White blood count, D-dimers, and ferritin levels as predictive factors of pulmonary embolism suspected upon admission in noncritically ill COVID-19 patients: The French multicenter CLOTVID retrospective study.

BACKGROUND: A high prevalence of pulmonary embolism (PE) has been described during COVID-19. Our aim was to identify predictive factors of PE in non-ICU hospitalized COVID-19 patients. METHODS: Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID-19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. RESULTS: A total of 88 patients (median [IQR] age of 68 years [60-78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D-dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3-74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3-1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7-553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D-dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0-397.9], P = .004). CONCLUSION: The white blood count, the D-dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non-ICU COVID-19 patients.

Early and short-term intensive management after discharge for patients hospitalized with acute heart failure: a randomized study (ECAD-HF).

AIMS: Hospitalization for acute heart failure (HF) is followed by a vulnerable time with increased risk of readmission or death, thus requiring particular attention after discharge. In this study, we examined the impact of intensive, early follow-up among patients at high readmission risk at discharge after treatment for acute HF. METHODS AND RESULTS: Hospitalized acute HF patients were included with at least one of the following: previous acute HF < 6 months, systolic blood pressure ≤ 110 mmHg, creatininaemia ≥ 180 µmol/L, or B-type natriuretic peptide ≥ 350 pg/mL or N-terminal pro B-type natriuretic peptide ≥ 2200 pg/mL. Patients were randomized to either optimized care and education with serial consultations with HF specialist and dietician during the first 2-3 weeks, or to standard post-discharge care according to guidelines. The primary endpoint was all-cause death or first unplanned hospitalization during 6-month follow-up. Among 482 randomized patients (median age 77 and median left ventricular ejection fraction 35%), 224 were hospitalized or died. In the intensive group, loop diuretics (46%), beta-blockers (49%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (39%) and mineralocorticoid receptor antagonists (47%) were titrated. No difference was observed between groups for the primary endpoint (hazard ratio 0.97; 95% confidence interval 0.74-1.26), nor for mortality at 6 or 12 months or unplanned HF rehospitalization. Additionally, no difference between groups according to age, previous HF and left ventricular ejection fraction was found. CONCLUSIONS: In high-risk HF, intensive follow-up early post-discharge did not improve outcomes. This vulnerable post-discharge time requires further studies to clarify useful transitional care services.

Intentionality in adherence to long-term therapies. Results from an online survey of 3,001 patients with cardio-metabolic pathologies in France.

PURPOSE: Some patients make a rational choice not to follow medical prescriptions; others fail to take their medications for reasons beyond their control, such as mere forgetfulness or a weak medication routine. The aim of this study was to elucidate the functioning of patient intentionality in medication adherence. PATIENTS AND METHODS: This online study was conducted in metropolitan France in 2019. A cross-sectional survey of 50 questions was conducted with 3001 respondents diagnosed with diabetes, hypertension, and/or hypercholesterolemia identified from a panel of 54,000 people. These questions included a validated six-item questionnaire to detect nonadherence, two questions to detect intentional nonadherence by patients, and three questions on the effects of habit. Our questionnaire also included questions on the feelings of respondents regarding their doctor's attitude to their problems and needs, their trust in general practitioners (GP) and specialists, their sense of being involved in treatment decisions, and the influence of side effects and habits on patients' adherence. This study used the strategy of focusing on strictly adherent patients in the hope of finding ways to improve adherence. For this reason, we defined adherence as the absence of a positive response to the 6-item nonadherence screening questionnaire. RESULTS: Of 3001 respondents, 1804 were diagnosed with hypertension, 1458 with hypercholesterolemia, and 774 with diabetes. Of the total number of patients, 72% were afflicted with one disease, 21% with two ailments, and 7% with three simultaneous illnesses. One-third (33%) of the patients did not tender a positive answer to the adherence questionnaire and were deemed adherent. 1) Thirty-two percent of the patients reported occasionally omitting their medication deliberately, and 84% said they had a reason for missing doses. These statements suggesting intentional nonadherence were negatively associated with adherence as identified via multivariate analysis (P = 0.0012 and P < 0.0001, for the first and second statement, respectively). 2) Univariate analyses revealed strong associations (P < 0.0001) between strict adherence on one hand and lack of intentional nonadherence, patient age, absence of drug side effects, taking drugs by habit, feeling involved in treatment decisions, getting information about treatment, and disease, and trust in doctors, on the other hand. 3) Specifically, univariate analysis of the absence of reported side effects revealed strong associations (P < 0.0001) with adequate information about medicines and diseases and trust in GP. These original data were consistent with the concept of the nocebo effect. 4) We observed a strong association between the absence of intentional nonadherence (statement of never deliberately missing medication) and respondent statements about generally sticking to the routine (P < 0.0001), ie, "I take my medication because I am used to taking it." This important result suggests that patients are strictly adherent in two ways: the absence of intentional nonadherence and reliance on habit, which we term as "unintentional adherence." 5) Finally, a multiple correspondence analysis illustrated all statistically significant relationships found in this study. CONCLUSION: We present a new global model of adherence in which patient adherence was improved both by reducing intentional nonadherence and by promoting the abovementioned unintentional adherence by habit. This model highlights the role of shared decision-making and the trust felt by patients in their doctors. These results could exert a major impact on medical practice and education by demonstrating the importance of physicians' attitudes, involving the patient in decisions (shared decision-making), offering information about medicines and diseases (patient education), understanding the problems of patients, and taking their needs into account (empathy). The development of these attitudes should be an important aspect of the medical curricula.

