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1.
JAMA ; 331(5): 425-435, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319329

RESUMO

Importance: Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer. Observations: Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma. Conclusions: Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Adenocarcinoma Folicular , Carcinoma Neuroendócrino , Imidazóis , Radioisótopos do Iodo , Oximas , Compostos de Fenilureia , Quinolinas , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/fisiopatologia , Neoplasias da Glândula Tireoide/terapia
5.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339042

RESUMO

We have previously proven the involvement of transient receptor potential ankyrin 1 (TRPA1) in stress adaptation. A lack of TRPA1 affects both urocortin 1 (member of the corticotropin-releasing hormone (CRH) family) content of the Edinger-Westphal nucleus. The noradrenergic locus ceruleus (LC) is also an important player in mood control. We aimed at investigating whether the TRPA1 is expressed in the LC, and to test if the response to chronic variable mild stress (CVMS) is affected by a lack of TRPA1. The TRPA1 expression was examined via RNAscope in situ hybridization. We investigated TRPA1 knockout and wildtype mice using the CVMS model of depression. Tyrosine hydroxylase (TH) and FOSB double immunofluorescence were used to test the functional neuromorphological changes in the LC. No TRPA1 expression was detected in the LC. The TH content was not affected by CVMS exposure. The CVMS-induced FOSB immunosignal did not co-localize with the TH neurons. TRPA1 is not expressed in the LC. A lack of functional TRPA1 receptor neither directly nor indirectly affects the TH content of LC neurons under CVMS.


Assuntos
Locus Cerúleo , Estresse Psicológico , Canal de Cátion TRPA1 , Animais , Camundongos , Hormônio Liberador da Corticotropina/metabolismo , Expressão Gênica , Locus Cerúleo/fisiopatologia , Urocortinas/metabolismo , Canal de Cátion TRPA1/genética , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Tirosina 3-Mono-Oxigenase/metabolismo
6.
PLoS One ; 19(2): e0297681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394186

RESUMO

AIM: We examined household food insecurity (HFI) and autonomic nervous system (ANS) function in a subset of low-income Latinos with type 2 diabetes with data from a stress management trial. METHODS: InclusionLatino or Hispanic, Spanish speaking, age less than 18 years, ambulatory status, type 2 diabetes more than 6 months, A1c less than 7.0%. ExclusionPain or dysfunction in hands (e.g., arthritis) precluding handgrip testing; medical or psychiatric instability. HFI was assessed with the 6-item U.S. household food security survey module; with responses to > = 1 question considered HFI. An ANS dysfunction index was calculated from xix autonomic function tests which were scored 0 = normal or 1 = abnormal based on normative cutoffs and then summed. Autonomic function tests were: 1) 24-hour heart rate variability as reflected in standard deviation of the normal-to-normal (SDNN) heart rate acquired with 3-channel, 7-lead ambulatory electrocardiogram (Holter) monitors; 2) difference between the highest diastolic blood pressure (DBP) during sustained handgrip and the average DBP at rest; 3) difference between baseline supine and the minimal BP after standing up; and, from 24-hour urine specimens 4) cortisol, 5) normetanephrine, and, 6) metanephrine. RESULTS: Thirty-five individuals participated, 23 (65.7%) of them were women, age mean = 61.6 (standard deviation = 11.2) years, HbA1c mean = 8.5% (standard deviation = 1.6) and 20 participants (57.1%) used insulin. Twenty-two participants (62.9%) reported HFI and 25 (71.4%) had one or more abnormal ANS measure. Independent t-tests showed that participants with HFI had a higher ANS dysfunction index (mean = 1.5, standard deviation = 0.9) than patients who were food secure (mean = 0.7, standard deviation = 0.8), p = 0.02. Controlling for financial strain did not change significance. Total ANS index was not related to glycemia, insulin use or other socioeconomic indicators. In this sample, HFI was associated with ANS dysfunction. Policies to improve food access and affordability may benefit health outcomes for Latinos with diabetes.


Assuntos
Sistema Nervoso Autônomo , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Masculino , Insegurança Alimentar , Abastecimento de Alimentos , Força da Mão , Hispânico ou Latino , Insulina , Sistema Nervoso Autônomo/fisiopatologia , Pessoa de Meia-Idade , Idoso
9.
N Engl J Med ; 390(3): 212-220, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38231622

RESUMO

BACKGROUND: The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter-defibrillators (ICDs). However, the effect of CRT on long-term survival is not known. METHODS: We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device. RESULTS: The trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P = 0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group. CONCLUSIONS: Among patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.).


Assuntos
Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Estimativa de Kaplan-Meier , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Eletrocardiografia , Seguimentos , Fatores de Tempo
12.
Science ; 383(6681): 354, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38271509
17.
Brain Res ; 1822: 148669, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37951562

RESUMO

Cerebral malaria (CM) pathogenesis is described as a multistep mechanism. In this context, monocytes have been implicated in CM pathogenesis by increasing the sequestration of infected red blood cells to the brain microvasculature. In disease, endothelial activation is followed by reduced monocyte rolling and increased adhesion. Nowadays, an important challenge is to identify potential pro-inflammatory stimuli that can modulate monocytes behavior. Our group have demonstrated that bradykinin (BK), a pro-inflammatory peptide involved in CM, is generated during the erythrocytic cycle of P. falciparum and is detected in culture supernatant (conditioned medium). Herein we investigated the role of BK in the adhesion of monocytes to endothelial cells of blood brain barrier (BBB). To address this issue human monocytic cell line (THP-1) and human brain microvascular endothelial cells (hBMECs) were used. It was observed that 20% conditioned medium from P. falciparum infected erythrocytes (Pf-iRBC sup) increased the adhesion of THP-1 cells to hBMECs. This effect was mediated by BK through the activation of B2 and B1 receptors and involves the increase in ICAM-1 expression in THP-1 cells. Additionally, it was observed that angiotensin-converting enzyme (ACE) inhibitor, captopril, enhanced the effect of both BK and Pf-iRBC sup on THP-1 adhesion. Together these data show that BK, generated during the erythrocytic cycle of P. falciparum, could play an important role in adhesion of monocytes in endothelial cells lining the BBB.


