OBJECTIVES:To assess the impact of rehabilitation in ICU on clinical outcomes.
DATA SOURCES:Secondary data analysis of randomized controlled trials published between 1998 and October 2019 was ...performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
STUDY SELECTION:We have selected trials investigating neuromuscular electrical stimulation or cycling exercises or protocolized physical rehabilitation as compared to standard of care in critically ill adults.
DATA EXTRACTION:Mortality, length of stay in ICU and at hospital, days on mechanical ventilator, and adverse events.
DATA SYNTHESIS:We found 43 randomized controlled trials (nine on cycling, 14 on neuromuscular electrical stimulation alone and 20 on protocolized physical rehabilitation) into which 3,548 patients were randomized and none of whom experienced an intervention-related serious adverse event. The exercise interventions had no influence on mortality (odds ratio 0.94 0.79–1.12, n = 38 randomized controlled trials) but reduced duration of mechanical ventilation (mean difference, –1.7 d –2.5 to –0.8 d, n = 32, length of stay in ICU (–1.2 d –2.5 to 0.0 d, n = 32) but not at hospital (–1.6 –4.3 to 1.2 d, n = 23). The effects on the length of mechanical ventilation and ICU stay were only significant for the protocolized physical rehabilitation subgroup and enhanced in patients with longer ICU stay and lower Acute Physiology and Chronic Health Evaluation II scores. There was no benefit of early start of the intervention. It is likely that the dose of rehabilitation delivered was much lower than dictated by the protocol in many randomized controlled trials and negative results may reflect the failure to implement the intervention.
CONCLUSIONS:Rehabilitation interventions in critically ill patients do not influence mortality and are safe. Protocolized physical rehabilitation significantly shortens time spent on mechanical ventilation and in ICU, but this does not consistently translate into long-term functional benefit. Stable patients with lower Acute Physiology and Chronic Health Evaluation II at admission (<20) and prone to protracted ICU stay may benefit most from rehabilitation interventions.
Abstract
Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is ...usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years,
P
= 0.007) and 5-year survival (29.4% vs. 64.6%,
P
= 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years,
P
= 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years,
P
= 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years,
P
< 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.
Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome.
We ...searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality.
Knowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose.
PRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pancreatic carcinoma remains one of the leading cancer-related causes of death worldwide and is generally characterized by a dismal prognosis and limited potential for oncologic treatment. A rare ...subvariant of pancreatic cancer, undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), has an unpredictable prognosis according to many previous studies, with unexpectedly long survival in individual cases. In this study, we collected, retrospectively, 13 cases of well-documented UCOGCs and performed immunohistochemistry focused on the expression of the programmed death-ligand 1 (PD-L1) and several other potential therapeutic and predictive markers (PanTRK, p53, MSH2, PMS2, and the number of tumor-infiltrating lymphocytes), to explore their correlation with the follow-up of the patients. As a control group, we examined 24 cases of conventional pancreatic ductal adenocarcinoma (PDAC). In our results, PanTRK was negative in all 24 cases. P53 did not show any significant differences between UCOGCs and PDACs, and the entire cohort was MSH2, MLH1, PMS2, and MSH6 positive. Significant differences were present in the analysis of PD-L1: UCOGCs were found to express PD-L1 significantly more frequently and have a higher number of tumor-infiltrating lymphocytes than PDAC. The expression of PD-L1 was related to significantly shorter survival in patients with UCOGC and in the entire cohort. Patients with PD-L1 negative UCOGCs displayed surprisingly long survival in comparison to PD-L1 positive UCOGCs and PDACs (both PD-L1+ and PD-L1−). We compared our results with previously published data, and, after statistical analysis, we were able to identify PD-L1 as an effective prognostic marker of UCOGC and suggest a strong need for a clinical trial of immune checkpoint immunotherapy in patients with advanced PD-L1 positive UCOGC.
Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms ...of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.
This study aimed to analyze the influence of the hospital admitting department on adherence to the Guidelines of European Society of Cardiology for management of acute coronary syndromes in patients ...after out-of-hospital cardiac arrest (OHCA) of coronary etiology.
We studied retrospective-prospective register of 102 consecutive patients with OHCA as a manifestation of acute coronary syndrome (ACS). Patients were admitted to the coronary care unit (CCU) 52, general intensive care unit (GICU) 21, or GICU after initial Cath lab treatment (CAG-GICU) 29. This study compared the differences in the management of ACS in patients with OHCA of coronary etiology based on the admitting department in a tertiary care institution.
