Spinal cord infarction after withdrawal of veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: A case report.

BACKGROUND: Spinal cord infarction is a rare central nervous system angiopathy that impairs motor, sensory, and autonomic nerves and occurs due to various reasons. This study reports a case of spinal cord infarction in a patient following myocardial infarction that was managed by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CASE SUMMARY: A 78-year-old Japanese man visited the emergency department with a complaint of chest tightness. He had a history of hypertension, dyslipidemia, diabetes, chronic renal failure, and postoperative bladder cancer. Myocardial infarction was diagnosed after ST elevation in lead aVR was identified by electrocardiogram during the visit, and cardiopulmonary arrest occurred twice during our examination and treatment. After percutaneous coronary intervention with an intra-aortic balloon pump and VA-ECMO, the patient was admitted to the intensive care unit. His circulation stabilized, and he was withdrawn from the intra-aortic balloon pump on day 3 of illness and from VA-ECMO on day 4. However, his consciousness remained impaired. When the patient's consciousness improved on day 14, lower limb weakness was identified. Magnetic resonance imaging conducted on the following day revealed spinal cord infarction in the 5th to 12th thoracic vertebrae. CONCLUSION: Spinal cord infarction due to VA-ECMO is extremely rare but has a poor neurological prognosis upon onset. Necessary countermeasures include conducting regular neurological examinations and high blood pressure maintenance, which is very difficult in VA-ECMO patients. Therefore, patient care will benefit from the experiences reported in such cases.

CT-Guided Pelvic Lymph Nodal Brachytherapy.

PURPOSE: This is a report of our initial experience using computed tomography (CT)-guided interstitial high dose rate (HDR) brachytherapy to treat bulky pelvic nodal metastases as a part of definitive radiotherapy. MATERIAL AND METHODS: Between February 2015 and April 2019, 14 cervical/endometrial cancer patients presenting with bulky pelvic node(s) underwent nodal interstitial brachytherapy boost in our institution. In total, 17 nodes were treated. The median maximum diameters of the positive nodes at the time of diagnosis and at the first nodal implant were 25 mm (range: 10-65 mm) and 16 mm (range: 9-51 mm), respectively. Dosimetry data of the lymph nodal target volume and small bowel were collected and compared using the paired-sample t-test. Treatment-related toxicities were classified using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up time for all patients was 26 months. Local recurrence in pelvic nodes occurred in one patient (7%) after 16 months. One patient experienced grade 3 bladder bleeding, and one patient experienced grade 2 pubic bone fracture. No patient had grade 2 or greater gastrointestinal toxicity. In the dosimetric analysis, the mean nodal brachytherapy D90% in terms of the total equivalent dose of 2 Gy (EQD2) was 65.6 Gyαß10. The mean small bowel dose (SBD)0.1cc and SBD1cc in terms of the total EQD2 were 60.4 and 56.5 Gyαß3, respectively. Nodal D90% was significantly higher in terms of the total EQD2 than the SBD0.1cc (p = 0.003) and SBD1cc (p < 0.001). The Kaplan-Meier 2-year pelvic control estimate was 90%. CONCLUSIONS: CT-guided interstitial HDR pelvic nodal brachytherapy appears to be well tolerated with excellent local control in cervical or endometrial cancer patients with bulky pelvic nodes. This approach may offer a useful therapeutic option for unresected bulky pelvic nodes.

Memo1-Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development.

Polarized, non-overlapping, regularly spaced, tiled organization of radial glial cells (RGCs) serves as a framework to generate and organize cortical neuronal columns, layers, and circuitry. Here, we show that mediator of cell motility 1 (Memo1) is a critical determinant of radial glial tiling during neocortical development. Memo1 deletion or knockdown leads to hyperbranching of RGC basal processes and disrupted RGC tiling, resulting in aberrant radial unit assembly and neuronal layering. Memo1 regulates microtubule (MT) stability necessary for RGC tiling. Memo1 deficiency leads to disrupted MT minus-end CAMSAP2 distribution, initiation of aberrant MT branching, and altered polarized trafficking of key basal domain proteins such as GPR56, and thus aberrant RGC tiling. These findings identify Memo1 as a mediator of RGC scaffold tiling, necessary to generate and organize neurons into functional ensembles in the developing cerebral cortex.

Progressive Site-Directed Therapy for Castration-Resistant Prostate Cancer: Localization of the Progressive Site as a Prognostic Factor.

