ICA Group Research Articles

Efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cancer: a retrospective study.

The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC). A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs). The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group. PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.

Incisional Hernia After Laparoscopic Right Colectomy for Colorectal Cancer: A Prospective Study with Retrospective Control on Intracorporeal Versus Extracorporeal Anastomosis.

Background: Incisional hernias often occur after laparoscopic colorectal surgery, but the precise risk factors are not fully understood. This study's primary aim was to compare the incidence of incisional hernias following laparoscopic right colectomy with intracorporeal anastomotic reconstruction (ICA) versus extracorporeal anastomotic reconstruction (ECA). Materials and Methods: A cohort study compared two groups of patients who underwent elective laparoscopic right colectomy for colon cancer following a standardized perioperative enhanced recovery program (ERP): a prospective group underwent ICA from January 2018 to February 2020 and a retrospective group underwent ECA from January 2013 to December 2016. The presence of incisional hernias was assessed by reviewing patients' follow-up computed tomography scans or evaluating the patients by telephone interview or outpatient office visit and diagnostic imaging. Secondary objectives included the hospital length of stay, postoperative complications, 30-day readmission rate, reoperation, and mortality. Results: The study included 89 patients who had laparoscopic right colectomy for malignant colon neoplasms. Among these, 48 underwent ECA (ECA group), and 41 had ICA (ICA group). At a median follow-up of 36 months, incisional hernia was observed in 1 patient (2.4%) in the ICA group, in contrast to 11 (22.9%) confirmed cases in the ECA group (P = .010). The length of hospital stay was similar between the two groups (5 days versus 4 days; P = .064). The two groups showed similarities in terms of postoperative complications (P = .093), hospital readmission (P = .999), and the rate of reoperation within 30 days (P = .461). Conclusions: The ICA technique was associated with a reduced risk of incisional hernias compared with the ECA technique, with similar outcomes in short-term postoperative complications and overall patient recovery.

The role of the amygdala in ictal central apnea: insights from brain MRI morphometry.

Ictal central apnea (ICA) is a frequent correlate of focal seizures, particularly in temporal lobe epilepsy (TLE), and regarded as a potential electroclinical biomarker of sudden unexpected death in epilepsy (SUDEP). Aims of this study are to investigate morphometric changes of subcortical structures in ICA patients and to find neuroimaging biomarkers of ICA in patients with focal epilepsy. We prospectively recruited focal epilepsy patients with recorded seizures during a video-EEG long-term monitoring with cardiorespiratory polygraphic recordings from April 2020 to September 2022. Participants were accordingly subdivided into two groups: patients with focal seizures with ICA (ICA) and without (noICA). A pool of 30 controls matched by age and sex was collected. All the participants underwent MRI scans with volumetric high-resolution T1-weighted images. Post-processing analyses included a whole-brain VBM analysis and segmentation algorithms performed with FreeSurfer. Forty-six patients were recruited (aged 15-60 years): 16 ICA and 30 noICA. The whole-brain VBM analysis showed an increased gray matter volume of the amygdala ipsilateral to the epileptogenic zone (EZ) in the ICA group compared to the noICA patients. Amygdala sub-segmentation analysis revealed an increased volume of the whole amygdala, ipsilateral to the EZ compared to controls [F(1, 76) = 5.383, pFDR = 0.042] and to noICA patients ([F(1, 76) = 5.383, pFDR = 0.038], specifically of the basolateral complex (respectively F(1, 76) = 6.160, pFDR = 0.037; F(1, 76) = 5.121, pFDR = 0.034). Our findings, while confirming the key role of the amygdala in participating in ictal respiratory modifications, suggest that structural modifications of the amygdala and its subnuclei may be valuable morphological biomarkers of ICA.

Predictive Factors for Clinical Outcome After Direct Mechanical Thrombectomy for Anterior Circulation Large Vessel Occlusion Within 4.5 h.

BackgroundRecent trials including DIRECT-MT, DEVT, and SKIP have found that direct mechanical thrombectomy (MT) is equally effective as the combination of MT and intravenous thrombolysis. However, the results of the other trials, namely MR-CLEAN NO-IV and the SWIFT-DIRECT trial have failed to confirm the non-inferiority of direct MT vs. the combination therapy.AimWe aimed to identify prognostic factors of direct MT for anterior circulation large vessel occlusion within 4.5 h.Materials and MethodsData from January 2018 to January 2022 were retrospectively collected and analyzed. Adult patients with confirmed anterior circulation large vessel occlusion within 4.5 h of onset with baseline NIHSS of ≥6 and baseline ASPECTS of ≥6 treated using direct MT within 6 h were recruited.ResultsA total of 140 patients were enrolled in the study with a median age of 65.5 years [interquartile range (IQR), 59–76.5], median baseline NIHSS of 13.5 (IQR, 11–16), and median baseline ASPECTS of 8 (IQR, 7–8). Direct MT was feasible in all patients (100%). Successful reperfusion (mTICI 2b-3) was achieved in 124/140 patients (88.6%) with a low rate of complications (8/140, 5.7%). Any type of intracranial hemorrhage (ICH) and symptomatic ICH occurred in 44/140 (31.4%) and 5/140 (3.6%), respectively. Overall, a good outcome (mRS 0–2) was achieved in 93/140 (66.4%), and the mortality rate was 9.3% (13/140 patients). Using multivariate analysis, lower age [odds ratio (OR), 0.96; 95% CI, 0.92–1.00; P = 0.05], low baseline NIHSS (OR, 0.82; 95% CI, 0.74–0.92; P = 0.00), and absence of ICH (OR, 0.29; 95% CI, 0.10–0.81; P = 0.02) were independently associated with favorable outcome. Independent predictors of mortality were baseline NIHSS (OR, 1.21; 95% CI, 1.01–1.46; P = 0.04), successful reperfusion (OR, 0.02; 95% CI, 0.00–0.58; P = 0.02), and ICH (OR, 0.12; 95% CI, 0.02–0.75; P = 0.02). Further analysis showed that the median mRS at 90 days was significantly better in the MCA occlusion group compared to the ICA plus M1 occlusion group [1 (IQR 0–3) vs. 2 (IQR 1–4); P = 0.05].ConclusionsOur findings suggest that direct thrombectomy may be an adequate clinical option for younger patients (≤70) experiencing proximal middle artery occlusion within 4.5 h and who have low baseline NIHSS (≤14).

Deep learning prediction of quantitative coronary angiography values using myocardial perfusion images with a CZT camera

PurposeEvaluate the prediction of quantitative coronary angiography (QCA) values from MPI, by means of deep learning. Methods546 patients (67% men) undergoing stress 99mTc-tetrofosmin MPI in a CZT camera in the upright and supine position were included (1092 MPIs). Patients were divided into two groups: ICA group included 271 patients who performed an ICA within 6 months of MPI and a control group with 275 patients with low pre-test probability for CAD and a normal MPI. QCA analyses were performed using radiologic software and verified by an expert reader. Left ventricular myocardium was segmented using clinical nuclear cardiology software and verified by an expert reader. A deep learning model was trained using a double cross-validation scheme such that all data could be used as test data as well. ResultsArea under the receiver-operating characteristic curve for the prediction of QCA, with > 50% narrowing of the artery, by deep learning for the external test cohort: per patient 85% [95% confidence interval (CI) 84%-87%] and per vessel; LAD 74% (CI 72%-76%), RCA 85% (CI 83%-86%), LCx 81% (CI 78%-84%), and average 80% (CI 77%-83%). ConclusionDeep learning can predict the presence of different QCA percentages of coronary artery stenosis from MPIs.

Intracorporeal anastomosis versus extracorporeal anastomosis after laparoscopic right hemicolectomy for colon cancer: morbidity comparison at long-term follow-up.

Minimally invasive right hemicolectomy is nowadays considered the gold standard for treatment of malignant right colon disease. What is still debated is instead the choice between intracorporeal or extracorporeal anastomosis. The aim of this study was to compare morbidity and the long-term results between these two techniques. This retrospective, double-center cohort study was performed between January 2013 and December 2014. A total of 197 patients were enrolled after laparoscopic right hemicolectomy for malignant disease. The extracorporeal anastomosis group (ECA) included 95 patients, while the intracorporeal anastomosis group (ICA) included 102 patients. All patients were followed up for 5 years after surgery. Data analysis was performed in February 2021. The ICA group showed a reduced rate of non-surgical complications Clavien-Dindo grade I-II (10% vs. 31%; P=0.001) as well as a lower rate of wound infections (2% vs. 12%; P=0.01). Most importantly, a decreased risk of incisional hernias in a five-year follow-up period (1% vs. 8%; P=0.01) has been underlined. Intracorporeal anastomosis technique after totally laparoscopic right hemicolectomy showed better outcomes as it significantly reduces the risk for short and long-term complications, namely, incisional hernias.

