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Article ; Online: Fibrinogen Deficiency with Thrombotic Manifestations.

Tamayo-Velasco, Álvaro / Cebeira, María José / Bombín-Canal, Carolina / Acevedo-García, Rosa María / Peñarrubia-Ponce, María Jesús

European journal of case reports in internal medicine

2022 Volume 9, Issue 6, Page(s) 3400

Abstract: Fibrinogen deficiencies are very rare. Qualitative fibrinogen deficiencies (dysfibrinogenaemia and hypodysfibrinogenemia) are functional disorders that can present with both haemorrhagic symptoms and with thrombotic phenomena as unique and paradoxical ... ...

Abstract	Fibrinogen deficiencies are very rare. Qualitative fibrinogen deficiencies (dysfibrinogenaemia and hypodysfibrinogenemia) are functional disorders that can present with both haemorrhagic symptoms and with thrombotic phenomena as unique and paradoxical manifestation. We present the case of a 77-year-old man being investigated for a partially thrombosed abdominal aortic aneurysm as well as an ischaemic stroke 20 years previously. Basic coagulation tests were normal but extended tests revealed a lengthened thrombin time (TT) combined with a significant drop in fibrinogen concentration measured with the Clauss assay and by nephelometry. After secondary fibrinogen deficiencies were ruled out, a heterozygous variant in the FGG gene was detected by next-generation sequencing, and congenital hypodysfibrinogenemia was diagnosed. Acenocumarol was initiated and no new thrombotic or haemorrhagic events had occurred after a year of follow-up. In almost 25% of cases, thrombotic events may be the only clinical manifestation of functional fibrinogen deficiencies. They are a rare cause of thrombophilia, and are probably underdiagnosed due to normal standard coagulation test results as well as a possible absence of haemorrhagic events. Consequently, a TT test (an initial 'rule out' test) should be requested in order to promptly identify these patients. Moreover, discrepancies in derived and Clauss fibrinogen test results should suggest a functional disorder. Finally, new coagulation techniques based on the functional characterization of clot formation, such as ROTEM or thrombin generation assay, could help characterize these entities and suggest new therapeutic approaches. Learning points: Functional fibrinogen deficiencies can present with thrombotic manifestations only, and are a rare and probably underdiagnosed cause of thrombophilia.Thrombin time is a highly sensitive test to rule out other conditions as aPTT and PT results may be within normal ranges, especially in functional deficiencies.Discrepancies between derived and Clauss fibrinogen findings, fibrinogen protein measurements and the use of new techniques (ROTEM or thrombin generation) are important for correct approach.
Language	English
Publishing date	2022-06-28
Publishing country	Italy
Document type	Journal Article
ISSN	2284-2594
ISSN (online)	2284-2594
DOI	10.12890/2022_003400
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Article: ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points.

Tamayo-Velasco, Álvaro / Peñarrubia-Ponce, María Jesús / Álvarez, Francisco Javier / de la Fuente, Ignacio / Pérez-González, Sonia / Andaluz-Ojeda, David

Frontiers in medicine

2022 Volume 9, Page(s) 882477

Abstract: The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe ... ...

Abstract	The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.
Language	English
Publishing date	2022-04-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.882477
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Article ; Online: Association of blood group A with hospital comorbidity in patients infected by SARS-CoV-2.

Tamayo-Velasco, Álvaro / Jiménez García, María Teresa / Sanchez Rodríguez, Alba / Hijas Villaizan, Milagros / Carretero Gómez, Juana / Miramontes-González, José Pablo

Medicina clinica (English ed.)

2022 Volume 159, Issue 1, Page(s) 27–30

Abstract: Background and objectives: In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The ... ...

Abstract	Background and objectives: In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The objective of this study was to evaluate whether patients with blood group A were associated with more important comorbidities, measured by the Charlson Index, which may explain their worse clinical evolution. Patients and methods: A prospective and consecutive study examined 100 patients diagnosed with COVID-19 and admitted in March 2020. A multivariate linear regression model was used to evaluate the association of blood group A with the Charlson Index. Results: Patients in group A had a higher Charlson Index ( Conclusions: Group A was independently associated with greater comorbidity, associated with an increase of 0.582 points in the Charlson Index compared to other blood groups. It was also associated with lower hospital mortality.
Language	English
Publishing date	2022-06-29
Publishing country	Spain
Document type	Case Reports
ISSN	2387-0206
ISSN (online)	2387-0206
DOI	10.1016/j.medcle.2021.06.028
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Article ; Online: COVID-19-associated pulmonary aspergillosis (CAPA) in hematological patients: Could antifungal prophylaxis be necessary? A nationwide study.

