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2.
Clin Biochem ; 126: 110745, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462204

RESUMO

INTRODUCTION: 2,3-dinor 11ß-Prostaglandin F2α (BPG) is an arachidonic acid derivative and the most abundant metabolic byproduct of prostaglandin D2, which is released during mast cell activation. Therefore, measurements of BPG in urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) provide a noninvasive method for evaluation and management of mast cell disorders. Measurements obtained by LC-MS/MS exhibit a high prevalence of chromatographic interferences resulting in challenges with optimal determination of BGP. In this investigation, differential mobility spectrometry (DMS) is utilized to overcome the limitations of current testing. METHODS: Urine samples were extracted using an automated solid-phase extraction method. Samples were then analyzed with and without DMS devices installed on two commercially available mass spectrometry platforms to assess the benefits of DMS. Following promising results from a preliminary analytical evaluation, LC-DMS-MS/MS measurements of BPG in urine were fully validated to assess the analytical implications of using this technology. RESULTS AND DISCUSSION: The addition of DMS devices to the LC-MS/MS systems evaluated in this investigation significantly reduced interferences observed in the chromatograms. Concomitantly, DMS reduced the number of discordant quantifier/qualifier fragment ion results that significantly exceeded the ± 20 % limits, suggesting greater analytical specificity. The validation studies yielded low interday imprecision, with %CVs less than 6.5 % across 20 replicate measurements. Validation studies assessing other aspects of analytical performance also met acceptance criteria. CONCLUSIONS: Incorporating DMS devices greatly improved the specificity of BPG measurements by LC-MS/MS, as evidenced by the comparison of chromatograms and fragment ion results. Validation studies showed exceptional performance for established analytical metrics, indicating that this technology can be used to minimize the impact of interferences without adversely impacting other aspects of analytical or clinical performance.


Assuntos
Dinoprosta , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Análise Espectral , 60705
3.
J Neurointerv Surg ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38453461

RESUMO

BACKGROUND: Limited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke. OBJECTIVE: T0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography. METHODS: We conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). RESULTS: The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κG) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κG=0.487; 95% CI 0.327 to 0.647 and κG=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups. CONCLUSIONS: Despite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

4.
J Food Sci ; 89(4): 2040-2053, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38391095

RESUMO

Utilizing lentil protein as a novel ingredient for producing texturized vegetable proteins (TVPs) can provide new opportunities for the production of next-generation hybrid meat products. TVPs from lentil protein isolate were manufactured using low-moisture extrusion cooking at different combinations of screw speed (SS), feed moisture content (MC), and barrel temperature (BT) profile. In total, seven different combinations of processing treatments were tested, and the resulting TVPs were characterized for their physical (rehydration ratio, texture profile analysis, color, and bulk density), techno-functional (oil and water holding capacities), and microstructural properties. The processing conditions of higher SS and lower MC resulted in increased values of several textural profile attributes (springiness, cohesiveness, and resilience), increased water holding capacity (WHC), and decreased bulk density. Compared to raw lentil protein, TVPs showed enhanced oil holding capacity, though WHC either decreased or remained constant. The extrusion response parameters (die pressure, torque, and specific mechanical energy) showed positive correlations with several physical properties (texture, WHC, and total color change), revealing their potential for serving as important TVP quality indicators. TVPs produced at SS, MC, and BT of 450 rpm, 30%, and 140°C, respectively, showed relatively better overall physical and techno-functional quality and can be used as meat extenders in hybrid meat patties. Overall, this research evidenced the viability of lentil protein as a potential ingredient for producing low-moisture TVPs.


Assuntos
Lens (Planta) , Produtos da Carne , Temperatura , Culinária/métodos , Carne
5.
Gene ; 906: 148233, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38331117

