Management of peri-surgical anemia in elective surgery. Conclusions and recommendations according to Delphi-UCLA methodology.

INTRODUCTION: Preoperative anemia affects approximately one third of surgical patients. It increases the risk of blood transfusion and influences short- and medium-term functional outcomes, increases comorbidities, complications and costs. The "Patient Blood Management" (PBM) programs, for integrated and multidisciplinary management of patients, are considered as paradigms of quality care and have as one of the fundamental objectives to correct perioperative anemia. PBM has been incorporated into the schemes for intensified recovery of surgical patients: the recent Enhanced Recovery After Surgery 2021 pathway (in Spanish RICA 2021) includes almost 30 indirect recommendations for PBM. OBJECTIVE: To make a consensus document with RAND/UCLA Delphi methodology to increase the penetration and priority of the RICA 2021 recommendations on PBM in daily clinical practice. MATERIAL AND METHODS: A coordinating group composed of 6 specialists from Hematology-Hemotherapy, Anesthesiology and Internal Medicine with expertise in anemia and PBM was formed. A survey was elaborated using Delphi RAND/UCLA methodology to reach a consensus on the key areas and priority professional actions to be developed at the present time to improve the management of perioperative anemia. The survey questions were extracted from the PBM recommendations contained in the RICA 2021 pathway. The development of the electronic survey (Google Platform) and the management of the responses was the responsibility of an expert in quality of care and clinical safety. Participants were selected by invitation from speakers at AWGE-GIEMSA scientific meetings and national representatives of PBM-related working groups (Seville Document, SEDAR HTF section and RICA 2021 pathway participants). In the first round of the survey, the anonymized online questionnaire had 28 questions: 20 of them were about PBM concepts included in ERAS guidelines (2 about general PBM organization, 10 on diagnosis and treatment of preoperative anemia, 3 on management of postoperative anemia, 5 on transfusion criteria) and 8 on pending aspects of research. Responses were organized according to a 10-point Likter scale (0: strongly disagree to 10: strongly agree). Any additional contributions that the participants considered appropriate were allowed. They were considered consensual because all the questions obtained an average score of more than 9 points, except one (question 14). The second round of the survey consisted of 37 questions, resulting from the reformulation of the questions of the first round and the incorporation of the participants' comments. It consisted of 2 questions about general organization of PBM programme, 15 questions on the diagnosis and treatment of preoperative anemia; 3 on the management of postoperative anemia, 6 on transfusional criteria and finally 11 questions on aspects pending od future investigations. Statistical treatment: tabulation of mean, median and interquartiles 25-75 of the value of each survey question (Tables 1, 2 and 3). RESULTS: Except for one, all the recommendations were accepted. Except for three, all above 8, and most with an average score of 9 or higher. They are grouped into: 1.- "It is important and necessary to detect and etiologically diagnose any preoperative anemia state in ALL patients who are candidates for surgical procedures with potential bleeding risk, including pregnant patients". 2.- "The preoperative treatment of anemia should be initiated sufficiently in advance and with all the necessary hematinic contributions to correct this condition". 3.- "There is NO justification for transfusing any unit of packed red blood cells preoperatively in stable patients with moderate anemia Hb 8-10g/dL who are candidates for potentially bleeding surgery that cannot be delayed." 4.- "It is recommended to universalize restrictive criteria for red blood cell transfusion in surgical and obstetric patients." 5.- "Postoperative anemia should be treated to improve postoperative results and accelerate postoperative recovery in the short and medium term". CONCLUSIONS: There was a large consensus, with maximum acceptance,strong level of evidence and high recommendation in most of the questions asked. Our work helps to identify initiatives and performances who can be suitables for the implementation of PBM programs at each hospital and for all patients.

Executive summary of the consensus document on the management of perioperative anemia in Spain.

Perioperative anemia is an independent risk factor for postoperative morbidity and mortality. However, conceptual, logistical and administrative barriers persist that hinder the widespread implementation of protocols for their management. The project coordinator convened a multidisciplinary group of 8 experienced professionals to develop perioperative anemia management algorithms, based on a series of key points (KPs) related to its prevalence, consequences, diagnosis and treatment. These KPs were assessed using a 5-point Likert scale, from "strongly disagree [1]" to "strongly agree [5]". For each KP, consensus was reached when receiving a score of 4 or 5 from at least 7 participants (>75%). Based on the 36 KPs agreed upon, diagnostic-therapeutic algorithms were developed that we believe can facilitate the implementation of programs for early identification and adequate management of perioperative anemia, adapted to the characteristics of the different institutions in our country.

