Asymmetric Intramolecular Dearomatization of Nonactivated Arenes with Ynamides for Rapid Assembly of Fused Ring System under Silver Catalysis.

Arene dearomatization is a straightforward method for converting an aromatic feedstock into functionalized carbocycles. Enantioselective dearomatizations of chemically inert arenes, however, are quite limited and underexplored relative to those of phenols and indoles. We developed a method for diazo-free generation of silver-carbene species from an ynamide and applied it to the dearomatization of nonactivated arenes. Transiently generated norcaradiene could be trapped by intermolecular [4 + 2] cycloaddition, synthesizing polycycles with five consecutive stereogenic centers. This protocol constitutes the first highly enantioselective reaction based on the diazo-free generation of silver-carbene species. Mechanistic investigations revealed a dearomatization followed by two different classes of pericyclic reactions, as well as the origin of the chemo- and enantioselectivity.

Intermolecular hydrogen bonding controlled stereoselective photocycloaddition of vinyl ethers to 1-cyanonaphthalenes.

With the aim of developing photoreactions that use intermolecular hydrogen bonding interactions to control the efficiency and stereochemistry, the 1,2-[2 + 2] photocycloaddition reactions of 1-cyanonaphthalene derivatives with vinyl ethers possessing hydroxy groups were examined. The photoreaction of 1-cyano-4-(hydroxymethyl)naphthalene (1a) with 2-hydroxyethyl vinyl ether (2a) at room temperature was found to produce cycloadducts, endo-3aa and exo-3aa, in a non-stereoselective manner (56 : 44). However, this photoreaction at -40 °C displays a high endo-selectivity (81 : 19). In the reaction of 1a with ethyl vinyl ether (2b), high endo selectivity was observed both at room temperature and at -40 °C. The endo selectivity in the [2 + 2] photocycloaddition process is attributed to the intermolecular hydrogen bonding interactions between the reacting partners in the ground and excited states. Evidence to support this conclusion comes from the results of VT NMR and fluorescence quenching experiments, as well as the photoreactions of deuterated substrates.

Valence-isomer selective cycloaddition reaction of cycloheptatrienes-norcaradienes.

The rapid and precise creation of complex molecules while controlling multiple selectivities is the principal objective in synthetic chemistry. Combining data science and organic synthesis to achieve this goal is an emerging trend, but few examples of successful reaction designs are reported. We develop an artificial neural network regression model using bond orbital data to predict chemical reactivities. Actual experimental verification confirms cycloheptatriene-selective [6 + 2]-cycloaddition utilizing nitroso compounds and norcaradiene-selective [4 + 2]-cycloaddition reactions employing benzynes. Additionally, a one-pot asymmetric synthesis is achieved by telescoping the enantioselective dearomatization of non-activated benzenes and cycloadditions. Computational studies provide a rational explanation for the seemingly anomalous occurrence of thermally prohibited suprafacial [6 + 2]-cycloaddition without photoirradiation.

Acute limb ischemia due to severe heparin-included thrombocytopenia with thrombosis during puerperium.

We present the case of a 39-year-old pregnant woman who had intrauterine fetal death and imminent uterine rupture and underwent cesarean section. She also underwent catheter embolization for hemorrhagic shock due to bleeding from the uterine artery, and heparin-containing saline was used. On day 7 of hospitalization, she felt severe pain in her right lower leg, and computed tomography (CT) revealed focal nonocclusive thrombus formations in the right common and external iliac artery. After intravenous heparin administration, she suddenly developed dyspnea, her blood pressure dropped, and her platelet count decreased. We diagnosed her with heparin-induced thrombocytopenia (HIT). Although we discontinued heparin and switched to argatroban, CT after 5 days revealed subtotal occlusion of the right iliac artery by a massive thrombus. We performed surgical thrombectomy using a Fogarty catheter, but blood flow was not restored. Therefore, we administered urokinase continuously with catheter-directed thrombolysis (CDT). The thrombus in the iliac artery gradually cleared and was successfully eliminated. However, the patient developed gangrene in her right lower leg, and we decided to perform an above-knee amputation of the right leg. She was discharged with a prosthetic leg and prescribed 15 mg of rivaroxaban per day. Learning objective: HIT is a known serious side effect of heparin administration, and it can sometimes be fatal. HIT treatment using aggressive thrombectomy procedures may be ineffective since such procedures may accelerate thrombus formation when the coagulation cascade is highly activated. In this case, CDT may have to be considered as the first-line treatment before Fogarty thrombectomy when argatroban therapy fails.

