Unusually Short H⋠⋠⋠H Contacts in Intramolecularly Cyclized Helically Fused Anthracenes.

The intramolecular coupling of dichloro-substituted helically fused anthracenes using the Yamamoto coupling yielded cyclized products with sterically congested molecular structures. The X-ray analysis and DFT calculations showed that the aromatic framework adopted a nonplanar structure with a twisted conformation about the newly formed single bond, which acts as a chiral axis. Interestingly, the X-ray structure obtained through the Hirshfeld atom refinement revealed short interatomic distances between the inner hydrogen atoms (1.648-1.692 Å), much shorter than the sum of their van der Waals radii. Owing to these unusually short contacts, the 1H NMR spectrum exhibited a significant deshielding (12.5 ppm) and a large nuclear Overhauser effect (44 %). Additionally, the IR spectrum displayed a high-frequency shift of the C-H stretching vibration. These observations, along with the noncovalent interaction plot indicative of a characteristic steric environment, strongly support the presence of steric hindrance. Moreover, dynamic NMR measurement of the mesityl-substituted derivative yielded a barrier to helical inversion of 84 kJ mol-1. The optical properties and crystal packing of the cyclized products are also reported.

Rationale and Design of Prospective, Multicenter, Double-Arm Clinical Trial to Investigate the Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus (TOP-HFPEF Trial).

BACKGROUND: Recent large clinical trials have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial. METHODS AND RESULTS: The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20 mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52 weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e' assessed by echocardiography from the baseline to the end of this study (52 weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function. CONCLUSIONS: The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus.

Corticobasal degeneration with visual hallucination as an initial symptom: A case report.

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.

Phase I/II study of nedaplatin and nab-paclitaxel for patients with previously untreated advanced squamous cell lung cancer: Kanto Respiratory Disease Study Group (KRSG) 1302.

BACKGROUND: Nedaplatin and nab-paclitaxel are each efficacious in the treatment of squamous cell lung cancer. PATIENTS AND METHODS: Eligibility criteria were: no prior chemotherapy, advanced squamous cell lung cancer; performance status 0-1, age > 20 years but < 75 years, and adequate hematologic, hepatic and renal function. Patients received escalating doses of nab-paclitaxel under a fixed dose of nedaplatin (100 mg/m2, day 1) every 3 weeks in phase I. The initial nab-paclitaxel dose was 100 mg/m2 on days 1 and 8 (level 1), and the next dose was 100 mg/m2 on days 1, 8, and 15 (level 2). In phase II, patients received the recommended doses. The primary endpoint was tumor response rate. RESULTS: In phase I, three patients at level 1 experienced no dose-limiting toxicities (DLTs) and two patients at level 2 experienced DLTs. Level 1 was thus determined as the recommended dose. Twenty-three patients were enrolled in phase II. The 3 patients in level 1 and 23 patients in phase II were included together for analyses. Three of these 26 patients were excluded from response analysis due to pneumonia and patient refusal. Response rate was 91.3% (95% confidence interval, 72.0-98.9%). Toxicities observed during all cycles were tolerable. CONCLUSIONS: The recommended dose for this combination was nedaplatin at 100 mg/m2 on day 1 and nab-paclitaxel at 100 mg/m2 on days 1 and 8 every 3 weeks. The combination of nedaplatin and nab-paclitaxel appears safe and efficacious in patients with untreated advanced squamous cell lung cancer.

Reasons for choice of glaucoma surgery in eyes not treated with anti-glaucoma medications.

