Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

IMPORTANCE: Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. OBJECTIVE: To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). INTERVENTIONS: Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day survival. RESULTS: Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed; P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05]; P = .47). There were no unexpected treatment-related severe adverse events in either group. CONCLUSION AND RELEVANCE: Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02875873.

Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

Importance: Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective: To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants: Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions: Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures: The primary end point was 90-day survival. Results: Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11; P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance: Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02875873.

A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial.

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P = 0.03). Grade ≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade ≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225.

Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution's Main Source of Income Influence the Results? An Analysis of 21,103 Patients.

OBJECTIVE: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions' main source of income (public or private). DESIGN: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014. SETTINGS: Brazilian public and private institutions. PATIENTS: Patients with sepsis admitted in the participant institutions. INTERVENTIONS: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle. MEASUREMENTS AND MAIN RESULTS: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods. CONCLUSION: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Experimental conical-head abutment screws on the microbial leakage through the implant-abutment interface: an in vitro analysis using target-specific DNA probes.

OBJECTIVES: The aim of this in vitro study was to identify and quantify up to 38 microbial species from human saliva penetrating through the implant-abutment interface in two different implant connections, external hexagon and tri-channel internal connection, both with conventional flat-head or experimental conical-head abutment screws. MATERIAL AND METHODS: Forty-eight two-part implants with external hexagon (EH; n = 24) or tri-channel internal (TI; n = 24) connections were investigated. Abutments were attached to implants with conventional flat-head or experimental conical-head screws. After saliva incubation, Checkerboard DNA-DNA hybridization was used to identify and quantify up to 38 bacterial colonizing the internal parts of the implants. Kruskal-Wallis test followed by Bonferroni's post-tests for multiple comparisons was used for statistical analysis. RESULTS: Twenty-four of thirty-eight species, including putative periodontal pathogens, were found colonizing the inner surfaces of both EH and TI implants. Peptostreptococcus anaerobios (P = 0.003), Prevotella melaninogenica (P < 0.0001), and Candida dubliniensis (P < 0.0001) presented significant differences between different groups. Means of total microbial count (×104 , ±SD) for each group were recorded as follows: G1 (0.27 ± 2.04), G2 (0 ± 0), G3 (1.81 ± 7.50), and G4 (0.35 ± 1.81). CONCLUSIONS: Differences in the geometry of implant connections and abutment screws have impacted the microbial leakage through the implant-abutment interface. Implants attached with experimental conical-head abutment screws showed lower counts of microorganisms when compared with conventional flat-head screws.

Alternatives for the enforcement of the right to health in Brazil.

In this article, the right to health is discussed as a social right and an essential requisite in the construction and guarantee of human rights, more precisely human dignity, considering this right as a complex but effective process in the transformation of the social reality. In the first place, the activities of the public power and its difficulties to guarantee universal access to health are highlighted. This scenario ends up inhibiting the practice of the right to health and prevents users from enjoying and using it. In that sense, this article challenges and explores some alternatives to solidify and put in practice the right to health in Brazil. Departing from the analysis of the Unified Health System (SUS) and social participation in Brazil, this article discusses the judicialization of health in the country, highlighting the difficulties the State faces to equitably offer universal healthcare to society. This context offers an opportunity for reflection and a paradigm change, from the "judicialization of health" to the "judicialization of health policies." Finally, the public health policies adopted by other countries are emphasized, in the attempt to construct the empowerment of human beings in the practice of their rights, particularly social participation and the discussion about the States' responsibility to put their citizens' right to health in practice. In conclusion, the political and collective construction of the right to health needs to be encouraged, distinguishing the legitimate interests of the different interlocutors involved.

Carbohydrate Management in Athletes with Type 1 Diabetes in a 10 km Run Competition.

