This study was undertaken to evaluate the clinical characteristics and outcomes of patients with cancer requiring nonpalliative ventilatory support.
This was a secondary analysis of a prospective ...cohort study conducted in 28 Brazilian ICUs evaluating adult patients with cancer requiring invasive mechanical ventilation (MV) or noninvasive ventilation (NIV) during the first 48 h of their ICU stay. We used logistic regression to identify the variables associated with hospital mortality.
Of 717 patients, 263 (37%) (solid tumors = 227; hematologic malignancies = 36) received ventilatory support. NIV was initially used in 85 patients (32%), and 178 (68%) received MV. Additionally, NIV followed by MV occurred in 45 patients (53%). Hospital mortality rates were 67% in all patients, 40% in patients receiving NIV only, 69% when NIV was followed by MV, and 73% in patients receiving MV only (P < .001). Adjusting for the type of admission, newly diagnosed malignancy (OR, 3.59; 95% CI, 1.28-10.10), recurrent or progressive malignancy (OR, 3.67; 95% CI, 1.25-10.81), tumoral airway involvement (OR, 4.04; 95% CI, 1.30-12.56), performance status (PS) 2 to 4 (OR, 2.39; 95% CI, 1.24-4.59), NIV followed by MV (OR, 3.00; 95% CI, 1.09-8.18), MV as initial ventilatory strategy (OR, 3.53; 95% CI, 1.45-8.60), and Sequential Organ Failure Assessment score (each point except the respiratory domain) (OR, 1.15; 95% CI, 1.03-1.29) were associated with hospital mortality. Hospital survival in patients with good PS and nonprogressive malignancy and without tumoral airway involvement was 53%. Conversely, patients with poor functional capacity and cancer progression had unfavorable outcomes.
Patients with cancer with good PS and nonprogressive disease requiring ventilatory support should receive full intensive care, because one-half of these patients survive. On the other hand, provision of palliative care should be considered the main goal for patients with poor PS and progressive underlying malignancy.
This work describes the chemical composition of MeOH seeds and flowers extracts of Tapirira guianensis, a known tree that occurs in the Brazilian Atlantic forest. The CH2Cl2 soluble fraction of seeds ...extract was submitted to chromatographic procedures to obtain a mixture of new alkenyl dihydrobenzofuranoids which were identified as 2-(10’Z)-dodec-10’-enyl-dihydro-1-benzofuran-5-ol, 2-(10’Z)-tridec-10’-enyl-dihydro-1-benzofuran-5-ol e 2-(10’Z)-pentadec-10’-enyl-dihydro-1-benzofuran-5-ol (1 - 3) besides β-sitosterol. From the EtOAc soluble fraction of flowers MeOH extract quercetin, quercitrin and gallic acid were obtained by chromatographic techniques. The fatty acid composition of oils from leaves and seeds were also determinate and the leaves’ oil is composed by 63.94% of saturated and 36.04% of unsaturated fatty acids while in the seeds the oil present 42.13% of saturated and 57.87% of unsaturated. All compounds and derivatives were identified by their spectrometric data analysis. The brine shrimp test of the extracts showed the seed CH2Cl2 and the EtOAc and BuOH soluble fractions of the flowers were actives and, the alkyl phenols are the responsible for this moderate activity. The antioxidant tests of the extracts indicated EtOAc soluble fraction of MeOH extract of flowers showed better results possibly due the presence of flavonoids and gallic acid.
The Surviving Sepsis Campaign (SSC or "the Campaign") developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior ...(process improvement) via bundles based on key SSC guideline recommendations.
A multifaceted intervention to facilitate compliance with selected guideline recommendations in the intensive care unit, emergency department, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the United States, Europe, and South America. Elements of the guidelines were "bundled" into two sets of targets to be completed within 6 hrs and within 24 hrs. An analysis was conducted on data submitted from January 2005 through March 2008.
A total of 15,022 subjects.
Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 yrs (p = .008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p = .001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 yrs (95% confidence interval, 2.5-8.4).
The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.
Objective
The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical ...behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes.
Design and setting
A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008.
Main results
Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (
P
< 0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (
P
= 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (
P
= 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5–8.4%).
Conclusions
The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.
Approximately 600-700 species of Ipomoea, Convolvulaceae, are found throughout tropical and subtropical regions of the world. Several of those species have been used as ornamental plants, food, ...medicines or in religious ritual. The present work reviews the traditional uses, chemistry and biological activities of Ipomoea species and illustrates the potential of the genus as a source of therapeutic agents. These species are used in different parts of the world for the treatment of several diseases, such as, diabetes, hypertension, dysentery, constipation, fatigue, arthritis, rheumatism, hydrocephaly, meningitis, kidney ailments and inflammations. Some of these species showed antimicrobial, analgesic, spasmolitic, spasmogenic, hypoglycemic, hypotensive, anticoagulant, anti-inflammatory, psychotomimetic and anticancer activities. Alkaloids, phenolics compounds and glycolipids are the most common biologically active constituents from these plant extracts.