Chicken eggshell powder more effectively alleviates bone loss comparted to inorganic calcium carbonate: an animal study performed on ovariectomized rats.

This study aimed to evaluate the effects of chicken eggshell powder rich in calcium and the inorganic form of calcium carbonate on osteoporotic bone structure using an animal model of ovariectomized rats. Animals were divided into four groups: sham-operated rats (SHAM group); ovariectomized rats untreated (OVX group); OVX rats treated with eggshell powder (Biomin H® OVX + ECa group; total Ca content 1.5%); and OVX rats receiving inorganic calcium carbonate (calcium carbonate precipitated, total Ca content 1.5%; OVX + ICa group) during 8 weeks. Ovariectomy increased total body weight, plasma alkaline phosphatase activity, cortical bone thickness, periosteal bone apposition, and considerably worsened the trabecular bone microarchitecture. Calcium supplementation in both OVX + ECa and OVX + ICa groups elevated blood supply in the cortical bone when compared to OVX rats. Treatment with eggshell powder, unlike the OVX + ICa group, significantly lowered bone resorption, increased plasma calcium level, relative volume of trabecular bone, and secondary osteon population density, which together contributes to the enhanced bone strength. In addition, sizes of Haversian canals and secondary osteons in OVX + ECa group reached the values of SHAM group. Our results suggest that chicken eggshell powder more effectively ameliorates bone loss in ovariectomized rats than precipitated calcium carbonate.

Elevation of MicroRNA-126 Levels in Intracranial Aneurysm and Bioinformatic Analysis of Potential Molecular Mechanisms

The study is to investigation of microRNA-126 levels in patients with intracranial aneurysm and bioinformatic analysis of the molecular mechanisms involved. A total of 166 patients with ICA who were hospitalized or examined in our hospital from September 2015 to December 2017 were used as the experimental group (ICA group). This group included 120 patients with unruptured intracranial aneurysm (UICA; UICA group) and 46 patients with ruptured intracranial aneurysm (RICA); RICA group). The UICA group was further subdivided into 42 surgical groups (S group) and 78 nonsurgical groups (NS group). Sixty-three normal people without intracranial aneurysms were selected as the control group. RT-PCR was used to quantitatively detect the relative expression of microRNA- 126 in peripheral blood mononuclear cells at the time of admission and immediately after surgery. The UCSC database was used to analyze the gene locus and homology of microRNA-126. The TargetScan database and CoMeTa database were used to predict the potential target genes of microRNA-126. The DAVID database was used to enrich the function of potential target genes of microRNA-126 (GO enrichment) and KEGG pathway enrichment for analysis. The expression level of microRNA-126 in peripheral blood was significantly higher in the ICA group than in the control group (P &lt;0.01), significantly higher in the RICA group than in the UICA group (P &lt;0.05). Expression was also higher in the NS group than in the S group but the difference was nonsignificant (P &gt;0.05). A total of 15 potential target genes including ITGA6, CRK, PCDH7, and ADAM9 were identified through the target gene prediction software and GO analysis and KEGG pathway analysis showed that the function of the microRNA-126 target gene was mainly focused on protein binding and the FAS signaling pathway. In Conclusion the microRNA-126 is up-regulated in ICA patients and affects ICA by regulating multiple target genes in the FAS signaling pathway.

