NR Group Research Articles

Sensitivity of doxorubicin-resistant osteosarcoma cells to doxorubicin regulated by long non-coding RNA NR_036444

Objective: To investigate the mechanism of long non-coding RNA (LncRNA) NR_036444 mediated sensitivity of multidrug-resistant osteosarcoma to doxorubicin. Methods: LncRNA-mRNA combined microarray was used to screen the differential expressions of lncRNA and mRNA in doxorubicin-resistant MG63/DXR osteosarcoma cells and their paired doxorubicin-sensitive MG63 cells; qRT-PCR was used to check the consistency of microarray. LncRNA NR_036444 was over-expressed in MG63/DXR cells by lentrvirus. CCK-8 array was used to evaluate cell proliferation and the sensitivity of cells to doxorubicin; Flow cytometry was used to evaluate cell cycle and apoptosis. The expressions of lncRNA NR_036444 in 60 cases of tumor tissues resected from osteosarcoma patients were detected by qRT-PCR and correlation analyses administrator were conducted. Results: Compared with those in MG63 cells, 1, 761 lncRNAs were significantly up-regulated and 1, 704 lncRNAs were dramatically down-regulated in MG63/DXR cells (P<0.05). 15 lncRNAs were selected randomly and their expressions were confirmed by qRT-PCR. The data showed that the differences in expression of 15 lncRNAs were consistent with microarray result. lncRNA NR_036444 with 22 folds down-regulation was identified as the most significant differential lncRNA in MG63/DXR cells. Half maximal inhibitory concentrations (IC(50)) in the blank group, negative control group and lncRNA NR_036444 overexpressed group were (12.73±0.50) μg/ml、(12.12±0.31) μg/ml and (5.77±0.25) μg/ml, respectively. Compared with that in negative control group, IC(50) in overexpressed group decreased by 49.6% (P<0.001). The percentages of G(1) phase cells in the overexpressed group, negative control group and blank group were(90.12±0.08)%, (33.36±0.85)% and (39.38±1.02)%. Compared with the negative control group and blank control group, the overexpression group had significantly more cells arrested in G(1) phase (both P<0.001). In the overexpressed group, negative control group and blank group, the percentages of late-apoptotic cells were (11.40±1.08)%, (4.23±1.12)% and (0.28±0.12)%, respectively. The percentages of early-apoptotic cells were (86.40±1.80)%, (4.35±2.03)% and (0.25±0.02) %, respectively. The percentages of early- and late-apoptotic cells were significantly increased in the overexpressed group when compared with those in control groups (P<0.01). Meanwhile, the expression of lncRNA NR_036444 in the tissues of chemoresistance group and chemosensitivity group was 19.67±1.53 and 77.67±2.52, respectively, with a statistically significant difference (P<0.01). The postoperative overall survival time of osteosarcoma patients with low expression of lncRNA NR_036444 was (24.6±2.4) months, significantly shorter than (48.2±1.8) months of patients with high expression of lncRNA NR_036444 (P<0.001). Conclusions: LncRNA NR_036444 may play a vital role in regulating osteosarcoma doxorubicin resistance and it may be a useful biomarker to assess the chemosensitivity and predict the prognosis of osteosarcoma patients in the future.

Positional Isomerism and Steric Effects in the Self-Assemblies of Phenylene Bis-Monothiooxalamides

The potential interplay of steric and substitution pattern effects of the monothiooxalamide side arms on the structure, conformational features, and self-assembly of a series of phenylene bis-monothiooxalamides was investigated. Herein we have demonstrated that phenylene bis-monothiooxalamides self-associate in the solid state, through intermolecular hydrogen bonding as meso-helices when the thioamide NR group is sBu and through dispersive CO···CX (X = O, S, π), S···S, and C–H···S interactions when R is tBu, independently from the substitution pattern in the phenyl ring. The helical structures are exclusively developed through NCSH···O hydrogen bonding. The steric strain imposed by the ortho-substitution pattern has the effect of moving both monothiooxalyl units out of the phenyl plane enabling dimerization through strong NCOH···O intermolecular hydrogen bonds and promotes the formation of meso-helices. The steric demand of the thioamide NR group rules the conformation adopted by meta-substituted derivati...

