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.

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.

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.

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.

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.

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.

[Epidural analgesia versus femoral or femoral-sciatic nerve block after total knee replacement: comparison of efficacy and safety]. / Comparación de la eficacia y seguridad de tres técnicas analgésicas (epidural, bloqueo femoral y bloqueo femoral-ciático) en el postoperatorio de prótesis total de rodilla.

OBJECTIVE: Pain after total knee replacement surgery is intense. The aim of this study was to compare 3 techniques for providing postoperative analgesia (epidural analgesia, femoral nerve block, and a combined femoral-sciatic nerve block) in total knee arthroplasty. MATERIAL AND METHODS: Observational study of 1550 elective primary unilateral total knee replacement operations. The safety and efficacy of the following 3 techniques were compared: epidural analgesia, femoral nerve block, and femoral-sciatic nerve block. Demographic, anesthetic, and surgical data were recorded. Study variables included pain intensity on a visual analog scale every 4 hours, need for rescue analgesia (morphine), complications and adverse events within 5 postoperative days. RESULTS: No significant differences were found in demographic, anesthetic, or surgical variables. In the first 24 hours after surgery, pain intensity was significantly less for patients who received a femoral-sciatic nerve block. The mean levels of morphine consumption in the first 96 hours after surgery were similar in the femoral-sciatic nerve block group (3.18 mg) and the epidural analgesia group (3.19 mg); morphine consumption in the femoral block group was significantly higher (4.51 mg). Epidural analgesia was associated with the highest rate of complications (17%). CONCLUSIONS: A sciatic nerve block combined with a femoral nerve block attenuates pain more effectively and is associated with less postoperative morphine consumption in comparison with a femoral nerve block alone. Peripheral nerve block techniques have fewer adverse side effects than epidural analgesia.

SMILE: first observational prospective cohort study of migraine in primary care in France. Description of methods and study population.

The SMILE study was conducted among migraine patients consulting in primary care in France. The first phase aimed to describe the study sample of patients at entry to the study, especially emotional dimension (Hospital Anxiety and Depression scale), functional impact (abridged Migraine Specific Questionnaire), stress (Perceived Stress Scale) and coping behaviours (brief COPE inventory avoidance subscale, Coping Strategies Questionnaire catastrophizing subscale), as well as treatments used and their effectiveness and treatments prescribed at end of consultation. Results indicate that consulting migraine patients suffer frequent migraine attacks, exhibit substantial levels of anxiety, functional impact and stress, and often use maladaptive coping strategies. Abortive treatments appear ineffective in most patients (74%). Patients with more affected psychometric variables and treatment ineffectiveness are more likely to be deemed eligible for prophylactic treatment. These data highlight the seriousness of migraine and maladjustment of patients consulting in primary care.

Anxiety, stress and coping behaviours in primary care migraine patients: results of the SMILE study.

The objectives of the SMILE study were to assess anxiety, stress, depression, functional impact and coping behaviours in migraine patients consulting in primary care in France. General practitioners (n = 1467) and 83 neurologists included 5417 consulting migraine patients. Of these patients, 67% were found anxious, of whom 59% were also depressive. Patients with both anxiety and depressive dimensions showed a profile similar to that of chronic migraine patients (severe attacks, poor treatment effectiveness and pronounced stress, functional impact and maladaptive behaviours). A quantitative progression in the levels of stress, maladaptive coping behaviours and functional impact was noted from patients with neither dimension to those with both anxious and depressive dimensions. Stress and maladaptive coping strategies were found to be major determinants of anxiety. Anxious and depressive dimensions were associated with elevated consumption of acute treatments for migraine and low treatment effectiveness. Stress and anxiety should be looked for carefully in migraine patients.

[An infrequent cause of pulmonary thromboembolism]. / Una causa infrecuente de tromboembolismo pulmonar.

We present a case of pulmonary thromboembolism in a young patient triggered by a long haul travel, in which a homocygotic mutation in the gene of the metilentetrahidrofolate reductase was demonstrated. This mutation can cause hyperhomocysteinemia that is a recognized risk factor for venous thromboembolism (VTE). In the management of these patients, the levels of homocysteine should be lowered, as well as use of thromboprophylaxis before transitory risk situations. It is important to know when the screening should be performed, because they are behind an important number of cases of VTE.

[Young's syndrome in the adult age: home treatment with a mechanical device of intrapulmonary percusive ventilation]. / Síndrome de Young en la edad adulta: tratamiento domiciliario mediante un dispositivo mecánico de percusión intrapulmonar.

We studied a man with bronchiectasis, chronic sinopulmonary infections and obstructive azoospermia diagnosed of Young's syndrome in the adult age. The patient was treated at home by a mechanical system of respiratory care based in intrapulmonary percussive ventilation (Percussionaire) reaching a significant clinical and functional improvement. Our case enhanced the importance to make a proper history of fertility in patients with bronchiectasis in order to establish the diagnostic. We review different methods of respiratory mechanical assistance in patients with bronchiectasis.

[Humidifier fever: and unusual variant of hypersensitivity pneumonitis]. / Fiebre de los humidificadores: una rara variante de neumonitis por hipersensibilidad.

A case of a patient suffering three episodes consistent in fever, lung infiltrates, lymphocitosis in bronchoalveolar lavage and non-caseificant granulomata in transbronchial biopsy is reported.A relationship between exposition to the air conditioner in the office and the clinical picture was stablished, and the patient was finally diagnosed from humidifiers fever. We enfatize the manifestations of this uncommon disease, probably infradiagnosed, and the patogenic mechanisms are reviewed.

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.

Lipophilic pro-oligonucleotides are rapidly and efficiently internalized in HeLa cells.

Model t-Bu-SATE pro-dodecathymidines labeled with fluorescein and exhibiting various lipophilicities were evaluated for their uptake by cells in culture. Pro-oligonucleotides with appropriate lipophilicity were found to permeate across the HeLa cell membrane much more extensively than the control phosphorothioate oligo or than the hydrophilic pro-oligos. Fluorescence patterns of internalization were consistent with a diffusion mechanism resulting in the appearance of a uniform cytoplasmic distribution and nuclear accumulation, as confirmed by confocal microscopy.

[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.

[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.