In the developing retina, precise coordination of cell proliferation, differentiation, and survival is essential for proper retinal maturation and function. We have previously reported evidence that ...interleukin-4 (IL-4) plays critical roles in neuronal differentiation and survival during retinal development. However, little is known about the role of IL-4 on retinal cell proliferation. In the current study, we investigated if IL-4 regulates cell proliferation induced by epidermal growth factor (EGF) and by fibroblast growth factor 2 (FGF2) in primary retinal cell cultures obtained from newborn rats. First, we show that EGF and FGF2 act as mitogens for glial cells, increasing proliferation of these cells in the retina. EGF- and FGF2-induced mitogenesis requires activation of distinct cell-intrinsic signals. In retinal cells exposed to FGF2, IL-4 downregulates p53 levels (a protein whose activation induces cell-cycle arrest) and increases mitogenic responsiveness to FGF2 through activation of protein kinase A (PKA) pathway. Conversely, in retinal cells exposed to EGF, IL-4 downregulates cyclin D1 levels (a protein required for cell-cycle progression), upregulates p53 levels, and decreases mitogenic responsiveness to EGF. The inhibitory effect induced by IL-4 on retinal cells exposed to EGF requires activation of Janus kinase 3 (JAK3), but not activation of PKA. Based on previous and current findings, we propose that IL-4 serves as a node of signal divergence, modulating multiple cell-intrinsic signals (e.g., cyclin D1, p53, JAK3, and PKA) and mitogenic responsiveness to cell-extrinsic signals (e.g., FGF2 and EGF) to control cell proliferation, differentiation, and survival during retinal development.
•EGF and FGF2 increase cell proliferation, acting as mitogens for retinal glial cells.•EGF- and FGF2-induced retinal cell proliferation requires distinct cell-intrinsic signals.•IL-4 ensures homeostatic proliferation by controlling mitogenic responsiveness to EGF and FGF2.•IL-4 increases mitogenic responsiveness to FGF2 through PKA activation and p53 downregulation.•IL-4 decreases mitogenic responsiveness to EGF through JAK3 activation, p53 upregulation, and cyclin D1 downregulation.
Trophic factors are involved in different cellular responses. Previously we demonstrated that IL-4 treatment induces an increase in retinal ganglion cell survival (RGCS) and regulates cholinergic ...differentiation of retinal cells in vitro. Data from literature show that IGF-1 also promotes RGCS, an effect mediated by PI-3K/AKT pathway. The aim of this study was to investigate the role of IGF-1 and IGF-1R on RGCS mediated by IL-4 treatment and the role of M1 acetylcholine receptors in this effect. Here we show that the effect of IL-4 on RGCS depends on IGF-1 and IGF-1R activation, the PI-3K/AKT and NFkB intracellular pathways and depends on M1 mAChRs activation. IGF-1 increases the levels of M1 mAChRs in 15min, 45min, 24 h and 48 h in mixed retinal cells culture, modulates the levels of IL-4, pIGF-1R, IGF-1R. IL-4 modulates IGF-1, pIGF-1R and IGF-1R levels in different time intervals. These results put in evidence a crosstalk between IL-4 and IGF-1 and a role of M1 mAChRs, IGF-1 and IGF-1R in RGCS mediated by IL-4.
•IL-4 depends on IGF-1 to mediate RGCS.•The RGCS induced by IGF-1 depends on M1-mAChRs.•IGF-1 regulates the levels of M1-mAChRs.•Crosstalk between IL-4 and IGF-1 in RCC.•IL-4 treatment activates IGF-1Rs.
Current guidelines and consensus recommend arterial and venous samples as equally acceptable for blood glucose assessment in point-of-care devices, but there is limited evidence to support this ...recommendation. We evaluated the accuracy of two devices for bedside point-of-care blood glucose measurements using arterial, fingerstick and catheter venous blood samples in ICU patients, and assessed which factors could impair their accuracy.
145 patients from a 41-bed adult mixed-ICU, in a tertiary care hospital were prospectively enrolled. Fingerstick, central venous (catheter) and arterial blood (indwelling catheter) samples were simultaneously collected, once per patient. Arterial measurements obtained with Precision PCx, and arterial, fingerstick and venous measurements obtained with Accu-chek Advantage II were compared to arterial central lab measurements. Agreement between point-of-care and laboratory measurements were evaluated with Bland-Altman, and multiple linear regression models were used to investigate interference of associated factors.