Tamayo-Velasco, Álvaro / López-Herrero, Rocío / Gómez-García, Lara María / Sánchez-de Prada, Laura / Aguilar-Monserrate, Gerardo / Martín-Fernández, Marta / Bardají-Carrillo, Miguel / Álvaro-Meca, Alejandro / Tamayo, Eduardo / Resino, Salvador / Miramontes-González, José Pablo / Peñarrubia-Ponce, María Jesús

Journal of infection and public health

2024 Volume 17, Issue 6, Page(s) 939–946

Abstract: Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as ... ...

Abstract	Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. Methods: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. Findings: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p < 0.001). Candida spp. showed higher rate in non-COVID-19 (74.2 % vs. 66.8 %; p = 0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4 % vs. 19.1 %; p < 0.001). IPA was diagnosed in 703 patients and 11.2 % (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9-3.1), p < 0.001]. B-cell malignancies - specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia - showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50 % and 72 %. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients. Conclusion: COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted.
Language	English
Publishing date	2024-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2467587-8
ISSN	1876-035X ; 1876-0341
ISSN (online)	1876-035X
ISSN	1876-0341
DOI	10.1016/j.jiph.2024.04.005
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Article ; Online: Environmental factors are associated to hospital outcomes in COVID-19 patients during lockdown and post-lockdown in 2020: A nationwide study

Sánchez-de Prada, Laura / Eiros-Bachiller, José María / Tamayo-Velasco, Alvaro / Martín Fernández, Marta / Alvarez, Javier / Giner-Baixauli, Carlos / Tamayo, Eduardo / Resino, Salvador / Alvaro-Meca, Alejandro

Environmental Research. 2023 Apr. 18, p.115904-

2023 , Page(s) 115904–

Abstract: This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown and post- ... ...

Abstract	This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown and post-lockdown 2020 period in Spain. We performed a nationwide population-based retrospective study on 208,744 patients admitted to Spanish hospitals due to COVID-19 based on the Minimum Basic Data Set (MBDS) during the first two waves of the pandemic in 2020. Environmental data were obtained from Copernicus Atmosphere Monitoring Service. The association was assessed by a generalized additive model. PM₂.₅ was the most critical environmental factor related to hospital admissions and hospital mortality due to COVID-19 during the lockdown in Spain, PM₁₀, NO₂, and SO2and also showed associations. The effect was considerably reduced during the post-lockdown period. ICU admissions in COVID-19 patients were mainly associated with PM₂.₅, PM₁₀, NO₂, and SO2 during the lockdown as well. During the lockdown, exposure to PM₂.₅ and PM₁₀ were the most critical environmental factors related to ICU mortality in COVID-19. Short-term exposure to air pollutants impacts COVID-19 out-comes during the lockdown, especially PM₂.₅, PM₁₀, NO₂, and SO2. These pollutants are associated with hospital admission, hospital mortality and ICU admission, while ICU mortality is mainly associated with PM₂.₅ and PM₁₀. Our findings reveal the importance of monitoring air pollutants in respiratory infectious diseases.
Keywords	COVID-19 infection ; acute exposure ; air ; data collection ; environmental factors ; hospitals ; models ; mortality ; pandemic ; research ; retrospective studies ; Spain ; COVID-19 ; Hospitalizations ; Hospital mortality ; Intensive care unit ; Air pollution ; Respiratory virus
Language	English
Dates of publication	2023-0418
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.115904
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Article: Immune checkpoint inhibitors in non-small cell lung cancer: from current perspectives to future treatments-a systematic review.

Olivares-Hernández, Alejandro / González Del Portillo, Elísabet / Tamayo-Velasco, Álvaro / Figuero-Pérez, Luis / Zhilina-Zhilina, Svetlana / Fonseca-Sánchez, Emilio / Miramontes-González, José Pablo

Annals of translational medicine

2023 Volume 11, Issue 10, Page(s) 354

Abstract: Background: The introduction of immunotherapy in the treatment of non-small cell lung cancer (NSCLC) has resulted in a radical change in patients' treatment responses and survival rates. The increased percentage of long survivors, improved toxicity ... ...

