Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 193
Filter
1.
J Drugs Dermatol ; 23(5): 376-379, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38709686

ABSTRACT

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.     doi:10.36849/JDD.8234  .


Subject(s)
Carcinoma, Merkel Cell , Kidney Transplantation , Pancreas Transplantation , Skin Neoplasms , Humans , Carcinoma, Merkel Cell/therapy , Carcinoma, Merkel Cell/surgery , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/pathology , Kidney Transplantation/adverse effects , Skin Neoplasms/pathology , Pancreas Transplantation/adverse effects , Male , Fatal Outcome , Middle Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Female , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Immunosuppression Therapy/adverse effects
2.
Front Immunol ; 15: 1354101, 2024.
Article in English | MEDLINE | ID: mdl-38495894

ABSTRACT

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.


Subject(s)
Glomerulosclerosis, Focal Segmental , Kidney Failure, Chronic , Kidney Transplantation , Transplants , Humans , Neoplasm Recurrence, Local/complications , Kidney Transplantation/adverse effects , Kidney Failure, Chronic/etiology
4.
Biomater Adv ; 158: 213765, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38242058

ABSTRACT

Diabetic complications present throughout a wide range of body tissues, however one of the most widely recognised complications remains to be chronic diabetic wounds. Current treatment options largely rely on standard wound treatment routines which provide no promotion of wound healing mechanisms at different physiological stages of repair. Recently materials produced using novel additive manufacturing techniques have been receiving attention for applications in wound care and tissue repair. Additive manufacturing techniques have recently been used in the interest of targeted drug delivery and production of novel materials resembling characteristics of native tissues. The potential to exploit these highly tailorable manufacturing techniques for the design of novel wound care remedies is highly desirable. In the present study two additive manufacturing techniques are combined to produce a scaffold for the treatment of diabetic wounds. The combination of microfluidic manufacturing of an antimicrobial liposome (LP) formulation and a coaxial electrospinning method incorporating both antimicrobial and proangiogenic factors allowed dual delivery of therapeutics to target both infection and lack of vascularisation at wound sites. The coaxial fibres comprised of a polyvinyl alcohol (PVA) core containing vascular endothelial growth factor (VEGF) and a poly (l-lactide-co-ε-caprolactone) (PLCL) shell blended with amoxicillin (Amox). Additionally, a liposomal formulation was produced to incorporate Amox and adhered to the surface of fibres loaded with Amox and VEGF. The liposomal loading provided the potential to deliver a much higher, more clinically relevant dose of Amox without detrimentally changing the mechanical properties of the material. The growth factor release was sustained up to 7-days in vitro. The therapeutic effect of the antibiotic loading was analysed using a disk diffusion method with a significant increase in zone diameter following LP adhesion, proving the full scaffold system had improved efficacy against both Gram-positive and Gram-negative strains. Additionally, the dual-loaded scaffolds show enhanced potential for supporting vascular growth in vitro, as demonstrated via a viability assay and tubule formation studies. Results showed a significant increase in the average total number of tubes from 10 in control samples to 77 in samples fully-loaded with Amox and VEGF.


Subject(s)
Anti-Infective Agents , Diabetes Mellitus , Humans , Amoxicillin/pharmacology , Amoxicillin/therapeutic use , Vascular Endothelial Growth Factor A , Liposomes
5.
Am J Transplant ; 24(3): 362-379, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37871799

ABSTRACT

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.


Subject(s)
Pancreas Transplantation , Transplantation, Homologous , Biopsy , Isoantibodies , T-Lymphocytes
6.
Int J Pharm ; 650: 123710, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38097147

ABSTRACT

With an increasing concern of global antimicrobial resistance, the efforts to improve the formulation of a narrowing library of therapeutic antibiotics must be confronted. The liposomal encapsulation of antibiotics using a novel and sustainable microfluidic method has been employed in this study to address this pressing issue, via a targeted, lower-dose medical approach. The study focusses upon microfluidic parameter optimisation, formulation stability, cytotoxicity, and future applications. Particle sizes of circa. 130 nm, with viable short-term (28-day) physical stability were obtained, using two different non-cytotoxic liposomal formulations, both of which displayed suitable antibacterial efficacy. The microfluidic method allowed for high encapsulation efficiencies (≈77 %) and the subsequent in vitro release profile suggested high limits of antibiotic dissociation from the nanovessels, achieving 90% release within 72 h. In addition to the experimental data, the growing use of poly(ethylene) glycol (PEG) within lipid-based formulations is discussed in relation to anti-PEG antibodies, highlighting the key pharmacological differences between PEGylated and non-PEGylated formulations and their respective advantages and drawbacks. It's surmised that in the case of the formulations used in this study, the addition of PEG upon the liposomal membrane would still be a beneficial feature to possess owing to beneficial features such as stability, antibiotic efficacy and the capacity to further modify the liposomal membrane.


