Towards individualised and optimalised positioning of non-ventilated COVID-19 patients: Putting the affected parts of the lung(s) on top?

The outbreak of COVID-19 led to an unprecedented inflow of hospitalised patients with severe acute respiratory syndrome (SARS), requiring high-flow non-invasive oxygenation, if not invasive mechanical ventilation. While the best option in terms of non-invasive systems of oxygen delivery is still a matter of debate, it also remains unclear as to whether or not the optimal in-bed positioning of patients might also help to improve their oxygen saturation levels. On the basis of three representative cases, it is possible to propose the following hypotheses: (i) how patients are positioned has a strong influence on their oxygen saturation levels; (ii) saturation-optimalised positions are patient-specific; (iii) prone positions require ergonomic devices; and (iv) saturation-optimalised positions should aim to place the most affected part(s) of the lung(s) on top. Considered together, these hypotheses have led us to recommend that COVID-19 patients should undergo a specific assessment at admission to determine their saturation-optimalised in-bed position. However, further studies are still needed to assess the benefits of such a strategy on clinical outcomes.

Benefits of Ophdiat, a telemedical network to screen for diabetic retinopathy: a retrospective study in five reference hospital centres.

AIM: One objective of Ophdiat, a telemedical network using digital non-mydriatic cameras in Ile-de-France, is to develop a comprehensive screening programme that provides access to annual fundus examinations to all diabetic patients. The aim of this study was to evaluate the benefits of this programme in a hospital setting. METHODS: A retrospective analysis of 500 case reports of diabetic patients hospitalized before and after Ophdiat setup was performed in five reference hospital centres. At each centre, 100 case reports (50 before, 50 after) of patients aged greater than 18 years, hospitalized for their annual check-up, with no known diabetic retinopathy (DR) before hospitalization and with the last fundus examination performed greater than 11 months previously, were randomly selected. The primary endpoint was the proportion of patients whose fundus examinations were performed during hospitalization; secondary endpoints were the number of cases of DR found and the time taken by ophthalmologists to make the diagnosis. RESULTS: The mean proportion of patients with fundus examinations was 50.4% and 72.4% before and after, respectively, Ophdiat (P<0.01). The prevalence of DR was 11.1% before and 12.7% after (not significant). The mean time taken by an ophthalmologist per diagnosis of DR was 0.90 half-day before and 0.32 half-day after Ophdiat. CONCLUSION: This evaluation shows that Ophdiat, combined with the availability of modern and effective devices, has improved DR screening in diabetology departments in hospitals. Additional human resources would certainly ensure more effective use of the system.

Abnormalities in insulin secretion in type 2 diabetes mellitus.

Type 2 diabetes mellitus is a multifactorial disease, due to decreased glucose peripheral uptake, and increased hepatic glucose production, due to reduced both insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including absence of pulsatility, loss of early phase of insulin secretion after glucose, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. beta-cell dysfunction is genetically determined and appears early in the course of the disease. The interplay between insulin secretory defect and insulin resistance is now better understood. In subjects with normal beta-cell function, increase in insulin is compensated by an increase in insulin secretion and plasma glucose levels remain normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate leads to a progressive elevation in plasma glucose levels, then to overt diabetes. When permanent hyperglycaemia is present, progressive severe insulin secretory failure with time ensues, due to glucotoxicity and lipotoxicity, and oxidative stress. A marked reduction in beta-cell mass at post-mortem examination of pancreas of patients with type 2 diabetes has been reported, with an increase in beta-cell apoptosis non-compensated by neogenesis.

Macular pattern dystrophy in MIDD: long-term follow-up.

A case of maternally inherited diabetes and deafness (MIDD)-associated macular pattern dystrophy with a 15-year follow-up is reported. On initial examination at age 37, visual acuity was normal, but chorioretinal atrophy at the posterior pole was already present in both eyes. At age 52, visual acuity remained normal in the right eye and was only slightly decreased in the left eye despite notable extension of the areas of chorioretinal atrophy in that eye. No evidence of diabetic retinopathy was present at any time. This case shows that visual acuity can remain stable in the long term despite extensive lesions of macular pattern dystrophy.

Muscle infarction in a young woman with brittle type 1 diabetes.

