Acute invasive fungal rhinosinusitis: MR imaging features and their impact on prognosis.

PURPOSE: Acute invasive fungal rhinosinusitis (AIFRS) is a life-threatening disease that is difficult to diagnose. Its overall imaging features have not been evaluated and the prognostic impact is unclear. The purpose of our study was to present MR imaging features and their impact on prognosis of AIFRS. METHODS: MR images and clinical records of 23 patients with AIFRS were retrospectively evaluated to identify the imaging features and to determine the factors affecting patients' survival. A multivariable Cox proportional hazard model was used to estimate the hazard ratio of the prognostic factors, and Kaplan-Meier survival curves were compared by using a log-rank test. RESULTS: All cases showed extra-sinonasal involvement and the orbit was the most common (65.2%, 15/23) location. The lesion enhancement pattern was classified into lack of contrast enhancement (LoCE) (47.8%, 11/23) and homogeneous (34.8%, 8/23) and heterogeneous (17.4%, 4/23) enhancement. Although LoCE showed variable signal intensity (SI), homogeneously or heterogeneously enhancing lesions showed exclusively low SI (100%, 12/12) on T2WI. Among various clinical and imaging factors, LoCE was correlated with coagulation necrosis, probably provoked by numerous fungal hyphae, and was found to be a sole independent prognostic factor for disease-specific mortality (hazard ratio = 16.819; 95% CI, 1.646-171.841, p = 0.017). In addition, patients with LoCE showed worse survival than patients without LoCE (p = 0.008). CONCLUSION: AIFRS showed frequent extra-sinonasal involvement and variable MR enhancement patterns. An enhancement pattern of LoCE was seen in about half of the cases and was a unique prognostic factor among the various clinico-radiologic factors.

Evaluation of a multi-kinase inhibitor KRC-108 as an anti-tumor agent in vitro and in vivo.

Kinases have been studied as potential cancer targets because they play important roles in the cellular signaling of tumors. A number of small molecules targeting kinases are prescribed in clinics and many kinase inhibitors are being evaluated in the clinical phase. Previously, we discovered a series of aminopyridines substituted with benzoxazole as orally active c-Met kinase inhibitors. One of the compounds, KRC-108, has been evaluated as an anti-cancer agent in vitro and in vivo. A kinase panel assay exhibited that KRC-108 is a potent inhibitor of Ron, Flt3 and TrkA as well as c-Met. Moreover, KRC-108 inhibited oncogenic c-Met M1250T and Y1230D more strongly than wild type c-Met. The anti-proliferative activity of KRC-108 was measured by performing a cytotoxicity assay on a panel of cancer cell lines. The GI(50) values (i.e., 50% inhibition of cell growth) for KRC-108 ranged from 0.01 to 4.22 µM for these cancer cell lines. KRC-108 was also effective for the inhibition of tumor growth in human HT29 colorectal cancer and NCI-H441 lung cancer xenograft models in athymic BALB/c nu/nu mice. This molecule should serve as a useful lead for inhibitors targeting kinases and may lead to new therapeutics for the treatment of cancer.

Synthesis and structure-activity relationship of aminopyridines with substituted benzoxazoles as c-Met kinase inhibitors.

A series of hydroxybenzoxazole derivatives was synthesized, and their c-Met kinase inhibitory activity was evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent benzoxazole scaffold, with particular focus on the hydroxyl substituent of the benzoxazole moiety.

Histopathology and surgical outcome of symptomatic treatment-related changes after gamma knife radiosurgery in patients with brain metastases.

A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI). Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD-PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRC-RN (4.06 cm3, p = 0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD-PD group (median 8.77 months, p = 0.004). Progression-free survival was significantly different among the three groups (p < 0.001), but not between TRC-RN and TRC-PD (post hoc test, p = 1.00), while no difference was observed in overall survival (p = 0.067). Brain metastases featured as TRCs after SRS frequently contained viable tumor cells. However, this histologic heterogeneity had a minor impact on benign local prognosis of TRCs after surgical resection.

Design and synthesis of triazolopyridazines substituted with methylisoquinolinone as selective c-Met kinase inhibitors.

A series of triazolopyridazines substituted with methylisoquinolinone were designed and synthesized. Some of the triazolopyridazines strongly inhibited c-Met kinase and showed good anti-proliferative activity against a panel of c-Met-amplified gastric cancer cell lines (MKN-45, SNU-5 and Hs746T).

(S)-[5-Methyl-3-(3-methyl-thio-phen-2-yl)-4,5-dihydro-isoxazol-5-yl]methanol.

