Application of white blood cell SPECT/CT to predict remission after a 6 or 12 week course of antibiotic treatment for diabetic foot osteomyelitis.

AIMS/HYPOTHESIS: Diabetic foot osteomyelitis is a major risk factor for amputation. Medical treatment allows remission in 53-82% of cases. However, the optimal duration of antibiotic therapy remains controversial as a validated marker of osteomyelitis remission is lacking. The aim of this cohort study was to assess prospectively the remission rate of diabetic foot osteomyelitis medically treated using white blood cell (WBC)-single-photon emission computed tomography (SPECT)/computed tomography (CT) as a predictive marker of remission. METHODS: Individuals with diabetic foot osteomyelitis that was non-surgically treated between April 2014 and December 2015 were included. All participants were treated with antibiotics alone. WBC-SPECT/CT was performed at 6 weeks and antibiotic treatment discontinued if the clinical signs of soft-tissue infection had resolved and there was no abnormal uptake of labelled WBCs. Treatment was otherwise continued for a total of 12 weeks and then discontinued. For these individuals, another WBC-SPECT/CT was performed at 12 weeks. Remission was defined as the absence of recurrence of osteomyelitis at the same location at 1 year. RESULTS: Forty-five individuals were included; overall remission rate was 84% at 1 year. A 6 week course of antibiotics was used in 23 participants, 22 of whom were in remission at 1 year (96%); a 12 week course was used for 22 participants, 16 of whom were in remission at 1 year (73%). Sensitivity of WBC-SPECT/CT at 12 weeks was 100%, specificity 56%, positive predictive value 46% and negative predictive value 100%. CONCLUSIONS/INTERPRETATION: The study suggests that WBC-SPECT/CT could predict remission at the end of antibiotic treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02927678.

Trends in the relation between hyperglycemia correction and active Charcot neuroarthropathy: results from the EPICHAR study.

INTRODUCTION: The pathophysiology of Charcot neuroarthropathy (CN) remains unclear. There are a number of hypotheses but these are not exclusive. In its clinical presentation, this complication intersects with the semiology of diabetic-induced neuropathy, such as peripheral hypervascularization and the appearance of arteriovenous shunt. The EPICHAR study is as yet an unpublished cohort of people living with diabetes complicated by CN (in active or chronic phase). Based on the findings of the EPICHAR study, this study aimed to investigate whether a reduction in the rate of hyperglycemia accompanies the onset of an active phase of CN. RESEARCH DESIGN AND METHODS: Hemoglobin A1c (HbA1c) levels were assessed 3 months (M3) and 6 months (M6) before the diagnosis of active CN (M0). RESULTS: 103 patients living with diabetes and presenting active CN were included between January and December 2019 from the 31 centers participating in this study (30 in France and 1 in Belgium). The mean age of the participants was 60.2±12.2 years; the vast majority were men (71.8%) living with type 2 diabetes (75.5%). Mean HbA1c levels significantly declined between M6 (median 7.70; Q1, Q3: 7.00, 8.55) and M3 (median 7.65; Q1, Q3: 6.90, 8.50) (p=0.012), as well as between M6 and M0 (median 7.40; Q1, Q3: 6.50, 8.50) (p=0.014). No significant difference was found between M3 and M0 (p=0.072). CONCLUSIONS: A significant reduction in HbA1c levels seems to accompany the onset of the active phase of CN. TRIAL REGISTRATION NUMBER: NCM03744039.

[Hypertriglyceridemia: therapeutic strategy]. / Existe-T-il un risque de pancréatite aiguë? Conduite a tenir devant une hypertriglycéridémie.

Causes of hypertriglyceridemia (HTG) vary according to their severity and to their character pure or mixed. Environmental factors including caloric intake excess, fructose overload, alcohol consumption, metabolic syndrom, diabetes, and drug exposure are mostly involved in pure, mild HTG. In contrast, the main etiology of mixed HTG (combined dyslipidemia) is familial combined hyperlipidemia which is commonly associated with metabolic syndrome. Major HTG (> 10 g/L) results mostly from genetic disorder in lipid metabolism with a variable contribution of environmental factors. The complications of HTG are an increased risk of acute pancreatitis (TG > 10 g/L) and a controversial atherogenic risk. Lifestyle modification is the treatment cornerstone. Nevertheless, statins are generally considered as the first drug if a medication is necessary for mixed hyperlipidemia. Fibrates may be used in combination with statin for patient with high atherogenic risk and simultaneous residual hypertriglycéridémie and low HDLc or in high risk patient with severe pure hypertriglyceridemia.

99mTc-white blood cell SPECT/CT to assess diabetic foot osteomyelitis remission: contribution of semi-quantitative scoring system.

