Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study.

OBJECTIVES: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA). DESIGN AND SETTING: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study. PARTICIPANTS: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort). OUTCOMES: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model. RESULTS: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080). CONCLUSION: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Phenotypic clustering of patients hospitalized in intensive cardiac care units: Insights from the ADDICT-ICCU study.

BACKGROUND: Intensive cardiac care units (ICCUs) were created to manage ventricular arrhythmias after acute coronary syndromes, but have diversified to include a more heterogeneous population, the characteristics of which are not well depicted by conventional methods. AIMS: To identify ICCU patient subgroups by phenotypic unsupervised clustering integrating clinical, biological, and echocardiographic data to reveal pathophysiological differences. METHODS: During 7-22 April 2021, we recruited all consecutive patients admitted to ICCUs in 39 centers. The primary outcome was in-hospital major adverse events (MAEs; death, resuscitated cardiac arrest or cardiogenic shock). A cluster analysis was performed using a Kamila algorithm. RESULTS: Of 1499 patients admitted to the ICCU (69.6% male, mean age 63.3±14.9 years), 67 (4.5%) experienced MAEs. Four phenogroups were identified: PG1 (n=535), typically patients with non-ST-segment elevation myocardial infarction; PG2 (n=444), younger smokers with ST-segment elevation myocardial infarction; PG3 (n=273), elderly patients with heart failure with preserved ejection fraction and conduction disturbances; PG4 (n=247), patients with acute heart failure with reduced ejection fraction. Compared to PG1, multivariable analysis revealed a higher risk of MAEs in PG2 (odds ratio [OR] 3.13, 95% confidence interval [CI] 1.16-10.0) and PG3 (OR 3.16, 95% CI 1.02-10.8), with the highest risk in PG4 (OR 20.5, 95% CI 8.7-60.8) (all P<0.05). CONCLUSIONS: Cluster analysis of clinical, biological, and echocardiographic variables identified four phenogroups of patients admitted to the ICCU that were associated with distinct prognostic profiles. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05063097.

Ticagrelor vs Clopidogrel in Clopidogrel-Naive Patients With Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.

Reduced Rate of Hospitalizations for Acute Diabetes Events Before and After FreeStyle Libre® System Initiation in Some People With Type 2 Diabetes on Insulin-Secretagogue Oral Drug Therapy Without Insulin in France.

Objective: Glycemic management in people with type 2 diabetes mellitus (T2DM) on insulin-secretagogue regimens without insulin is of importance, as this group still represents a significant proportion of patients. Risks for acute diabetes events (ADEs), including diabetic ketoacidosis (DKA) or hypoglycemia, using insulin-secretagogue drugs are well established. Few studies have suggested that continuous glucose monitoring (CGM) could be useful for monitoring glucose dynamics associated with the use of such therapies. To document this point an exploratory analysis was conducted in a group of individuals with noninsulin treated T2DM in France who are managed with oral insulin-secretagogues and initiating the FreeStyle Libre® system (FSL). Methods: A retrospective study of the French national SNDS reimbursement claims database (≈66 million French people) was conducted to identify people with T2DM on oral insulin-secretagogues and receiving a first reimbursement of FSL between August 1, 2017 and December 31, 2018. The analysis included data for the 12 months before and up to 24 months after FSL initiation. Hospitalizations for diabetes-related acute events were identified using ICD-10 codes as main or related diagnosis, for: hypoglycemic events; DKA events; comas; and hyperglycemia-related admissions. Results: A total of 1272 people with T2DM on insulin-secretagogues without insulin initiated FSL during the selection period. Of these, 7.15% had at least one hospitalization for any ADE in the year before FSL initiation, compared with 2.52% at 12 months and 2.83% at 24 months following FSL initiation. Reductions in ADEs were driven by -73% fewer admissions for ADEs related to diabetic ketoacidosis (DKA) or other hyperglycemia-related events. These patterns of reduced ADEs persisted after 2 years. Conclusions: This study suggests the value of the FSL system in reducing ADEs in some people with T2DM in France being treated with insulin-secretagogues without insulin. Characteristics of these patients remain to be documented.

Arthro-distension with early and intensive mobilization for shoulder adhesive capsulitis: A randomized controlled trial.

