Abstract
Background and Aims
Clotting within the membrane and/or venous ‘air trap’ chamber is common problems during continuous blood purification therapy. Frequent clotting during continuous blood ...purification therapy leads to inadequate solute removal, an increased circuit and filter cost, and an increased burden for the medical staff. Improvements in filter membrane materials may reduce the extent of clotting and prolong the filter life. The purpose of the present study was to clarify the characteristics of an NV polymer-embedded membrane (NV-PS) after long-term use, especially the adhesiveness of blood cells and changes in the solute removal performance.
Methods
Continuous hemofiltration (CHF) experiments using a permeate recycle mode were performed for 24 h using the same porcine whole blood divided into two portions to compare the NV-PS with a conventional polysulfone membrane (PS). The activated clotting time was adjusted to within a range of 300–400 s. The change in the dextran sieving coefficient (SC) of the membrane and the residual blood clots in the filters were evaluated after the completion of the CHF experiment.
Results
The increase in the transmembrane pressure and the pressure drop of the hemofilter were significantly smaller using the NV-PS than with the PS. For larger molecules (SC
$$ \leqq $$
≦
0.4), the reduction in SC after blood contact was significantly smaller for the NV-PS. Fewer blood cells remained in the residual blood clots when the NV-PS was used.
Conclusion
NV-PS has the advantages of showing a lower degree of reduction of the solute removal performance and also a lower degree of clogging of the hollow fibers during prolonged circulation. These characteristics may be expected to be advantageous when this membrane is used for continuous blood purification therapy in acute-phase patients.
Abstract
Background
When polymethyl methacrylate (PMMA) membranes are used in continuous renal replacement therapy, especially in patients with high cytokine levels, inflammatory cytokines and other ...substances are removed by the adsorption effect. However, such filters are prone to clogging, and the filter lifetime can be short. This study investigated the effects of hollow fiber inner diameter and membrane area on filter lifetime and protein removal performance using an in vitro continuous hemofiltration (CHF) experimental model with porcine blood.
Methods
Three types of filters with different hollow fiber inner diameters and membrane areas were used: CH-1.0N (membrane material, PMMA; membrane area, 1.0 m
2
; hollow fiber inner diameter, 200 µm), CH-1.0W (prototype: PMMA; 1.0 m
2
; 240 µm), and CH-1.8W (PMMA; 1.8 m
2
; 240 µm). During the experiment, pressure changes, filter lifetime measured from pressure and protein removal performance were measured using an in vitro CHF experimental model with porcine blood.
Results
The filter lifetime of CH-1.8W was significantly longer than those of CH-1.0N and CH-1.0W. The total protein adsorption was significantly higher for the CH-1.0W and CH-1.8W filters than for the CH-1.0N filter.
Conclusions
A larger membrane area from 1.0 to 1.8 m
2
contributed to a longer filter lifetime, while an increase in the hollow fiber inner diameter from 200 to 240 µm did not. On the other hand, the protein removal performance, especially the adsorption performance, was higher for membranes with a larger hollow fiber inner diameter from 200 to 240 µm.
We herein report the case of a 52-year-old man with stage IV lung adenocarcinoma. The patient was negative for epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated ...protein-like 4 (EML4) /anaplastic lymphoma kinase (ALK) rearrangement. He was treated with nivolumab as a third-line chemotherapy. After four cycles of nivolumab treatment, a partial response was observed in the brain and at the primary tumor site. Nivolumab treatment has been continued for 11 months without progression. Immunohistochemistry revealed that the programmed death-ligand 1 (PD-L1) expression was 0% (according to the tumor proportion score). Our case indicates that the efficacy of programmed cell death 1 inhibitors is not solely predicted by the PD-L1 status, and that immune checkpoint inhibitors might be effective for the treatment of central nervous system metastasis.
Background
Previous studies have described a role of oxidative stress in the pathogenesis of various pediatric disorders, but investigation into oxidative stress status in patients with severe ...disability remains limited. The aim of the present study was therefore to clarify the oxidative stress status in patients with severe disability, focusing specifically on intake of three major nutrients and micronutrients with antioxidant activities.
Methods
Thirty‐one patients with severe disability (mean age, 14.1 ± 7.8 years) were enrolled. Three in vivo biomarkers, plasma biological antioxidant potential (BAP), plasma reactive oxygen metabolite‐derived compounds (d‐ROM), and urinary 8‐hydroxydeoxyguanosine (8‐OHdG), were determined for evaluating oxidative status. The dietary intake of three major nutrients and various micronutrients was estimated from dietary records over a 3 day period.
Results
In patients with severe disability, BAP was significantly lower and d‐ROM and 8‐OHdG significantly higher than in historical controls. Among these markers, a significant positive correlation was found in BAP versus d‐ROM and d‐ROM versus 8‐OHdG. On multiple regression analysis, a significant inverse association between 8‐OHdG and carotenoid intake was seen.
Conclusion
The oxidative/antioxidative balance shifts towards oxidative status dominance in patients with severe disability. More research is needed on nutritional intake of antioxidative nutrients to determine whether they can be used to reduce oxidative stress.
