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The Lancet. Neurology Nov 2023Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining... (Randomized Controlled Trial)
Randomized Controlled Trial
Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.
BACKGROUND
Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months.
METHODS
We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed.
FINDINGS
Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest.
INTERPRETATION
After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission.
FUNDING
The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.
Topics: Humans; Oxygen; Intracranial Pressure; Brain Injuries, Traumatic; Brain; France; Hematoma; Death
PubMed: 37863590
DOI: 10.1016/S1474-4422(23)00290-9 -
MMW Fortschritte Der Medizin Mar 2024
Topics: Humans; Death; Pulmonary Disease, Chronic Obstructive
PubMed: 38453835
DOI: 10.1007/s15006-024-3704-y -
JAMA Network Open Nov 2023Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities....
IMPORTANCE
Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known.
OBJECTIVE
To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, multivariable Cox proportional hazards regression models were used to examine the association of sphingolipid species with SCD risk. The study population included 4612 participants in the Cardiovascular Health Study followed up prospectively for a median of 10.2 (IQR, 5.5-11.6) years. Baseline data were collected from January 1992 to December 1995 during annual examinations. Data were analyzed from February 11, 2020, to September 9, 2023.
EXPOSURES
Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons.
MAIN OUTCOME AND MEASURE
Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk.
RESULTS
Among the 4612 CHS participants included in the analysis (mean [SD] age, 77 [5] years; 2724 [59.1%] women; 6 [0.1%] American Indian; 4 [0.1%] Asian; 718 [15.6%] Black; 3869 [83.9%] White, and 15 [0.3%] Other), 215 SCD cases were identified. In adjusted Cox proportional hazards regression analyses, plasma ceramides and sphingomyelins with palmitic acid (Cer-16 and SM-16) were associated with higher SCD risk per higher SD of log sphingolipid levels (hazard ratio [HR] for Cer-16, 1.34 [95% CI, 1.12-1.59]; HR for SM-16, 1.37 [95% CI, 1.12-1.67]). Associations did not differ by baseline age, sex, race, or body mass index. No significant association of SCD with sphingolipids with very-long-chain saturated fatty acids was observed after correction for multiple testing (HR for ceramide with arachidic acid, 1.06 [95% CI, 0.90-1.24]; HR for ceramide with behenic acid, 0.92 [95% CI, 0.77-1.10]; HR for ceramide with lignoceric acid, 0.92 [95% CI, 0.77-1.09]; HR for sphingomyelin with arachidic acid, 0.83 [95% CI, 0.71-0.98]; HR for sphingomyelin with behenic acid, 0.84 [95% CI, 0.70-1.00]; HR for sphingomyelin with lignoceric acid, 0.86 [95% CI, 0.72-1.03]).
CONCLUSIONS AND RELEVANCE
The findings of this large, population-based cohort study of SCD identified that higher plasma levels of Cer-16 and SM-16 were associated with higher risk of SCD. Future studies are needed to examine the underlying mechanism of these associations.