Assuntos
Barreira Hematoencefálica , Bradicinina , Adesão Celular , Malária Cerebral , Malária Falciparum , Plasmodium falciparum , Humanos , Bradicinina/metabolismo , Adesão Celular/fisiologia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Eritrócitos/parasitologia , Malária Cerebral/metabolismo , Malária Cerebral/parasitologia , Malária Falciparum/metabolismo , Malária Falciparum/parasitologia , Monócitos/fisiologia , Plasmodium falciparum/fisiologia , Barreira Hematoencefálica/fisiopatologia
18.
Curr Opin Hematol ; 31(1): 6-15, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37905750

RESUMO

PURPOSE OF REVIEW: Activated or aged platelets are removed from circulation under (patho)physiologic conditions, the exact mechanism of platelet clearance under such conditions remains unclear and are currently being investigated. This review focuses on recent findings and controversies regarding platelet clearance and the disruption of platelet life cycle. RECENT FINDINGS: The platelet life span is determined by glycosylation of platelet surface receptors with sialic acid. Recently, it was shown that platelet activation and granule release leads to desialylation of glycans and accelerated clearance of platelets under pathological conditions. This phenomenon was demonstrated to be a main reason for thrombocytopenia being a complication in several infections and immune disorders. SUMMARY: Although we have recently gained some insight into how aged platelets are cleared from circulation, we are still not seeing the full picture. Further investigations of the platelet clearance pathways under pathophysiologic conditions are needed as well as studies to unravel the connection between platelet clearance and platelet production.


Assuntos
Plaquetas , Senescência Celular , Citofagocitose , Idoso , Humanos , Plaquetas/metabolismo , Plaquetas/fisiologia , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos , Trombocitopenia/etiologia , Trombocitopenia/metabolismo , Trombocitopenia/fisiopatologia , Senescência Celular/fisiologia , Citofagocitose/fisiologia
20.
Rev. bras. oftalmol ; 83: e0002, 2024. graf
Artigo em Português | LILACS | ID: biblio-1529930

RESUMO

RESUMO O propósito deste estudo foi reportar as alterações oculares observadas após picada de abelha com ferrão retido na córnea. Destacamos o tratamento e o desfecho de uma lesão de córnea incomum e sua patogênese. Trata-se de relato de caso e revisão da literatura de lesões oculares por picada de abelha. Paciente do sexo feminino, 63 anos, procurou atendimento oftalmológico de urgência devido à picada de abelha na córnea do olho direito há 6 dias. Queixava-se de embaçamento visual, dor e hiperemia ocular. Apresentou acuidade visual de vultos no olho afetado. Ao exame, notaram-se hiperemia moderada de conjuntiva bulbar, edema corneano com dobras de Descemet e presença do ferrão alojado na região temporal, no estroma profundo da córnea. A paciente foi internada para ser abordada no centro cirúrgico sob anestesia geral. Durante a cirurgia, o ferrão teve que ser retirado via câmara anterior, mediante a realização de uma paracentese e uma lavagem da câmara anterior, com dupla via e solução salina balanceada. Ainda não existe na literatura um tratamento padrão na abordagem de pacientes com lesões oculares por picada de abelha, sendo importantes a identificação e o reconhecimento precoce de possíveis complicações que ameacem a visão.


ABSTRACT The purpose of this study was to report the ocular changes observed after a bee sting with a stinger retained in the cornea. We show the treatment and outcome of an unusual corneal injury and its pathogenesis. This is a case report and literature review of ocular injuries caused by bee stings. A 63-year-old female patient sought emergency ophthalmic care because of a bee sting on the cornea of her right eye six days before. She complained of blurred vision, pain, and ocular hyperemia. She had glare sensitivity on visual acuity in the affected eye. Examination revealed moderate hyperemia of the bulbar conjunctiva, corneal edema with Descemet's folds and a stinger lodged in the temporal region, in the deep stroma of the cornea. The patient was admitted to the operating room under general anesthesia. During surgery, the stinger had to be removed via the anterior chamber, by performing a paracentesis and washing the anterior chamber with a double flushing and balanced saline solution. There is still no standard treatment in the literature for patients with eye injuries caused by bee stings, and early identification and recognition of possible sight-threatening complications is important.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Venenos de Abelha/efeitos adversos , Edema da Córnea/etiologia , Corpos Estranhos no Olho/complicações , Lesões da Córnea/etiologia , Mordeduras e Picadas de Insetos/complicações , Procedimentos Cirúrgicos Oftalmológicos/métodos , Edema da Córnea/diagnóstico , Edema da Córnea/fisiopatologia , Iridociclite , Corpos Estranhos no Olho/cirurgia , Corpos Estranhos no Olho/diagnóstico , Lesões da Córnea/cirurgia , Lesões da Córnea/diagnóstico , Microscopia com Lâmpada de Fenda , Gonioscopia , Mordeduras e Picadas de Insetos/cirurgia , Mordeduras e Picadas de Insetos/diagnóstico
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