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1.
Semin Liver Dis ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38701856

RESUMO

Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid-lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, antiproliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and nonviral etiologies of CLD and hepatocellular carcinoma (HCC), and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

2.
Circulation ; 147(14): 1067-1078, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36876483

RESUMO

BACKGROUND: How patient characteristics and outcomes vary according to the duration of heart failure (HF) is unknown in individuals with mildly reduced or preserved ejection fraction. We compared these, and the efficacy and safety of dapagliflozin, according to the time from diagnosis of HF in a prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). METHODS: HF duration was categorized as ≤6 months, >6 to 12 months, >1 to 2 years, >2 to 5 years, or >5 years. The primary outcome was the composite of worsening HF or cardiovascular death. The effect of treatment was examined by HF duration category. RESULTS: The number of patients in each category was as follows: 1160 (≤6 months), 842 (>6 to 12 months), 995 (>1 to 2 years), 1569 (>2 to 5 years), and 1692 (>5 years). Patients with longer-duration HF were older and had more comorbidities with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: ≤6 months, 7.3 (95% CI, 6.3 to 8.4); >6 to 12 months, 7.1 (6.0 to 8.5); >1 to 2 years, 8.4 (7.2 to 9.7); >2 to 5 years, 8.9 (7.9 to 9.9); and >5 years, 10.6 (9.5 to 11.7). Similar trends were seen for other outcomes. The benefit of dapagliflozin was consistent across HF duration category: the hazard ratio for the primary outcome in the ≤6-month group was 0.67 (95% CI, 0.50 to 0.91); >6 to 12 months, 0.78 (0.55 to 1.12); >1 to 2 years, 0.81 (0.60 to 1.09); >2 to 5 years, 0.97 (0.77 to 1.22); and >5 years, 0.78 (0.64 to 0.96; Pinteraction=0.41). The absolute benefit was greatest in longest-duration HF; the number needed to treat for HF >5 years was 24 versus 32 for ≤6 months. CONCLUSIONS: Patients with longer-duration HF were older, had more comorbidities and symptoms, and had higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration. Even patients with long-standing HF and generally mild symptoms are not stable, and it is not too late for such patients to benefit from a sodium-glucose cotransporter 2 inhibitor. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03619213.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Compostos Benzidrílicos/efeitos adversos , Glucosídeos/efeitos adversos , Modelos de Riscos Proporcionais , Volume Sistólico
3.
Pediatr Dermatol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978313

RESUMO

This study underscores the significance of identifying the clinical manifestations of pachyonychia congenita (PC) and emphasizes the patterns of genetic inheritance. A 12-month-old boy presented with a "white hairy tongue" and, following a comprehensive evaluation, was diagnosed with PC. His father exhibited similar symptoms. Genetic testing revealed a KRT16 pathogenic variant (c.616 T > G) in both the patient and his father, marking it as a novel variant in the PC literature. This case contributes to a broader understanding of PC's genetic diversity and its clinical presentations.

4.
Chem Biodivers ; 21(5): e202400380, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38498616

RESUMO

The chemical investigation of the stems of Knema globularia led to the isolation of two new benzoquinones derivatives, embenones A and B (1 and 2), along with three known compounds (3-5). The structures of the isolated compounds were determined using spectroscopic techniques, including HRESIMS, 1D and 2D NMR, in conjunction with comparison to existing literature data. Compounds 1 and 2 represent new carbon skeletons in nature. Furthermore, all isolated compounds were evaluated for their α-glucosidase inhibitory activity, with compounds 1-3 exhibiting superior potency relative to the positive control (acarbose, IC50 331 µM). Their IC50 values ranged from 1.40 to 96.1 µM.


