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1.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38763214

RESUMO

Myocarditis is defined as myocardial inflammation and its etiology is highly diverse, including infectious agents, drugs, and autoimmune diseases. The clinical presentation also varies widely, extending beyond the classic clinical picture of acute chest pain, and includes cases of cardiomyopathy of unknown cause whose etiology may be inflammatory. Because certain patients may benefit from targeted treatments, the search for the etiology should begin when myocarditis is first suspected. There remain several areas of uncertainty in the diagnosis and treatment of this disease. Consequently, this consensus document aims to provide clear recommendations for its diagnosis and treatment. Hence, a diagnostic algorithm is proposed, specifying when non-invasive diagnosis with cardiac MR is appropriate vs a noninvasive approach with endomyocardial biopsy. In addition, more novel aspects are discussed, such as when to suspect an underlying genetic etiology. The recommendations cover the management of myocarditis and inflammatory cardiomyopathy, both for general complications and specific clinical entities.

3.
Heliyon ; 10(6): e27360, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515664

RESUMO

Liquid biopsy-derived RNA sequencing (lbRNA-seq) exhibits significant promise for clinic-oriented cancer diagnostics due to its non-invasiveness and ease of repeatability. Despite substantial advancements, obstacles like technical artefacts and process standardisation impede seamless clinical integration. Alongside addressing technical aspects such as normalising fluctuating low-input material and establishing a standardised clinical workflow, the lack of result validation using independent datasets remains a critical factor contributing to the often low reproducibility of liquid biopsy-detected biomarkers. Considering the outlined drawbacks, our objective was to establish a workflow/methodology characterised by: 1. Harness the rich diversity of biological features accessible through lbRNA-seq data, encompassing a holistic range of molecular and functional attributes. These components are seamlessly integrated via a Machine Learning-based Ensemble Classification framework, enabling a unified and comprehensive analysis of the intricate information encoded within the data. 2. Implementing and rigorously benchmarking intra-sample normalisation methods to heighten their relevance within clinical settings. 3. Thoroughly assessing its efficacy across independent test sets to ascertain its robustness and potential utility. Using ten datasets from several studies comprising three different sources of biological material, we first show that while the best-performing normalisation methods depend strongly on the dataset and coupled Machine Learning method, the rather simple Counts Per Million method is generally very robust, showing comparable performance to cross-sample methods. Subsequently, we demonstrate that the innovative biofeature types introduced in this study, such as the Fraction of Canonical Transcript, harbour complementary information. Consequently, their inclusion consistently enhances prediction power compared to models relying solely on gene expression-based biofeatures. Finally, we demonstrate that the workflow is robust on completely independent datasets, generally from different labs and/or different protocols. Taken together, the workflow presented here outperforms generally employed methods in prediction accuracy and may hold potential for clinical diagnostics application due to its specific design.

4.
Front Immunol ; 15: 1352929, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545116

RESUMO

Background: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8+ T-cell response. Aims: To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8+ T-cell response. Methods: We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8+ cell effector function were correlated with HBsAg level. Results: A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8+ T-cell proliferation against at least two HBV epitopes was higher in HBsAg < 1,000 IU/ml group. CD8+ T-cell expansion after HBVpolymerase456-63-specific stimulation was impaired in HBsAg > 1,000 IU/ml group, while the response against HBVcore18-27 was preserved and response against envelope183-91 was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase456-63 CD8+ cell response had lower LS/duration of infection and APRI/duration of infection rates. HBV-polymerase456-63-specific CD8+ T-cell proliferation intensity was negatively correlated with LS/years of infection ratio. Conclusion: HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8+ T-cell response.


Assuntos
Produtos do Gene pol , Hepatite B Crônica , Humanos , Vírus da Hepatite B/fisiologia , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Inflamação , Cirrose Hepática , Linfócitos T CD8-Positivos , Alanina Transaminase , Fenótipo
5.
Drugs Context ; 132024.
Artigo em Inglês | MEDLINE | ID: mdl-38264404

RESUMO

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation.

