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1.
Biol Pharm Bull ; 47(2): 443-448, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38369343

RESUMO

This study aimed to investigate whether the approved sequence of vedolizumab and ustekinumab impacts the results of previous observational studies conducted in the European Union (EU), comparing the effectiveness of these drugs in Crohn's disease (CD) patients who failed anti-tumor necrosis factor-α (TNFα) treatment. We conducted this study in Japan, where the approved sequence of drugs is different from that of the EU. We extracted 256 patients diagnosed with CD, who had a history of anti-TNFα treatment and were prescribed either vedolizumab or ustekinumab, from JMDC claims database. The patients' backgrounds were adjusted by inverse probability of treatment weighting using propensity score. The primary outcome was treatment persistence. Secondary outcomes were a steroid-free period, time to hospitalization, and time to CD-related surgery. The hazard ratios (HR) for survival times were estimated using the Cox proportional hazard model. The treatment persistence (primary endpoint) was significantly longer for ustekinumab than vedolizumab (HR, 0.32; 95% confidence interval (CI), 0.15-0.72). The results of the secondary endpoints were as follows: steroid-free period (HR, 0.38; 95% CI, 0.10-1.48), time to hospitalization (HR, 1.07; 95% CI, 0.60-1.91), or time to CD-related surgery (HR, 0.33; 95% CI, 0.11-0.97). There were no outcomes indicating the superiority of vedolizumab. Our findings suggest that ustekinumab is a more effective treatment option than vedolizumab for CD patients who failed to anti-TNFα treatment, and this finding remains consistent across both Japan and the EU.


Assuntos
Anticorpos Monoclonais Humanizados , Doença de Crohn , Ustekinumab , Humanos , Ustekinumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fator de Necrose Tumoral alfa , Japão , Resultado do Tratamento , Necrose/induzido quimicamente , Estudos Retrospectivos
2.
Lakartidningen ; 1212024 Feb 13.
Artigo em Sueco | MEDLINE | ID: mdl-38369865

RESUMO

SGLT2i can induce euglycemic diabetic ketoacidosis (eDKA) in conditions with relative insulin deficiency, such as infections, surgery, or fasting state. In comparison with classical DKA, eDKA typically presents with lower blood glucose levels and more diffuse symptoms like tiredness, tachypnea, nausea and abdominal pain. The diagnosis is commonly delayed, and signs are often attributed to other factors. Early diagnosis and prevention are critical due to the risk of lethal outcome or prolonged hospital stay. Generous screening for ketonemia in risk situations allows identification of eDKA. To minimize the risk, we propose that SGLT2i should be discontinued 3-4 days before surgery (1-2 weeks prior to bariatric surgery) and during infections, acute disease, or poor oral intake. Postoperative slow infusion of low-dose insulin may prevent eDKA if SGLT2i could not be stopped in time or in prolonged fasting state. In this overview, the pathogenesis behind eDKA is discussed.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/diagnóstico , Insulina/uso terapêutico , Tempo de Internação
3.
Front Endocrinol (Lausanne) ; 15: 1332702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370356

RESUMO

Background/aim: Managing reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology. Method: A retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms. Result: Two patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and C-peptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms. Conclusion: These findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Metformina , Humanos , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Peptídeo C , Automonitorização da Glicemia , Glicemia , Hipoglicemia/induzido quimicamente , Metformina/uso terapêutico
4.
Drug Des Devel Ther ; 18: 443-452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370564

RESUMO

Purpose: Dexmedetomidine (Dex) is a potent and highly selective α2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC). Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 µg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded. Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P>0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P<0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P<0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P<0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P<0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P<0.05 for all). Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 µg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.