Lymph node ratio as a prognostic factor in gastric cancer patients following D1 resection. Comparison with the current TNM staging system

IntroductionNodal ratio (NR) has been demonstrated to be an independent prognostic factor in patients with gastric cancer. We evaluated the prognostic role of NR comparing it with the current TNM (2010) classification in gastric cancer patients treated with curative (R0) D1 resection. Materials and methodsWe retrospectively reviewed 110 patients who underwent R0 resection for gastric cancer at University Hospital of Larissa between 2002 and 2011. All patients had a D1 lymphadenectomy plus the nodes along the left gastric artery. Factors affecting survival as well as correlations between the N status, NR status and resected nodes were investigated. ResultsIn univariate analysis the N and NR status but not the numbers of retrieved nodes were significant prognostic factors. Inside N1 and N2 categories, patients with different NR groups were present and survival of some of these subpopulations was statistically different at long-rank test. There was a correlation between the nodes retrieved and N status but not with the NR category. In multivariate analysis both N status (HR=1.45; 95% C.I. = 1.19–1.89) and NR (HR=4.53; 95% C.I. = 1.86–11.03) found to be independent prognostic factors of survival. ConclusionPrognostic significance of N status and NR status was comparable. Unlike N status, NR is independent by the number of resected nodes, and therefore it is particularly useful in case of conventional lymphadenectomy.

Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.

Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein-Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.

Abstract P4-12-08: Use of an aptamer library based next generation omics platform for the development of a novel trastuzumab predictive assay

Abstract Introduction: Previous attempts to use individual aptamers as diagnostic reagents have failed to consistently achieve performance comparable to antibodies. Here we report a novel systems biology approach using poly-ligand aptamer libraries to identify responders and non-responders to traztuzumab-based regimens in metastatic breast cancer. Methods: To overcome the fundamental limitation of the individual aptamer binding affinities, large libraries (106 species) were created so that potentially thousands of aptamers could bind to each of a multitude of targets related to the whole cellular changes in response to trastuzumab therapy. A set of breast cancer patients, which received trastuzumab mono- or combined therapy for at least 7 months were classified as “Responders” (R); cases with particular regimen discontinued in the period not exceeding 5 months were classified as “Non-Responders”(NR). A library of 2x1012 unique 90-mer ssDNA oligodeoxynucleotides (ssODN) was trained on FFPE tissue of both R and NR patients. Partitioning of aptamer libraries was done by microdissection of the tumor tissue, after incubation of aptamer library with the entire tissue section, to drive selection pressure toward cancer cells. A total of 10 cases of R and NR, 6 Her2+ cases each, were used to train separate aptamer libraries, with 1 positive and 2 counter selection cases per enrichment. Enriched libraries were screened on 20 R and 20 NR cases (11 Her2+ cases each) by adopting modified immunohistochemistry protocol. Each library was used as an independent reagent (similar to an antibody in IHC) across all 40 cases to evaluate the efficacy of the aptamer library to distinguish differences between the R and NR groups. Staining (DAB chromogen) profiles were scored from 0 to 3+ (nuclear and cytoplasmic staining) by a pathologist without any knowledge of the clinical outcomes. Initial validation was done by t-test using raw histological scores. Four libraries showed significant p-values between groups of responders and non-responders, a classification algorithm was constructed and evaluated using area under the receiver-operator characteristic curve (AUC). The datasets of two best-performing libraries were combined into one model using logistic regression to further improved the classifier performance. Results: Of seventeen trained libraries, eight were evaluated and four showed significant correlation to clinical benefit with a minimum accuracy of 75% for each library when evaluated independently. Furthermore, two libraries showed exceptional performance (ROC curve AUC of 0.86 and 0.77). Combination of the profiling data from these two libraries using logistic regression resulted in an AUC of 0.985. A prospective validation of aptamer histochemical theranostic testing has been initiated. Summary: Enriched aptamer libraries appear to distinguish trastuzumab responsiveness in metastatic breast cancer. This technology could be used as an additional technique beyond FISH testing to determine sensitivity to anti-HER2 agents. The demonstrated platform is applicable to virtually any disease where the safe and effective use of corresponding drug is yet to be improved. Citation Format: Spetzler D, Domenyuk V, Santhanam R, Wei X, Stark A, Wang J, Gatalica Z, Miglarese M, Vidal G, Schwartzberg LS. Use of an aptamer library based next generation omics platform for the development of a novel trastuzumab predictive assay [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-08.