AIMS: We previously reported that 99mTc-White blood cell (WBC) single-photon emission computed tomography (SPECT/CT) could be a useful tool to assess diabetic foot osteomyelitis (DFO) remission and guide the duration of antibiotic treatment. The aim of the present study was to evaluate the performance and reproducibility of two analysis methods to diagnose DFO remission using 99mTc-WBC-SPECT/CT. METHODS: 99mTc-WBC-SPECT/CT performed for patients with DFO at the end of antibiotic treatment were retrospectively read by two nuclear physicians (one senior and one junior). Assessment by conventional visual analysis and by the use of a semi-quantitative scoring system, the composite score index (CSI), was performed. The performance and reproducibility of methods were compared between the two nuclear physicians. Successful treatment of DFO was defined by the absence of DFO relapse at the same site within 1 year. RESULTS: A total of 68 patients with 74 DFO were included. Three were excluded from the analysis due to the low quality of SPECT/CT; among the 71 DFO analyzed, 11 (15.5%) had a relapse during follow-up. Performances of 99mTc-WBC-SPECT/CT to predict DFO remission with conventional visual assessment were significantly lower for junior than for senior nuclear physician with moderate inter-rater agreement (Kappa: 0.417). Performances with the use of CSI were similar between the two readers with good inter-rater agreement (Kappa: 0.756). CONCLUSION: The study found that conventional visual assessment of 99mTc-WBC-SPECT/CT to assess DFO remission requires experience, and supported that CSI could be useful for junior nuclear physician to discriminate residual infections and inflammatory post-treatment uptake.

Congenital Hypothyroidism due to a Low Level of Maternal Thyrotropin Receptor-Blocking Antibodies.

INTRODUCTION: Maternal TSH receptor antibodies (TRAbs) can cross the placenta and affect fetal and neonatal thyroid function. Maternal TSH receptor-blocking antibodies (TBAbs) are a rare cause of congenital hypothyroidism. CASE REPORT: Following the discovery of a highly elevated TSH on her neonatal screening test, a 10-day-old girl with no familial history of thyroid disorder was referred to the pediatric endocrinology unit. Hypothyroidism was confirmed with a highly elevated TSH (817 mIU/L, reference range 0.4-3.1) and very low levels of FT4 (1.8 pmol/L, reference range 12-22). Anti-TPO antibodies were at 81 IU/mL (reference range <34), TRAbs at 1.7 IU/L (reference range <1.75), and thyroglobulin at 9.4 µg/L (reference range 3.5-77). The thyroid appeared normal on ultrasonography, and no radioiodine uptake was seen on the scintigraphy after the perchlorate discharge test. Concomitantly, a severe maternal hypothyroidism was discovered (TSH 224 mIU/L). The maternal ultrasound appeared normal, anti-TPO antibodies were moderately elevated, and TRAbs were at 3.2 IU/L. TBAbs activity was measured in the mother and her daughter, and a very high and similar blocking activity was observed in both patients (TBAbs 89%, reference range <10%). L-thyroxine treatment was introduced in the newborn and was successfully discontinued at 6.5 months of age, as the TBAbs activity decreased. CONCLUSION: We report herein a case of transient congenital hypothyroidism with a normal neonatal TRAbs level. In case of maternal TBAbs, similar activity of maternal TBAbs must be expected in the neonate, independently of the neonatal level of TRAbs.

Higher prevalence of incidental findings identified upon coronary calcium score assessment in type 2 and type 3 diabetes versus type 1 diabetes.

AIM: Noninvasive assessment of infraclinic coronary atherosclerosis by coronary artery calcium score (CAC) measurement leads to the identification of incidental findings. The aim of this study was to determine the prevalence of incidental findings following systematic CAC assessment in diabetic patients with high cardiovascular risk, to identify the determinants, and to assess the midterm consequences of these findings in patient care. METHODS: 732 consecutive asymptomatic patients (187 type 1 diabetes (TD1), 482 type 2 diabetes (TD2) and 63 type 3 diabetes (TD3)) aged 60.6±0.7 years who had a CAC assessment by Multiple Detector Computed Tomography between 2015 and 2017 were systematically included. Clinical and biological data were collected from medical electronic files. RESULTS: 117/732 diabetic patients (16.0%) had incidental findings of which 105 (14.3%) were unknown. Incidental findings were more frequent in TD3 (23.8%) and TD2 (17.0%) than in TD1 (10.7%) (p = 0.05). 76 diabetic patients (10.4%) had lung abnormalities, mainly pulmonary nodules (31 patients, 4.2%). The other incidental finding were pericardial (1.5%), vascular (1.2%), thymic (0.7%) and digestive diseases (0.5%). 42.6% of patients with incidental findings had an additional TDM and 56.8% a specialized medical advice. In 10 patients (9.3% of incidental findings), the identification of incidental finding led to a specific treatment of the underlying disease. In multivariate analysis, microalbuminuria, type of diabetes (TD2/TD3 vs TD1) and smoking were significantly associated with incidental findings (p = 0.003; p = 0.026; p = 0.050 respectively). CONCLUSIONS: Incidental findings are not rare in diabetic patients upon CAC assessment. A fraction of them are accessible to specific treatment. These findings raise the question if a systematic low dose chest TDM should be conducted in TD2 or TD3 patients and in any diabetic smokers by enlarging the window used for CAC assessment.