Abstract Background: Carnitine plays a pivotal role in a variety of cellular functions. Carnitine deficiency often occurs in severely disabled patients, especially under valproic acid administration. ...However, the possible causative factors underlying carnitine deficiency have not been fully identified. The present study aimed at clarifying the association of various anthropometric and biochemical variables, including dietary intake of carnitine, with carnitine levels in severely disabled patients. Methods: Twenty-six severely disabled patients (mean age: 14.1 years; s.d. 7.8) were enrolled. Plasma carnitine levels were evaluated by an enzyme cycling assay. Estimation of the dietary intake of carnitine was made based on dietary records over a 3-day period. Results: Plasma total and free carnitine levels in patients were significantly lower than those in controls obtained from the previous report. However, the ratios of free carnitine to total carnitine did not change significantly. Free carnitine levels were well correlated with a nutritional intake of carnitine. Administration of not only valproic acid but also other anti-epileptic drugs was found to cause a significant decrease of free carnitine levels after adjusting the nutritional intake of carnitine. Among various anthropometric or biochemical variables, albumin and uric acid showed a significant correlation with free carnitine levels. Conclusions: Physicians should be aware of the fact that severely disabled patients are at risk for carnitine deficiency even in the absence of valproic acid administration, and pay more attention to the nutritional intake of carnitine.
Although food hypersensitivity is a public health concern, its documentation among the elderly is limited. The current study aims to compare the prevalence and characteristics of food ...hypersensitivity among adolescent women between aged 18-24 with among older women >50 years of age.
660 female university students between the ages of 18 and 24 who volunteered were enrolled as adolescent subjects. 470 women >50 years old who visited the Health Care Centre of Kyoto Katsura Hospital for health check-ups were enrolled as the older subjects. A questionnaire created by ourselves asking the presence of food hypersensitivity, symptoms, causative food, personal or family history of other allergic disorders was distributed.
The prevalence of food hypersensitivity was statistically similar between adolescent (8.2%) and older women (8.9%). Among them, only 24.1% of the adolescent women and 26.2% of the older women had been diagnosed by physicians as having food allergy. The main causative foods (fruits, shellfish and fish) and the manifestations relating to food hypersensitivity were almost identical between adolescent and older women. In both adolescent and older women, food hypersensitivity positive group showed significantly higher prevalence of personal or family history of allergic disorders than that in food hypersensitivity negative group.
These data indicate that food hypersensitivity in older women should be given more attention because the prevalence of this condition was as common as that in adolescent women.
The aim of the present study was to clarify clinical factors in low birth weight infants and their mothers associated with exclusive breastfeeding at both neonatal intensive care unit (NICU) ...discharge and the start of complementary feeding. One hundred and fifteen low birth weight children and 98 mothers attending the follow-up clinic of two tertiary NICUs in Nara prefecture (Japan), between June and September, 2011, were enrolled. The relationship between the feeding categories at NICU discharge or the start of complementary feeding, and clinical factors of the mothers and low birth weight infants collected by either their charts or a face-to-face interview was analyzed. The prevalence of exclusive breastfeeding was 22.6% at NICU discharge, and 15.7% at the start of complementary feeding. In logistic analysis, exclusive breastfeeding at NICU discharge was associated with mother's younger age at delivery and an earlier start of oral nutrition. Among 26 exclusively breast-fed infants at NICU discharge, fifteen infants (57.7%) were still being exclusively breast-fed at the start of complementary feeding. In low birth weight infants, a shorter stay at NICU and an earlier start of oral nutrition were associated factors with exclusive breastfeeding at the start of complementary feeding. None of maternal factors were found to be associated with exclusive breastfeeding at the start of complementary feeding. Conclusively, starting of oral nutrition as early as possible is thought to be crucial for introducing exclusive breastfeeding in low birth weight infants both at NICU discharge and the start of complementary feeding.
Background
Osimertinib is recommended for non‐small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such ...patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M‐positive advanced NSCLC who progress on prior EGFR‐tyrosine kinase inhibitors (TKIs).
Methods
We conducted a prospective observational cohort study. Median BSA and BMI were used as cut‐off values to evaluate the impact of body size variables on osimertinib chemotherapy.
Results
The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2, respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression‐free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS.
Conclusion
The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M‐positive NSCLC who progress on prior EGFR‐TKIs.
The interaction of amyloid β-proteins (Aβ) with membrane gangliosides has been reported to be an early event in Aβ fibril formation in Alzheimer's disease (AD). Neuronal degeneration in AD has been ...postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD), and 11 non-demented age-matched pathological controls) were examined in order to detect anti-glycosphingolipid (GSL) antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα) antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides). However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90%, 9 of 10 cases) and VD (100%), respectively. Most surprisingly, anti-GQ1bα antibodies (IgM) were found in 90% (9/10) and 100% (6/6) in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.
Background
The standard treatment for patients with unresectable locally advanced (LA) non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT ...demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA‐NSCLC patients based on the PACIFIC criteria.
Methods
We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA‐NSCLC treated with CRT between January 2012 and June 2018.
Results
We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum‐based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41–317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two‐year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two‐year survival rate: 87% vs. 41%, respectively; P = 0.001).
Conclusions
Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA‐NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.
PDF
