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1.
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
2.
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
3.
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
4.
Lancet Haematol ; 11(2): e101-e113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302221

RESUMO

BACKGROUND: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma. METHODS: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1-2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, and on days 1 and 11 for cycles 3-4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1-28 for cycles 1-3; thereafter, up to 15 mg orally on days 1-28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1-6, and on day 1 for cycles 7-26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with ClinicalTrials.gov, NCT02495922, and is completed. FINDINGS: Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7-55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value, p=0·86), and 3-year progression-free survival rates were 69% (95% CI 61-77), 69% (61-76), 66% (58-74), and 67% (59-75) for patients treated with RVd/R, RVd/E-R, E-RVd/R, and E-RVd/E-R, respectively. Infections (grade 3 or worse) were the most frequently observed adverse event in all treatment groups (28 [20%] of 137 for RVd/R; 32 [23%] of 138 for RVd/E-R; 35 [25%] of 138 for E-RVd/R; and 48 [34%] of 142 for E-RVd/E-R). Serious adverse events (grade 3 or worse) were observed in 68 (48%) of 142 participants in the E-RVd/E-R group, 53 (39%) of 137 in the RVd/R, 53 (38%) of 138 in the RVd/E-R, and 50 (36%) of 138 in the E-RVd/R (36%) group. There were nine treatment-related deaths during the study. Two deaths (one sepsis and one toxic colitis) in the RVd/R group were considered lenalidomide-related. One death in the RVd/E-R group due to meningoencephalitis was considered lenalidomide and elotuzumab-related. Four deaths (one pulmonary embolism, one septic shock, one atypical pneumonia, and one cardiovascular failure) in the E-RVd/R group and two deaths (one sepsis and one pneumonia and pulmonary fibrosis) in the E-RVd/E-R group were considered related to lenalidomide or elotuzumab, or both. INTERPRETATION: Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma. FUNDING: Bristol Myers Squibb/Celgene and Chugai.


Assuntos
Anticorpos Monoclonais Humanizados , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Pneumonia , Sepse , Adulto , Masculino , Feminino , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Lenalidomida/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , Pneumonia/etiologia , Sepse/induzido quimicamente , Sepse/tratamento farmacológico
5.
Gut Microbes ; 16(1): 2310894, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312103

RESUMO

Gut microbiota and related metabolites are both crucial factors that significantly influence how individuals with Crohn's disease respond to immunotherapy. However, little is known about the interplay among gut microbiota, metabolites, Crohn's disease, and the response to anti-α4ß7-integrin in current studies. Our research utilized 2,4,6-trinitrobenzene sulfonic acid to induce colitis based on the humanized immune system mouse model and employed a combination of whole-genome shotgun metagenomics and non-targeted metabolomics to investigate immunotherapy responses. Additionally, clinical cases with Crohn's disease initiating anti-α4ß7-integrin therapy were evaluated comprehensively. Particularly, 16S-rDNA gene high-throughput sequencing and targeted bile acid metabolomics were conducted at weeks 0, 14, and 54. We found that anti-α4ß7-integrin therapy has shown significant potential for mitigating disease phenotypes in remission-achieving colitis mice. Microbial profiles demonstrated that not only microbial composition but also microbially encoded metabolic pathways could predict immunotherapy responses. Metabonomic signatures revealed that bile acid metabolism alteration, especially elevated secondary bile acids, was a determinant of immunotherapy responses. Especially, the remission mice significantly enriched the proportion of the beneficial Lactobacillus and Clostridium genera, which were correlated with increased gastrointestinal levels of BAs involving lithocholic acid and deoxycholic acid. Moreover, most of the omics features observed in colitis mice were replicated in clinical cases. Notably, anti-α4ß7 integrin provided sustained therapeutic benefits in clinical remitters during follow-up, and long-lasting remission was linked to persistent changes in the microbial-related bile acids. In conclusion, gut microbiota-mediated bile acid metabolism alteration could play a crucial role in regulating immunotherapy responses to anti-α4ß7-integrin in Crohn's disease. Therefore, the identification of prognostic microbial signals facilitates the advancement of targeted probiotics that activate anti-inflammatory bile acid metabolic pathways, thereby improving immunotherapy responses. The integrated multi-omics established in our research provide valuable insights into potential mechanisms that impact treatment responses in complex diseases.