Assuntos
Colecistectomia Laparoscópica , Dexmedetomidina , Humanos , Bradicardia/induzido quimicamente , Estudos Prospectivos , Anestesia Geral , Dor Pós-Operatória/tratamento farmacológico , Pré-Medicação/métodos , Método Duplo-Cego
5.
Ann Med ; 56(1): 2311843, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38316016

RESUMO

OBJECTIVE: Dupilumab has been approved for the treatment of severe asthma with type 2 inflammation by inhibiting interleukin (IL)-4 and IL-13 signaling. However, dupilumab-induced hypereosinophilia (HE) has been reported and should not be ignored. The aim of this study was to investigate the efficacy of dupilumab in Chinese patients with severe asthma, whether HE affects its efficacy, and the possible risk factors for HE. METHODS: 20 patients with severe asthma who received dupilumab treatment for at least 12 months in the First Affiliated Hospital of Guangzhou Medical University from 2019 to 2022 were included. We compared clinical data and laboratory tests results before dupilumab treatment and at 4 and 12 months after treatment. Based on whether dupilumab treatment triggers HE defined as blood eosinophil count (BEC) ≥ 1.5 × 109 cells/L, the patients were allocated into non-HE and HE groups. RESULTS: The patients showed a significant increase in asthma control test (ACT) scores, a decrease in the number of exacerbations, a decrease in the proportion of patients taking an oral corticosteroid (OCS) and in the dose, and a significant improvement in the pulmonary function parameters FEV1/FVC (%) and FEV1 (% predicted) after 4 and 12 months of treatment with dupilumab. For type 2 inflammatory biomarkers, the levels of fractional concentration of exhaled nitric oxide (FeNO), sputum eosinophil count percentage (SEC%) and total immunoglobulin E (TIgE) decreased significantly, whereas BEC were higher after 4 months of treatment, but returned to baseline levels after 12 months. 8 patients (40%) developed asymptomatic HE after dupilumab, and the efficacy was not significantly different between the HE and non-HE groups. The earliest BEC elevation appeared at 1 month after treatment, but most of them declined after 6 months, and basically returned to the baseline level around 12 months of treatment. In addition, we further found that when patients had FeNO ≥ 60 ppb, food allergens positive and combined eosinophilic otitis media (EOM), their BEC increased significantly more than that of the control group after 4 months as well as 12 months of treatment. CONCLUSIONS: This study demonstrated that dupilumab was efficacious in Chinese patients with severe asthma, and some patients developed asymptomatic, self-limited HE, which did not affect its efficacy. Additionally, FeNO ≥60 ppb, food allergens positive, and co-morbidities with EOM may be the risk factors for developing HE.


Assuntos
Asma , Eosinofilia , Humanos , Asma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Eosinofilia/induzido quimicamente , Eosinofilia/tratamento farmacológico , Fatores de Risco
6.
Sci Total Environ ; 918: 170678, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38316313

RESUMO

BACKGROUND: Exposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. METHODOLOGY: A hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance (1H NMR) to cover polar and non-polar fractions. A "meet-in-the-middle" statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. RESULTS: Fourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms.


Assuntos
Endometriose , Poluentes Ambientais , Fluorocarbonos , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Humanos , Feminino , Bifenilos Policlorados/análise , Praguicidas/análise , Endometriose/induzido quimicamente , Estudos de Casos e Controles , Hidrocarbonetos Clorados/análise , Poluentes Ambientais/análise , Hidroxibutiratos , Fluorocarbonos/análise
7.
Sci Total Environ ; 918: 170668, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38320701