Abstract	Background: The introduction of immunotherapy in the treatment of non-small cell lung cancer (NSCLC) has resulted in a radical change in patients' treatment responses and survival rates. The increased percentage of long survivors, improved toxicity profiles compared to chemotherapy, and the possible applications for different NSCLC scenarios, have led to immune checkpoint inhibitors (ICIs) becoming the cornerstone of NSCLC treatment. Therefore, the objective of this review is to describe the current and future perspectives of NSCLC treatment. Methods: A systematic review according to the PRISMA criteria has been performed based on clinical trials with immunotherapy in NSCLC from the start of these treatments until June 2022. Results: The use of ICIs is widespread across both first- and second-line treatments with anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs. New indications for immunotherapy in NSCLC have focused on adjuvant (atezolizumab) and neoadjuvant (nivolumab), with ICIs now present in all stages of NSCLC treatment. Given the promising results seen in clinical trials, new ICIs [anti- lymphocyte activation gene-3 (LAG-3) or IDO1] currently under development, will soon be used as standard treatment for NSCLC. Conclusions: Immunotherapy is the mainstay of NSCLC treatment in all stages, including adjuvant, neoadjuvant and advanced tumors. The development of new molecules will revolutionize the treatment of NSCLC in the coming years.
Language	English
Publishing date	2023-05-23
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2893931-1
ISSN	2305-5847 ; 2305-5839
ISSN (online)	2305-5847
ISSN	2305-5839
DOI	10.21037/atm-22-4218
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Article ; Online: Environmental factors are associated to hospital outcomes in COVID-19 patients during lockdown and post-lockdown in 2020: A nationwide study.

Sánchez-de Prada, Laura / Eiros-Bachiller, José María / Tamayo-Velasco, Álvaro / Martín-Fernández, Marta / Álvarez, F Javier / Giner-Baixauli, Carlos / Tamayo, Eduardo / Resino, Salvador / Alvaro-Meca, Alejandro

Environmental research

2023 Volume 229, Page(s) 115904

Abstract: Objective: This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown ... ...

Abstract	Objective: This study analyzed, at a postcode detailed level, the relation-ship between short-term exposure to environmental factors and hospital ad-missions, in-hospital mortality, ICU admission, and ICU mortality due to COVID-19 during the lockdown and post-lockdown 2020 period in Spain. Methods: We performed a nationwide population-based retrospective study on 208,744 patients admitted to Spanish hospitals due to COVID-19 based on the Minimum Basic Data Set (MBDS) during the first two waves of the pandemic in 2020. Environmental data were obtained from Copernicus Atmosphere Monitoring Service. The association was assessed by a generalized additive model. Results: PM Conclusion: Short-term exposure to air pollutants impacts COVID-19 out-comes during the lockdown, especially PM
MeSH term(s)	Humans ; COVID-19/epidemiology ; Air Pollution/analysis ; Nitrogen Dioxide/analysis ; Retrospective Studies ; Communicable Disease Control ; Air Pollutants/analysis ; Hospitals ; Particulate Matter/analysis ; Environmental Monitoring
Chemical Substances	Nitrogen Dioxide (S7G510RUBH) ; Air Pollutants ; Particulate Matter
Language	English
Publishing date	2023-04-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.115904
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Article ; Online: Endothelial Dysfunction and Neutrophil Degranulation as Central Events in Sepsis Physiopathology.

Martín-Fernández, Marta / Tamayo-Velasco, Álvaro / Aller, Rocío / Gonzalo-Benito, Hugo / Martínez-Paz, Pedro / Tamayo, Eduardo

International journal of molecular sciences

2021 Volume 22, Issue 12

Abstract: Sepsis is a major health problem worldwide. It is a time-dependent disease, with a high rate of morbidity and mortality. In this sense, an early diagnosis is essential to reduce these rates. The progressive increase of both the incidence and prevalence ... ...