Subject(s)
Amoxicillin , Microfluidics , Liposomes , Anti-Bacterial Agents , Polyethylene Glycols
7.
Clin Transl Sci ; 16(11): 2382-2393, 2023 11.
Article in English | MEDLINE | ID: mdl-37817405

ABSTRACT

More favorable clinical outcomes with medium-term follow-up have been reported among kidney transplant recipients receiving maintenance therapy consisting of "reduced-tacrolimus (TAC) dosing," mycophenolate mofetil (MMF), and low-dose corticosteroids. However, it is not clear whether long-term maintenance therapy with reduced-calcineurin inhibitor (CNI) dosing still leads to reduced renal function. A prospectively followed cohort of 150 kidney transplant recipients randomized to receive TAC/sirolimus (SRL) versus TAC/MMF versus cyclosporine microemulsion (CSA)/SRL, plus low-dose maintenance corticosteroids, now has 20 years of post-transplant follow-up. Average CNI trough levels over time among patients who were still alive with functioning grafts at 60, 120, and 180 months post-transplant were determined and ranked from smallest-to-largest for both TAC and CSA. Stepwise linear regression was used to determine whether these ranked average trough levels were associated with the patient's estimated glomerular filtration rate (eGFR) at those times, particularly after controlling for other significant multivariable predictors. Experiencing biopsy-proven acute rejection (BPAR) and older donor age were the two most significant multivariable predictors of poorer eGFR at 60, 120, and 180 months post-transplant (p < 000001 and 0.000003 for older donor age at 60 and 120 months; p = 0.00008 and <0.000001 for previous BPAR at 60 and 120 months). Assignment to CSA also implied a significantly poorer eGFR (but with less magnitudes of effect) in multivariable analysis at 60 and 120 months (p = 0.01 and 0.002). Higher ranked average CNI trough levels had no association with eGFR at any timepoint in either univariable or multivariable analysis (p > 0.70). Long-term maintenance therapy with reduced-CNI dosing does not appear to cause reduced renal function.


Subject(s)
Calcineurin Inhibitors , Kidney Transplantation , Humans , Infant , Child, Preschool , Child , Calcineurin Inhibitors/adverse effects , Immunosuppressive Agents , Kidney Transplantation/adverse effects , Graft Rejection/prevention & control , Graft Rejection/etiology , Tacrolimus/adverse effects , Sirolimus/therapeutic use , Mycophenolic Acid/adverse effects , Kidney/physiology , Adrenal Cortex Hormones , Drug Therapy, Combination
8.
Front Immunol ; 14: 1201619, 2023.
Article in English | MEDLINE | ID: mdl-37564655

ABSTRACT

Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to treat FSGS currently remain elusive. Since the podocyte appears to be the target of apparent circulating factor(s) that lead to recurrence of proteinuria following kidney transplantation, this article is focused on the podocyte. In the context of kidney transplantation, the performance of pre- and post-reperfusion biopsies, and the establishment of in vitro podocyte liquid biopsies/assays allow for the development of clinically relevant studies of podocyte biology. This has given insight into new pathways, involving novel targets in innate and adaptive immunity, such as SMPDL3b, cGAS-STING, and B7-1. Elegant experimental studies suggest that the successful clinical use of rituximab and abatacept, two immunomodulating agents, in our case series, may be due to direct effects on the podocyte, in addition to, or perhaps distinct from their immunosuppressive functions. Thus, tissue biomarker-directed therapy may provide a rational approach to validate the mechanism of disease and allow for the development of new therapeutics for FSGS. This report highlights recent progress in the field and emphasizes the importance of kidney transplantation and recurrent FSGS (rFSGS) as a platform for the study of primary FSGS.