Assuntos
Benzoquinonas , Inibidores de Glicosídeo Hidrolases , Caules de Planta , alfa-Glucosidases , Benzoquinonas/química , Benzoquinonas/isolamento & purificação , Benzoquinonas/farmacologia , Caules de Planta/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , alfa-Glucosidases/metabolismo , Vietnã , Relação Estrutura-Atividade , Estrutura Molecular , Conformação Molecular , População do Sudeste Asiático
5.
Chem Biodivers ; : e202400438, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581153

RESUMO

A bio-guided isolation was applied to the Vietnamese lichen Roccella montagnei based on alpha-glucosidase inhibition. Six compounds were isolated and structurally elucidated, including a new ortho depside, montagneside A (1), together with five known compounds, sekikaic acid (2), lanost-7-en-3ß-ol (3), ethyl orsellinate (4), D-montagnetol (5), and D-erythrin (6). Their chemical structures were identified by extensive 1D and 2D NMR analysis, high-resolution mass spectroscopy, and comparisons with those reported in the literature. D-Erythrin (6), a major component, was selected for further modification using Smiles rearrangement. Three erythritol derivatives 6a-6c were synthesized. Compounds 1-3, 6, and 6a-6c were evaluated for alpha-glucosidase inhibition. Compounds 2 and 6a-6c showed significant alpha-glucosidase inhibition with IC50 values ranging from 7.9 to 149 µM, respectively. Molecular docking was applied to the most active compound 6a to clarify the inhibitory mechanism.

6.
Emerg Infect Dis ; 29(10): 2130-2134, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37735771

RESUMO

We report on an outbreak of nongroupable Neisseria meningitidis-associated urethritis, primarily among men who have sex with men in southern Vietnam. Nearly 50% of N. meningitidis isolates were resistant to ciprofloxacin. This emerging pathogen should be considered in the differential diagnosis and management of urethritis.


Assuntos
Neisseria meningitidis , Minorias Sexuais e de Gênero , Uretrite , Masculino , Humanos , Uretrite/diagnóstico , Uretrite/epidemiologia , Vietnã/epidemiologia , Homossexualidade Masculina , Surtos de Doenças , Neisseria meningitidis/genética
7.
Small ; 19(21): e2204956, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36840671

RESUMO

Accurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.


Assuntos
Nanopartículas , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Próstata , Imageamento por Ressonância Magnética , Fibroblastos
8.
Cancer Invest ; : 1-17, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36719061

RESUMO

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

9.
BMC Infect Dis ; 23(1): 880, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102542

RESUMO

BACKGROUND: COVID-19 has caused millions of deaths globally, with vulnerable populations such as people experiencing homelessness (PEH) at higher risk. This systematic review and meta-analysis aims to identify the prevalence and key factors contributing to vaccine acceptance experienced by PEH. METHODS: The protocol of this study was registered in PROSPERO (CRD42023391659). We included studies that reported relevant information about vaccine acceptance or vaccine hesitant/refusal among PEH. Eight databases were systematically searched in January 2023. Meta-analysis was conducted for the prevalence of vaccine acceptance, vaccine uptake, and factors associated with vaccine acceptance. Attitudes toward vaccines were combined into bar charts. RESULT: A total of 29 papers were included in this systematic review and 19 papers were included for meta-analysis. The pooled prevalence of COVID-19 vaccine acceptance among PEH was 66% (95%CI: 58%-73%). Our meta-regression showed vaccine acceptance was significantly increased over time. Moreover, subgroup meta-analysis showed that PEH were more likely to accept the COVID-19 vaccine after June 2021 (78%, 95%CI: 65%-86%) compared with earlier period (56%, 95%CI: 54%-59%). Subgroup meta-analysis also revealed that women and participants without underlying medical condition (chronic diseases) were significantly less likely to accept the COVID-19 vaccine, compared to men and those with medical conditions, respectively. CONCLUSION: The study emphasizes the need for targeted public health interventions aimed at increasing vaccine acceptance among PEH, especially at the early stage of the pandemic, among females, those without underlying medical conditions, being Black (in Canada and the USA), and young people. These interventions should address the common concerns of vaccine safety, adverse effects, effectiveness, and distrust in health care systems. In addition to offering vaccinations in different areas convenient to them, education programs could be established to increase vaccine acceptance among PEH.


