Background & AimStem cell transplantation has emerged as a beneficial intervention for felines grappling with chronic kidney disease (CKD), showcasing both innovations and remarkable outcomes post-transplantation. Traditionally, when felines develop kidney disease due to medication or genetic factors, their inherent capacity for kidney recovery is notably constrained. Consequently, veterinarians often resort to conventional treatments such as fluid therapy, additives, and other life-expanding modalities. This study explores the efficacy of long-term stem cell transplantation for managing CKD in felines.Methods, Results & ConclusionThe study involved the categorization of felines into two groups based on their IRIS stages: Group 1 comprised felines at CKD stages 1 or 2, while Group 2 included felines at CKD stages 3 or 4. The research aimed to assess the outcomes of repeated transplantations once a month for over 1-year by analyzing key kidney indicators, including Blood Urea Nitrogen (BUN), Creatine (Cre), Phosphorus (IP), and Symmetric Dimethylarginine (SDMA).In Group 1, initially, all felines exhibited a marginal elevation in BUN, Cre, and SDMA. Subsequently, a progressive reduction in these parameters was observed, ultimately reaching within the normal range. Importantly, no adverse issues, such as ureter stones, were identified during this period. In Group 2, also consisting of three felines, demonstrated elevated concentrations of BUN, Cre, IP, and SDMA prior to stem cell intervention. Post-treatment, a marked reduction in these indices was noted, signifying a shift to a lower disease stage Notably, despite this positive response, none of the felines in Group 2 attained blood index levels within the normal range or advanced to stage 1 of chronic kidney disease.Notably, the consistent application of stem cell transplantation demonstrated favorable outcomes, manifesting in improved appetite and increased activity levels among the felines. Furthermore, the absence of clinical signs such as vomiting, and anorexia further supports the viability of regular stem cell transplantation as a valuable option in the management of CKD in felines.The findings of this study underscore the considerable benefits of stem cell transplantation for felines afflicted with CKD. Over the long term, regular transplantation emerged as an effective strategy, contributing to an enhanced quality of life and a reduction in the IRIS stage for these feline patients.
Abstract Funding Acknowledgements None. Background Veno-arterial extracorporeal membranous oxygenator (VA-ECMO) is one of the most powerful devices that rapidly restore sufficient organ perfusion in patients with cardiogenic shock. Despite abundant experiences of successful resuscitation with VA-ECMO, evidences for clinical benefit of VA-ECMO are still lacking. Purpose We summarised clinical outcomes related to VA-ECMO and investigated predictors regarding survival at discharge. Methods Patients who treated with peripheral VA-ECMO between 2006 and 2022 were included from a Hospital in South Korea. Eligible patients were analysed in stratification with ECMO initiation year (year 2006–2010, year 2011–2016, and year 2017–2022). Survival status at discharge were investigated. Results Among total of 693 patients included, 223 (32.2%) were survived at discharge. Survivors had stayed in hospital for median 28 (19–52) days. The overall volume of ECMO initiation (86 runs vs. 250 runs vs. 357 runs) and the rate of extracorporeal CPR (3.5% vs. 18.4% vs. 38.1%) have increased over time. The median duration of VA-ECMO treatment has increased over time (52.6 hours vs. 63.6 hours vs. 85.8 hours). The serum lactate test has been performed more frequently over time (15.1% vs. 79.6% vs. 99.2%). Among 470 patients who died in the index hospitalization, 154 (32.8%) patients died in the first 24 hours after initiation of VA-ECMO. In a multivariate regression model, age over 70 (OR, 0.54; 95% CI, 0.32–0.89), extracorporeal CPR (OR, 0.42; 95% CI, 0.24–0.71), and lactate level ≥8.0 mmol/L (OR, 0.24; 95% CI, 0.15–0.37) were associated with unfavorable outcome while hemoglobin was a predictor of favorable clinical outcome (OR, 1.16; 95% CI, 1.07–1.25). Conclusion The volume of VA-ECMO has increased and clinical severity has also become higher than before. The rate of survival at discharge after VA-ECMO treatment remains stable; however, the rate of patients who died in the first 24 hours is still high. Age, extracorporeal CPR, hemoglobin and lactate levels were predictors of clinical outcome after VA-ECMO treatment.