RESUMO

Semen production and quality are closely correlated with different environmental factors in bovines, particularly for the buffalo (Bubalus bubalis) bulls reared under tropical and sub-tropical conditions. Factors including DNA methylation patterns, an intricate process in sperm cells, have an impact on the production of quality semen in buffalo bulls under abiotic stress conditions. The present study was conducted to identify DNA methylome signatures for semen quality in Murrah buffalo bulls, acclaimed as a major dairy breed globally, under summer heat stress. Based on semen quality parameters that significantly varied between the two groups over the seasons, the breeding bulls were classified into seasonally affected (SA = 6) and seasonally non-affected (SNA = 6) categories. DNA was isolated from purified sperm cells and sequenced using the RRBS (Reduced Representation Bisulfite Sequencing) technique for genome-wide methylome data generation. During the hot summer months, the physiological parameters such as scrotal surface temperature, rectal temperature, and respiration rate for both the SA and SNA bulls were significantly higher in the afternoon than in the morning. Whereas, the global CpG% of SA bulls was positively correlated with the afternoon's scrotal surface and rectal temperature. The RRBS results conveyed differentially methylated cytosines in the promoter region of the genes encoding the channels responsible for Ca2+ exchange, NPTN, Ca2+ activated chloride channels, ANO1, and a few structure-related units such as septins (SEPT4 and SEPT6), SPATA, etc. Additionally, the hypermethylated set of genes in SA was significantly enriched for pathways such as the FOXO signaling pathway and oocyte meiosis. The methylation patterns suggest promoter methylation in the genes regulating the sperm structure as well as surface transporters, which could contribute to the reduced semen quality in the Murrah buffalo bulls during the season-related heat stress.


Assuntos
Análise do Sêmen , Sêmen , Animais , Masculino , Bovinos/genética , Sêmen/fisiologia , Búfalos/genética , Fosfatos , Espermatozoides , Metilação de DNA , Resposta ao Choque Térmico/genética , Motilidade dos Espermatozoides
6.
J Reprod Immunol ; 162: 104208, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367478

RESUMO

High HBV DNA levels predispose to mother to child transmission (MTCT) of HBV. Early nucleotide analogue (NA) therapy can reduce HBV DNA and minimize MTCT. We analysed immune-metabolic profile in pregnant mothers who received NA from 2nd trimester compared with untreated mothers. In 2nd trimester, there was no difference in immune profiles between Gr.1 and Gr.2 but high viral load women had downregulated pyruvate, NAD+ metabolism but in 3rd trimester, Gr.1 had significant reduction in HBV-DNA, upregulated pyruvate and NAD with increased IFN-2αA, CD8Tcells, NK cells and decreased Tregs, IL15, IL18, IL29, TGFß3 compared to Gr.2. In Gr.1, three eAg-ve women showed undetectable DNA and HBsAg. At delivery, Gr.1 showed no MTCT, with undetectable HBV DNA, HBsAg, high CD8 and NK cells in two women. We conclude, that starting NA from second trimester, reduces HBV load and MTCT, modulates NAD, induces immunity and suggest use of NA in early gestation in future trials.


Assuntos
Vírus da Hepatite B , Hepatite B , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Viremia , Criança , Feminino , Humanos , Gravidez , Linfócitos T CD8-Positivos , DNA Viral , Antígenos de Superfície da Hepatite B , Células Matadoras Naturais , NAD , Complicações Infecciosas na Gravidez/tratamento farmacológico , Segundo Trimestre da Gravidez , Piruvatos , Tenofovir , Viremia/imunologia , Hepatite B/imunologia , Hepatite B/transmissão
7.
J Minim Access Surg ; 20(1): 89-95, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38240384

RESUMO

INTRODUCTION: The most dreaded complication during laparoscopic cholecystectomy still remains to be injury to the common bile duct. The primary cause for bile duct injury during LC is misinterpretation of the biliary anatomy. Intra-operative cholangiography was introduced as a means of reducing the chances of biliary injury, done using Fluoroscopic imaging or Near-infrared fluorescence imaging method. NIRF is one of the most popular imaging methods in biomedical sciences. Indocyanine Green is sterile and water soluble which completely binds to albumin and is excreted in bile. PATIENTS AND METHODS: This prospective study was conducted among 70 patients between July 2020 and December 2021. Subjects were administered 5mg of ICG dye pre-operatively and procedure performed using Karl Storz HD image S1 system with a D-light P light source for NIRF imaging. RESULTS: The average duration of surgery was 58.10 minutes. After calot's dissection, the CBD was visualized in 88.71 % patients, with a mean time to visualization at 26.33 minutes. The cystic duct was visualized in 87.3% cases with a mean time of visualization of 32.10 minutes. The hepatic duct was visualized in 28.57% and the hepatic duct-CBD confluence was visualized in 34.28% patients. CONCLUSION: Near infrared imaging based intra-operative cholangiography, using Indocyanine Green dye, during Lap. Cholecystectomy is an easy, useful and inexpensive method of visualizing the biliary ductal anatomy.

8.
Eur Thyroid J ; 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189657

RESUMO

OBJECTIVE: This study aimed to describe real-world patient and physician characteristics, rearranged during transfection (RET) mutation testing and results, treatment patterns, and patient-reported outcomes (PROs) in advanced or metastatic medullary thyroid cancer (aMTC) across five populous European countries. METHODS: Cross-sectional physician and patient surveys were used to collect quantitative and qualitative data in France, Germany, Italy, Spain, and the UK from July to December 2020, prior to the introduction of selective RET inhibitors in Europe. Physicians completed patient record forms and a survey about their specialty and practice site. Patients were asked to provide PRO data using four validated instruments, including the EuroQol 5 Dimension (EQ-5D) questionnaire. RESULTS: The physician-reported sample included 275 patients with aMTC, including 79 patients with RET mutation-positive disease; median age was 60 and 56 years, respectively. Overall, 75% were tested for RET mutation (35% germline only, 21% somatic only, 44% both). Common physician-cited barriers to RET mutation testing included high cost, difficulty accessing latest tests, and time delay for results. First-line systemic therapy (most commonly vandetanib or cabozantinib) was prescribed for 69% of patients overall and 82% of the RET mutation-positive subgroup. Second-line therapy was prescribed for 12% of patients who received first-line therapy; most patients remained on first-line therapy at data capture. PROs revealed substantial disease/treatment burden. CONCLUSIONS: Patients with aMTC report substantial disease/treatment burden. Outcomes could be improved by identifying patients eligible for treatment with selective RET inhibitors through more optimal RET mutation testing.

9.
Br J Dermatol ; 190(3): 315-339, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36971254

RESUMO

BACKGROUND: Over 29 years of clinical application, the Dermatology Life Quality Index (DLQI) has remained the most used patient-reported outcome (PRO) in dermatology due to its robustness, simplicity and ease of use. OBJECTIVES: To generate further evidence of the DLQI's utility in randomized controlled trials (RCTs) and to cover all diseases and interventions. METHODS: The methodology followed PRISMA guidelines and included seven bibliographical databases, searching articles published from 1 January 1994 until 16 November 2021. Articles were reviewed independently by two assessors, and an adjudicator resolved any opinion differences. RESULTS: Of 3220 screened publications, 454 articles meeting the eligibility criteria for inclusion, describing research on 198 190 patients, were analysed. DLQI scores were primary endpoints in 24 (5.3%) of studies. Most studies were of psoriasis (54.1%), although 69 different diseases were studied. Most study drugs were systemic (85.1%), with biologics comprising 55.9% of all pharmacological interventions. Topical treatments comprised 17.0% of total pharmacological interventions. Nonpharmacological interventions, mainly laser therapy and ultraviolet radiation treatment, comprised 12.2% of the total number of interventions. The majority of studies (63.7%) were multicentric, with trials conducted in at least 42 different countries; 40.2% were conducted in multiple countries. The minimal clinically importance difference (MCID) was reported in the analysis of 15.0% of studies, but only 1.3% considered full score meaning banding of the DLQI. Forty-seven (10.4%) of the studies investigated statistical correlation of the DLQI with clinical severity assessment or other PRO/quality of life tools; and 61-86% of studies had within-group scores differences greater than the MCID in 'active treatment arms'. The Jadad risk-of-bias scale showed that bias was generally low, as 91.8% of the studies had Jadad scores of ≥ 3; only 0.4% of studies showed a high risk of bias from randomization. Thirteen per cent had a high risk of bias from blinding and 10.1% had a high risk of bias from unknown outcomes of all participants in the studies. In 18.5% of the studies the authors declared that they followed an intention-to-treat protocol; imputation for missing DLQI data was used in 34.4% of studies. CONCLUSIONS: This systematic review provides a wealth of evidence of the use of the DLQI in clinical trials to inform researchers' and -clinicians' decisions for its further use. Recommendations are also made for improving the reporting of data from future RCTs using the DLQI.


Assuntos
Dermatologia , Psoríase , Terapia Ultravioleta , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Psoríase/tratamento farmacológico , Qualidade de Vida
10.
Immunol Cell Biol ; 102(2): 85-86, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37655949

RESUMO

In this article, I discuss how my scientific career has evolved, starting in an immunology lab and ending up at the Medical Research Council of the UK.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38101284

RESUMO

Sulfated metabolites of vitamin D have been suggested to be in breastmilk, although current methods to measure sulfated vitamin D compounds in breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have not adequately accounted for increased aqueous solubility of these sulfated metabolites. The purpose of this study was to generate a method of LC-MS/MS for measuring vitamin D3-3-sulfate (VitD3-S) and 25-hydroxyvitamin D3-3-sulfate (25OHD3-S) specifically in human breastmilk. The resulting method uses methanol to precipitate protein and solid phase extraction to prepare the samples for LC-MS/MS. The limits of quantification for analytes in solvent were 0.23 ng/mL VitD3-S and 0.2 ng/mL 25OHD3-S. Various experiments observed concentrations ranging 0.53 to 1.7 ng/mL VitD3-S and ≤ 0.29 ng/mL 25OHD3-S. Both analytes were present in aqueous skim milk, demonstrating the enhanced aqueous solubility of these vitamin D sulfates. In conclusion, we describe an effective method for measuring VitD3-S and 25OHD3-S in breastmilk by LC-MS/MS.


Assuntos
Calcifediol , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Leite Humano , Sulfatos , 60705 , Vitamina D , Vitaminas , 25-Hidroxivitamina D 2
12.
J Med Virol ; 95(12): e29257, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38054548

RESUMO

Pregnancy being an immune compromised state, coronavirus disease of 2019 (COVID-19) disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses, therefore we aimed to analyze the change in plasma secretome, metabolome, and immune cells with disease severity in COVID-19 positive pregnant females and their cord blood. COVID-19 reverse transcriptase-polymerase chain reaction positive pregnant females (n = 112) with asymptomatic (Asy) (n = 82), mild (n = 21), or moderate (n = 9) disease, healthy pregnant (n = 18), COVID-19 positive nonpregnant females (n = 7) were included. Eighty-two cord blood from COVID-19 positive and seven healthy cord blood were also analyzed. Mother's peripheral blood and cord blood were analyzed for untargeted metabolome profiling and cytokines by using high-resolution mass spectrometry and cytokine bead array. Immune scan was performed only in mothers' blood by flow cytometry. In Asy severe acute respiratory syndrome coronavirus 2 infection, the amino acid metabolic pathways such as glycine, serine, l-lactate, and threonine metabolism were upregulated with downregulation of riboflavin and tyrosine metabolism. However, with mild-to-moderate disease, the pyruvate and nicotinamide adenine dinucleotide (NAD+ ) metabolism were mostly altered. Cord blood mimicked the mother's metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in Asy and NAD+ , riboflavin metabolism in mild and moderate. Additionally, with disease severity tumor necrosis factor-α, interferon (IFN)-α, IFN-γ, interleukin (IL)-6 cytokine storm, IL-9 was raised in both mothers and neonates. Pyruvate, NAD metabolism and increase in IL-9 and IFN-γ had an impact on nonclassical monocytes, exhausted T and B cells. Our results demonstrated that immune-metabolic interplay in mother and fetus is influenced with increase in IL-9 and IFN-γ regulated pyruvate, lactate tricarboxylic acid, and riboflavin metabolism with context to disease severity.


Assuntos
COVID-19 , SARS-CoV-2 , Recém-Nascido , Humanos , Feminino , Gravidez , SARS-CoV-2/metabolismo , Gestantes , Interleucina-9 , NAD , Citocinas , Interleucina-6 , Interferon-alfa , Gravidade do Paciente , Imunidade , Piruvatos , Glicina , Lactatos , Riboflavina , Serina , Treonina
13.
Sci Adv ; 9(48): eadj5873, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38039373

RESUMO

Satellite quantum key distribution (SatQKD) intermediated by a trusted satellite in a low-Earth orbit to ground stations along the satellite's path allows remote users to connect securely. To establish a secure connection, a SatQKD session must be conducted to each user over a dynamically changing free-space link, all within just a few hundred seconds. Because of the short time and large losses under which the QKD protocol will be implemented, it has not yet been possible to form a complete key by transmitting all the relevant information required within a single overpass of the satellite. Here, we demonstrate a real-time QKD system that is capable of forming a 4.58-megabit secure key between two nodes within an emulated satellite overpass. We anticipate that our system will set the stage for practical implementations of intercontinental quantum secure communications that can operate over large networks of nodes and enable the secure transmission of data globally.

