Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response.

Despite the efficacy of splenectomy for chronic immune thrombocytopenia (ITP), its considerable failure rate and its possible related complications prove the need for further research into potential predictors of response. The platelet sequestration site determined by 111 In-labelled autologous platelet scintigraphy has been proposed to predict splenectomy outcome, but without standardisation in clinical practice. Here, we conducted a single-centre study by analysing a cohort of splenectomised patients with ITP in whom 111 In-scintigraphy was performed at La Paz University Hospital in Madrid to evaluate the predictive value of the platelet kinetic studies. We also studied other factors that could impact the splenectomy outcome, such as patient and platelet characteristics. A total of 51 patients were splenectomised, and 82.3% responded. The splenic sequestration pattern predicted a higher rate of complete response up to 12 months after splenectomy (p = 0.005), with 90% sensitivity and 77% specificity. Neither age, comorbidities, therapy lines nor previous response to them showed any association with response. Results from the platelet characteristics analysis revealed a significant loss of sialic acid in platelets from the non-responding patients compared with those who maintained a response (p = 0.0017). Our findings highlight the value of splenic sequestration as an independent predictor of splenectomy response.

Controlling the target pattern of projected LED arrays for smart lighting.

High-resolution, pixelated LED arrays allow flexible illumination. By addressing certain areas of the LED matrix and projecting the emitted light, selective illumination can be achieved. When combined with computer vision, smart, autonomous lighting systems are within reach. However, limitations of the used projection optics, in combination with the fact that the LED array and camera can be at a different position, severely complicates the problem of calculating which LED pixels to address in order to achieve a desired target pattern. This work proposes a least-squares deconvolution-based calculation method to solve this problem. The method relies on an initial calibration step that characterizes the complete point-spread-function of the LED array for the considered illumination configuration. This allows using the system for various settings. The method is experimentally validated for an off-axis illumination configuration that demonstrates the accuracy and flexibility of the approach. Because the proposed algorithm is fast and guarantees a global optimum, it opens new avenues towards accurate, smart and adaptive illumination.

No changes in hemostasis after COVID-19-heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study.

Background: Several cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. Objectives: The objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. Methods: The present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). Results: Platelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. Conclusion: Our data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Procoagulant State of Sleep Apnea Depends on Systemic Inflammation and Endothelial Damage.

INTRODUCTION: Growing evidence shows a hypercoagulable state in obstructive sleep apnea (OSA) that could be a risk factor for thromboembolic disease. OBJECTIVES: We aimed to elucidate mechanisms involved in the procoagulant profile observed in patients with OSA and to investigate the potential utility of global tests in its characterization. METHODS: Thirty-eight patients with severe OSA without previous history of thrombosis and nineteen healthy age- and sex-matched controls were included. Kinetic of clot formation was determined using rotational thromboelastometry. Haemostatic capacity of plasma and microparticles was determined by Calibrated Automated Thrombinography. Platelet surface receptors, activation markers and formation of platelet/leukocytes aggregates were analyzed by flow cytometry. RESULTS: Thromboelastometry showed a procoagulant state in patients with OSA that did not seem to be related to a basal activation of platelets but by the increased existence of platelet/leukocyte aggregates. Patients with OSA presented many signs of endothelial damage such as increased plasma levels of E-selectin and cfDNA and enhanced thrombin generation due to the presence of microparticles rich in tissue-factor, which is related to OSA severity. CONCLUSIONS: OSA induces an enhancement in the dynamics of clot formation which appears to be caused by at least two pathological mechanisms. First, a greater formation of platelet-leukocyte aggregates; secondly, endothelial damage which provokes a greater procoagulant potential due to the increase in tissue factor-rich microparticles. Moreover, this study has identified thromboelastometry and thrombin generation assay as useful tools to evaluate the prothrombotic state in these patients.

Effect of the first year of COVID-19 pandemic on the collection and use of blood components in Colombia monitored through the national haemovigilance system.

