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Journal of Diabetes Research 2024Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients...
Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1 (SDF-1)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects" mediated by angiogenesis and "direct effects" of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.
Topics: Animals; Islets of Langerhans Transplantation; Diabetes Mellitus, Experimental; Myoblasts, Skeletal; Mice; Male; Insulin; Neovascularization, Physiologic; Hepatocyte Growth Factor; Mice, Inbred C57BL; Vascular Endothelial Growth Factor A; Islets of Langerhans; Chemokine CXCL12; Blood Glucose; Diabetes Mellitus, Type 1; Signal Transduction; Insulin Secretion; Cell Differentiation
PubMed: 38800586
DOI: 10.1155/2024/5574968 -
Transplantation Direct Jun 2024For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined...
BACKGROUND
For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined pancreas and kidney transplantation (PKT) is the therapy of choice. However, the shortage of available grafts and complex impact of risk factors call for individualized, impartial predictions of PKT and pancreas transplantation (PT) outcomes to support physicians in graft acceptance decisions.
METHODS
Based on a large European cohort with 3060 PKT and PT performed between 2006 and 2021, the 3 primary patient outcomes time to patient mortality, pancreas graft loss, and kidney graft loss were visualized using Kaplan-Meier survival curves. Multivariable Cox proportional hazards models were developed for 5- and 10-y prediction of outcomes based on 26 risk factors.
RESULTS
Risk factors associated with increased mortality included previous kidney transplants, rescue allocations, longer waiting times, and simultaneous transplants of other organs. Increased pancreas graft loss was positively associated with higher recipient body mass index and donor age and negatively associated with simultaneous transplants of kidneys and other organs. Donor age was also associated with increased kidney graft losses. The multivariable Cox models reported median C-index values were 63% for patient mortality, 62% for pancreas loss, and 55% for kidney loss.
CONCLUSIONS
This study provides an online risk tool at https://riskcalc.org/ptop for individual 5- and 10-y post-PKT and PT patient outcomes based on parameters available at the time of graft offer to support critical organ acceptance decisions and encourage external validation in independent populations.
PubMed: 38757051
DOI: 10.1097/TXD.0000000000001632 -
Transplantation Proceedings May 2024A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified...
BACKGROUND
A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation.
METHODS
First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz.
RESULTS
No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly.
CONCLUSION
Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality.
PubMed: 38749862
DOI: 10.1016/j.transproceed.2024.03.034 -
Patient Education and Counseling Aug 2024To confirm described dimensions of making care fit and explore how patients and clinicians collaborate to make care fit in clinical practice.
OBJECTIVE
To confirm described dimensions of making care fit and explore how patients and clinicians collaborate to make care fit in clinical practice.
METHODS
As part of an ongoing study, we audiotaped and transcribed patient-clinician consultations in diabetes care. We purposively selected consultations based on participants' demographical, biomedical and biographical characteristics. We analysed transcripts using reflexive thematic analysis. We combined a deductive and inductive approach, using the pre-described dimensions of making care fit and adding new (sub-)dimensions when pertinent.
RESULTS
We analysed 24 clinical consultations. Our data confirmed eight previously described dimensions and provided new sub-dimensions of making care fit with examples from clinical practice (problematic situation, influence of devices, sense of options, shared agenda setting, clinician context, adapting to changing organization of care, and possibility to reconsider).
CONCLUSION
Our study confirmed, specified and enriched the conceptualization of making care fit through practice examples. We observed patient-clinician collaboration in exploration of patients' context, and by responsively changing, adapting or maintaining care plans.
PRACTICE IMPLICATIONS
Our findings support clinicians and researchers with insights in important aspects of patient-clinician collaboration. Ultimately, this would lead to optimal design of care plans that fit well in each patient life.
Topics: Humans; Qualitative Research; Female; Male; Middle Aged; Physician-Patient Relations; Cooperative Behavior; Diabetes Mellitus; Referral and Consultation; Adult; Aged; Patient Participation; Communication
PubMed: 38749345
DOI: 10.1016/j.pec.2024.108295 -
Nature Communications May 2024The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an...
The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA-directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.
Topics: Humans; Protein Inhibitors of Activated STAT; Animals; Cell Line, Tumor; Mitosis; Mice; Thyroid Neoplasms; RNA Interference; Spindle Apparatus; Molecular Chaperones; Xenograft Model Antitumor Assays; Proteasome Endopeptidase Complex; Sumoylation; Carcinoma; Female
PubMed: 38744818
DOI: 10.1038/s41467-024-47751-1 -
Experimental and Clinical... Apr 2024The demographic disparities among surgeons in academic leadership positions is well documented. We aimed to characterize the present demographic details of abdominal... (Comparative Study)
Comparative Study
OBJECTIVES
The demographic disparities among surgeons in academic leadership positions is well documented. We aimed to characterize the present demographic details of abdominal transplant surgeons who have achieved academic and clinical leadership positions.
MATERIALS AND METHODS
We reviewed the 2022-2023 American Society of Transplant Surgeons membership registry to identify 1007 active abdominal transplant surgeons. Demographic details (academic and clinical titles) were collected and analyzed using the chi-square test, the Fisher exact test, and t tests. Multinomial logistic regressions were conducted.
RESULTS
Female surgeons (P < .001) and surgeons from racial-ethnic minorities (P = .027) were more likely to be assistants or associates rather than full professors. White male surgeons were more likely to be full professors than were White female (P < .001), Asian female (P = .008), and Asian male surgeons (P = .005). There were no Black female surgeons who were full professors. The frequency of full professorship increased with surgeon age (P < .001). Male surgeons were more likely to hold no academic titles (P < .001). Female surgeons were less likely to be chief of transplant(P = .025), chief of livertransplant (P = .001), chief of pancreas transplant (P = .037), or chair of surgery (P = .087, significance at 10%). Chief of kidney transplant was the most common clinical position held by a surgeon from a racial or ethnic minority group. Female surgeons were more likely to hold no clinical titles (P = .001).
CONCLUSIONS
The underrepresentation of women and people from racial and ethnic minority groups in academic and clinical leadership positions in the field of abdominal transplant surgery remains evident. White male physicians are more likely to obtain full professorship, and they comprise most of the clinical leadership positions overall. A continued push for representative leadership is needed.
Topics: Humans; Female; Leadership; Male; Physicians, Women; Surgeons; Organ Transplantation; Ethnic and Racial Minorities; Cultural Diversity; Race Factors; Faculty, Medical; Adult; Career Mobility; United States; Middle Aged; Sex Factors; Registries; Minority Groups
PubMed: 38742315
DOI: 10.6002/ect.2024.0035 -
Transplantation Proceedings May 2024Long-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunologic deterioration. Pretransplant C-reactive protein (CRP) and...
BACKGROUND
Long-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunologic deterioration. Pretransplant C-reactive protein (CRP) and albumin (ALB) levels impact kidney transplantation. We evaluated the effects of preoperative CRP, ALB, neutrophils (NEU), and platelet (PLT) counts on 1- and 5-year recipient survival after simultaneous pancreas and kidney transplantation (SPK).
METHODS
Among 103 SPK recipients, the parameters were as follows: CRP (mean: 4.5 ± 4.97 mg/L); NEU (mean: 5.12 ± 2.13 × 10/mm); PLT (mean: 244 ± 84 × 10/mm); ALB (mean 4.5 ± 0.75 g/dL) were obtained before transplantation. Cox regression, uni-, multivariate analysis for 1- and 5-year survivals were performed with 95% CIs, and the area under the receiver operating characteristic (ROC) curve (AUC) was assessed.
RESULTS
In Cox regression, ALB <3.65 g/dL significantly affected 1- and 5-year survivors with hazard ratios of 8 (95% CI, 1.5-38.28; P < .05) and 3.13 (95% CI, 1.45-6.73; P < .05), respectively. In univariate analysis, we found significantly decreased 1-year survival when PLT <180×10/mm, ALB <3.65 g/dL, NEU >5.8×10/mm and CRP >2.25 mg/L with odds ratios (OR) of 6.75 (95% CI, 2.12-21.15); 4.05 (95% CI, 1.3-12.09); 2.97 (95% CI, 1.02-8.64) and 5.51 (95% CI, 1.67-18.19), respectively. Independent factors for 5-year survival were CRP, ALB, and PLT with OR of 4.72 (95% CI, 1.67-13.29), 3.31 (95% CI, 1.18-9.25), and 4.2 (95% CI, 1.39-12.68), respectively. In multivariate analysis, we built 2 models for 1-year survival. Model 1 (ALB+PLT) with ORs of 3.12 (95% CI, 0.97-10.07) and 5.55 (95% CI, 1.67-18.4); and model 2 (CRP+PLT) with ORs of 5.51 (95% CI, 1.5-17.3) and 4.3 (95% CI, 1.2-15.06), respectively. The AUC for models 1 and 2 were 0.74 and 0.759, respectively.
CONCLUSIONS
NEU, PLT, ALB, and CRP levels assessed before transplantation are independent factors for 1- and 5-year SPK recipient survival.
PubMed: 38729832
DOI: 10.1016/j.transproceed.2024.03.030 -
Annals of Hepato-biliary-pancreatic... May 2024The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in...
BACKGROUNDS/AIMS
The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT.
METHODS
We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea.
RESULTS
The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, < 0.001).
CONCLUSIONS
HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.
PubMed: 38720612
DOI: 10.14701/ahbps.24-048 -
Frontiers in Clinical Diabetes and... 2024
PubMed: 38711746
DOI: 10.3389/fcdhc.2024.1388904 -
Transplantation Proceedings May 2024The aim of this study was to present a rare cause of recurrent urinary tract infections (UTIs) in a patient after kidney transplantation.
BACKGROUND
The aim of this study was to present a rare cause of recurrent urinary tract infections (UTIs) in a patient after kidney transplantation.
METHODS
The patient's consent was obtained, and full medical documentation was reviewed. After analyzing the literature, only 3 case reports of post-transplant nephroptosis were found.
RESULTS
A 32-year-old woman with a history of type 1 diabetes, after kidney and pancreas transplantation a year earlier, was admitted to the hospital due to another incident of fever, dysuria, and pain in the lower abdomen. UTIs had been recurring for several months despite prophylaxis, initially with co-trimoxazole and then with fosfomycin. There were no anatomic abnormalities, and tacrolimus concentrations always remained at the lower range of normal. Kinking of the ureter was suspected because of a change in the position of the transplanted kidney. Ultrasonography performed in the standing and lying positions confirmed the diagnosis. A double J catheter was inserted into the ureter. In the following months, no UTI or urinary retention recurrence was observed.
CONCLUSIONS
Nephroptosis of a transplanted kidney is extremely rare. The standard place for graft implantation-the iliac fossasignificantly limits the potential for migration. Kidneys implanted intraperitoneally also do not show clinically significant mobility due to postoperative adhesions. Floating kidneys potentially lead to serious complications. In addition to pain, a migrating graft may cause urine retention, predisposing to UTI and acute kidney injury.
PubMed: 38710603
DOI: 10.1016/j.transproceed.2024.04.008