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1.
Jing Ma Jianhui Li Meirui Qian Weili Han Miaomiao Tian Zengshan Li Zhe Wang Shuixiang He Kaichun Wu 《Diagnostic pathology》2018,13(1):91
Background
Immunohistochemistry (IHC) for programmed cell death ligand 1 (PD-L1) displays staining diversity. We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis.Methods
IHC using PD-L1 antibodies (clones SP142, 28–8 and E1L3N) in 315 formalin-fixed paraffin-embedded samples was qualitatively compared at the 1, 5 and 10% cut-off by two pathologists on total, tumor and immune/stromal cells. We used computer – assisted scoring to quantitatively analyze and compare the “H-score” of PD-L1 expression in 66 samples on total cells. The antibody clone SP142 was selected to investigate the infiltration of PD-L1+CD8+ T cells using automated quantitative immunofluorescence analyses (n?=?50) and the prognostic significance. The prognoses were assessed by log-rank test.Results
PD-L1 clones SP142 and 28–8 displayed great concordance by qualitative (κ?=?0.816, 0.810 for total cells and tumor cells at the 5% cut-off) and quantitative analyses (R2?=?0.7991, 0.8187 for positive percentage and “H-score”). PD-L1 clone SP142 showed the highest positivity in immune/stromal cells staining (18.41%) compared to 28–8 (7.62%), while clone E1L3N showed poor staining in both tumor and immune/stromal cells. Clone SP142, but not 28–8 and E1L3N, predicted a worse prognosis at the 5% cut-off (p?=?0.0243). Both the clone SP142 and 28–8 had high inter-pathologist correlation for tumor staining (R2?=?0.9805 and R2?=?0.9853), but a moderate correlation for stromal/immune cell staining (R2?=?0.5653 and R2?=?0.5745). Furthermore, a higher density of PD-L1+CD8+ T cells was correlated with a shorter survival time (R2?=?0.0909, p?=?0.0352).Conclusions
PD-L1 antibody clone SP142 was superior in cell staining, particularly in immune/stromal cell and prognosis. These findings are important for selection of PD-L1 antibody clones in the future diagnostic test.2.
Eyup Avci Tuncay Kiris Aykan Çelik Eser Variş Fatma Kayaalti Esin Diyar Köprülü Hasan Kadi 《BMC cardiovascular disorders》2018,18(1):226
Background
The prognostic significance of changes in mean platelet volume (MPV) during hospitalization in ST segment elevation myocardial infarction (STEMI) patients underwent primary percutaneous coronary intervention (pPCI) has not been previously evaluated. The aim of this study was to determine the association of in-hospital changes in MPV and mortality in these patients.Methods
Four hundred eighty consecutive STEMI patients were enrolled in this retrospective study. The patients were grouped as survivors (n?=?370) or non-survivors (n?=?110). MPV at admission, and at 48–72?h was evaluated. Change in MPV (MPV at 48–72?h minus MPV on admission) was defined as ΔMPV.Results
At follow-up, long-term mortality was 23%. The non-survivors had a high ΔMPV than survivors (0.37 (??0.1–0.89) vs 0.79 (0.30–1.40) fL, p?<? 0.001). A high ΔMPV was an independent predictor of all cause mortality ((HR: 1.301 [1.070–1.582], p?=?0.008). Morever, for long-term mortality, the AUC of a multivariable model that included age, LVEF, Killip class, and history of stroke/TIA was 0.781 (95% CI:0.731–0.832, p?<? 0.001). When ΔMPV was added to a multivariable model, the AUC was 0.800 (95% CI: 0.750–0.848, z?=?2.256, difference p?=?0.0241, Fig. 1). Also, the addition of ΔMPV to a multivariable model was associated with a significant net reclassification improvement estimated at 24.5% (p?=?0.027) and an integrated discrimination improvement of 0.014 (p?=?0.0198).Conclusions
Rising MPV during hospitalization in STEMI patients treated with pPCI was associated with long-term mortality.3.
Mi-Na Kim Seong-Mi Park Dong-Hyuk Cho Hack-Lyoung Kim Mi-Seung Shin Myung-A Kim Kyung-Soon Hong Wan-Joo Shim 《Biology of sex differences》2018,9(1):52
Background
Evidence suggests that epicardial adipose tissue (EAT) is closely related to coronary artery stenosis (CAS). However, sexual dimorphism may be present in adipose tissue, and its influence on CAS between men and women is controversial. We assessed the relationship between EAT and CAS by sex and menopausal status in patients with suspected angina.Methods
Six hundred twenty-eight consecutive patients (men/women n?=?257/371; mean age = 59.9?±?10.2?years) who had chest pain for angina and underwent coronary angiography were included. CAS was defined as >?50% luminal narrowing of at least one epicardial coronary artery. EAT thickness was measured by transthoracic echocardiography.Results
Of the 628 patients, 52.1% (n?=?134) of men and 35.3% (n?=?131) of women had CAS. The mean EAT thickness was not different between men and women and was larger in patients with CAS (8.04?±?2.39 vs 6.58?±?1.88?mm, P?<?0.001). EAT thickness was independently associated with CAS in both sexes (P?<?0.001). The odds ratio (OR) of EAT for the presence of CAS was higher in men (OR?=?1.43, 95% confidence interval [CI] 1.21–1.69) than in women (OR?=?1.24, 95% CI 1.10–1.40). EAT thickness was larger in postmenopausal women than in premenopausal women (7.59?±?2.25 vs 5.80?±?1.57?mm, P?<?0.001) and was independently related with CAS (OR?=?1.24, 95% CI 1.09–1.41). This was not the case in premenopausal women.Conclusion
In patients with suspected angina, an increase in EAT thickness was independently related to the presence of CAS in both men and women, with it being stronger in men. According to menopausal status in women, EAT thickness is significantly associated with CAS only in postmenopausal women.4.
Background
Except for testicular cancer and Hodgkin’s disease, baseline data on semen quality in case of cancers as well as systemic pathologies of the young adult are scarce or based on low sample size.Methods
Semen quality in patients having testicular cancer (TGCT, n?=?2315), Hodgkin’s disease (HD, n?=?1175), non-Hodgkin’s lymphoma (NHL, n?=?439), leukemia (L, n?=?360), sarcoma (S, n?=?208), brain tumour (BT, n?=?40), Behcet’s disease (Behcet’s, n?=?68) or multiple sclerosis (MS, n?=?73) was studied and compared to that of 1448 fertile men candidates for sperm donation (CSD) and 208 partners of pregnant women (PPW). All samples were studied following the same methodology in a single laboratory. Post freezing and thawing semen characteristics were also studied.Results
The percentage of normozoospermic men was only 37 % for L patients and lower than 60 % for TGCT, NHL, S and BT. The level of sperm production was differently decreased according to pathologies, the median total sperm count in TC and L patients being four times lower (p?<?0.01 when compared to CSD and PPW). The lowest percentage of progressively motile spermatozoa was found for L and BT patients (both, p?<?0.01 compared to CSD and PPW). The percentage of morphologically normal spermatozoa was also reduced in cancer patients, especially in BT patients. Progressive motility after thawing in patients was about half that observed among candidates for sperm donation. In almost half of the semen of patients with testicular cancer or leukemia, the total number of motile spermatozoa per straw was less than 0.5?×?106 compared to 4.3?×?106 in CSD.Conclusions
The present data confirm on large series the deleterious impact of various cancers of the young adult on semen quality, establishing thus baseline data for future studies. Owing to the post-thaw quality of the frozen straws, future fertility projects for the majority of the patients studied (in case there is no post-treatment recovery of spermatogenesis) should necessitate an ICSI to provide the best chance of paternity whatever the fertility check-up in the female partner.5.