BACKGROUND: There are several therapeutic options for the management of shoulder adhesive capsulitis (AC). The superiority of arthro-distension over intra-articular steroid injection (ISI) for AC remains controversial. OBJECTIVES: To evaluate the efficacy of a single arthro-distension procedure combined with early and intensive mobilization (ADM) and physiotherapy, versus ISI and physiotherapy, in people with AC lasting ≥3 months. METHODS: This was a prospective, 2 parallel-group, 2-center, observer-blind randomized controlled trial conducted in tertiary care settings. Adults with AC were randomly assigned to the treatment or control group. Efficacy was assessed using the self-administered Shoulder Pain and Disability Index (SPADI). Total, pain and disability SPADI scores 15 days, 6 weeks, and 3, 6 and 12 months after the procedure (total SPADI at 15 days: primary outcome; other outcomes were secondary) were compared between groups using analysis of covariance (ANCOVA). A post hoc analysis stratified on the initial range of passive glenohumeral abduction, which had not been pre-specified, was conducted. RESULTS: There were 33 participants in each group. Both groups improved over time. Mean (SD) total SPADI score at 15 days was 33.8 (19.6) in the treatment group and 32.8 (17.5) in the control group, p = 0.393. There were no significant differences for any variables in the overall sample. The post hoc analysis found ADM to be associated with a significant decrease in total SPADI score at 15 days compared with ISI (p = 0.049) in individuals with initial passive glenohumeral abduction >45°. CONCLUSIONS: The effects of ADM on pain and function were not statistically different from those of ISI. However, ADM may be useful in individuals with initial passive glenohumeral abduction >45°. DATABASE REGISTRATION: NCT00724113.

Effects of hemorrhagic shock and rhabdomyolysis on renal microcirculation, oxygenation and function in a female swine model.

BACKGROUND: Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors of acute kidney injury (AKI) after severe trauma, however the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion and morphology, in a pig model. METHODS: Forty-seven female pigs were divided into 5 groups: sham, RM, HS, HS and moderate RM (RM4/HS), HS and severe RM (RM8/HS). RM was induced by intramuscular injection of Glycerol 50% with a moderate dose (4 ml/kg for RM4/HS group) or a high dose (8 ml/kg for RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 hours. Macro and microcirculatory parameters measurements were performed. RESULTS: RM alone induced a decrease in creatinine clearance at 48 hours (19 (0-41) vs 102 (56-116) ml/min for RM and SHAM respectively; p = 0.0006) without alteration in renal perfusion and oxygenation. HS alone impaired temporarily renal microcirculation, function and oxygenation that were restored with fluid resuscitation. RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that were not improved by fluid resuscitation. Mortality was increased in RM8/HS and RM4/HS groups in the first 48 hours (73% vs 56% vs 9% for RM8/HS, RM4/HS and HS groups respectively). CONCLUSIONS: The combination of HS and RM induced an early deleterious effect on renal microcirculation, function and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone.

Design, cohort profile and comparison of the KTD-Innov study: a prospective multidimensional biomarker validation study in kidney allograft rejection.

There is an unmet need for robust and clinically validated biomarkers of kidney allograft rejection. Here we present the KTD-Innov study (ClinicalTrials.gov, NCT03582436), an unselected deeply phenotyped cohort of kidney transplant recipients with a holistic approach to validate the clinical utility of precision diagnostic biomarkers. In 2018-2019, we prospectively enrolled consecutive adult patients who received a kidney allograft at seven French centers and followed them for a year. We performed multimodal phenotyping at follow-up visits, by collecting clinical, biological, immunological, and histological parameters, and analyzing a panel of 147 blood, urinary and kidney tissue biomarkers. The primary outcome was allograft rejection, assessed at each visit according to the international Banff 2019 classification. We evaluated the representativeness of participants by comparing them with patients from French, European, and American transplant programs transplanted during the same period. A total of 733 kidney transplant recipients (64.1% male and 35.9% female) were included during the study. The median follow-up after transplantation was 12.3 months (interquartile range, 11.9-13.1 months). The cumulative incidence of rejection was 9.7% at one year post-transplant. We developed a distributed and secured data repository in compliance with the general data protection regulation. We established a multimodal biomarker biobank of 16,736 samples, including 9331 blood, 4425 urinary and 2980 kidney tissue samples, managed and secured in a collaborative network involving 7 clinical centers, 4 analytical platforms and 2 industrial partners. Patients' characteristics, immune profiles and treatments closely resembled those of 41,238 French, European and American kidney transplant recipients. The KTD-Innov study is a unique holistic and multidimensional biomarker validation cohort of kidney transplant recipients representative of the real-world transplant population. Future findings from this cohort are likely to be robust and generalizable.

Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1-phase 2a study.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2LD) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc. OBJECTIVE: We aimed to assess the safety and biological efficacy of IL-2LD in patients with SSc. METHODS: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6. RESULTS: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4+ T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period. CONCLUSION: IL-2LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2LD therapeutic efficacy in SSc.

Positive Impact of a New Compressive Garment in Patients with Genital Lymphedema: OLYMPY Study.

Purpose: Genital lymphedema is a chronic debilitating condition associated with highly impaired health-related quality of life (QoL). This prospective multicenter study evaluated the use of a new compressive garment in patients with secondary and primary genital lymphedema. Methods: Thirty-two patients prospectively enrolled were advised to wear the compressive garment for 12 weeks (day and night). The primary endpoint was change in patient-reported QoL at 12 weeks via the patient global impression of change (PGI-C) instrument. Secondary outcomes included change in other QoL measures at 12 weeks (visual analog scale, Lymphedema Quality of Life Inventory [LyQLI], and EQ-5D questionnaires), lymphedema severity (genital lymphedema score [GLS]), and physician assessment (Clinical Global Impression-Improvement [CGI-I]). Safety and tolerability were also assessed. Results: After 12 weeks, improvement was reported in 78.6% of patients (PGI-C). Physician assessment (CGI-I) indicated clinical improvement in 82.8% of patients. Patient assessment of lymphedema symptoms showed a significant decrease in discomfort (p = 0.02) and swelling (p = 0.01). Significant declines in the mean global GLS (p < 0.0001), and in the proportion of patients reporting heaviness, tightness, swelling, or urinary dysfunction (p < 0.05 for all), were also observed. LyQLI scores decreased (indicating improved QoL) in each of the physical, psychosocial (p = 0.05), and practical domains. The compressive garment was well tolerated with high compliance, and adverse events (due to swelling or discomfort) led to permanent discontinuation in only three patients. Conclusion: The use of a new genital compression garment over 12 weeks improves the QoL and clinical measures in patients with genital lymphedema (ClinicalTrials.gov ID: NCT04602559; Registration: October 20, 2020).

Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

Artificial intelligence-based prediction of diabetic retinopathy evolution (EviRed): protocol for a prospective cohort.

INTRODUCTION: An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution. METHODS AND ANALYSIS: A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms. ETHICS AND DISSEMINATION: The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients. TRIAL REGISTRATION NUMBER: NCT04624737.

A Comprehensive National Survey of Prostate-specific Antigen Testing and Prostate Cancer Management in France: Uncovering Regional and Temporal Disparities.

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed. Their management was analysed by age range and compared in the different French regions. Disparities were found in age at PSA testing and management approaches (surveillance, and local and systemic therapies). We found that 50% of men had received five PSA blood tests, but the first PSA test was taken late in life, with a peak in the decade between 65 and 75 yr of age. Adoption of monitoring was low (12%). Older men appeared to receive a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality, but cautious interpretation of our data is warranted in view of competing morbidities and other causes of death. The incidence of metastases at diagnosis, indicated by the use of systemic therapies, increased progressively from 2011 onwards. PATIENT SUMMARY: In this study, we report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men, including 692516 patients with PC. We found that the first prostate-specific antigen test is taken too late in life, leading to a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality.

Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker.

INTRODUCTION: Untreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout flares are self-limited inflammatory reactions involving multiple mediators. This study aimed to characterise the inflammatory profiles of gout at different phases. METHODS: Using the Olink targeted proteomics, levels of 92 inflammation-related proteins were measured in plasma samples of a prospective gout population (GOUTROS), collected at gout flare (T1), the intercritical phase (T2) and after reaching the target serum urate level under urate-lowering therapy (T3). Results were validated in an independent cohort (OLT1177-05) with plasmas collected at T1 and T2. Ex vivo and in vitro experiments were performed to assess the inflammatory properties of new biomarkers. RESULTS: In total, 21 inflammatory new biomarkers were differentially expressed during the three time-points of gout disease. The levels of four of these proteins (interleukin 6 (IL-6), colony-stimulating factor 1, vascular endothelial growth factor A and tumour necrosis factor superfamily 14 (TNFSF14)) were increased during gout flare in an independent cohort. IL-6 and TNFSF14 had the highest fold change in expression during T1 versus T2 or T3. TNFSF14 was produced at the inflamed joint and enhanced the inflammatory response induced by lipopolysaccharide and MSU crystal stimulation. Conversely, TNFSF14 blockade reduced the inflammatory response. Additionally, single nucleotide polymorphisms of TNFSF14 affected the ability of myeloid cells to produce inflammatory cytokines. CONCLUSION: Gout flare involves multiple inflammatory mediators that may be used as potential therapeutic targets.

