The influence of early intensified rehabilitation on the clinical outcome of critically ill patients

1 Exekutivní souhrn Hlavním cílem této práce bylo posoudit účinnost a bezpečnost inovativní fyzioterapeutické metody využívající moderních technologií - funkční elektrickou stimulací asistovanou bicyklovou ergometrii - u kriticky nemocných. Nejprve jsme (projekt A) zkoumali fyziologické změny vyvolané touto technikou u skupiny 14 zdravých dobrovolníků a porovnávali jsme ji ve zkříženém uspořádání s běžným volním cvičením na ergometru s nízkou intenzitou. Prokázali jsme zvýšení celotělového energetického výdeje podobné cvičení o výkonu 25 W. Dále (projekt B) jsme provedli metaanalýzu dosud dostupných randomizovaných kontrolovaných studií, abychom v populaci kriticky nemocných porovnali účinek neuromuskulární elektrické stimulace, pasivního cvičení na bicyklovém ergometru a časné protokolizované fyzioterapie. Zjistili jsme, že pozitivní vliv na výsledky zaměřené na pacienta má pouze časná protokolizovaná fyzioterapie. Nebyly publikovány žádné studie využívající funkční elektrickou stimulací asistovanou bicyklovou ergometrii. Nakonec (projekt C) jsme ve velké jednocentrové randomizované kontrolované studii testovali inovativní protokol časné fyzioterapie založený na využití funkční elektrickou stimulací asistované bicyklové ergometrie ve srovnání se standardní péčí u kriticky nemocných. Nezjistili jsme žádné...1 Executive Summary The overarching goal of this thesis was to assess the efficacy and safety of an innovative rehabilitation technique - functional electrical stimulation-assisted cycle ergometry - in critically ill patients. We firstly (Project A) investigated physiological changes induced by this technique in a group of 14 healthy volunteers and compared it, in a cross-over design, to normal volitional low intensity exercise. We have shown an increase in whole-body energy expenditure similar to 25 W exercise. Then (Project B) we have performed a meta-analysis of randomised-controlled studies available to date to compare in the population of critically ill patients the effect of neuromuscular electrical stimulation, passive cycling, and early goal-directed rehabilitation. We found that only goal directed rehabilitation has positive effects on patient-centred outcomes. There were no published studies using functional electrical stimulation-assisted cycle ergometry. Lastly (Project C) in a large, single centre randomised controlled trial we have tested an innovative functional electrical stimulation-assisted cycle ergometry-based early rehabilitation protocol compared to standard of care in critically ill patient. We have not found any significant differences in the physical function after six months of...Department of Anaesthesia and Intensive Care Medicine 3FM CU and UHKVKlinika anesteziologie a resuscitace 3. LF UK a FNKV3. lékařská fakultaThird Faculty of Medicin

Targeting out-of-hospital cardiac arrest: the effect of heparin administered during cardiopulmonary resuscitation (T-ARREST)

Introduction. Heparin administration during cardiopulmonary resuscitation (CPR) may prevent activation of coagulation after successful resuscitation for out-of-hospital cardiac arrest (OHCA). We hypothesize that such an approach is not associated with an increased rate of bleeding, but it has not been evaluated. We performed a pilot randomized clinical study assessing the safety of intra-arrest heparin administration in OHCA patients with suspected acute myocardial infarction (AMI) and its impact on their prognosis. Materials and Methods. OHCA patients were randomized during CPR to 10 000 units of intra-arrest intravenous heparin (Group H) or to treatment without heparin (Group C). The occurrence of major bleeding and the presence of a favourable neurological result 3 months after OHCA, were analyzed. Results. Out of 88 randomized patients, AMI was subsequently confirmed in 63 of them (71.6 %). There were 30 patients in group H and 33 in group C. No major bleeding event was observed in either group. Return of spontaneous circulation (ROSC, Group H: 40.0%, Group C: 45.4%, p=0.662) and a good neurological result 3 months after OHCA (Group H: 6.7 %, Group C: 9.1 %, p=0.921) did not differ between groups. Conclusions. Intravenous administration of 10 000 units of heparin during CPR for OHCA in patients with supposed AMI was safe. We did not find any improvement in prognosis for our sample of limited size. Though the procedure proved safe, we recommend postponing the administration of heparin until ROSC, assessment of clinical state and recording of a twelve-lead ECG