We present the first case of muscle infarction in a 30-year-old woman who had a 5-year history of type 1 diabetes mellitus that was not complicated by nephropathy, retinopathy or neuropathy. All common causes of muscle infarction were excluded, particularly microangiopathy and a hypercoagulable state. The differential diagnosis included infection (pyomyositis, necrotic fasciitis), focal inflammatory myositis, vascular events, trauma, tumor and diabetic amyotrophy, all of which were excluded. In spite of good glycaemic control, her diabetes remained brittle; alternating states of transient acute hypoglycaemia and hyperglycaemia may have been responsible for the infarction. Brittleness resumed after treatment with subcutaneous insulin infusion using a portable pump. No recurrence of muscle infarction was observed during a 18-month follow-up.

Occurrence of gestational diabetes mellitus, maternal and fetal outcomes beyond the 28th week of gestation in women at high risk of gestational diabetes. A prospective study.

AIM: Among the numerous guidelines defining the diagnostic strategy of gestational diabetes mellitus (GDM), none of them suggest a follow-up in women with risk factors beyond the 28th week of gestation (WG). The primary objective of this study was to assess the incidence of GDM beyond 28 WG in a group of women at high risk. The secondary objectives were to evaluate maternal and fetal outcomes in early and late GDM (between 24-28 WG, and beyond 28 WG), as well as to compare them to a normal glucose tolerance (NGT) group. METHODS: A prospective study conducted in 191 consecutive women. Between 24-28 WG, the diagnosis of GDM was performed in a two-step approach (50 then 75 g). Beyond the 28 WG, the diagnosis of GDM was based on self-monitoring blood glucose (SMBG). All women were educated about an individualized diabetic diet and to perform SMBG daily glucose profiles. RESULTS: Seventy-two percent of the women at risk had developed GDM. Among these, 54% had developed early GDM, between 24-28 WG, and 18% had developed late GDM, beyond the 28th WG. Gestational age of late GDM was estimated 30 WG. In late GDM, onset of diabetes seems to be predicted by an increase in capillary glucose value determined at 22:00 hours, but this needs to be confirmed. Women who develop GDM2 have a significantly higher rate of macrosomia and more important pre-pregnancy overweight, underlining this impact in the occurrence of macrosomia. Finally maternal outcomes were not different in the 3 groups with intensive intervention.

No evidence for left ventricular diastolic dysfunction in asymptomatic normotensive type 2 diabetic patients: a case-control study with new echocardiographic techniques.

OBJECTIVE: We sought to determine whether abnormalities of left ventricular structure and function could be detected in asymptomatic type 2 diabetic patients free of cardiovascular complications. RESEARCH DESIGN AND METHODS: We compared 48 subjects with type 2 diabetes (34 men, 50+/-6 years) without hypertension, coronary artery disease and microangiopathic complications with 30 age-matched healthy controls. Left ventricular diastolic function was assessed by conventional Doppler echocardiography and new echocardiographic techniques (tissue Doppler imaging, color M-mode propagation velocity). A pseudonormal (PN) pattern of left ventricular filling was screened by several methods including Valsalva maneuver. RESULTS: Systolic function was normal in all patients. There was no significant difference in conventional and new echocardiographic Doppler indices of diastolic function between patients and control subjects. A PN diastolic function frequently suggested by the Valsalva maneuver (20 patients) was excluded using the new parameters. CONCLUSIONS: Diastolic dysfunction is not as frequent as previously described in selected patients with type 2 diabetes free of microangiopathic complications. New Doppler echocardiographic methods provide, in contrast with the Valsalva maneuver, a reliable estimate of diastolic function and should be incorporated in the non-invasive screening for diabetic cardiomyopathy.

Zygomycosis: an uncommon cause for peripheral facial palsy in diabetes.

Mucormycosis is an emerging fungal infection with a high rate of mortality. Diabetic and immuno-compromised patients are the most frequent hosts. We report a case of rhino-orbito-cerebral mucormycosis revealed by facial palsy in a diabetic, immuno-compromised patient with difficult life conditions. He received intravenous antifungal treatment (amphotericin B) and early surgical debridement and completely recovered with no recurrence after 3 months of follow-up. Physicians should be aware of such atypical clinical presentations due to the need for early appropriate combined medical and surgical management to improve disease recovery and prognosis.

Kearns Sayre syndrome: an unusual form of mitochondrial diabetes.

Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by the emergence before age 20 of progressive external ophthalmoplegia, pigmentary retinopathy, together with other heterogeneous clinical manifestations, including cardiac conduction defects, muscle abnormalities and endocrinopathies. KSS is associated with large heteroplasmic deletions in mitochondrial DNA. We report the case of a 43-year-old woman, with diabetes mellitus as a first manifestation at age 19. Later, she exhibited bilateral ptosis and external ophthalmoplegia with progressive worsening. DNA analysis identified a large mitochondrial DNA (mtDNA) deletion, which confirmed the diagnosis of KSS. By reporting this case with diabetes mellitus as first manifestation, we aim at emphasizing problems of diagnosis in these subtypes of mitochondrial diabetes.

N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients.

AIMS: Hyperglycemia is linked to vascular dysfunction in patients with diabetes mellitus, either directly or through advanced glycation end product (AGE) formation. Experimental evidence has indicated the possible involvement of AGEs in the genesis of vascular complications. We investigated whether serum levels of AGEs and of the glycoxidation compound carboxymethyl-lysine (CML) were increased and correlated with vascular complications in type II diabetes mellitus. METHODS: Serum levels of AGEs and CML-human serum protein (CML-HSP) were measured by a specific immunoassay in 51 men and 26 women aged 58 +/- 6.1 years (mean +/- SD) who had been treated for type II diabetes mellitus for 11 +/- 8 years, and in a non-diabetic control group consisting of 39 men and 21 women aged 55.5 +/- 7.5 years. Patients with macroalbuminuria or abnormal creatinine clearance were excluded from the study. RESULTS: The serum levels of AGEs were significantly increased in patients with type II diabetes compared to controls (P<0.001). Blood levels of CML-HSP were significantly increased in diabetic patients compared to normal subjects [35.3 +/- 27.4 and 9.3 +/- 7.2 (mean +/- SD) pmol/mg of protein, respectively; P<0.0001]. In diabetic patients with retinopathy or microalbuminuria (urinary albumin excretion: UAE > 30 mg/24 h), CML-HSP levels were significantly higher (P<0.02), and even more elevated in patients with both complications. CONCLUSION: In patients with type II diabetes, CML-HSP levels that are at variance with the HbA(1c) index for blood glucose may be a biomarker of glycoxidation, and related to the development of microvascular complications.

Screening for diabetic retinopathy: the first telemedical approach in a primary care setting in France.

OBJECTIVES: Diabetic retinopathy (DR) remains a major cause of visual impairment in France, due to insufficient regular annual screening. Fundus photography is a sensitive alternative to ophthalmoscopy for DR screening. The aim of our study was to report the first telemedical approach to this screening in a primary care setting in France. METHODS: A DR screening centre equipped with a nonmydriatic camera was opened in the 18th district of northern Paris and placed at the disposal of general practitioners (GPs) of the Réseau de Santé Paris Nord (North Paris Health Network). These GPs were invited to send their diabetic patients who had no known DR and had had no fundus examination for more than one year to this screening center. Retinal photographs were taken by an orthoptist without pupillary dilation and sent for grading through the Internet to the Lariboisière Hopital Ophthalmology Department. RESULTS: During an 18-month period, 912 DR screening examinations were performed in 868 diabetic patients referred to the DR screening center by 240 GPs. Patients' mean +/- SD age was 59.9 +/- 11.1 years. Of these 868 patients, 260 (30%) said they never have had an ophthalmological examination. Diabetic retinopathy was detected in 197 patients (22.7%). The proportion of patients for whom fundus photographs of one or both eyes could not be assessed was 10.1%. 159 patients (18.3%) required referral to an ophthalmologist. CONCLUSION: Nonmydriatic photography, combined with teletransmission to a reading centre, proved to be a feasible valid method for the detection of DR. This screening method allowed the identification of patients requiring prompt referral to an ophthalmologist for further complete eye examination.

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

[Pathogenesis of type 2 diabetes mellitus]. / Physiopathologie du diabète de type 2.