The aim of this study was to identify the real consumption of CHO during a 10 km competitive run, to compare data with the recommended quantities according to current guidelines, and to analyse the clinical events associated with these different amounts. Protocol 1: observational study including 31 athletes with T1D and 127 athletes without diabetes, comparing data taken from dietary records of CHO intake on the competition day. Protocol 2: single-blind randomized trial in 18 athletes with T1D, testing a pre-exercise CHO supplement of 0.7 g CHO·kg(- 1) (n=10) or 0.35 g CHO·kg(- 1) (n=8). The results showed that T1D athletes consumed a lower quantity of CHO than athletes without diabetes at their usual breakfast and during the meal taken<1 h after the competition, but no differences were found in the supplement taken before the competition. In the randomized study, athletes consuming the higher dose of CHO (0.7 g CHO·kg(- 1)) showed increased glycemic levels, comparing with the lower dose (0.35 g CHO·kg(- 1)). In conclusion, athletes with T1D seem to increase CHO intake prior to the competition consuming similar amounts to those athletes without diabetes, but consuming smaller quantities of CHO than the recommended amounts. This appears to induce a more stable glycemic response, in comparison with supplements with high-CHO content.

[Sistematic review on the influence of leadership style on job satisfaction of health professionals]. / Revisión sistemática sobre la influencia del estilo de liderazgo en la satisfacción laboral de los profesionales de la salud.

INTRODUCTION AND OBJECTIVES: Healthcare organisations are highly complex entities that live with a high risk of instability. In order to minimise this instability, interactions and personal relationships play a major role and accordingly the figure of the leader gains full significance. The leadership style used can produce different reactions and lead to multiple outcomes, including job satisfaction. The aim of the present review is to correlate leadership style with job satisfaction in healthcare professionals. MATERIAL AND METHODS: A systematic review was carried out in BVS, Cochrane plus, CINAHL, ApaPsycinfo and Pubmed, selecting publications that mentioned leadership styles and job satisfaction in healthcare professionals. Publications search strategy were limited for the 5-10last years, full text availability and language of writing: English, French and Spanish. Review-type publications were excluded. Of the 1566 initial titles, 15 were selected for analysis. RESULTS AND CONCLUSIONS: The transformational style showed the highest number of positive correlations, followed by the authentic and transactional styles. On the other hand, the passive and laissez-faire styles showed a negative correlation regardless of the professional category to which they belonged. The results of this study provide a starting point for adopting effective leadership styles to optimise the recruitment and training processes of staff in management and coordination roles.

Capivasertib and fulvestrant for patients with hormone receptor-positive advanced breast cancer: characterization, time course, and management of frequent adverse events from the phase III CAPItello-291 study.

BACKGROUND: Capivasertib is a potent, selective pan-AKT inhibitor. In CAPItello-291, the addition of capivasertib to fulvestrant resulted in a statistically significant (P < 0.001) improvement in progression-free survival over fulvestrant monotherapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer and disease progression on or after aromatase inhibitor-based therapy. Characterization of the capivasertib-fulvestrant adverse event (AE) profile as managed in CAPItello-291 can inform future management guidance and optimize clinical benefit. PATIENTS AND METHODS: Seven hundred and eight patients were randomized 1 : 1 to capivasertib (400 mg twice daily; 4 days on, 3 days off) or placebo, plus fulvestrant, on a 4-week cycle. Dose reductions/interruptions for capivasertib/placebo were permitted (up to two dose reductions). Safety analyses included exposure, AE, and clinical laboratory data and were conducted in patients who received at least one dose of capivasertib, fulvestrant, or placebo. Frequent AEs associated with phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) pathway inhibition (diarrhea, rash, hyperglycemia) were characterized using group terms. AEs were summarized using descriptive statistics; time-to-event analyses were conducted. RESULTS: Safety analyses included 705 patients: capivasertib-fulvestrant (n = 355) and placebo-fulvestrant (n = 350). Frequent any-grade AEs with capivasertib-fulvestrant were diarrhea (72.4%), rash (38.0%), and nausea (34.6%); frequent grade ≥3 AEs were rash (12.1%), diarrhea (9.3%), and hyperglycemia (2.3%). Diarrhea, rash, and hyperglycemia occurred shortly after starting capivasertib-fulvestrant [median days to onset (interquartile range) of any grade: 8 (2-22), 12 (10-15), and 15 (1-51), respectively], and were managed with supportive medications, dose reductions, interruptions, and/or discontinuation. Discontinuation rates were 2.0%, 4.5%, and 0.3%, respectively. Overall, 13.0% discontinued capivasertib due to AEs. CONCLUSIONS: Frequent AEs associated with PI3K/AKT pathway inhibition occurred early and were manageable. The low rate of treatment discontinuations suggests that, when appropriately managed, these AEs do not pose a challenge to clinical benefit.

