Association of Pre- and Post-Donation Renal Function with Midterm Estimated Glomerular Filtration Rate in Living Kidney Donors: A Retrospective Study

PurposeThe estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR_6m) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR_6m <60 mL/min/1.73 m² (eGFR_6m <60) and identify the risk factors that can predict the occurrence of eGFR_6m <60 in living kidney donors.Materials and MethodsLiving kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR_6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR_6m <60 occurrence were determined using the Youden index.ResultsThe eGFR_6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR_6m <60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR_6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863–0.908] vs. 0.862 (95% CI, 0.838–0.887), p<0.001}.ConclusionThe incidence of eGFR_6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR_6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR_6m <60.     

Comprehensive genetic features of gastric mixed adenoneuroendocrine carcinomas and pure neuroendocrine carcinomas

We aimed to determine the pathogenesis of gastric mixed adenoneuroendocrine carcinoma (MANEC) and pure neuroendocrine carcinoma (NEC), which is largely unknown. Targeted DNA sequencing was performed on 34 tumor samples from 21 patients – 13 adenocarcinoma (ADC)/NEC components from MANECs and eight pure NECs – and 21 matched non‐neoplastic gastric tissues. Mutational profiles of MANECs/NECs were compared with those of other tumors using public databases. The majority (64.1%; 59/92) of mutations in MANEC were shared by both ADC and NEC components. TP53 was the most commonly mutated gene in MANEC (69.2%, 9/13) and pure NEC (87.5%, 8/9). All TP53 mutations in MANEC were pathogenic mutations and were shared by both ADC and NEC components. A subset of TP53^WT MANECs had a microsatellite‐unstable phenotype or amplifications in various oncogenes including ERBB2 and NMYC, and the only TP53^WT pure NEC harbored MYC amplification. Compared to NEC in other organs, NECs arising from the stomach had unique features including less frequent RB1 mutations. Differentially altered genes of MANEC ADC components were significantly associated with receptor tyrosine kinase signaling pathways, while differentially altered genes of MANEC NEC components were significantly associated with the NOTCH signaling pathway. Our data provide evidence suggesting a possible clonal origin of ADC and NEC components of MANEC, and we found that gastric MANECs and pure NECs are distinct entities with unique mutational profiles and underlying protein networks. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Gastrointestinal and non-gastrointestinal complication rates associated with diagnostic esophagogastroduodenoscopy under sedation

Esophagogastroduodenoscopy (EGD) under sedation may result in gastrointestinal (GI) and non-GI complications. However, no previous studies have reported 30-day GI and non-GI complications after diagnostic EGD under sedation.We conducted a retrospective, observational study of 30-day GI and non-GI complication rates after outpatient diagnostic EGD under sedation in subjects ≥18 years between January 2012 and December 2017 based on a common data model database. Thirty-day complication rates were compared with EGD under sedation or not, type of sedation drugs (midazolam only vs midazolam/propofol) and age groups (18-64 year vs ≥65 year) for GI (bleeding and perforation) and non-GI complications (pneumonia, acute myocardial infarction, congestive heart failure and cerebral stroke).In total, 39,910 were performed with sedation (midazolam only, n = 16,033 and midazolam/propofol, n = 23,864) and 22,894 were performed without sedation. Elderly patients significantly favored EGD without sedation (P < .01). GI and non-GI complication rates were similar between EGD under sedation and without sedation (all P > .1) except for acute myocardial infarction rate, which was significantly higher in EGD without sedation than EGD under sedation (1.7/10,000 vs 0.3/10,000 persons, P = .043). All GI and non-GI complications were also similar between the midazolam/propofol and midazolam only groups as well as between young and old patients (all P > .1).Outpatient diagnostic EGD under sedation has an excellent safety profile. In addition, it can be safely performed with midazolam only or midazolam/propofol and in young and old patients.     

Sleep duration and health-related quality of life in Korean adults: 2007-2015 Korea National Health and Nutrition Examination Survey

Sleep and Breathing - To evaluate the association of sleep duration with health-related quality of life (HRQOL) and examine the influence of age, sex, and common comorbidities on this association....     

Prophylactic anti-tumor effects in a B cell lymphoma model with DNA vaccines delivered on polyethylenimine (PEI) functionalized PLGA microparticles.

Idiotypic sequences, specific to the hypervariable regions of immunoglobulins expressed by malignant B cells offer a therapeutic target in B cell lymphoma. Efficient approaches have been described to clone a single chain fragment of the tumor immunoglobulin (Ig) comprising of heavy and light Ig chains (sFv) fused with proinflammatory chemokines. Tumor associated, poorly immunogenic self antigens encoded by plasmid DNA (pDNA) have been rendered immunogenic by chemokine fusion, thereby targeting to antigen presenting cells (APCs) which differentially express chemokine receptors. Here we present an injectable (parenteral) approach using synthetic polymer based cationic microparticle formulations for enhancing the potency of such chemokine/self antigen expressing plasmid construct. Branched and linear polyethyleneimine (PEI) were conjugated on poly (D, L lactide-co-glycolide) (PLGA) microparticles using carbodiimide chemistry followed by efficient loading of plasmid DNA. In addition to imparting significant buffering ability to these cationic microparticles, flow cytometry studies indicate that these DNA loaded microparticles significantly up regulate CD80 and MHC class II markers in phagocytic RAW264.7 cells, indicating intrinsic adjuvant effects. Intradermal injections in Balb/c mice with these formulations induced significant protection upon tumor challenge with 2.5 times the minimal lethal dose. Long term survival rates were significant (p < 0.05) in comparison with saline injected controls or blank microparticles. Further studies indicated that intramuscular delivery might provide better protection compared to intradermal injections and perform similar to gene gun mediated administration. We conclude, based on these promising in vivo results, that such surface-functionalized microparticles offer an attractive strategy to improve the potency of self antigen-based cancer DNA vaccines.     

