BACKGROUNDFor islet transplantation, pancreas preservation in UW solution is associated with disadvantages such as collagenase inhibition, resulting in poor islet yield and islets with poor ...viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution.
METHODSEJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory.
RESULTSWe first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5% and 7.7% of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared to UW solution.
CONCLUSIONAdvantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Introduction: For human, the resolution of images is important for diagnosis. Many clinical applications of artificial intelligence have been studied, however there are few reports on the difference ...in diagnosis between humans and artificial intelligence on the point of the renal pathological image resolution. Objectives: We examined whether the resolution of renal pathological images affects diagnosis of artificial intelligence and human. Patients and Methods: From 885 renal biopsy patients, we collected renal IgA immunofluorescent pathological images that resolution is 4, 16, 32, 64, 128, 256 and 512 pixels for each patient, and divided into training data set and validation data set, and created optimum deep learning models for each resolution. To compare with artificial intelligence nephrologist also tried to diagnose by using the same validation data set images. Results: We inputted IgA immunofluorescent pathological images into each optimum model. Human could not identify specific staining site with four pixels images, however, each resolution optimum model showed high accuracy, average over 80%. The each accuarcy was observed higher depending on the resolution. The area under the curve (AUC) showed higher diagnosis ratio depending on the resolution, too. Nephrologist performed high diagnosis sensitivity depending on resolution images as same as artificial intelligence. However, nephrologists’ diagnosis observed large variations in specificity depending on resolution. These results suggested that the resolution might affect specificity for human not artificial intelligence Conclusion: The resolution of images might be important for not AI but human on the point of specificity.
Stem cell therapies against renal injury have been advancing. The many trials for renal regeneration are reported to be effective in many kinds of renal injury models. Regarding the therapeutic ...mechanism, it is believed that stem cells contribute to make regeneration via not only direct stem cell differentiation in the injured space but also indirect effect via secreted factors from stem cells. Direct differentiation from stem cells to renal composed cells has been reported. They differentiate to renal composed cells and make functions. However, regarding renal regeneration, stem cells are discussed to secrete many kinds of growth factors, cytokines, and chemokines in paracrine or autocrine manner, which protect against renal injury, too. In addition, it is reported that stem cells have the ability to communicate with nearby cells via microvesicle-related RNA and proteins. Taken together from many reports, many secreted factors from stem cells were needed for renal regeneration orchestrally with harmony. In this review, we focused on the effects and insights of stem cells and regenerative factors from stem cells.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Artificial Intelligence (AI) imaging diagnosis is developing, making enormous steps forward in medical fields. Regarding diabetic nephropathy (DN), medical doctors diagnose them with clinical course, ...clinical laboratory data and renal pathology, mainly evaluate with light microscopy images rather than immunofluorescent images because there are no characteristic findings in immunofluorescent images for DN diagnosis. Here, we examined the possibility of whether AI could diagnose DN from immunofluorescent images. We collected renal immunofluorescent images from 885 renal biopsy patients in our hospital, and we created a dataset that contains six types of immunofluorescent images of IgG, IgA, IgM, C3, C1q and Fibrinogen for each patient. Using the dataset, 39 programs worked without errors (Area under the curve (AUC): 0.93). Five programs diagnosed DN completely with immunofluorescent images (AUC: 1.00). By analyzing with Local interpretable model-agnostic explanations (Lime), the AI focused on the peripheral lesion of DN glomeruli. On the other hand, the nephrologist diagnostic ratio (AUC: 0.75833) was slightly inferior to AI diagnosis. These findings suggest that DN could be diagnosed only by immunofluorescent images by deep learning. AI could diagnose DN and identify classified unknown parts with the immunofluorescent images that nephrologists usually do not use for DN diagnosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A 48-year-old Japanese female with left hypochondralgia presented at our hospital. Esophagogastroduodenoscopy (EGD) revealed gastric cancers and carpeting fundic gland polyposis (FGPs) without
...Helicobacter pylori
infection. Computed tomography showed multiple liver metastases. Total colonoscopy revealed a colonic tubular adenoma but not polyposis. She was diagnosed as having advanced gastric cancer with liver metastasis and received chemotherapy. Her mother had died from gastric cancer, and her elderly brother and niece had FGPs as revealed by EGD. Thus, the pedigree was diagnosed as gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Germline mutation analysis exhibited a point mutation in exon1B of the
APC
gene (c.-191T > C). Adenocarcinoma showed a gastric mucinous phenotype and was positive for a somatic mutation of
p53
, suggesting that
p53
mutation may play a role in FGPs carcinogenesis. This is the first family with GAPPS in Asia in whom germline mutation of
APC
exon 1B has been detected.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
Data on the long‐term outcomes of endoscopic submucosal dissection (ESD) performed in elderly patients with early colorectal cancer (CRC) are limited. We analyzed the prognosis of elderly ...CRC patients, not only from the viewpoint of treatment curability but also from the patients' baseline physical condition assessed by several indexes.