Assuntos
Vacinas contra COVID-19 , Pessoas Mal Alojadas , Aceitação pelo Paciente de Cuidados de Saúde , Vacinação , Feminino , Humanos , Masculino , Vacinas contra COVID-19/administração & dosagem , Vacinação/psicologia , Conhecimentos, Atitudes e Prática em Saúde
10.
Surg Endosc ; 37(8): 6185-6196, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37165173

RESUMO

BACKGROUND: Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. METHODS: Mannose-labelled magnetic tracer 'FerroTrace' and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n = 2) or via laparotomy (n = 6). RESULTS: Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. CONCLUSIONS: Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy.


Assuntos
Nanopartículas de Magnetita , Linfonodo Sentinela , Neoplasias Gástricas , Animais , Suínos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Verde de Indocianina , Biópsia de Linfonodo Sentinela/métodos , Manose , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Corantes , Excisão de Linfonodo , Corantes Fluorescentes , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia
11.
J Minim Invasive Gynecol ; 30(11): 884-889, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37422052

RESUMO

STUDY OBJECTIVE: To investigate the incidence of venous thromboembolism (VTE) in patients undergoing large specimen hysterectomy for benign indications. To evaluate the impact of route of surgery and operative time in the development of VTE in this population. DESIGN: Retrospective cohort study (Canadian Task Force Classification II2) of targeted hysterectomy data prospectively collected from the American College of Surgeons National Surgical Quality Improvement Program involving over 500 hospitals across the United States. SETTING: National Surgical Quality Improvement Program Database. PATIENTS: Women aged 18 years or older undergoing hysterectomy for benign indications between 2014 and 2019. Patients were further classified into 4 groups according to uterine weight: <100 g, 100-249 g, 250 g-499 g, and specimens ≥500 g. INTERVENTIONS: Current Procedural Terminology codes were used to identify cases. Variables including age, ethnicity, body mass index, smoking status, diabetes, hypertension, blood transfusion, and American Society of Anesthesiologists classification system scores were collected. Cases were stratified by route of surgery, operative time, and uterine weight. MEASUREMENTS AND MAIN RESULTS: A total of 122,418 hysterectomies occurring between 2014 and 2019 were included in our study, of which 28,407 (23.2%) patients underwent abdominal, 75,490 (61.7%) laparoscopic, and 18,521 (15.1%) vaginal hysterectomy. The overall rate of VTE in patients with large specimen hysterectomies (≥500 g) was 0.64%. After multivariable adjustment, there was no significant difference in the odds of VTE between uterine weight groups. Only 30% of the surgeries with uterine weight above 500 g were performed with minimally invasive surgical routes. Patients who underwent minimally invasive hysterectomy had lower odds of VTE via laparoscopic (adjusted odds ratio [aOR] 0.62; confidence interval [CI]: 0.48-0.81) and vaginal (aOR 0.46; CI: 0.31-0.69) routes compared to laparotomy. Prolonged operative time (>120 min) was associated with increased odds of VTE (aOR 1.86; CI:1.51-2.29). CONCLUSION: The occurrence of VTE after a benign large specimen hysterectomy is rare. The odds of VTE is higher with longer operative times and lower with minimally invasive approaches, even for markedly enlarged uteri.


Assuntos
Tromboembolia Venosa , Humanos , Feminino , Estados Unidos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Histerectomia/efeitos adversos , Histerectomia Vaginal/efeitos adversos
12.
Chem Biodivers ; 20(6): e202300319, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37183173

RESUMO

Sphaeranthus africanus L. is native in Vietnam. Little is known about α-glucosidase inhibition of Sphaeranthus africanus and its isolated compounds. A bioactive-guided isolation was applied to the Vietnamese Sphaeranthus africanus to find α-glucosidase inhibitory components. Eight compounds were detected and structurally elucidated. They are 3-angeloyloxy-5-[2'',3''-epoxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[3''-chloro-2''-hydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''R,3''R-dihydroxy-2''-methyl-butanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''R-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone, 3-O-methylquercetin, and chrysosplenol D. Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. 3-Angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone is a new compound. Isolated compounds were evaluated for the α-glucosidase inhibition. Isolated compounds showed moderate activity with IC50 values ranging from 128.9-274.3 µM while others are weak. A molecular docking study was conducted, indicating that isolated compounds are potent α-glucosidase inhibitory compounds.