Examining the role of social vulnerability, neighborhood characteristics, and geospatial patterns of firearm-related injuries and clinical outcomes in Milwaukee county.

BACKGROUND: Previous work has shown socioenvironmental factors can influence firearm injury. Milwaukee County, Wisconsin is a diverse midwestern county with historic disinvestment in marginalized communities yielding stark segregation along racial and ethnic lines. It is also one of the many U.S. counties burdened by surging firearm injuries. The differences among communities within Milwaukee County provides a unique opportunity to explore the intersection of socioenvironmental factors that may affect clinical outcomes and geospatial patterns of firearm injury. METHODS: The trauma registry from the regional adult level 1 trauma center was queried for patients who sustained a firearm-related injury from 2015 to 2022 (N = 2402). The Social Vulnerability Index (SVI) ranking was derived using patient residence addresses to evaluate its association with traumatic injury clinical outcomes (i.e., in-hospital mortality, length of hospital stay, ICU or ventilator treatment, or injury severity score) and risk screening results for alcohol use disorder (AUD), posttraumatic stress disorder (PTSD), and depression. We evaluated hotspots of firearm injury density over time for patient residences and injury locations and distances between locations. A spatially lagged regression model tested the association between firearm injury density and SVI domains, alcohol outlet types, and park coverage. RESULTS: Most firearm injury patients were younger, male, racial or ethnic minorities from disadvantaged neighborhoods (SVI total; M = 0.86, SD = 0.15). SVI was not associated with any clinical outcomes. Of those screened, 12.9% screened positive for AUD and 44.5% screened at risk for PTSD, depression, or both. Hotspot analysis indicated consistent concentrations of firearm injury density. There were no differences in clinical outcomes between those injured inside or outside the home. Census tracts with lower socioeconomic status, greater off-premises and lower on-premises alcohol outlet density were associated with greater firearm injury density. CONCLUSIONS: In Milwaukee County, firearm injury patients are injured in and often return to the same disadvantaged neighborhoods that may hamper recovery. Results replicate and expand previous work and implicate specific socioenvironmental factors for intervention and prevention of firearm injury.

Anthocyanin-Loaded Polymers as Promising Nature-Based, Responsive, and Bioactive Materials.

Anthocyanins are a specific group of molecules found in nature that have recently received increasing attention due to their interesting biological and colorimetric properties that have been successfully applied in several fields such as food preservation and biomedicine. Consequently, reviews devoted to a general overview of these flavonoids have proliferated in recent years. Meanwhile, the incorporation of anthocyanins into polymeric systems has become an interesting strategy to widen the applicability of these molecules and develop new smart and functional polymers in the above cited areas. However, anthocyanin-based polymers have been scarcely reviewed in the literature. Accordingly, this review aims to be a systematic summary of the most recent approaches for the incorporation of anthocyanins into macro-, micro-, or nanostructured polymers. Moreover, this work describes the fundamentals of the applicability of smart anthocyanin-based polymers and offers an updated review of their most interesting applications as sensors, biological regulators, and active materials.

One year follow-up in a group of half-marathon runners with type-1 diabetes treated with insulin analogues.

