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2.
Med. clín (Ed. impr.) ; 162(4): 163-169, Feb. 2024. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-230572

RESUMO

Objectives: COVID-19, caused by SARS-CoV-2, has spread around the world since 2019. In severe cases, COVID-19 can lead to hospitalization and death. Systemic arterial hypertension and other comorbidities are associated with serious COVID-19 infection. Literature is unclear whether antihypertensive therapy with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors affect COVID-19 outcomes. We aim to assess whether ACEI/ARB therapy is a risk factor for worse respiratory outcomes related to COVID-19 in hospitalized patients. Methods: Retrospective study enrolling admitted COVID-19-diagnosed patients by RT-PCR at the Hospital Geral de Fortaleza, Brazil, during 2021. Patient medical records, sociodemographic, and clinical data were analyzed. Chest CT images were analyzed using CAD4COVID-CT/Thirona™ software. Results: A total of 294 patients took part in the study. A cut-off point of 66% of pulmonary involvement was found by ROC curve, with patients having higher risk of death and intubation and lower 60-day survival. Advanced age (RR 1.025, P=0.001) and intubation (RR 16.747, P<0.001) were significantly associated with a higher risk of death. Advanced age (RR 1.023, P=0.001) and the use of noninvasive ventilation (RR 1.548, P=0.037) were associated with a higher risk of intubation. Lung involvement (>66%) increased the risk of death by almost 2.5-fold (RR 2.439, P<0.001) and by more than 2.3-fold the risk of intubation (RR 2.317, P<0.001). Conclusions: Altogether, our findings suggest that ACEI or ARB therapy does not affect the risk of death and disease course during hospitalization.(AU)


Objetivos: La COVID-19, causada por el SARS-CoV-2, se ha extendido por todo el mundo desde 2019. En casos graves, la COVID-19 puede provocar hospitalización y muerte. La hipertensión arterial sistémica y otras comorbilidades se asocian con una infección grave por COVID-19. La literatura no está clara si la terapia antihipertensiva con bloqueadores de los receptores de angiotensina (BRA) e inhibidores de la enzima convertidora de angiotensina (ECA) afecta los resultados de la COVID-19. Nuestro objetivo fue evaluar si la terapia BRA/ECA es un factor de riesgo de peores resultados respiratorios relacionados con COVID-19 en pacientes hospitalizados. Métodos: Estudio retrospectivo que incluyó pacientes ingresados con diagnóstico de COVID-19 mediante RT-PCR en el Hospital General de Fortaleza, Brasil, durante 2021. Se analizaron las historias clínicas de los pacientes, datos sociodemográficos y clínicos. Las imágenes de TC de tórax se analizaron utilizando el software CAD4COVID-CT/ThironaTM. Resultados: Participaron en el estudio un total de 294 pacientes. Mediante curva ROC se encontró un punto de corte del 66% de afectación pulmonar, teniendo los pacientes mayor riesgo de muerte e intubación y menor supervivencia a 60 días. La edad avanzada (RR 1,025; P=0,001) y la intubación (RR 16,747; P<0,001) se asociaron significativamente con un mayor riesgo de muerte. La edad avanzada (RR 1,023; P=0,001) y el uso de ventilación no invasiva (RR 1,548; P=0,037) se asociaron con un mayor riesgo de intubación. La afectación pulmonar (>66%) aumentó el riesgo de muerte casi 2,5 veces (RR 2,439; P<0,001) y más de 2,3 veces el riesgo de intubación (RR 2,317, P<0,001). Conclusiones: Se concluyó que el tratamiento con BRA o ECA no afecta el riesgo de muerte y el curso de la enfermedad durante la hospitalización.(AU)


Assuntos
Humanos , Masculino , Feminino , /diagnóstico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão , Comorbidade , /epidemiologia , Medicina Clínica , Estudos Retrospectivos , Brasil , Anti-Hipertensivos/efeitos adversos , Inteligência Artificial
4.
Pancreas ; 53(3): e268-e273, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300837

RESUMO

OBJECTIVES: We aimed to compare the efficacy and toxicity of palliative chemotherapy in elderly patients with pancreatic ductal adenocarcinoma (PDAC) with those in younger patients. METHODS: A total of 60 patients with locally advanced or metastatic PDAC who received FOLFIRINOX or nab-paclitaxel plus gemcitabine at our institution from January 2014 to December 2021 were analyzed. Patients 70 years or older were classified into an elderly group. RESULTS: The elderly group included 16 patients (26.7%). In the elderly group, nab-paclitaxel plus gemcitabine was used more than FOLFIRINOX compared with the young group (75.0% and 25.0% vs 34.1% and 64.9%, respectively; P = 0.008). The overall survival was not significantly different between the 2 groups (15.6 vs 13.4 months, P = 0.259). However, the elderly group showed better progression-free survival (11.4 vs 7.4 months, P = 0.034). The incidence of adverse events including neutropenia (75.0% vs 81.8%, P = 0.716), thrombocytopenia (25.0% vs 31.3%, P = 0.743), and anemia (50.0% vs 43.2%, P = 0.771) was not different between the 2 groups. Peripheral neuropathy was more common in the elderly group (18.3% vs 2.3%, P = 0.054), though not statistically significant. CONCLUSION: The efficacy and toxicity of chemotherapy in elderly patients with advanced PDAC were comparable with those in younger patients.


Assuntos
Neoplasias Pancreáticas , Humanos , Idoso , Neoplasias Pancreáticas/patologia , Gencitabina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/efeitos adversos , Paclitaxel/efeitos adversos , Fluoruracila/efeitos adversos , Leucovorina/efeitos adversos , Albuminas/efeitos adversos
5.
Cell Rep Med ; 5(2): 101398, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38301654

RESUMO

Prenatal dexamethasone exposure (PDE) can lead to increased susceptibility to various diseases in adult offspring, but its effect on gut microbiota composition and the relationship with disease susceptibility remains unclear. In this study, we find sex-differential changes in the gut microbiota of 6-month-old infants with prenatal dexamethasone therapy (PDT) that persisted in female infants up to 2.5 years of age with altered bile acid metabolism. PDE female offspring rats show abnormal colonization and composition of gut microbiota and increased susceptibility to cholestatic liver injury. The aberrant gut microbiota colonization in the PDE offspring can be attributed to the inhibited Muc2 expression caused by decreased CDX2 expression before and after birth. Integrating animal and cell experiments, we further confirm that dexamethasone could inhibit Muc2 expression by activating GR/HDAC11 signaling and regulating CDX2 epigenetic modification. This study interprets abnormal gut microbiota and disease susceptibility in PDT offspring from intrauterine intestinal dysplasia.


Assuntos
Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Ratos , Animais , Feminino , Lactente , Dexametasona/efeitos adversos , Ratos Wistar , Suscetibilidade a Doenças , Epigênese Genética
6.
Environ Sci Pollut Res Int ; 31(10): 15872-15884, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302837

RESUMO

Glyphosate-based herbicides (GBH) are the most widely used pesticides globally. Studies have indicated that they may increase the risk of various organic dysfunctions. Herein, we verified whether exposure to GBH during puberty increases the susceptibility of male and female mice to obesity when they are fed a high-fat diet (HFD) in adulthood. From the 4th-7th weeks of age, male and female C57Bl/6 mice received water (CTL group) or 50 mg GBH /kg body weight (BW; GBH group). From the 8th-21st weeks of age, the mice were fed a standard diet or a HFD. It was found that pubertal GBH exposure exacerbated BW gains and hyperphagia induced by HFD, but only in female GBH-HFD mice. These female mice also exhibited high accumulation of perigonadal and subcutaneous fat, as well as reduced lean body mass. Both male and female GBH-HFD displayed hypertrophic white adipocytes. However, only in females, pubertal GBH exposure aggravated HFD-induced fat accumulation in brown adipocytes. Furthermore, GBH increased plasma cortisol levels by 80% in GBH-HFD males, and 180% in GBH-HFD females. In conclusion, pubertal GBH exposure aggravated HFD-induced obesity, particularly in adult female mice. This study provides novel evidence that GBH misprograms lipid metabolism, accelerating the development of obesity when individuals are challenged by a second metabolic stressor, such as an obesogenic diet.