Arati Suvatha Sibin Madathan Kandi Dhananjaya Ishwara Bhat Narasinga Rao Vikas Vazhayil Chetan Ghati Kasturirangan 《Cellular & molecular biology letters》2017,22(1):25
Background
The rupture of a brain aneurysm causes bleeding in the subarachnoid space. This is known as aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the association of apolipoprotein E (APOE) polymorphism and the risk of aSAH in a South Indian population.Methods
The study was performed on 200 subjects with aSAH and 253 healthy control subjects. Blood samples (5 ml) were used to isolate DNA and genotyping was performed for rs7412 and rs429358 using a Taqman allelic discrimination assay. Statistical software R.3.0.11 was used to statistically analyze the data and a p value <?0.05 was considered as statistically significant.Results
We found a significant association with the risk of aSAH in ε3/ ε4 genetic model (OR?=?1.91, 95% CI?=?1.16–3.14, p?=?0.01). However, in the other genetic models and allele frequency, there was no significant association with the risk of aSAH. In subtyping, we found a significant association of ε2 allele frequency with posterior communicating artery (PCOM) aneurysm (OR?=?3.59, 95% CI?=?1.11–11.64, p?=?0.03).Conclusion
Our results suggest that APOE polymorphism has an influence on the risk of aSAH in this South Indian population, specifically in the PCOM subtype.6.
Background
Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT.Methods
We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately.Results
Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z?=???8.635, p?<?0.001) and peritumoral (median 113.53 vs. 82.48; Z?=???3.741, p?<?0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z?=???0.817,p?=?0.414) and peritumoral (median 402.56 vs. 390.84; Z?=???1.138,p?=?0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z?=???2.009, p?=?0.045) and peritumoral areas(median 63.31 vs. 98.48; Z?=???2.469, p?=?0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR?=?0.297; 95% CI, 0.109–0.810, p?=?0.018) and overall survival (HR?=?0.078; 95% CI, 0.010–0.598, p?=?0.014).Conclusions
NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.7.
Pierre-Jean Saulnier Manjula Darshi Kevin M. Wheelock Helen C. Looker Gudeta D. Fufaa William C. Knowler E. Jennifer Weil Stephanie K. Tanamas Kevin V. Lemley Rintaro Saito Loki Natarajan Robert G. Nelson Kumar Sharma 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):84
Introduction
Little is known about the association of urine metabolites with structural lesions in persons with diabetes.Objectives
We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.Methods
Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.Results
Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).Conclusions
Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.8.
Shayne Mason Karin Terburgh Roan Louw 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):74
Introduction
The analysis of limited-quantity samples remains a challenge associated with mouse models, especially for multi-platform metabolomics studies. Although inherently insensitive, the highly specific characteristics of nuclear magnetic resonance (NMR) spectroscopy make it an advantageous platform for global metabolite profiling, particularly in mitochondrial disease research.Objectives
Show method equivalency between a well-established standard operating protocol (SOP) and our novel miniaturized 1H-NMR method.Method
The miniaturized method was performed in a 2 mm NMR tube on a standard 500 MHz NMR spectrometer with a 5 mm triple-resonance inverse TXI probe at room temperature.Results
Firstly, using synthetic urine spiked with low (50 µM), medium (250 µM) and high (500 µM) levels (n?=?10) of nine standards, both the SOP and miniaturized method were shown to have acceptable precision (CV?<?15%), relative accuracy (80–120%), and linearity (R2?>?0.95), except for taurine. Furthermore, statistical equivalence was shown using the two one-sided test. Secondly, pooled mouse quadriceps muscle extract was used to further confirm method equivalence (n?=?3), as well as explore the analytical dynamics of this novel approach by analyzing more-concentrated versions of samples (up to 10× concentration) to expand identification of metabolites qualitatively, with quantitative linearity. Lastly, we demonstrate the new technique’s application in a pilot metabolomics study using minute soleus muscle tissue from a mouse model of Leigh syndrome using Ndufs4 KO mice.Conclusion
We demonstrate method equivalency, supporting our novel miniaturized 1H-NMR method as a financially feasible alternative to cryoprobe technology—for limited-quantity biological samples in metabolomics studies that requires a volume one-tenth of the SOP.9.