6.
Arch Bronconeumol ; 60(2): 88-94, 2024 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38160163

RESUMO

INTRODUCTION: The aim of this study was to analyze the clinical and genetic characteristics of young lung cancer cases, and to compare them with those of older cases. METHODS: We used the Thoracic Tumors Registry (TTR) as a data source representative of lung cancer cases diagnosed in Spain, and included all cases registered until 9/01/2023 which had information on age at diagnosis or the data needed to calculate it. We performed a descriptive statistical analysis and fitted logistic regressions to analyze how different characteristics influenced being a younger lung cancer patient. RESULTS: A total of 26,336 subjects were included. Lung cancer cases <50 years old had a higher probability of being women (OR: 1.38; 95% CI: 1.21-1.57), being in stage III or IV (OR: 1.32; 95% CI: 1.08-1.62), not having comorbidities (OR: 5.21; 95% CI: 4.59-5.91), presenting with symptoms at diagnosis (OR: 1.53; 95% CI: 1.29-1.81), and having ALK translocation (OR: 7.61; 95% CI: 1.25-46.32) and HER2 mutation (OR: 5.71; 95% CI: 1.34-24.33), compared with subjects ≥50 years. Among subjects <35 years old (n=61), our study observed a higher proportion of women (59.0% vs. 26.6%; p<0.001), never smokers (45.8% vs. 10.3%; p<0.001), no comorbidities (21.3% vs. 74.0%; p<0.001); ALK translocation (33.3% vs. 4.4%; p<0.001) and ROS1 mutation (14.3% vs. 2.3%; p=0.01), compared with subjects ≥35 years. CONCLUSIONS: Lung cancer displays differences by age at diagnosis which may have important implications for its clinical management.


Assuntos
Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , Receptores ErbB/genética , Proteínas Proto-Oncogênicas/genética , Mutação
7.
J Geriatr Cardiol ; 20(4): 247-255, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37122985

RESUMO

BACKGROUND: The prevalence of heart failure (HF) increases with age, and it is one of the leading causes of hospitalization and death in older patients. However, there are little data on in-hospital mortality in patients with HF ≥ 75 years in Spain. METHODS: A retrospective analysis of the Spanish Minimum Basic Data Set was performed, including all HF episodes discharged from public hospitals in Spain between 2016 and 2019. Coding was performed using the International Classification of Diseases, 10th Revision. Patients ≥ 75 years with HF as the principal diagnosis were selected. We calculated: (1) the crude in-hospital mortality rate and its distribution according to age and sex; (2) the risk-standardized in-hospital mortality ratio; and (3) the association between in-hospital mortality and the availability of an intensive cardiac care unit (ICCU) in the hospital. RESULTS: We included 354,792 HF episodes of patients over 75 years. The mean age was 85.2 ± 5.5 years, and 59.2% of patients were women. The most frequent comorbidities were renal failure (46.1%), diabetes mellitus (35.5%), valvular disease (33.9%), cardiorespiratory failure (29.8%), and hypertension (26.9%). In-hospital mortality was 12.7%, and increased with age [odds ratio (OR) = 1.07, 95% CI: 1.07-1.07, P < 0.001] and was lower in women (OR = 0.96, 95% CI: 0.92-0.97, P < 0.001). The main predictors of mortality were the presence of cardiogenic shock (OR = 19.5, 95% CI: 16.8-22.7, P < 0.001), stroke (OR = 3.5, 95% CI: 3.0-4.0, P < 0.001) and advanced cancer (OR = 2.6, 95% CI: 2.5-2.8, P < 0.001). In hospitals with ICCU, the in-hospital risk-adjusted mortality tended to be lower (OR = 0.85, 95% CI: 0.72-1.00, P = 0.053). CONCLUSIONS: In-hospital mortality in patients with HF ≥ 75 years between 2016 and 2019 was 12.7%, higher in males and elderly patients. The main predictors of mortality were cardiogenic shock, stroke, and advanced cancer. There was a trend toward lower mortality in centers with an ICCU.