Mean difference between Accu-chek arterial samples versus central lab was 10.7 mg/dL (95% LA -21.3 to 42.7 mg/dL), and between Precision PCx versus central lab was 18.6 mg/dL (95% LA -12.6 to 49.5 mg/dL). Accu-chek fingerstick versus central lab arterial samples presented a similar bias (10.0 mg/dL) but a wider 95% LA (-31.8 to 51.8 mg/dL). Agreement between venous samples with arterial central lab was the poorest (mean bias 15.1 mg/dL; 95% LA -51.7 to 81.9). Hyperglycemia, low hematocrit, and acidosis were associated with larger differences between arterial and venous blood measurements with the two glucometers and central lab. Vasopressor administration was associated with increased error for fingerstick measurements.
Sampling from central venous catheters should not be used for glycemic control in ICU patients. In addition, reliability of the two evaluated glucometers was insufficient. Error with Accu-chek Advantage II increases mostly with central venous samples. Hyperglycemia, lower hematocrit, acidosis, and vasopressor administration increase measurement error.
Early identification and treatment of severe sepsis can significantly reduce mortality rate. We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to ...standard care should be significantly related to 28-day survival.
Analysis of organ dysfunction data from two placebo-controlled severe sepsis trials (PROWESS and secretory phospholipase A2 inhibitor trials).
Research laboratory.
The placebo arms of two randomized, double-blind sepsis trials were combined (n = 1036). These patients met criteria for severe sepsis and received supportive standard intensive care and fluid resuscitation.
None.
Sequential Organ Failure Assessment (SOFA) scores were calculated daily using the most aberrant physiologic or laboratory variables. Baseline and post-baseline SOFA scores categorized as improved, unchanged, or worsened were used in regression analyses correlating organ dysfunction changes with 28-day mortality. Improvement in cardiovascular (p = .0010), renal (p < .0001), or respiratory (p = .0469) function from baseline to day 1 was significantly related to survival. Odds ratios (95% confidence intervals) associated with improved vs. worsened respiratory, cardiovascular, or renal function before start of day 1 were 0.56 (0.35-0.91), 0.33 (0.18-0.59), and 0.30 (0.17-0.52), respectively. Continued improvement in cardiovascular function before start of day 2 and start of day 3 was associated with further improvement in survival (p <. 0001), with odds ratios of 0.15 (0.06-0.39) and 0.11 (0.04-0.31) for patients who improved compared with those who worsened. No other organ system was retained in the model, and improvement beyond day 1 in any other organ function did not add to the model's predictive power.
These analyses suggest that outcomes for patients with severe sepsis are closely related to early (baseline to day 1 here) improvement, or lack thereof, in organ function. Also, clinical improvement on subsequent days may have little additional impact on the likelihood of survival.
Cancer patients are at risk for severe complications related to the underlying malignancy or its treatment and, therefore, usually require admission to intensive care units (ICU). Here, we evaluated ...the clinical characteristics and outcomes in this subgroup of patients.
Secondary analysis of two prospective cohorts of cancer patients admitted to ICUs. We used multivariable logistic regression to identify variables associated with hospital mortality.
Out of 2,028 patients, 456 (23%) had cancer-related complications. Compared to those without cancer-related complications, they more frequently had worse performance status (PS) (57% vs 36% with PS≥2), active malignancy (95% vs 58%), need for vasopressors (45% vs 34%), mechanical ventilation (70% vs 51%) and dialysis (12% vs 8%) (P<0.001 for all analyses). ICU (47% vs. 27%) and hospital (63% vs. 38%) mortality rates were also higher in patients with cancer-related complications (P<0.001). Chemo/radiation therapy-induced toxicity (6%), venous thromboembolism (5%), respiratory failure (4%), gastrointestinal involvement (3%) and vena cava syndrome (VCS) (2%) were the most frequent cancer-related complications. In multivariable analysis, the presence of cancer-related complications per se was not associated with mortality odds ratio (OR) = 1.25 (95% confidence interval, 0.94-1.66), P = 0.131. However, among the individual cancer-related complications, VCS OR = 3.79 (1.11-12.92), P = 0.033, gastrointestinal involvement OR = 3.05 (1.57-5.91), P = <0.001 and respiratory failure OR = 1.96(1.04-3.71), P = 0.038 were independently associated with in-hospital mortality.
The prognostic impact of cancer-related complications was variable. Although some complications were associated with worse outcomes, the presence of an acute cancer-related complication per se should not guide decisions to admit a patient to ICU.