Background
Anaplastic lymphoma kinase (ALK)‐positive lung cancer has a better long‐term prognosis with ALK‐inhibitor than other lung cancers. However, resistance to ALK‐inhibitors and the control of ...metastases in the central nervous system (CNS) remain to be a challenge in the management of ALK‐positive lung cancer.
Case
We present the case of a 23‐year‐old man who developed multiple brain metastases while receiving alectinib treatment for ALK‐positive lung cancer. After 3 months of lorlatinib initiation, brain metastases disappeared, and complete response (CR) was maintained.
Conclusion
While lorlatinib can be used as first line therapy, this drug may be considered as second line or later option for patients with multiple brain metastases if the patient has already been treated with other ALK‐inhibitors since lorlatinib is thought to have good CNS penetration. This treatment option should be verified by further research.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The magnetic properties and microstructure of Co80Pt20-30 vol % B2O3 granular medium deposited on nucleation layers (NLs) with Co80Pt20-30 vol % oxides (oxides: Nb2O5, WO3, Ta2O5, SiO2, TiO2, Al2O3, ...Cr2O3, and ZrO2) of various thicknesses were investigated. By introducing an NL, a granular medium with columnar growth of small magnetic grains can be obtained. Furthermore, magnetic grains are separated with an oxide grain boundary material from the initial growth region that promotes the decoupling of magnetic grains, which corresponds to an increase in coercivity. The degrees of diameter reduction and decoupling of magnetic grains depend on the NL thickness and the melting point of the oxide utilized in the NL.
Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke ...severity in patients with CE stroke divided by the type of AF.
Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between patients with PAF (n = 127) and PerAF (n = 231).
Patients with PerAF were more likely to take oral anticoagulants (OACs) than those with PAF (37% vs. 13%, P < 0.0001), even though still underuse of OAC in both patients. Regarding stroke severity on admission, patients with PerAF exhibited a tendency toward a higher score on the National Institutes of Health Stroke Scale (NIHSS) compared with patients with PAF (12 5-20 vs. 9 4-18; P = 0.12). Mortality and mRS score at discharge were higher in the PerAF than in the PAF group (13% vs. 4%; P = 0.005, and 3 1-5 vs. 2 1-4; P = 0.01, respectively). Multivariate analyses confirmed that PerAF was a significant determinant of severe stroke (NIHSS score > 8) on admission (odds ratio OR to PAF = 1.80; 95% confidence interval CI 1.08-2.98; P = 0.02) and of an mRS score ≥ 3 at discharge (OR = 2.07; 95% CI 1.24-3.46; P = 0.006). Patients with PerAF had three times more internal carotid artery occlusion evaluated by magnetic resonance angiography, which indicated a more severe cerebral embolism compared with patients with PAF.
We found underuse of OAC in high risk AF patients with CE stroke. PerAF is significantly associated with severe stroke on admission and an unfavorable functional outcome at discharge in Japanese patients with CE stroke.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In addition to its regulatory effect on bone mass, calcitonin has been shown to relieve pain and alleviate peripheral circulatory disturbance in patients with Raynaud’s syndrome and complex regional ...pain syndrome. In the present study, we investigated whether calcitonin ameliorates diminished blood flow and enhanced arterial contraction in response to noradrenaline in chronic constriction injury (CCI) of the sciatic nerve in rats. Following surgically induced CCI, laser Doppler flowmetry studies showed a significant decrease in plantar skin blood flow of the ipsilateral hind paw compared to the contralateral side. A subcutaneous bolus injection of elcatonin (20 U/kg), a synthetic derivative of eel calcitonin, significantly improved decreased skin blood flow in the ipsilateral side. In vitro analysis of plantar arteries isolated from the ipsilateral hind paw 7–13 days after the CCI procedure showed higher sensitivity to noradrenaline than the plantar arteries from the contralateral side. Elcatonin (0.1–10 nm) significantly reduced noradrenaline‐induced contraction in the arteries of the ipsilateral side, whereas it had little effect on those of the contralateral side. These results suggest that calcitonin selectively ameliorates enhanced arterial contractility in CCI neuropathic rats, thus leading to its alleviating effect on peripheral circulatory disturbance.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background: It is still controversial whether intravenous administration of β-blocker in the very acute phase of acute myocardial infarction (AMI) is beneficial. Landiolol is an ultra-short-acting ...β-blocker that has less effect on blood pressure, but little is known about its efficacy and safety for patients with AMI undergoing primary percutaneous coronary intervention (PCI). Methods and Results: A consecutive 96 patients with AMI not manifesting cardiogenic shock were prospectively randomized to landiolol (n=47) or a control group (n=49). Continuous administration of landiolol (3μg·kg-1·min-1 for 24h) was done just after PCI in the landiolol group, but not in the control group. Heart rate decreased by 9.4±1.7beats/min after initiation of landiolol (P<0.01), but was unchanged in the control group. Left ventricular ejection fraction assessed 6 months later was greater than that at 2 weeks in the landiolol group (52.0±1.5 vs. 49.1±1.5%, P=0.01), but remained unchanged in the control group. Left ventricular end-diastolic volume index assessed 6 months later was increased compared with that at 2 weeks in the control group (78.0±2.7 vs. 72.5±2.8ml/m2, P=0.02), whereas it was unchanged in the landiolol group. Conclusions: Early intravenous administration of landiolol in patients with AMI undergoing PCI is safe and has the potential to improve cardiac function and inhibit cardiac remodeling in the chronic phase. (Circ J 2012; 76: 439-445)
Aim
Denosumab prevents osteoporosis by potently inhibiting bone resorption, but requires oral therapy with calcium and vitamin D preparations to prevent the side effects of hypocalcemia. Generally, a ...combination drug containing calcium, natural vitamin D, and magnesium is used. However, if activated vitamin D has been used before the initiation of denosumab therapy, continued use of activated vitamin D is not uncommon. This study aimed to evaluate the combination vitamin D preparation, alfacalcidol, and eldecalcitol on the therapeutic effect on denosumab therapy, the preventive effect on hypocalcemia, and the effect on renal function, to determine the optimal choice of concomitant medication.