PURPOSE: Locoregional therapy for oligometastatic prostate cancer has generated great interest. However, its benefit for castration-resistant prostate cancer (CRPC) has not been fully demonstrated. Our objective was to evaluate the treatment outcome of progressive site-directed therapy (PSDT) for oligoprogressive CRPC (OP-CRPC). METHODS AND MATERIALS: This study cohort consisted of 101 patients with CRPC who underwent whole-body diffusion-weighted magnetic resonance imaging between 2014 and 2018, when a new line of anticancer therapy was being considered. For OP-CRPC, PSDT with radiation therapy and unchanged continuation of systemic therapy were recommended. RESULTS: Thirty-eight patients received a diagnosis of OP-CRPC, and 23 (61%) underwent PSDT at a median prostate-specific antigen (PSA) level of 7.8 ng/mL. The regional radiation therapy targets were the prostate/pelvic lymph nodes (n = 7), bone (n = 15), or both (n = 1). A decrease in PSA levels of at least 50% in response to PSDT (50% PSA decline) was observed in 16 cases (70%); the median time to PSA progression was 8.7 months. Intrapelvic localization of progressive lesions was a significant predictor of time to PSA progression (hazard ratio, 6.6; P = .007) as well as volumes of abnormal signal intensity on whole-body diffusion-weighted magnetic resonance imaging (hazard ratio, 0.5; P = .045). A 50% PSA decline was achieved in 16 of the 18 patients with intrapelvic OP-CRPC (89%) and in none of the 5 patients with non-intrapelvic OP-CRPC (P < .001). Intrapelvic OP-CRPC had a significantly longer time to PSA progression than non-intrapelvic OP-CRPC (10.1 vs 4.8 months, P = .0014). CONCLUSIONS: PSDT can be an effective treatment option for OP-CRPC. Progressive site localization was an important factor in good PSA response.

Outcomes of radiotherapy in advanced external auditory canal cancer.

External auditory canal cancer (EACC) is a rare malignant tumor. In the present study, we retrospectively evaluated the treatment results in patients with advanced EACC who were treated using external-beam radiotherapy (EBRT) combined with chemotherapy or radical surgery. Overall, 21 patients with Stage III (n = 8) or Stage IV (n = 13) EACC who underwent initial treatment at our hospital between 2003 and 2016 were enrolled in this study. The 2-year overall survival (OS) and locoregional control (LRC) rates of all patients were 62% and 71%, respectively. The 2-year OS and LRC rates in patients who had received EBRT and concurrent chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF, n = 6) were 100%. These results were higher than the 2-year OS and LRC rates of 62% and 69%, respectively, in patients who had received radical surgery and EBRT (n = 13). The rates were 0% in those who had neither received TPF nor undergone surgery in addition to EBRT (n = 2). Grade 3 bone or soft tissue necrosis was observed in 2 patients who had undergone surgery and postoperative EBRT. Our data suggest that the combination therapy of EBRT and surgery and/or chemotherapy may be the most effective treatment options for advanced EACC, and EBRT with concurrent chemotherapy with TPF is potentially the most acceptable.

Site-specific HNK-1 epitope on alternatively spliced fibronectin type-III repeats in tenascin-C promotes neurite outgrowth of hippocampal neurons through contactin-1.

The human natural killer-1 (HNK-1) carbohydrate epitope, composed of a unique sulfated trisaccharide (HSO3-3GlcAß1-3Galß1-4GlcNAc-R), is highly expressed during brain development and regulates higher brain function. However, it remains unclear which glycoprotein carries the HNK-1 epitope in the embryonic brain and the functional role it plays. Here, we showed that one of the major HNK-1 carrier proteins in the embryonic brain is tenascin-C (TNC), an extracellular matrix protein that regulates neurite outgrowth by interacting with the GPI-anchored protein contactin-1 (CNTN). Because the alternatively spliced fibronectin type-III (FNIII) repeats in TNC give rise to many isoforms and affect neuronal function, we evaluated neurite outgrowth of primary hippocampal neurons on purified recombinant FNIII repeats with or without the HNK-1 epitope as a substrate. We found that the presence of the HNK-1 epitope on the C domain of TNC promoted neurite outgrowth, and that this signal was mediated by CNTN, which is an HNK-1-expressing neuronal receptor. The neurite-promoting activity of the HNK-1 epitope on TNC required neuronal HNK-1 expression, which was defective in neurons lacking the glucuronyltransferases GlcAT-P and GlcAT-S. These results suggest that the HNK-1 epitope is a key modifier of TNC and CNTN in the regulation of embryonic brain development.