Assuntos
Dieta Hiperlipídica , Herbicidas , Camundongos , Masculino , Feminino , Animais , Dieta Hiperlipídica/efeitos adversos , Herbicidas/toxicidade , Obesidade/induzido quimicamente , Metabolismo dos Lipídeos
7.
J Endocrinol ; 261(1)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305305

RESUMO

Metabolic syndrome (MetS) is an increasing global health threat and strong risk factor for type 2 diabetes (T2D). MetS causes both hyperinsulinemia and islet size overexpansion, and pancreatic ß-cell failure impacts insulin and proinsulin secretion, mitochondrial density, and cellular identity loss. The low-density lipoprotein receptor knockout (LDLr-/-) model combined with high-fat diet (HFD) has been used to study alterations in multiple organs, but little is known about the changes to ß-cell identity resulting from MetS. Osteocalcin (OC), an insulin-sensitizing protein secreted by bone, shows promising impact on ß-cell identity and function. LDLr-/- mice at 12 months were fed chow or HFD for 3 months ± 4.5 ng/h OC. Islets were examined by immunofluorescence for alterations in nuclear Nkx6.1 and PDX1 presence, insulin-glucagon colocalization, islet size and %ß-cell and islet area by insulin and synaptophysin, and mitochondria fluorescence intensity by Tomm20. Bone mineral density (BMD) and %fat changes were examined by Piximus Dexa scanning. HFD-fed mice showed fasting hyperglycemia by 15 months, increased weight gain, %fat, and fasting serum insulin and proinsulin; concurrent OC treatment mitigated weight increase and showed lower proinsulin-to-insulin ratio, and higher BMD. HFD increased %ß and %islet area, while simultaneous OC-treatment with HFD was comparable to chow-fed mice. Significant reductions in nuclear PDX1 and Nkx6.1 expression, increased insulin-glucagon colocalization, and reduction in ß-cell mitochondria fluorescence intensity were noted with HFD, but largely prevented with OC administration. OC supplementation here suggests a benefit to ß-cell identity in LDLr-/- mice and offers intriguing clinical implications for countering metabolic syndrome.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Células Secretoras de Insulina , Ilhotas Pancreáticas , Síndrome Metabólica , Animais , Camundongos , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glucagon/metabolismo , Hiperinsulinismo/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Lipoproteínas LDL , Síndrome Metabólica/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteocalcina/metabolismo , Proinsulina/metabolismo , Aumento de Peso
8.
Viral Immunol ; 37(1): 12-15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315746

RESUMO

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Vacinas Virais , Criança , Humanos , Pessoa de Meia-Idade , Idoso , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Anticorpos Antivirais
9.
Life Sci ; 341: 122487, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38316265

RESUMO

Photoaging of skin, a chronic disease, can produce the appearance changes and cancer lesions of skin. Therefore, it is of great significance to investigate the mechanisms and explore effective methods to treat the disorder. Gut microbiota and intestinal metabolisms have critical roles in a variety of diseases. However, their roles on photoaging of skin were not well tested. In the present work, the results showed that compared with control group, the levels of MDA, SOD and CAT associated with oxidative stress, the levels of COL I, CER, and HA associated with skin function, and the mRNA levels of IL-1ß, IL-6, TNF-α associated with inflammation after long-term exposure to ultraviolet radiation in mice were significantly changed. Skin pathological tissue was also seriously damaged. The protein levels of AQP3 and FLG were significantly decreased. Ultraviolet exposure also promoted skin photoaging by activating TNFR1/TRAF2-mediated MAPK pathway, in which the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2 were significantly increased in model mice compared with control group. In fecal microbiota transplantation (FMT) experiment, we found that the intestinal microbiome of control mice alleviated skin photoaging via adjusting the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2. 16S rRNA sequencing found that 1639 intestinal bacteria were found, in which 15 bacteria including norank_f_Ruminococcaceae, Lachnospirac -eae_NK4A136_group, Lachnoclostridium, etc., were significantly different at the genus level. Untargeted GC-TOF/MS and UHPLC-MS/MS metabolomics showed 72 and 188 metabolites including taurine, ornithine, L-arginine, L-histidine, sucrose with significant differences compared with control group. Then, amino acid targeting assay showed 10 amino acids including L-ornithine, L-arginine and L-citrulline with higher levels in control group compared with model group. In addition, we also found that the variation of Lachnoclostridium abundance may regulate L-arginine metabolism to affect skin photoaging. Some intestinal bacteria and metabolites including amino acids may be closely related to skin photoaging, which should provide new methods to treat skin photoaging in the future.