BACKGROUND: In the real world, some glaucoma patients can undergo an incisional glaucoma surgery without using medication. The rate of cases with no medication treatment at the time of surgery among those that underwent incisional glaucoma surgeries performed in our department was reported. METHODS: The department database of Shimane University Hospital for eyes that underwent incisional surgeries to manage glaucoma at the hospital between April 2018 and September 2020 were searched. By reviewing the medical charts of 1,417 consecutive eyes listed, 90 (6.4%) eyes of 67 subjects (mean age of 72 ± 16 years; 22 men, 29 eyes; 45 women, 61 eyes) who underwent a surgery without use of antiglaucoma medication were identified. The types of glaucoma, glaucoma procedures, and reasons for choosing the glaucoma surgeries rather than medical therapy were collected for the 90 eyes. RESULTS: Among the 90 eyes, primary angle-closure disease (PACD) (60%) was the most frequent type of glaucoma followed by EXG (17%), POAG (16%), and others (8%). Among the reasons for the choice of incisional surgery, relief of angle closure (64%) was the most frequent, the second most frequent was the incidental diagnosis of glaucoma during the ocular examinations both for that eye's cataract surgery or the contralateral glaucoma surgery (13%). Other reasons included poor medication adherence (10%), dementia (6%), multiple medication allergy (3%), and acute IOP elevation other than PACD (3%). Cataract extraction (CE) alone (33%) was the most frequent glaucoma procedures performed in these eyes, followed by CE combined with goniosynechialysis (27%), CE + iStent (16%), CE + goniotomy by Tanito microhook ab interno trabeculotomy or using the Kahook Dual Blade (11%), Ahmed Glaucoma valve implantation (11%), and trabeculectomy (2%). CONCLUSION: In the real-world, 6.4% of incisional glaucoma surgeries were performed in the absence of medication use; of them, 32 eyes (2.3%) were with open angle glaucoma. In open angle glaucoma, the reasons can be classified into; 1) patients' inability to instill the medication, 2) incidental diagnosis of glaucoma during the pre-surgical examinations, and 3) the eyes with acute IOP rise.

Repeated Cardioembolic Stroke after COVID-19 mRNA Vaccination: A Case Report.

OBJECTIVE: There have been no reports suggesting a relationship between the COVID-19 mRNA vaccines that encodes the spike glycoprotein of SARS-CoV-2 and cerebrovascular disease. A case of repeated cardioembolic stroke after vaccination with the BNT162b2 (Pfizer) COVID-19 mRNA vaccine is presented. METHODS: Imaging and laboratory findings, treatment decisions, and the outcome of this case are presented. RESULTS: An 83-year-old Japanese woman developed right hemiplegia and motor aphasia three days after receiving her first dose of the BNT162b2 (Pfizer) COVID-19 mRNA vaccine. She had been taking rivaroxaban for persistent atrial fibrillation for 10 years, but had no symptomatic ischemic strokes. On magnetic resonance imaging (MRI) the left middle cerebral artery (MCA) was occluded. Intravenous recombinant tissue-plasminogen activator (rt-PA) therapy and mechanical thrombectomy were performed, and she recovered almost fully. However, three days after the second dose, she developed left hemiplegia and left hemispatial neglect. MRI showed occlusion of the right MCA. Only mechanical thrombectomy was performed again, but it could not be resumed due to the hard thrombus. DISCUSSION: In this case, it is difficult to exclude a causal relationship between the COVID-19 mRNA vaccine and ischemic stroke. This association needs to be carefully monitored.

Predictors of Reperfusion and 90-day Functional Outcome After Mechanical Thrombectomy for Large Vessel Occlusion Strokes.

OBJECTIVES: Whether elderly patients with adverse comorbidities or strong vascular meandering benefit from mechanical thrombectomy to the same degree as patients who participated in the pivotal randomized controlled trials on this procedure (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, DAWN, and DEFUSE 3) remains unknown. We aimed to investigate the predictors of reperfusion and 90-day functional outcome using real-world clinical data, without excluding elderly patients with adverse comorbidities or patients in whom vascular access could not be achieved. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients with acute ischemic stroke who underwent or in whom mechanical thrombectomy was attempted at Japanese Red Cross Matsue Hospital from April 2015 to June 2020. RESULTS: Altogether, 111 mechanical thrombectomies in 111 patients (average age 77.2 years) were attempted for acute ischemic stroke. Vascular access was not achieved in 8 (7.2%) cases. In the multivariable analysis, age ≥85 years (odd ratio [OR] 0.191, 95% confidence interval [CI] 0.057-0.641, p = 0.007) and presence of adverse comorbidities (OR 0.265, 95% CI 0.090-0.659, p = 0.016) were associated with failed reperfusion. The diffusion-weighted imaging (DWI)-ASPECT score ≥6 (OR 4.650, 95% CI 1.610-13.40, p = 0.005) was associated with good 90-day functional outcomes. Presence of adverse comorbidities was not a predictor, but it had a relatively strong correlation with poor functional outcome. CONCLUSIONS: Mechanical thrombectomy in elderly patients should be considered very carefully if they are aged ≥85 years, have low DWI-ASPECT score and have clear evidence of pre-existing adverse comorbidities.