Abstract 209: Association Between Medicare High Risk Criteria and Long Outcomes Following Carotid Revascularization Procedures

Background: Centers of Medicare and Medicaid Services (CMS) has defined a set of high-risk criteria to help define patients who would likely benefit from CAS over CEA. The purpose of this study was to evaluate the postoperative outcomes in patients undergoing CAS vs. CEA, and whether those outcomes vary based on the CMS high-risk criteria. Methods: All patients undergoing CAS or CEA recorded in the Vascular Quality Initiative database (2013-2016) were included. Patients were stratified as being normal-risk (Nr) or high-risk (Hr) for undergoing CEA based on published CMS criteria. 30-day and 2-year outcomes [stroke, myocardial infarction (MI), death] were compared for CAS vs. CEA in both the Nr and Hr groups using 1:1 coarsened exact matching and multivariable Cox proportional hazards modelling. Results: A total of 55,765 patients (CAS=8,538; CEA=47,227) underwent carotid revascularization during the study period. A significantly higher proportion of CAS were classified as being Hr (75.1% vs. 38.5%; P&lt;0.001). Among Nr patients, 30-day stroke (2.2% vs. 1.0%) and death (4.9% vs. 2.9%) occurred more frequently after CAS vs. CEA (P&lt;0.001), whereas the rate of MI was similar (0.8% vs. 0.6%; P=0.17). Among the Hr patients, 30-day stroke (2.8% vs. 1.3%) and death (7.9% vs. 6.2%) also occurred more frequently after CAS vs. CEA (P&lt;0.001), but the rate of MI was higher after CEA (0.8% vs. 1.1%, P=0.03). After matching 5,440 pairs of patients on 14 preoperative variables, the risk of 2-year stroke/death remained higher after CAS in both the Nr (HR 1.58; 1.17-2.15) and Hr (HR 1.37; 1.13-1.66) groups (Figure). Conclusions: In this matched cohort of patients, CAS carries a persistently higher risk of stroke/death than CEA regardless of operative risk. However, the performance difference between the two procedures dissipates in the Hr patients. Thus, CAS utilization should be considered in this group.

Is Remnant Preservation Truly Beneficial to Anterior Cruciate Ligament Reconstruction Healing? Clinical and Magnetic Resonance Imaging Evaluations of Remnant-Preserved Reconstruction