Assuntos
Microbioma Gastrointestinal , Envelhecimento da Pele , Animais , Camundongos , Metaloproteinase 1 da Matriz , RNA Ribossômico 16S/genética , Receptores Tipo I de Fatores de Necrose Tumoral , Fator 2 Associado a Receptor de TNF , Espectrometria de Massas em Tandem , Raios Ultravioleta/efeitos adversos , Metabolômica , Arginina , Citrulina , Ornitina
10.
JAMA Netw Open ; 7(2): e2354916, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38319661

RESUMO

Importance: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. Objective: To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. Design, Setting, and Participants: In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. Main Outcomes and Measures: The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. Results: A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. Conclusions and Relevance: In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.


Assuntos
Fatores de Coagulação Sanguínea , Tratamento Conservador , Hemostáticos , Humanos , Feminino , Idoso , Masculino , Estudos de Coortes , Estudos Retrospectivos , Fator IX , Hemostáticos/uso terapêutico , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Anticoagulantes/efeitos adversos
11.
J Agric Food Chem ; 72(8): 4074-4088, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38323407

RESUMO

Sialylated immunoglobulin G (IgG) is a vital glycoprotein in breast milk with the ability to promote the growth of Bifidobacterium in gut microbiota and relieve inflammatory bowel disease (IBD) symptoms in vitro. Here, it was found that the microcapsules with sialylated IgG could protect and release sialylated IgG with its structure and function in the intestine. Furthermore, the sialylated IgG microcapsules alleviated the clinical symptoms (body weight, feed quantity, and colon length loss), decreased disease activity index score, suppressed the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, and MCP-1) and endotoxin (lipopolysaccharide), and enhanced the intestinal mucosal barrier (Claudin1, Muc2, Occludin, and ZO-1) in dextran sulfate sodium (DSS)-induced colitis mice. Additionally, the sialylated IgG microcapsules improved the gut microbiota by increasing the relative abundance of critical microbe Bifidobacterium bifidum and promoted the production of short-chain fatty acids (SCFAs). Correlation analysis indicated that the key microbes were strongly correlated with pro-inflammatory factors, clinical symptoms, tight junction protein, and SCFAs. These findings suggest that the sialylated IgG microcapsules have the potential to be used as a novel therapeutic approach for treating IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Humanos , Feminino , Animais , Camundongos , Imunoglobulina G , Sulfato de Dextrana/efeitos adversos , Cápsulas , Colite/induzido quimicamente , Colite/tratamento farmacológico , Citocinas , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo
12.
Scand J Work Environ Health ; 50(2): 53-60, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38323897

RESUMO

OBJECTIVE: This paper discusses the failure and success of society to decrease the adverse health effects of asbestos exposure on workers' health in relation to scientific knowledge. METHODS: The findings are based on a narrative literature review. RESULTS: Early warnings of the adverse health effects of workplace exposure to asbestos were published already in the 1930s. Serious health effects, such as malignancies and fibrosis due to occupational asbestos exposure, were highlighted in major medical journals and textbooks in late 1960s. New technologies could detect also asbestos fibers in the lung of non-occupational exposed persons in the 1970s. The first bans for using asbestos came in the early 1970s, and more general bans by authorities came in the 1980s and continue until today. CONCLUSIONS: The rather late recognition of adverse effects of asbestos exposure in the general population and measures to decrease the exposure through more general bans came rather late. However, the very strong measures such as general bans in many countries have been a success. A Swedish study showed that the general ban and other measures have decreased the risk of malignancies due to occupational exposure. The effect of the bans on adverse effects in the general population has yet to be studied. Analysis of fibers in the lungs of persons born after the bans could be an efficient method.