Reliability and Safety of Bedside Blind Bone Biopsy Performed by a Diabetologist for the Diagnosis and Treatment of Diabetic Foot Osteomyelitis.

OBJECTIVE: Bone biopsy (BB) performed by a surgeon or an interventional radiologist is recommended for suspicion of osteomyelitis underlying diabetic foot ulcer (DFU). To facilitate its practice, we developed a procedure allowing bedside blind bone biopsy (B4) by a diabetologist. RESEARCH DESIGN AND METHODS: We conducted a three-step observational study consisting of a feasibility and safety phase (phase 1) to assess the success and side effects of B4, a validity phase (phase 2) to compare DFU outcomes between positive (B4+) and negative (B4-) bone cultures, and a performance phase (phase 3) to compare B4 with the conventional surgical or radiological procedure basic bone biopsy (B3). Primary end points were the presence of bone tissue (phase 1) and complete DFU healing with exclusive medical treatment at 12 months (phases 2 and 3). RESULTS: In phase 1, 37 consecutive patients with clinical and/or radiological suspicion of DFU osteomyelitis underwent B4. Bone tissue was collected in all patients with few side effects. In phase 2, a B4+ bone culture was found in 40 of 79 (50.6%) participants. Among B4+ patients, complete wound healing after treatment was 57.5%. No statistical difference was observed with patients with B4- bone culture not treated with antibiotics (71.8%, P = 0.18). In phase 3, the proportion of patients with positive BB was lower in B4 (40 of 79, 50.6%) than in B3 (34 of 44, 77.3%, P < 0.01). However, complete healing was similar (64.6% vs. 54.6%, P = 0.28). No difference in rate of culture contamination was observed. CONCLUSIONS: B4 is a simple, safe, and efficient procedure for the diagnosis of DFU osteomyelitis with a similar proportion of healing to conventional BB.

D-Dimer Level and Neutrophils Count as Predictive and Prognostic Factors of Pulmonary Embolism in Severe Non-ICU COVID-19 Patients.

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55-77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6-4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1-537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4-29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5-67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.

High prevalence of glucose-6-phosphate dehydrogenase deficiency without gene mutation suggests a novel genetic mechanism predisposing to ketosis-prone diabetes.

CONTEXT: Ketosis-prone diabetes (KPD) is mostly observed in males of West African descent and is characterized by phasic or permanent insulin dependence without apparent autoimmune process. OBJECTIVE: KPD subjects display a propensity to hyperglycemia-induced acute insulin deficiency, suggesting that they exhibit a propensity to oxidative stress in beta-cells. The enzyme glucose-6-phosphate dehydrogenase (G6PD) is a defense mechanism against oxidative stress, and G6PD deficiency, an X-linked genetic disorder with male predominance, is frequent in West Africans. We hypothesized that mutations in the G6PD gene could predispose to KPD. DESIGN: We studied G6PD erythrocyte enzyme activity and the insulin secretory reserve (glucagon-stimulated C peptide) in a cohort of hospitalized West Africans with KPD (n = 59) or type 2 diabetes (T2DM; n = 59) and in normoglycemic controls (n = 55). We also studied the G6PD gene in an extended population of KPD patients (n = 100), T2DM patients (n = 59), and controls (n = 85). RESULTS: The prevalence of G6PD deficiency was higher in KPD than in T2DM and controls (42.3%; 16.9%; 16.4%; P = 0.01). In KPD, but not in T2DM, insulin deficiency was proportional to the decreased G6PD activity (r = 0.33; P = 0.04). We found no increase in the prevalence of G6PD gene mutations in KPD compared with T2DM and controls. Rather, we found a 20.3% prevalence of G6PD deficiency in KPD without gene mutation. CONCLUSIONS: This study suggests that 1) G6PD deficiency alone is not causative of KPD; and 2) alterations in genes controlling both insulin secretion and G6PD-mediated antioxidant defenses may contribute to the predisposition to KPD in West Africans.

Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance.

