Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ...ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed.
We conducted a systematic review and meta-analysis of randomized controlled trials in septic ICU patients to assess the effects of this combination therapy.
PubMed, Embase, and the Cochrane library databases were searched from inception to March of 2021. Data were extracted independently by two authors. The main outcome was the change in Sequential Organ Failure Assessment score within 72 hours. Secondary outcomes included renal composite endpoints (acute kidney injury) Kidney Disease - Improving Global Outcome organization stage 3 or need for renal replacement therapy, vasopressor duration, and 28-day mortality.
We included randomized controlled trials with patients admitted to the ICU with sepsis or septic shock.
The trials compared a combination of thiamine, ascorbic acid, and hydrocortisone to standard care or placebo in patients admitted to ICU with sepsis or septic shock.
We included eight randomized controlled trials (n = 1,335 patients). Within 72 hours, the median of mean improvement was -1.8 and -3.2 in the control and intervention groups, respectively (eight randomized controlled trials, n = 1,253 patients); weighted mean difference -0.82 (95% CI, -1.15 to -0.48). Data were homogeneous and the funnel plot did not suggest any publication bias. Duration of vasopressor requirement was significantly reduced in the intervention group (six randomized controlled trials). There was no evidence of a difference regarding the ICU mortality and the renal composite outcome (acute kidney injury KDIGO 3 or need for renal replacement therapy, seven randomized controlled trials).
Metabolic resuscitation cocktail administrated in ICU septic patients improves change in Sequential Organ Failure Assessment score within 72 hours. However, this improvement is modest and its clinical relevance is questionable. The impact on renal failure and mortality remains unclear.
Multiplex polymerase chain reaction (mPCR) for respiratory virus testing is increasingly used in community-acquired pneumonia (CAP), however data on one-year outcome in intensive care unit (ICU) ...patients with reference to the causative pathogen are scarce.
We performed a single-center retrospective study in 123 ICU patients who had undergone respiratory virus testing for CAP by mPCR and with known one-year survival status. Functional status including dyspnea (mMRC score), autonomy (ADL Katz score) and need for new home-care ventilatory support was assessed at a one-year post-ICU follow-up. Mortality rates and functional status were compared in patients with CAP of a bacterial, viral or unidentified etiology one year after ICU admission.
The bacterial, viral and unidentified groups included 19 (15.4%), 37 (30.1%), and 67 (54.5%) patients, respectively. In multivariate analysis, one-year mortality in the bacterial group was higher compared to the viral group (HR 2.92, 95% CI 1.71-7.28, p = 0.02) and tended to be higher compared to the unidentified etiology group (p = 0.06); but no difference was found between the viral and the unidentified etiology group (p = 0.43). In 64/83 one-year survivors with a post-ICU follow-up consultation, there were no differences in mMRC score, ADL Katz score and new home-care ventilatory support between the groups (p = 0.52, p = 0.37, p = 0.24, respectively). Severe dyspnea (mMRC score = 4 or death), severe autonomy deficiencies (ADL Katz score ≤ 2 or death), and major adverse respiratory events (new home-care ventilatory support or death) were observed in 52/104 (50.0%), 47/104 (45.2%), and 65/104 (62.5%) patients, respectively; with no difference between the bacterial, viral and unidentified group: p = 0.58, p = 0.06, p = 0.61, respectively.
CAP of bacterial origin had a poorer outcome than CAP of viral or unidentified origin. At one-year, impairment of functional status was frequently observed, with no difference according to the etiology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Septic shock is one of the most common reasons for admission to the Intensive Care Unit (ICU) and is associated with high mortality. Fundamentally, its management rests on antibiotics, ...fluid therapy and vasopressor use while many adjunctive therapies have shown disappointing results. Thiamine has recently gained interest as a metabolic resuscitator, though recent trials have tempered this enthusiasm, more specifically when thiamine is associated with ascorbic acid. However, thiamine use alone has been poorly investigated.
Design
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in septic shock patients to assess the effects of thiamine without ascorbic acid as an adjunctive therapy.
Setting
PubMed, Embase and the Cochrane library databases were searched from inception to April of 2023. Data were extracted independently by two authors. The main outcome was mortality.
Subjects
We included RCTs comparing standard care using thiamine alone, to standard care or placebo, in patients admitted to the ICU with sepsis or septic shock.
Main results
We included 5 RCTs (
n
= 293 patients). In this analysis, use of thiamine alone did not significantly change mortality, RR 0.87 (95%CI 0.65; 1.16,
I
2
= 21%)
p
= 0.34.
Conclusion
Current RCTs did not show an improvement in mortality when using thiamine in septic shock patients as an adjunctive therapy. However, these trials are largely underpowered for a definitive conclusion to be drawn. Further studies are therefore needed to assess the effects of thiamine without ascorbic acid as an adjunctive therapy.
