Factors related to the development of high antibody titres against SARS-CoV-2 in convalescent plasma donors from the ConPlas-19 trial.

BACKGROUND AND OBJECTIVES: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels. MATERIALS AND METHODS: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA. RESULTS: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06). CONCLUSION: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.

Red Blood Cell Transfusion after Postpartum Hemorrhage: Clinical Variables Associated with Lack of Postpartum Hemorrhage Etiology Identification.

Postpartum hemorrhage (PPH) remains a significant obstetric emergency worldwide and a leading cause of maternal death. However, it is commonly underreported, which can represent a major concern for maternal morbidity and mortality. This retrospective case series study analyzed patients with red blood cell transfusion (RBCt) in the postpartum period over a four-year interval at a specific center. A total of 18,674 patients delivered between January 2018 and December 2021. Patients with postpartum RBCt were classified into two groups: those with identified PPH (i-PPH) and those without (non-i-PPH). Clinical variables, delivery details, blood loss data, and treatment information were collected. Statistical analysis involved a comparison of variables between the i-PPH and non-i-PPH groups. Univariate and multivariate analyses were performed, aiming to identify significant associations between the clinical variables and a lack of PPH identification. The incidence of RBCt was 1.26% (236 cases). Patients receiving RBCt had higher rates of cesarean delivery, twin pregnancy, labor induction, and previous cesarean section. Among patients with postpartum RBCt, 34.3% lacked an identified PPH. The rarity of postpartum RBCt contrasts with the increasing rates of PPH, highlighting the importance of diagnosing PPH and postpartum anemia. A strategy of systematic quantification of blood loss during delivery could help detect PPH and anemia before adverse consequences occur.

Myocardial revascularization failure among patients requiring cardiac catheterization and secondary revascularization in contemporary clinical practice: Results of the REVASEC multicenter registry.

BACKGROUND: Myocardial revascularization failure (MRF) and Secondary revascularization (SR) are contemporary interventional cardiology challenges. AIM: To investigate the characteristics, management, and prognosis of patients with myocardial revascularization failure (MRF) and need for secondary revascularization (SR) in contemporary practice. METHODS: The REVASEC study is a prospective registry (NCT03349385), which recruited patients with prior revascularization referred for coronary angiography at 19 centers. The primary endpoint is a patient-oriented composite (POCE) at 1 year, including death, myocardial infarction, or repeat revascularization. RESULTS: A total of 869 patients previously revascularized by percutaneous intervention (83%) or surgery (17%) were recruited. MRF was found in 83.7% (41.1% stent/graft failure, 32.1% progression of coronary disease, and 10.5% residual disease). SR was performed in 70.1%, preferably by percutaneous intervention (95%). The POCE rate at 1 year was 14% in the overall cohort, with 6.4% all-cause death. In the multivariate analysis, lower POCE rates were found in the groups without MRF (9.4%) and with disease progression (11%) compared with graft/stent failure (17%) and residual disease (18%), hazard ratio 0.67 (95% confidence interval: 0.45-0.99), p = 0.043. At 1 year, the SR group had less chronic persistent angina (19% vs. 34%, p < 0.001), but a higher rate of repeat revascularization (9% vs. 2.9%, p < 0.001). CONCLUSION: MRF was found in 84% of patients with prior revascularization referred for coronary angiography. Stent/graft failure and residual coronary disease were associated with a worse prognosis. SR provided better symptom control at the expense of a higher rate of new revascularization.

Comprehensive Assessment of Myocardial Ischemia Mechanisms in the Catheterization Laboratory: Design and Rationale of the Advanced Invasive Diagnosis Strategy for Patients with Stable Coronary Syndromes Undergoing Coronary ANGIOgraphy - the AID-ANGIO Study.

