Intraoperative goal-directed hemodynamic therapy through fluid administration to optimize the stroke volume: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the clinical impact of optimizing stroke volume (SV) through fluid administration as part of goal-directed hemodynamic therapy (GDHT) in adult patients undergoing elective major abdominal surgery. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO database in January 2024. The intervention was defined as intraoperative GDHT based on the optimization or maximization of SV through fluid challenges, or by using dynamic indices of fluid responsiveness, including stroke volume variation, pulse pressure variation, and plethysmography variation index compared to usual fluid management. The primary outcome was postoperative complications. Secondary outcome variables included postoperative acute kidney injury (AKI), length of stay (LOS), intraoperative fluid administration, and 30-day mortality. RESULTS: A total of 29 randomized controlled trials (RCTs) met the inclusion criteria. There were no significant differences in the incidence of postoperative complications (RR 0.89; 95% CI, 0.78-1.00), postoperative AKI (OR 0.97; (95% IC, 0.55-1.70), and mortality (OR 0.80; 95% CI, 0.50-1.29). GDHT was associated with a reduced LOS compared to usual care (SMD: -0.17 [-0.32; -0.03]). The subgroup in which hydroxyethyl starch was used for hemodynamic optimization was associated with fewer complications (RR 0.79; 95% CI, 0.65-0.94), whereas the subgroup of patients in whom crystalloids were used was associated with an increased risk of postoperative complications (RR 1.08; 95% CI, 1.04-1.12). CONCLUSIONS: In adults undergoing major surgery, goal-directed hemodynamic therapy focused on fluid-based stroke volume optimization did not reduce postoperative morbidity and mortality.

Guidelines for inhaled sedation in the ICU.

INTRODUCTION AND OBJECTIVES: Sedation is used in intensive care units (ICU) to improve comfort and tolerance during mechanical ventilation, invasive interventions, and nursing care. In recent years, the use of inhalation anaesthetics for this purpose has increased. Our objective was to obtain and summarise the best evidence on inhaled sedation in adult patients in the ICU, and use this to help physicians choose the most appropriate approach in terms of the impact of sedation on clinical outcomes and the risk-benefit of the chosen strategy. METHODOLOGY: Given the overall lack of literature and scientific evidence on various aspects of inhaled sedation in the ICU, we decided to use a Delphi method to achieve consensus among a group of 17 expert panellists. The processes was conducted over a 12-month period between 2022 and 2023, and followed the recommendations of the CREDES guidelines. RESULTS: The results of the Delphi survey form the basis of these 39 recommendations - 23 with a strong consensus and 15 with a weak consensus. CONCLUSION: The use of inhaled sedation in the ICU is a reliable and appropriate option in a wide variety of clinical scenarios. However, there are numerous aspects of the technique that require further study.

Classification of light Yorkshire pigs at different production stages using ordinary least squares and machine learning methods.

Pig homogeneity and growth are major concerns for the pig industry today. Variability in pigs' size has a strong impact on profitability as uniformity plays a key role in the overall economic value of pigs produced. This research focused on statistical methods to identify pigs at risk of growth retardation at different stages of production. Data from 125 083 Yorkshire pigs at weaning (18-28 d), 59 533 pigs at the end of the nursery period (70-82 d) and 48 862 pigs at slaughter (155-170 d) were analyzed under three different cut-points (lowest 10, 20 and 30%) to characterize light animals. Records were randomly split into 2:1 training:testing sets, and each training data set was analyzed through an ordinary least squares approach and four machine learning algorithms (decision tree, random forest, and two alternative boosting approaches). A wide range of weighting functions were applied to give increased relevance to lighter pigs. Each resulting classification norm was used to classify light pigs in the testing data set. Both sensitivity and specificity were retained to construct the receiver operating characteristic curve, and the statistical performance of each analytical approach was evaluated by the area under the curve (AUC). In all production stages and cut-points, the random forest machine learning algorithm provided the highest AUC, closely followed by boosting procedures. For weaning BW (WW), factors related to birth BW and litter size accounted for more than 75% of the important prediction factors for light pigs. BW at the end of the nursery period and slaughter BW analyses revealed a similar pattern where WW and BW at the end of the nursery period accounted for more than 40 and 50% of statistical importance among the prediction factors, respectively. Machine learning algorithms are useful tools to easily evaluate the risk factors affecting the efficiency and homogeneity in swine. Since the BW at birth and weaning are key factors, sow nutrition and feeding management during gestation and lactation, along with piglet management during lactation, are identified as important influences on pig weight variability.