Artificial Intelligence Uncovered Clinical Factors for Cardiovascular Events in Myocardial Infarction Patients with Glucose Intolerance.

PURPOSE: Glucose intolerance (GI), defined as either prediabetes or diabetes, promotes cardiovascular events in patients with myocardial infarction (MI). Using the pooled clinical data from patients with MI and GI in the completed ABC and PPAR trials, we aimed to identify their clinical risk factors for cardiovascular events. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 415,328 combinations of < 4 clinical parameters. RESULTS: We identified 242 combinations that predicted the occurrence of hospitalization for (1) percutaneous coronary intervention for stable angina, (2) non-fatal MI, (3) worsening of heart failure (HF), and (4) all causes, and we analyzed combinations in 1476 patients. Among these parameters, the use of proton pump inhibitors (PPIs) or plasma glucose levels > 200 mg/dl after 2 h of a 75 g oral glucose tolerance test were linked to the coronary events of (1, 2). Plasma BNP levels > 200 pg/dl were linked to coronary and cardiac events of (1, 2, 3). Diuretics use, advanced age, and lack of anti-dyslipidemia drugs were linked to cardiovascular events of (1, 3). All of these factors were linked to (4). Importantly, each finding was verified by independently drawn Kaplan-Meier curves, indicating that the determined factors accurately affected cardiovascular events. CONCLUSIONS: In most previous MI patients with GI, progression of GI, PPI use, or high plasma BNP levels were linked to the occurrence of coronary stenosis or recurrent MI. We emphasize that use of AI may comprehensively uncover the hidden risk factors for cardiovascular events.

Plasma BNP Levels and Diuretics Use as Predictors of Cardiovascular Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance.

PURPOSE: Although impaired glucose tolerance (IGT) promotes cardiovascular events, our Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance (ABC) study showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with myocardial infarction (MI) and IGT. The aim of the present study was to identify potential clinical factors for cardiovascular events in patients with MI and IGT. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters. RESULTS: We identified 380 combinations predicting the occurrence of (1) all-cause hospitalization, (2) hospitalization due to worsening of heart failure (HF), (3) hospitalization due to non-fatal MI, and (4) hospitalization due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels ≥ 200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalization, (2) hospitalization due to worsening of HF, and (3) hospitalization due to a non-fatal MI, with plasma BNP levels ≥ 200 pg/dl being the sole predictor of hospitalization due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina. CONCLUSIONS: In patients with MI and IGT, high plasma BNP levels predicted the occurrence of coronary stenosis, recurrent MI, and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF.

A dipeptidyl peptidase-IV inhibitor improves diastolic dysfunction in Dahl salt-sensitive rats.

To date, there is no established treatment for heart failure with preserved ejection fraction (HFpEF). Dipeptidyl peptidase-IV (DPP-IV) inhibitors reportedly have improved not only diabetes mellitus but also heart failure with systolic dysfunction in experimental models. We investigated the effects of a DPP-IV inhibitor on HFpEF in rats. Dahl salt-sensitive rats were fed either high-salt (high-salt diet (HSD): 8% NaCl) or low-salt diets (0.3% NaCl) from 6.5 weeks of age. They were then treated with or without a DPP-IV inhibitor, vildagliptin (10 mg/kg/day, orally), from 11 weeks of age for 9 weeks and analyzed at the age of 20 weeks. HSD rats mimicked the pathophysiology of HFpEF. There were no differences in heart rate, blood pressure, left ventricular (LV) systolic function, or the extent of LV hypertrophy between HSD rats with or without vildagliptin. However, vildagliptin decreased LV end-diastolic pressure, the most reliable hemodynamic parameter of HFpEF in HSD rats. Vildagliptin also decreased the LV distensibility index, a sensitive marker of LV diastolic function in HSD rats. Vildagliptin decreased the expression of collagen genes in HSD hearts and attenuated LV interstitial fibrosis (HSD with vehicle and vildagliptin, 2.9% vs. 1.9%; P < 0.05). Furthermore, vildagliptin administration reduced both plasma renin activity and aldosterone concentrations in HSD rats. A DPP-IV inhibitor, vildagliptin, improved the severity of LV fibrosis, and thus, diastolic dysfunction of HFpEF in Dahl salt-sensitive hypertensive rats. DPP-IV inhibitors are promising medicines for treatment of HFpEF in patients with diabetes mellitus.

AST-120, an Adsorbent of Uremic Toxins, Improves the Pathophysiology of Heart Failure in Conscious Dogs.

PURPOSE: Several lines of evidence suggest that renal dysfunction is associated with cardiovascular toxicity through the action of uremic toxins. The levels of those uremic toxins can be reportedly reduced by the spherical carbon adsorbent AST-120. Because heart failure (HF) causes renal dysfunction by low cardiac output and renal edema, the removal of uremic toxins could be cardioprotective. METHOD: To determine whether blood levels of the uremic toxin indoxyl sulfate (IS) increase in HF and whether AST-120 can reduce those levels and improve HF. We induced HF in 12 beagle dogs by 6 weeks of rapid right ventricular pacing at 230 beats per min. We treated six dogs with a 1-g/kg/day oral dosage of AST-120 for 14 days from week 4 after the start of rapid ventricular pacing. The other six dogs did not receive any treatment (control group). RESULTS: In the untreated dogs, IS levels increased as cardiac function deteriorated. In contrast, plasma IS levels in the treated dogs decreased to baseline levels, with both left ventricular fractional shortening and pulmonary capillary wedge pressure also improving when compared with untreated dogs. Finally, AST-120 treatment was shown to reduce both myocardial apoptosis and fibrosis along with decreases in extracellular signal-regulated kinase phosphorylation, the Bax/Bcl-2 ratio, and TGF-ß1 expression and increases in AKT phosphorylation. CONCLUSIONS: IS levels are increased in HF. AST-120 treatment reduces the levels of IS and improves the pathophysiology of HF in a canine model. AST-120 could be a novel candidate for the treatment of HF.

Hatched "egg" of thymoma with sarcoidosis.

BACKGROUND: While calcification of thymoma is common, "eggshell" calcification is rare. We report a case of an eggshell calcified thymoma that "hatched" after 4 years of follow-up. Pathologically, it revealed that sarcoidosis accompanied this case of thymoma, which might cause in calcification. CASE PRESENTATION: The patient was a 68-year-old female. A 20-mm anterior mediastinal nodule completely covered with calcification was noted in an annual health check-up. However, as the nodule did not change during 6 months of follow-up, she discontinued regular examinations. Four years later, an abnormality in her chest X-ray was noted again. The tumor grew outside the calcification to reach 63 mm. She underwent resection of this anterior mediastinal tumor. Pathologically, the tumor was diagnosed as thymoma of type B1 in the WHO classification. The histology of the tumor inside and outside of the calcification was not different, suggesting that the tumor grew from the inside of the calcification. The calcification was located within the fibrotic capsule of thymoma. Sarcoidosis also presented in her lung and mediastinal lymph nodes. CONCLUSIONS: Although the mechanism of calcification of the capsule was not clear, sarcoidosis might be related to this case because macrophage accumulation and altered lipid metabolism in sarcoidosis present with similar dystrophic calcification.

[Benefit of Adjuvant Chemotherapy after Curative Resection of Liver and Lung Metastases in Colorectal Cancer].

