Improvements in Artery Occlusion by Low‐Density Lipoprotein Apheresis in a Patient with Peripheral Arterial Disease

Abstract: Peripheral arterial disease (PAD; arteriosclerosis obliterans) shows ischemic symptoms along the peripheral arteries due to reduced blood flow, and the number of patients with PAD is increasing. Several papers have reported on the clinical effect of low‐density lipoprotein apheresis (LDL‐A) on PAD, but there has been no report so far on the improvement of total peripheral artery stenosis by LDL‐A. We report on the clinical course of a female PAD patient with intractable decubitus in her heel due to the complete occlusion of anterior tibial artery who was treated by a series of LDL‐A sessions. The complete occlusion of the anterior tibial artery improved as seen on angiography, and the decubitus in her heel also markedly improved after LDL‐A therapy. This report supports the clinical benefit of LDL‐A for the treatment of PAD.     

Changes in muscle sympathetic nerve activity during sleep in humans.

We microneurographically recorded muscle sympathetic nerve activity (MSA) during sleep in 12 healthy volunteers while simultaneously recording EEG, EOG, ECG, respiration, and blood pressure and determined the number of pulse-synchronous MSA bursts per minute (burst rate) for non-rapid eye movement (nonREM) sleep and rapid eye movement (REM) sleep. MSA decreased during nonREM sleep with progressively deeper sleep stages. During REM sleep, the burst rate of MSA increased and was associated with marked fluctuations in arterial blood pressure. During sleep stage 2, MSA bursts occurred approximately 1 second after spontaneous K-complexes. We conclude that (1) the decreases in MSA during nonREM sleep stages may indicate sleep-stage dependent central suppression of MSA activity; (2) increases in MSA during REM sleep suggest instability of the autonomic nervous system; and (3) a common pathway may exist for MSA bursts and K-complexes.     

Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria

Journal of Gastroenterology - The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for...     

What modifies the relation between tumour size and lymph node metastases in T1 breast carcinomas?

AIMS: To evaluate which pathological and clinical parameters modify the relation between tumour size and lymph node metastases in invasive breast carcinomas < 20 mm. METHODS: In a retrospective study, 1075 patients with pT1 invasive breast carcinoma and with known nodal status were analysed. The size of the infiltrating tumour was microscopically evaluated, and the in situ component was not considered. The additional pathological parameters considered were: tumour grade, peritumoral vascular invasion, multicentricity, and angiogenesis. The immunophenotype of the tumour was determined as: the expression of oestrogen (ER) and progesterone (PR) receptors, p53, and c-erbB2. The patients were grouped by age as follows: < 50, 51-70, and > 70 years old. RESULTS: Three hundred and seventy four patients (34.8%) were node positive. Univariate analysis showed that nodal positivity was significantly correlated with large tumour size (> 10 mm), vascular invasion, grade 2-3, multicentricity, and high angiogenesis (> 100 microvessels/x20 high power frame). No significant correlation was found between nodal positivity and ER, PR, p53, or c-erbB2 status. Interestingly, the association with in situ carcinoma was correlated with lower nodal positivity in tumours presenting equally sized infiltrating components. Age was an independent variable and significantly modified the risk of nodal positivity in tumours < 1 cm. In fact, in patients under 51 years of age, the proportion of nodal positivity in pT1a tumours was sevenfold higher than in older patients. In patients from 51 to 70 years old, nodal positivity correlated with tumour size, and multicentricity was an additional risk factor. CONCLUSIONS: These data suggest that, together with tumour size, the presence of in situ carcinoma, and vascular invasion, age is one of the most important predictors of metastatic diffusion in breast carcinomas.     

EML4-ALK Fusion in Lung

This Correspondence relates to EML4-ALK Rearrangement in Non-Small Cell Lung Cancer and Non-Tumor Lung Tissues by Martelli et al (Am J Pathol 2009 174:661–670)     

EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.).     

Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: Scaffold design and its performance when seeded with goat bone marrow stromal cells

Recent studies suggest that bone marrow stromal cells are a potential source of osteoblasts and chondrocytes and can be used to regenerate damaged tissues using a tissue-engineering (TE) approach. However, these strategies require the use of an appropriate scaffold architecture that can support the formation de novo of either bone and cartilage tissue, or both, as in the case of osteochondral defects. The later has been attracting a great deal of attention since it is considered a difficult goal to achieve. This work consisted on developing novel hydroxyapatite/chitosan (HA/CS) bilayered scaffold by combining a sintering and a freeze-drying technique, and aims to show the potential of such type of scaffolds for being used in TE of osteochondral defects. The developed HA/CS bilayered scaffolds were characterized by Fourier transform infra-red spectroscopy, X-ray diffraction analysis, micro-computed tomography, and scanning electron microscopy (SEM). Additionally, the mechanical properties of HA/CS bilayered scaffolds were assessed under compression. In vitro tests were also carried out, in order to study the water-uptake and weight loss profile of the HA/CS bilayered scaffolds. This was done by means of soaking the scaffolds into a phosphate buffered saline for 1 up to 30 days. The intrinsic cytotoxicity of the HA scaffolds and HA/CS bilayered scaffolds extract fluids was investigated by carrying out a cellular viability assay (MTS test) using Mouse fibroblastic-like cells. Results have shown that materials do not exert any cytotoxic effect. Complementarily, in vitro (phase I) cell culture studies were carried out to evaluate the capacity of HA and CS layers to separately, support the growth and differentiation of goat marrow stromal cells (GBMCs) into osteoblasts and chondrocytes, respectively. Cell adhesion and morphology were analysed by SEM while the cell viability and proliferation were assessed by MTS test and DNA quantification. The chondrogenic differentiation of GBMCs was evaluated measuring the glucosaminoglycans synthesis. Data showed that GBMCs were able to adhere, proliferate and osteogenic differentiation was evaluated by alkaline phosphatase activity and immunocytochemistry assays after 14 days in osteogenic medium and into chondrocytes after 21 days in culture with chondrogenic medium. The obtained results concerning the physicochemical and biological properties of the developed HA/CS bilayered scaffolds, show that these constructs exhibit great potential for their use in TE strategies leading to the formation of adequate tissue substitutes for the regeneration of osteochondral defects.     

Influence of Semicrystalline Morphology on the Glass Transition of Poly(L‐lactic acid)

Summary: Semicrystalline specimens of poly(L ‐lactic acid) (PLLA) were prepared by isothermal cold‐ or melt‐crystallization over a wide temperature range. The morphologies at different length scales were characterized using polarized optical microscopy, WAXS and SAXS. The glass transition temperature (T_g), determined calorimetrically, exhibited a general decrease with an increase in crystallization temperature (T_c) for either cold‐ or melt‐crystallized specimens. The measurements of the heat capacity increment at T_g indicated that a significant amount of the rigid amorphous fraction coexisted with the crystalline and mobile amorphous phases in semicrystalline PLLA. A three‐phase model (crystalline phase, mobile amorphous phase and rigid amorphous phase) is, therefore, appropriate for the interpretation of the structure of semicrystalline PLLA. According to a one‐dimensional layer stack model, the layer thicknesses of the three phases were further evaluated approximately. The increasing of T_g was found to be correlated to significant decreasing thickness of the crystalline layer, gradual decreasing thickness of the rigid amorphous layer, and a slight increasing trend in the thickness of the mobile amorphous layer. We suggest that the rigid amorphous layer of semicrystalline PLLA may possibly play a role in loosening the constraints imposed by the crystalline layer on the amorphous chain motions inherent to the glass transition.

The optical microscopy photograph shows the spherulitic morphologies developed after melt crystallization at 140 °C.