A critical review of the perioperative fluid therapy and hemodynamic monitoring recommendations of the Enhanced Recovery of the Adult Pathway (RICA): A position statement of the fluid therapy and hemodynamic monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR).

In an effort to standardize perioperative management and improve postoperative outcomes of adult patients undergoing surgery, the Ministry of Health, through the Spanish Multimodal Rehabilitation Group (GERM), and the Aragonese Institute of Health Sciences, in collaboration with multiple Spanish scientific societies and based on the available evidence, published in 2021 the Spanish Intensified Adult Recovery (RICA) guideline. This document includes 12 perioperative measures related to fluid therapy and hemodynamic monitoring. Fluid administration and hemodynamic monitoring are not straightforward but are directly related to postoperative patient outcomes. The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR) has reviewed these recommendations and concluded that they should be revised as they do not follow an adequate methodology.

Fluid challenges in operating room: A planned sub study of the Fluid Day observational study.

BACKGROUND: Intraoperative fluid administration is a ubiquitous intervention in surgical patients. But inadequate fluid administration may lead to poor postoperative outcomes. Fluid challenges (FCs), in or outside the so-called goal-directed fluid therapy, allows testing the cardiovascular system and the need for further fluid administration. Our primary aim was to evaluate how anesthesiologists conduct FCs in the operating room in terms of type, volume, variables used to trigger a FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. METHODS: This was a planned substudy of an observational study conducted in 131 centres in Spain in patients undergoing surgery. RESULTS: A total of 396 patients were enrolled and analysed in the study. The median [interquartile range] amount of fluid given during a FC was 250ml (200-400). The main indication for FC was a decrease in systolic arterial pressure in 246 cases (62.2%). The second was a decrease in mean arterial pressure (54.4%). Cardiac output was used in 30 patients (7.58%), while stroke volume variation in 29 of 385 cases (7.32%). The response to the initial FC did not have an impact when prescribing further fluid administration. CONCLUSIONS: The current indication and evaluation of FC in surgical patients is highly variable. Prediction of fluid responsiveness is not routinely used, and inappropriate variables are frequently evaluated for assessing the hemodynamic response to FC, which may result in deleterious effects.

Research priorities in perioperative fluid therapy and hemodynamic monitoring: A Delphi Consensus Survey from the Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR).

BACKGROUND: Research in fluid therapy and perioperative hemodynamic monitoring is difficult and expensive. The objectives of this study were to summarize these topics and to prioritize these topics in order of research importance. METHODS: Electronic structured Delphi questionnaire over three rounds among 30 experts in fluid therapy and hemodynamic monitoring identified through the Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care. RESULTS: 77 topics were identified and ranked in order of prioritization. Topics were categorized into themes of crystalloids, colloids, hemodynamic monitoring and others. 31 topics were ranked as essential research priority. To determine whether intraoperative hemodynamic optimization algorithms based on the invasive or noninvasive Hypotension Prediction Index versus other management strategies could decrease the incidence of postoperative complications. As well as whether the use of renal stress biomarkers together with a goal-directed fluid therapy protocol could reduce hospital stay and the incidence of acute kidney injury in adult patients undergoing non-cardiac surgery, reached the highest consensus. CONCLUSIONS: The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care will use these results to carry out the research.

A new protocol reduces median door-to-needle time to the benchmark of 30 minutes in acute stroke treatment.