Assuntos
Colite , Doença de Crohn , Microbioma Gastrointestinal , Animais , Camundongos , Doença de Crohn/tratamento farmacológico , Multiômica , Integrinas/genética , Integrinas/uso terapêutico , Colite/induzido quimicamente , Colite/terapia , Ácidos e Sais Biliares/uso terapêutico , Imunoterapia
6.
NEJM Evid ; 3(1): EVIDoa2300172, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38320514

RESUMO

High-Dose Glucocorticoids for Sudden Hearing LossThis trial compared courses of high-dose intravenous prednisolone or high-dose oral dexamethasone versus standard-dose oral prednisone in adults with idiopathic sudden sensorineural hearing loss. At 30 days, systemic high-dose glucocorticoid therapy was not superior to a lower-dose regimen with respect to change in hearing threshold, and it was associated with a higher risk of side effects.


Assuntos
Glucocorticoides , Perda Auditiva Súbita , Adulto , Humanos , Dexametasona , Perda Auditiva Súbita/induzido quimicamente , Prednisona , Resultado do Tratamento
7.
BMC Oral Health ; 24(1): 184, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317122

RESUMO

OBJECTIVE: The objective of the present study was to investigate oral health status, oral health related quality of life, and identify risk factors associated with invasive dental treatment and medication related osteonecrosis of the jaw in patients with multiple myeloma. MATERIAL AND METHODS: Patients newly diagnosed with multiple myeloma (n = 144) referred between January 2015 and September 2022 were retrospectively included. The patients underwent a thorough clinical and radiological oral examination and odontogenic infections were treated before the start of bisphosphonate treatment. The patients were followed annually, including clinical and radiological examinations. The oral health related quality of life was investigated by the OHIP-14 questionnaire. RESULTS: Dental treatment (RR = 7.75), receiving combination antineoplastic therapy≥3 (RR =4.13), periodontitis (RR = 4.21), and reduced number of teeth (RR = 2.87) were associated with an increased risk of medication related osteonecrosis of the jaw. The response rate of the OHIP-14 questionnaire was 70.2%. Oral pain or discomfort in the mouth related to the medical treatment was reported by 30.5%. CONCLUSION: Dental screening and treatment planning in patients with Multiple Myeloma may result in fewer oral infections and fewer interruptions of the medical treatment of myeloma.


Assuntos
Conservadores da Densidade Óssea , Mieloma Múltiplo , Osteonecrose , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/induzido quimicamente , Mieloma Múltiplo/complicações , Conservadores da Densidade Óssea/efeitos adversos , Saúde Bucal , Estudos Longitudinais , Estudos Retrospectivos , Qualidade de Vida , Difosfonatos/efeitos adversos , Osteonecrose/induzido quimicamente , Osteonecrose/prevenção & controle , Assistência Odontológica
8.
BMC Oral Health ; 24(1): 183, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317151

RESUMO

BACKGROUND: In the pediatric oncology population, oral mucositis as a consequence of chemotherapy is a highly prevalent complication which strongly affects both the quality of life and treatment possibilities of the patients. Still, the etiopathological mechanisms carrying to its development are not fully understood, although a possible role of oral dysbiosis has been previously investigated with unclear conclusions. The aim of this systematic review was to assess the available evidence on the role of microbiota in the development of oral mucositis. METHODS: A systematic literature search was performed following PRISMA guidelines. Three electronic databases were searched up until April 2023 and a following manual search included the reference lists of the included studies and reviews. Studies reporting microbiological and clinical data of pediatric patients treated by antineoplastic drugs were included. RESULTS: Thirteen studies met the inclusion criteria, reporting an average mucositis prevalence of 57,6%. Candida albicans infections were frequently observed in studies performing microbiological analysis on oral lesions, in contrast with the low rate detection of the Herpes simplex viruses. Bacterial species such as coagulase-negative Staphylococci and Streptococcus viridans were detected more frequently on lesion sites. Studies reporting a quantitative analysis of the general flora did not show comparable results. Risk of bias assessment among studies was generally considered high or very high. CONCLUSIONS: While the specific role of certain microbiological agents, such as Candida albicans, was frequently reported among studies, data regarding the general dynamics of oral microbiota in the development of oral mucositis are lacking in the current literature. Thus, more studies are needed to provide the knowledge required in order to improve protocols for the prevention and treatment of this threatening complication.