OBJECTIVE: This work aimed to establish the effects of the COVID-19 pandemic on blood collection and blood product usage at the end of the first year. BACKGROUND: The arrival of SARS-CoV-2 to Colombia on March 6, 2020, triggered closure of borders and mandatory lockdown from March 23, 2020. METHODS/MATERIALS: The Colombian National Institute of Health administers the National database of confirmed cases of SARS-CoV-2 and the National Haemovigilance System. We examined positive SARS-CoV-2 cases identified between March 6, 2020, and March 6, 2021, using positive RT-PCR testing (72.8%) or reactive antigen (27.2%). We also analysed accepted and deferred donors' information provided by 100% of blood banks and transfused patients notified by 83% of health care facilities nationwide, between March 1, 2019, to February 28, 2021. RESULTS: Colombia registered 2 273 245 SARS-CoV-2 cases. From these, 60 412 people died from COVID-19 (2.7%) and 2 172 418 individuals recovered (95.6%). There were 11 659 216 SARS-CoV-2 processed samples nationwide. People between the ages of 20 and 39 years concentrated 44.4% of the SARS-CoV-2 cases. There were 773 569 blood donations, mainly from a 20-39-year-old population (60.5%). The pandemic caused a reduction of 155 393 blood donations (16.7%) and 51 823 total deferrals (33.7%). An 18.4% drop in volunteer donors and a 37.3% increase in donations from family/replacements members were observed. There were 399 453 transfused patients and 1 179 895 blood components administered (-8.7% and - 13.9% compared to March 2019-February 2020). CONCLUSION: Mandatory lockdowns in Colombia decreased blood collection and usage, resulting in a reduction of blood components transfused to individual patients.

The Importance of Platelet Glycoside Residues in the Haemostasis of Patients with Immune Thrombocytopaenia.

Loss of sialic acid from the carbohydrate side chains of platelet glycoproteins can affect platelet clearance, a proposed mechanism involved in the etiopathogenesis of immune thrombocytopaenia (ITP). We aimed to assess whether changes in platelet glycosylation in patients with ITP affected platelet counts, function, and apoptosis. This observational, prospective, and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. We measured platelet activation markers and assayed platelet glycosylation and caspase activity, analysing samples using flow cytometry. Platelets from patients with ITP with a platelet count <30 × 103/µL presented less sialic acid. Levels of α1,6-fucose (a glycan residue that can directly regulate antibody-dependent cellular cytotoxicity) and α-mannose (which can be recognised by mannose-binding-lectin and activate the complement pathway) were increased in the platelets from these patients. Platelet surface exposure of other glycoside residues due to sialic acid loss inversely correlated with platelet count and the ability to be activated. Moreover, loss of sialic acid induced the ingestion of platelets by human hepatome HepG2 cells. Changes in glycoside composition of glycoproteins on the platelets' surface impaired their functional capacity and increased their apoptosis. These changes in platelet glycoside residues appeared to be related to ITP severity.

Insights into the Procoagulant Profile of Patients with Systemic Lupus Erythematosus without Antiphospholipid Antibodies.

We aimed to identify the key players in the prothrombotic profile of patients with systemic lupus erythematosus (SLE) not mediated by antiphospholipid antibodies, as well as the potential utility of global coagulation tests to characterize hemostasis in these patients. Patients with SLE without antiphospholipid antibodies and without signs of thrombosis were included. The kinetics of clot formation were determined by ROTEM®. Platelet activation markers were determined by flow cytometry. Thrombin generation associated with Neutrophil Extracellular Traps (NETs) and microparticles (MPs) was measured by calibrated automated thrombogram (CAT). The plasma levels of PAI-1 were also determined. ROTEM® showed a procoagulant profile in SLE patients. SLE patients had activated platelets and more leukocyte/platelet aggregates at basal conditions. The plasma PAI-1 and platelet aggregates correlated with several ROTEM® parameters. The thrombin generation associated withthe tissue factor (TF) content of MPs and with NETs was increased. Our results suggest the utility of global tests for studying hemostasis in SLE patients because they detect their procoagulant profile, despite having had neither antiphospholipid antibodies nor any previous thrombotic event. A global appraisal of hemostasis should, if possible, be incorporated into clinical practice to detect the risk of a thrombotic event in patients with SLE and to consequently act to prevent its occurrence.

Registry of patients with congenital bleeding disorders and COVID-19 in Madrid.

INTRODUCTION: We present the first registry of patients with congenital bleeding disorders and COVID-19. The study has been carried out in the Community of Madrid, which has the highest number of cases in Spain. The objective is to understand the incidence of COVID-19, the course of the disease if it occurs and the psychosocial and occupational impact on this population. METHODS: We included 345 patients (246 of haemophilia, 69 of von Willebrand Disease, two rare bleeding disorders and 28 carriers of haemophilia). A telephone survey was used to collect the data. RESULTS: Forty-two patients presented symptoms suggestive of infection by COVID-19, and in six cases, the disease was confirmed by RT-PCR. The cumulative incidence of our series was 1.73%. It is worth noting the complexity of the management of COVID-19 in two patients on prophylaxis with non-factor replacement therapy. Adherence to the prescribed treatment was maintained by 95.5% of patients. Although 94% were independent for daily living activities, 42.4% had a recognized disability and 58% required assistance, provided by the Madrid Haemophilia Association (Ashemadrid) in 75% of cases. Only 4.4% of consultations were held in person. CONCLUSIONS: Patients with congenital bleeding disorders infected with SARS-CoV-2 presented a mild course of the disease that did not require admission. Their identification and treatment by a specialist team from a Haemophilia Treatment Center are essential to make a correct assessment of the risk of haemorrhage/thrombosis. COVID-19 had a major impact on the psychosocial aspects of these patients which must be remedied with recovery plans.