In the title compound, C(10)H(13)NO(2)S, the thio-phene and isoxazoline rings are almost coplanar, the dihedral angle between their least-squares planes being 2.08 (1)°. The O-H atoms of the methyl hy-droxy group and the N atom of the isoxazole ring are orientated in the same direction to allow for the formation of inter-molecular O-H⋯N hydrogen bonds that lead to a supra-molecular chain along the a axis.

Direct cardiac rupture associated with sternal fracture following blunt trauma: A report of two case.

Traumatic cardiac injury is not rare. Especially cardiac contusion with sternal fracture due to blunt trauma in common. But cardiac rupture due to direct injury from fractured sternum in very rare. There were two case of cardiac injury supposed to be due to direct injury from fractured sternum. We operated immediately, so we could save these patients. Our cases show that it's rare but blunt trauma could make sternum fracture with direct injury to right side heart.

Expandability of Cephalic Veins after Brachial Plexus Block in Arteriovenous Fistula Formation for Hemodialysis.

BACKGROUND: Arteriovenous fistula (AVF) for hemodialysis is essential for patients with end-stage renal disease. However, it is difficult to maintain AVF reliably. It is vitally important to select proper blood vessels for AVF formation. In a previous study, a minimum diameter of 3 mm for the autologous vein was proposed. However, patients who did not meet the minimum vascular diameter before anesthesia, but fulfilled other criteria, showed satisfactory venous dilatation after brachial plexus block (BPB). This study investigated the extent of vein expansion by BPB and the surgical outcomes of dilated veins after BPB. METHODS: Sixty-one patients who underwent AVF formation using an autologous vein between August 2018 and December 2019 were included in the study. The clinical characteristics of the patient groups, hemodynamic parameters including the diameter of blood vessels before and after BPB, and complications were investigated. Based on the venous diameter measured by sonography before anesthesia, patients were divided into group A (26 patients) and group B (35 patients), with venous diameters <3 mm and ≥3 mm, respectively. RESULTS: The venous diameter expanded after anesthesia by 41% overall, by 62% in group A, and by 25% in group B. This difference between groups A and B was statistically significant (p=0.001). No other variables showed statistically significant differences. CONCLUSION: Sufficient venous dilatation was observed after BPB. Therefore, if the vein is sufficiently dilated after BPB, even in patients with a pre-anesthesia venous diameter <3 mm, surgery may still be performed with an expected desirable outcome.

Discovery of aminopyridines substituted with benzoxazole as orally active c-Met kinase inhibitors.

We report the synthesis and biological evaluation of aminopyridines substituted with benzoxazole. The SAR of the aminopyridines was explored to improve the inhibitory activity against c-Met and to decrease hERG affinity. These studies led to the discovery of amide 24 which showed good c-Met inhibitory potency, low affinity to hERG and favorable pharmacokinetic properties in rats.

Localized Pretibial Varicose Vein Caused by an Intraosseous Venous Anomaly.

A 36-year-old man presented to the hospital with protruding blood vessels in his left lower leg accompanied by cramping. An ultrasonographic examination of the leg revealed focal reflux without truncal vein reflux. During phlebectomy, the varix was found to be connected to the intraosseous vein through a tibial opening. Postoperative computed tomography and magnetic resonance imaging showed an osteolytic lesion in the tibial shaft and an intraosseous vascular anomaly. The patient was discharged without complications and scheduled for periodic follow-ups. This young man's varicose vein seemed to be from a tibial intraosseous vascular anomaly, which is extremely rare.

Resuscitative endovascular balloon occlusion of the aorta for retroperitoneal hemorrhage and shock after ipsilateral antegrade angioplasty with vascular closure device.

Percutaneous intervention is widely used to treat peripheral vascular disease. Ipsilateral antegrade femoral arterial access for femoropopliteal disease provides a mechanical advantage with regard to wire and stent control; however, it is associated with vascular complications and significant morbidity and mortality secondary to retroperitoneal hemorrhage from a high puncture site or vascular closure device (VCD) failure. Currently, resuscitative endovascular balloon occlusion of the aorta (REBOA) is performed as damage control surgery in patients with non-compressible torso hemorrhage. We describe a patient with hemorrhagic shock secondary to VCD failure, who was successfully treated by REBOA as damage control surgery. To our knowledge, this is the first reported case in the English literature of successful REBOA in a patient with hemorrhagic shock secondary to VCD failure.

Clinical Outcomes of Arteriovenous Graft in End-Stage Renal Disease Patients with an Unsuitable Cephalic Vein for Hemodialysis Access.