Tumor lysis syndrome after sorafenib for hepatocellular carcinoma: a case report.

We encountered a patient who developed marked renal impairment and hyperuricemia in a short period after sorafenib administration, which suggested tumor lysis syndrome (TLS). A 79-year-old woman with hepatitis C-related liver cirrhosis was found to have intermediate hepatocellular carcinoma (HCC) according to Barcelona Clinic Cancer staging classification. Pre-treatment laboratory tests showed mild renal impairment. On the 10th day of sorafenib intake, the creatinine and uric acid levels rose to 2.99 and 16.1 mg/dl, respectively, and arterial blood gas analysis showed respiratory compensated metabolic acidosis, which suggested grade I clinical TLS according to the diagnostic criteria of TLS as defined by Cairo-Bishop. TLS is a group of metabolic abnormalities that arise from the rapid breakdown of many tumor cells upon the initiation of malignant tumor chemotherapy, resulting in the release of intracellular metabolites that exceed the ability of the kidney to excrete them. TLS occurs more rarely in solid tumors, including HCC, than in hematologic malignancies. Sorafenib is administered to patients with renal impairment at recommended doses. However, the drug may cause TLS or severe renal impairment in advanced HCC patients with preexisting mild renal impairment, necessitating reduced-dose therapy and careful follow-up after the start of therapy to facilitate early diagnosis and treatment. This is a very rare complication developed in a short period treated with sorafenib as a single-agent for an advanced HCC.

Effects of Lutein and Astaxanthin Intake on the Improvement of Cognitive Functions among Healthy Adults: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Fruits and vegetables are generally rich in antioxidants such as carotenoids. Consumption of carotenoids is expected to have benefits on cognitive functions in humans. However, previous randomized controlled trials (RCT) using carotenoids have reported inconsistent results. Therefore, this systematic review (SR) aimed to summarize the effect of carotenoid intake on cognitive functions in humans. METHOD: PubMed, Cochrane Library, Web of Science, and PsychoINFO were searched for research papers on carotenoid intake with the criteria that 1) oral carotenoid intake was evaluated using RCTs, 2) participants were healthy young, middle-aged, or older, and 3) cognitive functions were measured using RCTs. RESULTS: Five studies using lutein and two studies using astaxanthin met the inclusion criteria. Consumption of lutein and its isomer showed consistent results in selective improvement of visual episodic memory in young and middle-aged adults while inhibition was observed in middle-aged and older adults. One of the two included astaxanthin studies reported a significant improvement of verbal episodic memory performance in middle-aged adults. CONCLUSION: This SR showed that the 10 mg lutein per day for twelve months can lead to improvement of cognitive functions. Due to the small number of studies, it is difficult to conclude whether astaxanthin would have a positive effect on cognitive functions.

Mediastinal lung herniation associated with pulmonary sequestration.

Mediastinal lung herniation is a rare condition characterized by protrusion of 1 lower lung through behind the heart into the opposite side of the chest, usually from right to left. We present a case of mediastinal lung herniation associated with pulmonary sequestration, which was confirmed both surgically and pathologically in a 13-year-old girl initially admitted with a diagnosis of pneumonia. Contrast-enhanced computed tomographic images using a multidetector-row computed tomography clearly demonstrated the right lung herniation toward the left and 2 aberrant systemic arteries supplying the sequestered lung mass. These arteries run through the herniated lung from right to left. Additionally, on the basis of pleural anatomy, we discuss herein the difference between a mediastinal lung herniation and horseshoe lung.