Subject(s)
Glomerulosclerosis, Focal Segmental , Nephrotic Syndrome , Podocytes , Humans , Podocytes/metabolism , Glomerulosclerosis, Focal Segmental/drug therapy , Kidney Glomerulus , Adaptive Immunity
9.
Transpl Int ; 36: 10938, 2023.
Article in English | MEDLINE | ID: mdl-37091963

ABSTRACT

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.


Subject(s)
COVID-19 , Organ Transplantation , Vaccines , Adult , Humans , Ad26COVS1 , BNT162 Vaccine , COVID-19/prevention & control , SARS-CoV-2 , Transplant Recipients , Immunoglobulin G , Antibodies, Viral
10.
Pediatr Nephrol ; 38(1): 145-159, 2023 01.
Article in English | MEDLINE | ID: mdl-35507150

ABSTRACT

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.


Subject(s)
Glomerulosclerosis, Focal Segmental , Podocytes , Adult , Child , Humans , Young Adult , Glomerulosclerosis, Focal Segmental/drug therapy , Glomerulosclerosis, Focal Segmental/pathology , Abatacept/therapeutic use , Proteinuria/drug therapy , Proteinuria/etiology , Podocytes/pathology , Staining and Labeling , Recurrence
11.
Cells ; 11(22)2022 11 16.
Article in English | MEDLINE | ID: mdl-36429063

ABSTRACT

Diabetes is the leading cause of chronic kidney disease worldwide. Despite the burden, the factors contributing to the development and progression of diabetic kidney disease (DKD) remain to be fully elucidated. In recent years, increasing evidence suggests that mitochondrial dysfunction is a pathological mediator in DKD as the kidney is a highly metabolic organ rich in mitochondria. Furthermore, low grade chronic inflammation also contributes to the progression of DKD, and several inflammatory biomarkers have been reported as prognostic markers to risk-stratify patients for disease progression and all-cause mortality. Interestingly, the term "sterile inflammation" appears to be used in the context of DKD describing the development of intracellular inflammation in the absence of bacterial or viral pathogens. Therefore, a link between mitochondrial dysfunction and inflammation in DKD exists and is a hot topic in both basic research and clinical investigations. This review summarizes how mitochondria contribute to sterile inflammation in renal cells in DKD.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Humans , Diabetic Nephropathies/metabolism , Inflammation/metabolism , Mitochondria/metabolism , Kidney/pathology , Biomarkers/metabolism , Diabetes Mellitus/metabolism
12.
J Am Soc Nephrol ; 33(12): 2153-2173, 2022 12.
Article in English | MEDLINE | ID: mdl-36198430

ABSTRACT

BACKGROUND: The signaling molecule stimulator of IFN genes (STING) was identified as a crucial regulator of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway, and this signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI. However, the role of STING in causing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown. METHODS: To investigate whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome, immortalized human and murine podocytes were differentiated for 14 days and treated with a STING-specific agonist. We used diabetic db/db mice, mice with experimental Alport syndrome, C57BL/6 mice, and STING knockout mice to assess the role of the STING signaling pathway in kidney failure. RESULTS: In vitro, murine and human podocytes express all of the components of the cGAS-STING pathway. In vivo, activation of STING renders C57BL/6 mice susceptible to albuminuria and podocyte loss. STING is activated at baseline in mice with experimental DKD and Alport syndrome. STING activation occurs in the glomerular but not the tubulointerstitial compartment in association with autophagic podocyte death in Alport syndrome mice and with apoptotic podocyte death in DKD mouse models. Genetic or pharmacologic inhibition of STING protects from progression of kidney disease in mice with DKD and Alport syndrome and increases lifespan in Alport syndrome mice. CONCLUSION: The activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Targeting STING may offer a therapeutic option to treat glomerular diseases of metabolic and nonmetabolic origin or prevent their development, progression, or both.