AIM: The objective was to describe the strategies that type-1 diabetic runners treated with insulin analogues apply in a half-marathon race and the changes after a year of experience participating in long-distance athletic competitions. METHODS: Fourteen male amateur athletes with type-1 diabetes treated with insulin analogues, participating in two consecutive editions of the same half-marathon were assessed. Data about insulin dosage and carbohydrate intake from their regular daily training and from the two half-marathons were compared. Capillary glycemic values from throughout the competition and in the following 24 h period were monitored and the frequency of hypoglycemia and glucose fluctuations was compared, using MAGE method. RESULTS: During the half-marathon day, athletes reduced total insulin doses a 18.3% in 2006 and 14.2% in 2007, with a reduction of basal insulin (23.3% in 2006 vs 20.4% in 2007, P<0.05) and of short-insulin at breakfast prior to the competition (31.7% in 2006 vs 15.3% in 2007, P<0.001). Carbohydrate consumption during competition was higher in second edition (49.0±16.4 g vs 59.1±11.2 g, P<0.05). Glycaemic excursions, assessed by MAGE, were higher in the first edition (108.1±47.3 mg/dL vs 62.2±45.6 mg/dL, P<0.05). CONCLUSION: Type-1 diabetes athletes, treated with insulin analogues, participating in half-marathon competitions exhibited less insulin reduction in comparison with traditional guidelines and they needed to take an important quantity of carbohydrate supplements to avoid hypoglycemia during and after the competition. We suggest reconsidering traditional recommendations of insulin therapy and carbohydrate supplementation (amount and timing) to athletes treated with current insulin analogues participating in long-distance competitions.

Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil.

BACKGROUND: Mobilization of critically ill patients is safe and may improve functional outcomes. However, the prevalence of mobilization activities of ICU patients in Brazil is unknown. METHODS: A one-day point prevalence prospective study with a 24-hour follow-up period was conducted in Brazil. Demographic data, ICU characteristics, prevalence of mobilization activities, level of patients' mobilization, and main reasons for not mobilizing patients were collected for all adult patients with more than 24hs of ICU stay in the 26 participating ICUs. Mobilization activity was defined as any exercise performed during ICU stay. RESULTS: In total, 358 patients were included in this study. Mobilization activities were performed in 87.4% of patients. Patients received mobilization activities while under invasive mechanical ventilation (44.1%), noninvasive ventilation (11.7%), or without any ventilatory support (44.2%). Passive exercises were more frequently performed [46.5% in all patients; 82.3% in mechanically ventilated patients]. Mobilization activities included in-bed exercise regimen (72.2%). Out-of-bed mobility was reported in 39.9% of mobilized patients, and in 16.3% of patients under invasive mechanical ventilation. The presence of an institutional early mobility protocol was associated with early mobilization (OR, 3.19; 95% CI, 1.23 to 8.22; p = 0.016), and with out-of-bed exercise (OR, 5.80; 95% CI, 1.33 to 25.30; p = 0.02). CONCLUSION: Mobilization activities in critically ill patients in Brazil was highly prevalent, although there was almost no active mobilization in the mechanically ventilated patients. Moreover, the presence of an institutional early mobility protocol was associated with a threefold higher chance of ICU mobilization during that day.

Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial.

BACKGROUND: Transfusion of blood components prior to invasive procedures in cirrhosis patients is high and associated with adverse events. OBJECTIVES: We compared three transfusion strategies prior to central venous catheterization in cirrhosis patients. PATIENTS/METHODS: Single center randomized trial that included critically ill cirrhosis patients with indication for central venous line in a tertiary private hospital in Brazil. INTERVENTIONS: Restrictive protocol, thromboelastometry-guided protocol, or usual care (based on coagulogram). The primary endpoint was the proportion of patients transfused with any blood component (ie, fresh frozen plasma, platelets, or cryoprecipitate). The secondary endpoints included incidence of bleeding and transfusion-related adverse events. RESULTS: A total of 57 patients (19 per group; 64.9% male; mean age, 53.4 ± 11.3 years) were enrolled. Prior to catheterization, 3/19 (15.8%) in the restrictive arm, 13/19 (68.4%) in the thromboelastometry-guided arm, and 14/19 (73.7%) in the coagulogram-guided arm received blood transfusion (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01-0.45; P = .002 for restrictive versus coagulogram-guided arm; OR, 0.09; 95% CI, 0.01-0.56; P = .006 for restrictive versus thromboelastometry-guided arm; and OR, 0.77; 95% CI, 0.14-4.15; P = .931 for thromboelastometry-guided versus coagulogram-guided arm). The restrictive protocol was cost saving. No difference in bleeding, length of stay, mortality, and transfusion-related adverse events was found. CONCLUSIONS: The use of a restrictive strategy is associated with a reduction in transfusion prior to central venous catheterization and costs in critically ill cirrhosis patients. No effect on bleeding was found among the groups.

Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis.

BACKGROUND: Infection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. The aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction. METHODS: A total of 41 patients were prospectively enrolled: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. A total of 17 healthy volunteers were included as a control group. Patients were admitted to the Intensive Care Units and Emergency Rooms of Hospital Sao Paulo (Federal University of Sao Paulo) and Hospital Santa Marcelina, Sao Paulo, Brazil. Toll-like receptor (TLR)2, TLR4, CD11b, CD11c and CD66b expression on neutrophil surfaces and oxidative metabolism measured by non-fluorescent dichlorofluorescein (DCFH) oxidation in neutrophils and monocytes, using whole blood, were evaluated using flow cytometry. Organ dysfunction was measured using the sepsis-associated organ failure assessment (SOFA) score. RESULTS: TLR2 expression on neutrophils was found to be downregulated in septic shock patients compared to healthy volunteers (p = 0.05). No differences were found in CD11b and CD11c expression. CD66b expression was increased in the patient group compared to the control group (p = 0.01). Neutrophil and monocyte oxidative burst was increased in septic patients compared to the control group at baseline and after stimulation with phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) and Staphylococcus aureus (p < 0.001 and p < 0.01, respectively, for neutrophils and monocytes in all tested conditions). A strong correlation was observed between neutrophil and monocyte oxidative metabolism. A SOFA score of 7 discriminated patients between survivors and non-survivors (area under the curve for reactive oxygen species (ROS) was 0.78; p = 0.02). ROS generation in patients with sepsis and septic shock with SOFA scores > 7 was higher than in patients with SOFA scores < 7, both in neutrophils and monocytes. However, oxidative burst in patients with sepsis was as high as in septic shock. CONCLUSION: Surface receptors expression on neutrophils may be modulated across the continuum of sepsis, and enhanced or decreased expression may be found depending on the receptor considered. ROS generation is upregulated both in neutrophils and monocytes in septic patients, and it is differently modulated depending on the stage of the disease and the stimuli used.

[Experimental laparoscopic renal autograft as learning laparoscopic model]. / Autotrasplante renal laparoscópico experimental como modelo de aprendizaje de técnica laparoscópica.

INTRODUCTION: Laparoscopic surgery requires a long training period of time in which the complexity of the training is increased. GOALS: The technique presented in this paper has been developed in order to find an experimental model that allows us to improve the learning of the vascular suture. Our main goal was to evaluate this technique as an experimental model for the vacular anastomosis, not to obtain a functional autotransplant. In this regard, here we summarize our experience during the first two cases performed. MATERIAL AND METHODS: Laparoscopic renal autotransplant was perfomed in female lab pigs weighing 15-20 kg. International Experimental Animal Care rules were accomplished. RESULTS: After sacrifizing the animals, only one case of vascular thrombosis was observed. The other cases showed normal arterial and venous flow. CONCLUSIONS: Experimental Renal Laparoscopic autotransplant constitutes a good surgical model. We are trying to implement the technique in the clinics in the next future.

Readmission to the Intensive Care Unit: Incidence, Risk Factors, Resource Use, and Outcomes. A Retrospective Cohort Study.