Rationale: Patients who survive critical illnesses frequently develop muscle weakness, termed ICU-acquired weakness. Calf circumference (CC) is an easy and common measure of muscle loss in the inpatients; however, there are still very few studies on CC in neurosurgical (NS) patients. Methods: This study was conducted on 60 patients who were admitted in the NS ICU. The values of CC were measured in each patient using a tape by trained dietitian and collected anthropometric, biochemical, clinical, and dietary data. The patients were divided into two groups according to the time at which the values were obtained: a short-term admission group (SAG, 33 patients, ≤7 days after admission) and a long-term admission group (LAG, 27 patients, >7 days after admission). Difference in continuous variables were analyzed using paired t-tests. Difference in non-continuous variables were analyzed with the chi-square test. Results: There were no notable differences in patient characteristics between the two groups, including age, gender, the body mass index (BMI), energy expenditure values using indirect calorimetry and the nutrition assessment by Subjective global assessment (p=0.077). The BMI, a representative value of anthropometry, was also not different between the two groups (SAG: 24.2 ± 3.5 kg/㎡; LAG: 23.4 ± 4.9 kg/㎡, p=0.455) and even though more patients received bedside physical therapy in LAG (p=0.000), the CC in the LAG was significantly lower than that in the SAG (SAG: 32.7 ± 3.3 cm; LAG: 30.0 ± 4.2 cm, p=0.006). Conclusion: An accurate assessment of muscle loss is critical for the treatment of seriously ill patients. Our study showed that even if the same BMI is shown, there may be a difference in CC. Through this, we suggest that CC could be used as an initial marker for muscle loss in neurosurgery patients. Disclosure of Interest: None declared
Background: New-onset diabetes after transplantation (NODAT) is a frequent complication in kidney transplant (KT) recipients with unfavorable outcomes, although a nationwide study on epidemiology and clinical outcome of NODAT in Korean KT recipients remain rare.Methods: We identified KT recipients by using the Health Insurance Review and Assessment Service of South Korea from the year of 2008 to 2017.We excluded patients with preexisting diabetes, multi-organ transplantation, and being progressed to graft failure less than 1 year after KT.NODAT was defined as consecutive 30 days prescription history of antidiabetic medication after KT.We analyzed the impact of NODAT on death censored graft failure (DCGF), death without graft failure (DWGF), and major adverse cardiovascular events (MACE) by time-dependent Cox analysis.Results: Among a total of 16,719 KT recipients, 10,311 were included after exclusion.The 19.8% of KT recipients were diagnosed to NODAT.The proportion of patients developing NODAT tended to increase, and 64% of NODAT was diagnosed within the first 6-months after KT.NODAT patients were older, more men, having longer pre-KT dialysis vintages, and being exposed more basiliximab induction and more rejection episodes requiring high-dose steroids treatment after KT.During follow-up, 520 DCGF, 180 DWGF, and 213 MACE events were occurred.NODAT patients showed higher risks of DCGF (adjusted hazard ratio [aHR], 1.87; 95% confidence interval [CI], 1.52-2.3;P<0.001), DWGF (aHR, 1.77; 95% CI, P<0.001), and MACE (aHR, 1.46; 95% CI, P=0.013) than patients without NODAT.Twenty-one percent of NODAT patients could be stopped their anti-diabetic medications after the diagnosis, although this did not affect the clinical outcomes.Conclusions: About 20% of diabetes-naive KT recipients were diagnosed with NODAT with a recently increasing pattern.NODAT in KT recipients affected worse graft and patients outcomes as well as MACE.