The Clinical Outcomes of Transcatheter Microcoil Embolization in Patients with Active Lower Gastrointestinal Bleeding in the Small Bowel

Objective

To assess the clinical outcomes of the transcatheter microcoil embolization in patients with active lower gastrointestinal (LGI) bleeding in the small bowel, as well as to compare the mortality rates between the two groups based on the visualization or non-visualization of the bleeding focus determined by an angiography.

Materials and Methods

We retrospectively evaluated all of the consecutive patients who underwent an angiography for treatment of acute LGI bleeding between January 2003 and October 2007. In total, the study included 36 patients who underwent a colonoscopy and were diagnosed to have an active bleeding in the LGI tracts. Based on the visualization or non-visualization of the bleeding focus, determined by an angiography, the patients were classified into two groups. The clinical outcomes included technical success, clinical success (no rebleeding within 30 days), delayed rebleeding (> 30 days), as well as the major and minor complication rates.

Results

Of the 36 patients, 17 had angiography-proven bleeding that was distal to the marginal artery. The remaining 19 patients did not have a bleeding focus based on the angiography results. The technical and clinical success rates of performing transcatheter microcoil embolizations in patients with active bleeding were 100% and 88%, respectively (15 of 17). One patient died from continued LGI bleeding and one patient received surgery to treat the continued bleeding. There was no note made on the delayed bleeding or on the major or minor complications. Of the 19 patients without active bleeding, 16 (84%) did not have recurrent bleeding. One patient died due to continuous bleeding and multi-organ failure.

Conclusion

The superselective microcoil embolization can help successfully treat patients with active LGI bleeding in the small bowel, identified by the results of an angiography. The mortality rate is not significantly different between the patients of the visualization and non-visualization groups on angiography.     

Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.

The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.     

Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation

Roflumilast, a potent and selective phosphodiesterase 4 (PDE4) inhibitor, has been demonstrated to be an effective anti-inflammatory agent in airway inflammatory diseases. In the present study, we investigated the mechanism of anti-inflammatory effects of roflumilast in murine macrophage cell line RAW264.7 cells. Roflumilast inhibited NO, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta production via suppression of their gene expressions in lipopolysaccharide (LPS)-stimulated macrophages. To elucidate the mechanism by which roflumilast inhibits the production of inflammatory mediators, we examined the effect of roflumilast on the activation of nuclear factor-kappaB (NF-kappaB) in these cells. Roflumilast inhibited the DNA binding activity of NF-kappaB by preventing inhibitor kappaBalpha phosphorylation and degradation. The phosphorylation of mitogen-activated protein (MAP) kinases, including stress-activated protein kinase/c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, was also markedly inhibited by roflumilast. Similar to the effects of roflumilast, treatment of either SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole] or SP600125 [anthra(1,9-cd)pyrazol-6(2H)-one 1,9-pyrazoloanthrone], specific inhibitors of p38 MAP kinase and JNK, respectively, suppressed NO, TNF-alpha, and IL-1beta production. Consistent with in vitro results, administration of roflumilast recovered the survival rate of LPS-treated mice, with concurrent suppression of plasma levels of nitrite/nitrate, TNF-alpha, and IL-1beta. These results suggest that the inhibitory activity of roflumilast on the production of inflammatory mediators seems to be mediated via inhibition of NF-kappaB, p38 MAP kinase, and JNK activation in macrophages.     

Functional characterization of mesenchymal stem cells labeled with a novel PVP‐coated superparamagnetic iron oxide

Magnetic resonance imaging of cells labeled with superparamagnetic iron oxide (SPIO) could be a valuable tool for tracking transplanted cells in living organisms. Human bone marrow‐derived mesenchymal stem cells (hBMMSC) were labeled with a novel polyvinyl pyrrolidone (PVP)‐coated SPIO. Prussian blue staining and electron microscopy revealed that almost all of the cells were efficiently labeled with PVP–SPIO nanoparticles. There were no signs of cytotoxicity, even at concentrations of up to 1600 µg Fe/ml of the nanoparticles, and the labeled cells were successfully visualized by in vitro cellular MRI. In addition, there was no significant alteration of the phenotype or the adipo/osteo/chondrogenic differentiation potential of the cells. This was in contrast to Feridex IV labeling that led to the inhibition of hBMMSC chondrogenesis. Following intramuscular injection in a rabbit hind limb ischemia model, the intercellular migration of the labeled cells toward the ablated site was clearly tracked through in vivo MRI. The localization of the transplanted cells observed by MRI correlated well with postmortem histological studies. These results demonstrate that the novel PVP–SPIO nanoparticles appear to be efficient MR contrast agents and may enable non‐invasive in vivo tracking of stem cells in experimental and clinical settings during cell therapy. Copyright © 2009 John Wiley & Sons, Ltd.     

Diphenylacetylene Polymer Nanofiber Mats Fabricated by Freeze Drying: Preparation and Application for Explosive Sensors

Finely structured diphenylacetylene polymer nanofibers were successfully prepared by a freeze drying method. SEM revealed that the morphology and structure of the fibers were significantly dependent on the concentration of the polymer solution, the ‘frozen in’ quenching temperature and the chemical structure of the polymer derivatives. Polarized fluorescence spectroscopy revealed that the polymer chains within the nanofiber were uniaxially oriented and highly elongated. The polymer nanofiber was remarkably sensitive to explosive nitroaromatic compounds when compared to the corresponding thin films. The fluorescence of polymer nanofiber obtained from 0.003 wt.‐% cryogenic benzene solution rapidly decreased to 50% of its initial value in ≈35 s by exposing to 2,4‐dinitrotoluene.