Anatomical study of the ventral neurovascular structures and hypoglossal canal for the surgery of the upper cervical spine

The aim of this study is to evaluate the anatomical relationship between the bony structures and ventral neurovascular structures around craniovertebral junction (CVJ).Eleven fresh-frozen cadaveric specimens were dissected around CVJ. The anatomical relationships were evaluated between C1 bony structures (midline, lateral margin of the C1 lateral mass (LM) and C1 transverse process (TP)) and ventral neurovascular structure such as ICA and HN. Morphometric evaluation of occipital condyle was also performed.The diameter of the HN and the ICA was 2.4 ± 0.5 mm and 5.1 ± 0.2 mm. The ICA was located lateral to the C1 LM in 44.4% (ICA Group 1) and in front of lateral half of the C1 LM in 55.6% (ICA Group 2). The HN was located lateral to the C1 LM in 85% (HN Group 1) and in front of lateral half of the C1 LM in 15% (HN Group 2). HN Group 2 was significantly more common in ICA Group 2 (p < 0.05, OR = 2.00, 95% CI: 1.07–3.71). There was significant correlation between ICA and HN in terms of the distance from the midline, C1 LM and TP (r = 0.67, 0.87 and 0.76 respectively, P < 0.01).In conclusion, the HN location is related with ICA location and the medially located ICA is a risk factor of the HN located ventral to the C1 LM. These results demonstrate the vulnerability of the neurovascular structures during CVJ surgery and suggest that preoperative 3D-CTA or enhanced CT scan can be useful in guiding surgical technique.

Perioperative characteristics, histological diagnosis, and outcome in cats undergoing surgical treatment of primary hyperparathyroidism.

To report perioperative characteristics, complications, histopathologic diagnosis and outcome in cats undergoing surgical treatment for primary hyperparathyroidism (PHPT). Multi-institutional, retrospective case series. Thirty-two client-owned cats. Medical records of cats treated with surgical removal of 1 or more parathyroid gland(s) with confirmed histopathologic evaluation were reviewed. Cats were divided into preoperative ionized calcium (iCa) groups corresponding to the 33rd, 67th, and 100th percentiles of the preoperative iCa results of the study population. Follow-up consisted of phone conversation with owners or primary veterinarian. Ionized calcium was above reference range in all cats (median 1.8 mmol/L [interquartile range, 1.5-1.9]). Abnormal tissue was excised after cervical exploration in all cats. The most common histopathologic diagnoses were parathyroid adenoma in 20 of 32 (62.5%) cats and parathyroid carcinoma in 7 of 32 (21.9%) cats. At discharge, 6 of 32 (18.8%) cats had hypercalcemia, 5 of 32 (15.6%) had hypocalcemia, and 21 of 32 (65.6%) were normocalcemic. Preoperative iCa did not correlate with postoperative iCa. The median follow-up time was 332 days (range, 7-3156). Overall median survival time was 1109 days (95% CI, 856-1332). Survival time was not associated with preoperative iCa group, hypocalcemia at discharge, hypercalcemia at discharge, or diagnosis of carcinoma. In this cohort of cats, parathyroid adenoma was the most common cause of PHPT, and surgical treatment resulted in very good median survival time. Preoperative iCa was not predictive of postoperative hypocalcemia. Surgical parathyroidectomy for treatment of PHPT in cats provides a favorable prognosis.

Icariin Reduces Cartilage Degeneration in a Mouse Model of Osteoarthritis and is Associated with the Changes in Expression of Indian Hedgehog and Parathyroid Hormone-Related Protein.

BackgroundThe aim of this study was to determine the role of icariin, a Chinese traditional herbal medicine extracted from Epimedium, in osteoarthritis (OA), using the murine anterior cruciate ligament transection (ACLT)-induced model of OA and micromass culture of murine chondrocytes.Material/MethodsTwenty-four three-month-old C57/6J mice were randomly divided into three groups: the sham group (no surgery and joint injection with normal saline) (N=8); the ACLT + ICA group (ACLT surgery and icariin treatment) (N=8); and the ACLT group (ACLT surgery and joint injection with normal saline) (N=8). At 12 weeks after ACLT surgery, murine articular cartilage was harvested from all mice for histological evaluation of any differences in cartilage degeneration. In vitro micromass culture of mouse chondrocytes was used to study the effects of icariin on chondrocyte differentiation and growth from the three mouse groups.ResultsIcariin treatment (mice in the ACLT + ICA group) significantly reduced degeneration of cartilage in OA with increased cartilage thickness, associated with increased expression of collagen type II alpha 1 (COL2A1), decreased chondrocyte hypertrophy, and decreased expression of collagen type X (ColX) and matrix metalloproteinase 13 (MMP13). In vitro, icariin promoted chondrocyte differentiation by upregulating the expression of agrrecan, Sox9 and parathyroid hormone-related protein (PHrP) and down-regulation of Indian hedgehog (Ihh) and genes regulated by Ihh.ConclusionsIn a mouse model of OA icariin treatment reduced destruction of cartilage, promoted chondrocyte differentiation, upregulated expression of PHrP and down-regulated the expression of Ihh.

