FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer.

FMS-like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co-altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co-alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non-FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.

A Comparison of Outcomes Based on Vessel Type (Native Artery vs. Bypass Graft) and Artery Location (Below-Knee Artery vs. Non-Below-Knee Artery) Using a Combination of Multiple Endovascular Techniques for Acute Lower Limb Ischemia.

BACKGROUND: To evaluate outcomes of endovascular treatment (EVT) using a combination of multiple endovascular techniques for acute lower limb ischemia (ALLI) and to compare outcomes based on vessel type and artery location. METHODS: A total of 95 consecutive patients with ALLI (mean age, 72.0 years; 65 males; 104 lower limbs) who received emergency EVT using a combination of multiple endovascular techniques including thrombolysis, aspiration thrombectomy, stenting, and balloon angioplasty with or without surgical thromboembolectomy, between January 2005 and December 2017 were included. Vessel type was classified into native artery occlusion (native occlusion) and bypass graft occlusion (graft occlusion), including prosthetic and vein graft. Additionally, native arteries were categorized into below-knee occlusion and non-below-knee occlusion. Technical success, perioperative death (POD), ALLI-related death, amputation, amputation-free survival (AFS), and complications were compared according to vessel type (native occlusion vs. graft occlusion) and artery location (below-knee occlusion vs. non-below-knee occlusion). RESULTS: Of all patients with ALLI, 16.8% underwent a single endovascular technique, whereas 83.2% underwent a combination of multiple endovascular techniques. The technicalsuccess, POD, and ALLI-related death rates in the total number of patients were 94.7%, 11.6%, and 4.2%, respectively. A total of 67 patients (75 limbs) and 28 patients (29 limbs) were classified as having native occlusion and graft occlusion (prosthetic, 24 limbs; vein, 5 limbs), respectively. No significant differences in technical success (native occlusion: 92.5% vs. graft occlusion: 100%), POD (14.9% vs. 3.6%), and ALLI-related death (6.0% vs. 0%) were noted between native occlusion and graft occlusion. However, the 30-day AFS rate of native occlusion was significantly lower than that of graft occlusion (75.2% vs. 96.3%, P=0.01). The amputation rate (P=0.03) and AFS rate (P=0.03) of below-knee occlusion were significantly worse for below-knee occlusion patients than for non-below-knee occlusion patients. CONCLUSIONS: EVT using multiple endovascular techniques for ALLI is effective and safe. A combination of multiple endovascular techniques is crucial for successful treatment. However, native occlusion may have a lower AFS rate than graft occlusion, and below-knee occlusion may have a higher risk of amputation than non-below-knee occlusion.

An Extremely Rare Complication: Abdominal Aortic Aneurysm Rupture Caused by Migration of a Zenith Main Body Years After Repair of the Suprarenal Stent Separation.

PURPOSE: To report an unusual case of an abdominal aortic aneurysm (AAA) rupture caused by migration of a Zenith stent-graft main body years after its separation from the suprarenal stent. CASE REPORT: A 72-year-old man underwent endovascular aneurysm repair with a Zenith stent-graft for an infrarenal AAA in year 2000. At that time, a femorofemoral bypass was performed because the left external iliac and common femoral arteries were dissected during treatment. In 2013, follow-up computed tomography (CT) showed disconnection of the uncovered proximal stent, which led to a type Ia endoleak. An additional Zenith main body and Large Palmaz XL balloon-expandable stent were deployed; the endoleak disappeared. In 2016, the patient had abdominal pain, and emergency CT showed AAA rupture caused by migration of the first main body deployed in 2000 under the distal edge of the contralateral (left) leg of the additional main body from 2013, which led to a type IIIa endoleak between the 2 main bodies. A converter and iliac legs were deployed to successfully seal the type IIIa endoleak. The patient remains well 18 months after the second repair; CT scans document stable stent-grafts and no endoleak. CONCLUSION: Physicians should be aware of the potential risk for AAA rupture caused by late main body migration after treatment for suprarenal stent separation from a Zenith stent-graft.

Feasibility study of cancer genome alterations identified by next generation sequencing: ABC study.