INTRODUCTION: Recent analyses emphasise that The Benchmark Stroke Door-to-Needle Time (DNT) should be 30min. This study aimed to determine if a new in-hospital IVT protocol is effective in reducing door-to-needle time and correcting previously identified factors associated with delays. MATERIAL AND METHODS: In 2014, we gradually introduced a series of measures aimed to reduce door-to-needle time for patients receiving IVT, and compared it before (2009-2012) and after (2014-2017) the new protocol was introduced. RESULTS: The sample included 239 patients before and 222 after the introduction of the protocol. Median overall door-to-needle time was 27min after the protocol was fully implemented (a 48% reduction on previous door-to-needle time [52min], P<.001)]. Median door-to-needle time was lower when pre-hospital code stroke was activated (22min). We observed a 26-min reduction in the median time from onset to treatment (P<.001). After the protocol was implemented, the "3-hour-effect" did not affect door-to-needle time (P=.98). Computed tomography angiography studies performed before IVT were associated with increased door-to-needle time (P<.001); however, the test was performed after IVT was started in most cases. CONCLUSIONS: Hospital reorganisation and multidisciplinary collaboration brought median door-to-needle time below 30min and corrected previously identified delay factors. Furthermore, overall time from onset to treatment was also reduced and more stroke patients were treated within 90min of symptom onset.

Intraoperative crystalloid utilization variability and association with postoperative outcomes: A post hoc analysis of two multicenter prospective cohort studies.

BACKGROUND: The optimal regimen for intravenous administration of intraoperative fluids remains unclear. Our goal was to analyze intraoperative crystalloid volume administration practices and their association with postoperative outcomes. METHODS: We extracted clinical data from two multicenter observational studies including adult patients undergoing colorectal surgery and total hip (THA) and knee arthroplasty (TKA). We analyzed the distribution of intraoperative fluid administration. Regression was performed using a general linear model to determine factors predictive of fluid administration. Patient outcomes and intraoperative crystalloid utilization were summarized for each surgical cohort. Regression models were developed to evaluate associations of high or low intraoperative crystalloid with the likelihood of increased postoperative complications, mainly acute kidney injury (AKI) and hospital length of stay (LOS). RESULTS: 7580 patients were included. The average adjusted intraoperative crystalloid infusion rate across all surgeries was to 7.9 (SD 4) mL/kg/h. The regression model strongly favored the type of surgery over other patient predictors. We found that high fluid volume was associated with 40% greater odds ratio (OR 1.40; 95% confidence interval 1.01-1.95, p = 0.044) of postoperative complications in patients undergoing THA, while we found no associations for the other types of surgeries, AKI and LOS CONCLUSIONS: A wide variability was observed in intraoperative crystalloid volume administration; however, this did not affect postoperative outcomes.

The role of miRNAs as biomarkers in prostate cancer.

There is an urged need of non-invasive biomarkers for the implementation of precision medicine. These biomarkers are required to these days for improving prostate cancer (PCa) screening, treatment or stratification in current clinical strategies. There are several commercial kits (Oncotype DX genomic prostate score®, Prolaris®, among others) that use genomic changes, rearrangement or even non-coding RNA events. However, none of them are currently used in the routine clinical practice. Many recent studies indicate that miRNAs are relevant molecules (small single-stranded non-coding RNAs that regulate gene expression of more than 30% of human genes) to be implement non-invasive biomarkers. However, contrasting to others tumors, such as breast cancer where miR-21 seems to be consistently upregulated; PCa data are controversial. Here we reported an extended revision about the role of miRNAs in PCa including data of AR signaling, cell cycle, EMT process, CSCs regulation and even the role of miRNAs as PCa diagnostic, prognostic and predictive tool. It is known that current biomedical research uses big-data analysis like Next Generation Sequencing (NGS) analysis. We also conducted an extensive online search, including the main platforms and kits for miRNAs massive analysis (like MiSeq, Nextseq 550, or Ion S5™ systems) indicating their pros, cons and including pre-analytical and analytical issues of miRNA studies.

Efficacy of a multidisciplinary approach on postoperative morbidity and mortality of elderly patients with hip fracture.