"Common" type 2 diabetes mellitus is a multifactorial disease. Hyperglycemia is related to a decrease in glucose peripheral uptake, and to an increase in hepatic glucose production, due to reduced insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including loss of basal pulsatility, lack of early phase of insulin secretion after intravenous glucose administration, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. These genetically determined abnormalities appear early in the course of the disease. Insulin resistance affects muscle, liver, and adipose tissue. For the same plasma insulin levels, peripheral glucose uptake and hepatic glucose production suppressibility are lower in diabetic patients than in controls. It results from aging of the population and from "western" lifestyle, with progressive increase in mean body weight, due to excess in energy intake, decreased energy expenses and low physical activity level. NEW ASPECTS: The role of beta-cell dysfunction, as well as the interplay between insulin secretory defect and insulin resistance are now better understood. In subjects with normal beta-cell function, increase in insulin needs secondary to insulin resistance is compensated by an increase in insulin secretion adjusted to maintain plasma glucose levels to normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate for increased needs is responsible for a progressive elevation in plasma glucose levels, then for overt type 2 diabetes. This adaptative phenomenon is called beta-cell compensation of insulin resistance. The lack of compensation is responsible for type 2 diabetes. When permanent hyperglycemia is present, progressive insulin secretory failure with time ensues, due to glucotoxicity and to lipotoxicity. PERSPECTIVES: Simple changes in lifestyle, such regular moderate physical activity, and control of body weight, should permit to avoid the explosion in prevalence of type 2 diabetes. This has been evidenced by the results of prospective studies aiming at preventing conversion from impaired glucose tolerance to diabetes. In patients with permanent hyperglycemia not controlled by lifestyle changes, metabolic defects are the targets of specific therapy intervention with antidiabetic oral agents, such as insulin secretagogues, insulin sensitizers, and inhibitors of hepatic glucose production.

Diagnosis of follicular lesions of undetermined significance in fine-needle aspirations of thyroid nodules.

Aim. We aimed to analyze the diagnostic criteria proposed by the Bethesda System for Reporting Thyroid Cytopathology for follicular lesions of undetermined significance (FLUS), the risk of cancer and diagnostic improvement with use of immunocytochemistry. Methods. For each FLUS diagnosis, we analyzed the cytological criteria (9 Bethesda criteria), secondary fine-needle aspiration (FNA) results, surgical procedures, contribution of immunocytochemistry with the antibodies cytokeratin 19 (CK19) and monoclonal anti-human mesothelial cell (HBME1). Results. Among patients with 2,210 thyroid FNAs, 244 lesions (337 nodules) were classified as FLUS (11% of all thyroid FNAs). The 3 criteria most often applied were cytological atypia suggesting papillary carcinoma (36%), microfollicular architecture but sparse cellularity (23.1%), cytological atypia (21.5%). With secondary FNA, 48.8% of nodules were reclassified as benign. For about half of all cases (41.4% for the first FNA, 57.6% for the second FNA), immunocytochemistry helped establishing a diagnosis favoring malignant or benign. No benign immunocytochemistry results were associated with a malignant lesion. In all, 22.5% of the 39 removed nodules were malignant. Conclusion. The FLUS category is supported by well-described criteria. The risk of malignancy in our series was 22.5%. Because we had no false-negative immunocytochemistry results, immunocytochemistry could be helpful in FLUS management.

[Methods of screening of gestational diabetes between 24 and 28 weeks' gestation]. / Méthodes du dépistage et du diagnostic du diabète gestationnel entre 24 et 28 semaines d'aménorrhée.

The aim of this review is to answer the question "how to detect the gestational diabetes mellitus (GDM) between 24 and 28 weeks of gestation?". Two approaches are well established: one-step approach (75 g-OGTT) and two-steps approach (50 g followed 100g-OGTT). The analysis of the literature shows that each of these methods has a good reproducibility close to 80 %, without requiring preliminary dietetics. The HAPO study provides consistent data about the 75 g-OGTT materno-fetal morbidity related. Furthermore, the one-step approach, relationship two-steps approach, has several advantages: reduction of time of diagnosis and primary care, better tolerance, simpler memorization. We recommend for the screening and the diagnosis of GDM an 75 g-OGTT with three measures: FPG, 1-h and 2-h. The various alternative methods are discussed. The measure of the fasting blood glucose isolated between 24 and 28 weeks of gestation is not a relevant approach. None of the other alternative methods (HbA1c, fructosamine, glycosuria, random and postprandial plasma glucose) cannot be recommended. Indeed, these methods have been addressed in little numerous studies, among heterogeneous populations, using variable criteria, and variable sensitivity values. Only the HbA1c might be useful to detect a pre-pregnancy diabetes mellitus.

Methods for the screening and diagnosis of gestational diabetes mellitus between 24 and 28 weeks of pregnancy.