Background
General anesthesia has been linked to impaired brain development in immature animals and young children. In this study the influence of orthopedic surgery under general anesthesia on the intelligence of school age children has been evaluated.Methods
A total of 209 subjects aged 6–12 years were recruited and allocated into 4 groups according to the duration of general anesthesia, including a control group (n?=?30), short (< 1 h, n?=?49), moderate- (1–3 h, n?=?51) and long-duration groups (> 3 h, n?=?79), respectively. The intelligence quotient (IQ) of the subjects was measured by the Raven’s Standard Progressive Matrices (RSPM) before and after orthopedic surgery under general anesthesia of various durations (vide supra).Results
The IQ score decreased significantly in the long-duration group at 1 month post-operation compared with the pre-operation score (P?<?0.001), and IQ did not recover completely at 3 months postoperatively (P?<?0.05), but had recovered when measured at the 1-year follow-up. Moreover, this study showed that the development of children’s intelligence was affected by the exposure time to anesthetics at a younger age (OR?=?5.26, 95% CI:2.70–8.41, P?<?0.001), having a mother with a low education level (OR?=?2.71, 95% CI:1.24–6.14, P?=?0.014) and premature birth (OR?=?2.76, 95% CI:1.34–5.46, P?=?0.005).Conclusions
More than 3 h general anesthesia influenced the IQ of school age children for up to 3 months after orthopedic surgery. Beside extended exposure time to anesthetics additional factors for post-operative IQ reduction were younger children age, mothers with low educational levels and premature birth.Trial registration
Chinese Clinical Trial Registry with registration number ChiCTR-OOC-17013497 retrospectively registered on 11/23/2017.10.
Background
Chest compression is a decisive element of cardio-pulmonary resuscitation (CPR). By applying a mechanical CPR device, compression interruptions can be minimised. We examined the efficiency of manual and device-assisted resuscitation as well as the effects of cardiovascular risk factors on the outcome of resuscitation.Methods
In our retrospective, randomised 3-year study the data of adult patients suffering non-traumatic, out-of-hospital, sudden cardiac death (SCD) were analysed (n?=?287). The data were retrieved by processing case reports, Utstein sheets and acute coronary syndrome sheets. We compared the data of patients undergoing manual (n?=?232) and device-assisted resuscitation (LUCAS-2, n?=?55). The primary endpoint was the on-site restoration of spontaneous circulation (ROSC).Results and conclusion
In 37% of the cases ROSC happened. With respect to ROSC an insignificantly more favourable tendency was demonstrated in the case of device-assisted resuscitation (p =?0.072). In the Lucas group, a higher success rate occurred even in the case of prolonged resuscitation. We found a better outcome in the Lucas group in the case of CPR started a longer time after the SCD (p?<?0.05). A positive correlation was established between age and unsuccessful resuscitation (p?=?<?0.017; r?=?0.125). An unfavourable correlation was observed between hypertension and the outcome of resuscitation (p?=?0.018; r?=?0.143). According to our results the presence of left ventricular hypertrophy poses 5.1-fold risk of unsuccessful CPR (CI: 4.97–5.29).Advanced age and structural heart diseases can play a role in the genesis of SCD. Importantly, left ventricular hypertrophy and hypertension negatively affect survival.11.
Tao Cong Jinping Gu Alex Pui-Wai Lee Zhijuan Shang Yinghui Sun Qiaobing Sun Hong Wei Na Chen Siyao Sun Tingting Fu 《Cardiovascular ultrasound》2018,16(1):13
Background
Atrial fibrillation (AF) can result in atrial functional mitral regurgitation (MR), but the mechanism remains controversial. Few data about the relationship between the 3-dimensional morphology of the MV and the degree of MR in AF exist.Methods
Real-time 3-dimensional transesophageal echocardiography (3D-TEE) of the MV was acquired in 168 patients with AF (57.7% persistent AF), including 25 (14.9%) patients with moderate to severe MR (the MR+ group) and 25 patients without AF as controls. The 3-dimensional geometry of the MV apparatus was acquired using dedicated quantification software.Results
Compared with the group of patients with no or mild MR (the MR- group) and the controls, the MR+ group had a larger left atrium (LA), a more dilated mitral annulus (MA), a reduced annular height to commissural width ratio (AHCWR), indicating flattening of the annular saddle shape, and greater leaflet surfaces and tethering. MR severity was correlated with the MA area (r2?=?0.43, P?<?0.01) and the annulus circumference (r2?=?0.38, P?<?0.01). A logistic regression analysis indicated that the MA area (OR: 1.02, 95% CI: 1.01–1.03, P?<?0.01), AHCWR (OR: 0.24, 95% CI: 0.14–0.35, P?=?0.04) and MV tenting volume (OR: 3.24, 95% CI: 1.16–9.08, P?=?0.03) were independent predictors of MR severity in AF patients.Conclusions
The mechanisms of “atrial functional MR” are complex and include dilation of the MA, flattening of the annular saddle shape and greater leaflet tethering.12.