Assuntos
Antineoplásicos , Microbiota , Neoplasias , Estomatite , Humanos , Criança , Qualidade de Vida , Antineoplásicos/efeitos adversos , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Neoplasias/complicações
9.
BMC Public Health ; 24(1): 370, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317153

RESUMO

BACKGROUND: Recent studies suggested inconclusive associations between bisphenols exposure and hyperuricemia risk. Our objective was to assess the potential association of bisphenol A (BPA) and its substitutes bisphenol S and F (BPS and BPF) exposure with serum uric acid (SUA) levels, hyperuricemia, and gout prevalence among US adults within the NHANES 2013-2016 datasets. METHODS: Multivariable linear and logistic regression models were used to explore the associations of urinary bisphenols concentrations with SUA levels, hyperuricemia, and gout prevalence, in total population and different sex groups. The restricted cubic spline (RCS) model was used to explore the dose-response relationship. RESULTS: In total population, doubling of urinary BPS and ∑BPs concentrations showed associations with an increase of 2.64 µmol/L (95% CI: 0.54, 4.74) and 3.29 µmol/L (95% CI: 0.59, 5.99) in SUA levels, respectively. The RCS model indicated a significantly "J"-shaped dose-response relationship between BPS exposure and SUA levels. Compared to the reference group of urinary BPS, males in the highest quartile displayed a 13.06 µmol/L (95% CI: 0.75, 25.37) rise in SUA levels. For females, doubling of urinary BPS concentrations was associated with a 3.30 µmol/L (95% CI: 0.53, 6.07) increase in SUA levels, with a significant linear dose-response relationship. In total population, doubling of urinary BPA concentrations showed a 1.05-fold (95% CI: 0.97, 1.14) adjusted risk of having hyperuricemia, with an inverted "U" curve. Doubling of urinary ∑BPs concentrations was associated with a 1.05-fold (95% CI: 0.96, 1.14) adjusted risk of hyperuricemia in total population, with a significant monotonic dose-response relationship. In females, doubling of urinary BPS concentrations was associated with a 1.45-fold (95% CI: 1.01, 2.08) adjusted increased risk of having gout, with a "J" shaped relationship. CONCLUSIONS: BPA and BPS exposure to some extent were associated with elevated SUA levels and increased risk of hyperuricemia, with different dose-response relationships and sex differences.


Assuntos
Gota , Hiperuricemia , Fenóis , Sulfonas , Adulto , Humanos , Masculino , Feminino , Hiperuricemia/induzido quimicamente , Hiperuricemia/epidemiologia , Ácido Úrico , Estudos Transversais , Prevalência , Inquéritos Nutricionais , Gota/epidemiologia , Compostos Benzidrílicos
10.
Respir Res ; 25(1): 66, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317159

RESUMO

BACKGROUND: Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD. METHODS: Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603. RESULTS: HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-ß1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-ß1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-ß1 induced cell migration. CONCLUSIONS: These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-ß1/Smad2/3 signalling pathway.


Assuntos
Carbamatos , Fumar Cigarros , Oxazóis , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Remodelação das Vias Aéreas , Fator de Crescimento Transformador beta1/farmacologia , Fumar Cigarros/efeitos adversos , Ocludina , Desacetilase 6 de Histona/metabolismo , Desacetilase 6 de Histona/farmacologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Transição Epitelial-Mesenquimal , Caderinas/metabolismo , Células Epiteliais/metabolismo
11.
JAMA ; 331(5): 396-407, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319332

RESUMO

Importance: Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. Objective: To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Exposure: Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Main Outcomes and Measures: Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Results: Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. Conclusions and Relevance: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Doenças do Recém-Nascido , Vacinação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Vacinação/efeitos adversos , Vacinação/métodos , Vacinação/estatística & dados numéricos , Suécia/epidemiologia , Noruega/epidemiologia , Doenças do Recém-Nascido/induzido quimicamente , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia
12.
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
13.
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
14.
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
15.
Int J Immunopathol Pharmacol ; 38: 3946320241227103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323796

