Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study

Purpose

Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality.

Methods

A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up).

Results

Among the 306 included patients, 126 (41.2%; 95% CI 35.6–46.9) died and 180 (58.8%; 95% CI 53.3–64.3) survived during the follow-up period [13 (3–24) days], including 51/180 patients (28.3%, 95% CI 21.9–35.5) who eventually required limb amputations, with a median number of 3 (1–4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR)?=?1.03 (1.02–1.04); p?<?0.001], lower leucocytes [HR 0.83 (0.69–0.99); p?=?0.034] and platelet counts [HR 0.77 (0.60–0.91); p?=?0.007], and arterial blood lactate levels [HR 2.71 (1.68–4.38); p?<?0.001] were independently associated with hospital death, while a neck stiffness [HR?0.51 (0.28–0.92); p?=?0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06–3.38); p?=?0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis.

Conclusion

Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation.

Trials registration

NCT03216577.

     

Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis

In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner.     

Design of melt-recyclable poly(ε-caprolactone)-based supramolecular shape-memory nanocomposites

A novel poly(epsilon-caprolactone) (PCL) supramolecular network exhibiting shape-memory behavior was successfully constructed with pendant UPy units that are highly able to dimerize. The dynamic network was obtained by a simple and versatile strategy consisting of chain-extension reaction between α,ω-dihydroxyoligoPCL and hydroxylated UPy units in the presence of hexamethylene diisocyanate as a coupling agent and further intermolecular dimerization of the UPy along the polyurethane backbone. ¹H NMR analyses confirmed the dynamic features of the system, and DMTA in tensile mode was investigated to assess the SMP properties. Recyclability was also assessed by taking advantage of these supramolecular networks. Further addition of cellulose nanocrystals into the polymer network enabled adjustment of the extent of the net-points and therefore the SMP features. As confirmed by dispersion tests in solution and SEM observations, these bio-based nanofillers were homogeneously distributed in the network via supramolecular interaction between the hydroxyl groups present on their surface and UPy moieties along the polyurethane backbone. Thus, the here developed nanomaterials might reveal applicability in areas where a combination of SMP and biocompatibility is needed.

Novel melt-recyclable poly(ε-caprolactone)/cellulose nanocrystals supramolecular nanocomposite networks with shape-memory behavior have been successfully constructed by playing with UPy chemistry.     

Oral antineoplastic agents: how do we care about adherence?

AimsOral therapies, including hormone‐based or targeted therapies, have recently taken an increasing place in cancer treatment. In this context, a state of the art of the available studies dealing with the adherence of adult patients to oral anticancer treatment is warranted. The purpose of this review is to address (i) the association between assessment methods and measured adherence, (ii) the putative factors related to adherence and (iii) new ways of improving adherence to oral cancer therapies.MethodsWe conducted a literature‐based narrative review of studies obtained from Pubmed using medical subject heading terms and free‐text terms combining concepts related to oral anticancer medication and adherence.ResultsThe analysis is based on 48 studies published since 1990, mostly assessing hormone‐based therapy in breast cancer and targeted therapies in chronic myeloid leukaemia. Various methods of adherence were reported including self‐report, medication measurement or combinations of methods. Adherence rates were found to vary from 14% to 100%. Beside patient related‐factors, adherence rate discrepancies were found to be dependent on the method used. Furthermore, there was no consensual definition of adherence even regarding the same methods, some of them tolerating a period of interruption during the treatment period. Finally, several studies addressing persistence found a progressive decrease in adherence with time.ConclusionAdherence to novel oral therapies is a major issue and further research is warranted to standardize adherence assessment in clinical studies better and to define better the most appropriate approaches to improve long term adherence in oncology practice.     

Impact of the longitudinal quantitative assessment of juvenile systemic lupus erythematosus severity on the disease outcome

Clinical Rheumatology - This study on juvenile SLE patients aimed to evaluate retrospectively the impact of a tertiary center’s management policy of the disease severity on its long-term...     