Assuntos
Amianto , Asbestose , Neoplasias Pulmonares , Mesotelioma , Neoplasias , Exposição Ocupacional , Saúde Ocupacional , Humanos , Saúde Pública , Amianto/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Mesotelioma/epidemiologia , Neoplasias Pulmonares/epidemiologia , Asbestose/epidemiologia
13.
J Affect Disord ; 351: 904-914, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325605

RESUMO

BACKGROUND: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). METHODS: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (≥50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. RESULTS: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). LIMITATIONS: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. CONCLUSIONS: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.


Assuntos
Transtorno Depressivo Maior , Pirazóis , Adulto , Feminino , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Pregnanolona/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
J Am Dent Assoc ; 155(2): 118-137.e1, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38325970

RESUMO

BACKGROUND: This systematic review aimed to investigate whether vital pulp therapy and root canal treatment (RCT) promote different postoperative pain. STUDIES REVIEWED: The authors searched PubMed, Cochrane Library, Embase, and Latin American and Caribbean Health Sciences Literature databases for studies published through June 30, 2022. The authors included randomized clinical trials if they reported on the assessment of postoperative pain after direct pulp capping, partial pulpotomy, pulpotomy, or single-visit RCT. The authors assessed the frequency of no, mild, moderate, and severe postoperative pain. They conducted meta-analyses to compare postoperative pain after full pulpotomy (PULP) and RCT. RESULTS: The qualitative synthesis included 57 studies, and the authors conducted meta-analysis of 3. PULP leads to more asymptomatic cases (relative risk [RR], 1.06; 95% CI, 1.01 to 1.11; P < .01; I2 = 67%) and to a lower occurrence of mild (RR, 0.89; 95% CI, 0.79 to 0.99; P < .04; I2 = 37%) and moderate (RR, 0.70; 95% CI, 0.51 to 0.95; P < .02; I2 = 57%) postoperative pain than RCT. The frequency of severe pain was very low for both vital pulp therapy and RCT. Moderate to severe postoperative pain was more common at 48 hours through 72 hours after RCT and up to 36 hours after PULP. Pain intensity after PULP was higher using calcium-enriched material compared with using mineral trioxide aggregate at 12, 18, and 36 hours (P < .001). PRACTICAL IMPLICATIONS: PULP showed a significantly higher incidence of no pain and a lower incidence of mild and moderate pain than single-visit RCT. Clinical decisions for RCT or PULP should not be based on differences in postoperative pain. When analgesia is indicated, it probably should be limited to a short time after PULP.


Assuntos
Cavidade Pulpar , Tratamento do Canal Radicular , Humanos , Tratamento do Canal Radicular/efeitos adversos , Assistência Odontológica/efeitos adversos , Pulpotomia/efeitos adversos , Dor Pós-Operatória/etiologia
16.
Blood Adv ; 8(5): 1084-1093, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38330190

RESUMO

ABSTRACT: Clinically significant cytomegalovirus infection (csCMVi) is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT) and prophylaxis with letermovir is commonly adopted. However, the clinical benefit of letermovir prophylaxis according to graft sources has not been sufficiently elucidated. We retrospectively analyzed 2194 recipients of HSCT who were CMV-seropositive (236 with letermovir prophylaxis and 1958 without prophylaxis against CMV). csCMVi was significantly less frequent in patients with letermovir prophylaxis than in those without (23.7% vs 58.7% at 100 days after HSCT, P < .001) and the same trend was seen when recipients of bone marrow (BM), peripheral blood stem cell (PBSC), or cord blood (CB) transplantation were separately analyzed. In recipients of BM, nonrelapse mortality (NRM) was significantly lower in the letermovir group at 6 months after HSCT (5.0% vs 14.9%, P = .018), and the same trend was observed in recipients of PBSCs (14.7% vs 24.8%, P = .062); however, there was no statistical significance at 1 year (BM, 21.1% vs 30.4%, P = .67; PBSCs, 21.2% vs 30.4%, P = .096). In contrast, NRM was comparable between recipients of CB with and without letermovir prophylaxis throughout the clinical course (6 months, 23.6% vs 24.3%, P =.92; 1 year, 29.3% vs 31.0%, P = .77), which was confirmed by multivariate analyses. In conclusion, the impact of letermovir prophylaxis on NRM and csCMVi should be separately considered according to graft sources.