RESUMO

BACKGROUND: Transient receptor potential (TRP) ankyrin 1 (TRPA1) could mediate ozone-induced lung injury. Optic Atrophy 1 (OPA1) is one of the significant mitochondrial fusion proteins. Impaired mitochondrial fusion, resulting in mitochondrial dysfunction and ferroptosis, may drive the onset and progression of lung injury. In this study, we examined whether TRPA1 mediated ozone-induced bronchial epithelial cell and lung injury by activating PI3K/Akt with the involvement of OPA1, leading to ferroptosis. METHODS: Wild-type, TRPA1-knockout (KO) mice (C57BL/6 J background) and ferrostatin-1 (Fer-1)-pretreated mice were exposed to 2.5 ppm ozone for 3 h. Human bronchial epithelial (BEAS-2B) cells were treated with 1 ppm ozone for 3 h in the presence of TRPA1 inhibitor A967079 or TRPA1-knockdown (KD) as well as pharmacological modulators of PI3K/Akt-OPA1-ferroptosis. Transcriptome was used to screen and decipher the differential gene expressions and pathways. Oxidative stress, inflammation and ferroptosis were measured together with mitochondrial morphology, function and dynamics. RESULTS: Acute ozone exposure induced airway inflammation and airway hyperresponsiveness (AHR), reduced mitochondrial fusion, and enhanced ferroptosis in mice. Similarly, acute ozone exposure induced inflammatory responses, altered redox responses, abnormal mitochondrial structure and function, reduced mitochondrial fusion and enhanced ferroptosis in BEAS-2B cells. There were increased mitochondrial fusion, reduced inflammatory responses, decreased redox responses and ferroptosis in ozone-exposed TRPA1-KO mice and Fer-1-pretreated ozone-exposed mice. A967079 and TRPA1-KD enhanced OPA1 and prevented ferroptosis through the PI3K/Akt pathway in BEAS-2B cells. These in vitro results were further confirmed in pharmacological modulator experiments. CONCLUSION: Exposure to ozone induces mitochondrial dysfunction in human bronchial epithelial cells and mouse lungs by activating TRPA1, which results in ferroptosis mediated via a PI3K/Akt/OPA1 axis. This supports a potential role of TRPA1 blockade in preventing the deleterious effects of ozone.


Assuntos
Ferroptose , Lesão Pulmonar , Doenças Mitocondriais , Oximas , Ozônio , Humanos , Camundongos , Animais , Lesão Pulmonar/induzido quimicamente , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ozônio/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/induzido quimicamente , Células Epiteliais , Doenças Mitocondriais/metabolismo , Pulmão/metabolismo , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/farmacologia , Canal de Cátion TRPA1/metabolismo
8.
PLoS One ; 19(2): e0298396, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38330029

RESUMO

Chemotherapy is often a life-saving treatment, but the development of intractable pain caused by chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity that restricts cancer survival rates. Recent reports demonstrate that paclitaxel (PTX) robustly increases anti-inflammatory CD4+ T cells in the dorsal root ganglion (DRG), and that T cells and anti-inflammatory cytokines are protective against CIPN. However, the mechanism by which CD4+ T cells are activated, and the extent cytokines released by CD4+ T cells target DRG neurons are unknown. Here, we are the first to detect major histocompatibility complex II (MHCII) protein in mouse DRG neurons and to find CD4+ T cells breaching the satellite glial cell barrier to be in close proximity to neurons, together suggesting CD4+ T cell activation and targeted cytokine release. MHCII protein is primarily expressed in small nociceptive neurons in male and female mouse DRG but increased after PTX in small nociceptive neurons in only female DRG. Reducing one copy of MHCII in small nociceptive neurons decreased anti-inflammatory IL-10 and IL-4 producing CD4+ T cells in naïve male DRG and increased their hypersensitivity to cold. Administration of PTX to male and female mice that lacked one copy of MHCII in nociceptive neurons decreased anti-inflammatory CD4+ T cells in the DRG and increased the severity of PTX-induced cold hypersensitivity. Collectively, our results demonstrate expression of MHCII protein in mouse DRG neurons, which modulates cytokine producing CD4+ T cells in the DRG and attenuates cold hypersensitivity during homeostasis and after PTX treatment.


Assuntos
Síndromes Periódicas Associadas à Criopirina , Paclitaxel , Doenças do Sistema Nervoso Periférico , Ratos , Camundongos , Masculino , Feminino , Animais , Paclitaxel/toxicidade , Paclitaxel/metabolismo , Gânglios Espinais/metabolismo , Hiperalgesia/etiologia , Ratos Sprague-Dawley , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Citocinas/metabolismo , Neurônios/metabolismo , Anti-Inflamatórios/uso terapêutico
9.
J Dtsch Dermatol Ges ; 22(2): 186-194, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38345266