Control of mean arterial pressure using a closed-loop system for norepinephrine infusion in severe brain injury patients: the COMAT randomized controlled trial.

Brain injury patients require precise blood pressure (BP) management to maintain cerebral perfusion pressure (CPP) and avoid intracranial hypertension. Nurses have many tasks and norepinephrine titration has been shown to be suboptimal. This can lead to limited BP control in patients that are in critical need of cerebral perfusion optimization. We have designed a closed-loop vasopressor (CLV) system capable of maintaining mean arterial pressure (MAP) in a narrow range and we aimed to assess its performance when treating severe brain injury patients. Within the first 48 h of intensive care unit (ICU) admission, 18 patients with a severe brain injury underwent either CLV or manual norepinephrine titration. In both groups, the objective was to maintain MAP in target (within ± 5 mmHg of a predefined target MAP) to achieve optimal CPP. Fluid administration was standardized in the two groups. The primary objective was the percentage of time patients were in target. Secondary outcomes included time spent over and under target. Over the four-hour study period, the mean percentage of time with MAP in target was greater in the CLV group than in the control group (95.8 ± 2.2% vs. 42.5 ± 27.0%, p < 0.001). Severe undershooting, defined as MAP < 10 mmHg of target value was lower in the CLV group (0.2 ± 0.3% vs. 7.4 ± 14.2%, p < 0.001) as was severe overshooting defined as MAP > 10 mmHg of target (0.0 ± 0.0% vs. 22.0 ± 29.0%, p < 0.001). The CLV system can maintain MAP in target better than nurses caring for severe brain injury patients.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

Association Between Early Patient Characteristics and IgE-Mediated Allergy in the Perioperative Setting.

BACKGROUND: Early recognition of perioperative anaphylaxis, a life-threatening, usually IgE-mediated, immediate hypersensitivity, is essential, but bedside diagnosis is not always straightforward because clinical presentation may vary. OBJECTIVES: To describe early characteristics of perioperative immediate hypersensitivity, with special attention to cutaneous phenotypes, and identify risk factors for IgE-mediated allergy. METHODS: We retrospectively analyzed data from adults with suspected perioperative immediate hypersensitivity who were investigated in two academic medical centers. Multivariable logistic regression was conducted to evaluate associations among patient, clinical, and paraclinical characteristics and IgE-mediated allergy. RESULTS: Of 145 enrolled patients, 99 (68.3%) and 46 (31.7%) were respectively categorized in the IgE-mediated allergy and non-allergy groups. Cutaneous vasoconstriction phenotype (pallor, piloerection, thelerethism, and sweating with or without cyanosis) occurring within minutes (or even 1 minute) of drug exposure was strongly associated with IgE-mediated allergy (adjusted odds ratio [aOR] = 28.02; 95% CI, 4.41-305.18). IgE-mediated allergy was always life-threatening in this setting. Other early factors associated with allergy were low end-tidal carbon dioxide 25 mm Hg or less (aOR = 5.45; 95% CI, 2.39-26.45), low mean arterial pressure 60 mm Hg or less (aOR = 3.82; 95% CI, 1.28-17.31), and early cutaneous vasodilation (erythema, urticaria, and/or angioedema) (aOR = 2.78; 95% CI, 0.73-20.54). Late cutaneous vasodilation after restoration of hemodynamics corroborated the diagnosis of allergy (aOR = 23.67; 95% CI, 4.94-205.09). The best-fit model including three readily available variables (cutaneous phenotype involving the three modalities [reference lack of cutaneous signs], low mean arterial pressure, and low end-tidal carbon dioxide) had an area under the curve of 0.91. CONCLUSIONS: Cutaneous vasoconstriction phenotype is associated with the strongest risk of life-threatening allergy and thus may be regarded as pathognomonic of perioperative IgE-mediated anaphylaxis.