Membrane and capillary blood components of diffusion capacity of the lung for carbon monoxide in pulmonary sarcoidosis: relation to exercise gas exchange

BACKGROUND: Resting pulmonary diffusing capacity of the lung for carbon monoxide (DLCO) is known to be the best predictor of arterial desaturation during exercise in patients with sarcoidosis. However, the relative contribution of each of the two components of DLCO-alveolar membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc)-remains unclear. STUDY OBJECTIVES: To evaluate which component is responsible for the decrease of resting DLCO in patients with sarcoidosis, and to determine which resting pulmonary function test, including Dm and Vc, is the best predictor of gas exchange abnormalities during submaximal exercise. DESIGN: Prospective analysis of patients referred to our department of respiratory medicine. PATIENTS: Twenty four patients with pulmonary sarcoidosis were separated into two groups according to chest radiographic findings: group 1, stages 2 and 3 (n = 15); group 2, stage 4 (n = 9). All the patients completed pulmonary function tests (flows, volumes, single-breath DLCO, transfer coefficient [Ka], Dm, Vc) and submaximal exercise (two steady-state levels of mild and moderate exercise corresponding respectively to a target oxygen consumption of approximately 10 to 15 mL/min/kg). RESULTS: DLCO was reduced in the two groups (group 1, 63 +/- 16% of predicted; group 2, 64 +/- 16% of predicted). Dm was severely decreased (group 1, 58 +/- 24% of predicted; group 2, 51 +/- 15% of predicted), whereas Vc was unchanged or only mildly decreased (group 1, 81 +/- 18% of predicted; group 2, 85 +/- 28% of predicted). Whatever the group of patients and the exercise level, Dm and DLCO were the strongest predictors (p < 0.001) of gas exchange abnormalities. Ka or volumes were weak predictors, and Vc or flows were not related with exercise gas exchange. CONCLUSIONS: This study demonstrates that a decrease in Dm mostly accounts for resting DLCO reduction, and that Dm as well as DLCO are highly predictive of gas exchange abnormalities at exercise in patients with sarcoidosis.     

Electrophysiologically guided pulmonary vein isolation during sustained atrial fibrillation

INTRODUCTION: Sustained atrial fibrillation (AF) is frequently encountered during pulmonary vein (PV) isolation. The aim of this study was to evaluate the feasibility and safety of PV isolation during sustained AF. METHODS AND RESULTS: Thirty-seven patients (30 men, age 54 +/- 10 years) underwent Lasso-guided isolation of 87 PVs during sustained AF. Baseline PV electrogram patterns were classified into one of two types: organized, with consistent PV activation sequence; or disorganized, with constant variation of PV activation sequence. In disorganized activity, radiofrequency ablation was performed circumferentially around the Lasso while the earliest PV potential was targeted during organized activity. Complete left atrial (LA) to PV block during AF was identified by abolition or dissociation of all sharp potentials recorded within the vein. PV isolation then was verified during sinus rhythm. Baseline activation patterns of PV potential were organized in 32 PVs (37%) [more frequently in inferior veins than superior veins (53% vs 26%, P = 0.01)] and disorganized in 55 PVs (63%). In 59 of 87 PVs, isolation was begun and completed during AF. Radiofrequency ablation organized PV activation sequence in 75% prior to isolation. LA-PV block was confirmed during sinus rhythm in 54 (92%) of 59 PVs. In 28 of 87 PVs, sinus rhythm was restored before complete LA-PV block. Complete isolation was achieved in all 87 PVs without complications. CONCLUSION: PV isolation can be effectively and safely performed during sustained AF, preceded in most cases by organization of PV electrogram activity. This strategy may be the preferred alternative to multiple intraprocedural cardioversions.     

Heart failure and diabetes mellitus: epidemiology and management of an alarming association

Diabetes mellitus is a growing epidemic with a prevalence among patients with heart failure (HF) approaching 30%. Diabetes worsens the prognosis of HF, and the pathophysiology is complex and multifactorial. Early detection of subtle alterations in cardiac function by modern tools, such as Doppler echocardiography or brain natriuretic peptide dosage, is thus important in these patients. All drugs known to be effective in HF with systolic dysfunction are also effective in patients with diabetes. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists also seem particularly useful. Overall, however, little is known about the treatment of diabetic patients with HF, especially in case of preserved systolic function. Ongoing and future trials should help to determine the best treatment for these patients with or without associated diabetes. This review assesses the relationships between diabetes mellitus and HF and discusses the various medical strategies.     

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.