Methods
A retrospective analysis of 729 patients aged ≥75 years who underwent ESD for Tis/T1 CRC in 16 institutions was conducted. The patients were classified into three groups based on curability: curative ESD (Group A, n = 582), non‐curative ESD with additional surgery (Group B, n = 60), and non‐curative ESD without additional surgery (Group C, n = 87). Overall survival (OS) was compared among the groups, and factors associated with reduced OS were investigated.
Results
The median follow‐up periods in Groups A, B, and C were 41, 49, and 46 months, respectively (P = 0.62), during which 92 patients died. Two patients (0.3%) in Group A, none (0%) in Group B, and three (3.4%) in Group C died of CRC. Three‐year OS rates in Groups A, B, and C were 93.9%, 96.1%, and 90.1%, respectively, without a significant difference (P = 0.07). Multivariate analysis indicated low (<96.3) geriatric nutritional risk index (GNRI) as the sole independent predictor for reduced OS (hazard ratio 3.37; 95% confidence interval 2.18–5.22; P < 0.0001).
Conclusions
Low GNRI, but not the curability attained by ESD, was independently associated with reduced OS in patients with early CRC aged ≥75 years.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Objectives
To analyze the effect and impact of low‐dose rituximab induction therapy on cytomegalovirus infection in living‐donor renal transplantation.
Methods
A total of 92 recipients undergoing ...living‐donor renal transplantation at Okayama University Hospital from May 2009 to August 2018 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: (i) ABO major mismatch; (ii) ABO minor mismatch; (iii) donor‐specific anti‐human leukocyte antigen antibody‐positive; and (iv) focal segmental glomerulosclerosis. We excluded four recipients who were followed <3 months, five who received >200 mg/body rituximab and seven who received prophylactic therapy for cytomegalovirus.
Results
There were 59 patients in the rituximab group and 17 in the non‐rituximab group. Groups differed significantly in age (median age 53 vs 37 years, respectively; P = 0.04), but not in sex (male 64% vs 65%, P = 1.00), focal segmental glomerulosclerosis (3% vs 0%, P = 1.00) or percentage of cytomegalovirus‐seronegative recipients of renal allografts from cytomegalovirus‐seropositive donors (12% vs 18%, P = 0.68). The estimated glomerular filtration rate did not differ significantly between groups until 24 months after transplantation. Cytomegalovirus clinical symptoms (10% vs 24%, P = 0.22), including fever ≥38°C (5% vs 12%, P = 0.31) and gastrointestinal symptoms (5% vs 12%, P = 0.31), and the 5‐year survival rates of death‐censored graft loss (90% vs 83%, P = 0.43) did not differ significantly between groups.
Conclusions
Low‐dose rituximab induction therapy is effective in immunological high‐risk recipients without increasing cytomegalovirus infection in the absence of valganciclovir prophylaxis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as ...well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism.
Methods
Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders.
Results
Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 m
2
) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m
2
). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of “masked” CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of “reversible” CKD status in hypothyroidism.
Conclusions
We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.