The value of Coronary Artery computed Tomography as the first-line anatomical test for stable patients with indications for invasive angiography due to suspected Coronary Artery Disease: CAT-CAD randomized trial

BackgroundThe aim of this prospective, randomized trial was to evaluate whether the use of coronary computed tomography angiography (CCTA) as the first-line anatomical test in patients with suspected significant coronary artery disease (CAD) may reduce the number of coronary invasive angiographies (ICA), and expand the use of CCTA in patients currently diagnosed invasively. Methods120 patients (age:60.6 ± 7.9 years, 35% female) with indications to ICA were randomized 1:1 to undergo CCTA versus direct ICA. Outcomes were evaluated during the diagnostic and therapeutic periods. ResultsThe number of invasively examined patients was reduced by 64.4% in the CCTA group as compared to the direct ICA group (21vs59,p < 0.0001). The number of patients with ICAs not followed by coronary intervention was reduced by 88.1% with the CCTA strategy (5vs42,p < 0.0001). Over the diagnostic and therapeutic course there were no significant differences regarding the median volume of contrast (CCTA 80.3 ml[65.0–165.0] vs ICA 90.0 ml[55.0–100.0], p = 0.099), while a non-significant trend towards higher radiation dose in the CCTA group was observed (9.9 mSv[7.0–22.1] vs 9.4 mSv[5.2–14.0], p = 0.05). There were no acute cardiovascular events. ConclusionsCCTA may hypothetically act as an effective ‘gatekeeper’ to the catheterization laboratory in the diagnosis of stable patients with current indications for ICA. This strategy may result in non-invasive, outpatient-based triage of two thirds of individuals without actionable CAD, obviating unnecessary invasive examinations. However, the longer follow-up is indispensable. ClinicalTrials.gov numberNCT02591992

Association Between agr Type, Virulence Factors, Biofilm Formation and Antibiotic Resistance of Staphylococcus aureus Isolates From Pork Production.

Livestock-associated Staphylococcus aureus colonization and/or infections exist in pigs and people in frequent contact with pigs. In this study, a total of 130 S. aureus isolates obtained from different stages of pork production were subjected to antimicrobial susceptibility, biofilm formation, as well as PCR screening to identify virulence genes, and the accessory gene regulator alleles (agr). Among all 130 S. aureus isolates, 109 (83.8%, 109/130) isolates were positive for agr. All swine farms isolates belonged to agr IV, whereas S. aureus isolated from slaughterhouse and retail indicated diverse agr types. All isolates exhibited biofilm formation ability, and raw meat isolates (belonging to agr I) exhibited a greater ability to form strong biofilms than swine farms isolates (belonging to agr IV). agr-positive isolates were associated with more virulence genes than agr-negative isolates. Most biofilm-producing isolates were positive for microbial surface component recognizing adhesive matrix molecule (MSCRAMM), capsule type and ica group genes. The results illustrate a significant association between the prevalence rate of MSCRAMM, capsule type and ica group genes among isolates producing weak, moderate and strong biofilms. The high prevalence of resistance to ciprofloxacin, gentamicin, tetracycline, clarithromycin, clindamycin, and trimethoprim-sulfamethoxazole were mainly observed in moderate and weak biofilm producers. Our findings indicate that S. aureus isolates from pork production displayed diverse molecular ecology.

Equivocal tests after contrast stress-echocardiography compared with invasive coronary angiography or with CT angiography: CT calcium score in mildly positive tests may spare unnecessary coronary angiograms

BackgroundImaging stress tests are not ideally accurate to predict anatomically obstructive CAD, leading to a non-trivial rate of unnecessary iCA. This may depend on the threshold used to indicate iCA, and maybe CTA or, one step earlier, CT calcium score could spare most unnecessary iCA in only mildly positive cSE. We assessed the diagnostic accuracy of contrast stress-echocardiography (cSE) in comparison with invasive coronary angiography (iCA), and CT angiography (CTA) only in case of equivocal tests, to find hints helping reduce falsely positive cSE in the suspicion of coronary artery disease (CAD).MethodsPatients who were indicated cSE for suspected CAD between 2012 and 2016, who also underwent iCA were selected and diagnostic results compared. A second group, specifically with equivocal cSE who underwent CTA was also analyzed.Results137 subjects with equivocal cSE and CTA and 314 with cSE (any result) and iCA were selected. In the CTA-equivocal cSE group, an Agatston score < 105 and a coronary flow reserve (CFR-LAD) <1.7 had very high negative predictive value (99%, 92% respectively) to exclude obstructive CAD. The Agatston score was the most significant incremental predictor of CAD beyond clinical variables (chi square 31 to 47, p < 0.001). In the iCA group a more-than-mild reversible wall motion abnormality (WMA) demonstrated high positive predictive value for CAD (89%), while CFR-LAD appeared less useful. More-than-mild reversible WMA was the most significant predictor of CAD beyond clinical variables (chi square 37.5 to 56, p < 0.001).ConclusionsOur data suggest iCA should be indicated only for more-than-mild reversible WMA at cSE, due to the very high positive predictive value for CAD of this finding, while mildly positive tests should be shifted to non-invasive CT, with CTA performed only for coronary calcium Agatston score > 100, since lower scores demonstrated very high negative predictive value for CAD, not justifying proceeding to CTA and even less to iCA.

Effect of icariin on fracture healing in an ovariectomized rat model of osteoporosis.

Osteoporosis is frequently asymptomatic, presenting a significant clinical and economic burden, particularly following an osteoporosis-associated fracture. Icariin has been reported to inhibit osteoporosis in vitro, and the present study investigated whether icariin also promoted bone fracture healing in ovariectomized osteoporotic (OVX) rats in vivo. A total of 30 female rats were randomly divided into three groups (n=10 per group): i) Sham surgery; ii) OVX; and iii) OVX with icariin (OVX + ICA) groups. At 3 months after the ovariectomy, a unilateral cross-tibia fracture was made at the proximal right tibia. Animals were then sacrificed after 5 weeks of oral treatment. X-rays were taken at 1 week, 3 weeks and 5 weeks of treatment, and dual energy X-ray absorptiometry was used to measure the bone mineral density (BMD). Changes to the osteocalcin (BGLAP), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and estradiol levels in blood were measured. Callus formation and bone union were observed, the BMD was significantly higher and the BGLAP, ALP and TRAP levels were reduced, but no significant increase was observed in the blood estradiol level in the OVX + ICA group compared with the OVX group. The present findings indicate that icariin has potential as a novel alternative therapeutic agent for fracture healing in postmenopausal osteoporosis.

Abstract WP1: Evaluation of Clinical and Radiographic Variables Related to False Positive Detection of Tandem Carotid Artery Occlusion on CT Angiography

Background and purpose: CT angiography has been shown to result in up to 30% false positive detection of extracranial ICA occlusion in patients with acute ICA terminus occlusion. This may confound planning for acute endovascular intervention and cause inaccurate patient exclusion from related clinical trials of acute stroke therapy. We explored demographic, clinical variables, recanalization rates and outcomes that are associated with this radiographic artifact. Methods: Retrospective review of a prospectively maintained database of acute endovascular therapy at UPMC between 2002 and 2015. Patients with isolated terminus ICA occlusion were selected from a previously derived cohort of cases with or without pseudo-occlusion of the extracranical ICA on pre-procedural CTA (false positives and true negatives). Comparisons between these two groups were evaluated with univariate analysis. Results: We reviewed 69 cases of isolated ICA terminus occlusion. 21 patients had false-positive occlusion of the extracranial ICA (group 1) and 48 patients had adequate CTA diagnosis (true negatives, group 2). Rates of IV tPA (33% vs. 29%) and median CTA to groin puncture time (98 vs. 80 min) were similar between the two groups. Terminus ICA occlusion types were as follows: ICA-I (19% vs 6 %), ICA-L (67% vs. 56%), ICA-T (14% vs. 37%). Manual aspiration thrombectomy was used in 68% of cases in group 1 compared to 38% of cases in group 2 (P=0.03), no difference in use of recanalization devices were found. TICI 2b/3 recanalization was achieved to similar extent (42% vs. 33%). Favorable outcome (90-day modified Rankin Scale ≤ 2) was achieved in 26% vs. 40% between the two groups (P=0.52). Conclusions: Patients with acute terminus ICA occlusion who are misclassified as having tandem ICA occlusions on CTA have similar characteristics than their respective controls in this small cohort. Although future studies with larger sample sizes are needed to tease out preliminary trends, the data support the need for optimization of current screening methods for tandem ICA occlusion in the acute setting.