Subject(s)
Diabetic Nephropathies , Nephritis, Hereditary , Podocytes , Mice , Humans , Animals , Nephritis, Hereditary/genetics , Nephritis, Hereditary/metabolism , Mice, Inbred C57BL , Podocytes/metabolism , Proteinuria/metabolism , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Mice, Knockout , Nucleotidyltransferases/metabolism
13.
J Clin Med ; 11(5)2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35268424

ABSTRACT

Background: We previously reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss in kidney transplantation. Here, among 150 prospectively-followed kidney transplant recipients at 18 years post-transplant, we provide: updated (longer-term) estimates of cause-specific graft loss probabilities, risk factors for developing GFNA, and detailed characterizations of patients' overt nonadherent (NA) behavior, including timing, extent, and clinical consequences. Methods: Determination of the patient becoming NA in taking his/her immunosuppressive medications, and the underlying cause of graft loss, were determined prospectively by the attending physicians. For never-functioning-graft, GFNA, GF due to causes other than NA (Other GF), and death with a functioning graft (DWFG), cumulative incidence functions were used to estimate the cumulative probabilities of cause-specific graft loss. Cox stepwise regression was used to determine significant multivariable predictors for the hazard rate of developing GFNA. Results: GFNA was a major cause of graft loss (22/150 patients), particularly among African-American and Hispanic recipients <50 years of age-at-transplant (20/56 experienced GFNA), with estimated percentages of such patients ever developing GFNA ranging between 36.9 and 41.5%. These patients were also at a higher risk of developing Other GF. For the remaining patients (2/94 experienced GFNA), estimated percentages of ever-developing GFNA were much lower (range: 0.0−6.7%). The major cause of graft loss among recipients ≥50 years of age was DWFG; GFNA rarely occurred among older recipients. In 21/22 GFNA patients, NA behavior lasted continuously from the time of developing NA until GFNA. In total, 28/150 patients became NA, and 67.9% (19/28) occurred beyond 36 months post-transplant. A total of 25 of 28 NA patients (89.3%) developed biopsy-proven acute rejection and/or chronic rejection that was directly attributed to the NA behavior. Lastly, 25/28 admitted to NA behavior, with financial and psychological components documented in 71.4% (20/28) and 96.4% (27/28) of NA cases, respectively. Conclusions: These results highlight the importance of performing serial monitoring of patients for overt NA behavior throughout their post-transplant follow-up. Financial and psychological components to NA behavior need to be simultaneously addressed with the goal of achieving complete avoidance/elimination of NA behavior among higher risk patients.

15.
Transplantation ; 106(8): 1647-1655, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35019897

ABSTRACT

BACKGROUND: The long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group. METHODS: A global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey. RESULTS: The survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation. CONCLUSIONS: This international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.


Subject(s)
Diabetes Mellitus, Type 1 , Islets of Langerhans Transplantation , Pancreas Transplantation , Blood Glucose/metabolism , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/surgery , Glycated Hemoglobin , Humans , Islets of Langerhans Transplantation/adverse effects , Islets of Langerhans Transplantation/methods , Pancreas/metabolism , Pancreas Transplantation/adverse effects
16.
Transplantation ; 106(4): 709-721, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34310100

ABSTRACT

Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.


Subject(s)
Graft Rejection , Kidney Transplantation , Adult , Child , Graft Rejection/prevention & control , Humans , Kidney , Kidney Transplantation/adverse effects , Reoperation , Tissue Donors
17.
Sensors (Basel) ; 21(16)2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34450768

ABSTRACT

In light of the COVID-19 pandemic, the Medicines and Healthcare products Regulatory Agency administered the standards for producing a Rapidly Manufactured Ventilator System (RMVS) free of charge due to the United Kingdom's shortfall of ventilator systems throughout health centers. The standards delineate the minimum requirements in which a Rapidly Manufactured Ventilator System must encompass to be admissible for usage within hospitals. This work commences by evaluating the standards provided by the government to identify any potential security vulnerabilities that may arise due to the succinct development standards provided by the MHRA. This research investigates what cyber considerations are taken to safeguard a patient's health and medical data to improve situational awareness. A tool for a remotely accessible, low-cost ventilator system is developed to reveal what a malicious actor may be able to inflict on a modern ventilator and its adverse impact.