8.
Clin Transl Oncol ; 25(10): 3021-3031, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37036596

RESUMO

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Trombose , Neoplasias da Bexiga Urinária , Tromboembolia Venosa , Humanos , Inibidores de Checkpoint Imunológico , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Bexiga Urinária , Oncologia , Neoplasias Renais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Albumina Sérica , Fatores de Risco
9.
Artigo em Inglês | MEDLINE | ID: mdl-36767982

RESUMO

Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness of the cranial and skeletal muscles, however, neuropathies are extremely rare. In this case report we present a case of a 61-year-old man diagnosed Myasthenia gravis who came to our attention due to a 1 week of acute deep pain [NPRS 8/10] in the anterior and medial right knee which occurred during walking [NPRS 8/10] or stair climbing [NPRS 9/10]. A complete medical record and clinical examination based on physical exploration and ultrasound assessment confirmed a infrapatellar saphenous neuralgia. Therapeutic interventions included Percutaneous nerve electrical stimulation combined with pain neuroscience education, neural mobilization of the saphenous nerve and quadriceps resistance exercises. After 4 weeks, pain intensity [NRPS = 1/10], knee functionality [OKS = 41/48] and lower limb functionality [LLFI = 80%] were notably improved, nevertheless, fatigue [RPE = 2/10] was similar than baseline. At 2 months of follow-up, the effect on intensity of pain NRPS [0/10] and functionality OKS [40/48] and LLFI [82%] was maintained, however, no significant clinical changes were detected on perceived fatigue RPE Scale [2/10]. Despite the important methodological limitations of this study, our case report highlights the efficacy of percutaneous electrical nerve stimulation combined with physical agents modalities for pain and functionality of infrapatellar saphenous neuralgia in the context of Myasthenia gravis.


Assuntos
Miastenia Gravis , Neuralgia , Estimulação Elétrica Nervosa Transcutânea , Masculino , Humanos , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Miastenia Gravis/terapia , Miastenia Gravis/diagnóstico , Músculo Esquelético , Fadiga
10.
Clin Exp Dent Res ; 9(1): 100-111, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36600477

RESUMO

OBJECTIVE: Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for upper lower airways and kidneys. The etiology remains unknown although it may originate from different stimuli, in genetically susceptible patients. MATERIALS AND METHODS: A detailed database search was performed. The variables were demographics, localization, histopathological findings, antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA) tests, treatment, and follow-up. RESULTS: Fifty-two cases were identified; the mean age was 49.6 years, with a range from 6 to 87 years. It was most frequently seen in females (57.7%). The most common race was white (59.6%). The most frequent location was in the maxillary gingiva (28.8%), followed by both the upper and lower gingiva (19.2%). The most common clinical presentation was "strawberry gingivitis" (61.5%). The main symptom was pain, in 50%. Regarding the c-ANCA test, it was positive in 71.2% of cases. The most common therapy was prednisone and cyclophosphamide, utilized in 51.9%. The average follow-up was 23.6 months, and 88.5% of patients were still alive at follow-up. CONCLUSION: The diagnosis initially was difficult to establish, an early diagnosis and treatment are mandatory. If untreated the disease can be associated with morbidity and mortality. For the oral clinician, this disease needs to be addressed in the differential diagnosis of oral lesions.


Assuntos
Granulomatose com Poliangiite , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/terapia , Granulomatose com Poliangiite/complicações , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Ciclofosfamida/uso terapêutico
11.
IEEE Rev Biomed Eng ; 16: 192-207, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34847043

RESUMO

Healthcare agents, in particular in the oncology field, are currently collecting vast amounts of diverse patient data. In this context, some decision-support systems, mostly based on deep learning techniques, have already been approved for clinical purposes. Despite all the efforts in introducing artificial intelligence methods in the workflow of clinicians, its lack of interpretability - understand how the methods make decisions - still inhibits their dissemination in clinical practice. The aim of this article is to present an easy guide for oncologists explaining how these methods make decisions and illustrating the strategies to explain them. Theoretical concepts were illustrated based on oncological examples and a literature review of research works was performed from PubMed between January 2014 to September 2020, using "deep learning techniques," "interpretability" and "oncology" as keywords. Overall, more than 60% are related to breast, skin or brain cancers and the majority focused on explaining the importance of tumor characteristics (e.g. dimension, shape) in the predictions. The most used computational methods are multilayer perceptrons and convolutional neural networks. Nevertheless, despite being successfully applied in different cancers scenarios, endowing deep learning techniques with interpretability, while maintaining their performance, continues to be one of the greatest challenges of artificial intelligence.