A randomized comparison of HBP versus RVP: Effect on left ventricular function and biomarkers of collagen metabolism

Background: Right ventricular pacing (RVP) can result in pacing-induced cardiomyopathy (PICM). It is unknown whether specific biomarkers reflect differences between His bundle pacing (HBP) and RVP and predict a decrease in left ventricular function during RVP. Aims: To compare the effect of HBP and RVP on the LV ejection fraction (LVEF) and to study how they affect serum markers of collagen metabolism. Methods: Ninety-two high-risk PICM patients were randomized to HBP or RVP. Their clinical characteristics, echocardiography, and serum levels of TGF-β1, MMP-9, ST2-IL, TIMP-1, and Gal-3 were studied before and six months after pacemaker implantation. Results: Fifty-three patients were randomized to HBP and 39 patients to RVP. HBP failed in 10 patients, which crossed over to the RVP group. Patients with RVP had significantly lower LVEF compared to HBP after six months of pacing (−5% and −4% in as-treated and intention-to-treat analysis, respectively). Levels of TGF-β1 after 6 months were lower in HBP than RVP (mean difference −6 ng/ml; P = 0.009) and preimplant Gal-3 and ST2-IL levels were higher in RVP patients with a decline in the LVEF ≥ 5% compared to those with a decline of < 5% (mean difference 3 ng/ml and 8 ng/ml; P = 0.02 for both). Conclusion: In high-risk PICM patients, HBP was superior to RVP in providing more physiological ventricular function, as reflected by higher LVEF and lower levels of TGF-β1. Among RVP patients, LVEF declined more in those with higher baseline Gal-3 and ST2-IL levels than those with lower levels

Left Ventricular Myocardial Septal Pacing in Close Proximity to LBB Does Not Prolong the Duration of the Left Ventricular Lateral Wall Depolarization Compared to LBB Pacing

Background: Three different ventricular capture types are observed during left bundle branch pacing (LBBp). They are selective LBB pacing (sLBBp), non-selective LBB pacing (nsLBBp), and myocardial left septal pacing transiting from nsLBBp while decreasing the pacing output (LVSP). Study aimed to compare differences in ventricular depolarization between these captures using ultra-high-frequency electrocardiography (UHF-ECG). Methods: Using decremental pacing voltage output, we identified and studied nsLBBp, sLBBp, and LVSP in patients with bradycardia. Timing of ventricular activations in precordial leads was displayed using UHF-ECGs, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. The durations of local depolarizations (Vd) were determined as the width of the UHF-QRS complex at 50% of its amplitude. Results: In 57 consecutive patients, data were collected during nsLBBp (n = 57), LVSP (n = 34), and sLBBp (n = 23). Interventricular dyssynchrony (e-DYS) was significantly lower during LVSP 16 ms (21; 11), than nsLBBp 24 ms (28; 20) and sLBBp 31 ms (36; 25). LVSP had the same V1d-V8d as nsLBBp and sLBBp except for V3d, which during LVSP was shorter than sLBBp; the mean difference 9 ms (16; 1), p = 0.01. LVSP caused less interventricular dyssynchrony and the same or better local depolarization durations than nsLBBp and sLBBp irrespective of QRS morphology during spontaneous rhythm or paced QRS axis. Conclusions: In patients with bradycardia, LVSP in close proximity to LBB resulted in better interventricular synchrony than nsLBBp and sLBBp and did not significantly prolong depolarization of the left ventricular lateral wall

The influence of early intensified rehabilitation on the clinical outcome of critically ill patients