•Delayed intubation in severe COVID-19 patients associated with mortality.
Switzerland experienced two waves of COVID-19 in 2020, but with a different ICU admission and treatment management strategy. ...The timing of ICU admission and intubation remains a matter of debate in severe patients. The aim of our study was to describe the characteristics of ICU patients between two subsequent waves of COVID-19 who underwent a different management strategy and to assess whether the timing of intubation was associated with differences in mortality.
We conducted a prospective observational study of all adult patients with acute respiratory failure due to COVID-19 who required intubation between the 9th of March 2020 and the 9th of January 2021 in the intensive care unit (ICU) at Geneva University Hospitals, Switzerland.
Two hundred twenty-three patients were intubated during the study period; 124 during the first wave, and 99 during the second wave. Patients admitted to the ICU during the second wave had a higher SAPS II severity score (52.5 vs. 60; p = 0.01). The time from hospital admission to intubation was significantly longer during the second compared to the first wave (4 days IQR, 1-7 vs. 2 days IQR, 0-4; p < 0.01). All-cause ICU mortality was significantly higher during the second wave (42% vs. 23%; p < 0.01). In a multivariate analysis, the delay between hospital admission and intubation was significantly associated with ICU mortality (OR 3.25 95% CI, 1.38-7.67; p < 0.05).
In this observational study, delayed intubation was associated with increased mortality in patients with severe COVID-19. Further randomised controlled trials are needed.
Acute Kidney Injury (AKI) is a very frequent condition, occurring in about one in three patients admitted to an intensive care unit (ICU). AKI is a syndrome defined as a sudden decrease in glomerular ...filtration rate. However, this unified definition does not reflect the various mechanisms involved in AKI pathophysiology, each with its own characteristics and sensitivity to therapy. In this study, we aimed at developing an innovative machine learning based method able to subphenotype AKI according to its pattern of risk factors.
We adopted a three-step pipeline of analyses. First, we looked for factors associated with AKI using a generalized additive model. Second, we calculated the importance of each identified AKI related factor in the estimated AKI risk to find the main risk factor for AKI, at the single patient level. Lastly, we clusterized AKI patients according to their profile of risk factors and compared the clinical characteristics and outcome of every cluster. We applied this method to a cohort of severe COVID-19 patients hospitalized in the ICU of the Geneva University Hospitals.
Among the 248 patients analyzed, we found 7 factors associated with AKI development. Using the individual expression of these factors, we identified three groups of AKI patients, based on the use of Lopinavir/Ritonavir, baseline eGFR, use of dexamethasone and AKI severity. The three clusters expressed distinct characteristics in terms of AKI severity and recovery, metabolic patterns and hospital mortality.
We propose here a new method to phenotype AKI patients according to their most important individual risk factors for AKI development. When applied to an ICU cohort of COVID-19 patients, we were able to differentiate three groups of patients. Each expressed specific AKI characteristics and outcomes, which probably reflect a distinct pathophysiology.
(1) Background: Increased thromboembolic events and an increased need for continuous renal replacement therapy (CRRT) have been frequently reported in COVID-19 patients. Our aim was to investigate ...CRRT filter lifespan in intensive care unit (ICU) COVID-19 patients. (2) Methods: We compared CRRT adjusted circuit lifespan in COVID-19 patients admitted for SARS-CoV-2 infection to a control group of patients admitted for septic shock of pulmonary origin other than COVID-19. Both groups underwent at least one session of CRRT for AKI. (3) Results: Twenty-six patients (13 in each group) were included. We analysed 117 CRRT circuits (80 in the COVID-19 group and 37 in the control group). The adjusted filter lifespan was shorter in the COVID-19 group (17 vs. 39 h,
< 0.001). This trend persisted after adjustment for confounding factors (-14 h,
= 0.037). Before CRRT circuit clotting, the COVID-19 group had a more procoagulant profile despite higher heparin infusion rates. Furthermore, we reported a decreased relation between activated partial thromboplastin time (aPTT) and cumulative heparin dose in COVID-19 patients when compared to historical data of 23,058 patients, suggesting a heparin resistance. (4) Conclusion: COVID-19 patients displayed a shorter CRRT filter lifespan that could be related to a procoagulant profile and heparin resistance.
OBJECTIVES:To compare estimated glomerular filtration rate using classical static and kinetic equations with measured glomerular filtration rate assessed by plasma iohexol clearance in a mixed ...population of critical care patients.
PATIENTS:Unselected patients older than 18 and admitted to a general ICU.
DESIGN:Interventional prospective single center study.
INTERVENTION:Measurement of glomerular filtration rate by the plasma clearance of an IV single dose of iohexol and estimation of glomerular filtration rate with creatinine or cystatin C–based standard and kinetic equations as well as urinary creatinine clearance.