Twelve of the 21 (57.1%) patients admitted to the GICU were evaluated as having ACS on-site where they experienced OHCA. In the CCU group, 50 out of 52 (96.2%) and 28 of 29 (100%) patients in the CAG-GICU group (P<0.001). Coronary angiography was performed in 10 of 21 patients (48%) admitted to the GICU. It was performed in 49 out of 52 (94%) CCU patients and, in the CAG-GICU group, 28 out of 29 patients. The mean time to CAG differed significantly across groups (that is, GICU 200.7 min., CCU 71.2 min., and CAG-GICU 7.5 min. (P<0.001)). Aspirin was used in 48% of GICU, 96% of CCU, and 79% of CAG-GICU patients (P<0.001), while in the pre-hospital phase, aspirin was used in 9.5% of GICU, 71.2% of CCU, and 50% of CAG-GICU patients (P<0.001). P2Y12 inhibitor prescriptions were lower in patients admitted to the GICU (33% vs. 89% CCU and 57% CAG-GICU, P<0.001). The department's choice significantly affected the time to initiation of antithrombotics, which was the longest in the GICU.
The choice of admission department for patients with OHCA caused by ACS was found to affect the extent to which the recommended treatments were used. An examination of OHCA patients by a cardiologist upon admission to the hospital increased the likelihood of an early diagnosis of ACS as the cause of OHCA.
Abstract
Context
Impaired diurnal blood pressure (BP) variability is related to higher cardiovascular risk.
Objective
To assess diurnal variability of BP and its relation to target organ damage (TOD) ...and catecholamine phenotype in a consecutive sample of pheochromocytoma/paraganglioma (PPGL).
Design
We included 179 patients with PPGL All patients underwent 24 hours of ambulatory BP monitoring to determine dipping status. Differences in plasma metanephrine or urine adrenaline were used to distinguish catecholamine biochemical phenotype. To evaluate TOD, renal functions, presence of left ventricle hypertrophy (LVH), and the subgroup (n = 111) carotid-femoral pulse wave velocity (PWV) were assessed. Structural equation modeling was used to find the relationship among nocturnal dipping, catecholamine phenotype, and TOD parameters.
Results
According to the nocturnal dipping, patients were divided into the three groups: dippers (28%), nondippers (40%), and reverse dippers (32%). Reverse dippers were older (P < 0.05), with a higher proportion of noradrenergic (NA) phenotype (P < 0.05), a higher prevalence of diabetes mellitus (P < 0.05), and sustained arterial hypertension (P < 0.01) and its duration (P < 0.05), as opposed to the other groups. All parameters of TOD were more pronounced only in reverse dippers compared with nondippers and dippers. The presence of NA phenotype (=absence of adrenaline production) was associated with reverse dipping and TOD (LVH and PWV).
Conclusions
Patients with reverse dipping had more substantial TOD compared with other groups. The NA phenotype plays an important role, not only in impaired diurnal BP variability but also independently from dipping status in more pronounced TOD of heart and vessels.
Predominantly pure noradrenaline, without concomitant adrenaline overproduction, has a long-term effect on the cardiovascular system in pheochromocytoma/functional paraganglioma.
Impaired myocardial bioenergetics is a hallmark of many cardiac diseases. There is a need of a simple and reproducible method of assessment of mitochondrial function from small human myocardial ...tissue samples. In this study we adopted high-resolution respirometry to homogenates of fresh human cardiac muscle and compare it with isolated mitochondria. We used atria resected during cardiac surgery (n = 18) and atria and left ventricles from brain-dead organ donors (n = 12). The protocol we developed consisting of two-step homogenization and exposure of 2.5% homogenate in a respirometer to sequential addition of 2.5 mM malate, 15 mM glutamate, 2.5 mM ADP, 10 μM cytochrome c, 10 mM succinate, 2.5 μM oligomycin, 1.5 μM FCCP, 3.5 μM rotenone, 4 μM antimycin and 1 mM KCN or 100 mM Sodium Azide. We found a linear dependency of oxygen consumption on oxygen concentration. This technique requires < 20 mg of myocardium and the preparation of the sample takes <20 min. Mitochondria in the homogenate, as compared to subsarcolemmal and interfibrillar isolated mitochondria, have comparable or better preserved integrity of outer mitochondrial membrane (increase of respiration after addition of cytochrome c is up to 11.7±1.8% vs. 15.7±3.1%, p˂0.05 and 11.7±3.5%, p = 0.99, resp.) and better efficiency of oxidative phosphorylation (Respiratory Control Ratio = 3.65±0.5 vs. 3.04±0.27, p˂0.01 and 2.65±0.17, p˂0.0001, resp.). Results are reproducible with coefficient of variation between two duplicate measurements ≤8% for all indices. We found that whereas atrial myocardium contains less mitochondria than the ventricle, atrial bioenergetic profiles are comparable to left ventricle. In conclusion, high resolution respirometry has been adapted to homogenates of human cardiac muscle and shown to be reliable and reproducible.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-carbonic buffer power (β
NC
) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van ...Slyke equation used for Base excess estimation in blood. So far, β
NC
has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO
2
tonometry to assess β
NC
in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cell membrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The β
NC
of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of β
NC
and pCO
2
on the Base excess of blood was examined. In the control samples, β
NC
was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that β
NC
rose by 0.36 mmol/L for each 1 mEq/l reduction in plasma strong ion difference (
p
< 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO
2
titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium was more pronounced in lactic acidosis. Lastly, we found that the rise of β
NC
in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO
2
.
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