Background: Remnant-preserved anterior cruciate ligament (ACL) reconstruction was introduced to improve clinical outcomes and biological healing. However, the effects of remnant preservation and the influence of the delay from injury until reconstruction on the outcomes of this technique are still uncertain. Purpose/Hypothesis: The purposes of this study were to evaluate whether remnant preservation improved the clinical outcomes and graft incorporation of ACL reconstruction and to examine the influence of the delay between ACL injury and reconstruction on the usefulness of remnant preservation. We hypothesized that remnant preservation improves clinical results and accelerates graft incorporation and that its effect is dependent on the delay between ACL injury and reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 151 consecutive patients who underwent double-bundle ACL reconstruction using a semitendinosus graft were enrolled in this study: 74 knees underwent ACL reconstruction without a remnant (or the remnant was <25% of the intra-articular portion of the graft; NR group), while 77 knees underwent ACL reconstruction with remnant preservation (RP group). These were divided into 4 subgroups based on the time from injury to surgery: phase 1 was <3 weeks (n = 24), phase 2 was 3 to less than 8 weeks (n = 70), phase 3 was 8 to 20 weeks (n = 32), and phase 4 was >20 weeks (n = 25). Clinical measurements, including KT-1000 arthrometer side-to-side anterior tibial translation measurements, were assessed at 3, 6, 12, and 24 months after reconstruction. Magnetic resonance imaging evaluations of graft maturation and graft-tunnel integration of the anteromedial and posterolateral bundles were assessed at 3, 6, and 12 months after reconstruction. Results: There was no difference in side-to-side anterior tibial translation between the NR and RP groups. There was also no difference in graft maturation between the 2 groups. Furthermore, the time from ACL injury until reconstruction did not affect graft maturation, except in the case of very long delays before reconstruction (phase 4). Graft-tunnel integration was significantly increased in both groups in a time-dependent manner. However, there was no difference between the NR and RP groups. Conclusion: Remnant preservation did not improve knee stability at 2 years after ACL reconstruction. Furthermore, remnant preservation did not accelerate graft incorporation, especially during the acute and subacute injury phases.

Clinical Features of Refractory Ascites in Outpatients

OBJECTIVES:To present the clinical features and outcomes of outpatients who suffer from refractory ascites.METHODS:This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month.RESULTS:The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R) and 11 non-refractory ascites (NR)]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034). The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively). Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262).CONCLUSION:Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

Nasal obstructive disorders induce medical treatment failure in paediatric persistent allergic rhinitis (The NODPAR Study).

Allergic rhinitis (AR) is the most common chronic disease among children. To characterize the disease, a modified classification of severity (m-ARIA) has recently been validated in AR children. When medical treatment fails, surgery for nasal obstructive disorders (NOD) may be a therapeutic option. Our objective was to assess the prevalence of NOD and their influence in medical treatment response among children with persistent AR (PER). In a prospective, real-life study, 130 paediatric PER patients (13.1±2.8years, females 31.5%, severe rhinitis 49%) referred from Allergy to ENT department were assessed for their response (R, responders; NR, non-responders) to medical treatment (intranasal steroids and antihistamines or antileukotrienes) by direct questioning and nasal symptom visual analogue scale, the presence of NOD (septal deformity, turbinate enlargement and adenoidal hyperplasia), comorbidities, nasal symptoms, rhinitis severity (modified ARIA criterion) and asthma control (International Consensus On Pediatric Asthma criterion). After 2months of treatment, the NR group presented a higher prevalence of obstructive septal deformity and severe inferior turbinate enlargement when compared with the R group. Higher septal deformity and turbinate enlargement scores were strongly associated with treatment refractoriness. The prevalence of severe PER was also higher for the NR group. Higher asthma control scores were associated with the probability of treatment-induced improvement. In paediatric PER patients, medical therapy refractoriness was associated with NOD, mainly septal deformity and turbinate enlargement. In those patients, ENT examination will facilitate an early NOD diagnosis in order to indicate potential corrective surgery.

Feline Injection-Site Sarcoma.