Abstract	Sepsis is a major health problem worldwide. It is a time-dependent disease, with a high rate of morbidity and mortality. In this sense, an early diagnosis is essential to reduce these rates. The progressive increase of both the incidence and prevalence of sepsis has translated into a significant socioeconomic burden for health systems. Currently, it is the leading cause of noncoronary mortality worldwide and represents one of the most prevalent pathologies both in hospital emergency services and in intensive care units. In this article, we review the role of both endothelial dysfunction and neutrophil dysregulation in the physiopathology of this disease. The lack of a key symptom in sepsis makes it difficult to obtain a quick and accurate diagnosis of this condition. Thus, it is essential to have fast and reliable diagnostic tools. In this sense, the use of biomarkers can be a very important alternative when it comes to achieving these goals. Both new biomarkers and treatments related to endothelial dysfunction and neutrophil dysregulation deserve to be further investigated in order to open new venues for the diagnosis, treatment and prognosis of sepsis.
MeSH term(s)	Animals ; Endothelium, Vascular/pathology ; Humans ; Neutrophils/pathology ; Sepsis/etiology ; Sepsis/physiopathology
Language	English
Publishing date	2021-06-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22126272
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Article ; Online: Association of blood group A with hospital comorbidity in patients infected by SARS-CoV-2.

Tamayo-Velasco, Álvaro / Jiménez García, María Teresa / Sánchez Rodríguez, Alba / Hijas Villaizan, Milagros / Carretero Gómez, Juana / Miramontes-González, José Pablo

Medicina clinica

2021 Volume 159, Issue 1, Page(s) 27–30

Title translation	Asociación del grupo sanguíneo A con mayor comorbilidad hospitalaria en pacientes infectados por SARS-CoV-2.
Abstract	Background and objectives: In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The objective of this study was to evaluate whether patients with blood group A were associated with more important comorbidities, measured by the Charlson Index, which may explain their worse clinical evolution. Patients and methods: A prospective and consecutive study examined 100 patients diagnosed with COVID-19 and admitted in March 2020. A multivariate linear regression model was used to evaluate the association of blood group A with the Charlson Index. Results: Patients in group A had a higher Charlson Index (P=.037), rate of lymphopenia (P=.039) and thrombopenia (P=.014), and hospital mortality (P=.044). Blood group A was an independent factor associated with the Charlson Index (B 0.582, 95% CI 0.02-1.14, P=0.041). Conclusions: Group A was independently associated with greater comorbidity, associated with an increase of 0.582 points in the Charlson Index compared to other blood groups. It was also associated with lower hospital mortality.
MeSH term(s)	Blood Group Antigens ; COVID-19/complications ; COVID-19/epidemiology ; Comorbidity ; Hospital Mortality ; Hospitals ; Humans ; Prospective Studies ; SARS-CoV-2
Chemical Substances	Blood Group Antigens
Language	Spanish
Publishing date	2021-07-15
Publishing country	Spain
Document type	Case Reports
ZDB-ID	411607-0
ISSN	1578-8989 ; 0025-7753
ISSN (online)	1578-8989
ISSN	0025-7753
DOI	10.1016/j.medcli.2021.06.017
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Article: Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic.

Tamayo-Velasco, Álvaro / Bombín-Canal, Carolina / Cebeira, María José / Sánchez-De Prada, Laura / Miramontes-González, José Pablo / Martín-Fernández, Marta / Peñarrubia-Ponce, María Jesús

Journal of clinical medicine

2022 Volume 11, Issue 12

Abstract: The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 ... ...

Abstract	The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 hospitalized COVID-19 patients followed up during the first 18 months of the pandemic to completely characterize any TE. Major TEs showed a 3.45% incidence rate. TEs were associated with increased intubation/90-day mortality risk [OR = 1.71, 95% CI (1.12−2.61), p < 0.013]. Venous thrombotic events (VTEs) were more frequent than arterial thrombotic events (ATEs) (72% vs. 28%), associated with enhanced levels of D-dimer (cross-linked fibrin derivatives formed during thrombolysis), which were related to mortality but more useful for early detection of thrombosis. In this regard, D-dimer plasma levels above 2014 µg/mL at hospital admission identify TEs with 91% accuracy (AUC = 0.91, p < 0.001), rising to almost 95% (AUC = 0.94, p < 0.001) with a cut-off value of 2666 µg/mL in VTEs. Moreover, 41% of TEs occurred in patients receiving LMWH thromboprophylactic treatments in hospital or domiciliary therapies. SARS-CoV-2 infection along with a sedentary lifestyle derived from the confinement in 2020 could be more determinant than a procoagulant state in patients with risk factors for TEs. Furthermore, the normal results obtained from the thrombophilia study after the acute process are linked to this independent procoagulant state and to SARS-CoV-2-derived coagulopathy.
Language	English
Publishing date	2022-06-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11123443
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