[Community acquired urinary tract infections in older adults]. / Infecciones del tracto urinario de la comunidad en el paciente adulto mayor.

Background Community acquired urinary tract infections (caUTI) in adults are common ailments. Older adults are prone to infectious diseases, diagnosis can be difficult, their etiologic and antimicrobial resistance are poorly known. Objectives To evaluate the incidence discriminated by sex, symptoms, and to determine pathogens and their antimicrobial resistance rate. Methods A retrospective, descriptive and comparative study. We analyze uricultures among 2013 in the Hospital Nacional de Clinicas (Córdoba-Argentina). Patients over 65 years old, admitted with a caUTI diagnose were included; we exclude those with urinary catheter. Variables used: Sex, symptoms, pathogen isolation, antimicrobial resistance. For symptom variable was performed a comparative test. Descriptive statistics were used to analyze remaining variables. Results Were analyzed 349 patients: 1) Positive uricultures 191 (case), negative 158 (control). 2) Average age 77 (76% women, 24% men). 3) Symptoms: fever (45%), sepsis criteria (17%), altered mental status (14%), heart failure (11%). 4) Uriculture: monomicrobial 95.29%. 5) Isolation and resistance rate: Escherichia coli (67,7%): ampicillin/sulbactam 52.7%, ciprofloxacin 51.9%, trimethoprim/sulfamethoxazole 45.7%, cefotaxime: 12,9 %, amikacin: 3,9 %, Klebsiella pneumoniae (11,97%): ciprofloxacin 60.8%, trimethoprim/ sulfamethoxazole 50%, cefotaxime 47.8%, amikacin 4.7%. Enterococcus spp. (9,89%): ampicillin 0%, vancomycin 0%. Also isolated: Cándida spp. (3.66%), Proteus mirabilis (2,6%), Staphylococcus aureus (2,6%), Enterobacter cloacae (1,56%), Pseudomonas aeruginosa (1,56%). There were no imipenem resistances among gram negatives. Conclusions Isolations were mostly monomicrobial and at female gender. E. coli was the main uropathogen. The elevated resistance rate to ciprofloxacin, ampicillin/sulbactam and trimethoprim/sulfamethoxazole is remarkable. We suggest to avoid their empiric use in this population.

Metástasis cutáneas de cáncer de mama: revisión de la literatura / Breast cancer cutaneous metastasis: literature review

Introducción: El cáncer de mama es uno de los tumores malignos más frecuentes en mujeres, y representa el principal carcinoma que genera metástasis cutáneas (MC), excluyendo al melanoma. Objetivos: Realizar una revisión de las MC del carcinoma mamario y mostrar las principales formas de presentación clínica. Discusión: Las MC pueden presentarse mediante diferentes manifestaciones dermatológicas, aunque lo más frecuente es un infiltrado eritematoso papulonodular único o múltiple, generalmente localizado en la piel subyacente o próxima al área del tumor primario. Las células tumorales alcanzan la piel por 3 vías de diseminación: hemática, linfática y por contigüidad. Los carcinomas mamarios, normalmente, se diseminan por la vía linfática y llegan a zonas de la piel cercanas; así, las MC de mama adoptan como sitio de implantación principal la piel del tórax. Conclusiones: Las MC pueden ser la manifestación inicial de un cáncer, o bien un signo de recurrencia de este. Es necesario tener un alto nivel de sospecha diagnóstica debido a su gran polimorfismo clínico.

Introduction: Breast cancer is one of the most frequent malignant tumors in women and is the main carcinoma leading cutaneous metastasis (CMs), excluding melanoma. Objectives: To present a literature review about CMs from breast cancer and to show the mainly clinical forms. Discussion: CMs can present different skin manifestations, but single or multiple papulonodular erythematosus infiltrate are the most common, generally located in the underlying skin or close to the primary tumor area. Tumor cells reach the skin through three dissemination forms -hematogeneus, lymphatic, and contiguity-. Breast carcinomas normally disseminate through lymphatic via and reach close skin zones; thus, breast CMs mainly allocate in the thorax skin. Conclusions: CMs can be the initial manifestation of a cancer or a sign of its recurrence. There must be a high level of suspicion because its clinical polymorphism.