Feline injection-site sarcoma (FISS) is an aggressive tumor believed to arise from the proliferation of fibroblasts and myofibroblasts in areas of chronic inflammation, particularly at sites of injection. Local recurrence is frequent after surgical excision. Gelatinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) are endopeptidases pivotal in extracellular matrix remodeling and therefore in tumor invasiveness. The aim of this study was to investigate the immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in FISS to assess their usefulness as prognostic factors. Size, soft tissue sarcoma (STS) grading system, depth of infiltration, surgical margins, and Ki-67 index were evaluated as additional prognostic markers. Twenty-four cases of primary FISS were classified according to clinical follow-up as nonrecurrent (NR, n = 14; 58.3%) and recurrent (R, n = 10; 41.7%). MMP-2, MMP-9, and TIMP-2 were variably expressed in the FISS examined, confirming their role in tumor invasiveness, yet they did not show significant differences between the R and NR groups. These results could be due to different tumor stages or to the multiple activities of these enzymes, not limited to ECM remodeling. The immunohistochemical expression of these enzymes considered alone does not seem to be useful as a prognostic marker. STS grading system, depth of infiltration, surgical margins, and Ki-67 index did not relate to recurrence. Instead, the size of the tumor, measured after formalin fixation, with an optimal cutoff of 3.75 cm (accuracy = 86%; P < .05), and the mitotic count, with an optimal cutoff of 20 mitoses/10 HPF (accuracy = 80%; P < .05), could be evaluated as useful prognostic markers.

Oxygen flux reduces Cux1 positive neurons and cortical growth in a gestational rodent model of growth restriction

BackgroundThe mammalian cerebral cortex forms in an inside-out manner, establishing deep cortical layers before superficial layers and is regulated by transcription factors which influence cell differentiation. Preterm birth interrupts the trajectory of normal neurodevelopment and adverse perinatal exposures have been implicated in cortical injury. We hypothesise that growth restriction (GR) and fluctuating hyperoxia (ΔO2) impair cortical laminar development. MethodsSprague-Dawley rats received 18% (non-restricted, NR) or 9% (growth restricted, GR) protein diet from E15-P7. Litters were reared in air or fluctuating hyperoxia (circa 10kPa) from P0 to P7. Cortical laminae were stained and measured. Neuronal subtypes were quantified using immunofluorescence for subtype-specific transcription factors (Satb2, Cux1, Ctip2, Tbr1). ResultsΔO2 did not affect brain weight at P7 but reduced cortical thickness in both NR (p<0.05) and GR groups (p<0.001). ΔO2 resulted in superficial cortical thinning in both groups and in the deep layers of GR pups (p<0.001). Cell density was preserved. ΔO2 did not affect proportions of callosal, corticothalamic and corticospinal neurons but resulted in a reduction of neurons expressing Cux1 (p<0.01) implicated in dendritic branching and synapse formation. ConclusionPostnatal ΔO2, a modifiable factor in neonatal care, impairs cortical development in a rodent model with preferential disadvantage to superficial neurons.

Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients.

The maintenance of chronic immune activation due to leishmaniasis or even due to microbial translocation is associated with immunosenescence and may contribute to frequent relapses. Our aim was to investigate whether patients with HIV-associated visceral leishmaniasis (VL/HIV) who experience a single episode of VL have different immunological behaviors in comparison to those who experience frequent relapses. VL/HIV patients were allocated to non-relapsing (NR, n = 6) and relapsing (R, n = 11) groups and were followed from the active phase of VL up to 12 months post-treatment (mpt). The patients were receiving highly active antiretroviral therapy (HAART) and secondary prophylaxis after VL therapy. During active VL, the two groups were similar in all immunological parameters, including the parasite load. At 6 and 12 mpt, the NR group showed a significant gain of CD4+ T cells, a reduction of lymphocyte activation, and lower soluble CD14 and anti-Leishmania IgG3 levels compared to the R group. The viral load remained low, without correlation with the activation. The two groups showed elevated but similar percentages of senescent T cells. These findings suggest a decreased ability of the R group to downmodulate immune activation compared to the NR group. Such functional impairment of the effector response may be a useful indicator for predicting clinical prognosis and recommending starting or stopping secondary prophylaxis.

Improvement in aerobic capacity during cardiac rehabilitation in coronary artery disease patients: Is there a role for autonomic adaptations?