European beech dieback after premature leaf senescence during the 2018 drought in northern Switzerland.

During the particularly severe hot summer drought in 2018, widespread premature leaf senescence was observed in several broadleaved tree species in Central Europe, particularly in European beech (Fagus sylvatica L.). For beech, it is yet unknown whether the drought evoked a decline towards tree mortality or whether trees can recover in the longer term. In this study, we monitored crown dieback, tree mortality and secondary drought damage symptoms in 963 initially live beech trees that exhibited either premature or normal leaf senescence in 2018 in three regions in northern Switzerland from 2018 to 2021. We related the observed damage to multiple climate- and stand-related parameters. Cumulative tree mortality continuously increased up to 7.2% and 1.3% in 2021 for trees with premature and normal leaf senescence in 2018, respectively. Mean crown dieback in surviving trees peaked at 29.2% in 2020 and 8.1% in 2019 for trees with premature and normal leaf senescence, respectively. Thereafter, trees showed first signs of recovery. Crown damage was more pronounced and recovery was slower for trees that showed premature leaf senescence in 2018, for trees growing on drier sites, and for larger trees. The presence of bleeding cankers peaked at 24.6% in 2019 and 10.7% in 2020 for trees with premature and normal leaf senescence, respectively. The presence of bark beetle holes peaked at 22.8% and 14.8% in 2021 for trees with premature and normal leaf senescence, respectively. Both secondary damage symptoms occurred more frequently in trees that had higher proportions of crown dieback and/or showed premature senescence in 2018. Our findings demonstrate context-specific differences in beech mortality and recovery reflecting the importance of regional and local climate and soil conditions. Adapting management to increase forest resilience is gaining importance, given the expected further beech decline on dry sites in northern Switzerland.

Long-term soil water limitation and previous tree vigor drive local variability of drought-induced crown dieback in Fagus sylvatica.

Ongoing climate warming is increasing evapotranspiration, a process that reduces plant-available water and aggravates the impact of extreme droughts during the growing season. Such an exceptional hot drought occurred in Central Europe in 2018 and caused widespread defoliation in mid-summer in European beech (Fagus sylvatica L.) forests. Here, we recorded crown damage in 2021 in nine mature even-aged beech-dominated stands in northwestern Switzerland along a crown damage severity gradient (low, medium, high) and analyzed tree-ring widths of 21 mature trees per stand. We aimed at identifying predisposing factors responsible for differences in crown damage across and within stands such as tree growth characteristics (average growth rates and year-to-year variability) and site-level variables (mean canopy height, soil properties). We found that stand-level crown damage severity was strongly related to soil water availability, inferred from tree canopy height and plant available soil water storage capacity (AWC). Trees were shorter in drier stands, had higher year-to-year variability in radial growth, and showed higher growth sensitivity to moisture conditions of previous late summer than trees growing on soils with sufficient AWC, indicating that radial growth in these forests is principally limited by soil water availability. Within-stand variation of post-drought crown damage corresponded to growth rate and tree size (diameter at breast height, DBH), i.e., smaller and slower-growing trees that face more competition, were associated with increased crown damage after the 2018 drought. These findings point to tree vigor before the extreme 2018 drought (long-term relative growth rate) as an important driver of damage severity within and across stands. Our results suggest that European beech is less likely to be able to cope with future climate change-induced extreme droughts on shallow soils with limited water retention capacity.

Antibodies to M-type phospholipase A2 receptor (PLA2R) in membranous lupus nephritis.