14.
Indian J Microbiol ; 63(3): 369-372, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37781012

RESUMO

Post vaccination with Covaxin (BBV152), Serum from healthcare professionals of Microbiology Department at apex tertiary referral hospital of India were tested for SARS-CoV-2 specific IgG antibodies. 70% individuals at 14-30 days, 63.1% individuals at 30-60 days but only 36.8% individuals at 60-90 days after second dose of vaccine had detectable SARS-CoV-2 spike protein specific IgG antibodies. However, 80% individuals at 14-30 days, 89.4% individuals at 30-60 days while 94.7% individuals at 60-90 days after second dose of vaccine had detectable SARS-CoV-2 whole cell antigen specific IgG antibodies. Males were lacking SARS-CoV-2 spike protein specific IgG antibodies in higher proportion than females and had lower index wherever detected. Age and co-morbidities were non-significant factors for post vaccination IgG response but not in breakthrough infection. 8.3% individuals developed mild COVID-19 symptoms post 14-90 days of second dose and none had severe COVID-19. SARS-CoV-2 spike protein specific IgG antibodies induced by Covaxin are drastically reduced in 60-90 days among fully vaccinated individuals which could be a potential risk for breakthrough SARS-CoV-2 infection, if not severe COVID-19. It may be essential to have additional antigenic stimulations/boosters for continued protection.

15.
Biomedicines ; 11(10)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37893156

RESUMO

Alzheimer's disease (AD) is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology of AD is senile dementia, which is linked to amyloid-beta (Aß) deregulation and tau perivascular pathogeny. Hyperphosphorylated tau has a propensity for microtubules, which elevate the instability and tau-protein congregates, leading to accumulation of neurofibrillary tangles (NFTs). Tau hyperphosphorylation is susceptible to GSK-3, which has led to an emerging hypothesis regarding the pathogenesis of AD. Accordingly, attempts have been made to conduct investigations and achieve further advancements on new analogues capable of inhibiting the GSK-3 protein, which are currently in the clinical trials. In this analysis, we have evaluated certain GSK-3 inhibitor variants utilising scaffolding and framework devised techniques with pharmacological characteristics, accompanied by computational screenings (pharmacokinetics and docking). The structure-based designed analogues interacted effectively with the active amino acids of GSK-3ß target protein. The in silico pharmacokinetic studies revealed their drug-like properties. The analogues with best interactions and binding scores will be considered in the future to completely demonstrate their potential relevance as viable GSK-3 inhibitors.

16.
Glob Ment Health (Camb) ; 10: e46, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854432

RESUMO

Healthcare personnel who deal with COVID-19 experience stigma. There is a lack of national-level representative qualitative data to study COVID-19-related stigma among healthcare workers in India. The present study explores factors associated with stigma and manifestations experienced by Indian healthcare workers involved in COVID-19 management. We conducted in-depth interviews across 10 centres in India, which were analysed using NVivo software version 12. Thematic and sentiment analysis was performed to gain deep insights into the complex phenomenon by categorising the qualitative data into meaningful and related categories. Healthcare workers (HCW) usually addressed the stigma they encountered when doing their COVID duties under the superordinate theme of stigma. Among them, 77.42% said they had been stigmatised in some way. Analyses revealed seven interrelated themes surrounding stigma among healthcare workers. It can be seen that the majority of the stigma and coping sentiments fall into the mixed category, followed by the negative sentiment category. This study contributes to our understanding of stigma and discrimination in low- and middle-income settings. Our data show that the emergence of fear of the virus has quickly turned into a stigma against healthcare workers.

17.
N Engl J Med ; 389(20): 1851-1861, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37870969

RESUMO

BACKGROUND: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear. METHODS: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety. RESULTS: A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P<0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. CONCLUSIONS: Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.).


Assuntos
Antineoplásicos , Piridinas , Neoplasias da Glândula Tireoide , Humanos , Progressão da Doença , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/genética , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico
18.
Diagnostics (Basel) ; 13(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37835901