Background It has been previously shown in patients with heart failure that exercise-based rehabilitation programmes may improve functional capacity and autonomic response. The aim of this study was to investigate this issue further by evaluating whether an association exists between autonomic adaptations and improvements of aerobic capacity in a general population of coronary artery disease patients undergoing cardiac rehabilitation. Methods Ninety consecutive patients (age 60 ± 11 years) attended a rehabilitation programme of moderate continuous training (25 ± 8 sessions, 2-3 sessions/week). Functional capacity expressed as oxygen uptake (peak VO2) and autonomic function expressed as chronotropic response and heart rate recovery were evaluated by cardiopulmonary exercise tests before and after the rehabilitation programme. According to the expected mean increase in functional capacity, coronary artery disease patients were divided into two groups: those who improved peak VO2 by more than 2.6 ml/kg/min (R group) and those who did not (NR group). Effects of the rehabilitation programme were compared in R and NR groups. Results The number and intensity of exercise sessions did not differ between R ( N = 39) and NR ( N = 51) groups. However, only R patients improved chronotropic response (R: from 45.1 ± 16.9% to 72.7 ± 34.1%, P < 0.01; NR: from 49.3 ± 18.6% to 48.2 ± 36.5%, P = NS) and heart rate recovery (R: from 16.9 ± 7.0 bpm to 21.0 ± 8.7 bpm, P < 0.01; NR: from 15.2 ± 9.9 bpm to 15.8 ± 8.5 bpm, P = NS). After training both chronotropic response and heart rate recovery were significantly higher in R than NR patients. Conclusions The improvement in aerobic capacity of coronary artery disease patients following exercise-based cardiac rehabilitation programmes is associated with positive adaptations of autonomic function.

Factors associated with the relapse of cryptogenic and secondary organizing pneumonia.

Organizing pneumonia (OP) is a histopathological response pattern to lung inflammation. It is clinically classified into cryptogenic OP and secondary OP, which is associated with various clinical conditions. Rapid resolution with corticosteroids and frequent relapses are common in OP. However, few studies have investigated the factors associated with OP relapse. The medical records of 75 patients with biopsy-proven OP, diagnosed between January 2010 and August 2015, who underwent corticosteroid therapy were retrospectively reviewed. Initially, the patients were all treated successfully; however, 31 patients experienced relapse thereafter (R group), whereas the others did not (NR group; 44 patients). The clinical, radiological, and pathological characteristics and administered corticosteroid doses were compared between the two groups. The neutrophil percentage in the bronchoalveolar lavage (BAL) fluid and the level of fibrin deposition in lung biopsy specimens were higher in the R group than in the NR group (P=0.01 and P=0.002, respectively). The multivariate analysis demonstrated that both factors were statistically significant predictors of OP relapse. A high neutrophil percentage in the BAL and the level of fibrin deposition in lung biopsy specimens are considered predictive factors of OP relapse during the tapering or after the cessation of steroid therapy. Patients without these findings may be treated with low-dose corticosteroids.

Preoperative prediction for regaining ambulatory ability in paretic non-ambulatory patients with metastatic spinal cord compression.

Retrospective multicenter study. To analyze the predictive factors for postoperative ambulatory recovery in paretic non-ambulatory patients with metastatic spinal cord compression (MSCC). Japan. Eighty-two consecutive patients (74.4% men; mean age, 66.2 years) who could not walk before surgery due to cervical or thoracic MSCC and underwent posterior decompressive surgery between 2003 and 2014 were included. Patients were divided into two groups according to ambulatory status at 6 weeks after surgery: recovery (group R) and non-recovery (group NR). To evaluate the speed of progression of motor deficits, we assessed the period from onset of neurological symptoms to gait inability (T1). Fifty patients (61.0%) regained the ability to walk (group R). The period of T1 demonstrated a positive correlation with probability of ambulatory recovery (P=0.00; Kendall's tau-b=0.38), and a receiver operating characteristic curve analysis showed that the cutoff value of T1 was 5 days (area under the curve=0.72; P=0.001). In multivariate analysis, <6 days of T1 was one of the independent risk factors for failing to regain ambulatory ability (odds ratio, 8.74; P=0.00). The speed of progression of motor deficits can independently and powerfully predict the chance of postoperative ambulatory recovery as well as previously identified predictors. Since information about the speed of progression can be obtained easily by interviewing patients or family members, even if the patient is in an urgent state, our results will be helpful in clinical decision-making.