BACKGROUND: To confirm the feasibility and explore the clinical applicability of amplicon sequencing by next generation sequencing (NGS) of biopsy samples from patients with advanced solid tumors, we conducted a prospective study. METHODS: Patients with unresectable, advanced, or recurrent solid tumors were included. Key eligibility criteria were as follows: 20 years or older, any planned systemic therapy, adequate lesion for biopsy, and written informed consent. Samples were fixed in 10% buffered formalin and embedded in paraffin. Cancer-derived DNA was extracted, and amplicon sequencing was performed using Ion AmpliseqTM Cancer Hotspot Panel version 1.0 or version 2.0 by central vendor. We evaluated the success rate of sequencing, and the proportion of the patients with actionable mutations. We organized an expert panel to share the results of targeted sequence, make annotations and reports, and discuss concomitant ethical/legal/social issues. RESULTS: A total of 232 patients were included, and 208 were successfully analyzed (success rate of 89.7%). The biopsy procedures were safe, with only one case of Grade 3 vasovagal reaction. The proportion of actionable/druggable mutations was 38.9% (81/208), which was not significantly different between the cancer panel version 1.0 and version 2.0 (P = 0.476). Expert panel could discuss the findings and make sufficient reports. CONCLUSIONS: We confirmed the feasibility of NGS-based amplicon sequencing using biopsy samples, making the basis for nationwide genome screening for cancer patients using biopsy samples. Our results suggest that focused panel may be sufficient to detect major mutations.

Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery.

OBJECTIVES: To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. METHODS: Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. RESULTS: In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. CONCLUSIONS: Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. KEY POINTS: • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.

Appropriate Relevancy and Reliability of Real-World Data for the Utilization of Regulatory Submission.

The extraction of data that contribute to regulatory approval from real-world data (RWD) is difficult because of the lack of a standardized data format and extraction methodology. Additionally, when real-world evidence (RWE) is used as an external control group, the similarity between internal and external control data is not evaluated. To investigate the data extraction methodology for the external control data of rare molecular subtypes, we have initiated the "REALISE" study. In this study, we aim to elucidate the "relevance" and "reliability" of RWD/RWE necessary for regulatory approval. As most databases are not designed for regulatory use in the creation phase, we will investigate retrospective methodologies to ensure RWD/RWE reliability. This study will compare the "relevance" and "reliability" of the ARCAD global database, SCRUM-Japan Registry, SCRUM-Japan observational study, and Flatiron Health RWD, and statistically analyze the differences and similarities among the four databases. We will also examine the methodology for extracting sufficiently relevant data from the SCRUM-Japan observational study. Additionally, if the reliability of the RWD/RWE does not reach the required level for regulatory approval, we will examine the methodologies to ensure the "reliability" of the SCRUM-Japan observational study for regulatory approval. The obtained results will be submitted to the "Consultation for Development of Registry" in the Pharmaceuticals and Medical Devices Agency, and we will discuss the standard methodology. The procedures and findings identified in the REALISE study will be organized from the perspectives of "database construction," "data analysis," and "outcome evaluation" and will be issued as "the draft guidelines."

Trajectory for the Regulatory Approval of a Combination of Pertuzumab Plus Trastuzumab for Pre-treated HER2-positive Metastatic Colorectal Cancer Using Real-world Data.

Utilizing real-world data (RWD) for effective clinical implementation is becoming more and more appealing as the cost of drug development rises, especially for patients with rare diseases and rare molecular subtypes for whom conducting randomized controlled trials is challenging. If a regulatory approval methodology based on RWD as an external control group can be established, drug development for rarer fractions can be accelerated by lowering costs and time, as well as reducing physical and emotional burdens on both patients and healthcare professionals. Since 2017, we have been prospectively collecting the clinical data of standard therapies in patients with rare molecular fractions under the SCRUM-Japan Registry platform, which is a qualified registry utilized as external control data for regulatory submission. Based on the results of the phase II TRIUMPH study (UMIN000027887) and the extracted data from the SCRUM-Japan Registry, the pharmaceutical company submitted an application for pertuzumab and trastuzumab in patients with HER2-positive metastatic colorectal cancer in April 2021. Pertuzumab and trastuzumab were approved as expanded indications on March 28, 2022, as 6 cases out of 14 extracted from the SCRUM-Japan Registry were classified and utilized as "evaluation material" under the review process of the Pharmaceuticals and Medical Devices Agency (PMDA). Through the TRIUMPH study and the SCRUM-Japan Registry, we have paved the way for regulatory approval of RWD in Japan. In future, we must define the steps for constructing regulatory-grade registries and the method/process for utilizing RWD by accumulating case experiences.