Assuntos
Asteraceae , Extratos Vegetais , Extratos Vegetais/química , Simulação de Acoplamento Molecular , alfa-Glucosidases , Asteraceae/química , Componentes Aéreos da Planta/química , Estrutura Molecular
13.
Chem Biodivers ; 20(11): e202301013, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37749933

RESUMO

From the moss Erythrodontium julaceum Paris growing in Vietnam, julacelide (1), a new 3-benzylphthalide, along with methyl orsellinate (2), ethyl orsellinate (3), 4-O-methylhaematommic acid (4), and zeorin (5), were isolated and structurally elucidated. Their chemical structures were elucidated through extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as through comparisons to the existing literature. Compound 4-O-methylhaematommic acid was a new natural product. The absolute configuration of julacelide was defined using time-dependent density functional theory (TDDFT) calculations. Julacelide was evaluated for α-glucosidase inhibition.


Assuntos
alfa-Glucosidases , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , alfa-Glucosidases/metabolismo , Teoria da Densidade Funcional
14.
Perfusion ; 38(6): 1308-1310, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35580365

RESUMO

An allergy to insect stings is one of the most frequent causes of anaphylactic reactions. Such reactions can be fatal, even on the first reaction, although it very rarely happens. The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) in refractory anaphylactic shock was previously described. We report a case of a 31-year-old female who presented with refractory anaphylactic shock after bee stings without the presence of cutaneous manifestations other than the rashes in her neck. The toxic component of bee venom and systemic allergic response plays a vital role in pathophysiology. She did not respond to conventional advanced life support, but following urgent VA ECMO, she survived neurologically intact. Despite an uncommon indication for anaphylaxis, ECMO support may be possible and effective in patients with refractory shock.


Assuntos
Anafilaxia , Venenos de Abelha , Oxigenação por Membrana Extracorpórea , Mordeduras e Picadas de Insetos , Feminino , Animais , Abelhas , Anafilaxia/etiologia , Anafilaxia/terapia , Mordeduras e Picadas de Insetos/complicações , Mordeduras e Picadas de Insetos/terapia , Choque Cardiogênico
15.
Circulation ; 143(4): 298-309, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33040613

RESUMO

BACKGROUND: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure). We also examined the effect of dapagliflozin on kidney function after randomization. METHODS: Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min-1·1.73 m-2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min-1·1.73 m-2) and used eGFR at baseline as a continuous measure, as well. Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time. RESULTS: Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min-1·1.73 m-2. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59-0.86) versus 0.77 (0.64-0.93) in those with an eGFR ≥60 mL·min-1·1.73 m-2 (interaction P=0.54). The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44-1.16]; P=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.40 to -0.77) versus placebo -2.85 (-3.17 to -2.53) mL·min-1·1.73 m-2 per year (P<0.001). This was observed in those with and without type 2 diabetes (P for interaction=0.92). CONCLUSIONS: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/farmacologia , Feminino , Glucosídeos/farmacologia , Insuficiência Cardíaca/complicações , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Volume Sistólico
16.
Biomacromolecules ; 23(8): 3130-3141, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35451812

RESUMO

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.


Assuntos
Nanopartículas Metálicas , Neoplasias , Pontos Quânticos , Transferência Ressonante de Energia de Fluorescência/métodos , Ouro , Humanos , Microambiente Tumoral
17.
Psychooncology ; 31(6): 938-949, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35048471