[Screening of silent myocardial ischemia in diabetic patients: Practical details and issues]. / Dépistage de l'ischémie myocardique silencieuse des patients diabétiques : modalités et enjeux.

Silent myocardial ischemia is more frequent in diabetic patients. Nevertheless, its prevalence depends on global cardiovascular risk. Although this is a factor of overmortality, its screening is discussed. In fact, crucial issue is the demonstration of a benefit from revascularizing immediately any coronary stenosis in silent diabetic patients. Recent studies report no benefit of revascularization by endovascular treatment versus medical treatment in patients with stable coronary disease in general population and in diabetic patients. Screening of silent myocardial ischemia should be only proposed to diabetic patients with a very high probability of multivessel disease. Only these patients could benefit from surgical revascularization. For the other diabetic patients, it seems to be reasonable that only patients with cardiovascular risk factors not controlled by medical treatment should benefit from screening, whose optimal practical details stay discussed.

Prevalence and function of anti-lipoprotein lipase auto-antibodies in type V hyperchylomicronemia.

PURPOSE: Type V hyperlipidemia (HTG V) characterized by accumulation of both chylomicrons and VLDL results from a complex combination of genetic and environmental factors. However, a large proportion of sporadic cases remains largely unexplained. In a few cases, in a context of autoimmunity, auto-antibodies inhibiting lipoprotein lipase (LPL) activity have been incriminated. To establish their contribution to common type V hyperlipidemia in subjects with no apparent evidence of autoimmune background, we systematically screened the presence of these antibodies and their inhibition properties. METHODS: Screening for circulating anti-human LPL immunoglobulin G (anti-hLPL IgG) was carried out by western blotting in 63 subjects with HTG V and 77 controls. Inhibition of lipolytic activity by plasma from these patients was measured ex vivo. RESULTS: Anti-hLPL IgG was detectable in plasma from both controls and subjects with HTG V. After establishment of a threshold value corresponding to the 95th percentile of the control population, 27% of subjects with HTG V were found to have abnormal antibody levels (P<0.001). Only plasma obtained from these hyperchylomicronemic subjects with a high level of anti-hLPL IgG inhibited triglyceride hydrolysis whereas plasma from controls or HTG subjects with normal anti-hLPL IgG levels had no inhibitory effect (-13.5+/-3.4% vs 1.6+/-3.4%; P=0.04). However, no correlation was observed between anti-hLPL IgG levels, inhibitory effect and plasma triglyceride concentration. CONCLUSION: High levels of anti-hLPL immunoreactivity could be detected in only one out of four adult patients with type V hyperchylomicronemia. Furthermore, only a minority of these subjects (less than 10%) displayed both high anti-hLPL IgG levels and substantial inhibition (>20%) of plasma lipolysis. These auto-antibodies, in this setting only, might contribute to the occurrence of a minority of sporadic type V dyslipidemia cases.

Increased lipid peroxidation in LDL from type-2 diabetic patients.

Increased oxidative stress is associated with type-2 diabetes and related cardiovascular diseases, but oxidative modification of LDL has been partially characterized. Our aim was to compare the lipid and fatty acid composition as well as the redox status of LDL from diabetic patients and healthy subjects. First, to ensure that isolation of LDL by sequential ultracentrifugation did not result in lipid modifications, lipid composition and peroxide content were determined in LDL isolated either by ultracentrifugation or fast-protein liquid chromatography. Both methods resulted in similar concentrations of lipids, fatty acids, hydroxy-octadecadienoic acid (HODE) and malondialdehyde (MDA). Then, LDLs were isolated by ultracentrifugation from eight type-2 diabetic patients and eight control subjects. Compared to control LDL, diabetic LDL contained decreased cholesteryl esters and increased triglyceride concentrations. Ethanolamine plasmalogens decreased by 49%. Proportions of linoleic acid decreased in all lipid classes, while proportions of arachidonic acid increased in cholesteryl esters. Total HODE concentrations increased by 56%, 12- and 15-hydroxy-eicosatetraenoic acid by 161 and 86%, respectively, and MDA levels increased by twofold. alpha-Tocopherol concentrations, expressed relative to triglycerides, were lower in LDL from patients compared to controls, while gamma-tocopherol did not differ. Overall, LDL from type-2 diabetic patients displayed increased oxidative stress. Determination of hydroxylated fatty acids and ethanolamine plasmalogen depletion could be especially relevant in diabetes.