus of tumour cells, in contrast to the cytoplasmic staining observed in normal cells. Importantly, IGFBP-1 expression was stronger in NPC tumour tissues compared to peritumoural tissues. In contrast, IGF-1 expression was weak or absent in NPC and NPE cell lines, with the exception of the EBV-infected C666 cell line, and was found to be expressed at lower levels in tumour tissues compared to tumour-adjacent normal tissue. Levels of serum IGFBP-1 were shown to be significantly higher in patients with NPCs compared to healthy control individuals (55.23\u2009\ub1\u200941.25\ua0\u3bcg/L vs . 32.08\u2009\ub1\u200929.73\ua0\u3bcg/L, P \u2009<\u20090.001), whereas serum levels of IGF-1 were significantly lower in NPC patients compared to healthy controls (98.14\u2009\ub1\u200971.48\ua0\u3bcg/L vs . 164.01\u2009\ub1\u200992.08\ua0\u3bcg/L, P \u2009=\u20090.001). Consistently, the IGFBP-1/IGF-1 serum ratio was shown to be significantly higher in NPC patients compared to healthy control individuals ( P \u2009=\u20090.002). Serum levels of IGFBP-1 and the IGFBP-1/IGF-1 ratio significantly correlated with age ( P \u2009=\u20090.020 ; P \u2009=\u20090.016), WHO histological classification ( P ..
Mammographic breast density and risk of breast cancer in women with atypical hyperplasia: an observational cohort study from the Mayo Clinic Benign Breast Disease (BBD) cohort
Abstract
Background
Atypical hyperplasia (AH) and mammographic breast density (MBD) are established risk factors for breast cancer (BC), but their joint contributions are not well understood. We examine associations of MBD and BC by histologic impression, including AH, in a sub\ufeffcohort of\ua0women from the Mayo Clinic Benign Breast Disease Cohort.
Methods
Women with a diagnosis of BBD and mammogram between 1985 and 2001 were eligible. Histologic impression was assessed via pathology review and coded as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and AH. MBD was assessed clinically using parenchymal pattern (PP) or BI-RADS criteria and categorized as low, moderate or high. Percent density (PD) was also available for a subset of women. BC and clinical information were obtained by questionnaires, medical records and the Mayo Clinic Tumor Registry. Women were followed from date of benign biopsy to BC, death or last contact. Standardized incidence ratios (SIRs) compared the observed number of BCs to expected counts. Cox regression estimated multivariate-adjusted MBD hazard ratios.
Results
Of the 6271 women included in the study, 1132 (18.0%) had low MBD, 2921 (46.6%) had moderate MBD, and 2218 (35.4%) had high MBD. A total of 3532 women (56.3%) had NP, 2269 (36.2%) had PDWA and 470 (7.5%) had AH. Over a median follow-up of 14.3\ua0years, 528 BCs were observed. The association of MBD and BC risk differed by histologic impression (p-interaction\u2009=\u20090.03), such that there was a strong MBD and BC association among NP ( p \u2009<\u20090.001) but non-significant associations for PDWA ( p \u2009=\u20090.27) and AH ( p \u2009=\u20090.96). MBD and BC associations for AH women were not significant within subsets defined by type of MBD measure (PP vs. BI-RADS), age at biopsy, number of foci of AH, type of AH (lobular vs. ductal) and body mass index, and after adjustment for potential confounding variables. Women with atypia who also had high PD (>50%) demonstrated marginal evidence of increased BC risk (SIR 4.98), but results were not statistically significant.
Conclusion
..
The marine triterpene glycoside frondoside A induces p53-independent apoptosis and inhibits autophagy in urothelial carcinoma cells
Abstract
Background
Advanced urothelial carcinomas represent a considerable clinical challenge as they are difficult to treat. Platinum-based combination regimens obtain response rates ranging from 40 to 70% in first-line therapy of advanced urothelial carcinoma. In the majority of cases, however, the duration of these responses is limited, and when progression occurs, the outcome is generally poor. Therefore, novel therapeutic strategies are urgently needed. The purpose of the current research is to investigate the anticancer effects and the mode of action of the marine triterpene glycoside frondoside A in p53-wild type and p53-deficient human urothelial carcinoma cells.
Methods
Activity of frondoside A was examined in the human urothelial carcinoma cell lines RT112, RT4, HT-1197, TCC-SUP, T-24, and 486p. Effects of frondoside A on cell viability, either alone or in combination with standard cytotoxic agents were investigated, and synergistic effects were analyzed. Pro-apoptotic activity was assessed by Western blotting and FACS, alone and in combination with a caspases-inhibitor. The impact of functional p53 was investigated by siRNA gene silencing and the p53 inhibitor pifithrin-\u3b1. Effects on autophagy were studied using LC3B-I/II and SQSTM/p62 as markers. The unpaired Student\u2019s t -test was used for comparison of the data sets.
Results
Frondoside A shows high cytotoxicity in urothelial carcinoma cells with IC
50s
ranging from 0.55 to 2.33\ua0\u3bcM while higher concentrations of cisplatin are required for comparable effects (IC
50
\u2009=\u20092.03\u2009~\u20095.88\ua0\u3bcM). Induction of apoptosis by frondoside A was associated with the regulation of several pro-apoptotic factors, like caspase-3, -8, and -9, PARP, Bax, p21, DNA fragmentation, and externalization of phosphatidylserine. Remarkably, inhibition of p53 by gene silencing or pifithrin-\u3b1 pretreatment, as well as caspase inhibition, did not suppress apoptotic activity of frondoside A, while cisplatin activity, in contrast, was significantly decreased. Frondoside A inhibited pro-survival autophagy, a known mechanism of drug resistance in urothelial carcinoma and showed synergistic activity with cisplatin and ..