Prognostic value of metabolic tumor burden calculated using dual-time-point 18F-fluorodeoxyglucose positron emission tomography/CT in patients with oropharyngeal or hypopharyngeal cancer.

BACKGROUND: This study investigates the prognostic value of metabolic tumor burden calculated using dual-time-point 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in patients with locally advanced cancer. METHODS: This study examines 42 patients (35 men and 7 women, 38-73 years old) with locally advanced oropharyngeal or hypopharyngeal cancer who had undergone FDG-PET/CT before receiving chemoradiotherapy. Maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for the early and delayed phases. Statistical analyses included receiver operating characteristic curve, univariate and multivariate analysis. RESULTS: ΔSUVmax , both phases of MTV2.5 and TLG2.5 , early TLG40% , ΔTLG2.5 , and ΔTLG40% were significantly associated with progression-free survival (PFS). In multivariate analysis, early TLG2.5 (P = .005) was an independent prognostic factor of PFS. CONCLUSION: Not the percent change but the value calculated in the early phase in several parameters using dual-time-point FDG-PET/CT is significantly associated with the outcomes of patients with locally advanced oropharyngeal or hypopharyngeal cancer.

Hypothalamic hypopituitarism secondary to suprasellar metastases from small cell lung cancer: a case report and review of the literature.

BACKGROUND: Metastasis to the pituitary gland is an infrequent clinical problem, and the symptoms caused by metastases have been reported in only 2.5-18.2% of the cases. However, metastasis to the suprasellar lesion has rarely been reported in the literature. To the best of our knowledge, only nine cases of hypothalamic hypopituitarism due to metastases of solid tumors have been reported in English-language journals. CASE PRESENTATION: A 67-year-old Japanese man presented to our hospital with generalized weakness, lethargy, and weight loss. Laboratory data showed hypoglycemia together with low thyroid-stimulating hormone and free thyroxine. We suspected hypopituitarism and performed imaging of the head, which revealed multiple tumors, one of which was in the suprasellar region. Computed tomography of the chest showed a tumor shadow, and a bronchoscopic biopsy pathologically showed small cell lung cancer. Hormone profiling demonstrated hypothalamic pan-hypopituitarism. We diagnosed hypothalamic hypopituitarism secondary to metastases from the primary lung cancer and initiated radiation, chemotherapy, and hormone replacement, but the patient died 10 months later. CONCLUSIONS: We report a case of a 67-year-old man with hypothalamic hypopituitarism secondary to a suprasellar metastasis from a primary small cell lung cancer, and we review ten cases of hypothalamic hypopituitarism due to metastases, including our patient. Recognizing hypopituitarism can be challenging, especially in the elderly, whose symptoms such as lethargy and visual decline may be mistaken for the natural aging process. In patients with established metastatic conditions, the symptoms may be wrongly attributed to malignancy or to the side effects of therapy. When a patient is suspected of having hypopituitarism, a hormone load test can help to diagnose the type of hypopituitarism. It is important to evaluate the brain and the whole body to confirm whether metastasis and primary cancer exist. Because the mortality rate is very high, aggressive intervention for both diagnosis and therapy is required in cases of hypothalamic hypopituitarism secondary to tumor metastasis.

High Cardiac Troponin I Is Associated With Transesophageal Echocardiographic Risk of Thromboembolism and Ischemic Stroke Events in Non-Valvular Atrial Fibrillation Patients.

BACKGROUND: Abnormalities in the left atrium (LA) detected on transesophageal echocardiography (TEE) are reliable predictors of thromboembolism in patients with atrial fibrillation (AF). Cardiac troponin I, a marker of subclinical myocardial damage, may also be a predictor of thromboembolic events in patients with AF. The relationship between cardiac troponin I and thromboembolic risk on TEE, however, remains unclear.Methods and Results:TEE and laboratory data, including high sensitivity cardiac troponin I (hs-cTnI) and CHA2DS2-VASc score, were analyzed in 199 patients with non-valvular AF (NVAF). Patients were stratified into those with or without LA abnormality, defined as LA appendage flow velocity <20 cm/s or dense spontaneous echo contrast. On multiple logistic analysis of the clinical variables, hs-cTnI was associated with LA abnormality (95% CI: 1.0003-1.020, P=0.034). The area under the curve for LA abnormality increased on addition of hs-cTnI to CHA2DS2-VASc score. The incidence rate of ischemic stroke was higher in the high hs-cTnI group than in the low-hs-cTnI group (log-rank test, P<0.05). CONCLUSIONS: Elevated hs-cTnI was independently associated with LA abnormality in NVAF patients. hs-cTnI level may be a useful biomarker for risk stratification of thromboembolism in NVAF patients.