1 Executive Summary The overarching goal of this thesis was to assess the efficacy and safety of an innovative rehabilitation technique - functional electrical stimulation-assisted cycle ergometry - in critically ill patients. We firstly (Project A) investigated physiological changes induced by this technique in a group of 14 healthy volunteers and compared it, in a cross-over design, to normal volitional low intensity exercise. We have shown an increase in whole-body energy expenditure similar to 25 W exercise. Then (Project B) we have performed a meta-analysis of randomised-controlled studies available to date to compare in the population of critically ill patients the effect of neuromuscular electrical stimulation, passive cycling, and early goal-directed rehabilitation. We found that only goal directed rehabilitation has positive effects on patient-centred outcomes. There were no published studies using functional electrical stimulation-assisted cycle ergometry. Lastly (Project C) in a large, single centre randomised controlled trial we have tested an innovative functional electrical stimulation-assisted cycle ergometry-based early rehabilitation protocol compared to standard of care in critically ill patient. We have not found any significant differences in the physical function after six months of..

Impact of frailty, biomarkers and basic biochemical parameters on outcomes of comatose patients in status epilepticus: a single-center prospective pilot study

Abstract Background Status epilepticus (SE) is a severe acute condition in neurocritical care with high mortality. Searching for risk factors affecting the prognosis in SE remains a significant issue. The primary study’s aim was to test the predictive values of the Clinical Frailty Scale (CFS) and the Modified 11-item Frailty Index (mFI-11), the biomarkers and basic biochemical parameters collected at ICU on the Glasgow Outcome Scale (GOS) assessed at hospital discharge (hosp), and three months later (3 M), in comatose patients with SE. The secondary aim was to focus on the association between the patient’s state at admission and the duration of mechanical ventilation, the ICU, and hospital stay. Methods In two years single-centre prospective pilot study enrolling 30 adult neurocritical care patients with SE classified as Convulsive SE, A.1 category according to the International League Against Epilepsy (ILAE) Task Force without an-/hypoxic encephalopathy, we evaluated predictive powers of CFS, mFI-11, admission Status Epilepticus Severity Score (STESS), serum protein S100, serum Troponin T and basic biochemical parameters on prognosticating GOS using univariate linear regression, logistic regression and Receiver Operating Characteristic (ROC) analysis. Results Our study included 60% males, with a mean age of 57 ± 16 years (44–68) and a mean BMI of 27 ± 5.6. We found CFS, mFI-11, STESS, and age statistically associated with GOS at hospital discharge and three months later. Among the biomarkers, serum troponin T level affected GOS hosp (p = 0.027). Serum C-reactive protein significance in prognosticating GOS was found by logistic regression (hosp p = 0.008; 3 M p = 0.004), and serum calcium by linear regression (hosp p = 0.028; 3 M p = 0.015). In relation to secondary outcomes, we found associations between the length of hospital stay and each of the following: age (p = 0.03), STESS (p = 0.009), and serum troponin T (p = 0.029) parameters. Conclusions This pilot study found promising predictive powers of two frailty scores, namely CFS and mFI-11, which were comparable to age and STESS predictors regarding the GOS at hospital discharge and three months later in ICU patients with SE. Among biomarkers and biochemical parameters, only serum troponin T level affected GOS at hospital discharge

Paraspinal muscle volume in patients with Scheuermann’s Kyphosis

Purpose: To measure the cross-sectional area (CSA) of paraspinal muscles in Scheuermann’s kyphosis (SK) patients. Methods:  Preoperative MRI images of 16 SK patients were analysed and compared to 16 patients with normal MRI images (CG, control group). The CSAs were measured at L3-4 and L4-5.Results: Both groups showed similar demographics and patient characteristics. The multifidus muscles CSA were found to be significantly smaller at L3/4 level in SKG (p=0.022 on the left and p=0.016 on the right side compared to CG). There was no significant change in multifidus CSA found at L4/5. The mean CSA of the extensor spinae muscles group were significantly smaller at all levels in the SKG: p=0.001 bilaterally at L3/4 level and p=0.015 right side and p=0.009 left side at L4/5 level. Conclusions: This study shows that patients with SK deformity have significantly smaller CSA of lumbar multifidus and extensor spinae muscles

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan–Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson’s chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC