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1.
Nat Metab ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499766

RESUMO

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin's effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the effects of metformin on food intake and body weight. Lastly, mediation analyses support a role for Lac-Phe as a downstream effector of metformin's effects on body mass index in participants of a large population-based observational cohort, the Multi-Ethnic Study of Atherosclerosis. Together, these data establish Lac-Phe as a critical mediator of the body weight-lowering effects of metformin.

2.
Childs Nerv Syst ; 40(5): 1367-1375, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38240786

RESUMO

OBJECTIVE: Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs. METHODS: We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022. RESULTS: Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up. CONCLUSION: Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.


Assuntos
Carcinoma de Células Renais , Cistos do Sistema Nervoso Central , Cistos , Neoplasias Renais , Humanos , Criança , Masculino , Feminino , Adolescente , Estudos Retrospectivos , Cistos do Sistema Nervoso Central/cirurgia
4.
Gynecol Oncol ; 180: 132-138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38091772

RESUMO

OBJECTIVES: The uterine cancer (UC) mortality rate in the UK is significantly higher for women who belong to a Black ethnic group compared to those from other ethnic groups. This study aimed to understand the views and experiences of UC amongst Black ethnic minority women in the UK, with a focus on awareness and presentation of red-flag symptoms. METHODS: Women of Black African, Caribbean, Black British and Mixed-Black ethnicity were purposefully recruited to participate in focus groups and individual semi-structured interviews. RESULTS: Twenty women from different regions in England participated in the study. Reflexive thematic analysis of the data led to the identification of three main themes: 1) Healthcare inequities; 2) Support and sense making with other Black women; and 3) Knowledge dissemination, mobilisation, and empowerment. Perceptions of inequitable healthcare provision and distrust influenced how participants, and their peer networks, approached seeking assistance from healthcare professionals. Concerns were also raised about culturally insensitive information resources, including issues of language, literacy, and representation, all of which served as potential barriers for women within Black ethnic minority groups. CONCLUSIONS: The deficiency of targeted knowledge mobilisation and specific UC information aimed at Black ethnicity women living in the UK, reportedly contributes to the dissemination of misconceptions and an atmosphere of apprehension around a UC diagnosis. The insights from this study highlight the significance of designing culturally sensitive strategies to promote informed decision-making and empower the dissemination of accurate health knowledge amongst Black women.


Assuntos
Etnicidade , Neoplasias Uterinas , Humanos , Feminino , Grupos Minoritários , Região do Caribe , Inglaterra
5.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469305

RESUMO

Abstract The aim of the present study is to assess the effects of selenium nanoparticles on the growth, hematology and nutrients digestibility of Labeorohita fingerlings. Fingerlings were fed with seven isocaloric sunflower meal-based diet supplemented with different concentrations of nanoparticles naming T1 to T7 (0, 0.5, 1, 1.5, 2, 2.5, and 3 mg/kg), with 5% wet body weight while chromic oxide was used as an indigestible marker. After experimentation for 90 days T3 treated group (1mg/kg -1Se-nano level) showed the best result in hematological parameters (WBCs 7.97 ×103mm-3, RBCs 2.98 ×106 mm-3 and Platelet count 67), nutrient digestibility (crude protein: 74%, ether extract: 76%, gross energy: 70%) and growth performance (weight gain 13.24 g, weight gain% 198, feed conversion ratio 1.5, survival rate 100%) as compared to the other treatment groups. Specific growth rates were found significantly higher in T5 than in other groups. The present study indicated positive effect of 1 mg/kg Se-nanoparticles on growth advancement, hematological parameters, and nutrients digestibility of L. rohita fingerlings.


Resumo O objetivo do presente estudo é avaliar os efeitos das nanopartículas de selênio no crescimento, hematologia e digestibilidade dos nutrientes de alevinos de Labeo rohita. Os alevinos foram alimentados com sete dietas isocalóricas à base de farinha de girassol suplementada com diferentes concentrações de nanopartículas, nomeando T1 a T7 (0, 0,5, 1, 1,5, 2, 2,5 e 3 mg / kg), com 5% do peso corporal úmido enquanto o óxido crômico foi usado como um marcador indigesto. Após a experimentação por 90 dias, o grupo tratado com T3 (nível 1mg / kg -1Se-nano) mostrou o melhor resultado em parâmetros hematológicos (WBCs 7,97 × 103mm-3, RBCs 2,98 × 106mm-3 e contagem de plaquetas 67), digestibilidade dos nutrientes (proteína bruta: 74%, extrato de éter: 76%, energia bruta: 70%) e desempenho de crescimento (ganho de peso 13,24 g, ganho de peso % 198, taxa de conversão alimentar 1,5, taxa de sobrevivência 100%) em comparação com os outros grupos de tratamento. As taxas de crescimento específicas foram encontradas significativamente mais altas em T5 do que em outros grupos. O presente estudo indicou efeito positivo de 1 mg / kg de nanopartículas de Se no avanço do crescimento, parâmetros hematológicos e digestibilidade de nutrientes de alevinos de L. rohita.

6.
Braz. j. biol ; 84: e253555, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355900

RESUMO

Abstract The aim of the present study is to assess the effects of selenium nanoparticles on the growth, hematology and nutrients digestibility of Labeorohita fingerlings. Fingerlings were fed with seven isocaloric sunflower meal-based diet supplemented with different concentrations of nanoparticles naming T1 to T7 (0, 0.5, 1, 1.5, 2, 2.5, and 3 mg/kg), with 5% wet body weight while chromic oxide was used as an indigestible marker. After experimentation for 90 days T3 treated group (1mg/kg -1Se-nano level) showed the best result in hematological parameters (WBC's 7.97 ×103mm-3, RBC's 2.98 ×106 mm-3 and Platelet count 67), nutrient digestibility (crude protein: 74%, ether extract: 76%, gross energy: 70%) and growth performance (weight gain 13.24 g, weight gain% 198, feed conversion ratio 1.5, survival rate 100%) as compared to the other treatment groups. Specific growth rates were found significantly higher in T5 than in other groups. The present study indicated positive effect of 1 mg/kg Se-nanoparticles on growth advancement, hematological parameters, and nutrients digestibility of L. rohita fingerlings.


Resumo O objetivo do presente estudo é avaliar os efeitos das nanopartículas de selênio no crescimento, hematologia e digestibilidade dos nutrientes de alevinos de Labeo rohita. Os alevinos foram alimentados com sete dietas isocalóricas à base de farinha de girassol suplementada com diferentes concentrações de nanopartículas, nomeando T1 a T7 (0, 0,5, 1, 1,5, 2, 2,5 e 3 mg / kg), com 5% do peso corporal úmido enquanto o óxido crômico foi usado como um marcador indigesto. Após a experimentação por 90 dias, o grupo tratado com T3 (nível 1mg / kg -1Se-nano) mostrou o melhor resultado em parâmetros hematológicos (WBC's 7,97 × 103mm-3, RBC's 2,98 × 106mm-3 e contagem de plaquetas 67), digestibilidade dos nutrientes (proteína bruta: 74%, extrato de éter: 76%, energia bruta: 70%) e desempenho de crescimento (ganho de peso 13,24 g, ganho de peso % 198, taxa de conversão alimentar 1,5, taxa de sobrevivência 100%) em comparação com os outros grupos de tratamento. As taxas de crescimento específicas foram encontradas significativamente mais altas em T5 do que em outros grupos. O presente estudo indicou efeito positivo de 1 mg / kg de nanopartículas de Se no avanço do crescimento, parâmetros hematológicos e digestibilidade de nutrientes de alevinos de L. rohita.


Assuntos
Animais , Nanopartículas , Helianthus , Nutrientes , Suplementos Nutricionais , Dieta , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal
7.
Nature ; 624(7991): 267-274, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38092906

RESUMO

The phase-coherent frequency division of a stabilized optical reference laser to the microwave domain is made possible by optical-frequency combs (OFCs)1,2. OFC-based clockworks3-6 lock one comb tooth to a reference laser, which probes a stable atomic transition, usually through an active servo that increases the complexity of the OFC photonic and electronic integration for fieldable clock applications. Here, we demonstrate that the Kerr nonlinearity enables passive, electronics-free synchronization of a microresonator-based dissipative Kerr soliton (DKS) OFC7 to an externally injected reference laser. We present a theoretical model explaining this Kerr-induced synchronization (KIS), which closely matches experimental results based on a chip-integrated, silicon nitride, micro-ring resonator. Once synchronized, the reference laser captures an OFC tooth, so that tuning its frequency provides direct external control of the OFC repetition rate. We also show that the stability of the repetition rate is linked to that of the reference laser through the expected frequency division factor. Finally, KIS of an octave-spanning DKS exhibits enhancement of the opposite dispersive wave, consistent with the theoretical model, and enables improved self-referencing and access to the OFC carrier-envelope offset frequency. The KIS-mediated enhancements we demonstrate can be directly implemented in integrated optical clocks and chip-scale low-noise microwave generators.

8.
bioRxiv ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37961394

RESUMO

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformin's effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite Lac-Phe in mice as well as in two independent human cohorts. In cell culture, metformin drives Lac-Phe biosynthesis via inhibition of complex I, increased glycolytic flux, and intracellular lactate mass action. Other biguanides and structurally distinct inhibitors of oxidative phosphorylation also increase Lac-Phe levels in vitro. Genetic ablation of CNDP2, the principal biosynthetic enzyme for Lac-Phe, in mice renders animals resistant to metformin's anorexigenic and anti-obesity effects. Mediation analyses also support a role for Lac-Phe in metformin's effect on body mass index in humans. These data establish the CNDP2/Lac-Phe pathway as a critical mediator of the effects of metformin on energy balance.

9.
ACS Omega ; 8(43): 40517-40531, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37929092

RESUMO

The prediction of the yields of light olefins in the direct conversion of crude oil to chemicals requires the development of a robust model that represents the crude-to-chemical conversion processes. This study utilizes artificial intelligence (AI) and machine learning algorithms to develop single and ensemble learning models that predict the yields of ethylene and propylene. Four single-model AI techniques and four ensemble paradigms were developed using experimental data derived from the catalytic cracking experiments of various crude oil fractions in the advanced catalyst evaluation reactor unit. The temperature, feed type, feed conversion, total gas, dry gas, and coke were used as independent variables. Correlation matrix analyses were conducted to filter the input combinations into three different classes (M1, M2, and M3) based on the relationship between dependent and independent variables, and three performance metrics comprising the coefficient of determination (R2), Pearson correlation coefficient (PCC), and mean square error (MSE) were used to evaluate the prediction performance of the developed models in both calibration and validations stages. All four single models have very low R2 and PCC values (as low as 0.07) and very high MSE values (up to 4.92 wt %) for M1 and M2 in both calibration and validation phases. However, the ensemble ML models show R2 and PCC values of 0.99-1 and an MSE value of 0.01 wt % for M1, M2, and M3 input combinations. Therefore, ensemble paradigms improve the performance accuracy of single models by up to 58 and 62% in the calibration and validation phases, respectively. The ensemble paradigms predict with high accuracy the yield of ethylene and propylene in the catalytic cracking of crude oil and its fractions.

10.
Cureus ; 15(10): e46720, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021516

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) has been proven efficacious in the removal of CBD stones. Even after endoscopic stone removal, recurring cholangitis due to a residual common bile duct (CBD) stone is prevalent in clinical practice with a residual recurrence rate of 4-24% after successful stone retrieval. This comprehensive study and meta-analysis aimed to determine if preventive saline irrigation of the bile duct (PSIB) reduces the amount of residual CBD stones. Through a comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science until November 20, 2022, we identified 164 articles comparing the efficacy of PSIB and non-PSIB post-endoscopic CBD stone removal. After stringent selection, three studies were included for meta-analysis using ReviewManager (ReVman version 5.4.1; Cochrane, London, UK). Using a random effect (RE) model, we derived a pooled odds ratio (OR) with confidence interval (CI) (95%CI). A total of three studies have been included in the analysis. Out of which, two are randomized controlled trials (RCTs) and one is a non-randomized study. Out of 323 patients, 157 underwent PSIB after an endoscopic stone removal of CBD stones to reduce the residual of CBD stones, whereas 166 did not undergo saline irrigation (non-PSIB). In our analysis, PSIB significantly reduced the risk of residual stones (OR: 0.22, 95%CI: 0.11-0.45). However, there was no notable link between PSIB and post-irrigation cholangitis (OR: 1.08, 95%CI: 0.21-2.21). Although not statistically significant, PSIB showed a trend toward lowered risks of post-procedural pancreatitis (OR: 0.65), bleeding (OR: 0.68), and other complications (OR: 0.64). PSIB effectively reduces residual CBD stones after endoscopy, offering a cost-effective alternative to invasive procedures such as intraductal ultrasound (IDUS). However, larger RCTs are needed to validate its definitive role.

11.
Nat Metab ; 5(10): 1656-1672, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37872285

RESUMO

Metabolomic epidemiology is the high-throughput study of the relationship between metabolites and health-related traits. This emerging and rapidly growing field has improved our understanding of disease aetiology and contributed to advances in precision medicine. As the field continues to develop, metabolomic epidemiology could lead to the discovery of diagnostic biomarkers predictive of disease risk, aiding in earlier disease detection and better prognosis. In this Review, we discuss key advances facilitated by the field of metabolomic epidemiology for a range of conditions, including cardiometabolic diseases, cancer, Alzheimer's disease and COVID-19, with a focus on potential clinical utility. Core principles in metabolomic epidemiology, including study design, causal inference methods and multi-omic integration, are briefly discussed. Future directions required for clinical translation of metabolomic epidemiology findings are summarized, emphasizing public health implications. Further work is needed to establish which metabolites reproducibly improve clinical risk prediction in diverse populations and are causally related to disease progression.


Assuntos
Metabolômica , Medicina de Precisão , Humanos , Metabolômica/métodos , Prognóstico , Fenótipo , Progressão da Doença
13.
JACC Case Rep ; 22: 101996, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37790765

RESUMO

We present the case of a 60-year-old man who presented with a post-myocardial infarction ventricular septal rupture caused by a delayed presentation of myocardial infarction. Despite revascularization, hemodynamic stability, and a 10-day delay until operative management to allow for tissue healing, the patient experienced a fatal recurrent postoperative ventricular septal rupture. (Level of Difficulty: Beginner.).

14.
Cell Metab ; 35(9): 1646-1660.e3, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37582364

RESUMO

Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelian randomization (MR) analyses, we identified putative causal protein-to-metabolite associations. We experimentally validated top MR associations in proof-of-concept plasma metabolomics studies in three murine knockout strains of key protein regulators. These analyses identified previously unrecognized associations between bioactive proteins and metabolites in human plasma. We provide publicly available data to be leveraged for studies in human metabolism and disease.


Assuntos
Metabolômica , Proteômica , Humanos , Animais , Camundongos , Transdução de Sinais , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética
15.
Clin J Am Soc Nephrol ; 18(11): 1416-1425, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37533140

RESUMO

BACKGROUND: Sickle cell trait affects approximately 8% of Black individuals in the United States, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence suggests that sickle cell trait is associated with lower eGFR and higher risk of kidney diseases, including kidney failure. The mechanisms underlying these associations remain poorly understood. We used proteomic profiling to gain insight into the pathobiology of sickle cell trait. METHODS: We measured proteomics ( N =1285 proteins assayed by Olink Explore) using baseline plasma samples from 592 Black participants with sickle cell trait and 1:1 age-matched Black participants without sickle cell trait from the prospective Women's Health Initiative cohort. Age-adjusted linear regression was used to assess the association between protein levels and sickle cell trait. RESULTS: In age-adjusted models, 35 proteins were significantly associated with sickle cell trait after correction for multiple testing. Several of the sickle cell trait-protein associations were replicated in Black participants from two independent cohorts (Atherosclerosis Risk in Communities study and Jackson Heart Study) assayed using an orthogonal aptamer-based proteomic platform (SomaScan). Many of the validated sickle cell trait-associated proteins are known biomarkers of kidney function or injury ( e.g. , hepatitis A virus cellular receptor 1 [HAVCR1]/kidney injury molecule-1 [KIM-1], uromodulin [UMOD], ephrins), related to red cell physiology or hemolysis (erythropoietin [EPO], heme oxygenase 1 [HMOX1], and α -hemoglobin stabilizing protein) and/or inflammation (fractalkine, C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 [MCP-1], and urokinase plasminogen activator surface receptor [PLAUR]). A protein risk score constructed from the top sickle cell trait-associated biomarkers was associated with incident kidney failure among those with sickle cell trait during Women's Health Initiative follow-up (odds ratio, 1.32; 95% confidence interval, 1.10 to 1.58). CONCLUSIONS: We identified and replicated the association of sickle cell trait with a number of plasma proteins related to hemolysis, kidney injury, and inflammation.


Assuntos
Insuficiência Renal , Traço Falciforme , Humanos , Feminino , Estados Unidos , Proteoma , Estudos Prospectivos , Hemólise , Proteômica , Biomarcadores , Inflamação
16.
medRxiv ; 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37609271

RESUMO

Background: Black adults have higher incidence of all-cause death and worse cardiovascular outcomes when compared to other populations. The Duffy chemokine receptor is not expressed in a large majority of Black adults and the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and long-term cardiovascular outcomes in Black members of two contemporary, longitudinal cohort studies (the Jackson Heart Study and Multi-Ethnic Study of Atherosclerosis). Data on 4,307 Black participants (2,942 Duffy null and 1,365 Duffy receptor positive, as defined using Single Nucleotide Polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was not independently associated with elevated levels of serum hs-CRP levels once conditioning for known CRP locus alleles in linkage disequilibrium with the Duffy gene. Duffy null status was not found to be independently associated with higher incidence of all-cause mortality or secondary outcomes after adjusting for possible confounders in Black participants. Conclusions: These findings suggest that increased levels of hs-CRP found in Duffy null individuals is due to co-inheritance of CRP alleles known to influence circulating levels hs-CRP and that Duffy null status was not associated with worse adverse outcomes over the follow-up period in this cohort of well-balanced Black participants.

17.
Circulation ; 148(12): 936-946, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37621213

RESUMO

BACKGROUND: Current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) have limited performance and were developed for individuals treated with warfarin. This study develops and validates a clinical risk score to personalize estimates of bleeding risk for individuals with atrial fibrillation taking direct-acting oral anticoagulants (DOACs). METHODS: Among individuals taking dabigatran 150 mg twice per day from 44 countries and 951 centers in this secondary analysis of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy), a risk score was developed to determine the comparative risk for bleeding on the basis of covariates derived in a Cox proportional hazards model. The risk prediction model was internally validated with bootstrapping. The model was then further developed in the GARFIELD-AF registry (Global Anticoagulant Registry in the Field-Atrial Fibrillation), with individuals taking dabigatran, edoxaban, rivaroxaban, and apixaban. To determine generalizability in external cohorts and among individuals on different DOACs, the risk prediction model was validated in the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) pooled clinical trial cohort and the Quebec Régie de l'Assurance Maladie du Québec and Med-Echo Administrative Databases (RAMQ) administrative database. The primary outcome was major bleeding. The risk score, termed the DOAC Score, was compared with the HAS-BLED score. RESULTS: Of the 5684 patients in RE-LY, 386 (6.8%) experienced a major bleeding event, within a median follow-up of 1.74 years. The prediction model had an optimism-corrected C statistic of 0.73 after internal validation with bootstrapping and was well-calibrated based on visual inspection of calibration plots (goodness-of-fit P=0.57). The DOAC Score assigned points for age, creatinine clearance/glomerular filtration rate, underweight status, stroke/transient ischemic attack/embolism history, diabetes, hypertension, antiplatelet use, nonsteroidal anti-inflammatory use, liver disease, and bleeding history, with each additional point scored associated with a 48.7% (95% CI, 38.9%-59.3%; P<0.001) increase in major bleeding in RE-LY. The score had superior performance to the HAS-BLED score in RE-LY (C statistic, 0.73 versus 0.60; P for difference <0.001) and among 12 296 individuals in GARFIELD-AF (C statistic, 0.71 versus 0.66; P for difference = 0.025). The DOAC Score had stronger predictive performance than the HAS-BLED score in both validation cohorts, including 25 586 individuals in COMBINE-AF (C statistic, 0.67 versus 0.63; P for difference <0.001) and 11 945 individuals in RAMQ (C statistic, 0.65 versus 0.58; P for difference <0.001). CONCLUSIONS: In individuals with atrial fibrillation potentially eligible for DOAC therapy, the DOAC Score can help stratify patients on the basis of expected bleeding risk.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa , Dabigatrana/efeitos adversos , Rivaroxabana , Anticoagulantes/efeitos adversos
18.
West Afr J Med ; 40(8): 792-798, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37639291

RESUMO

BACKGROUND: Neonatal septicaemia (NNS) occurs during the first 28 days of life and is characterized by systemic bacterial infection proven by blood culture. It is a leading cause of morbidity and mortality in neonates. Determinants of NNS vary between locations forming the basis for this study. OBJECTIVE: To determine the prevalence and the predisposing factors to neonatal septicaemia among neonates admitted to the neonatal intensive care unit (NICU) of Federal Medical Centre, Bida (FMC Bida). METHODS: This was a one-year prospective observational study, 167 neonates admitted to the neonatal intensive care unit (NICU) of FMC Bida, were selected by purposive sampling method to participate in the study from 13th May, 2015 to 30th April, 2016. A structured questionnaire was filled out by consenting parents and blood samples were collected for laboratory analysis. The data was analyzed using SPSS version 20 (2016). The data were summarized using frequency distributions, means, standard deviation, charts and tables while statistical significance was determined using the chisquare test and Fisher's exact test at a 5% level of significance as well as Odd's Ratio (OR) as appropriate. RESULTS: Of the 167 neonates recruited, 97(58.1%) were males, 70(41.9%) were females and a male: female ratio of 1.4:1. Outborns were 100 (60%), inborns were 67(40%). Mean age was 4.3 ± 1.5 days and the mean weight of 2589 ± 743.9g. The overall prevalence of neonatal sepsis was 2.33% while the blood culture's positive rate was 9.58%. Risk factors identified in the neonates in this study were prolonged rupture of membranes (PROM), chorioamnionitis, meconium-stained liquor, foul-smelling vaginal discharge, being an outborn, having a low birth weight, inability to cry at birth and prematurity but, PROM was the only risk factor significantly associated with septicaemia (OR 5.4; 95% CI 2.2-13.5) while Escherichia coli was the leading bacterial isolate. CONCLUSION: In conclusion, prolonged rupture of membrane was mostly responsible for neonatal septicaemia in this study.


CONTEXTE: La septicémie néonatale (SN) survient au cours des 28premiers jours de vie et se caractérise par une infection bactérienne systémique prouvée par hémoculture. C'est l'une des principales causes de morbidité et de mortalité chez les nouveau-nés. Les déterminants de la NNS varient d'un endroit à l'autre, ce qui constitue la base de cette étude. OBJECTIF: Déterminer la prévalence et les facteurs prédisposant à la septicémie néonatale parmi les nouveau-nés admis dans l'unité de soins intensifs néonatals (USIN) du Centre médical fédéral de Bida (CMF Bida). MÉTHODES: Il s'agissait d'une étude observationnelle prospective d'un an, 167 nouveau-nés admis à l'unité de soins intensifs néonatals (USIN) du FMC Bida, ont été sélectionnés par la méthode d'échantillonnage à dessein pour participer à l'étude du 13 mai 2015 au 30 avril 2016. Un questionnaire structuré a été rempli par les parents consentants et des échantillons de sang ont été prélevés pour des analyses de laboratoire. Les données ont été analysées à l'aide de SPSS version 20 (2016). Les données ont été résumées à l'aide des distributions de fréquence, des moyennes, de l'écart-type, des graphiques et des tableaux, tandis que la signification statistique a été déterminée à l'aide du test du chi-carré et du test exact de Fisher à un niveau de signification de 5 %, ainsi que du rapport d'Odd (OR), le cas échéant. RÉSULTATS: Sur les 167 nouveau-nés recrutés, 97 (58,1 %) étaient des garçons, 70 (41,9 %) étaient des filles, soit un rapport hommes/femmes de 1,4:1. Les nouveau-nés étaient au nombre de 100 (60 %) et les nouveau-nés au nombre de 67 (40 %). L'âge moyen était de 4,3 ± 1,5 jours et le poids moyen de 2589 ± 743,9g. La prévalence globale de la septicémie néonatale était de 2,33 %, tandis que le taux d'hémoculture positive était de 9,58 %. Les facteurs de risque identifiés chez les nouveaunés de cette étude étaient la rupture prolongée des membranes (RPM), la chorioamnionite, la liqueur méconiale, les pertes vaginales nauséabondes, la naissance d'un enfant, le faible poids de naissance, l'incapacité à pleurer à la naissance et la prématurité, mais la RPM était le seul facteur de risque significativement associé à la septicémie (OR 5,4 ; 95% CI 2,2-13,5) tandis qu'Escherichia coli était l'isolat bactérien principal. CONCLUSION: En conclusion, la rupture prolongée des membranes était principalement responsable de la septicémie néonatale dans cette étude. Mots-clés: Nouveau-nés, Septicémie, Facteurs de risque.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Gravidez , Feminino , Masculino , Humanos , Pré-Escolar , Sepse Neonatal/epidemiologia , Nigéria/epidemiologia , Sepse/epidemiologia , Hospitais , Hospitalização , Escherichia coli
19.
Cureus ; 15(6): e41040, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37519607

RESUMO

This case report describes an unusual paraneoplastic leukemoid response presenting in a rare instance of gallbladder (GB) adenosquamous carcinoma (ASC). Adenocarcinoma is the most prevalent histological subtype of GB carcinoma, which is most frequently diagnosed in people in their sixth and seventh decades of life. Adenosquamous and squamous variations are uncommon. Rarely have reports of paraneoplastic leukemoid reaction (PLR) in GB carcinoma been made; this reaction is characterized by a white cell count exceeding 50,000/mm3 in combination with solid malignancy. PLR has most commonly been found in association with lung carcinoma.  In this instance, a 40-year-old man presented with right upper abdominal pain and a total leukocyte count of 26 x 109/L. The patient was initially treated on the lines of acute cholecystitis. But when the abdominal symptoms and leukocytosis did not settle, open cholecystectomy was performed. The results of the histopathological analysis showed that the GB had adenosquamous cancer. The white cell count increased even after surgery. Leukocytosis in the patient was looked into further to rule out hematological malignancy and other possible reasons. Sadly, the patient expired before any treatment could be started. The cancer GB carcinoma is uncommon and aggressive. Despite its rarity, ASC should be included in the differential diagnosis. PLR is an unusual manifestation associated with GB carcinoma. A thorough investigation, including a complete blood count, can help identify this paraneoplastic syndrome in patients with elevated white cell counts.