BACKGROUND: Antibodies to M-type phospholipase A2 receptor (a-PLA2R) have been identified in most patients with idiopathic membranous nephropathy, but the prevalence in membranous lupus nephritis (MLN) is still unclear. The objective of this study was to assess the prevalence of a-PLA2R antibodies in a large cohort of patients with lupus nephritis. METHODS: a-PLA2R antibodies were measured by ELISA in serum from patients with systemic lupus erythematosus ( n = 190), of whom 37 had a biopsy-proven MLN. Positive samples were confirmed by commercial ELISA kit, Western blot and immunohistochemistry in renal tissue. RESULTS: A total of 10 from 190 patients (5.3%) with systemic lupus erythematosus had circulating a-PLA2R measured by in-house ELISA assay. The antibodies were detected in 7 patients with MLN (18.9%) and 3 patients with non-renal lupus disease (3.2%). PLA2R staining was detected in the kidney biopsy of 5 of the 7 (71.4%) patients with MLN. a-PLA2R levels were associated with active disease but not proteinuria levels. Presence of a-PLA2R antibodies at baseline was associated with worse remission rates and longer time to remission compared to those patients serologically negative. CONCLUSIONS: a-PLA2R antibodies can be detected with low prevalence in MLN patients, but their detection is associated with a worse renal prognosis.

Strain intermittency due to avalanches in ferroelastic and porous materials.

The avalanche statistics in porous materials and ferroelastic domain wall systems has been studied for slowly increasing compressive uniaxial stress with stress rates between 0.2 and 17 kPa s-1. Velocity peaks [Formula: see text] are calculated from the measured strain drops and used to determine the corresponding Energy distributions [Formula: see text]. Power law distributions [Formula: see text] have been obtained over 4-6 decades. For most of the porous materials and domain wall systems an exponent [Formula: see text] was obtained in good agreement with mean-field theory of the interface pinning transition. For charcoal, shale and calcareous schist we found significant deviations of the exponents from mean-field values in agreement with recent acoustic emission experiments.

[Implementation of blood sparing programs in Spain: results of a survey of departments of anesthesiology and resuscitation]. / Implementación de los programas de ahorro de sangre en España: resultados de la encuesta a los servicios de anestesiología y reanimación.

The objective of this article is to determine the availability of a perioperative transfusion management program (Patient Blood Management [PBM]) in various hospitals through a survey that included a description of the preanesthesia visit, the availability and use of the various blood-sparing techniques and the factors limiting their implementation in elective surgery. The survey included 42 questions, directed at the representative departments of anesthesiology of hospitals in Spain (n=91). The survey was conducted from September to November 2012. We analyzed the 82 surveys in which all the questions were answered (90%). Preoperative consultations are routinely performed (>70%) in 87% of the hospitals. The time from the consultation to surgery varied between 1 week and 2 months for 74% of the patients scheduled for orthopedic or trauma surgery, 78% of those scheduled for oncologic surgery and 77% of those scheduled for cardiac surgery. Almost all hospitals (77, 94%) had a transfusion committee, and 90% of them had an anesthesiologist on the committee. Seventy-nine percent of the hospitals had a blood-sparing program, and the most widely used technique was the use of antifibrinolytic agents (75% of hospitals), followed by intraoperative and postoperative blood recovery in equal proportions (67%). Optimization of preoperative hemoglobin was routinely performed with intravenous iron in 39% of the hospitals and with recombinant erythropoietin in 28% of the hospitals. The absence of a well-established circuit and the lack of involvement and collaboration with the surgical team were the main limiting factors in implementing PBM. Currently, the implementation of PBM in Spain could be considered acceptable, but it could also be improved, especially in the treatment of preoperative anemia. The implementation of PBM requires multidisciplinary collaboration among all personnel responsible for perioperative care, including the health authorities.

[The first pillar of patient blood management. Types of anemia and diagnostic parameters]. / Primer pilar del "Patient Blood Management". Tipos de anemia y parámetros diagnósticos.

Patient Blood Management (PBM) is the design of a personalized, multimodal multidisciplinary plan for minimizing transfusion and simultaneously achieving a positive impact on patient outcomes. The first pillar of PBM consists of optimizing the erythrocyte mass. The best chance for this step is offered by preoperative preparation. In most cases, a detailed medical history, physical examination and laboratory tests will identify the cause of anemia. A correct evaluation of parameters that assess the state and function of iron, such as ferritin levels, and the parameters that measure functional iron, such as transferrin saturation and soluble transferrin receptor levels, provide us with essential information for guiding the treatment with iron. The new blood count analyzers that measure hypochromia (% of hypochromic red blood cells and reticulocyte hemoglobin concentrations) provide us useful information for the diagnosis and follow-up of the response to iron treatment. Measuring serum folic acid and vitamin B12 levels is essential for treating deficiencies and thereby achieving better hemoglobin optimization.