Assuntos
Neoplasias Encefálicas , Oncologistas , Humanos , Inteligência Artificial , Aprendizado de Máquina , Redes Neurais de Computação
12.
Orthop J Sports Med ; 10(10): 23259671221130710, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36329951

RESUMO

Background: Glenohumeral arthropathy after surgery for traumatic shoulder instability is a condition whose etiology and long-term course are still unknown. Purpose: To evaluate the risk factors for the onset of arthropathy and to assess the relationship between the degree of arthropathy and final outcomes. Study Design: Case series; Level of evidence, 4. Methods: We included patients who underwent surgery for a shoulder instability at a single institution between 2000 and 2004. The following variables were studied for relationship with functional outcomes: sex, age, body mass index, smoking at the time of surgery, number of episodes of shoulder dislocation, and time from first dislocation to surgery. The number of anchors used and their position were also evaluated. Functional outcomes were assessed using the Constant-Murley, Western Ontario Shoulder Instability Index, and Rowe scores, and results were compared with the onset of arthropathy according to Buscayret classification. Spearman and Pearson correlations were performed for the association between glenohumeral arthritis (Buscayret grade) and the study variables, the Mann-Whitney U test and Student t test were used to compare outcome scores with the study variables, and the Kruskal-Wallis test was used to compare Buscayret grade and outcome scores. Results: A total of 26 shoulders in 25 patients were analyzed, finding a high rate (54%) of arthropathy at a minimum follow-up of 16 years. Patients with Buscayret grade 4 had the worst functional results (P = .007). However, 80% of patients with Buscayret grade ≤3 had excellent Constant-Murley scores. A significant relationship was found between degree of arthropathy and patients who were smokers before surgery (P < .01). No relationship was found between the onset of arthropathy and the other variables analyzed. Conclusion: Postinstability glenohumeral arthropathy was not correlated with functional outcomes except in those patients with advanced arthroplasty (Buscayret grade 4). A direct relationship was found between smoking before surgery and the onset of glenohumeral arthropathy.

13.
ACS Appl Nano Mater ; 5(9): 12951-12961, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36185167

RESUMO

Extracellular vesicles (EVs) are nanosized circulating assemblies that contain biomarkers considered promising for early diagnosis within neurology, cardiology, and oncology. Recently, acoustic wave biosensors, in particular based on quartz crystal microbalance with dissipation monitoring (QCM-D), have emerged as a sensitive, label-free, and selective EV characterization platform. A rational approach to further improving sensing detection limits relies on the nanostructuration of the sensor surfaces. To this end, inorganic inverse opals (IOs) derived from colloidal self-assembly present a highly tunable and scalable nanoarchitecture of suitable feature sizes and surface chemistry. This work systematically investigates their use in two-dimensional (2D) and three-dimensional (3D) for enhanced QCM-D EV detection. Precise tuning of the architecture parameters delivered improvements in detection performance to sensitivities as low as 6.24 × 107 particles/mL. Our findings emphasize that attempts to enhance acoustic immunosensing via increasing the surface area by 3D nanostructuration need to be carefully analyzed in order to exclude solvent and artifact entrapment effects. Moreover, the use of 2D nanostructured electrodes to compartmentalize analyte anchoring presents a particularly promising design principle.

14.
Sci Rep ; 12(1): 15622, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114256

RESUMO

The early detection of symptoms and rapid testing are the basis of an efficient screening strategy to control COVID-19 transmission. The olfactory dysfunction is one of the most prevalent symptom and in many cases is the first symptom. This study aims to develop a machine learning COVID-19 predictive tool based on symptoms and a simple olfactory test, which consists of identifying the smell of an aromatized hydroalcoholic gel. A multi-centre population-based prospective study was carried out in the city of Reus (Catalonia, Spain). The study included consecutive patients undergoing a reverse transcriptase polymerase chain reaction test for presenting symptoms suggestive of COVID-19 or for being close contacts of a confirmed COVID-19 case. A total of 519 patients were included, 386 (74.4%) had at least one symptom and 133 (25.6%) were asymptomatic. A classification tree model including sex, age, relevant symptoms and the olfactory test results obtained a sensitivity of 0.97 (95% CI 0.91-0.99), a specificity of 0.39 (95% CI 0.34-0.44) and an AUC of 0.87 (95% CI 0.83-0.92). This shows that this machine learning predictive model is a promising mass screening for COVID-19.


