Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes:a case report

Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis. Case presentation: A 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with “indeterminate colitis” and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis. Conclusions: Our patient’s improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an ‘insulin free T1D’, our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D

Academic Primer Series: Five Key Papers for Consulting Clinician Educators.

INTRODUCTION: Clinician educators are often asked to perform consultations for colleagues. Invitations to consult and advise others on local problems can help foster great collaborations between centers, and allows for an exchange of ideas between programs. In this article, the authors identify and summarize several key papers to assist emerging clinician educators with the consultation process. METHODS: A consensus-building process was used to generate a list of key papers that describe the importance and significance of educational consulting, informed by social media sources. A three-round voting methodology, akin to a Delphi study, determined the most impactful papers from the larger list. RESULTS: Summaries of the five most highly rated papers on education consultation are presented in this paper. These papers were determined by a mixed group of junior and senior faculty members, who have summarized these papers with respect to their relevance for their peer groups. CONCLUSION: Five key papers on the educational consultation process are presented in this paper. These papers offer background and perspective to help junior faculty gain a grasp of consultation processes

Concurrent Primary Cardiac Tumors in a High-Risk Patient Presenting With Tamponade.

Primary cardiac tumors are rare, particularly in the elderly population. The patient described in this report presented with symptoms of dyspnea on exertion, leg swelling, and weight gain and was found to have two histologically distinct cardiac masses: atrial myxoma with concurrent aortic fibroelastoma. Given her history of cirrhosis and end-stage renal disease, the patient was a poor surgical candidate but opted for excision of both masses. The patient eventually succumbed to her cirrhosis six weeks after presentation. In this report, we advocate for further research into medical management for the unique presentation of concurrent primary cardiac tumors in high-operative-risk patients, particularly those whose symptoms are mostly due to tamponade

1058-71 Visualization of the effect of atrial-ventricular and right-left delay on cardiac output during biventricular pacing

Aprovada pel gerent de l'Institut Municipal d'Hisenda el 15-04-201

A Cadaveric Study on the Anomalous Origin of Renal and Gonadal Vasculature: An Observational Study

Background: Due to the increasing prevalence of kidney transplantation, a greater awareness of variations in the surrounding vasculature is of surgical importance. During embryological development, both the renal and gonadal arteries arise from lateral mesonephric branches of the dorsal aorta. In adults, gonadal arteries are paired vessels that normally arise from the aorta at the level of the second lumbar vertebra. Methods: Routine cadaveric dissection completed by first-year medical students and dental students incidentally revealed anatomical anomalies. Results: We describe two cadaveric findings in male cases which demonstrate unilateral and bilateral variations of testicular arteries originating from an aberrant renal artery in one case and an accessory renal artery in the other. Conclusion: By increasing awareness of anomalous testicular arteries we hope to encourage the standardization of preoperative vasculature exploration to both minimize intra-operative risk to living male kidney donors and increase patients’ understanding of potential risks and complications prior to consenting to the procedure providing more accurate information prior to surgery

Preferences for Peer Support Amongst Families Engaged in Paediatric Screening Programmes:The Perspectives of Parents Involved in Screening for Type 1 Diabetes in Children Aged 3–13

Introduction: This work describes a secondary analysis of a qualitative data set originally used to understand parent participants' preferences for the design and implementation of a screening programme for paediatric Type 1 diabetes (T1D). From this, their spontaneous preferences for peer support emerged, described here in the context of existing peer support programmes for the newly diagnosed alongside suggestions for their incorporation into screening programmes for T1D and a range of other conditions. Methods: Data were collected from semi‐structured interviews conducted with parents of children aged 3–13 years to explore their expectations, perceptions and preferences of a T1D paediatric screening programme. A secondary analysis of interviews from participants who spontaneously raised preferences for peer support was used to populate a novel framework informed by NHS England's key principles for the same, namely, Shared experiences and reciprocated support, Accessibility and inclusivity and Person‐centred and integrated peer support. Results: Parents in 29 of 33 interviews spontaneously described the potential value of peer support if receiving a result indicating a positive (presymptomatic T1D result) from a screening programme. Specifically, the value of ‘Shared experiences and reciprocated support’ in terms of emotional support and reassurance, and access to more directly interpretable and relevant information related to the condition; ‘Accessibility and inclusivity’ relating to access to a community of similar individuals, whether in person or online; ‘Person‐centred and integrated peer‐support’ and the need for support reflecting the changing need of the child and the integration of peer support with clinical care. Conclusions: The needs of peer support described by parents involved in T1D paediatric screening appear to be shared with those of families with children diagnosed with a range of life‐altering conditions. Although the needs of peer support for paediatric screening may differ across conditions, our findings are a valuable starting point for its design both in T1D and other examples of similar population screening programmes. Patient or Public Contribution: Patients and the public have been involved throughout the design of the ELSA study and have worked with us to inform the study process. They contributed to the design and content of patient‐facing materials, the content of our topic guides and the analysis and interpretation of our findings

Progression and treatment of incident lower urinary tract symptoms ( LUTS ) among men in the C alifornia M en's H ealth S tudy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110063/1/bju12810.pd

Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention

Inflammageing leads to uncontrolled leukocyte trafficking in response to inflammatory insults. Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in ageing. We then analysed whether PEPITEM could modulate leukocyte migration in older adults. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions

Regional Structural Orientation of the Mount Sharp Group Revealed by In Situ Dip Measurements and Stratigraphic Correlations on the Vera Rubin Ridge

Ground‐based bedding orientation measurements are critical to determine the geologic history and processes of sedimentation in Gale crater, Mars. We constrain the dip of lacustrine strata of the Blunts Point, Pettegrove Point, and Jura members of the Murray formation using a combination of regional stratigraphic correlations and bed attitude measurements from stereo Mastcam images taken by the Mars Science Laboratory Curiosity rover. In situ bed attitude measurements using a principal component analysis‐based regression method reveal a wide range of dips and dip azimuths owing to a combination of high stereo errors, postdepositional deformation of strata (e.g., fracturing, rotation, and impact cratering), and different primary depositional dips. These constrain regional dips to be within several degrees of horizontal on average. Stratigraphic correlations between targets observed in the Glen Torridon trough and at the Pettegrove Point‐Jura member contact of Vera Rubin ridge (VRR) constrain dips to be between 3°SE and 2°NW, consistent with nearly flat strata deposited horizontally on an equipotential surface. The Jura member is determined to be stratigraphically equivalent to the northern portion of the Glen Torridon trough. Rover‐based dip magnitudes are generally significantly shallower than the orientation of VRR member contacts measured from High Resolution Imaging Science Experiment‐based traces, suggesting the sedimentary strata and VRR member contacts may be discordant