Evaluation of engraftment of superparamagnetic iron oxide-labeled mesenchymal stem cells using three-dimensional reconstruction of magnetic resonance imaging in photothrombotic cerebral infarction models of rats.

ObjectiveTo evaluate engraftment by visualizing the location of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) three-dimensionally in photothrombotic cerebral infarction (PTCI) models of rats.Materials and MethodsMagnetic resonance imaging (MRI) of an agarose block containing superparamagnetic iron oxide (SPIO)-labeled hBM-MSCs was performed using a 3.0-T MRI, T2-(T2WI), T2*-(T2*WI), and susceptibility-weighted images (SWI). PTCI was induced in 6 rats, and 2.5 × 105 SPIO-labeled hBM-MSCs were infused through the ipsilateral internal carotid artery (ICA group) or tail vein (IV group). MRI was performed on days 1, 3, 7, and 14 after stem cell injection. Dark signal regions were confirmed using histology. Three-dimensional MRI reconstruction was performed using the clinical workflow solution to evaluate the engraftment of hBM-MSCs. Volumetric analysis of the engraftment was also performed.ResultsThe volumes of SPIO-labeled hBM-MSCs in the phantom MRI were 129.3, 68.4, and 25.9 µL using SWI, T2*WI, and T2WI, respectively. SPIO-labeled hBM-MSCs appeared on day 1 after injection, encircling the cerebral infarction from the ventral side. Dark signal regions matched iron positive cells and human origin (positive) cells. The volume of the engraftment was larger in the ICA group on days 1, 3, and 7, after stem cell injection (p < 0.05 on SWI). SWI was the most sensitive MRI pulse sequence (p < 0.05). The volume of infarction decreased until day 14.ConclusionThe engraftment of SPIO-labeled hBM-MSCs can be visualized and evaluated three-dimensionally in PTCI models of rats. The engraftment volume was larger in the ICA group than IV group on early stage within one week.

Relationships Between Icariin and Anti-Apoptotic miRNA-21 in Mouse Blastocyst Development In vitro

In this study, the effect of icariin, a flavonoid from the Chinese traditional medicine epimedium, on miRNA-21 of mouse developmental blastocysts in vitro and the development of preimplantation embryos were studied. The possible effective targets of icariin promoting preimplantation embryo development in vitro and anti-apoptosis were determined. The embryos were cultured in modified CZB medium (mCZB) as control group. The experimental group (Ica group) was supplemented with 0.6 μg mL−1 icariin. Mouse pronuclear embryos were cultured in vitro until blastocysts. The development rates of preimplantation embryos were observed. The total cell number, apoptotic cell number and the rate of apoptotic cells in blastocysts were analysed by the staining of Hoechst33342 and labeling of TUNEL and detected under a laser confocal scanning microscope. The miRNA-21 expression, the mRNA levels of pro-apoptotic Caspase3, and the target genes of miRNA-21: pro-apoptotic PTEN, anti-apoptotic Bcl-2 were detected by real-time RT-PCR. The results showed that percentages of morulaes and blastocysts in Ica group were both extremely higher than control group ((85.14±6.57)% vs. (72.04±11.58)%; (82.50±7.11)% vs. (66.80±11.70)%, respectively, P<0.01). The total cell number of blastocysts had extreme difference between Ica group and control group ((61.40±9.64) vs. (46.23±4.50), P<0.01). The apoptotic cell number and rate of apoptotic cells of blastocysts were both reduced in Ica group ((1.47±0.51) vs. (2.94±0.66); (2.40±0.27)% vs. (6.25±0.62)%, respectively, P<0.01). Compared to control group, addition of icariin into mCZB extremely increased the expression of anti-apoptotic miRNA-21 (P<0.01), down-regulated pro-apoptotic Caspase3 (P<0.05) and PTEN (P<0.01), up-regulated anti-apoptotic Bcl-2 (P<0.01). In conclusion, icariin could reduce the apoptosis, promote the embryo development in vitro by enhancing miRNA-21 expression to up-regulated anti-apoptotic genes and down-regulated pro-apoptotic genes. These apoptosis-related genes were regulated by miRNA-21.