RATIONALE: Readmission to the intensive care unit (ICU) is associated with poor clinical outcomes, increased length of ICU and hospital stay, and higher costs. Nevertheless, knowledge of epidemiology of ICU readmissions, risk factors, and attributable outcomes is restricted to developed countries. OBJECTIVES: To determine the effect of ICU readmissions on in-hospital mortality, determine incidence of ICU readmissions, identify predictors of ICU readmissions and hospital mortality, and compare resource use and outcomes between readmitted and nonreadmitted patients in a developing country. METHODS: This retrospective single-center cohort study was conducted in a 40-bed, open medical-surgical ICU of a private, tertiary care hospital in São Paulo, Brazil. The Local Ethics Committee at Hospital Israelita Albert Einstein approved the study protocol, and the need for informed consent was waived. All consecutive adult (≥18 yr) patients admitted to the ICU between June 1, 2013 and July 1, 2015 were enrolled in this study. RESULTS: Comparisons were made between patients readmitted and not readmitted to the ICU. Logistic regression analyses were performed to identify predictors of ICU readmissions and hospital mortality. Out of 5,779 patients admitted to the ICU, 576 (10%) were readmitted to the ICU during the same hospitalization. Compared with nonreadmitted patients, patients readmitted to the ICU were more often men (349 of 576 patients [60.6%] vs. 2,919 of 5,203 patients [56.1%]; P = 0.042), showed a higher (median [interquartile range]) severity of illness (Simplified Acute Physiology III score) at index ICU admission (50 [41-61] vs. 42 [32-54], respectively, for readmitted and nonreadmitted patients; P < 0.001), and were more frequently admitted due to medical reasons (425 of 576 [73.8%] vs. 2,998 of 5,203 [57.6%], respectively, for readmitted and nonreadmitted patients; P < 0.001). Simplified Acute Physiology III score (P < 0.001), ICU admission from the ward (odds ratio [OR], 1.907; 95% confidence interval [CI], 1.463-2.487; P < 0.001), vasopressors need during index ICU stay (OR, 1.391; 95% CI, 1.130-1.713; P = 0.002), and length of ICU stay (P = 0.001) were independent predictors of ICU readmission. After adjusting for severity of illness, ICU readmission (OR, 4.103; 95% CI, 3.226-5.518; P < 0.001), admission source, presence of cancer, use of vasopressors, mechanical ventilation or renal replacement therapy, length of ICU stay, and nighttime ICU discharge were associated with increased risk of in-hospital death. CONCLUSIONS: Readmissions to the ICU were frequent and strongly related to poor outcomes. The degree to which ICU readmissions are preventable as well as the main causes of preventable ICU readmissions need to be further determined.

Defining the optimal sequence for the systemic treatment of metastatic breast cancer.

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.

Study protocol for the Balanced Solution versus Saline in Intensive Care Study (BaSICS): a factorial randomised trial.

BACKGROUND: The effectiveness and safety of balanced crystalloid fluids compared with saline (0.9% sodium chloride) as a fluid of choice in critically ill patients remain unclear. The effects of different fluid infusion rates on outcomes are also unknown. OBJECTIVES: To test the hypothesis that a balanced crystalloid solution, compared with saline, decreases 90-day all-cause mortality among critically ill patients; and to test the hypothesis that slow, compared with rapid, infusion rate decreases 90-day mortality in this population of patients. METHODS: The Balanced Solution versus Saline in Intensive Care Study (BaSICS) is a pragmatic, 2 ??2 factorial, randomised controlled trial. A total of 11 000 patients will be recruited from at least 100 Brazilian intensive care units. Patients will be randomised to receive Plasma-Lyte 148 or saline, and to rapid infusion (999 mL/h) or slow infusion (333 mL/h). Study fluids will be used for resuscitation episodes (at rapid or slow infusion rates), dilution of compatible medications and maintenance solutions. Patients, health care providers and investigators will be blinded to the solutions being tested. The rate of bolus infusion will not be blinded. OUTCOMES: The primary outcome is 90-day all-cause mortality. Secondary outcomes are: incidence of renal failure requiring renal replacement therapy within 90 days, incidence of acute kidney injury (Kidney Disease: Improving Global Outcomes stages 2 and 3), incidence of non-renal organ dysfunction assessed by Sepsis-related Organ Failure Assessment score at Days 3 and 7, and number of mechanical ventilationfree days within the first 28 days after randomisation. RESULTS AND CONCLUSIONS: The BaSICS trial will provide robust evidence on whether a balanced crystalloid, compared with saline, improves important patient outcomes in critically ill patients. BaSICS will also provide relevant information on whether bolus infusion rate affects outcomes in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02875873.