RESUMO

BACKGROUND: Few prospective studies exist with an evaluation of a dose-response relationship between use of some photosensitizing antihypertensive medications and skin cancer. PATIENT AND METHODS: We used prospective data from the Women's Health Initiative Observational Study to investigate the association between antihypertensive use and risk of non-melanoma skin cancer (NMSC) and melanoma in postmenopausal women aged 50-79 years at baseline (n  =  64,918). Multivariable Cox proportional hazards regression models were used and hazard ratios (HRs) and 95 confidence intervals (CIs) were calculated. RESULTS: 8,777 NMSC and 1,227 melanoma cases were observed. Use of antihypertensives (HR [95% CI]: 1.12 [1.07-1.18]), ACE inhibitors (1.09 [1.01-1.18]), calcium channel blockers (1.13 [1.05-1.22]), diuretics (1.20 [1.12-1.27]), loop diuretics (1.17 [1.07-1.28]), and thiazides (1.17 [1.03-1.33]) were each associated with higher NMSC risk. NMSC risk linearly increased with use of multiple antihypertensives (p-trend  =  0.02) and with longer duration of use (p-trend < 0.01). Antihypertensives (1.15 [1.00-1.31]), angiotensin-II receptor blockers (1.82 [1.05-3.15]), and diuretics (1.34 [1.13-1.59]) were each associated with elevated melanoma risk. Effect modification by solar radiation exposure was found between antihypertensive use and incidence of melanoma (p-interaction  =  0.02). CONCLUSIONS: Use of antihypertensives overall, and several individual classes thereof, were associated with higher incidence of NMSC and melanoma with dose-response relationship.


Assuntos
Dermatite Fototóxica , Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Anti-Hipertensivos/efeitos adversos , Melanoma/epidemiologia , Estudos Prospectivos , Pós-Menopausa , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Diuréticos
10.
Int J Implant Dent ; 10(1): 5, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321262

RESUMO

PURPOSE: Complications of implant prostheses have direct correlation with the increased use of implants for dental rehabilitation. In this study, we present cases of peri-implant oral malignancies (PIOM) around dental implants and a retrospective analysis of patients treated for PIOM. METHODS: The retrospective analysis was performed with patients treated for PIOM at the Department of Oral and Maxillofacial Surgery of the Seoul National University Dental Hospital between 2006 and 2014. The patient records were thoroughly screened for previous medical issues, human papilloma virus infections, and other clinical data with a focus on relevant information such as localization, time from implant insertion to the development of the carcinoma, implant type and prosthetic rehabilitation. RESULTS: Twenty-one patients were diagnosed with PIOM. The male-to-female ratio was 1.625. The mean age of the patients was 60.42 ± 9.35 years old. Three patients reported ongoing alcohol/tobacco consumption. Five patients had a history of previous oral cancer surgery or exhibited mucosal lesions. The time from implant placement until carcinoma diagnosis was 49.13 ± 33.63 months on average. Most PIOM patients (95.2%) were diagnosed with SCC. All patients had previously been treated for peri-implantitis. In 85.7% of the patients, prostheses were observed on the opposing teeth where PIOM occurred. CONCLUSION: Based on the review of these cases, it can be deduced that there is a possibility that implant treatment and galvanic currents between prosthesis may constitute an irritant and/or inflammatory cofactor which contributes to the formation and/or development of malignant tumors. Patients at potential risk may benefit from individualized recall intervals and careful evaluations.


Assuntos
Carcinoma , Implantes Dentários , Neoplasias Bucais , Peri-Implantite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Implantes Dentários/efeitos adversos , Estudos Retrospectivos , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/complicações , Carcinoma/induzido quimicamente , Carcinoma/complicações
11.
Aging Clin Exp Res ; 36(1): 23, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321321