Methods
This is a retrospective and single‐center study. Among 39 patients who had used denosumab (60 mg dose) for at least 12 months between November 2013 and October 2015, those who used the combination medication concomitantly as the standard treatment, those who used alfacalcidol concomitantly, and those who used eldecalcitol concomitantly were compared.
Results
Denosumab therapy markedly increased lumbar spine and femoral neck bone densities at 12 months in the three groups, showing no particular difference in the rate of increase of bone density. The three groups had marked decreases in bone metabolism markers, but had no intergroup differences. No hypocalcemia, hypercalcemia, or obvious renal dysfunction occurred over 12 months.
Conclusion
This study indicates that the use of activated vitamin D preparations, as concomitant medications with denosumab therapy, is appropriate considering the therapeutic efficacy of denosumab, prevention of hypocalcemia, and influence on renal function.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Introduction The impact of atrial natriuretic peptide (ANP) value for predicting paroxysmal atrial fibrillation (pAF) in ischemic stroke patients remains uncertain. Methods The consecutive 222 ...ischemic stroke patients (median 77 IQR 68-83 years old, 93 females) within 48 hours after onset were retrospectively studied. Plasma ANP and brain natriuretic peptide (BNP) levels were simultaneously measured at admission. Of all, 158 patients had no evidence of atrial fibrillation (AF) (sinus rhythm SR group), 25 patients had pAF (pAF group), and the other 39 patients had chronic AF (cAF group). We investigated predicting factors for pAF, with focus on ANP, BNP, and ANP/BNP ratio. Results ANP value was significantly higher in the pAF than in the SR group (97 50-157 mg/dL versus 42 26-72 mg/dL, P < .05) and further increased in the cAF group (228 120-392, P < .05 versus pAF and SR groups). Similarly, the BNP value was higher in the pAF than in the SR group (116 70-238 mg/dL versus 34 14-72 mg/dL, P < .05) and further increased in the cAF group (269 199-423, P < .05 versus pAF and SR groups). ANP/BNP ratio was lower in the pAF and cAF groups than in the SR group (.6 .5-1.2 and .7 .5-1.0 versus 1.3 .8-2.4, both P < .05. Multivariate analysis in the SR and pAF groups (n = 183) demonstrated that age, congestive heart failure, ANP, and BNP, but not ANP/BNP ratio, were independent predictors for detecting pAF. Receiver operating characteristic curve analysis further showed that area under the curve was similar between ANP and BNP (.76 and .80). Conclusions ANPmay be clinically useful for detecting pAF in ischemic stroke patients as well as BNP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
An observation system of centimeter-order of view of magnetic domain with local magnetization direction was developed by designing a telecentric optical system of finite design through the extension ...of microscope technology. The field of view realized in the developed system was 1.40 × 1.05 cm as suppressing defocus and distortion. Detection of the local magnetization direction has become possible by longitudinal Kerr observation from the orthogonal two directions. This system can be applied to the domain observation of rough surface samples and time resolved analysis for soft magnetic materials such as amorphous foil strips and soft magnetic thin films.
Measurement of the stacking faults (SFs) formed in a pseudo-hexagonal closed packed (pseudo-hcp) film is proposed using a laboratory-scale x-ray diffractometer. The pseudo-hcp structure includes (1 1 ...1)-oriented face-centred-cubic (fcc), c-plane oriented hcp and their mediate structures with the SFs. Diffractions from the (11.0) and (10.0) planes, DH and DL, were observed in the in-plane x-ray diffraction (XRD) profiles of the pseudo-hcp materials. The structure factor revealed that DH and DL originate from the number of total atomic layers and the imbalance of the number of A, B and C atomic layers, respectively. Therefore, the intensity ratio of DH to DL, corrected by Lorentz and atomic scattering factors (corrected IL/IH), is defined as the degree of SFs for pseudo-hcp materials from the stacking probability, independent of thickness, compositional atoms and lattice constants. Theoretical values of the corrected IL/IH are 0.25 for perfect hcp stacking and 0 for perfect fcc stacking and statistical calculations revealed that this index is very sensitive to the approach of perfect hcp stacking order rather than that of perfect fcc stacking order. By applying this evaluation to experimentally sputtered thin films, it was clarified that: (1) in Pt based alloy films, addition of Cr, Mo and W is found to stabilize -A-B-A- stacking, (2) the corrected IL/IH for a c-plane oriented Co film is only 0.04, which corresponds to an hcp stacking probability of 0.9 for a pure Co film and (3) in both cases of Co-Ir and Co-Pt alloy films, the atomic-layered structure approaches perfect hcp stacking for additive alloying element contents of 22-25 at%, which is considered to be one of the factors contributing to the large absolute value of uniaxial magnetocrystalline anisotropy.
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