Transesophageal echocardiographic thromboembolic risk is associated with smoking status in patients with atrial fibrillation.

BACKGROUND: Smoking is a risk factor for cardiovascular diseases, but it is unclear whether smoking status, including environmental tobacco smoke, increases stroke risk in patients with atrial fibrillation (AF). Abnormalities of the left atrium (LA) and aortic atherosclerosis, as detected by transesophageal echocardiography (TEE), are risk factors for stroke and thromboembolism in AF patients. We investigated the impact of smoking status on thromboembolic risk by TEE in patients with nonvalvular AF. METHODS: In 122 patients with AF (mean age, 63 years; chronic AF 50%) who underwent TEE before catheter ablation of AF or for detection of the potential cardioembolic source, urinary concentrations of cotinine and clinical variables including smoking status and the CHA2DS2-VASc score were determined. RESULTS: Severe aortic atherosclerosis and increased aortic wall thickness were more frequently detected by TEE in current smokers than in non-smokers (p<0.05), though these findings did not significantly differ between non-smokers and environmental smokers. Patients in AF rhythm during TEE, who were environmental smokers and at relatively low risk, as stratified by their CHA2DS2-VASc score (≤ 2), showed lower LA appendage flow velocity than those without environmental smoking (47±22 vs. 34±13 cm/sec, p<0.05). CONCLUSIONS: TEE findings indicated that smoking status could be associated with thromboembolic risk in patients with AF.

APC sets the Wnt tone necessary for cerebral cortical progenitor development.

Adenomatous polyposis coli (APC) regulates the activity of ß-catenin, an integral component of Wnt signaling. However, the selective role of the APC-ß-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated ß-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-ß-catenin pathway indicates that the maintenance of appropriate ß-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates ß-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. ß-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of ß-catenin or inhibition of ß-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated ß-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development.

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal ß-Oxidation of Very-long-chain Fatty Acids.

Acyl-CoA binding domain-containing 5 (ACBD5) is a peroxisomal protein that carries an acyl-CoA binding domain (ACBD) at its N-terminal region. The recent identification of a mutation in the ACBD5 gene in patients with a syndromic form of retinal dystrophy highlights the physiological importance of ACBD5 in humans. However, the underlying pathogenic mechanisms and the precise function of ACBD5 remain unclear. We herein report that ACBD5 is a peroxisomal tail-anchored membrane protein exposing its ACBD to the cytosol. Using patient-derived fibroblasts and ACBD5 knock-out HeLa cells generated via genome editing, we demonstrate that ACBD5 deficiency causes a moderate but significant defect in peroxisomal ß-oxidation of very-long-chain fatty acids (VLCFAs) and elevates the level of cellular phospholipids containing VLCFAs without affecting peroxisome biogenesis, including the import of membrane and matrix proteins. Both the N-terminal ACBD and peroxisomal localization of ACBD5 are prerequisite for efficient VLCFA ß-oxidation in peroxisomes. Furthermore, ACBD5 preferentially binds very-long-chain fatty acyl-CoAs (VLC-CoAs). Together, these results suggest a direct role of ACBD5 in peroxisomal VLCFA ß-oxidation. Based on our findings, we propose that ACBD5 captures VLC-CoAs on the cytosolic side of the peroxisomal membrane so that the transport of VLC-CoAs into peroxisomes and subsequent ß-oxidation thereof can proceed efficiently. Our study reclassifies ACBD5-related phenotype as a novel peroxisomal disorder.

Impact of persistent smoking on long-term outcomes in patients with nonvalvular atrial fibrillation.