BACKGROUND: As the population of patients with end-stage renal disease has grown older, the proportion of patients with poorly preserved vasculature has concomitantly increased. Thus, arteriovenous grafts (AVG) have been used more frequently to access blood vessels for hemodialysis. Despite this increasing demand, studies of AVG are limited. In this study, we examined the surgical outcomes of upper-limb AVG creation. METHODS: Among the arteriovenous fistula formation procedures performed between January 2014 and March 2019 at Dankook University Hospital, 42 cases involved AVG creation. We compared patients in whom the axillary vein was used (group A; brachioaxillary AVG [B-Ax AVG]; n=20) with those in whom upper limb veins were used (group B; brachiobasilic AVG or brachioantecubital AVG; n=22). RESULTS: The 1-year primary patency rate was higher in group A than in group B (57.9% vs. 41.7%; p=0.262). The incidence of postoperative complications was not significantly different between groups. CONCLUSION: AVG using the axillary vein showed no major differences in safety or functionality compared to AVG using other veins. Therefore, accounting for age, underlying disease, and expected patient lifespan, B-Ax AVG can be considered an acceptable surgical method.

Surgical treatment of native valve Aspergillus endocarditis and fungemic vascular complications.

Systemic infection with Aspergillus is an opportunistic disease that affects mainly immunocompromised hosts, and is associated with a high mortality rate. It typically occurs in patients with several predisposing factors, but Aspergillus endocarditis of native valves is rare and experience in diagnosis and treatment is limited. We report a case of native valve endocarditis caused by Aspergillus. A 35-yr-old male patient who underwent pericardiocentesis four months previously for pericardial effusion of unknown etiology presented with right leg pain and absence of the right femoral artery pulse. Cardiac echocardiography revealed severe mitral insufficiency with large mobile vegetations, and computed tomographic angiography showed embolic occlusion of both common iliac arteries. We performed mitral valve replacement and thromboembolectomy, and Aspergillus was identified as the vegetation. We started intravenous amphotericin B and oral itraconazole, but systemic complications developed including superior mesenteric artery aneurysm and gastrointestinal bleeding. After aggressive management, the patient was discharged 78 days post surgery on oral itraconazole. He was well at 12 months post discharge but died in a traffic accident 13 months after discharge.

(7-Dimethylamino-1-hydroxy-3-naphthyl)(morpholino)methanone.

In the title compound, C(17)H(20)N(2)O(3), the morpholine ring is in a slightly distorted chair form. The crystal structure is stabilized by an inter-molecular O-H⋯O hydrogen bond between the H atom of the hydroxyl group and the O atom of a neighbouring carbonyl group. A weak inter-molecular C-H⋯π inter-action is also present.

In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria.

Sulfometuron methyl (SM) is an inhibitor of acetohydroxyacid synthase (AHAS), the first common enzyme in the branched-chain amino acid biosynthetic pathway, and shows activity against Mycobacterium tuberculosis both in vitro and in vivo. To develop AHAS inhibitor derivatives with more potent activity, 100 sulfonylurea analogues were screened for antimycobacterial activity against M. tuberculosis and non-tuberculous mycobacteria (NTM), and then evaluated for intracellular activity using mouse macrophages. Three new compounds with antimycobacterial activity comparable with that of SM were identified. These compounds exhibit significant activity against intracellular M. tuberculosis (including the drug-resistant M. tuberculosis strains), and NTM Mycobacterium abscessus and Mycobacterium kansasii, respectively.

Delayed massive hemothorax requiring surgery after blunt thoracic trauma over a 5-year period: complicating rib fracture with sharp edge associated with diaphragm injury.

Delayed massive hemothorax requiring surgery is relatively uncommon and can potentially be life-threatening. Here, we aimed to describe the nature and cause of delayed massive hemothorax requiring immediate surgery. Over 5 years, 1,278 consecutive patients were admitted after blunt trauma. Delayed hemothorax is defined as presenting with a follow-up chest radiograph and computed tomography showing blunting or effusion. A massive hemothorax is defined as blood drainage >1,500 mL after closed thoracostomy and continuous bleeding at 200 mL/hr for at least four hours. Five patients were identified all requiring emergency surgery. Delayed massive hemothorax presented 63.6±21.3 hours after blunt chest trauma. All patients had superficial diaphragmatic lacerations caused by the sharp edge of a broken rib. The mean preoperative chest tube drainage was 3,126±463 mL. We emphasize the high-risk of massive hemothorax in patients who have a broken rib with sharp edges.

Clinical Results of Arteriovenous Fistulas Constructed Using Autologous Vessels in End-Stage Renal Disease Patients on Hemodialysis.