[Algorithm for treating preoperative anemia]. / Algoritmo para el tratamiento de la anemia preoperatoria.

Hemoglobin optimization and treatment of preoperative anemia in surgery with a moderate to high risk of surgical bleeding reduces the rate of transfusions and improves hemoglobin levels at discharge and can also improve postoperative outcomes. To this end, we need to schedule preoperative visits sufficiently in advance to treat the anemia. The treatment algorithm we propose comes with a simple checklist to determine whether we should refer the patient to a specialist or if we can treat the patient during the same visit. With the blood count test and additional tests for iron metabolism, inflammation parameter and glomerular filtration rate, we can decide whether to start the treatment with intravenous iron alone or erythropoietin with or without iron. With significant anemia, a visit after 15 days might be necessary to observe the response and supplement the treatment if required. The hemoglobin objective will depend on the type of surgery and the patient's characteristics.

[Therapeutic approach to postoperative anemia]. / Aproximación terapéutica a la anemia postoperatoria.

Postoperative anemia is a common finding in patients who undergo major surgery, and it can affect early rehabilitation and the return to daily activities. Allogeneic blood transfusion is still the most widely used method for restoring hemoglobin levels rapidly and effectively. However, the potential risks of transfusions have led to the review of this practice and to a search for alternative measures for treating postoperative anemia. The early administration of intravenous iron appears to improve the evolution of postoperative hemoglobin levels and reduce allogeneic transfusions, especially in patients with significant iron deficiency or anemia. What is not clear is whether this treatment heavily influences rehabilitation and quality of life. There is a lack of well-designed, sufficiently large, randomized prospective studies to determine whether postoperative or perioperative intravenous iron treatment, with or without recombinant erythropoietin, has a role in the recovery from postoperative anemia, in reducing transfusions and morbidity rates and in improving exercise capacity and quality of life.

[Treatment of preoperative anemia in major orthopedic surgery]. / Tratamiento de la anemia preoperatoria en cirugía ortopédica mayor.

The prevalence of preoperative anemia in major orthopedic surgery is high and is the main predictive factor for allogeneic blood transfusion. The scheduling of a preoperative visit with sufficient notice (at least 3 weeks before surgery), with a blood count test and a basic iron metabolism study, enables us to treat the anemia and/or improve preoperative hemoglobin levels, thereby reducing the need for transfusion and the risks associated with transfusions. Intravenous iron and/or erythropoietin are treatments for optimizing preoperative anemia, with good levels of scientific evidence.

[Treatment of anemia in Patient Blood Management from an economic perspective]. / Tratamiento de la anemia en el "Patient Blood Management" desde una perspectiva económica.

The liberal use of transfusions is not only a risk for patients but also represents a significant healthcare expenditure. The rational use of allogeneic blood transfusions and the use of transfusion alternatives, such as the optimization of preoperative hemoglobin levels, can offer substantial savings to health departments by reducing the cost of transfusions and the morbidity related to the transfusions.

Forum for debate: Safety of allogeneic blood transfusion alternatives in the surgical/critically ill patient.

In recent years, several safety alerts have questioned or restricted the use of some pharmacological alternatives to allogeneic blood transfusion in established indications. In contrast, there seems to be a promotion of other alternatives, based on blood products and/or antifibrinolytic drugs, which lack a solid scientific basis. The Multidisciplinary Autotransfusion Study Group and the Anemia Working Group España convened a multidisciplinary panel of 23 experts belonging to different healthcare areas in a forum for debate to: 1) analyze the different safety alerts referred to certain transfusion alternatives; 2) study the background leading to such alternatives, the evidence supporting them, and their consequences for everyday clinical practice, and 3) issue a weighted statement on the safety of each questioned transfusion alternative, according to its clinical use. The members of the forum maintained telematics contact for the exchange of information and the distribution of tasks, and a joint meeting was held where the conclusions on each of the items examined were presented and discussed. A first version of the document was drafted, and subjected to 4 rounds of review and updating until consensus was reached (unanimously in most cases). We present the final version of the document, approved by all panel members, and hope it will be useful for our colleagues.

