Cytokines play a central role in the pathophysiology of autoimmune and inflammatory diseases. Several cytokines signal through the JAK-STAT pathway, which is now recognized as a major target to ...inhibit the effect of a wide array of cytokines. JAK inhibitors are increasingly used in the setting of inflammatory and autoimmune diseases. While the currently approved drugs are panJAK inhibitors, more selective small molecules are being developed and tested in various rheumatic disorders. In this extensive review, we present evidence- or hypothesis-based perspectives for these drugs in various rheumatologic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, giant cell arteritis, and autoinflammatory diseases.
•Several cytokines signal through the JAK-STAT pathway•JAK inhibition is an efficient strategy for multiple inflammatory or autoimmune diseases.•More selective small molecules are being developed and tested in various rheumatic disorders.
We evaluated mortality rates and underlying causes of death among French decedents with sarcoidosis from 2002 to 2011.We used data from the French Epidemiological Centre for the Medical Causes of ...Death to 1) calculate sarcoidosis-related mortality rates, 2) examine differences by age and gender, 3) determine underlying and nonunderlying causes of death, 4) compare with the general population (observed/expected ratios), and 5) analyse regional differences.1662 death certificates mentioning sarcoidosis were recorded. The age-standardised mortality rate was 3.6 per million population and significantly increased over the study period. The mean age at death was 70.4 years (versus 76.2 years for the general population). The most common underlying cause of death was sarcoidosis. Sarcoidosis decedents were more likely to be males when aged <65 years. When sarcoidosis was the underlying cause of death, the main other mentions on death certificates were chronic respiratory and cardiovascular diseases. The overall observed/expected ratio was >1 for infectious disease, tuberculosis and chronic respiratory disease, and <1 for neoplasms. We observed a north-south gradient of age-standardised mortality ratio at the country level.Despite the limitation of possibly capturing the more severe cases of sarcoidosis, this study may help define and prioritise preventive interventions.
Background
The term dermatoporosis (DP) is used to describe the clinical signs and functional consequences of age‐related extreme skin fragility. It is associated with potentially severe ...complications, including deep dissecting hematomas and extended skin lacerations. No studies have evaluated the prevalence and risk factors of DP in adults aged 75 and older.
Methods
The aim of our study was to assess the prevalence, complications, and risk factors of DP in a cohort of older patients hospitalized in a rehabilitation center. A case–control, single‐center study was conducted between September and October 2020 in our rehabilitation ward, Rothschild Hospital, Paris, France. A senior dermatologist and a resident in geriatric medicine performed a systematic dermatological examination. The presence of DP, its stage, its location, and complications were collected, as were demographical data, comorbidities, past sun exposure, skin phototype, treatments, and biological data.
Results
A total of 101 patients (62 women, median age 86 years extreme values 75–104) were included. The overall prevalence of DP was 27%. Stage 1 was the most frequent. DP was mainly located on the upper limbs. Ten (37%) patients had a DP complication: eight (30%) skin lacerations and two (7%) deep dissecting hematomas. Multivariate analysis revealed a significant association between DP and age (odds ratio OR 5.82, 95% confidence interval CI 1.67–24.92, p = 0.009), smoking (OR 8.67, 95% CI 2.59–34.85, p = 0.001), recreational sun exposure (OR 4.23, 95% CI 1.30–15.21, p = 0.02), and anticoagulant therapy (OR 4.53, 95% CI 1.32–17.26, p = 0.02).
Conclusion
Our study is the first to analyze the prevalence and risk factors of DP in older adults in rehabilitation. Frequency of DP makes it relevant for the geriatrician and should be described more to prevent potential severe complications. A multicentric study, with inpatients and outpatients, could evaluate the prevalence of DP in a more representative older adult population.
End-of-life (EOL) decisions are a serious ethical dilemma and are frequently carried out in intensive care units (ICUs). The aim of this systematic review was to investigated the different approaches ...used in ICUs and reported in randomized controlled trials (RCTs) to address EOL decisions and compare the impact of these different strategies regarding potential bias and mortality estimates.
We identified relevant RCTs published in the past 15 years via PubMed, EMBASE, and CINAHL. In addition, we searched The Cochrane Library and checked registries, including ClinicalTrials.gov to assess concordance between declared and published outcomes. Among the journals we screened were the 3 ICU specialty journals and the four general medicine journals with the highest impact factor. Only RCTs were selected in which in-ICU mortality was the primary or secondary outcome. The primary outcome was information regarding EOL decisions, and the secondary outcome was how EOL decisions were treated in the study analysis.