Clinical utility of early use of tolvaptan in very elderly patients with acute decompensated heart failure.

OBJECTIVE: The establishment of an optimal strategy for elderly patients with acute decompensated heart failure (ADHF) is currently an important issue. Particularly in very elderly (VE) patients, ADHF is associated with a poor prognosis. We therefore aimed to evaluate the efficacy and safety of the early use of tolvaptan (TLV) in VE patients. METHODS: Of 245 patients with ADHF admitted between March 2013 and July 2014, we prospectively enrolled 111 patients with TLV first administered within 24 h of hospitalization. These were divided into two groups according to the age: VE (≥85 years, n=45) and not very elderly (NVE, <85 years, n=66). The endpoints were the incidence of worsening renal function, death by any cause, or the length of hospital stay. RESULTS: There were no significant differences between the two groups in the incidence of worsening renal function (26.7% in VE vs. 25.8% in not VE, p=0.92), dose of TLV after hospitalization (7.4±0.7 vs. 7.5±1.3 mg/day, p=0.63), mean duration of the use of TLV (4.3±3.5 vs. 5.4±4.8 days, p=0.17), or mean length of hospital stay (16.5±7.8 vs. 15.7±8.0 days, p=0.64). CONCLUSION: TLV shows similar efficacy and safety in both VE and NVE groups. Even for VE patients with ADHF, initiation of TLV with standard diuretic treatment may have the potential not to increase the incidence of worsening renal function.

Individualized antiplatelet therapy after drug-eluting stent deployment: Implication of clinical trials of different durations of dual antiplatelet therapy.

At present, there is consensus that prolonged dual antiplatelet therapy (DAPT) is effective to reduce cardiovascular events at the expense of bleeding complication events. A causal relationship of prolonged DAPT with an increase in mortality remains debatable, however, it appears to be obvious that bleeding complications are associated with an increase in cardiac events. Thus, individualized optimal DAPT duration balancing the risk and benefit of DAPT should be applied. In addition, strategy to minimize bleeding complications is highly recommended. Several risk scores have been reported to discriminate the risk and benefits of DAPT. However, in general, bleeding risk and event risk are correlated with each other, thus predictability of these scores is limited to moderate. Therefore, interpretation of previous trials is important to overcome the shortcome in outcomes. In this review, we provide an overview of DAPT trials and clarify the shortfalls to consider in Japan. Finally, possible future trends with reference to the results of recent clinical trials will be presented.

Diffusion-weighted MR imaging of early-stage Creutzfeldt-Jakob disease: typical and atypical manifestations.

Creutzfeldt-Jakob disease causes progressive dementia and, eventually, death. The infectious agent is thought to be proteinaceous scrapie particles. Prompt diagnosis is essential to prevent human-to-human transmission. Progressive brain atrophy and areas of high signal intensity in the cerebral cortex and basal ganglia are well-known features of Creutzfeldt-Jakob disease depicted on T2-weighted magnetic resonance (MR) images. However, in the early stage of disease, the appearance of the brain on T2-weighted MR images often is normal, and it may be impossible on that basis to reach a diagnosis. Diffusion-weighted imaging therefore has gained attention as a useful modality for the early diagnosis of Creutzfeldt-Jakob disease. Even before the appearance of the characteristic periodic synchronous discharges on the electroencephalogram, diffusion-weighted images in most cases of Creutzfeldt-Jakob disease depict areas of abnormal signal hyperintensity in the cortex and in the basal ganglia or thalamus. These imaging abnormalities are accompanied by decreased apparent diffusion coefficient values suggestive of restricted diffusion within the tissue. However, if diffusion-weighted imaging findings of abnormal high signal intensity are restricted to the cerebral cortex, it may be necessary to differentiate between Creutzfeldt-Jakob disease and other conditions that may produce progressive dementia (eg, venous hypertensive en-cephalopathy; chronic herpes encephalitis; and the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes).