RESUMO

The real efficacy of Acetyl-cholinesterase-inhibitors (AChEI) has been questioned. In this narrative review we evaluated their effect on cognitive decline, measured by Mini Mental State Examination (MMSE), and on total mortality rates in patients with Alzheimer's disease (AD) recruited into post-marketing open/non-randomized/retrospective studies. In AD patients treated with AChEI, the mean MMSE loss ranged from 0.2 to 1.37 points/years, compared with 1.07-3.4 points/years in non-treated patients. Six studies also reported data about survival; a reduction in total mortality relative risk between 27% and 42% was observed, over a period of 2-8 years. The type of studies and the use of MMSE to assess cognitive decline, may have introduced several biases. However, the clinical effects of AChEI seem to be of the same order of magnitude as the drugs currently used in most common chronic disorders, as regards progression of the disease and total mortality. In the absence of long-term randomized trials on "standard" unselected AD outpatients, open/retrospective studies and health databases represent the best available evidence on the possible effect of AChEI in the real-word setting. Our data support the clinical benefit of AChEI in older patients affected by AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Inibidores da Colinesterase/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Estudos Retrospectivos , Disfunção Cognitiva/induzido quimicamente , Colinesterases/uso terapêutico
12.
BMC Ophthalmol ; 24(1): 52, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308203

RESUMO

BACKGROUND: To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). RESULTS: The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P < 0.05). After pupil dilation, there were no changes in iris blood flow and PD in the T1DM group compared to healthy children, whereas the T2DM group showed a significantly smaller PD compared to healthy adults. Multivariate regression analysis revealed that in the T2DM group, glycated hemoglobin was an independent factor of PD after dilation (ß=-0.490, p = 0.031), with no such factors identified in the T1DM group. CONCLUSION: The insufficiently dilated pupil diameter after drug-induced mydriasis is correlated to the level of glycated hemoglobin among T2DM patients. TRIAL REGISTRATION: The registration number on the clinical trial website was NCT03631108.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Midríase , Adulto , Criança , Humanos , China , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Dilatação Patológica , Hemoglobinas Glicadas , Pressão Intraocular , Iris , Midríase/induzido quimicamente , Pupila/fisiologia , Tomografia de Coerência Óptica , Masculino , Feminino
13.
Rinsho Ketsueki ; 65(1): 24-29, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311385

RESUMO

Immune checkpoint inhibitor (ICI)-induced thrombocytopenias are rare immune-related adverse events (irAE), but ICI-related thrombotic thrombocytopenic purpura (TTP) is extremely rare. A 79-year-old woman with non-small cell lung cancer received maintenance therapy with the anti-human PD-L1 monoclonal antibody durvalumab. Four weeks after the last infusion, she developed overt TTP. Remission was achieved by plasma exchange and prednisolone, and the patient has now been recurrence-free for over 12 months. To our knowledge, this is the first report of TTP occurring as an irAE of durvalumab.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Púrpura Trombocitopênica Trombótica , Feminino , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/etiologia , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etiologia , Anticorpos Monoclonais/efeitos adversos , Troca Plasmática/efeitos adversos
14.
Rinsho Ketsueki ; 65(1): 41-46, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311388

RESUMO

The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCRγδ+CD8- atypical cells, leading to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). The patient was refractory to CHOP and DA-EPOCH, and therefore received cord blood transplantation with myeloablative conditioning. CT showed reduced in hepatosplenomegaly and peripheral blood examination showed LDH 165 U/l and plt 180,000/µl, so the patient was discharged on day117. HSTCL is a tumor of immature γδT cells with a Vδ1 mutation in the spleen, and immunodeficiency has been implicated in its pathogenesis. Patients with inflammatory bowel disease treated with azathioprine are known to have an increased risk of lymphoproliferative disease. In this case, use of immunosuppressive drugs for Crohn's disease may have caused malignant transformation of γδ cells in the intestinal epithelium. Although the patient was refractory to chemotherapy, he was able to achieve remission with early cord blood transplantation and long-term survival is expected.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença de Crohn , Neoplasias Hepáticas , Linfoma de Células T , Neoplasias Esplênicas , Masculino , Humanos , Adulto Jovem , Adulto , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Azatioprina/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Imunossupressores/uso terapêutico , Linfoma de Células T/etiologia , Linfoma de Células T/terapia , Linfoma de Células T/diagnóstico , Neoplasias Esplênicas/etiologia
15.
Pharmacoepidemiol Drug Saf ; 33(2): e5756, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38357810