BACKGROUND: The diagnostic yield of invasive coronary angiography (ICA) to identify obstructive coronary artery disease in the context of chronic coronary syndromes (CCS) is very low. Furthermore, myocardial ischemia may have a non-obstructive origin, which cannot be detected by ICA. METHODS: AID-ANGIO is an observational, prospective, single-cohort, multicenter study, intended to evaluate the diagnostic yield of adopting a hierarchical strategy to assess obstructive and non-obstructive causes of myocardial ischemia in an all-comers population of patients with CCS at the time of ICA. The primary endpoint will investigate the additional diagnostic value of such strategy over angiography alone regarding the identification of ischemia-generating mechanisms. SUMMARY: An estimated sample of consecutive 260 patients with CCS referred by their clinicians to ICA, will be enrolled. In a stepwise manner, a conventional ICA will be performed as the initial diagnostic tool. Those patients with severe-grade stenosis will not undergo further assessment and an obstructive origin for myocardial ischemia will be assumed. Subsequently, the remainder with intermediate-grade stenosis will be assessed with pressure guidewires. Those with a negative result from physiological evaluation and those without epicardial coronary stenosis will be further studied for ischemia of non-obstructive origin, including microvascular dysfunction and vasomotor disorders. The study will be conducted in two steps. Firstly, ICA images will be displayed to patient's referring clinicians, who will be asked to identify the existent epicardial stenosis, their angiographic severity and probable physiological relevance, together with a tentative therapeutic approach. Then, the diagnostic algorithm will continue to be applied and, considering the whole gathered information, a definite therapeutic plan will be consensually established by the interventional cardiologist and patient's referring clinicians. CONCLUSION: The AID-ANGIO study will assess the additional diagnostic yield of a hierarchical strategy over ICA alone to identify ischemia-generating mechanisms in patients with CCS and its impact on therapeutic approach. Positive results of the study might support a streamlined invasive diagnostic process for patients with CCS.

Estimate of activity discharged into the sewer network in neuroendocrine treatments with 177Lu-DOTA-TATE.

The urine of patients treated for neuroendocrine tumors with 177Lu is a liquid radioactive waste. The total body activity retained by the patient is quantified with SPECT-CT image 1 day after administration. From the activity of 177Lu in patient after 1 day Apat_Lu177_1d, the activity in urine after 1 day Aurine_Lu177_1d is determined, as well as the activity of 177mLu Aurine_Lu177m_1d that accompanies 177Lu as an impurity. Admitting the patient 24 hours in a dedicated room with storage tanks reduces the discharged activity below the permitted limits.

Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study.

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD10+ diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD10- diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms.

Design and Rationale for a Real-World Prospective, Multicenter Registry of Myocardial Revascularization Failure and Secondary Revascularization: The REVASEC Study.

AIM: To investigate key aspects of the problem of myocardial revascularization failure (MRF) and repeat or secondary myocardial revascularization (SR) in contemporary practice. METHODS: The registry of secondary revascularization (REVASEC) is an investigator-initiated, multicenter, prospective registry enhanced with data monitoring and independent event adjudication (ClinicalTrials.govNCT03349385). It includes patients with prior revascularization referred to coronary angiography for suspected MRF with broad inclusion criteria. The main objectives are to describe the characteristics of patients with prior revascularization referred for repeat angiography, to describe and the rate and mechanisms of MRF (stent or graft failure, coronary artery disease progression or residual coronary artery disease); to evaluate the management including medical treatment and SR of these patients; and to assess the prognosis according to the outlined causative mechanisms. The registry has one year follow up for the primary endpoint (Patient-oriented composite endpoint including all-cause death, any myocardial infarction or any new unplanned revascularization according to subsets of MRF), but extended follow-up will be carried out up to 5 years. CONCLUSION: The REVASEC Registry will provide updated data on the characteristics, patterns of treatment, and 1-year outcomes of patients with MRF and SR in contemporary clinical practice.

Graft survival of Pinus engelmannii Carr. in relation to two grafting techniques with dormant and sprouting buds.

Developing methods for successfully grafting forest species will be helpful for establishing asexual seed orchards and increasing the success of forest genetic improvement programs in Mexico. In this study we investigated the effects of two grafting techniques (side veneer and top cleft) and two phenological stages of the scion buds (end of latency and beginning of sprouting), in combination with other seven grafting variables, on the sprouting and survival of 120 intraspecific grafts of Pinus engelmannii Carr. The scions used for grafting were taken from a 5.5-year-old commercial forest plantation. The first grafting was performed on January 18 (buds at the end of dormancy) and the second on February 21 (buds at the beginning of sprouting). The data were examined by analysis of variance and a test of means and were fitted to two survival models (the Weibull's accelerated failure time and the Cox's proportional hazards model) and the respective hazard ratios were calculated. Survival was higher in the top cleft grafts made with buds at the end of latency, with 80% sprouting and an estimated average survival time of between 164 and 457 days after the end of the 6-month evaluation period. Four variables (grafting technique, phenological stage of the scion buds, scion diameter and rootstock height) significantly affected the risk of graft death in both survival models. Use of top cleft grafts with buds at the end of the latency stage, combined with scion diameters smaller than 11.4 mm and rootstock heights greater than 58.5 cm, was associated with a lower risk of death.