BACKGROUND: Although smoking is a risk factor for cardiovascular diseases, little is known about the impact of smoking on long-term outcomes in patients with atrial fibrillation (AF). METHODS: In 426 consecutive patients with nonvalvular AF (mean age, 66 years; 307 men; mean follow-up, 5.8±3.2 years), clinical variables including smoking status, CHADS2, and CHA2DS2-VASc score, incidences of cardiovascular events (stroke, myocardial infarction, or admission for heart failure), bleeding, and mortality were determined. RESULTS: Incidences of intracranial bleeding (0.7% vs 0.1%/year, p<0.01), all-cause mortality (4.9% vs 2.6%/year, p<0.01), and death from stroke (0.8% vs 0.2%/year, p<0.05) were higher in patients with history of smoking than in those without it. Incidence of intracranial bleeding was significantly higher in persistent smokers than in non-persistent smokers (1.2% vs 0.2%/year, p<0.01). History of smoking predicted all-cause mortality [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.7-4.5; p<0.01] and death from stroke (HR 4.7; 95% CI 1.0-22.3; p<0.05) independent of age, antithrombotic treatment, CHADS2, and CHA2DS2-VASc score. Persistent smoking predicted intracranial bleeding (HR 4.4; 95% CI 1.1-17.6; p<0.05) independent of age and antithrombotic treatment. CONCLUSIONS: Smoking status, independent of age, antithrombotic treatment, and clinical risk factors, predicted long-term adverse outcomes including bleeding events in patients with nonvalvular AF. There might be an obvious impact of persistent smoking on intracranial bleeding.

Hyperuricemia and transesophageal echocardiographic thromboembolic risk in patients with atrial fibrillation at clinically low-intermediate risk.

BACKGROUND: There is no clear consensus on thromboprophylaxis in patients with nonvalvular atrial fibrillation (AF) at low-intermediate thromboembolic risk. Although hyperuricemia is a risk factor for cardiovascular diseases, the relationship between serum uric acid (UA) levels and thromboembolic risk has not been fully elucidated in patients with AF. METHODS AND RESULTS: Serum UA levels and the score for congestive heart failure, hypertension, age, diabetes mellitus, prior stroke/transient ischemic attack, vascular disease and sex (ie, CHA2DS2-VASc score) were determined in 470 patients with nonvalvular AF who underwent transesophageal echocardiography (TEE) to evaluate their risk of thromboembolism. Serum UA levels were similar between the low-intermediate risk (CHA2DS2-VASc score=0 or 1) and high-risk (≥2) groups, although serum D-dimer levels were lower in the low-intermediate risk than in the high-risk group. Among patients at low-intermediate risk, serum UA levels were higher in those with TEE thromboembolic risk (TEE risk: low left atrial appendage flow, spontaneous echo contrast, thrombi, or aortic atherosclerosis) than in those without TEE risk. On multivariate analysis, the serum UA level was an independent predictor of TEE risk in AF patients at low-intermediate risk (odds ratio, 1.45; 95% confidence interval 1.09-2.00; P=0.016). CONCLUSIONS: The serum UA level was associated with thromboembolic risk on TEE in patients with nonvalvular AF at low-intermediate risk stratified by clinical risk factors.

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer.

BACKGROUND: Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. MATERIALS AND METHODS: The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. RESULTS: Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. CONCLUSION: Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Cervical lymph node metastasis from early-stage squamous cell carcinoma of the oral tongue.

CONCLUSIONS: The findings of this study demonstrated that the wait-and-watch strategy for neck metastasis from squamous cell carcinoma (SCC) of oral tongue is a reliable option and that salvage by surgical treatment is effective. However, younger patients should be closely monitored for recurrence. Adjuvant therapy may be recommended for patients with pathologically advanced disease. OBJECTIVES: Metastatic involvement of cervical lymph nodes is the most important prognostic indicator in patients with oral tongue SCC. With the objective of determining the most appropriate treatment strategy for regional recurrence, we conducted a retrospective review of clinicopathologic factors. METHODS: The clinicopathologic features of 103 patients with oral tongue SCC, in whom the local lesions were treated successfully by low-dose interstitial brachytherapy (LD-IBT), but who subsequently developed cervical lymph node metastases and were treated by salvage surgery, were reviewed. RESULTS: In the patients who underwent surgical treatment at our hospital, 5-year disease-free survival and regional control rates were 69.3% and 85.3%, respectively. The clinicopathologic factors significantly associated with unfavorable disease-free survival were the presence of extracapsular spread (hazard ratio (HR) = 3.005, p = 0.045), multiple and large lymph nodes (HR = 2.850, p = 0.010 and HR = 3.112, p = 0.007, respectively), younger age (HR = 2.429, p = 0.048), and shorter interval from the LD-IBT to detection of neck metastasis (HR = 1.749, p = 0.013).

Permanent interstitial re-irradiation with Au-198 seeds in patients with post-radiation locally recurrent uterine carcinoma.