Mona M. Khamis Teagan Holt Hanan Awad Anas El-Aneed Darryl J. Adamko 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):115
Introduction
Urine is an ideal matrix for metabolomics investigation due to its non-invasive nature of collection and its rich metabolite content. Despite the advancements in mass spectrometry and 1H-NMR platforms in urine metabolomics, the statistical analysis of the generated data is challenged with the need to adjust for the hydration status of the person. Normalization to creatinine or osmolality values are the most adopted strategies, however, each technique has its challenges that can hinder its wider application. We have been developing targeted urine metabolomic methods to differentiate two important respiratory diseases, namely asthma and chronic obstructive pulmonary disease (COPD).Objective
To assess whether the statistical model of separation of diseases using targeted metabolomic data would be improved by normalization to osmolality instead of creatinine.Methods
The concentration of 32 metabolites was previously measured by two liquid chromatography-tandem mass spectrometry methods in 51 human urine samples with either asthma (n?=?25) or COPD (n?=?26). The data was normalized to creatinine or osmolality. Statistical analysis of the normalized values in each disease was performed using partial least square discriminant analysis (PLS-DA). Models of separation of diseases were compared.Results
We found that normalization to creatinine or osmolality did not significantly change the PLS-DA models of separation (R2Q2?=?0.919, 0.705 vs R2Q2?=?0.929, 0.671, respectively). The metabolites of importance in the models remained similar for both normalization methods.Conclusion
Our findings suggest that targeted urine metabolomic data can be normalized for hydration using creatinine or osmolality with no significant impact on the diagnostic accuracy of the model.13.
R. Rozemeijer M. Voskuil J. P. Greving M. L. Bots P. A. Doevendans P. R. Stella 《Netherlands heart journal》2018,26(5):242-251
Background
Dual antiplatelet therapy (DAPT) remains the cornerstone therapy in the prevention of ischaemic events following drug-eluting stent (DES) implantation. Mandatory duration of DAPT after DES however, is a matter of debate. We aimed to evaluate safety and efficacy of short-term (up to 6 months) versus long-term (12 months) DAPT after DES implantation.Methods
We searched PubMed, EMBASE, Cochrane databases, and international meetings for randomised clinical trials (RCTs) comparing short with long DAPT. We performed a systematic review and meta-analysis of major trials with primary outcomes: all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding event.Results
Nine RCTs with a total number of 19,099 patients were pooled in the present meta-analysis. When compared with long DAPT, short DAPT was associated with a significant reduction in major bleeding events (0.62% vs. 1.10%, risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.86, p?<?0.007, I2?=?21%), whereas all-cause death (1.65% vs. 1.84%, RR 0.90, 95% CI 0.73 to 1.11, p?=?0.34, I2?=?0%), myocardial infarction (1.91% vs. 1.68%, RR 1.14, 95% CI 0.92 to 1.40, p?=?0.23, I2?=?0%), definite or probable stent thrombosis (0.62% vs. 0.47%, RR 1.25, 95% CI 0.84 to 1.86, p?=?0.27, I2?=?0%), and stroke (0.60% vs. 0.67%, RR 0.91, 95% CI 0.63 to 1.31, p?=?0.61, I2?=?0%) were similar.Conclusions
Short DAPT following DES implantation results in a significant reduction of major bleeding events with no apparent increase in all-cause death, myocardial infarction, stent thrombosis, or stroke. Future dedicated trials should investigate the optimal strategies for patient-tailored DAPT in various subgroups.14.