Criticality in the slowed-down boiling crisis at zero gravity.

Boiling crisis is a transition between nucleate and film boiling. It occurs at a threshold value of the heat flux from the heater called CHF (critical heat flux). Usually, boiling crisis studies are hindered by the high CHF and short transition duration (below 1 ms). Here we report on experiments in hydrogen near its liquid-vapor critical point, in which the CHF is low and the dynamics slow enough to be resolved. As under such conditions the surface tension is very small, the experiments are carried out in the reduced gravity to preserve the conventional bubble geometry. Weightlessness is created artificially in two-phase hydrogen by compensating gravity with magnetic forces. We were able to reveal the fractal structure of the contour of the percolating cluster of the dry areas at the heater that precedes the boiling crisis. We provide a direct statistical analysis of dry spot areas that confirms the boiling crisis at zero gravity as a scale-free phenomenon. It was observed that, in agreement with theoretical predictions, saturated boiling CHF tends to zero (within the precision of our thermal control system) in zero gravity, which suggests that the boiling crisis may be observed at any heat flux provided the experiment lasts long enough.

SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation.

The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153, an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

Boiling crisis as a critical phenomenon.

We present the first experimental study of intermittency and avalanche distribution during a boiling crisis. To understand the emergence of power law statistics we propose a simple spin model capturing the measured critical exponent. The model suggests that behind the critical heat flux is a percolation phenomenon involving drying-rewetting competition close to the hot surface.

[Low-dose aspirin doesn't increase surgical bleeding nor transfusion rate in total knee arthroplasty]. / El tratamiento preoperatorio con aspirina a dosis bajas no aumenta la hemorragia quirúrgica ni la tasa transfusional en la prótesis total de rodilla.

OBJECTIVES: Surgical bleeding. transfusion rate and cardiovascular complications were analized in patients undergoing chronic treatment with low-doses aspirin and scheduled to unilateral primary knee arthroplasty. PATIENTS AND METHODS: We retrospectively studied 117 patients between 2005 and 2006 scheduled for elective knee replacement that received antiplatelet therapy with aspirin (100mg/day). Aspirin medication was maintained or discontinued preoperatively according to medical criteria. We analyzed the biological, clinical and anesthetic data, blood-saving techniques used, surgical bleeding, allogeneic blood transfusion rate, cardiocirculatory complications (myocardial, cerebral or peripheral ischemia), hospital stay and mortality. This population was compared with 190 patients (control group) who underwent the same operation at the same time interval but did not receive aspirin therapy. RESULTS: The aspirin-treated group was significantly older, with higher weight and poorer health state (higher incidence of ischemic heart disease, cerebral ischemia and diabetes). The hidden and external surgical bleeding and transfusion rate were similar if the aspirin were interrupted or not, preoperatively. Bleeding and transfusion rates were independent of time of interruption of the aspirin. Hospital mortality was zero in the 2 groups. A acute myocardial infarction and a transient stroke happened in two patients wich aspirin treatment was discontinued. CONCLUSIONS: Preoperative treatment with low doses of aspirin does not increase surgical bleeding and transfusion rate in total knee arthroplasty. Preoperative discontinuation can cause severe cardiocirculatory complications.

Clinical determinants of migraine preventive treatment: contribution of SMILE, an observational survey of primary care migraine management in France.

METHODS: SMILE was an observational study carried out in France among office-based general practitioners (GPs) and neurologists from November 2005 to July 2006 to assess the determinants of prescription of migraine preventive therapy in primary care medicine. A total of 1467 GPs and 83 neurologists were included, treating 5417 and 248 migraine sufferers, respectively. RESULTS: The main factors leading physicians to deem a patient eligible for preventive treatment were perceived medication overuse and frequency of headaches, and secondarily, severity of headaches and functional impact. On the other hand, patient satisfaction with the acute treatment of attacks and triptan use, and secondarily, a long migraine history were found to influence patient eligibility negatively. DISCUSSION/CONCLUSION: Noticeably, psychiatric disorders (anxiety, stress) did not appear, aside from somatic factors, among the determinants that significantly influence physicians' judgment about the option of establishing a preventive treatment. However, they are important features of migraine condition and should be listed among the factors guiding choices about migraine preventive therapy.