Efficacy of Targeted Trials and Signaling Pathway Landscape in Advanced Gastrointestinal Cancers From SCRUM-Japan GI-SCREEN: A Nationwide Genomic Profiling Program.

PURPOSE: Genomic profiling programs have been implemented to apply next-generation sequencing (NGS) for facilitating trial enrollment. SCRUM-Japan GI-SCREEN is a large-scale genomic profiling program in advanced gastrointestinal cancers using a validated genomic assay with the goal of facilitating enrollment in targeted clinical trials, generating real-world data, and performing clinicogenomic analysis for biomarker discovery. PATIENTS AND METHODS: Genotyping of tumor tissue samples from 5,743 patients with advanced gastrointestinal cancers enrolled in GI-SCREEN was centrally performed with NGS. Patients were enrolled in matched trials of targeted agents affiliated with GI-SCREEN on the basis of genotyping results. RESULTS: A total of 11 gastrointestinal cancers were included, with colorectal cancer being the most common. The median age ranged from 59 to 70.5 years across cancer types. Patients enrolled after initiation of first-line treatment had significantly longer overall survival (OS) than that before treatment initiation with a median survival time difference of 8.9 months and a hazard ratio (HR) ranging from 0.25 to 0.73 across cancer types, demonstrating an immortal time bias. One hundred and forty-nine patients received matched therapies in clinical trials on the basis of their identified alterations. Among patients with colorectal cancer harboring actionable alterations, the median OS was significantly longer in patients who received matched therapies in trials than in those who did not (HR, 0.52; 95% CI, 0.26 to 1.01; P = .049). Cancer-specific pathway alterations were significantly associated with shorter survival and related to primary resistance to matched trial therapies. CONCLUSION: Our genomic profiling program led to patient enrollment in targeted clinical trials and improved survival of patients with colorectal cancer who received matched therapies in clinical trials. To avoid immortal time bias, precautions are needed when using data from patients who have undergone NGS testing after initiation of the evaluated treatment line.

Successful embolization of an intrahepatic portosystemic shunt using balloon-occluded retrograde transvenous obliteration: A case report.

BACKGROUND: A congenital intrahepatic portosystemic shunt (IPSVS) is a rare vascular abnormality that is characterized by an anomalous intrahepatic venous tract that connects the intrahepatic portal vein with the hepatic venous system. Hepatic encephalopathy is an indication for IPSVS embolization, which is technically challenging because rapid blood flow through shunts can induce the migration of embolization material to systemic veins. This case report discusses the efficacy of percutaneous balloon-occluded retrograde transvenous obliteration for treating patients with IPSVSs. CASE SUMMARY: A 75-year-old woman presented with a six-month history of repeated hepatic encephalopathy due to an IPSVS without liver cirrhosis. We successfully embolized the IPSVS using percutaneous balloon-occluded retrograde transvenous obliteration with interlocking detachable coils. After the procedure, the patient exhibited no symptoms of hepatic encephalopathy for 14 mo. CONCLUSION: Balloon-occluded retrograde transvenous obliteration with detachable coils can be effective for the endovascular treatment of an IPSVS.

Balloon-assisted Transcatheter arterial embolization using N-butyl cyanoacrylate for iatrogenic arterial bleeding by groin puncture: a new technology.