Ayesha Iqbal Amna Jabbar Siddiqui Jian-Hua Huang Saqib Hussain Ansari Syed Ghulam Musharraf 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):27
Introduction and objective
Fatty acids (FAs) influence cell and tissue metabolism, function, responsiveness to hormonal and other signals in addition to maintenance of membrane integrity of cells. β-Thalassemia is a prevalent inherited blood disorder characterized by abnormal red cell membrane structure and function. Induction of HbF by hydroxyurea (HU) is an enduring therapeutic intervention to manage this. Therefore, in the present study we have carried out the quantification of thirteen free fatty acids to disclose the prognosis of HU in β-thalassemia.Methods
FAs quantification was carried out using GC–MRM–MS method in the serum of 98 cases of β-thalassemia patients and out of which samples from 34 patients were collected before and after treatment with HU in addition to healthy controls (n?=?31).Results
Using the combination of random forest (RF) with GC–MRM–MS we were able to establish a classification and prediction model that can discriminate the β-thalassemia from healthy as well as from HU treated group. Docosanoic acid (C-22:0) was most significantly altered in β-thalassemia as compared to healthy at p-value of 8.3?×?10?09 while erucic acid (C-22:1 Δcis-13) can be used as potential marker of HU prognosis because its level became significantly dissimilar at p-value of 3.7?×?10?04 in same patients in response to HU. However, nervonic acid (C-24:1 Δcis-15) was found to be the key player in effectively separating three groups.Conclusion
In inference, we have noticed that HU therapy also rectifies the serum fatty acid profile in addition to its reported affect i.e. HbF induction in β-thalassemia patients.15.
Objectives
Establish a method to indirectly measure evaporation in microwell-based cell culture systems and show that the proposed method allows compensating for liquid losses in fed-batch processes.Results
A correlation between evaporation and the concentration of Na+ was found (R2?=?0.95) when using the 24-well-based miniature bioreactor system (micro-Matrix) for a batch culture with GS-CHO. Based on these results, a method was developed to counteract evaporation with periodic water additions based on measurements of the Na+ concentration. Implementation of this method resulted in a reduction of the relative liquid loss after 15 days of a fed-batch cultivation from 36.7?±?6.7% without volume corrections to 6.9?±?6.5% with volume corrections.Conclusion
A procedure was established to indirectly measure evaporation through a correlation with the level of Na+ ions in solution and deriving a simple formula to account for liquid losses.16.
Naoko Sato Yoshimi Hasegawa Asami Saito Fuyuhiko Motoi Kyohei Ariake Yu Katayose Kei Nakagawa Kei Kawaguchi Shin Fukudo Michiaki Unno Fumiko Sato 《BioPsychoSocial medicine》2018,12(1):13
Background
Pancreatic cancer (PC) has poorer prognosis and higher surgical invasiveness than many other cancers, with associated psychiatric symptoms including depression and anxiety. Perioperative depression has not been investigated in PC patients regarding surgical stress and relevant interventions.Methods
We evaluated chronological depressive changes and subjective physical symptoms in surgically treated PC patients preoperatively and at 3 and 6 months postoperatively.Enrolled patients undergoing pancreatic tumor surgery completed questionnaires based on the Self-Rating Depression Scale (SDS) and Functional Assessment of Cancer Therapy for Patients with Hepatobiliary Cancer (FACT-Hep) preoperatively, and at 3 and 6 months postoperatively. Responses were analyzed with JMP® Pro using one-way and two-way ANOVA, Spearman’s rank correlation coefficient, and multiple regression analysis.Results
Malignancy was diagnosed in 73 of 101 patients postoperatively; SDS score was significantly higher in these patients than in those with benign tumors at all timepoints: malignant/benign, 41.8/37.9 preoperatively (p?=?0.004); 43.5/37.8 3 months postoperatively (p?=?0.006); and 42.9/37.7 6 months postoperatively (p?=?0.020). SDS scores were significantly higher in patients <?65 years old with malignancy at 3 months than at 6 months postoperatively (44.6/42.5, p?=?0.046) and in patients with malignancy who underwent pancreaticoduodenectomy at 3 months postoperatively than preoperatively (43.4/41.1; p?=?0.028). SDS scores moderately correlated with 8 physical symptom-related FACT-Hep items 3 months postoperatively (p?<?0.05), showing low-to-moderate correlation with 16 physical symptom-related FACT-Hep items at 6 months postoperatively (p?<?0.05). Multiple regression analysis of FACT-Hep symptoms significantly correlated with SDS scores revealed the following significant variables: “lack of energy” (p?<?0.000) and “pain” (p?=?0.018) preoperatively (R2?=?0.43); “able to perform usual activities” (p?=?0.031) and “lack of energy” (p?<?0.000) at 3 months postoperatively (R2?=?0.51); and “stomach swelling or cramps” (p?=?0.034) and “bowel control” (p?=?0.049) at 6 months postoperatively (R2?=?0.52).Conclusions
PC patients experience persistently high levels of depression preoperatively through 6 months postoperatively, with associated subjective symptoms including pain and gastrointestinal symptoms.Trial registration
UMIN Clinical Trials Registry 000009592, Registered 20 December 2012.17.