Topics: Humans; Female; Aged; Male; Sphingomyelins; Ceramides; Eicosanoic Acids; Cohort Studies; Fatty Acids; Sphingolipids; Death, Sudden, Cardiac
PubMed: 37976059
DOI: 10.1001/jamanetworkopen.2023.43854 -
Risk of Arrhythmic Death in Patients With Nonischemic Cardiomyopathy: JACC Review Topic of the Week.Journal of the American College of... Aug 2023Nonischemic cardiomyopathy (NICM) is common and patients are at significant risk for early mortality secondary to ventricular arrhythmias. Current guidelines recommend... (Review)
Review
Nonischemic cardiomyopathy (NICM) is common and patients are at significant risk for early mortality secondary to ventricular arrhythmias. Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy to decrease sudden cardiac death (SCD) in patients with heart failure and reduced left ventricular ejection fraction. However, in randomized clinical trials comprised solely of patients with NICM, primary prevention ICDs did not confer significant mortality benefit. Moreover, left ventricular ejection fraction has limited sensitivity and specificity for predicting SCD. Therefore, precise risk stratification algorithms are needed to define those at the highest risk of SCD. This review examines mechanisms of sudden arrhythmic death in patients with NICM, discusses the role of ICD therapy and treatment of heart failure for prevention of SCD in patients with NICM, examines the role of cardiac magnetic resonance imaging and computational modeling for SCD risk stratification, and proposes new strategies to guide future clinical trials on SCD risk assessment in patients with NICM.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Cardiomyopathies; Heart Failure; Death, Sudden, Cardiac
PubMed: 37587585
DOI: 10.1016/j.jacc.2023.05.064 -
Journal of the American College of... Sep 2023Patients with congenital heart disease associated with a higher risk for ventricular arrhythmias (VA) and sudden cardiac death (SCD) can be divided conceptually into... (Review)
Review
Patients with congenital heart disease associated with a higher risk for ventricular arrhythmias (VA) and sudden cardiac death (SCD) can be divided conceptually into those with discrete mechanisms for reentrant monomorphic ventricular tachycardia (VT) (Group A) and those with more diffuse substrates (Group B). Part I of this review addresses Group A lesions, which predominantly consist of tetralogy of Fallot and related variants. Well-defined anatomic isthmuses for reentrant monomorphic VT are interposed between surgical scars and the pulmonary or tricuspid annulus. The most commonly implicated critical isthmus for VT is the conal septum that divides subpulmonary from subaortic outlets. Programmed ventricular stimulation can be helpful in risk stratification. Although catheter ablation is not generally considered an alternative to the implantable cardioverter-defibrillator (ICD) for prevention of SCD, emerging data suggest that there is a subset of carefully selected patients who may not require ICDs after successful monomorphic VT ablation.
Topics: Humans; Adult; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Heart Defects, Congenital; Catheter Ablation; Defibrillators, Implantable
PubMed: 37673512
DOI: 10.1016/j.jacc.2023.06.034 -
Experimental and Clinical... Apr 2024The definition of death remains unresolved. To define death, one has to define the characteristics of a living person and to confirm whether an individual with brain...
The definition of death remains unresolved. To define death, one has to define the characteristics of a living person and to confirm whether an individual with brain death fulfils any of these characteristics. Although the concept of irreversible cessation of brain function is clear, controversy remains on the treatment of individuals with brain death and beating hearts. An individual with brain death but a beating heart is not breathing on his own and is dependent on medications and machines to maintain respiration, heartbeat, and blood pressure. Muslim scholars remain divided over the issue of whether death also means irreversible cessation of brain function. Questions remain on when it is permissible to remove vital organs for organ transplant. Groups have advocated for uniformity in law and medical practice on the definition of brain death.
Topics: Humans; Attitude to Death; Brain Death; Death; History, 20th Century; History, 21st Century; Islam; Organ Transplantation; Religion and Medicine; Terminology as Topic; Tissue and Organ Procurement
PubMed: 38775693
DOI: 10.6002/ect.BDCDSymp.L8 -
The Journal of Clinical Investigation Sep 2023BACKGROUNDSevere, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected...