Anti-Müllerian hormone dynamics during GNRH-antagonist short protocol for IVF/ICSI in women with varying ovarian reserve levels.

Data on variations in anti-Müllerian hormone (AMH) levels according to ovarian reserve are scant. The aim of this study was to investigate changes in AMH levels during controlled ovarian hyperstimulation with a GnRH-antagonist protocol for in vitro fertilization (IVF). Prospective, observational study of 46 women. The subjects were divided into three cohorts according to ovarian reserve levels: polycystic ovary syndrome (PCOS; N.=19), low ovarian reserve (LOR; N.=11), and normoreserve (NR; N.=16). Serum AMH concentration was measured at baseline (cycle day 2-3 before follicle stimulating hormone [FSH] administration) and just prior to GnRH-antagonist and human chorionic gonadotropin (hCG) administration. AMH concentration in follicular fluid (FF) was assessed on the day of oocyte retrieval. AMH serum concentration decreased significantly (P<0.001) and progressively in all three groups from baseline (initiation of stimulation) to all subsequent assessments. Serum AMH levels were significantly higher in the PCOS group at all determinations: (AMH1: 8.18±6.26ng/mL, AMH2: 5.3±3.97ng/mL, AMH3: 2.19±1.31ng/mL) versus the NR group (AMH1: 2.94±1.53ng/mL, AMH2: 1.44±0.77ng/mL, AMH3: 0.71±0.57ng/mL) and LOR group (AMH1: 0.63±0.42ng/mL, AMH2: 0.58±0.4ng/mL, AMH3: 0.31±0.2ng/mL). No significant between-group differences were observed for AMH levels in FF (PCOS: 3.56±3.19ng/mL, NR: 4.06±5.44ng/mL, LOR: 1.31±0.47ng/mL) nor for fertilization rate, number of top quality embryos, or clinical pregnancy rates. Serum AMH levels gradually decrease during GnRH-antagonist protocol for IVF. This decrease starts at the beginning of the follicular phase and continues up to the day of hCG administration. These results underscore the important role that AMH plays in the process of folliculogenesis and dominant follicle selection.

A comparison of the effectiveness of the streamlined liner of pharyngeal airway in paralyzed and nonparalyzed patients undergoing gynecological surgery: a randomized trial

Study ObjectiveTo compare the effectiveness of streamlined liner of pharyngeal airway (SLIPA) in paralyzed and nonparalyzed, anesthetized patients undergoing gynecological surgery. DesignProspective randomized double-blind clinical trial. SettingIntraoperative. PatientsA total of 80 female patients with American Society of Anesthesiologists class I or II and who were undergoing gynecological surgery. InterventionsThe patients were randomly allocated to either the nonparalyzed group (group NR, n=40) or the paralyzed group (group R, n=40). MeasurementsOropharyngeal leakage pressure was the primary outcome. Insertion time; number of insertion attempts; success rate at first insertion; involuntary movement; peak inspiratory pressure (PIP); leakage fraction; hemodynamic changes; complications, such as blood tinging, regurgitation, and sore throat; and recovery time were also evaluated for secondary outcomes. Main ResultsOropharyngeal leakage pressure, which is primary outcome, was no difference among the groups. Insertion time, number of insertion attempts, success rate at first insertion, involuntary movement, leakage fraction, hemodynamic changes, and complications were not statistically different among the groups. The PIP in group NR was significantly increased compared to that of group R (P=.002). Recovery time was significantly longer in group R than in group NR (P<.001). ConclusionsSLIPA had good performance in both paralyzed and nonparalyzed patients. There was no difference in SLIPA performance or complications irrespective of muscle relaxant use, except decrease in PIP and prolong recovery time in paralyzed patients.