RESUMO

OBJECTIVES: Perceived cancer-related stigma can affect mental health and potentially treatment choices for patients with cancer. Nevertheless, perceived stigma is not very well understood in Asia. This study investigated across six developing Asian countries: (1) the prevalence of perceived stigma among advanced cancer patients, (2) its risk factors, and (3) its association with patient treatment preferences. METHODS: This cross-sectional study recruited patients receiving oncology care across major hospitals in Bangladesh, China, India, Philippines, Sri Lanka and Vietnam. Participants (N = 1358) were adults diagnosed with stage IV metastatic solid cancer who completed self-reported surveys. Multi-variable logistic regression and ordered logit models examined the associations with perceived stigma and variables of interest. RESULTS: Across the countries, 35%, 95% CI [32%, 38%] of patients reported experiencing at least one facet of cancer-related stigma often or always, while 60% [57%, 63%] reported it occurring occasionally. Top-endorsed facets of perceived stigma across the Asian countries suggest a distinct pattern. Having knowingly engaged in health-risk behaviours (OR = 2.03-2.24, 95% CI [1.14-1.19, 3.43-4.41]), unemployment (2.64 [1.67, 4.19]) and body image change (1.57 [1.00, 2.45]) were associated with higher odds of perceived stigma, while time mitigated perceived stigma (0.49-0.65 [0.30-0.45, 0.76-0.92]). Perceived stigma was associated with lower odds of preference for life-extending treatments, although the associations did not hold up in the adjusted model. CONCLUSIONS: Perceived stigma is unique among Asian advanced cancer patients. Stigma is important to assess and address, taking into consideration the various sociodemographic, clinical and psychological factors of cancer patients.


Assuntos
Neoplasias , Estigma Social , Adulto , Povo Asiático , Estudos Transversais , Humanos , Índia , Neoplasias/terapia
18.
Br J Clin Pharmacol ; 88(11): 4773-4783, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35562168

RESUMO

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.


Assuntos
Alprazolam , Fármacos Neuromusculares , Idoso , Diclofenaco , Interações Medicamentosas , Gabapentina , Humanos , Medicare , Fármacos Neuromusculares/efeitos adversos , Omeprazol , Estados Unidos/epidemiologia
19.
Dermatol Ther ; 35(8): e15590, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35583958

RESUMO

The cutaneous side effects of COVID-19 vaccines are being studied and their immunogenicity is most likely linked to the pathophysiology of psoriasis. Although uncommon, several cases of exacerbation and new onset of psoriasis have been reported globally after vaccination. To contribute to the literature on this intriguing topic, we present three cases of de novo psoriasis in adult patients following COVID-19 vaccination. Our observations and a literature review show that this occurrence is independent of the type and brand of vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Psoríase , Vacinas , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/etiologia , Vacinação/efeitos adversos
20.
Dig Dis Sci ; 67(9): 4574-4580, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35486203

RESUMO

OBJECTIVES: During the summer of 2021, case reports began to emerge documenting a small number of individuals who developed autoimmune hepatitis (AIH) following COVID-19 vaccination. These cases are rare and novel, and very little is known. In our systematic review, we analyzed every published case of AIH and reviewed their characteristic findings, treatment, and outcomes. METHODS: We searched PubMed, Embase, and Web of Science from December 1, 2019, to November 1, 2021. Two researchers independently extracted information from the articles about vaccine type, patient history, laboratory values, histology results, treatment regimens, and disease course. RESULTS: Thirty-two patients developed AIH-like syndromes after receiving a COVID-19 vaccine. Jaundice was the most frequently reported symptom (81%), and 19% of patients were initially asymptomatic and presented with elevated liver enzymes found during routine bloodwork. Mean alanine transaminase, aspartate transaminase, and total bilirubin were 1231 U/L, 921 U/L, and 14 mg/dL, respectively. Anti-nuclear antibody was positive in 56%, and anti-smooth muscle antibody in 28% of patients. Steroids were used in 75% of patients. Improvement or complete resolution was seen in 97% of patients. One patient died despite aggressive steroid treatment. CONCLUSION: COVID-19 vaccine-induced AIH is an uncommon association with just 32 documented cases in the literature. Clinicians should be vigilant for AIH in patients who present with liver injury following vaccination. These new findings should under not deter individuals from getting vaccinated, as the benefits of vaccination far outweigh the risks. Fortunately, COVID-19 vaccine-induced AIH appears amendable to corticosteroid therapy and appears to have a favorable outcome.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hepatite Autoimune , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/etiologia , Humanos , Vacinação
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