RESUMO

Introduction: Dry eye is a common ocular condition causing discomfort and visual disturbances. Anti-inflammatory agents like Cyclosporine A (CsA) are often used in its treatment. However, the impact of CsA on ocular flora remains understudied. This research aimed to evaluate changes in conjunctival and nasal microflora in patients receiving topical cyclosporine for dry eye. Methods: In this cross-sectional study, conjunctival and nasal samples were collected from two groups of dry eye patients. Group 1 consisted of 38 patients using CsA eye drops, while Group 2 included 34 patients using preservative-free artificial tear drops. Bacterial cultures were grown from the samples, and the identified organisms underwent antibiotic susceptibility testing. Additionally, alpha diversity metrics were employed to assess the diversity of bacterial species in the samples. Results: Bacterial growth was observed in 75% of conjunctival samples and 97.22% of nasal samples. Staphylococcus epidermidis was the predominant organism in both groups. Alpha diversity analysis showed no significant differences in Shannon diversity and OTU richness between the groups for most bacterial species. Antibiotic susceptibility tests revealed no substantial variations in resistance patterns between the groups. Conclusion: This study provides valuable insights into the impact of CsA eye drops on conjunctival and nasal flora in dry eye patients. The findings suggest that CsA does not significantly influence the composition, diversity, or antibiotic resistance patterns of ocular flora. Long-term topical cyclosporine treatment for dry eye does not significantly impact conjunctival microflora or lead to antibiotic resistance. These results have important implications for the safe use of CsA in patients undergoing ocular treatments, particularly those at risk of intraocular infections.


Assuntos
Ciclosporina , Síndromes do Olho Seco , Humanos , Estudos Transversais , Síndromes do Olho Seco/induzido quimicamente , Soluções Oftálmicas , Antibacterianos
17.
Support Care Cancer ; 32(3): 147, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38326487

RESUMO

PURPOSE: Delirium is a common and serious comorbidity in patients with advanced cancer, necessitating effective management. Nonetheless, effective drugs for managing agitated delirium in patients with advanced cancer remain unclear in real-world settings. Thus, the present study aimed to explore an effective pharmacotherapy for this condition. METHODS: We conducted a secondary analysis of a multicenter prospective observational study in Japan. The analysis included patients with advanced cancer who presented with agitated delirium and received pharmacotherapy. Agitation was defined as a score of the Richmond Agitation-Sedation Scale for palliative care (RASS-PAL) of ≥ 1. The outcome was defined as -2 ≤ RASS-PAL ≤ 0 at 72 h after the initiation of pharmacotherapy. Multiple propensity scores were quantified using a multinomial logistic regression model, and adjusted odds ratios (ORs) were calculated for haloperidol, chlorpromazine, olanzapine, quetiapine, and risperidone. RESULTS: The analysis included 271 patients with agitated delirium, and 87 (32%) showed -2 ≤ RASS-PAL ≤ 0 on day 3. The propensity score-adjusted OR of olanzapine was statistically significant (OR, 2.91; 95% confidence interval, 1.12 to 7.80; P = 0.030). CONCLUSIONS: The findings suggest that olanzapine may effectively improve delirium agitation in patients with advanced cancer.


Assuntos
Antipsicóticos , Delírio , Neoplasias , Humanos , Antipsicóticos/uso terapêutico , Olanzapina/uso terapêutico , Japão , Delírio/etiologia , Delírio/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico
18.
BMC Nephrol ; 25(1): 47, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311719

RESUMO

BACKGROUND: Chronic inflammation, reflected by an increased blood C-reactive protein (CRP) level, is common in patients with chronic kidney disease (CKD) and is involved in the development of renal anemia. This systematic review aims to investigate the impacts of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of renal anemia in patients with CKD. METHODS: We conducted a comprehensive search of electronic databases including Pubmed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and the International Clinical Trials Registry Platform (ICTRP), from their inception to May 19, 2022. We systematically reviewed evidence from randomized controlled trials using HIF-PHIs for renal anemia treatment. The mean difference (MD) in changes in hemoglobin concentration (∆Hb) before and after treatment served as the meta-analysis outcome, utilizing a random-effects model. We compared groups with CRP levels greater than or equal to the upper limit of normal (ULN) and less than the ULN. Additionally, further analysis was conducted in the CRP ≥ ULN group comparing HIF-PHIs and erythropoiesis-stimulating agents (ESA). RESULTS: A total of 7 studies from 6 publications were included in the analysis. In the comparison between the CRP ≥ ULN group and the CRP < ULN group, 524 patients from 4 studies were incorporated into the analysis. All patients received roxadustat as the primary intervention. The pooled results revealed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (Mean Difference: 0.00, 95% Confidence Interval: -0.32 to 0.33, P = 0.99). Moreover, within the CRP ≥ ULN group, three studies involving 1399 patients compared the efficacy of roxadustat and erythropoiesis-stimulating agents (ESAs). The results indicated no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (Mean Difference: 0.24, 95% Confidence Interval: -0.08 to 0.56, P = 0.14). In terms of medication dosage, an increase in ESA dose over time was observed across various studies, particularly evident in the CRP ≥ ULN group, while the dose of roxadustat remains constant over time and is not influenced by the baseline levels of CRP. CONCLUSIONS: Our systematic review demonstrates that roxadustat exhibits similar efficacy across different CRP levels. Moreover, within the CRP ≥ ULN group, roxadustat can maintain efficacy comparable to ESA without the necessity for dose escalation. TRIAL REGISTRATION: CRD42023396704.