20.
West Afr J Med ; 40(7): 742-747, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37516926

RESUMO

BACKGROUND: Covid-19 vaccination is recommended for the prevention of Covid-19 infection. However, there is paucity of studies assessing post-vaccination side effects, especially in Africa, and thus, the need for this study. OBJECTIVES: To determine the prevalence of post-covid-19 vaccination side effects; the frequency of occurrence of each side effect and the willingness to receive the second dose of the vaccine. METHODS: A descriptive cross-sectional study was conducted among Corp members undergoing the three-week compulsory orientation course in a National Youth Service Corps (NYSC) orientation camp in Keffi, North-Central Nigeria. A total of 552 Corp members received the Covid-19 vaccine (AstraZeneca), 268 consented and were enrolled in the study. Data were obtained through online Google forms and were analyzed using SPSS version 26. RESULTS: The mean age of the respondents was 25 years (SD = 2.5). The prevalence of post-covid-19 vaccination side effects was 90.7%, 95% CI (86.8 - 93.8). The most common side effects were weakness (53.5%), pain at the injection site (52.7%), and headache (52.7%). There was a weak association between the duration of symptoms and intake of medications (Cramer's V = 0.148) which was not statistically significant. About a quarter, 62 (24.0%), of the respondents who received the first dose of the vaccine, were unwilling to accept the second dose, mainly due to their fear of the side effects - 53 (85.5%). CONCLUSION: Our study population had a high prevalence of post-covid-19 vaccination side effects. Thus, the need to educate recipients on possible side effects and remedies.


CONTEXTE: La vaccination contre le Covid-19 est recommandée pour la prévention de l'infection par le Covid-19. Cependant, il existe peu d'études évaluant les effets secondaires post-vaccinaux, en particulier en Afrique, d'où la nécessité de cette étude. OBJECTIFS: Déterminer la prévalence des effets secondaires post-vaccination contre le Covid-19, la fréquence d'apparition de chaque effet secondaire et la volonté de recevoir la deuxième dose du vaccin. MÉTHODES: Une étude descriptive transversale a été menée parmi les membres du Corps qui suivaient le cours d'orientation obligatoire de trois semaines dans un camp d'orientation du National Youth Service Corps (NYSC) à Keffi, dans le centrenord du Nigeria. Au total, 552 membres du Corps ont reçu le vaccin Covid-19 (AstraZeneca), 268 ont consenti à participer à l'étude. Les données ont été obtenues à l'aide de formulaires Google en ligne et ont été analysées à l'aide de SPSS version 26. RÉSULTATS: L'âge moyen des personnes interrogées était de 25 ans (écart-type = 2,5). La prévalence des effets secondaires post-vaccination était de 90,7 %, IC à 95 % (86,8 - 93,8). Les effets secondaires les plus fréquents étaient la faiblesse (53,5%), la douleur au point d'injection (52,7 %) et les maux de tête (52,7 %). Il y avait une faible association entre la durée des symptômes et la prise de médicaments (V de Cramer = 0,148) qui n'était pas statistiquement significative. Environ un quart, 62 (24,0%), des répondants ayant reçu la première dose du vaccin, n'ont pas voulu accepter la seconde dose, principalement en raison de leur crainte des effets secondaires - 53 (85,5%). CONCLUSION: Notre population étudiée présentait une prévalence élevée d'effets secondaires post-vaccination. D'où la nécessité d'informer les bénéficiaires sur les effets secondaires possibles et les remèdes. Mot-clés: COVID-19, Vaccination, Effets secondaires.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adolescente , Humanos , Adulto , Vacinas contra COVID-19/efeitos adversos , Nigéria/epidemiologia , Prevalência , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação/efeitos adversos
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