BACKGROUNDSevere, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, thus preventing accurate patient counseling. We investigated the use of maternal serum protein and ultrasound measurements at diagnosis to predict fetal or neonatal death and 3 secondary outcomes: fetal death or delivery at or before 28+0 weeks, development of abnormal umbilical artery (UmA) Doppler velocimetry, and slow fetal growth.METHODSWomen with singleton pregnancies (n = 142, estimated fetal weights [EFWs] below the third centile, less than 600 g, 20+0 to 26+6 weeks of gestation, no known chromosomal, genetic, or major structural abnormalities) were recruited from 4 European centers. Maternal serum from the discovery set (n = 63) was analyzed for 7 proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease, and 5 proteins identified through pooled liquid chromatography and tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n = 60), with final models calculated from combined data.RESULTSThe most discriminative model for fetal or neonatal death included the EFW z score (Hadlock 3 formula/Marsal chart), gestational age, and UmA Doppler category (AUC, 0.91; 95% CI, 0.86-0.97) but was less well calibrated than the model containing only the EFW z score (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery at or before 28+0 weeks included maternal serum placental growth factor (PlGF) concentration and UmA Doppler category (AUC, 0.89; 95% CI, 0.83-0.94).CONCLUSIONUltrasound measurements and maternal serum PlGF concentration at diagnosis of severe, early-onset FGR predicted pregnancy outcomes of importance to patients and clinicians.TRIAL REGISTRATIONClinicalTrials.gov NCT02097667.FUNDINGThe European Union, Rosetrees Trust, Mitchell Charitable Trust.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Fetal Death; Fetal Growth Retardation; Perinatal Death; Placenta Growth Factor; Pregnancy Outcome
PubMed: 37712421
DOI: 10.1172/JCI169199 -
The American Journal of Cardiology Feb 2024Hypertrophic cardiomyopathy (HCM) is a complex, heterogeneous disorder that affects approximately 1 in every 500 persons worldwide and about 750,000 Americans. It is... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a complex, heterogeneous disorder that affects approximately 1 in every 500 persons worldwide and about 750,000 Americans. It is characterized by left ventricular hypertrophy that is usually asymmetric, with enlarged myocytes in disarray, unexplained by loading conditions. Obstruction to left ventricular outflow occurs in approximately 60% of patients. The natural history and cardiac morphology of HCM are quite heterogeneous. Although most patients with HCM are asymptomatic or mildly symptomatic, a minority are disabled by dyspnea, angina, or syncope, develop advanced heart failure, or die suddenly.
Topics: Humans; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Heart Failure; Heart Ventricles; Hypertrophy, Left Ventricular; Syncope
PubMed: 38368032
DOI: 10.1016/j.amjcard.2023.10.075 -
Acta Paediatrica (Oslo, Norway : 1992) Jul 2023As it is now 20 years since the San Diego definition of sudden infant death syndrome (SIDS) was proposed, it is timely to examine the impact of this consensus statement. (Review)
Review
AIM
As it is now 20 years since the San Diego definition of sudden infant death syndrome (SIDS) was proposed, it is timely to examine the impact of this consensus statement.
RESULTS
Concerns at the time were expressed that 'death scene' had been replaced by circumstances of death and so it may have been more useful to have a more inclusive statement of 'death scene, including circumstances of death'. The category of unclassified sudden infant deaths (USID) that was proposed has not been widely adopted. More disturbing, however, is the increasing failure to use either the San Diego or earlier definitions in published research, with recent studies showing that almost two-thirds of peer-reviewed SIDS publications (2019-2021) did not quote or reference internationally accepted definitions. This is a decrease of 33% from the 68% of papers that correctly used SIDS definitions in 2011. The definition is therefore not being uniformly applied and in addition, diagnostic shift is occurring, with more pathologists favouring 'undetermined' over a designation of SIDS.
CONCLUSIONS
Given these developments, how can we correctly interpret conclusions relating to SIDS research, and can we accurately monitor trends in SIDS mortality? The authors would suggest that unfortunately, at present we cannot with any precision.
Topics: Infant; Humans; Sudden Infant Death; Sleep
PubMed: 36965047
DOI: 10.1111/apa.16777 -
The American Journal of Cardiology Aug 2023High-risk athletes with implanted cardioverter-defibrillators who are competing in intense sports represent a controversial issue in cardiovascular medicine. Such...
High-risk athletes with implanted cardioverter-defibrillators who are competing in intense sports represent a controversial issue in cardiovascular medicine. Such devices have the capability to protect patients with a variety of cardiovascular diseases from sudden death and have aborted potentially lethal events during competitive sports but they can also lead to adverse clinical consequences for athletes with implants and other participants. In conclusion, clinicians and athletes should consider the data presented here in making prudent and informed recommendations regarding the eligibility of this patient group with implanted cardioverter-defibrillators for intense competitive sports.
Topics: Humans; Defibrillators, Implantable; Death, Sudden, Cardiac; Sports; Athletes; Electric Countershock
PubMed: 37393157
DOI: 10.1016/j.amjcard.2023.05.050