This study sought to analyze the outcome of patients with post-treatment locally recurrent uterine carcinoma treated with Au-198 seed permanent interstitial re-irradiation (Au-198 IRI). A retrospective review of the data of 15 patients with post-treatment locally recurrent uterine carcinoma treated with Au-198 IRI between 1991 and 2009 was performed to evaluate the disease response, local control, overall survival and complication rates. All the patients had received definitive radiation therapy or surgery as the initial treatment. None were judged as being suitable candidates for surgical treatment, and were referred for Au-198 IRI. Au-198 IRI was performed for the vaginal wall in 8 patients, vaginal stump in 4 patients, vulva in 2 patients, and cervix in 1 patient. The median tumor volume was 1.3 cm(3)(range, 0.4-6.9), the median treated volume was 6.3 cm(3)(range, 1.8-11), and the median prescribed dose was 76 Gy (range, 68-90). At a median follow-up duration of 19 months (range, 4.3-146.9), 13 of 15 patients (87%) showed complete responses after Au-198 IRI, although 10 of these 13 patients (77%) developed repeat central recurrence again between 2.5 and 49.7 months after the Au-198 IRI (median, 12.5 months). The overall 2-year local control rate and 2-year overall survival rate in the 15 patients were 33% and 64%, respectively. Two (13%) of the 15 patients experienced late complications that were more severe than Grade III. As a result, Au-198 IRI is considered to be one of the salvage treatment modalities with tolerable complications for inoperable centrally recurrent uterine carcinoma.

Clinical and transesophageal echocardiographic variables for prediction of thromboembolic events in patients with nonvalvular atrial fibrillation at low-intermediate risk.

BACKGROUND: There is no clear consensus about antithrombotic treatment in atrial fibrillation (AF) patients at low-intermediate thromboembolic risk. Transesophageal echocardiography (TEE) is useful for prediction of thromboembolic events in AF. METHODS AND RESULTS: Of 498 patients with nonvalvular AF, incidence of stroke, cardiac events, and mortality was investigated in 280 patients with CHADS(2) score 0 or 1 (mean age 64 years, mean follow-up 6.4 ± 3.1 years). Left atrial abnormality (low left atrial appendage flow, spontaneous echo contrast, or thrombi), complex aortic plaque (mobile, ulcerated, pedunculate, or thickness ≥ 4mm), or both were defined as TEE risk. The incidences of ischemic stroke, cardiovascular events, and death were higher in patients with TEE risk than in those without the risk (2.0%/year vs. 0.5%/year, p<0.05; 4.7%/year vs. 1.9%/year, p<0.01; and 4.7%/year vs. 2.0%/year, p<0.01, respectively). This was also true for patients with CHADS(2) score of 0 (1.7%/year vs. 0.3%/year, p<0.05; 4.1%/year vs. 1.6%/year, p<0.05; and 3.9%/year vs. 1.4%/year, p<0.01; respectively). On multivariate analysis, TEE risk predicted ischemic stroke, cardiovascular events, and mortality independently of clinical variables or CHADS(2) score. CONCLUSIONS: TEE could be useful for further stratification of patients with nonvalvular AF stratified at low-intermediate risk (CHADS(2) score 0 or 1) and could indicate who should receive anticoagulation treatment.

Transesophageal echocardiographic findings are independent and relevant predictors of ischemic stroke in patients with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Not only clinical factors, including the CHADS(2) score, but also echocardiographic findings have been reported to be useful for predicting the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it remains to be determined which of these factors might be more relevant for evaluation of the risk of stroke in each patient. METHODS: In 490 patients with NVAF who underwent transesophageal echocardiography (TEE), we examined the long-term incidence of ischemic stroke events (mean follow-up time, 5.7±3.3 years). For each patient, the predictive values of gender, the CHADS(2) risk factors (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, history of cerebral ischemia), the CHADS(2) score, and the findings on echocardiography, including TEE risk markers, were assessed. RESULTS: The ischemic stroke rate was significantly correlated with the CHADS(2) score (p<0.05). According to the results of univariate analyses, age ≥75 years, history of cerebral ischemia, CHADS(2) score ≥2, and presence of TEE risk were significantly correlated with the incidence of ischemic stroke. Cox proportional hazards regression analyses identified age ≥75 years and presence of TEE risk as significant predictors of subsequent ischemic stroke events in patients with NVAF. As compared with that in persons below 75 years of age without TEE risk, the ischemic stroke rate was significantly higher in persons who were ≥75 years of age with TEE risk (4.3 vs. 0.56%/year, adjusted hazard ratio=8.94, p<0.001). CONCLUSIONS: TEE findings might be more relevant predictors of ischemic stroke than the CHADS(2) score in patients with NVAF. The stroke risk was more than 8-fold higher in patients aged ≥75 years with TEE risk.