BACKGROUND: For hemodialysis patients with end-stage renal disease (ESRD), it is important to construct an efficient vascular access with a superior patency rate. This study investigated the factors influencing the efficiency of arteriovenous fistulas (AVFs) constructed using an autologous vessel and evaluated the necessity of ultrasonography as a preoperative tool for AVF construction. METHODS: A retrospective analysis was performed of 250 patients in whom an AVF was constructed using an autologous vessel due to ESRD at our institution from January 2009 to April 2016. RESULTS: The 1-, 3-, and 5-year patency rates for all subjects were 87.6%, 85.6%, and 84.4%, respectively. The patients who underwent a preoperative evaluation of their vessels via ultrasonography had better patency rates than those who did not. Superior patency rates were found in patients under 65 years of age or with an anastomotic vein diameter of 3 mm or more. The 1-year patency rate and the diameter of the anastomotic vein showed a positive relationship. CONCLUSION: Ultrasonography is strongly recommended for AVF construction, and efforts should be made to increase the patency rate in patients over 65. Superior clinical results can be expected when an AVF is made using an autologous vessel with an anastomotic vein diameter of at least 3 mm.

Surgical Outcomes of Forearm Loop Arteriovenous Fistula Formation Using Tapered versus Non-Tapered Polytetrafluoroethylene Grafts.

BACKGROUND: Tapered grafts, which have a smaller diameter on the arterial side, have been increasingly used for arteriovenous fistula (AVF) formation. We compared the outcomes of 4-6-mm tapered and 6-mm straight forearm loop arteriovenous grafts. METHODS: A total of 103 patients receiving forearm loop arteriovenous grafts between March 2005 and March 2015 were retrospectively analyzed and separated into 2 groups (group A, 4- to 6-mm tapered grafts, n=78; group B, 6-mm straight grafts, n=25). In each group, complications and patency rates after surgery were assessed. RESULTS: Clinical characteristics and laboratory results, except for cerebrovascular disease history (group A, 7.7%; group B, 28.0%; p=0.014), were similar between the groups. No significant differences were found for individual complications. Kaplan-Meier survival analysis revealed no significant differences in 1-year, 3-year, and 5-year patency rates between groups (61.8%, 44.9%, and 38.5% vs. 62.7%, 41.1%, and 35.3%, respectively). CONCLUSION: We found no significant differences in complication and patency rates between the tapered and straight graft groups. If there are no differences in complication and patency between the two graft types, tapered grafts may be a valuable option for AVF formation in light of their other advantages.

Genome-wide screening of genomic alterations and their clinicopathologic implications in non-small cell lung cancers.

PURPOSE: Although many genomic alterations have been observed in lung cancer, their clinicopathologic significance has not been thoroughly investigated. This study screened the genomic aberrations across the whole genome of non-small cell lung cancer cells with high-resolution and investigated their clinicopathologic implications. EXPERIMENTAL DESIGN: One-megabase resolution array comparative genomic hybridization was applied to 29 squamous cell carcinomas and 21 adenocarcinomas of the lung. Tumor and normal tissues were microdissected and the extracted DNA was used directly for hybridization without genomic amplification. The recurrent genomic alterations were analyzed for their association with the clinicopathologic features of lung cancer. RESULTS: Overall, 36 amplicons, 3 homozygous deletions, and 17 minimally altered regions common to many lung cancers were identified. Among them, genomic changes on 13q21, 1p32, Xq, and Yp were found to be significantly associated with clinical features such as age, stage, and disease recurrence. Kaplan-Meier survival analysis revealed that genomic changes on 10p, 16q, 9p, 13q, 6p21, and 19q13 were associated with poor survival. Multivariate analysis showed that alterations on 6p21, 7p, 9q, and 9p remained as independent predictors of poor outcome. In addition, significant correlations were observed for three pairs of minimally altered regions (19q13 and 6p21, 19p13 and 19q13, and 8p12 and 8q11), which indicated their possible collaborative roles. CONCLUSIONS: These results show that our approach is robust for high-resolution mapping of genomic alterations. The novel genomic alterations identified in this study, along with their clinicopathologic implications, would be useful to elucidate the molecular mechanisms of lung cancer and to identify reliable biomarkers for clinical application.

Tangential Resection of a Popliteal Vein Aneurysm in a Patient Complaining of Localized Popliteal Pain.

A 48-year old man presented with left popliteal pain. A 2.2×1.6 cm sized saccular aneurysm at the level of the left popliteal fossa was diagnosed by ultrasonography. Tangential aneurysmectomy and popliteal vein repair was performed uneventfully. The patient fared well for a year without symptoms. Popliteal vein aneurysms are rare and typically found in patients with fatal thromboembolic features without warning symptoms. Fortunately, our patient had localized pain which was helpful in its early diagnosis and treatment.