Assuntos
Acetatos , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Quinazolinas , Humanos , Estudos Retrospectivos , Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/prevenção & controle
17.
Blood Cancer J ; 14(1): 27, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331870

RESUMO

Despite recent advances in frontline therapy for diffuse large B-cell lymphoma (DLBCL), at least a third of those diagnosed still will require second or further lines for relapsed or refractory (rel/ref) disease. A small minority of these can be cured with standard chemoimmunotherapy/stem-cell transplant salvage approaches. CD19-directed chimeric antigen receptor T-cell (CAR-19) therapies are increasingly altering the prognostic landscape for rel/ref patients with DLBCL and related aggressive B-cell non-Hodgkin lymphomas. Long-term follow up data show ongoing disease-free outcomes consistent with cure in 30-40% after CAR-19, including high-risk patients primary refractory to or relapsing within 1 year of frontline treatment. This has made CAR-19 a preferred option for these difficult-to-treat populations. Widespread adoption, however, remains challenged by logistical and patient-related hurdles, including a requirement for certified tertiary care centers concentrated in urban centers, production times of at least 3-4 weeks, and high per-patients costs similar to allogeneic bone-marrow transplantation. Bispecific antibodies (BsAbs) are molecular biotherapies designed to bind and activate effector T-cells and drive them to B-cell antigens, leading to a similar cellular-dependent cytotoxicity as CAR-19. May and June of 2023 saw initial approvals of next-generation BsAbs glofitamab and epcoritamab in DLBCL as third or higher-line therapy, or for patients ineligible for CAR-19. BsAbs have similar spectrum but generally reduced severity of immune related side effects as CAR-19 and can be administered in community settings without need to manufacture patient-specific cellular products. To date and in contrast to CAR-19, however, there is no convincing evidence of cure after BsAbs monotherapy, though follow up is limited. The role of BsAbs in DLBCL treatment is rapidly evolving with trials investigating use in both relapsed and frontline curative-intent combinations. The future of DLBCL treatment is bound increasingly to include effector cell mediated immunotherapies, but further optimization of both cellular and BsAb approaches is needed.


Assuntos
Anticorpos Biespecíficos , Linfoma Difuso de Grandes Células B , Humanos , Anticorpos Biespecíficos/uso terapêutico , Recidiva Local de Neoplasia/etiologia , Linfoma Difuso de Grandes Células B/patologia , Imunoterapia , Linfócitos T , Imunoterapia Adotiva/efeitos adversos
18.
CNS Neurosci Ther ; 30(2): e14594, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332538

RESUMO

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Fármacos Neuroprotetores , Ácido Palmítico , Ácidos Esteáricos , Animais , Camundongos , Ratos , Apoptose , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Anidrase Carbônica III/efeitos dos fármacos , Anidrase Carbônica III/metabolismo
19.
CNS Neurosci Ther ; 30(2): e14553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334231

RESUMO

In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane- and isoflurane-induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane- and isoflurane-induced neurotoxicity.


Assuntos
Anestésicos Inalatórios , Ferroptose , Isoflurano , Éteres Metílicos , Humanos , Criança , Idoso , Isoflurano/efeitos adversos , Sevoflurano/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Transtornos Neurocognitivos , Homeostase
20.
J Nat Med ; 78(2): 427-438, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38334900

RESUMO

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl4) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-ß (TGF-ß) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl4-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1ß, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl4-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1ß expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1ß expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.


Assuntos
Cirrose Hepática , Transdução de Sinais , Camundongos , Animais , 5-Metoxipsoraleno/efeitos adversos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Células Estreladas do Fígado , Fator de Crescimento Transformador beta/farmacologia , Fígado
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