Nonautoimmune ketosis-prone diabetic syndromes are increasingly frequent in nonwhite populations. We have characterized a cohort of patients of sub-Saharan African origin who had ketosis-prone type 2 diabetes (n = 111), type 1 diabetes (n = 21), and type 2 diabetes (n = 88) and were admitted to a hospital for management of uncontrolled diabetes. We compared epidemiological, clinical, and metabolic features at diabetes onset and measured insulin secretion (glucagon-stimulated C-peptide) and insulin action (short intravenous insulin tolerance test) during a 10-year follow-up. Ketosis-prone type 2 diabetes shows a strong male predominance, stronger family history, higher age and BMI, and more severe metabolic decompensation than type 1 diabetes. In ketosis-prone type 2 diabetes, discontinuation of insulin therapy with development of remission of insulin dependence is achieved in 76% of patients (non-insulin dependent), whereas only 24% of patients remain insulin dependent. During evolution, ketosis-prone type 2 diabetes exhibit specific beta-cell dysfunction features that distinguish it from type 1 and type 2 diabetes. The clinical course of non-insulin-dependent ketosis-prone type 2 diabetes is characterized by ketotic relapses followed or not by a new remission. Progressive hyperglycemia precedes and is a strong risk factor for ketotic relapses (hazard ratio 38). The probability for non-insulin-dependent ketosis-prone type 2 diabetes to relapse is 90% within 10 years, of whom approximately 50% will become definitively insulin dependent. Insulin sensitivity is decreased in equal proportion in both ketosis-prone type 2 diabetes and type 2 diabetes, but improves significantly in non-insulin-dependent ketosis-prone type 2 diabetes, only after correction of hyperglycemia. In conclusion, ketosis-prone type 2 diabetes can be distinguished from type 1 diabetes and classical type 2 diabetes by specific features of clinical pathophysiology and also by the natural history of beta-cell dysfunction and insulin resistance reflecting a propensity to glucose toxicity.

Aspirin alters arterial function in patients with chronic heart failure treated with ACE inhibitors: a dose-mediated deleterious effect.

BACKGROUND: By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF). AIM: Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs. METHODS AND RESULTS: Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day. Single blind prospective assessment of reflected wave and time reflection by radial applanation tonometry; pulse wave velocity; blood pressure; thromboxane B2 (TxB2) and prostaglandins in plasma and urine was performed. Aspirin 325 mg/day induced a significant increase in augmentation index of reflected wave (P<0.0001 and P=0.0013 vs. placebo and aspirin 100 mg, respectively) and a significant decrease in reflected wave traveling times (P=0.0007 vs. placebo). Aspirin 100 mg/day produced a similar, though non-significant, trend in these parameters compared with placebo. Both aspirin treatments produced a statistically significant decrease in serum TxB2 (P<0.0001) but did not have an effect on the metabolite of prostaglandin I2 (P=0.136). CONCLUSION: This study demonstrates the existence of a dose-mediated deleterious effect of aspirin upon arterial functional properties in CHF patients treated with ACEI.

A rare localization in right-sided endocarditis diagnosed by echocardiography: a case report.

BACKGROUND: Right-sided endocarditis occurs predominantly in intravenous drug users, patients with pacemakers or central venous lines and with congenital heart diseases. The vast majority of cases involve the tricuspid valve. CASE PRESENTATION: A case of a 31-year-old woman with intravenous drug abuse who had a right-sided vegetation attached to the muscular bundle of the right ventricle is presented. Transthoracic echocardiography revealed a vegetation in the right ventricular outflow tract. Transesophageal echocardiography clearly showed that the 1.8 cm vegetation was not adherent to the pulmonary valve but attached to a muscular bundle. CONCLUSIONS: Our case points to an unusual location of right-sided endocarditis in intravenous drug users. It confirms that TTE remains an easy and highly sensitive first-line examination for the diagnosis of right-sided endocarditis.

High incidence of myocardial ischemia during postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia. METHODS: On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia. RESULTS: A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty-eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively) and increased heart rate (> 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels. CONCLUSIONS: These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients.

PAX4 gene variations predispose to ketosis-prone diabetes.

Ketosis-prone diabetes (KPD) is a rare form of type 2 diabetes, mostly observed in subjects of west African origin (west Africans and African-Americans), characterized by fulminant and phasic insulin dependence, but lacking markers of autoimmunity observed in type 1 diabetes. PAX4 is a transcription factor essential for the development of insulin-producing pancreatic beta-cells. Recently, a missense mutation (Arg121Trp) of PAX4 has been implicated in early and insulin deficient type 2 diabetes in Japanese subjects. The phenotype similarities between KPD and Japanese carriers of Arg121Trp have prompted us to investigate the role of PAX4 in KPD. We have screened 101 KPD subjects and we have found a new variant in the PAX4 gene (Arg133Trp), specific to the population of west African ancestry, and which predisposes to KPD under a recessive model. Homozygous Arg133Trp PAX4 carriers were found in 4% of subjects with KPD but not in 355 controls or 147 subjects with common type 2 or type 1 diabetes. In vitro, the Arg133Trp variant showed a decreased transcriptional repression of target gene promoters in an alpha-TC1.6 cell line. In addition, one KPD patient was heterozygous for a rare PAX4 variant (Arg37Trp) that was not found in controls and that showed a more severe biochemical phenotype than Arg133Trp. Clinical investigation of the homozygous Arg133Trp carriers and of the Arg37Trp carrier demonstrated a more severe alteration in insulin secretory reserve, during a glucagon-stimulation test, compared to other KPD subjects. Together these data provide the first evidence that ethnic-specific gene variants may contribute to the predisposition to this particular form of diabetes and suggest that KPD, like maturity onset diabetes of the young, is a rare, phenotypically defined but genetically heterogeneous form of type 2 diabetes.