RESUMO

BACKGROUND: Distinguishing warfarin-related bleeding risk at the bedside remains challenging. Studies indicate that warfarin therapy should be suspended when international normalized ratio (INR) ≥ 4.5, or it may sharply increase the risk of bleeding. We aim to develop and validate a model to predict the high bleeding risk in valve replacement patients during hospitalization. METHOD: Cardiac valve replacement patients from January 2016 to December 2021 across Nanjing First Hospital were collected. Five different machine-learning (ML) models were used to establish the prediction model. High bleeding risk was an INR ≥4.5. The area under the receiver operating characteristic curve (AUC) was used for evaluating the prediction performance of different models. The SHapley Additive exPlanations (SHAP) was used for interpreting the model. We also compared ML with ATRIA score and ORBIT score. RESULTS: A total of 2376 patients were finally enrolled in this model, 131 (5.5%) of whom experienced the high bleeding risk after anticoagulation therapy of warfarin during hospitalization. The extreme gradient boosting (XGBoost) exhibited the best overall prediction performance (AUC: 0.882, confidence interval [CI] 0.817-0.946, Brier score, 0.158) compared to other prediction models. It also shows superior performance compared with ATRIA score and ORBIT score. The top 5 most influential features in XGBoost model were platelet, thyroid stimulation hormone, body surface area, serum creatinine and white blood cell. CONCLUSION: A model for predicting high bleeding risk in valve replacement patients who treated with warfarin during hospitalization was successfully developed by using machine learning, which may well assist clinicians to identify patients at high risk of bleeding and allow timely adjust therapeutic strategies in evaluating individual patient.


Assuntos
Anticoagulantes , Varfarina , Humanos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Valvas Cardíacas/cirurgia , Aprendizado de Máquina
16.
Am J Case Rep ; 25: e942242, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311849

RESUMO

BACKGROUND Reye syndrome is a rare, yet potentially life-threatening disease characterized by acute encephalopathy and hepatic failure. This report presents the case of an 8-year-old girl with Reye syndrome and seizures after the use of naproxen. CASE REPORT An 8-year-old girl experienced a 3-day episode of fever and abdominal pain. After receiving naproxen (375 mg twice daily) starting from day -3, she exhibited hypotension, tonic seizure, and loss of consciousness (day 1). Physical examination and laboratory test results revealed acute kidney injury, metabolic acidosis, and elevated levels of lactate dehydrogenase (LDH), liver enzymes, and ferritin. On day 2, the maximum values of aspartate aminotransferase, alanine aminotransferase, LDH, creatinine, and ferritin were 955 U/L, 132 U/L, 8040 U/L, 2 mg/dL, and >40000 ug/L, respectively. She was given supportive care and recovered after 11 days (day 12), with normalization of kidney function and metabolic abnormalities. To identify possible genetic polymorphisms associated with the patient's symptoms, genotypes were tested using a drug metabolizing enzymes and transporters (DMET) gene chip. Among genes involved in the metabolism of naproxen, UGT1A6 (*1/*2) and UGT2B7 (*1/*2) resulted in possibly decreased function. Other results which may have had clinical significance included homozygote results for NAT2*6/*6 (rs1799930). CONCLUSIONS A rare case of Reye syndrome after administration of naproxen was presented in this case. A DMET gene chip was used to screen for possible genetic polymorphisms associated with Reye syndrome, but the result was inconclusive.


Assuntos
Arilamina N-Acetiltransferase , Síndrome de Reye , Feminino , Humanos , Criança , Síndrome de Reye/induzido quimicamente , Síndrome de Reye/genética , Naproxeno/efeitos adversos , Testes Farmacogenômicos , Febre , Convulsões , Ferritinas
17.
Hawaii J Health Soc Welf ; 83(2): 45-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344694

RESUMO

Thyrotoxicosis as the presenting syndrome of an underlying ß-hCG-secreting malignancy is well described. It has been previously theorized, but not reported, that the surge of ß-hCG secondary to chemotherapy induction may inadvertently trigger thyrotoxicosis. After thorough review, this is the first documented case of such event in peer-reviewed medical literature published in the English language. This is a case of a 21-year-old male with stage IIIc non-seminomatous germ cell tumor who developed paraneoplastic hyperthyroidism within 4 days of the first cycle of chemotherapy. Management considerations are suggested based on this case and review of the literature.