Assuntos
COVID-19 , Olfato , COVID-19/diagnóstico , Humanos , Aprendizado de Máquina , Programas de Rastreamento , Estudos Prospectivos
15.
Clin Breast Cancer ; 22(7): 634-641, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36002343

RESUMO

Genomic platforms have proven to be more accurate as a prognostic tool than immunohistochemistry studies in patients with early, hormone receptor positive, HER 2 negative breast cancer and, in some cases, have also demonstrated predictive ability for chemotherapy benefit. They are now widely applied in node-negative disease, but their use in node-positive disease is more recent and more controversial, especially in premenopausal patients. In this article, we review the use of these tests in node-positive disease.


Assuntos
Neoplasias da Mama , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Feminino , Genômica , Humanos , Prognóstico
16.
Int J Infect Dis ; 123: 97-103, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35987472

RESUMO

OBJECTIVES: Severe COVID-19 is associated with immune dysregulation and hyperinflammation (lymphocyte exhaustion and elevated interleukin 6. Pembrolizumab (P; immune-activating anti-programmed cell death-1 antibody) plus tocilizumab (TCZ; anti- interleukin 6 receptor antibody) might interrupt the hyperinflammation and restore cellular immunocompetence. We assessed the efficacy and safety of P + TCZ + standard of care (SOC) in high-risk, hospitalized patients with COVID-19 pneumonia without mechanical ventilation. METHODS: Randomized, controlled, open-label, phase II trial in patients with severe SARS-CoV-2 infection to assess the hospitalization period to discharge. RESULTS: A total of 12 patients were randomized (P + TCZ + SOC, n = 7; SOC, n = 5). Nine (75%) were males, with a median age of 68 (41-79) years. The median time to discharge for P + TCZ + SOC and SOC was 10 and 47.5 days (P = 0.03), with zero (n = 1 patient had P-related grade 5 myositis) and two COVID-19-related deaths, respectively. CONCLUSION: The addition of P and TCZ to SOC reduced the hospitalization period, with higher and faster discharges without sequelae than SOC alone.


Assuntos
Tratamento Farmacológico da COVID-19 , Idoso , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Interleucina-6 , Masculino , Estudo de Prova de Conceito , Receptores de Interleucina-6 , SARS-CoV-2 , Resultado do Tratamento
17.
J Clin Med ; 11(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35806866

RESUMO

COVID-19 has overloaded health system worldwide; thus, it demanded a triage method for an efficient and early discrimination of patients with COVID-19. The objective of this research was to perform a model based on commonly requested hematological variables for an early featuring of patients with COVID-19 form other viral pneumonia. This investigation enrolled 951 patients (mean of age 68 and 56% of male) who underwent a PCR test for respiratory viruses between January 2019 and January 2020, and those who underwent a PCR test for detection of SARS-CoV-2 between February 2020 and October 2020. A comparative analysis of the population according to PCR tests and logistic regression model was performed. A total of 10 variables were found for the characterization of COVID-19: age, sex, anemia, immunosuppression, C-reactive protein, chronic obstructive pulmonary disease, cardiorespiratory disease, metastasis, leukocytes and monocytes. The ROC curve revealed a sensitivity and specificity of 75%. A deep analysis showed low levels of leukocytes in COVID-19-positive patients, which could be used as a primary outcome of COVID-19 detection. In conclusion, this investigation found that commonly requested laboratory variables are able to help physicians to distinguish COVID-19 and perform a quick stratification of patients into different prognostic categories.