Objective: To evaluate the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) version 2018 ancillary features for the diagnosis of hepatocellular carcinoma (HCC) from LR-4 ('probably HCC') lesions using gadoxetic acid-enhanced magnetic resonance imaging.Methods: This retrospective study evaluated 166 LR-4 lesions including ancillary features in 114 high-risk cases imaged with gadoxetic acid-enhanced magnetic resonance imaging between March 2015 and December 2017.Two radiologists evaluated the imaging features using LI-RADS v2018.All lesions were confirmed as HCC or benign lesions by pathological assessment or >2 years of follow-up imaging.The diagnostic contribution of ancillary features was assessed using simple and multivariable logistic regression and generalised estimating equations.Results: In all, 114 HCCs (68.7%) and 52 benign lesions (31.3%) were confirmed.Simple logistic regression analysis revealed that mild to moderate T2 hyperintensity (p = 0.014), restricted diffusion (p < 0.001), and intralesional fat (p = 0.018) were statistically significant for differentiating HCCs from benign lesions; however, multivariable logistic analysis revealed that only restricted diffusion was statistically significant (adjusted odds ratio = 9.703, p < 0.001).Restricted diffusion had lower sensitivity (48.2%) and higher specificity (90.4%) for the diagnosis of HCC; however, the diagnostic values improved when combined with mild to moderate T2 hyperintensity and hepatobiliary phase hypointensity (sensitivity: 73.8%, specificity: 80.8%).Conclusion: Among ancillary LI-RADS v2018 imaging features, restricted diffusion is the diagnostic feature most accurately distinguishing HCCs from benign abnormalities in LR-4 lesions.
The cell therapy field is experiencing rapid growth with several recent regulatory approvals and further therapies in clinical testing. The Gibco™ CTS™ DynaCellect™ Magnetic Separation System and single-use kits have been designed for scalable and robust cell processing with the CTS Dynabeads™ platform. Using the Gibco CTS DynaCellect Cell Isolation Kit with CTS Dynabeads, >85% isolation efficiency of target cells with >95% purity is consistently achieved with no effect on cell viability.
Background: Gut microbiota may affect host immunity and therefore it may be associated with the immunologic response of kidney transplantation (KT) recipients, given their risk for allograft rejection.The aim of this study is to explore the association between gut dysbiosis and early acute rejection (EAR) in KTs.Methods: Stool samples from a tertiary hospital were collected from KT recipients before transplantation and metagenomic shotgun sequencing was performed for taxonomic profiling and detection of microbiota-derived genes.Their clinical data were gathered, including demographic factors, immunologic risks, immunosuppressive treatment, and the outcome defined as biopsy-proven EAR within 2 weeks of KT.Using a trainset, EAR prediction models were built in combination of clinical data, microbiota taxonomy, and microbiota-derived gene families, and tested the change of statistical power for EAR prediction and possibility for validation in the independent cohort.Results: A total of 78 and 71 stool samples were collected for a train-test set and a validation set, respectively.EAR was found in 26 (33.3%) and 20 (28.2%) in each set, respectively.There was no specific difference in clinical characteristics except a higher proportion of hypertension in validation set.Recipients experiencing EAR showed a higher body mass index, number of HLA mismatch, and a higher rate of delayed graft function compared to nonrejection recipients.In taxonomic profiling, the abundance of Bacteroides eggerthii, Phascolarctobacterium faecium, and Desulfovibrio piger decreased in rejection group.In gene families analysis, a total of 532 genes including 85 metabolism pathway related genes were differentially expressed.Predictability of EAR was enhanced (C-statistics, 0.77; 95% confidence interval, 0.59-0.86)when we add on the differently expressed microbiota-derived genes and taxonomic profiles to the clinical model (C-statistics, 0.57; 95% confidence interval, 0.35-0.67).In addition, the optimized model showed a modest performance with 64.8% of accuracy in the validation cohort.Conclusions: The gut microbiome-driven metagenomic signatures may have an additive role in predicting EAR after KT when combined with clinical and immunologic features.