Seasonal and Regional Influences on Alcohol Consumption: An Analysis of Near-Real-Time Urine Drug Test Results in Those Seeking Health Care.

AIMS: To examine the probability of detecting alcohol via urine drug testing (UDT) as influenced by age, gender, seasonality, geography, COVID-19, and time in those seeking health care. METHODS: A cross-sectional study of UDT results from January 1, 2013, to December 31, 2020, was conducted using adult patient specimens submitted for testing by health care professionals as part of routine care. The UDT analysis used LC-MS/MS to detect two alcohol metabolites, ethyl glucuronide and ethyl sulfate. Seasonal adjustment of positivity rates was accomplished using the STL method; trend analysis was performed on seasonally adjusted rates. Logistic regression was used to associate demographic features, and an interaction term for collection year and U.S. census division was included to help understand the changing nature of alcohol use over time and across divisions. RESULTS: Alcohol positivity rate shows strong seasonal changes with an oscillating profile that peaks in the summer and is at a low point in winter. The highest predicted positivity rate for alcohol was in male patients, 45-64 years of age, and from a primary care setting. Alcohol positivity peaked in 2016 and declined the following year. While remaining relatively steady since 2017, a small but significant increase was noted after the COVID-19 emergency declaration on March 13, 2020. The probability of being alcohol-positive varies significantly by geographic region, and not all regions are changing at the same rate. CONCLUSIONS: Alcohol positivity in UDT in patients seeking health care is influenced by multiple factors and has increased during the COVID-19 pandemic.

Acute management of a stroke-like episode in MELAS syndrome: What should we know?

•Acute management of SLEs differs from usual therapy in classic stroke patients.•IV L-Arginine should be administered urgently in the setting of a SLE.•If mental status is altered, an EEG should be performed to rule out a non-convulsive status.

Consideraciones para el manejo seguro en brote de enfermedad por coronavirus (COVID-19). ¿Cómo preparar una unidad quirúrgica? / Safe handling considerations in a coronavirus outbreak (COVID-19). How to prepare a surgical unit?

Resumen: Mientras el mundo enfrenta una pandemia por el agente vírico 2019-nCoV, las áreas críticas como la unidad quirúrgica se deben preparar para evitar la contaminación del personal de atención médica y el entorno. Los objetivos de este artículo son presentar las recomendaciones actuales para el uso de equipo de protección personal, dar a conocer los dispositivos útiles en la práctica de la anestesia y explicar las modificaciones y adecuaciones que se deben hacer a los recursos humanos y a los materiales dentro del área quirúrgica.

Abstract: While the world is facing a pandemic caused by the virus 2019-nCoV, critical hospital areas like the surgical unit must be ready to prevent contamination of the environment and the healthcare provider. The main purpose of this article is to review the current recommendations for using personal protection equipment, introduce devices that can prove useful for the practice of anesthesia and to explain the modifications and adaptations that must be made to both human and material resources in the surgical unit.

Spatial genetic structure in Pinus cembroides Zucc. at population and landscape levels in central and northern Mexico.

BACKGROUND: Spatial genetic structure (SGS) analysis is a powerful approach to quantifying gene flow between trees, thus clarifying the functional connectivity of trees at population and landscape scales. The findings of SGS analysis may be useful for conservation and management of natural populations and plantations. Pinus cembroides is a widely distributed tree species, covering an area of about 2.5 million hectares in Mexico. The aim of this study was to examine five natural seed stands of P. cembroides in the Sierra Madre Occidental to determine the SGS at population (within the seed stand) and landscape (among seed stands) levels in order to establish guidelines for the conservation and management of the species. We hypothesized that P. cembroides, in which the seeds are dispersed by birds and mammals, creates weaker SGS than species with wind-dispersed seeds. METHODS: DNA fingerprinting was performed using the amplified fragment length polymorphism (AFLP) technique. In order to estimate the SGS at population and landscape levels, we measured the geographical (spatial) distance as the Euclidean distance. We also estimated the genetic distances between individuals using the pairwise kinship coefficient. RESULTS: The results showed non-significant autocorrelation in four out of five seed stands studied (i.e., a mainly random distribution in the space of the genetic variants of P. cembroides at population level). DISCUSSION: SGS was detected at the landscape scale, supporting the theory of isolation by distance as a consequence of restricted pollen and seed dispersal. However, the SGS may also have been generated by our sampling strategy. We recommended establishing a close network of seed stands of P. cembroides to prevent greater loss of local genetic variants and alteration of SGS. We recommend seed stands of P. cembroides of a minimum width of 225 m.