Assuntos
Anemia , Hematínicos , Insuficiência Renal Crônica , Humanos , Proteína C-Reativa , Ensaios Clínicos Controlados Aleatórios como Assunto , Anemia/tratamento farmacológico , Anemia/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente , Hematínicos/uso terapêutico , Doença Crônica , Glicina/efeitos adversos , Isoquinolinas
19.
Mol Biol Rep ; 51(1): 277, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319443

RESUMO

BACKGROUND: The most widely used food additive monosodium glutamate (MSG) has been linked to immunopathology. Conversely, quercetin (Q), a naturally occurring flavonoid has been demonstrated to have immunomodulatory functions. Therefore, the purpose of the study is to determine if quercetin can mitigate the deleterious effects of MSG on immune cells, and the possible involvement of TLR, if any.  METHODS AND RESULTS: This study was conducted on Q, to determine how it affects the inflammatory response triggered by MSG in primary cultured thymocytes and splenocytes from rats (n = 5). Q shielded cells by augmenting cell survival and decreasing lactate dehydrogenase leakage during MSG treatment. It decreased IL-1ß, IL-6, IL-8, and TNF-α expression and release by hindering NF-kB activation and by inhibiting the JAK/STAT pathway. Moreover, Q prevented NLRP3 activation, lowered IL-1ß production, and promoted an anti-inflammatory response by increasing IL-10 production. Q reduced MSG-induced cellular stress and inflammation by acting as an agonist for PPAR-γ and LXRα, preventing NF-kB activation, and lowering MMP-9 production via increasing TIMP-1. Additionally, Q neutralized free radicals, elevated intracellular antioxidants, and impeded RIPK3, which is involved in inflammation induced by oxidative stress, TNF-α, and TLR agonists in MSG-treated cells. Furthermore, it also modulated TYK2 and the JAK/STAT pathway, which exhibited an anti-inflammatory effect. CONCLUSIONS: MSG exposure is associated with immune cell dysfunction, inflammation, and oxidative stress, and Q modulates TLR to inhibit NF-kB and JAK/STAT pathways, providing therapeutic potential. Further research is warranted to understand Q's downstream effects and explore its potential clinical applications in inflammation.


Assuntos
NF-kappa B , Transdução de Sinais , Animais , Ratos , Anti-Inflamatórios , Inflamação/induzido quimicamente , Janus Quinases , Quercetina/farmacologia , Glutamato de Sódio/toxicidade , Baço , Fatores de Transcrição STAT , Timócitos , Fator de Necrose Tumoral alfa
20.
Rheumatology (Oxford) ; 63(SI): SI96-SI106, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320592

RESUMO

In this review, we discuss the current evidence on classic and newer oral anticoagulant therapy, older drugs such as HCQ and statins, and new potential treatment targets in APS. Vitamin K antagonists (VKAs) remain the cornerstone treatment for thrombotic events in APS. In patients fulfilling criteria for definite APS presenting with a first venous thrombosis, treatment with VKAs with a target international normalized ratio (INR) 2.0-3.0 is recommended. In patients with arterial thrombosis, treatment with VKA with target INR 2.0-3.0 or 3.0-4.0 is recommended by recent guidelines, considering the individual's bleeding and thrombosis recurrence risk. A combination of VKAs and low-dose aspirin (75-100 mg/daily) may also be considered. According to available evidence direct oral anticoagulants should be avoided in patients with arterial thrombosis and/or those with triple aPL positivity. Adjunctive treatment with HCQ and/or statins can be considered, especially in anticoagulation treatment-refractory APS. Potential targeted treatments in APS include B-cell targeting, complement inhibition, mammalian target of rapamycin inhibition, IFN targeting, adenosine receptors agonists, CD38 targeting or chimeric antigen receptor T-cell therapy. The safety and efficacy of these treatment targets needs to be examined in well-designed randomized controlled trials.


Assuntos
Síndrome Antifosfolipídica , Inibidores de Hidroximetilglutaril-CoA Redutases , Trombose , Humanos , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Trombose/induzido quimicamente , Hemorragia
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