BACKGROUND: Balloon-assisted transcatheter arterial embolization (TAE) using n-butyl cyanoacrylate (NBCA) and lipiodol (Lp) mixture is a new endovascular treatment technique for iatrogenic arterial bleeding by groin puncture. It is less invasive compared to surgical repair, and NBCA migration into the circulation can be prevented by temporary balloon occlusion of the parent artery without ultrasound-guidance. This study aimed to report on the technical aspects and evaluate the efficacy and safety of fluoroscopically guided balloon-assisted transcatheter arterial embolization using NBCA for iatrogenic arterial bleeding by groin puncture. MATERIALS AND METHODS: The study included five patients (mean age 54.6 years; 3 male and 2 female) with iatrogenic arterial bleeding by groin puncture. We performed transcatheter arterial embolization using NBCA while occluding the responsible artery with a balloon catheter during the embolization to prevent NBCA migration. Two sheaths were inserted into the common femoral artery. A microcatheter was advanced into the pseudoaneurysm or extravasation via the contralateral sheath. A balloon catheter was advanced into the responsible artery until the balloon portion covered the leakage site via another sheath. After balloon inflation, the NBCA and Lip mixture was slowly injected until the pseudoaneurysm, or the extravasation was filled without touching the balloon. The microcatheter was removed immediately after the filling. We assessed technical success, overall success, and complications. RESULTS: The injured arteries were the external iliac artery (n = 1), the common femoral artery (n = 2), and the proximal portion of the superficial femoral artery (n = 2). NBCA was injected once in four cases and twice in one case where complete hemostasis could not be achieved with one injection. The technical and overall success rate was 100% with no complications, including distal embolization of NBCA. CONCLUSIONS: Balloon-assisted TAE using NBCA is a feasible, effective, and safe treatment for iatrogenic arterial bleeding by groin puncture. It may also be applicable in other arterial bleeding situations where the potential risk of distal embolization can be decreased by applying the balloon-assisted technique.

Idiopathic Orbital Inflammation Appearing on the Affected Side of Preceding Myasthenia Gravis.

The patient was a 70-year-old man with idiopathic orbital inflammation (IOI) that appeared on the severely affected side of preceding myasthenia gravis (MG). The patient was diagnosed with MG 5 years prior to the onset of IOI. When IOI was diagnosed, an edrophonium test was negative. IOI was considered because he complained of left orbital pain, eyelid swelling, and cerebral MRI exhibited the enhanced lesions along the left orbital periosteum. A biopsy specimen revealed pathological findings compatible with IOI. The administration of corticosteroids was effective for improving the ocular symptoms. IOI should be considered when ocular symptoms deteriorated with soft tissue swelling/pain in MG patients.

Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies.

Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients.

Epidemiology of Adverse Events and Medical Errors in the Care of Cardiology Patients.

OBJECTIVES: There have been epidemiological studies of adverse events (AEs) among general patients but those of patients cared by cardiologist are not well scrutinized. We investigated the occurrence of AEs and medical errors (MEs) among adult patients with cardiology in Japan. METHODS: We conducted a cross-sectional study of adult outpatients at a Japanese teaching hospital from February through November 2006. We measured AE and ME incidents from patient report, which were verified by medical records, laboratory data, incident reports, and prescription queries. Two independent physicians reviewed the incidents to determine whether they were AEs or MEs and to assess severity and symptoms. RESULTS: We identified 144 AEs and 30 MEs (16.3 and 3.9 per 100 patients, respectively). Of the 144 AEs, 99 were solely adverse drug events (ADEs), 20 were solely non-ADEs, and the remaining 25 were both causes. The most frequent symptoms of ADEs were skin and allergic reactions due to medication. The most frequent symptoms of non-ADEs were bleeding due to therapeutic interventions. Among AEs, 12% was life threatening. Life-threatening AEs were 25% of non-ADEs and 5% of ADEs (P = 0.0003). Among the 30 MEs, 21MEs (70%) were associated with drugs. CONCLUSIONS: Adverse events were common among cardiology patients. Adverse drug events were the most frequent AEs, and non-ADEs were more critical than ADEs. Such data should be recognized among practicing physicians to improve the patients' outcomes.

Endovascular Treatment Strategy Using Catheter-Directed Thrombolysis, Percutaneous Aspiration Thromboembolectomy, and Angioplasty for Acute Upper Limb Ischemia.