STUDY OBJECTIVE: We evaluated the efficacy of a multidisciplinary approach to reduce postoperative complications and 1-year mortality in patients, undergoing hip fracture surgery and the impact of surgical delay on mortality. DESIGN: A non-randomized intervention study with a historical control group (CG). SETTING: During the hospital stay of patients undergoing hip fracture surgery and subsequent follow-up during 12 months post-discharge. PATIENTS: 240 patients undergoing hip fracture surgery were included in the CG. 272 patients were included in the intervention group (IG). INTERVENTIONS: CG patients received the standard care given at our hospital. Patients in the IG received a new model of multidisciplinary approach to care. MEASUREMENTS: The following variables were collected: study group, age, gender, ASA physical status, comorbidity, type of fracture, type of anaesthesia, surgical delay, postoperative complications, hospital stay, destination after discharge and postoperative mortality. MAIN RESULTS: 512 patients (CG = 240; IG = 272). Mean age was 83.8 years in CG and 84.9 years in IG. Patients in the IG had a worse health status according to ASA (III-IV: 68.8% vs 51.7%; p < 0.001) and took more drugs (p < 0.001). Surgery was performed within 48 h of admission in 55.1% of patients of the IG (38.3% CG; p < 0.001). Incidence of postoperative complications (67.3% IG vs 76.2% CG p = 0.025) and hospital stay was shorter in the IG (p < 0.001). A surgical delay of >48 h (HR = 0.61; CI95%: 0.42-0.88) and allocation to the IG (HR = 0.64; CI95%: 0.44-0.93) were the protective factors for mortality. CONCLUSIONS: The multidisciplinary approach could be associated with a decrease in postoperative complications, hospital stay and mortality. Surgical delay may not increase the risk of mortality. The main objective in the management of these patients should be the optimization of their general health status before surgery rather than surgical delay.

Methodology for Y Chromosome Capture: A complete genome sequence of Y chromosome using flow cytometry, laser microdissection and magnetic streptavidin-beads.

This study is a comparison of the efficiency of three technologies used for Y chromosome capture and the next-generation sequencing (NGS) technologies applied for determining its whole sequence. Our main findings disclose that streptavidin-biotin magnetic particle-based capture methodology offers better and a deeper sequence coverage for Y chromosome capture, compared to chromosome sorting and microdissection procedures. Moreover, this methodology is less time consuming and the most selective for capturing only Y chromosomal material, in contrast with other methodologies that result in considerable background material from other, non-targeted chromosomes. NGS results compared between two platforms, NextSeq 500 and SOLID 5500xl, produce the same coverage results. This is the first study to explore a methodological comparison of Y chromosome capture and genetic analysis. Our results indicate an improved strategy for Y chromosome research with applications in several scientific fields where this chromosome plays an important role, such as forensics, medical sciences, molecular anthropology and cancer sciences.

Genetic markers a landscape in prostate cancer.

Prostate cancer (PC) is one of the most common cancers worldwide. The observed variability in progression and responses to the same treatment between patients underlie the genetic heterogeneity of the disease. Nowadays, screening and follow-up biomarkers in PC are still having a deep lack of information, which makes difficult the cancer diagnosis, prognosis and the selection of the most suitable therapies. This is making that currently unnecessary biopsies, over-treatments and hormonoresistances have high rates of prevalence among patients. New biomarkers are urgently needed and in this sense genomic biomarkers could be the most suitable tools. These genetic markers will be helpful for improving the precision of prognostic and the predictive current tools which are employed in the clinical practice. A recent literature search up was conducted, including clinical trials and pre-clinical basic research studies. Keywords included germline variants, prostate cancer, biomarkers, androgen deprivation therapy, screening and liquid biopsy; among others. We have reviewed how germline variants, CNVs and repetitive regions are relevant to prostate carcinogenesis, treatment and progression. Moreover, we have also considered novel biomarkers for PC prognosis based on differentially expressed genes. Finally, we have included new strategies in recent markers of liquid biopsy or updated technologies for minimal samples analysis. The improvement of genetic markers use and their application to the clinical practice, will enhance the variability of simple, non-invasive, tools such as liquid biopsy and germline variants, these will reduce the number of PC needle biopsies and current over-treatments that are usual in the management of this cancer.

Absence of Relationship between Mitochondrial DNA Haplogroups and Cisplatin-Induced Hearing Loss.