18.
Nat Commun ; 13(1): 3913, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35798748

RESUMO

Cognitive function relies on a balanced interplay between excitatory and inhibitory neurons (INs), but the impact of estradiol on IN function is not fully understood. Here, we characterize the regulation of hippocampal INs by aromatase, the enzyme responsible for estradiol synthesis, using a combination of molecular, genetic, functional and behavioral tools. The results show that CA1 parvalbumin-expressing INs (PV-INs) contribute to brain estradiol synthesis. Brain aromatase regulates synaptic inhibition through a mechanism that involves modification of perineuronal nets enwrapping PV-INs. In the female brain, aromatase modulates PV-INs activity, the dynamics of network oscillations and hippocampal-dependent memory. Aromatase regulation of PV-INs and inhibitory synapses is determined by the gonads and independent of sex chromosomes. These results suggest PV-INs are mediators of estrogenic regulation of behaviorally-relevant activity.


Assuntos
Aromatase , Parvalbuminas , Animais , Aromatase/genética , Estradiol/farmacologia , Feminino , Hipocampo/fisiologia , Interneurônios/fisiologia , Masculino , Camundongos , Parvalbuminas/genética , Parvalbuminas/metabolismo , Sinapses/metabolismo
19.
Cancers (Basel) ; 14(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35681606

RESUMO

Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.

20.
ESC Heart Fail ; 9(5): 3071-3078, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35748119

RESUMO

AIMS: Hyperkalaemia (HK) is common in heart failure (HF) patients, related to renal dysfunction and medical treatment. It limits medical therapy optimization, which impacts prognosis. New potassium (K) binders help control HK, allowing better medical management of HF. METHODS AND RESULTS: A retrospective multicentre register included all outpatients with HF and HK (K ≥ 5.1 mEq/L) treated with patiromer according to current recommendations. We evaluated analytic and clinical parameters before starting the treatment and at 7, 30 and 90 days, as well as adverse events related to patiromer and treatment optimization. We included 74 patients (71.6% male) with a mean age of 70.8 years (SD 9.2). Sixty-seven patients (90.5%) presented HK in the previous year. Forty patients (54.1%) underwent down-titration of a renin-angiotensin-aldosterone inhibitor (RAASi) or a mineralocorticoid receptor antagonist (MRA), and 27 (36.5%) stopped any of them due to HK. Initial K was 5.5 mEq/L (SD 0.6), with a significantly reduction at 7 days (4.9 mEq/L (SD 0.8); P < 0.001), maintained at 90 days (4.9 mEq/L (SD 0.8); P < 0.001). There were no other electrolyte disturbances, with a slight improvement in renal function [glomerular filtration rate 39.6 mL/min (SD 20.4) to 42.7 mL/min (SD 23.2); P = 0.005]. Adverse events were reported in 33.9% of patients, the most common being hypomagnesaemia (16.3%), gastrointestinal disturbances (14.9%) and HK (2.8%). Withdrawal of patiromer was uncommon (12.2%) due to gastrointestinal disturbances in 66.7% of cases. Nine patients (12.2%) started on a RAASi, and 15 patients (20.3%) on an MRA during the follow-up. Forty-five patients (60.8%) increased the dose of RAASi or MRA, increasing to target doses in 5.4 and 10.8% of patients, respectively. At 90 days, NTproBNP values were reduced from 2509.5 pg/mL [IQR 1311-4,249] to 1396.0 pg/mL [IQR 804-4263]; P = 0.003, but the reduction was only observed in those who optimized HF medical treatment [NTproBNP from 1950.5 pg/mL (IQR 1208-3403) to 1349.0 pg/mL (IQR 804-2609); P < 0.01]. NYHA functional class only improved in 7.5% of patients, corresponding with those who optimized HF medical treatment. Compared with the previous 3 months before patiromer treatment, the rate of hospitalization was reduced from 28.4 to 10.9% (P < 0.01), and the emergency room visits from 18.9 to 5.4% (P < 0.01). CONCLUSIONS: In a real-life cohort of patients with HF, patiromer reduced and maintained K levels during 3 months of follow-up. The most common adverse events were hypomagnesaemia and gastrointestinal disturbances. Patiromer helps optimize medical treatment, increasing the percentage of patients treated with RAASi and MRA at target doses. At the end of follow-up, natriuretic peptides values and hospital visits were reduced, suggesting the benefit of optimizing HF medical treatment.


Assuntos
Insuficiência Cardíaca , Hiperpotassemia , Idoso , Feminino , Humanos , Masculino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/etiologia , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Polímeros , Potássio , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
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