Abstract WP207: Serum Urate As A Potential Risk Factor For Intracranial Atherosclerotic Disease

Introduction While serum urate is associated with cardiovascular disease, the relationship between serum urate and cerebrovascular atherosclerotic diseases remains controversial. Intracranial atherosclerotic disease (ICAD) is more prone to affect Asian population and the most common cause of ischemic stroke in China. There are few studies observed the associations between serum urate and ICAD. Hypothesis We assessed the hypothesis that elevated serum urate level is associated with intracranial atherosclerotic disease and serum urate is a potential risk factor for intracranial atherosclerotic disease. Methods Clinical data of 411 patients undergoing cerebral angiography were analyzed, and they were separated into groups according to the findings of cerebral angiography: Extracranial cerebral artery atherosclerosis (ECAA) group included 115 patients had at least one of extracranial carotid or vertebral arteries was stenosised beyond 50%; intracranial atherosclerotic disease(ICAD) group included 173 patients had at least one of intracranial large artery was stenosised beyond 50%; control group included 123 patients had none cerebral large artery stenosis. The relationship between serum urate level and ICAD was explored. Results The mean serum urate level of ICA group(345.50±95.83μmol/L) and ECCA group(337.71±98.72μmol/L) are significantly higher than control group(298.21±83.85μmol/L, P &lt;0.01), and the ICAD group had a markedly higher rate of patients that had abnormal serum urate level than control group (the proportion of patients that serum urate level above 420μmol/L in ICAD and control group is 23.4% and 11% respectively, P &lt;0.05). The proportion of ICAD patients increased significantly with the raise of serum urate level (we divided all the patients into 4 groups according to the quartiles of serum urate level, the proportion of ICAD patients of each group is 31.9%, 36.2%, 47.1% and 52.9% respectively, χ 2 = 7.898 , P =0.048). Logistic regression analysis shows that serum urate level is one of the independent risk factors of ICAD (OR=1.0007, 95%CI:1.003-1.011, P &lt;0.05). Conclusion The elevated serum urate level is correlate with ICAD and is a underlying independent risk factors of ICAD.

Intravenous Tissue Plasminogen Activator Thrombolysis in Patients without Major Arterial Occlusion Seems to Be Safe and Effective

Background: It is not clear whether tissue plasminogen activator (t-PA) thrombolysis in patients without major arterial occlusion is effective or safe. Methods: Consecutive anterior circulation stroke patients treated with t-PA within 3 h of onset were studied. The patients were divided into three groups according to magnetic resonance angiography findings before t-PA infusion: ICA group, ICA occlusion; MCA group, M1 and M2 occlusion, and no occlusion group. Clinical characteristics, the presence of hemorrhagic transformation on T₂* at 24 h after t-PA thrombolysis, and outcome at 3 months were compared among the three groups. Results: 112 patients were enrolled. The no occlusion group had 21 (18.8%) patients, the ICA group had 29 (25.9%), and the MCA group had 62 (55.4%). The frequency of hemorrhagic transformation was only 4.8% in the no occlusion group (31.0% for the ICA group, and 48.4% for the MCA group, p = 0.0012). At 3 months after t-PA therapy, 61.5% of the no occlusion group had a favorable outcome (modified Rankin score 0–1), which was the highest among the three groups (15.0% for the ICA group, and 41.5% for the MCA group, p = 0.0203). Conclusion: Intravenous t-PA therapy in acute stroke patients without major artery occlusion seems to be safe and effective.