Assuntos
Antineoplásicos , Hipertireoidismo , Neoplasias Embrionárias de Células Germinativas , Tireotoxicose , Masculino , Humanos , Adulto Jovem , Adulto , Gonadotropina Coriônica/metabolismo , Gonadotropina Coriônica/uso terapêutico , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/complicações , Tireotoxicose/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Antineoplásicos/uso terapêutico
18.
FASEB J ; 38(4): e23487, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38345808

RESUMO

Increasing attention is being paid to the mechanistic investigation of exercise-associated chronic inflammatory disease improvement. Ulcerative colitis (UC) is one type of chronic inflammatory bowel disease with increasing incidence and prevalence worldwide. It is known that regular moderate aerobic exercise (RMAE) reduces the incidence or risk of UC, and attenuates disease progression in UC patients. However, the mechanisms of this RMAE's benefit are still under investigation. Here, we revealed that ß-hydroxybutyrate (ß-HB), a metabolite upon prolonged aerobic exercise, could contribute to RMAE preconditioning in retarding dextran sulfate sodium (DSS)-induced mouse colitis. When blocking ß-HB production, RMAE preconditioning-induced colitis amelioration was compromised, whereas supplementation of ß-HB significantly rescued impaired ß-HB production-associated defects. Meanwhile, we found that RMAE preconditioning significantly caused decreased colonic Th17/Treg ratio, which is considered to be important for colitis mitigation; and the downregulated Th17/Treg ratio was associated with ß-HB. We further demonstrated that ß-HB can directly promote the differentiation of Treg cell rather than inhibit Th17 cell generation. Furthermore, ß-HB increased forkhead box protein P3 (Foxp3) expression, the core transcriptional factor for Treg cell, by enhancing histone H3 acetylation in the promoter and conserved noncoding sequences of the Foxp3 locus. In addition, fatty acid oxidation, the key metabolic pathway required for Treg cell differentiation, was enhanced by ß-HB treatment. Lastly, administration of ß-HB without exercise significantly boosted colonic Treg cell and alleviated colitis in mice. Together, we unveiled a previously unappreciated role for exercise metabolite ß-HB in the promotion of Treg cell generation and RMAE preconditioning-associated colitis attenuation.


Assuntos
Colite Ulcerativa , Colite , Humanos , Camundongos , Animais , Linfócitos T Reguladores/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Ácido 3-Hidroxibutírico/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Colite Ulcerativa/metabolismo , Colo/metabolismo , Diferenciação Celular , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células Th17/metabolismo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
19.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345991

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory reaction syndrome caused by genetic or acquired immune dysregulation. The majority of adult HLH cases are caused by tumors, rheumatic immune disorders, and infections. However, drug-induced HLH is rarely reported. METHODS: We report a case of HLH in an adult caused by the administration of lamotrigine, to our knowledge, only nine other cases of lamotrigine-associated HLH have been reported in adult patients. RESULTS: After discontinuing lamotrigine and using steroid hormones for the HLH, the patient's condition has been brought under control. CONCLUSIONS: This case confirms that dexamethasone is also effective for drug-induced HLH. Usually, after discontinuing the relevant medications, there is no need for further maintenance treatment.


Assuntos
Linfo-Histiocitose Hemofagocítica , Doenças Reumáticas , Adulto , Humanos , Lamotrigina/efeitos adversos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Síndrome
20.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345994

RESUMO

BACKGROUND: Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. METHODS: Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1ß, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). RESULTS: The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1ß, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. CONCLUSIONS: Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.


Assuntos
Colite , Labetalol , Ratos , Animais , Labetalol/efeitos adversos , Molécula 1 de Adesão Intercelular/metabolismo , Sulfassalazina/efeitos adversos , Ratos Wistar , Colo/patologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Ácido Acético/efeitos adversos , Ácido Acético/metabolismo
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