PURPOSE: To evaluate the usefulness and safety of endovascular treatments for acute upper limb ischemia (AULI) by using multiple techniques, and to compare catheter-directed thrombolysis (CDT) and percutaneous aspiration thromboembolectomy (PAT) as initial procedures. MATERIALS AND METHODS: The study included 18 patients (4 men and 14 women) with AULI, who underwent a total of 20 sessions of endovascular treatment using various endovascular techniques between January 2005 and April 2016. The patients were initially treated with CDT [n = 9, CDT-based group (C-G)], PAT [n = 6, PAT-based group (P-G)], or angioplasty (n = 3). In case of residual emboli, we performed additional endovascular techniques. We assessed technical success, clinical success, and complications. Additionally, we compared the urokinase dosage between the groups. RESULTS: The mean patient age was 74.4 years. Technical and clinical success was obtained in all patients. Among the 18 patients, 1 underwent CDT only, 2 underwent PAT only, 1 underwent angioplasty only, and 14 underwent multiple techniques. Two patients from the C-G experienced major complications (cerebellar hemorrhage 1; pseudo-aneurysm in a branch of the ulnar artery 1). The mean urokinase dosage was lower in the P-G than in the C-G (40,000 vs. 246,667 IU; Mann-Whitney U test, P = 0.004). CONCLUSION: Endovascular treatment is effective and safe for AULI. A combination of multiple endovascular techniques is important for successful treatment. PAT is suggested as an initial procedure among endovascular techniques, in terms of a lower dosage of urokinase and a lower complication rate. LEVEL OF EVIDENCE: IV, Case-control studies.

Evaluation of the relationship between hepatocellular carcinoma location and transarterial chemoembolization efficacy.

AIM: To evaluate the relationship between the location of hepatocellular carcinoma (HCC) and the efficacy of transarterial chemoembolization (TACE). METHODS: We evaluated 115 patients (127 nodules), excluding recurrent nodules, treated with TACE between January 2011 and June 2014. TACE efficacy was evaluated according to mRECIST. The HCC location coefficient was calculated as the distance from the central portal portion to the HCC center (mm)/liver diameter (mm) on multiplanar reconstruction images rendered (MPR) to visualize bifurcation of the right and left branches of the portal vein and HCC center. The HCC location coefficient was compared between complete response (CR) and non-CR groups in Child-Pugh grade A and B patients. RESULTS: The median location coefficient of HCC among all nodules, the right lobe, and the medial segment was significantly higher in the CR group than in the non-CR group in the Child-Pugh grade A patients (0.82 vs 0.62, P < 0.001; 0.71 vs 0.59, P < 0.01; 0.81 vs 0.49, P < 0.05, respectively). However, there was no significant difference in the median location coefficient of the HCC in the lateral segment between in the CR and in the non-CR groups (0.67 vs 0.65, P > 0.05). On the other hand, in the Child-Pugh grade B patients, the HCC median location coefficient in each lobe and segment was not significantly different between in the CR and in the non-CR groups. CONCLUSION: Improved TACE efficacy may be obtained for HCC in the peripheral zone of the right lobe and the medial segment in Child-Pugh grade A patients.

Combination Therapy of Interventional Radiology and Surgery for Infarction of the Small Intestine Caused by Portal Vein and Mesenteric Vein Thrombosis: A Patient Report.

We report the case of a man in his 70s who suffered from intestinal infarction caused by acute portal vein and mesenteric vein thrombosis (PVMVT). Combination therapy with percutaneous transcatheter thrombectomy and surgical bowel resection was successfully performed, and a satisfactory outcome was achieved. Intestinal infarction caused by PVMVT can be fatal and has a high mortality rate even if surgical resection is performed. The combination therapy of interventional radiology and surgery might be a safe and effective method for patients with this life-threatening condition.

Anatomical relationship between the common carotid artery and the internal jugular vein during head rotation.

This study investigated the anatomical relationship between the common carotid artery and internal jugular vein during head rotation for the effective performance of percutaneous transjugular procedures. The subjects included 30 volunteers who had never undergone internal jugular vein cannulation. In the supine position, two-dimensional ultrasonographic images of the right internal jugular vein and common carotid artery were obtained, 2 and 4 cm above the clavicle, along the lateral border of the sternal head of the sternocleidomastoid muscle. Ultrasonographic images were examined for head rotation at 0°, 15°, 30°, 45°, 60°, and 75° from the midline to the left. The percentage of overlap of the common carotid artery by the internal jugular vein and the flattening of the internal jugular vein at each head rotation position were measured and evaluated. The overlap of the common carotid artery by the internal jugular vein significantly increased at ≥45° of head rotation 2 cm above the clavicle (P < 0.01) and at ≥30° of head rotation 4 cm above the clavicle (P < 0.01), compared with that observed in the neutral position. The flattening of the internal jugular vein significantly decreased at ≥45° of head rotation 2 cm above the clavicle (P < 0.01) and at ≥30° of head rotation 4 cm above the clavicle (P < 0.01). Head rotation should be kept to <45° at 2 cm above the clavicle and <30° at 4 cm above the clavicle to decrease the risk of accidental puncture of the common carotid artery during internal jugular vein puncture. Moreover, flattening of the internal jugular vein gradually decreases during head rotation to the side.