Drug safety surveillance within a strategy for the management of non-chemotherapy drug-induced neutropenia.

Background Severe non-chemotherapy drug-induced neutropenia is a rare idiosyncratic drug reaction that is considered potentially fatal. Objective To report, in terms of drug safety surveillance, the results of an institutional strategy for NCDIN. Method An observational and prospective study including all adult patients who received filgrastim for the treatment of NCDIN from June 2015 to December 2017 was carried out by hematologists and clinical pharmacists. Results 13 patients with severe NCDIN were included in the study. The median age was 51 (range 24-80) years old and 46.2% were male. Seven patients had one or more negative prognostic factors (age > 65 years, renal impairment, autoimmune diseases and/or a neutrophil count at diagnosis < 0.1 × 109 cells/L). A single drug was identified as causative in 3 patients, while in 10 cases, 2-3 drugs were considered as potentially causative. The most frequent drugs were metamizole, piperacillin/tazobactam, dexketoprofen and linezolid, among others. Seven patients developed NCDIN during their hospital stay while 6 were admitted to the emergency department. Patients were using a median of 11 drugs (IQR 8-15) at the time of diagnosis. No deaths were recorded. Conclusion Metamizole and piperacillin/tazobactam are the most common drugs linked to non-chemotherapy drug-induced neutropenia in our cohort.

Sliding Mode Control with Dynamical Correction for Time-Delay Piezoelectric Actuator Systems.

In piezoelectric actuators (PEAs), which suffer from inherent nonlinearities, sliding mode control (SMC) has proven to be a successful control strategy. Nonetheless, in micropositioning systems with time delay, integral proportional control (PI), and SMC, feedback control schemes have a tendency to overcompensate and, consequently, high controller gains must be rejected. This may produce a slow and inaccurate response. This paper presents a novel control strategy that deals with time-delay micropositioning systems aimed at achieving precise positioning by combining an open-loop control with a modified SMC scheme. The proposed SMC with dynamical correction (SMC-WDC) uses the dynamical system model to adapt the SMC inputs and avoid undesirable control response caused by delays. In order to develop the SMC-WDC scheme, an exhaustive analysis on the micropositioning system was first performed. Then, a mixed control strategy, combining inverse open-loop control and SMC-WDC, was developed. The performance of the presented control scheme was analyzed and compared experimentally with other control strategies (i.e., PI and SMC with saturation and hyperbolic functions) using different reference signals. It was found that the SMC-WDC strategy presents the best performance, that is, the fastest response and highest accuracy, especially against sudden changes of reference setpoints (frequencies >10 Hz). Additionally, if the setpoint reference frequencies are higher than 10 Hz, high integral gains are counterproductive (since the control response increases the delay), although if frequencies are below 1 Hz the integral control delay does not affect the system's accuracy. The SMC-WDC proved to be an effective strategy for micropositioning systems, dealing with time delay and other uncertainties to achieve the setpoint command fast and precisely without chattering.

Progressive multifocal leukoencephalopathy 11 years after liver transplantation: a case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system caused by JC virus. Only ten cases of PML have been reported so far in liver transplant recipients. We present a case of liver posttransplantation PML with characteristic clinical and brain MRI findings, but with an atypical late onset, developed 11 years after transplantation and after single-drug, long-term (8 years), and low-dose (750 mg twice a day) immunosuppression with mycophenolate mofetil (MMF). This is the latest onset of PML associated to liver transplant reported. The present case should help physicians to be aware of PML after transplantation, even in the long term and even under low doses of immunosuppressants, especially MMF.