The survival benefit of adjuvant chemotherapy after resection of liver and pulmonary metastases in colorectal cancer(CRC) remains controversial. We enrolled9 0 CRC patients who underwent hepatic metastasectomy and2 5 CRC patients who underwent pulmonary metastasectomy between April 2005 and March 2017 to clarify the efficacy of adjuvant chemotherapy after hepatic andpulmonary metastasectomy. Forty-two patients receivedad juvant chemotherapy after hepatic metastasectomy, and1 0 patients receivedad juvant chemotherapy after pulmonary metastasectomy. Patients who underwent hepatic metastasectomy andreceivedad juvant chemotherapy hadlonger overall survival(OS)(p=0.043)andrelapse -free survival (RFS)(p=0.043)than those who underwent surgery alone. There were no significant differences in OS(p=0.84)andRFS (p=0.87)between patients receiving adjuvant chemotherapy after pulmonary metastasectomy and those receiving surgery alone. On multivariate analysis, adjuvant chemotherapy was independently associated with favorable OS in patients who underwent hepatic metastasectomy(hazardratio: 0.473, 95% confidence interval: 0.23-0.97, p=0.04). No prognostic factor associatedwith OS andRFS was identifiedin patients undergoing pulmonary metastasectomy. These results suggest that patients who undergo hepatic metastasectomy couldhave an OS andRFS benefit from adjuvant chemotherapy, but those who undergo pulmonary metastasectomy would not.

Association between Serum Uric Acid Level and Activity of Daily Living in Japanese Patients with Ischemic Stroke.

BACKGROUND: An association between serum uric acid and outcomes of ischemic stroke has been reported, but the results are controversial. The aim of this study is to clarify how uric acid may affect activities of daily living after acute ischemic stroke. METHODS: Consecutive Japanese patients with acute ischemic stroke were analyzed. Serum uric acid quartiles and activities of daily living at hospitalization and discharge in men and women were examined. Activities of daily living were evaluated using the modified Rankin scale score, and a score of 3 or higher was defined as poor activities of daily living. P values less than .05 were considered significant. RESULTS: A total of 987 patients with acute ischemic stroke (591 men; mean age, 72.3 years) were analyzed in this study. We observed a U-shaped relationship between serum uric acid and poor activities of daily living in both men and women at hospitalization and discharge. Multivariate analysis demonstrated that the first quartile group of serum uric acid was significantly associated with poor activities of daily living in both men and women, using the third quartile group as the reference. CONCLUSIONS: Lower serum uric acid can be a marker for predicting poor activities of daily living in patients with acute ischemic stroke, irrespective of sex.

Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression.

Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer.

Plasma Brain Natriuretic Peptide is a Marker of Prognostic Functional Outcome in Non-Cardioembolic Infarction.

BACKGROUND: High plasma levels of brain natriuretic peptide (BNP) may also be observed in patients with non-cardioembolic infarction (CEI). We aimed to evaluate the relation between plasma BNP level, clinical parameters, and functional outcome in patients with and without CEI. METHOD: This study analyzed consecutive Japanese patients with acute ischemic stroke. Correlations between plasma BNP level and conventional risk factors for ischemic stroke were examined. Values of P less than .05 were considered statistically significant. RESULTS: This study analyzed 718 acute ischemic stroke patients (445 men and 273 women; mean age, 73.9 years). Mean plasma level of BNP was significantly higher for CEI (366.6 pg/ml) than for non-CEI (105.6 pg/ml; P < .01). Poor outcome (modified Rankin Scale score ≥3) at hospitalization and discharge were associated with significantly higher plasma BNP level than good outcome (modified Rankin Scale score ≤2) for both CEI and non-CEI. On multiple regression analysis, log-BNP was significantly associated with female sex, smoking, triglyceride, and creatinine clearance in CEI. In non-CEI, log-BNP was significantly associated with systolic/diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and creatinine clearance. CONCLUSION: Irrespective of the presence of CEI, plasma BNP offers a marker of prognostic functional outcome. We clarified the characteristics and differences associated with plasma BNP in CEI and non-CEI, and our results suggest that plasma BNP can provide a useful marker of brain damage and neurohumoral dynamics in acute ischemic stroke.

Metabolic syndrome is linked to the incidence of pancreatic cancer.

Background: Although previous studies have showed that metabolic syndrome is one of the contributors of pancreatic cancer, there is no clear consensus that early stages of metabolic syndrome are linked to increased incidence of pancreatic cancer. Therefore, we confirmed the linkage between metabolic syndrome and pancreatic cancer, and shown that even early stage of metabolic syndrome is linked to pancreatic cancer in the retrospective observational study. Methods: We recruited approximately 4.6 million Japanese in 2005 and followed up these subjects for more than 10 years. At the time of the enrollment, after obtaining clinical data with prescribed drugs and examining the presence or absence of metabolic syndrome (MetS), we followed up on these subjects with and without MetS to examine the incidence of pancreatic cancer. The modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) were used to define MetS. Findings: During the 40.7-month average follow-up period for 2,707,296 subjects with complete data for identifying MetS and important risk factors without pancreatic cancer before the enrollment, 87,857 suffered from pancreatic cancer. Pancreatic cancers occurred in 16,154 of 331,229 subjects (4.9%) in the MetS group and 71,703 of 2,376,067 patients (3.0%) in the non-MetS group (hazard ratio (HR), 1.37; 95% confidence interval [CI], 1.34-1.39; p < 0.0001 after the adjustment with age, smoking and sex). As the number of the constituent factors of MetS increased from one to five, the incidence of pancreatic cancer correspondingly increased (HR: 1.11, 1.23, 1.42, 1.66 and 2.03 using Cox proportional hazard models, p < 0.0001 each). When we defined MetS using the Japanese criteria, the results are in accord with the results using NCEP/ATPIII. Especially pre-metabolic syndrome (pre-MetS) in the Japanese criteria was tightly linked to the incidence of pancreatic cancers. Interpretation: MetS is confirmed to be linked to pancreatic cancer. Although we cannot conclude causality. We also demonstrated the link between pre-MetS and pancreatic cancer. Funding: The sponsors of the study were Japanese Heart Foundation and Japan Cardiovascular Research Foundation. This is also partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development.

Predicting heart failure onset in the general population using a novel data-mining artificial intelligence method.

We aimed to identify combinations of clinical factors that predict heart failure (HF) onset using a novel limitless-arity multiple-testing procedure (LAMP). We also determined if increases in numbers of predictive combinations of factors increases the probability of developing HF. We recruited people without HF who received health check-ups in 2010, who were followed annually for 4 years. Using 32,547 people, LAMP was performed to identify combinations of factors of fewer than four factors that could predict the onset of HF. The ability of the method to predict the probability of HF onset based on the number of matching predictive combinations of factors was determined in 275,658 people. We identified 549 combinations of factors for the onset of HF. Then we classified 275,658 people into six groups who had 0, 1-50, 51-100, 101-150, 151-200 or 201-250 predictive combinations of factors for the onset of HF. We found that the probability of HF progressively increased as the number of predictive combinations of factors increased. We identified combinations of variables that predict HF onset. An increased number of matching predictive combinations for the onset of HF increased the probability of HF onset.

Surgical resection of a thymoma developed in a case with isolated persistent left superior vena cava.

INTRODUCTION: Persistent left superior vena cava (PLSVC) is one of the most common vascular abnormalities in the chest. In approximately 10 % of cases, the right superior vena cava is missing, which is called isolated persistent left superior vena cava (IPLSVC). PRESENTATION OF CASE: The case is an 85 years-old female. An anterior mediastinal tumor was accidentally revealed when the patient was admitted after a traffic accident. As the tumor became larger within four months, a thymectomy was planned. The anterior mediastinal tumor was in front of the ascending aorta, which was close to the confluence of the left and right brachiocephalic veins in normal anatomy. However, in this case, the right superior vena cava was missing, and the right brachiocephalic vein flowed into the left superior vena cava by the chest computed tomography. Preoperative examinations found no accompanying cardiac abnormality. Robot-assisted thymectomy was performed. No tumor infiltration was observed in the right brachiocephalic vein. No abnormality was found in either phrenic nerve. The tumor could be safely resected, and her postoperative course was uneventful. The pathological diagnosis was a thymoma. DISCUSSION: A case of thymectomy with IPLSVC is quite rare. A careful observation of the preoperative computed tomography images helps to diagnose IPLSVC. Technically, thymectomy was not much different from normal, other than the reversed location of the veins. However, it should be noted that IPLSVC cases may have cardiac malformations. CONCLUSION: Thymectomy for thymoma with IPLSVC can be safely performed when the left and right veins are reversed.