Publications by authors named "Thomas Kay"

Objective: Type1Screen offers islet autoantibody testing to Australians with a family history of type 1 diabetes (T1D) with the dual aims of preventing diabetic ketoacidosis (DKA) and enabling use of disease-modifying therapy. We describe screening and monitoring outcomes 2 years after implementing in-home capillary blood spot sampling.

Research Design And Methods: Data from 2,064 participants who registered between July 2022 and June 2024 were analyzed: 1,507 and 557 chose blood spot and venipuncture screening respectively.

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Type 1 diabetes (T1D) is an autoimmune disease that develops when T cells destroy the insulin-producing beta cells that reside in the pancreatic islets. Immune cells, including T cells, infiltrate the islets and gradually destroy the beta cells. Human islet-infiltrating CD4 T cells recognize peptide epitopes derived from proinsulin, particularly C-peptide.

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Granuloma faciale is a benign and rare skin disease, which usually presents as well-defined red-purple asymptomatic plaques or nodules on the face but can also present extra-facially. It poses a significant therapeutic challenge, with varying degrees of success reported by a range of medical and surgical treatments. We describe a 41-year-old lady with biopsy-confirmed facial granuloma faciale, affecting her nose, cheeks, upper lip, and forehead, who had failed a variety of medical treatments, UVB phototherapy, and pulsed dye laser.

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Article Synopsis
  • * Current research seeks to understand T1D and develop new treatments, including immune system modulation, β-cell regeneration, and advanced insulin delivery methods like closed-loop pumps and stem cell therapies.
  • * Recent studies suggest that TNF-α inhibitors could help preserve β-cell function in people with advanced T1D, prompting experts to convene and plan pivotal clinical trials to further evaluate their effectiveness.
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Introduction: The National Registry of Rare Kidney Diseases (RaDaR) collects data from people living with rare kidney diseases across the UK, and is the world's largest, rare kidney disease registry. We present the clinical demographics and renal function of 25,880 prevalent patients and sought evidence of bias in recruitment to RaDaR.

Methods: RaDaR is linked with the UK Renal Registry (UKRR, with which all UK patients receiving kidney replacement therapy [KRT] are registered).

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Chronic destruction of insulin-producing pancreatic β cells by T cells results in autoimmune diabetes. Similar to other chronic T cell-mediated pathologies, a role for T cell exhaustion has been identified in diabetes in humans and NOD mice. The development and differentiation of exhausted T cells depends on exposure to Ag.

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Objective: To develop a follow-up algorithm for urinary stone patients after definitive treatment.

Materials And Methods: The panel performed a systematic review on follow-up of urinary stone patients after treatment (PROSPERO: CRD42020205739). Given the lack of comparative studies we critically evaluated the literature and reached a consensus on the follow-up scheme.

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Introduction: Chronic activation of self-reactive T cells with beta cell antigens results in the upregulation of immune checkpoint molecules that keep self-reactive T cells under control and delay beta cell destruction in autoimmune diabetes. Inhibiting PD1/PD-L1 signaling results in autoimmune diabetes in mice and humans with pre-existing autoimmunity against beta cells. However, it is not known if other immune checkpoint molecules, such as TIGIT, can also negatively regulate self-reactive T cells.

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Article Synopsis
  • - Persistent exposure to antigens leads to the development of exhausted T cells, which are less effective in responding to threats, and this phenomenon typically occurs during chronic infections and cancer, raising questions about its role in autoimmune diabetes.
  • - In a study using nonobese diabetic (NOD) mice, exhausted CD8+ T cells targeting the islet antigen IGRP were found in the pancreas, while more of these cells were preserved in peripheral lymphoid organs.
  • - By creating transgenic NOD mice that express IGRP in cells outside the islet, researchers showed that exposure to IGRP in these extraislet areas resulted in severely exhausted T cells, which ultimately protected the mice from developing diabetes.
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β-cells are a type of endocrine cell found in pancreatic islets that synthesize, store and release insulin. In type 1 diabetes (T1D), T-cells of the immune system selectively destroy the insulin-producing β-cells. Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.