The aim of this review is to provide answers to the question "How does one screen for and diagnose gestational diabetes mellitus (GDM) between 24 and 28 weeks gestation?" Two methods are currently widely used: a one-step approach (the 75g-Oral Glucose Tolerance Test, OGTT) and a two-step approach (the 50g Glucose Challenge Test, GCT, followed by 100g-OGTT). A review of the literature showed that both methods had good reproducibility (around 80%), whilst neither required preliminary diet changes. The data of the Hyperglycaemia Adverse Pregnancy Outcomes (HAPO) study on materno-foetal morbidity provided consistent support in favour of the 75g-OGTT. In addition, this one-step method presents several advantages over the two-step method, i.e. it provides a faster diagnosis time, better tolerance and it is easier to remember. We thus recommend a 75g-OGTT including three measures of the glycaemia at times 0, 1 and 2 hours for the diagnosis of GDM between 24-28 weeks of pregnancy. A discussion of alternative methods revealed that measuring Fasting Glycaemia (FG) between 24 and 28 weeks of pregnancy was unsuitable, and that measuring HbA1c, fructosamine, glycosuria, or random and postprandial plasma glucose was not advisable. This is based on the fact that too few studies have evaluated these methods, and that the studies usually involved heterogeneous populations in varying numbers, using differing criteria and sensitivity values. However, HbA1c measurements may prove useful in detecting pre-pregnancy diabetes mellitus.

[Mitochondrial diabetes: clinical features, diagnosis and management]. / Diagnostic clinique et biologique du diabète mitochondrial et particularités de sa prise en charge.

Mitochondrial diabetes affects up to 1% of patients with diabetes and is often unrecognised by the physicians. Maternally inherited diabetes and deafness (MIDD) resulting from the mutation 3243A>G of the mitochondrial DNA is the most frequent mutation associated with mitochondrial diabetes. This review summarizes the range of clinical phenotypes associated with MIDD and outlines the advances in genetic diagnosis, pathogenesis and management of these patients.

Switching fibrate to statin in type 2 diabetic patients: consequences on lipid profile.

UNLABELLED: Interest of statins in terms of morbid-mortality reduction in primary and secondary prevention in type 2 diabetic patients has broadly been proven in recent studies, while evidence for fibrates preventive effect is considerably weaker. HMGCoA reductase inhibitors are known to decrease low density lipoprotein cholesterol (LDL C) in a greater extension than triglycerides (TG). In type 2 diabetic patients, the dyslipidemic profile is commonly associated with reduced high-density lipoproteins (HDL C), increased TG and normal or mildly elevated LDL C. PATIENTS AND METHODS: Type 2 diabetic outpatients (n=45) treated with fibrate with or without history of cardiovascular disease were included. Mean age was 57.7+/-13.2 yr, sex ratio was 16/39 (F/M), and BMI was 29.3+/-4.4 kg/m(2). Non-inclusion criteria were TG>or=3.5 g/L and intolerance to statins or a combined lowering lipid therapy. Serum lipid profile, HbA(1c) and creatin kinase (CK) were assessed under treatment with fibrate, then after a 3-month wash-out period, and after a 6-month treatment with a low dose of atorvastatin (10 mg/day). RESULTS: After a 3-month wash-out period, total cholesterol (TC) was 1.98+/-0.31 g/L (m+/-SD), TG 1.63+/-1.09 g/L, HDL C 0.46+/-0.12 g/L, and LDL C 1.22+/-0.31 g/L. Comparing lipid profile with atorvastatin vs fibrate, we observed a significant decrease in TC and LDL C (1.56 vs 1.79 g/L P=0.001, and 0.84 vs 1.09 g/L, P=0.001, respectively). No significant difference between treatments was observed for TG (1.35 vs 1.17 g/L, P=0.06), and HDL C (0.44 vs 0.48 g/L, P=0.15). When treated with atorvastatin, 90% of patients achieved a LDL C<1 g/L, compared to 51% when treated with fibrate (P=0.001). HbA(1c) remained about 7.6+/-1.5%, and CK in the normal range. CONCLUSION: In well-controlled type 2 diabetic patients previously treated with fibrate, short-term (6 months) treatment with low-dose atorvastatin (10 mg/day) improves TC and LDL C levels, without any alteration in TG and HDL C levels.