Significance of ST-segment morphology noted on electrocardiography during the recovery phase after exercise in patients with ischemic heart disease as analyzed with simultaneous dual-isotope single photon emission tomography.

BACKGROUND: The significance of differences in electrocardiographic morphology that occur during the recovery phase after exercise has not been clarified. We investigated the relationship between postexercise electrocardiographic morphology and the pattern of residual ischemia measured at that time. METHODS: Exercise dual-isotope single photon emission computed tomography was performed on 171 consecutive patients with chest pain syndrome. After injection of technetium-99m tetrofosmin at peak exercise and thallium-201 at 3 minutes after exercise, dual-isotope single photon emission computed tomographic images were obtained simultaneously. After cross-talk compensation, the extent of ischemia and its localization were measured at both peak exercise and after exercise. RESULTS: When 64 patients with angiographically and scintigraphically proven ischemic heart disease were grouped by morphology of ST-segment depressions at 3 minutes after exercise, 38 patients with the downsloping type had ischemia localized mainly to the middle and basal levels as compared with the more rapid resolution of ischemia in 12 patients with horizontal type and 14 patients with no ischemic electrocardiographic response (apical level 18.4% [7/38], 8.3% [1/12], and 0% [0/14], P = not significant, middle level 47.4% [18/38], 16.7% [2/12], and 7.1% [1/14], P <.01, basal level 57.9% [22/38], 33.3% [4/12], and 14.3% [2/14], P <.02, respectively) independent of the extent or localization of any ischemia noted during exercise (all levels, P = not significant). CONCLUSION: Electrocardiographic morphology during the recovery phase of exercise reflects the extent and localization of residual ischemia at that time independent of ischemic changes noted during exercise.

Emergency percutaneous balloon aortic valvuloplasty using a triple balloon technique to a patient with severe aortic stenosis.

A 76-year-old male who had already been diagnosed with ischemic heart disease and severe aortic stenosis was transferred to our hospital in a state of cardiogenic shock. We finally diagnosed him with severe aortic stenosis. We decided to perform emergency balloon aortic valvuloplasty (BAV) as a bridge treatment to surgical repair. We first performed BAV with a double balloon technique, and next with a triple balloon technique. As a result, the blood pressure recovered, and surgical aortic valve repair could thus be successfully performed.

Serial diffusion-weighted MRI of Creutzfeldt-Jakob disease.

OBJECTIVE: The objective of our study was to evaluate the clinical usefulness of MRI findings, including diffusion-weighted imaging, in relation to the clinical signs and symptoms of Creutzfeldt-Jakob disease (CJD). MATERIALS AND METHODS: We reviewed nine cases of CJD in which MRI was performed from the early to terminal phase of the disease. MRI findings were correlated before (early phase) and after (intermediate phase) the onset of the characteristic clinical findings of myoclonus and periodic synchronous discharges on electroencephalograms. The chronologic changes in imaging findings were followed from the akinetic mutism to the terminal phase of the disease (terminal phase). T2-weighted images had been obtained in all the patients, and diffusion-weighted images and FLAIR images had been obtained in six patients. We evaluated the images for the presence and location of abnormal signal intensities. RESULTS: During the early phase, the T2-weighted images showed no abnormal findings. The diffusion-weighted images, however, revealed abnormal high signal intensities in the cortex in all patients and in the basal ganglia in five patients. In two cases, there were abnormal signals on FLAIR images that corresponded to diffusion-weighted imaging abnormalities. During the intermediate phase, the area of the high signal intensities on the diffusion-weighted images had expanded and progressive cerebral atrophy had become apparent. During the terminal phase, abnormal high signal intensities in the cerebral cortex and basal ganglia on the diffusion-weighted images in one patient disappeared. CONCLUSION: Diffusion-weighted imaging is extremely useful in detecting CJD during the very early phase-even before the onset of characteristic clinical findings.