A total of 178 relevant trials were identified. The details regarding the methodological aspects resulting from EOL decisions were reported in only 62 articles (35%). The manner in which EOL decisions were considered in the study analysis was very heterogeneous, often leading to a high risk of bias.
There is a heterogeneity regarding the management of data on EOL decisions in randomized control trials with mortality endpoints. Recommendations or rules are required regarding the inclusion of patients with potential EOL decisions in RCT analyses and how to manage such decisions from a methodological point of view.
PROSPERO website (CRD42013005724).
Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive ...genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inactive by two kinases (PKN1/2). The consequences of MEFV mutations on inflammasome activation are still poorly understood. Here, we demonstrate that PKC superfamily inhibitors trigger inflammasome activation in monocytes from FMF patients while they trigger a delayed apoptosis in monocytes from healthy donors. The expression of the pathogenic p.M694V MEFV allele is necessary and sufficient for PKC inhibitors (or mutations precluding Pyrin phosphorylation) to trigger caspase‐1‐ and gasdermin D‐mediated pyroptosis. In line with colchicine efficacy in patients, colchicine fully blocks this response in FMF patients’ monocytes. These results indicate that Pyrin inflammasome activation is solely controlled by Pyrin (de)phosphorylation in FMF patients while a second control mechanism restricts its activation in healthy donors/non‐FMF patients. This study paves the way toward a functional characterization of MEFV variants and a functional test to diagnose FMF.
Synopsis
Familial Mediterranean fever (FMF) is a systemic auto‐inflammatory disease associated with MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor. The link between MEFV mutations and the dysregulated activation of the Pyrin inflammasome observed in FMF patients is unclear.
Pyrin dephosphorylation is insufficient to trigger full inflammasome activation in healthy donors'monocytes while it is sufficient in FMF patients monocytes.
The pathogenic MEFV mutation most frequently observed in FMF patients triggers constitutive inflammasome activation only when combined to a phosphonull MEFV mutation.
UCN‐01‐induced dephosphorylation of Pyrin triggers inflammasome activation in FMF patients’ monocytes but not in monocytes from other patients paving the way to a functional diagnosis of FMF.
Familial Mediterranean fever (FMF) is a systemic auto‐inflammatory disease associated with MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor. The link between MEFV mutations and the dysregulated activation of the Pyrin inflammasome observed in FMF patients is unclear.
Data on the long-term outcomes of gastric peroral endoscopic myotomy (G-POEM) for refractory gastroparesis are lacking. We report the results of a large multicenter long-term follow-up study of ...G-POEM for refractory gastroparesis.
This was a retrospective multicenter study of all G-POEM operations performed in seven expert French centers for refractory gastroparesis with at least 1 year of follow-up. The primary endpoint was the 1-year clinical success rate, defined as at least a 1-point improvement in the Gastroparesis Cardinal Symptom Index (GCSI).
76 patients were included (60.5 % women; age 56 years). The median symptom duration was 48 months. The median gastric retention at 4 hours (H4) before G-POEM was 45 % (interquartile range IQR 29 % - 67 %). The median GCSI before G-POEM was 3.6 (IQR 2.8 - 4.0). Clinical success was achieved in 65.8 % of the patients at 1 year, with a median rate of reduction in the GCSI score of 41 %. In logistic regression analysis, only a high preoperative GCSI satiety subscale score was predictive of clinical success (odds ratio OR 3.41, 95 % confidence interval CI 1.01 - 11.54;
= 0.048), while a high rate of gastric retention at H4 was significantly associated with clinical failure (OR 0.97, 95 %CI 0.95 - 1.00;
= 0.03).
The results confirm the efficacy of G-POEM for the treatment of refractory gastroparesis, as evidenced by a 65.8 % clinical success rate at 1 year. Although G-POEM is promising, prospective sham-controlled trials are urgently needed to confirm its efficacy and identify the patient populations who will benefit most from this procedure.
A real public health problem, namely, malnutrition in the hospital, also concerns intensive care patients. The diagnosis and prevention of malnutrition are major issues in the multidisciplinary ...management of patients hospitalized in the intensive care unit (ICU). To our knowledge, few data describe dietary management in French ICUs, and few international scientific publications mention professional practices or how dieticians are integrated in this type of specialized and technical sector. The objective of this study is to identify the practices of dieticians in the ICU at a national level.
This study is based on the use of an electronic questionnaire distributed to registered dietician nutritionists practising in intensive care.
A total of 185 dieticians participated in this survey, which allowed us to describe the practices of 174 ICUs. Among the respondents (n = 185), 95% were women with a median age of 37 31; 52. The respondents graduated a median of 14 years ago 8.5; 30 and have been practising in intensive care for 5 years 2; 10. With a median number of 12 beds 10; 18 (n = 174), the ICU has a median of 0.1 0.05; 0.25 (n = 185) full-time equivalent dieticians. The solicitation of the dietitian is variable in different ICUs. Nevertheless, information from dietitians is frequently sought. Dietary initiatives mainly concern acts relating to oral nutrition and enteral nutrition. A nutrition protocol was present in 38% of the ICUs (n = 174). The integration felt by dieticians in the service is heterogeneous. Statistical analysis reveals that a dietitian who spends more than 4 h a week in the ICU, has a nutrition protocol in his or her department and does not encounter any obstacles, such as the absence of a doctor's prescription, is more likely to be integrated into an ICU.
This research work has made it possible to describe and make visible the role and involvement of dieticians working in ICUs in France and oversea departments and territories. Proposals to increase the involvement of dieticians in these sectors were reported at the end of this analysis.
•Data on dietitians' practices in French ICUs are lacking.•The study shows an important heterogeneity of practices.•Results are discussed to help increase the integration dietitian in ICUs.
STUDY DESIGN.Electronic survey.
OBJECTIVE.The aim of this study was to identify the international nuances in surgical treatment patterns for severals lumbar degenerative conditions, specifically, to ...identify differences in responses in each country groupand different treatment trends across countries.
SUMMARY OF BACKGROUND DATA.Significant variations in treatment of lumbar degenerative conditions exist among spine surgeons, related to the lack of established consensus in the literature.
METHODS.An online survey with preformulated answers was submitted to 52 orthopedic surgeons, 50 neurosurgeons from four different countries (United States, France, Spain, and Germany) regarding five vignette-cases. Cases includedmultilevel stenosis, monolevel stenosis, lytic spondylolisthesis, isthmic lysis, and degenerative scoliosis. The variability for each country was calculated according to the Index of Qualitative Variation (IQV = 0no variability and 1maximal variability). We used Fleiss kappa (rangefrom −1, poor agreement, to 1, almost perfect agreement) for assessing the reliability of agreement between the participants concerning specialties, countries, and age groups.
RESULTS.For the two stenosis cases, US surgeons were more likely to propose decompression (IQV multilevel = 0.47 and monolevel = 0.32) comparing with European countries more heterogeneous (all IQV >0.70) and more frequently proposing fusion. As regards degenerative scoliosis, all attitudes were extremely heterogeneous with IQV >0.8. Fusion for isthmic spondylolisthesis was more consensual (all IQV <0.63), but attitudes were more heterogeneous for isthmic lysis (IQV ranged from 0.48 to 0.76) with anterior approach proposed in France (37%) and United States (19.2%).The overall interrater agreement was equally slight not only for neurosurgeons (Fleiss Kappa = 0.04) and orthopedic surgeons (Kappa = 0.13), but also for countries (Kappa <0.13) and age groups (Kappa <0.1).
CONCLUSION.In this study, we found substantial agreement for some spinal conditions but a high variability in some othersintranational and international variations were observed, reflecting the lack of literature consensus.Level of Evidence2
Abstract Sarcoidosis is an inflammatory disease marked by a paradoxical immune status. The anergic state, which results from various immune defects, contrasts with the inflammatory formation of ...granulomas. Sarcoidosis patients may be at risk for opportunistic infections (OIs) and a substantial number of cases have been reported, even in untreated sarcoidosis. It is not clear how OIs in patients with sarcoidosis are different from other groups at risk. In this review, we discuss the most common OIs: mycobacterial infection (including tuberculosis), cryptococcosis, progressive multifocal leukoencephalopathy, and aspergillosis. Unlike peripheral lymphocytopenia, corticosteroids are a major risk factor for OIs but the occurrence of Ols in untreated patients suggests more complex predisposing mechanisms. Opportunistic infections presenting with extrapulmonary features are often misdiagnosed as new localizations of sarcoidosis. Aspergillomas mostly develop on fibrocystic lungs. Overall, physicians should be aware of the possible occurrence of OIs during sarcoidosis, even in untreated patients.
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