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Objective: This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies.

Research Design And Methods: Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS.

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Background: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction.

Methods: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma.

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Introduction: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria.

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Article Synopsis
  • A phase 2 trial investigated the effects of baricitinib, a JAK inhibitor, on β-cell function in patients with early-stage type 1 diabetes, comparing it to a placebo over 48 weeks.
  • Results showed that the baricitinib group had a significantly higher mean C-peptide level, indicating better β-cell function, and required a lower daily insulin dose compared to the placebo group.
  • While baricitinib improved certain measures of insulin production and glycemic control, the overall levels of glycated hemoglobin were similar between both groups, with no notable differences in adverse events reported.
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Purpose: To map current literature and provide an overview of upcoming future diagnostic and prognostic methods for upper tract urothelial carcinoma (UTUC), including translational medical science.

Methods: A scoping review approach was applied to search the literature. Based on the published literature, and the experts own experience and opinions consensus was reached through discussions at the meeting Consultation on UTUC II in Stockholm, September 2022.

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CXCL10 is an IFNγ-inducible chemokine implicated in the pathogenesis of type 1 diabetes. T-cells attracted to pancreatic islets produce IFNγ, but it is unclear what attracts the first IFNγ -producing T-cells in islets. Gut dysbiosis following administration of pathobionts induced CXCL10 expression in pancreatic islets of healthy non-diabetes-prone (C57BL/6) mice and depended on TLR4-signaling, and in non-obese diabetic (NOD) mice, gut dysbiosis induced also CXCR3 chemokine receptor in IGRP-reactive islet-specific T-cells in pancreatic lymph node.

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Purpose: To summarise the current knowledge regarding diagnostics, prognostication and follow-up in upper tract urothelial carcinoma (UTUC).

Methods: A scoping review combined with expert opinion was applied to provide an overview of the current research field. Based on the published literature and the experts' own experience and opinions, consensus was reached through presentations and discussions at the meeting Consultation on UTUC II in Stockholm 2022.

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Article Synopsis
  • * Ongoing research focuses on understanding T-cell responses and developing effective disease-modifying agents that could be useful in the early stages of T1D.
  • * Advanced profiling techniques at the single-cell level aim to discover new biomarkers and improve assays for characterizing antigen-specific T cells, enhancing the ability to predict disease progression and treatment responses.
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Type 1 diabetes is an autoimmune disease with onset from early childhood. The insulin-producing pancreatic beta cells are destroyed by CD8 cytotoxic T cells. The disease is challenging to study mechanistically in humans because it is not possible to biopsy the pancreatic islets and the disease is most active prior to the time of clinical diagnosis.

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This study examined correlations between continuous glucose monitoring (CGM)-based composite metrics and standard glucose metrics within CGM data sets from individuals with recent-onset and long-duration type 1 diabetes. First, a literature review and critique of published CGM-based composite metrics was undertaken. Second, composite metric results were calculated for the two CGM data sets and correlations with six standard glucose metrics were examined.

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Fournier's gangrene is a rare and potentially fatal condition that affects the external genitalia and perineum as a necrotizing soft-tissue infection. It is equally prevalent in men and women and although there are many ways to manage the condition, it must be done so effectively because there is a chance that life-threatening complications could develop. This retrospective study set out to fill any knowledge gaps, compare reconstructive options to those described in the literature, and promote reflection on current management.

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Unlabelled: Intrahepatic islet transplantation for type 1 diabetes is limited by the need for multiple infusions and poor islet viability posttransplantation. The development of alternative transplantation sites is necessary to improve islet survival and facilitate monitoring and retrieval. We tested a clinically proven biodegradable temporizing matrix (BTM), a polyurethane-based scaffold, to generate a well-vascularized intracutaneous "neodermis" within the skin for islet transplantation.

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