BACKGROUND: Many drugs used for cancer chemotherapy produce reactive oxygen species, thus leading to various complications including nephrotoxicity, cardiotoxicity, and ototoxicity. OBJECTIVE: We have provided a haplogroup analysis of a cohort of cancer patients treated with chemotherapy and compared factors associated with associated hearing loss. STUDY DESIGN AND METHODS: This observational cohort study includes a pure-tone audiometry of the patients who underwent chemotherapeutic treatment. Medical history, presence of risk factors for hearing loss, toxic habits, and association with haplogroups have been determined. RESULTS: 40% of patients developed hearing loss after administration of cisplatin, which was bilateral and symmetrical and of high frequencies. The most frequent haplogroup was H with a slight overexpression of groups V and K and a low frequency of groups J and T. No association of the haplogroup types with the hearing loss has been found; however age was revealed as an important determining factor. CONCLUSIONS: Ototoxicity caused by cisplatin is manifested as bilateral, symmetrical, and predominantly high frequency hearing loss. Although we did not find a strong correlation of haplogroups with ototoxicity, our results revealed the existence of a risk group of elderly patients over 60, which are more susceptible to hearing loss induced by cisplatin, than young adults, regardless of preexisting hearing loss.

Circulating Tumor Cells: Markers and Methodologies for Enrichment and Detection.

Cancer is a leading cause of disease worldwide; however, nowadays many points of its initiation processes are unknown. In this chapter, we are focusing on the role of liquid biopsies in cancer detection and progression. CTCs are one of the main components of liquid biopsies, they represent a subset of tumor cells that have acquired the ability to disseminate from the primary tumor and intravasate to the circulatory system. The greatest challenge in the detection of CTCs is their rarity in the blood. Human blood consists of white blood cells (5-10 × 106/mL), red blood cells (5-9 × 109/mL), and platelets (2.5-4 × 108/mL); very few CTCs will be present even in patients with known metastatic disease, with often less than one CTC per mL of blood. CTCs are found in frequencies on the order of 1-10 CTCs per mL of whole blood in patients with metastatic disease, and it is reduced in half for non-metastatic stages. Therefore, accurate methodologies for their capture and analysis are really important. The main aim of the present chapter is to describe different methodologies for CTCs capturing and analysis.

Somatic Mutations in Prostate Cancer: Closer to Personalized Medicine.

The molecular cause of prostate cancer (PCa) is still unclear; however, its progression involves androgen, PI3K/Akt, and PTEN signaling, as cycle and apoptotic pathways. Alterations in oncogenes and tumor suppressor genes as PIK3CA, BRAF, KRAS and TP53 are not very common. Recently, somatic mutations have been discovered in relation to cancer progression mainly in genes such as PIK3CA; however, little data has been described in PCa. Nowadays genetic tools allow us to investigate multiple details about the biological heterogeneity of PCa, to better understand the mechanisms of disease progression and treatment resistance. Therefore, if the most relevant somatic mutations were included during screening, we could identify the best treatment for the right patient, bringing us closer to personalized medicine. The main objective of this article is to provide a review of the principal somatic mutations that appear to have a relevant role in hormonal cancers, like prostate cancer.

The cancer stem-cell signaling network and resistance to therapy.

The study of cancer stem cells (CSCs) has shown that tumors are driven by a subpopulation of self-renewing CSCs that retain the capacity to engender the various differentiated cell populations that form tumors. The characterization of CSCs has indicated that CSCs are remarkably resistant to conventional radio- and chemo-therapy. Clinically, the remaining populations of CSC are responsible for metastasis and recurrence in patients with cancer, which can lead to the disease becoming chronic and incurable. Therefore, the elimination of CSCs is an important goal of cancer treatments. Furthermore, CSCs are subject to strong regulation by the surrounding microenvironment, which also impacts tumor responses. In this review, we discuss the mechanisms by which pathways that are defective in CSCs influence ultimately therapeutic and clinical outcomes.

Update in the management of critically ill burned patients.

The management of critically ill burn patients is challenging. These patients have to be managed in specialized centers, where the expertise of physicians and nursing personnel guarantees the best treatment. Mortality of burn patients has improved over the past decades due to a better understanding of burn shock pathophysiology, optimal surgical management, infection control and nutritional support. Indeed, a more aggressive resuscitation, early excision and grafting, the judicious use of topical antibiotics, and the provision of an adequate calorie and protein intake are key to attain best survival results. General advances in critical care have also to be implemented, including protective ventilation, glycemic control, selective decontamination of the digestive tract, and implementation of sedation protocols.