Background
It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression.Methods
Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H3-cholesterol loading THP-1 cell models.Results
ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2–836.8) vs 458.2 (356.8–755.6), P?=?0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58?±?2.06 vs 12.51?±?2.83%, P?<?0.0001; DM: 13.62?±?2.57 vs 12.34?±?3.16%, P?=?0.0099]. ANGPTL8 was inversely correlated with cholesterol efflux capacity (r?=???0.188, P?<?0.01). Regression analysis revealed that plasma ANGPTL8 was an independent contributor to cholesterol efflux capacity (standardized β?=???0.143, P?=?0.023).Conclusion
ANGPTL8 presents a negative effect on HDL-mediated cholesterol efflux capacity.18.
Objective
This study aimed to understand clinicopathological characteristics of gastrointestinal stromal tumors (GISTs) and correlation between pathologic features and clinical outcome.Methods
We used 76 cases diagnosed as primary GISTs during January 2007 to July 2017 at Army Institute of Pathology, Thailand. Clinical, survival, and pathological data were collected and analyzed.Results
Ages of the patients ranged from 15 to 88?years (M:F?=?1:1). The most common presentation was gastrointestinal bleeding (39.7%). The most common site was the stomach (64.5%). Tumor size ranged from 0.6 to 25.5?cm (average 8.78?cm). Histologic types were spindle cell type (75%), mixed spindled-epithelioid type (17.1%), and epithelioid type (7.9%). The majority of histologic subtype was diffuse hypercellularity (67.1%). Tumor necrosis was found in 38.1% and 80% showed low mitotic counts. Most gastrointestinal stromal tumors (27.6%) are low-risk category according to Miettinen and Lasota’s algorithm. Metastasis was found in 27.7%, mostly occurs within 2?years, and is correlated with tumor size >?10?cm (P?=?0.023), non-spindle cell histologic type (P?=?0.027), mitotic count >?5/5mm2 (P?=?0.000), myxoid change (P?=?0.011), and mucosal invasion (P?=?0.002). Recurrence was found in 8.1%, mostly occurs within 7?years, and correlated with myxoid change (P?=?0.045).Conclusion
We found that most of GISTs show spindle cell type and low-risk category. Metastasis was correlated with tumor size >?10?cm, non-spindle cell histologic type, mitotic count >?5/5mm2, myxoid change, and mucosal invasion. Recurrence was correlated with myxoid change.19.
Background
Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS).Methods
For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS.Results
MACE occurred in 23 patients (1.5?%): death (3, 0.2?%), myocardial infarction (4, 0.3?%) and late revascularisation (16, 1.3?%). Multivariate analysis showed an independent prognostic value of CCTA (p?<?0.001), CACS of 100–400 (p?=?0.035) and CACS of >?400 (p?=?0.021). CCTA showed obstructive CAD in 3.1?% of patients with CACS?=?0. No events occurred in patients with CACS?=?0 without obstructive CAD at CCTA, whereas 2/23 patients (9?%) with CACS?=?0 with obstructive CAD had a MACE.Conclusions
Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS?=?0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.20.
Zhipeng Yan Xiang Tong Yao Ma Sitong Liu Lingjing Yang Xin Yang Xue Yang Min Bai Hong Fan 《BMC pulmonary medicine》2017,17(1):205