Endoplasmic Reticulum Stress Predicts Clinical Response to Cyclosporine Treatment in Primary Membranous Nephropathy

Background: Little is known about the endoplasmic reticulum stress (ERS) marker glucose regulated protein 78 (GRP78) and calcineurin in the kidney in primary membranous nephropathy (PMN) and if they could predict post-cyclosporine treatment outcome. Methods: This is a retrospective study using a dataset of biopsy-confirmed PMN from Peking Union Medical College Hospital from 1996 to 2014. Seventy-six adult patients treated with cyclosporine as primary immunosuppression for at least 6 months were studied. Immunohistochemistry was used to detect GRP78 and calcineurin in the kidney. Serum calcineurin was assayed by ELISA. Patients were grouped into no-remission (NR, n = 17), partial remission (PR, n = 39), or complete remission (CR, n = 20) at the end of 6 months of treatment. Results: There was no difference of initial dose of cyclosporine among NR, PR, and CR groups. Kidney calcineurin expression in PMN was significantly increased compared to that in controls (p < 0.0083). The glomerular GRP78 in NR PMN was higher than that in control, CR and PR patients (p < 0.0083). Kidney calcineurin expression and GRP78 expression was positively correlated. However, there were no differences in either serum calcineurin levels or kidney calcineurin expressions among NR, PR or CR groups. There was a negative correlation between serum calcineurin activity and whole kidney calcineurin expression (p = 0.034) or glomerular calcineurin expression (p = 0.007). Neither kidney calcineurin nor GRP78 expression was correlated with proteinuria. Conclusions: ERS marker GRP78 in the glomeruli but not serum or kidney calcineurin expression could be a useful marker in PMN to negatively predict the response to cyclosporine treatment at the sixth month.

Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs

BackgroundTo investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. MethodsForty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. ResultsHemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). ConclusionPyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn.

Timeline of blood pressure changes after intra-arterial therapy for acute ischemic stroke based on recanalization status.

There is sparse literature on the natural history of blood pressure (BP) after intra-arterial therapy (IAT) for acute ischemic stroke (AIS). A retrospective analysis was performed of patients with AIS who underwent IAT without endotracheal intubation for internal carotid artery terminus (ICA-T) or M1 middle cerebral artery occlusion from January 2008 to February 2012. Systolic BP (SBP) values at the beginning (First) and end (End) of IAT and for 36 h after the procedure were collected. Successful recanalization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b-3. Sixty-two patients (14 (22.5%) ICA-T, 46 (74.2%) M1, 2 (3.2%) ICA-T+M1) met the study criteria and 37 (59.7%) achieved successful recanalization. The First and End SBP values were similar in the successful (Group R) and unsuccessful (Group NR) recanalization groups. Taking the whole cohort, End SBP was significantly lower than First SBP, but this decline was significant only in Group R. Subsequently, absolute SBP values in Group R were not significantly different from Group NR. However, when comparing the hourly decline of SBP with First SBP, Group R demonstrated a greater fall than Group NR and the decline was significantly different from hours 8 to 12 post-procedure. The SBP in Group NR then decreased further, and its difference from baseline was similar to Group R from hour 14 onwards. Mean SBP and SBP variability over 36 h were similar between the two groups. SBP falls significantly in patients with AIS with large vessel occlusion who recanalize with IAT. While SBP in non-recanalized patients also drops from baseline, it occurs to a lesser degree and stays higher only for a short period of time before falling to similar levels as in recanalized patients.