Anemia and the risk of contrast-induced nephropathy in patients with renal insufficiency undergoing contrast-enhanced MDCT.

PURPOSE: The purpose of this study was to assess the effect of anemia on the incidence of contrast-induced nephropathy (CIN) in patients with renal impairment undergoing MDCT. MATERIALS AND METHODS: Institutional review board approval was waived for this retrospective review of 843 patients with stable renal insufficiency (eGFR between 15 and 60 mL/min) who had undergone contrast-enhanced MDCT. Baseline hematocrit and hemoglobin values were measured. Serum creatinine (SCr) was assessed at the baseline and at 48-72 h after contrast administration. RESULTS: The overall incidence of CIN in the patient population with renal insufficiency was 6.9%. CIN developed in 7.8% (54 of 695) of anemic patients, and in 2.8% (4 of 148) of non-anemic patients (P=.027). After adjustment for confounders, low hemoglobin and low hematocrit values remained independent predictors of CIN (odds ratio 4.6, 95% CI 1.0-20.5, P=.046). CONCLUSIONS: Anemia is associated with a higher incidence of CIN in patients with renal insufficiency. Anemia is a potentially modifiable risk factor for CIN, and has an unfavorable impact on prognosis in patients with renal insufficiency undergoing contrast-enhanced MDCT.

Calcification of aortic smooth muscle cells isolated from spontaneously hypertensive rats.

Although hypertension and vascular calcification are well established as important risk factors for several cardiovascular diseases, the relationship between them is unknown. Here, we investigated whether hypertension is relevant to vascular calcification by examining aortic smooth muscle cells (SMCs) isolated from the descending thoracic aortas of Wistar Kyoto rats (WKY) as normotensive rats and spontaneously hypertensive rats (SHR), a typical rat model of hypertension. Cells were cultured in DMEM containing 10% FBS for 6 days after reaching confluence. Von Kossa staining revealed that the positively stained calcified area of aortic SMCs from SHR increased rapidly compared to that from WKY. The gene expressions of calcification-regulating proteins including msh homeobox homolog 2, Osterix (a master transcription factor for osteogenesis), and alkaline phosphatase (ALP) (a marker of vascular calcification) were significantly increased in aortic SMCs from SHR compared to SMCs from WKY. On the other hand, Runx2, another osteogenic transcription factor, did not upregulate. Furthermore, we confirmed that ALP activity was strongly increased in aortic SMCs from SHR compared to SMCs from WKY. These results suggest that aortic SMCs from SHR tend to become easily calcified via an Msx2-Osterix signaling pathway.

Role of corticotropin-releasing factor receptor type 2 beta in urocortin-induced vasodilation of rat aortas.

Urocortin has a high affinity for the corticotropin-releasing factor receptor type 2beta (CRF-R2beta). This study was conducted to reveal the role of CRF-R2beta in blood vessels. CRF-R2beta expressions were detected both in smooth muscle and endothelium from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) aortas, and there was no significant difference between them. Urocortin reduced phenylephrine-induced contraction of aorta with endothelium dose-dependently in both rats. However, deendothelialization significantly but not completely (about 50%) reduced the vasodilation. The reduction of vasodilatory action of urocortin by deendothelialization was age-dependent in SHR. An adenylyl cyclase inhibitor, SQ22536, significantly inhibited urocortin-induced relaxation in denuded WKY and SHR aortas, while in preparations with endothelium, neither SQ22536 nor L-NMMA reduced the relaxation. However, simultaneous addition of both drugs significantly reduced the relaxation. In contrast to young rats (7-week-old), in aged rats (19-week-old), L-NMMA successfully reduced urocortin-induced relaxation of aorta with endothelium. These results suggest that urocortin relaxes aorta at least partly via two signal pathways, that is, an increase in intracellular cAMP by binding to CRF-R2beta expressed in smooth muscle cells and NO production from endothelium evoked by binding to the receptors expressed in endothelium and that aging increases the role of the latter system.