RESUMO

AIM: The study aims to test the hypothesis that concentrations of adropin and afamin differ between patients in various stages of chronic kidney disease when compared with healthy controls. The study also investigates the association of the biomarkers (adropin and afamin) with CKD-MBD and traditional cardiovascular risk parameters in CKD patients. METHODOLOGY: The cross-sectional study includes the subjects divided into four groups comprising the control group (healthy volunteers = 50), CKD stages 1-2 patients (n = 50), CKD stages 3-4 patients (n = 50), CKD stage 5 patients (n = 50). Serum concentrations of adropin and afamin were determined using ELISA. Clinical variables (renal, lipid, and CKD-MBD parameters) were correlated to adropin and afamin concentrations. RESULTS: Afamin concentration was found to be higher in group IV, followed by groups III and II when compared to the control group, i.e., (83.243 ± 1.46, 64.233 ± 0.99, and 28.948 ± 0.72 vs. 14.476 ± 0.5) mg/L (p < 0.001), and adropin concentration was found to be lower in group IV as compared to groups III, II, and I (200.342 ± 8.37 vs. 284.682 ± 9.89 vs. 413.208 ± 12.32 vs. 706.542 ± 11.32) pg/mL (p < 0.001), respectively. Pearson correlation analysis showed that afamin was positively correlated with traditional cardiovascular risk biomarkers, while adropin showed a negative correlation. CONCLUSIONS: Adropin and afamin may potentially serve as futuristic predictors for the deterioration of renal function and may be involved in the pathological mechanisms of CKD and its associated complications such as CKD-MBD and high lipid levels.

19.
PLoS One ; 18(10): e0292592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37824482

RESUMO

BACKGROUND: People with disabilities are vulnerable because of the many challenges they face attitudinal, physical, and financial. The National Policy for Persons with Disabilities (2006) recognizes that Persons with Disabilities are valuable human resources for the country and seeks to create an environment that provides equal opportunities, and protection of their rights, and full. There are limited studies on health care burden due to disabilities of various types. AIM: The present study examines the socioeconomic and state-wise differences in the prevalence of disabilities and related household financial burden in India. METHODS: Data for this study was obtained from the National Sample Survey (NSS), 76th round Persons with Disabilities in India Survey 2018. The survey covered a sample of 1,18,152 households, 5,76,569 individuals, of which 1,06,894 of had any disability. This study performed descriptive statistics, and bivariate estimates. RESULTS: The finding of the analysis showed that prevalence of disability of any kind was 22 persons per 1000. Around, one-fifth (20.32%) of the household's monthly consumption expenditure was spent on out-of-pocket expenditure for disability. More than half (57.1%) of the households were pushed to catastrophic health expenditure due to one of the members being disabled. Almost one-fifth (19.1%) of the households who were above the poverty line before one of members was treated for disability were pushed below the poverty line after the expenditure of the treatment and average percentage shortfall in income from the poverty line was 11.0 percent due to disability treatment care expenditure. CONCLUSION: The study provides an insight on the socioeconomic differentials in out-of-pocket expenditure, catastrophic expenditure for treatment of any kind of disability. To attain SDG goal 3 that advocates healthy life and promote well-being for all at all ages, there is a need to recognize the disadvantaged and due to disability.


Assuntos
Pessoas com Deficiência , Humanos , Pobreza , Renda , Características da Família , Gastos em Saúde , Índia/epidemiologia , Doença Catastrófica
20.
Ann Med Surg (Lond) ; 85(9): 4543-4546, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37663741

RESUMO

Introduction and importance: The omentum appears as an apron-like extension of the peritoneum. Case presentation: A 30-year-old male patient, presented to the emergency department with the chief complaints of acute nonradiating pain localized in the right-side abdomen for the past 3 days. The patient had a past medical history of sclerosing cholangitis (SC) with inflammatory bowel disease (IBD). The patient reported the pain as persistent, pressure-like, and moderate. The patient also had a low-grade fever and nausea at the time of admission. On examination, the vital signs were found as normal. The patient reported that the abdominal pain gets exacerbated after the meals, and increase in physical activity and movement. Due to the patient's complaints and history of SC and IBD, these were considered as the possible diagnosis. After the diagnostic procedures, the patient was finally diagnosed with OT. Clinical discussion: This report presents a case of a patient suffering from omental torsion having history of SC and IBD. During the laparoscopic procedure, the diagnosis of omental torsion was confirmed. To our knowledge, no case report of omental torsion with IBD and SC is published in the literature. Conclusion: This seems to be a major diagnostic challenge as patients with IBD almost resembles the same clinical signs and symptoms as in the omental torsion. The possibility of misdiagnosis and delayed diagnosis could result in the unfavorable outcome. Therefore, the healthcare fraternities are advised to include the rare diseases such as OT as the differential diagnosis.

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