Subject(s)
COVID-19 , Pandemics , Awareness , Delivery of Health Care , Humans , SARS-CoV-2
18.
Front Pediatr ; 9: 687396, 2021.
Article in English | MEDLINE | ID: mdl-34322462

ABSTRACT

Introduction: The diagnosis of a post-surgical uroenteric fistula can be challenging and may be delayed for months after symptoms begin. A normal anion gap metabolic acidosis has been reported in up to 100% of patients after ureterosigmoidostomy, and bladder substitution using small bowel and/or colonic segments. Here, we describe a rare case of a pediatric patient who developed a uroenteric fistula from the transplant ureters into the small bowel, after an en-bloc kidney transplantation resulting in profound acidosis and deceptive watery diarrhea. Case Presentation: The patient is an 8-year-old girl with end stage kidney disease (ESKD) secondary to focal segmental glomerulosclerosis. Through a right retroperitoneal approach, she underwent a right native nephrectomy and a pediatric deceased donor en-bloc kidney transplant including two separate ureters. One month later, she had a renal allograft biopsy for suspected rejection. During the week after the biopsy, she experienced abdominal pain followed by watery diarrhea and metabolic acidosis requiring continuous bicarbonate/acetate infusions. An extensive gastro-intestinal evaluation for the cause of the diarrhea including endoscopy was inconclusive. The urine output decreased to <500 ml daily; although, the kidney function remained normal. After 2 weeks of unexplained watery diarrhea a magnetic resonance urogram with contrast was performed which demonstrated extravasation of urine from both ureters with fistulization into the small bowel. She underwent corrective surgery which identified the fistulous tract, which was resected and both ureters were re-implanted. The diarrhea and acidosis resolved, and she has maintained normal renal allograft function for over 1 year. Conclusion: An important aspect in the early diagnosis of a uroenteric fistula is the sudden onset of severe hyperchloremic metabolic acidosis that results when urine is diverted into the intestinal tract. The mechanism is similar to that described in cases of urinary diversions and/or bladder augmentation using the intestine. Important diagnostic tools are the measurements of solute excretion and pH in the urine as compared to the "watery diarrhea" or bowel output. Summary: We describe a case of a uroenteric fistula in a pediatric-en-bloc kidney transplant patient that went undiagnosed for almost 3 weeks due to the deceptive nature of the watery diarrhea which was actually urine. A uroenteric fistula should be considered in the differential diagnosis of diarrhea and hyperchloremic metabolic acidosis as a complication of kidney transplant. The simultaneous comparison of stool and urine pH and solute excretions may lead to the diagnosis, appropriate imaging and surgical intervention.

19.
JSLS ; 25(2)2021.
Article in English | MEDLINE | ID: mdl-34248334

ABSTRACT

BACKGROUND/OBJECTIVES: Laparoscopic living donor nephrectomy (LLDN) of the right kidney is currently considered as part of standard of care; however, dealing with the renal hilum when performing ligation/division of its renal vessels is still a main concern. Here, we describe a simple-to-perform technique, i.e., flipping the fully mobilized right kidney to the midline so that the renal artery becomes anteriorly, which offers better visualization and easier dissection of the renal vessels (achieving maximized lengths) when performing hand-assisted LLDN of the right kidney. METHODS: Living donors who underwent hand-assisted LLDN of the right kidney, along with their respective renal transplant recipients, were included in this report. Donor characteristics included renal artery and vein lengths; recipient characteristics included creatinine at months 12 - 36. Graft vein and arterial anastomosis data were also reported. RESULTS: Nineteen living donors and 19 recipients, with median donor and recipient ages being 39 (24 - 60) and 53 (3 - 81) years, respectively, were included. None of the 38 patients had intra- or postoperative complications. Donor renal vein was anastomosed to the right external iliac vein (n = 16), right common iliac vein (n = 2), and inferior vena cava (n = 1). Gonadal vein (n = 1) and deceased donor iliac vein (n = 2) were used to increase the right renal vein length in 3 cases. Four donor kidneys had 2 arteries reconstructed side by side. None of the recipients developed any vascular or urological complications. CONCLUSIONS: The laparoscopic technique described is safe and allows better visualization of the right hilum, mainly the renal artery, and helps in stapling the renal vein and renal artery.


Subject(s)
Hand-Assisted Laparoscopy/methods , Kidney Transplantation/methods , Kidney/surgery , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Adult , Female , Humans , Living Donors , Male , Middle Aged , Renal Artery/surgery , Renal Veins/surgery , Rotation , Treatment Outcome , Young Adult
20.
Am J Transplant ; 21 Suppl 3: 17-59, 2021 09.
Article in English | MEDLINE | ID: mdl-34245223

ABSTRACT

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.


Subject(s)
Diabetes Mellitus, Type 1 , Kidney Transplantation , Pancreas Transplantation , Graft Survival , Humans , Quality of Life , Renal Dialysis
SELECTION OF CITATIONS
SEARCH DETAIL
...