MEASUREMENTS AND MAIN RESULTS:Sixty-three patients were included with a median age of 66 years old. The median measured glomerular filtration rate was 51 mL/min/1.73 m (interquartile range, 19–85 mL/min/1.73 m). All used equations displayed significant biases, high errors, and poor accuracy when compared with measured glomerular filtration rate, overestimating renal function. The highest accuracy and lowest error were observed with cystatin C–based chronic kidney disease epidemiology collaboration equations. Both modification of diet in renal disease and Cockcroft-Gault equations displayed the lowest performance. Kinetic models did not improve performances, except in patients with unstable creatinine levels. Creatinine- but not cystatin C–based estimations largely derived over ICU stay, which appeared more related to sarcopenia than fluid balance. Finally, estimated glomerular filtration rate misclassified patients according to classical glomerular filtration rate categories in approximately half of the studied cases.
CONCLUSIONS:All known estimated glomerular filtration rate equations displayed high biases and unacceptable errors when compared with measured glomerular filtration rate in a mixed ICU population, with the lowest performance related to creatinine-based equations compared with cystatin C. In the ICU, we advocate for caution when using creatinine based estimated glomerular filtration rate equations. Drifting of serum creatinine levels over time should also be taken into consideration when assessing renal function in the ICU.
Structural abnormalities were detected in bilateral primary sensorimotor areas in writer's cramp. Evidence in other primary dystonia, including blepharospasm and cervical dystonia, suggest that ...structural abnormalities may be observed in other brain areas such as the cerebellum in writer's cramp.
To test the hypothesis that structural abnormalities are present along the sensorimotor and cerebellar circuits in patients with writer's cramp.
Using voxel-based morphometry, the authors compared the brain structure of 30 right-handed patients with writer's cramp with that of 30 healthy control subjects matched for gender, age, and handedness.
Gray matter decrease was found in the hand area of the left primary sensorimotor cortex, bilateral thalamus, and cerebellum (height threshold p < 0.01, cluster significant at p < 0.05 corrected for multiple comparisons).
These results demonstrate in writer's cramp the presence of structural abnormalities in brain structures interconnected within the sensorimotor network including the cerebellum and the cortical representation of the affected hand. These abnormalities may be related to the pathophysiology of writer's cramp, questioning the role of the cerebellum, or to maladaptive plasticity in a task-related dystonia.
Background: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10–60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and ...frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability. Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor. Findings: A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA250–299 alleles were detected in 1.7% of both groups. Eight of 14 index cases with GAA250-299 repeats had other causal pathogenic variants (4/14) and/or discordance of co-segregation (5/14), arguing against GAA causality. We compared the clinical signs in 127 GAA≥300 carriers to cases with non-expanded GAA ataxia resulting in defining a key phenotype triad: onset after 45 years, downbeat nystagmus, episodic ataxic features including diplopia; and a frequent absence of dysarthria. All maternally transmitted alleles above 100 GAA were unstable with a median expansion of +18 repeats per generation (r2 = 0.44; p < 0.0001). In comparison, paternally transmitted alleles above 100 GAA mostly decreased in size (−15 GAA (r2 = 0.63; p < 0.0001)), resulting in the transmission bias observed in SCA27B pedigrees. Interpretation: SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA250-299 repeats, the absence of documented familial transmission and a presentation deviating from the key SCA27B phenotype, should prompt the search for an alternative cause. Affected fathers have a reduced risk of having affected children, which has potential implications for genetic counseling. Funding: This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux – France (to GS) and by the European Union’s Horizon 2020 research and innovation program under grant agreement No 779257 (“SOLVE-RD” to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL.
OBJECTIVE To determine whether there are diffusion abnormalities along the fibers connecting sensorimotor regions, including the primary sensorimotor areas and the striatum, in patients with writer's ...cramp using voxel-based diffusion analysis and fiber tracking. Recent studies have shown structural changes in these regions in writer's cramp. DESIGN Patient and control group comparison. SETTING Referral center for movement disorders. PARTICIPANTS Twenty-six right-handed patients with writer's cramp and 26 right-handed healthy control subjects matched for sex and age. INTERVENTIONS Clinical motor evaluations. MAIN OUTCOME MEASURES Fractional anisotropy changes and results of fiber tracking in writer's cramp. RESULTS Diffusion-tensor imaging revealed increased fractional anisotropy bilaterally in the white matter of the posterior limb of the internal capsule and adjacent structures in the patients with writer's cramp. Fiber tracking demonstrated that fractional anisotropy changes involve fiber tracts connecting the primary sensorimotor areas with subcortical structures. CONCLUSIONS Diffusion abnormalities are present in fiber tracts connecting the primary sensorimotor areas with subcortical structures in writer's cramp. These abnormalities strengthen the role of the corticosubcortical pathways in the pathophysiologic mechanisms of writer's cramp.Arch Neurol. 2009;66(4):502-508-->
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