Living donor kidney transplantation has been increasing in South Korea. Considering rapid changes in lifestyle and chronic diseases in South Korea over the years, time-trend exploration and comparison of metabolic risk in live donors and healthy controls may help to estimate the future risk of live donors.
Abstract Background: APOBEC3B is a cytosine deaminase implicated in host immune defense to virus and mutagenesis in cancer. Germline APOBEC3B deletion is known as risk factors for breast cancer with hypermutation and immune activation from previous database-based studies. This study was aimed to evaluate the incidence of germline APOBEC3B deletion in Korean patients with operable breast cancer. Method: The copy number variants of germline APOBEC3B deletion was analyzed from leukocyte DNA of 103 breast cancer patients whose bloods were collected in 2009 for pharmacogenomic study at Seoul National University Bundang Hospital. Hybrid-capture based next-generation sequencing panel targeting 53 hereditary cancer genes were used. We also measured tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor or immune cell with a rabbit monoclonal antibody (E1L3N). Results: Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3Bdel/del), one-one copy deletion (A3Bdel/wt) and no deletion (A3Bwt/wt), respectively. In non-APOBEC3B analysis, 9 (8.7%) patients were identified as pathogenic variant: RAD51D(n=1), GJB2(n=1), BRCA1(n=1), BRCA2 (n=2), ATM(n=1), USH2A(n=1), RET(n=1), BARD1(n=1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer such as age, family history of cancer, and bilateral breast cancer. Triple-negative subtype was associated with A3Bwt/wt Tumors (35.1% in A3Bwt/wt vs. 5.6% in A3Bdel/wt vs20% in A3Bdel/del; P=0.018). After a median follow-up time of 92.8 months, APOBEC3B deletion was not predictive of recurrence or survival. In patients with sufficient tumor samples for the assessment of TIL (n=63) and PD-1 (n=71), A3Bdel/del tumor was associated with higher TILs (>10%) than other tumor types (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher's exact test in A3Bdel/del, P=0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients >1% PD-L1 in A3Bdel/del vs. 4/26 in A3Bdel/wt vs. 8/38 in A3Bwt/wt: P=0.901). Germline APOBEC3B deletion and TILs (n=63) TIL (0-10%)TIL (>10%)TotalA3B(wt/wt)17 (53.1%)15 (46.9%)32A3B(del/wt)11 (45.8%)13 (54.2%)24A3B(del/del)1 (14.3%)6 (85.7%)7 Conclusion: We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del tumor and high TILs suggests that these tumors might be potential candidates for future immunotherapy. Citation Format: Kim SH, Koung Jin S, Kim YJ, Ahn S, Park SY, Chae SM, Kang E, Kim E-K, Kim IA, Kim JH. Identifying germline APOBEC3B deletion using hereditary cancer panel in Korean patients with operable breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-10.
Neither lowering of blood lipid levels nor treatment with statins definitively improves renal outcomes. Ezetimibe, a non-statin antilipidemic agent, is known to not only decrease blood lipid levels but also reduce inflammatory response and activate autophagy. We evaluated the effect of adding ezetimibe to a statin on renal outcome compared with statin monotherapy by analyzing longitudinal data of 4537 patients treated with simvastatin 20 mg plus ezetimibe 10 mg (S + E) or simvastatin 20 mg alone (S) for more than 180 days. A propensity-score-based process was used to match baseline characteristics, medical history, and estimated glomerular filtration rate (eGFR) between S + E and S groups. Changes in serum creatinine and incidence of renal events, defined as doubling of serum creatinine to ≥1.5 mg/dL or occurrence of end-stage renal disease after the first day of treatment initiation, were compared between the groups. Among 3104 well-matched patients with a median follow-up of 4.2 years, the S + E group showed a significantly lower risk of renal events than the S group (hazard ratio 0.58; 95% CI 0.35-0.95, P = 0.032). In addition, the S + E group tended to preserve renal function compared with the S group throughout follow-up, as assessed by serum creatinine changes (P-values for time–group interactions <0.001). These data support the beneficial effects on renal function when combining ezetimibe with a statin.