Mastocitosis cutánea: reporte de un caso / Cutaneous mastocytosis: A case report

Introducción La mastocitosis representa un grupo de enfermedades caracterizadas por una acumulación excesiva de mastocitos en uno o múltiples tejidos. Puede limitarse a la piel o tener un compromiso sistémico, siendo de baja prevalencia y pronóstico benigno en la infancia. Objetivo Reportar un caso de urticaria pigmentosa como subtipo de mastocitosis cutánea y hacer una revisión bibliográfica enfocada en los hallazgos clínicos, el diagnóstico y el manejo inicial básico. Caso clínico Lactante de 6 meses de edad con múltiples máculas y pápulas de color café claro localizadas en el tronco, los brazos y las piernas, cuadro compatible con una urticaria pigmentosa, confirmada mediante biopsia. Se solicitaron exámenes para descartar compromiso sistémico. La paciente fue tratada con medidas generales, educación y antihistamínicos, con excelente evolución. Conclusiones La mastocitosis cutánea es una enfermedad poco común, de buen pronóstico. En la infancia generalmente bastan las medidas generales y educación para obtener resultados favorables. La terapia farmacológica de primera línea son los antagonistas H1.

Introduction Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. Objective To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. Clinical case A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. Conclusions Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.

Pigmented basal cell carcinoma mimicking a superficial spreading melanoma. / Carcinoma de células basales pigmentado simulando un melanoma de extensión superficial.

Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

El carcinoma basocelular es el cáncer de piel más frecuente, especialmente en personas de edad avanzada. El carcinoma basocelular pigmentado es una variante poco común que se ha descrito en la literatura como una lesión nodular hiperpigmentada. En raras ocasiones puede presentarse en forma de una extensa placa pigmentada, la cual puede ser clínicamente indistinguible del melanoma maligno de extensión superficial y de la enfermedad de Bowen. La dermatoscopía tiene una alta sensibilidad en el diagnóstico del carcinoma basocelular, cuando se utilizan los criterios de Menzies, aunque el diagnóstico final es histopatológico. El objetivo del presente trabajo es reportar y analizar el caso de una paciente con un extenso carcinoma basocelular superficial pigmentado, que simula un melanoma maligno de extensión superficial.

[Cutaneous mastocytosis: A case report]. / Mastocitosis cutánea: reporte de un caso.

INTRODUCTION: Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. OBJECTIVE: To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. CLINICAL CASE: A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. CONCLUSIONS: Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.

A hybrid tool for spectral ray tracing simulations of luminescent cascade systems.

To perform adequate simulations of luminescent cascade systems, a hybrid method combining a commercial ray tracer and a programming tool is presented. True Monte Carlo algorithms for luminescent materials, treating each ray individually, are adapted to allow wavelength conversion of ray sets. Two solutions for the wavelength conversion of ray sets are discussed: a random approach, where absorption events are randomly selected to create emission events, and a combined approach, where information from multiple absorption events is combined to create emission events. Both methods are applied to simulate the performance of a virtual remote phosphor light-emitting diode module. When using the combined approach, the required computation time to achieve sufficient accuracy is a factor 2 lower, compared to the time required when applying the random approach.

Power and photon budget of a remote phosphor LED module.

Light-emitting diodes (LEDs) are becoming increasingly important for general lighting applications. The remote phosphor technology, with the phosphor located at a distance from the LEDs, offers an increased extraction efficiency for phosphor converted LEDs compared to intimate phosphor LEDs where the phosphor is placed directly on the die. Additionally, the former offers new design possibilities that are not possible with the latter. In order to further improve the system efficiency of remote phosphor LEDs, realistic simulation models are required to optimize the actual performance. In this work, a complete characterization of a remote phosphor converter (RPC) consisting of a polycarbonate diffuser plate with a phosphor coating on one side via the bi-directional scattering distribution function (BSDF) is performed. Additionally, the bi-spectral BSDF which embraces the wavelength conversion resulting from the interaction of blue light with the RPC is determined. An iterative model to predict the remote phosphor module power and photon budget, including the recuperation of backward scattered light by a mixing chamber, is introduced. The input parameters for the model are the bi-spectral BSDF data for the RPC, the emission of the blue LEDs and the mixing chamber efficiency of the LED module. A good agreement between experimental and simulated results was found, demonstrating the potential of this model to analyze the system efficiency with errors smaller than 4%.