Impairment of Microcirculation Parameters in Patients with a History of Diabetic Foot Ulcers

Background and Objectives: According to the International Working Group on Diabetic Foot (IWGDF) risk classification, the estimated risk of developing a diabetic foot ulcer (DFU) is much higher in patients with a history of DFUs (Grade 3) compared to those with a peripheral neuropathy but without a history of DFUs (Grades 1 and 2). It has been suggested that microcirculation impairment is involved in DFU genesis and could be taken into account to refine the existing risk classification. The aim of this study was to evaluate microcirculation parameters in patients with diabetes according to their estimated DFU risk. Materials and Methods: A total of 172 patients with type 2 diabetes associated with a peripheral neuropathy and/or a history of DFUs were included and classified into two groups (Grade 1–2 and Grade 3) according to the IWGDF classification. All patients underwent an evaluation of peripheral neuropathy, plantar sudomotor function, and skin microcirculation parameters. These different parameters were compared between both groups. Results: There was no significant difference between the two groups in terms of age, diabetes duration, transcutaneous oxygen pressure level, skin microcirculatory reactivity, neuropathy disability score, neuropathy symptom score, or thermal sensitivity. Patients in Grade 3 were more likely to present with retinopathy (OR 3.15, 95%CI [1.53; 6.49]) and severe sudomotor dysfunction (OR 2.73 95%CI [1.29; 5.80] but less likely to have abnormal VPT (OR 0.20 95%CI [0.05; 0.80]). Conclusions: The present study found more retinopathy and a more pronounced alteration to sudomotor function in Grade 3 patients, suggesting that these parameters could be considered to better identify patients at high risk of DFUs

Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up

International audienceHypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10-46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common (n = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors

Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up

Hypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10–46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common (n = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors.</jats:p

Poorly differentiated thyroid carcinoma with pleomorphic giant cells—a case report

International audienc

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets.: Oxidative stress and metabolic syndrome

International audienceAIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. METHODS: The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. RESULTS: Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A(2), and through increased thromboxane B(2) formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. CONCLUSIONS/INTERPRETATION: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation