To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) ...protocol for up to 3 years of follow-up in "real-life" practice.
This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed.
One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters,
= 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5,
= 0.1) and 64.0 ± 20.1 letters (+3.4,
= 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm,
< 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively.
Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.
To determine the long-term visual and systemic outcomes of uveitis patients with biopsy-proven sarcoidosis.
A retrospective study of biopsy-proven sarcoid uveitis, with a 3-year minimum follow-up, ...seen at Lyon University Hospital, between April 2004 and January 2016.
A total of 83 patients were included, with a median age at onset of 52 (37-62) years and an unbalanced gender ratio (women 77.1%). Thirty-one patients had original systemic sarcoidosis in addition to ocular localisation, whereas 52 initially presented with isolated sarcoid uveitis. Among the latter, 7.7% (n=4) developed an extraocular disease after a median follow-up duration of 60 (44-110) months. The systemic spread in these patients included cutaneous sarcoids (n=2), arthritis (n=1) and multiple mononeuritis (n=1). Complete visual recovery was obtained for 60.2% of all patients and 89.2% had retrieved best-corrected visual acuity (BCVA) >20/50 in both eyes. A unilateral loss of BCVA of worse than 20/200 was documented in two patients in the isolated sarcoid uveitis group. No patient suffered from bilateral severe visual impairment or blindness. Factors linked to a poor visual prognosis, defined by BCVA ≤20/50 in at least one eye, were chronic macular oedema (p=0.009) and persistent ocular inflammation (p=0.0005).
In this large European series of biopsy-proven sarcoidosis to date, with a prolonged follow-up, sarcoid uveitis was suggestive of a favourable systemic and visual outcome. Clinically isolated uveitis that revealed sarcoidosis remained a strictly ocular condition in most cases.
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.
The study objectives were to evaluate septic shock-induced alterations in skeletal muscle hemoglobin oxygenation saturation (StO2) using near-infrared spectroscopy (NIRS) and forearm skin blood flow ...velocity using laser Doppler (LD) to determine the relationship of macroperfusion and microperfusion parameters, and to test the relationship of the worst NIRS parameters during the first 24 hours of shock with 28-day prognosis.
A prospective, observational study was performed in a 21-bed university hospital surgical intensive care unit. Forty-three septic shock patients with at least another organ failure underwent a 3-minute, upper arm (brachial artery) vascular occlusion test (VOT). Microperfusion parameters (thenar eminence StO2 and forearm LD skin blood flow) were collected on days 1, 2 and 3, before (baseline StO2 and LD values) and during the 3-minute VOT with calculation of occlusion and reperfusion slopes for StO2 and LD. Daily Sequential Organ Failure Assessment (SOFA) score, macrohemodynamic parameters (systolic arterial blood pressure, cardiac output (pulmonary artery catheter or transesophageal Doppler), mixed venous oxygen saturation (pulmonary artery or superior vena cava catheter)) and metabolic parameters (pH, base excess, lactate) were determined.
Baseline StO2 (82% (75 to 88) vs. 89% (85 to 92), P = 0.04) and reperfusion slope (2.79%/second (1.75 to 4.32) vs. 9.35%/second (8.32 to 11.57), P < 0.0001) were lower in septic shock patients than in healthy volunteers. StO2 reperfusion slope correlated with occlusion slope (P < 0.0001), cardiac output (P = 0.01) and LD reperfusion slope (P = 0.08), and negatively with lactate level (P = 0.04). The worst StO2 reperfusion slope during the first day of shock was lower in nonsurvivors than in survivors (P = 0.003) and improved significantly the predictive value of Simplified Acute Physiology Score II and SOFA scores.
The alteration of StO2 reperfusion slope in septic shock patients compared with healthy volunteers was related with macrohemodynamic, microhemodynamic and metabolic parameters. The addition of the worst value of the day 1 StO2 reperfusion slope improved the outcome prediction of Simplified Acute Physiology Score II and SOFA scores.
Abstract
Background and study aims
ESD in the colon is more challenging technically than in other locations. Here, we report the first comparative case series of colon ESD using a systematic ...countertraction strategy using two clips and a rubber band.
Patients and methods
Retrospective comparative study of classic versus countertraction colon ESD performed in colon ESD cases collected prospectively at Lyon Edouard Herriot Hospital and Limoges University Hospital from January 2016 until December 2017.
Results
The study included 192 cases (control = 76, countertraction = 116). Countertraction using the double clip and rubber band technique versus the control group resulted in a significant decrease in the procedure time (94.7
vs
. 117 min;
P
= 0.004) and significant increases in procedure speed (28.2
vs
. 16.7 mm
2
/min;
P
< 0.0001), en bloc resection rate (95.7 %
vs
. 76.3 %,
P
< 0.0001), and R0 resection rate (78.5 %
vs
. 64.5 %,
P
= 0.04).
At an individual operator point of view, results varied between operators but the double clip countertraction strategy significantly increased the en bloc resection rate, R0 resection rate, and speed of dissection for each of the 4 operators.
Conclusion
Systematic countertraction using a double clip and rubber band facilitates colon ESD. This strategy should become the standard for colon ESD.
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.
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