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1.
Fitoterapia ; 175: 105898, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38467280

RESUMO

Underutilized fruits are thought to be nutrient and antioxidant gold mines. Despite their high nutritive value, therapeutic properties, and ability to grow in adverse soil and climatic conditions, they have received little attention. However, these underutilized fruits are an important component of traditional foods, particularly in arid and semiarid regions of Rajasthan. Lasoda (Cordia myxa) contains numerous phytochemicals that contribute to its antioxidant potential, including tannins, flavonoids, phenolic acids, xanthones, terpenes, and saponins. The primary goal of this review is to emphasize the importance of extracting bioactive compounds from lasoda and evaluating their antioxidant potential. Furthermore, this review emphasizes the major areas for the application of lasoda and its extract as prospective positive health agents that can be used in the preparation of functional foods. The use of lasoda may also improve the value of bakery products and meat quality and prevent postharvest losses. This review is a pilot article that can aid in the nutritional profiling of Cordia fruits and seeds, and it provides information on the effective and efficient use of this underutilized fruit in the food and nutraceutical industries.


Assuntos
Antioxidantes , Frutas , Compostos Fitoquímicos , Antioxidantes/farmacologia , Frutas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Alimento Funcional , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Valor Nutritivo , Flavonoides/análise , Flavonoides/farmacologia , Flavonoides/isolamento & purificação
2.
J Cyst Fibros ; 23(3): 388-397, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38388234

RESUMO

After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Padrão de Cuidado , Humanos , Fibrose Cística/terapia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Aconselhamento Genético , Testes Genéticos/métodos , Recém-Nascido
3.
Clin Radiol ; 79(3): 197-204, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38101998

RESUMO

AIM: To investigate whether T2-weighted imaging-fluid-attenuated inversion recovery (T2/FLAIR) mismatch, T2∗ dynamic susceptibility contrast (DSC) perfusion, and magnetic resonance spectroscopy (MRS) correlated with the histological diagnosis and grading of IDH (isocitrate dehydrogenase)-mutant, 1p/19q non-co-deleted/ATRX (alpha-thalassemia mental retardation X-linked)-mutant astrocytoma. MATERIALS: Imaging of 101 IDH-mutant diffuse glioma cases of histological grades 2-3 (2019-2021) were analysed retrospectively by two neuroradiologists blinded to the molecular diagnosis. T2/FLAIR mismatch sign is used for radio-phenotyping, and pre-biopsy multiparametric MRI images were assessed for grading purposes. Cut-off values pre-determined for radiologically high-grade lesions were relative cerebral blood volume (rCBV) ≥2, choline/creatine ratio (Cho/Cr) ≥1.5 (30 ms echo time [TE]), Cho/Cr ≥1.8 (135 ms TE). RESULTS: Sixteen of the 101 cases showed T2/FLAIR mismatch, all of which were histogenetically confirmed IDH-mutant 1p/19q non-co-deleted/ATRX mutant astrocytomas; 50% were grade 3 (8/16) and 50% grade 2 (8/16). None showed contrast enhancement. Nine of the 16 had adequate multiparametric MRI for analysis. Any positive value by combining rCBV ≥2 with Cho/Cr ≥1.5 (30 ms TE) or Cho/Cr ≥1.8 (135 ms TE) predicted grade 3 histology with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%. CONCLUSION: The T2/FLAIR mismatch sign detected diffuse astrocytomas with 100% specificity. When combined with high Cho/Cr and raised rCBV, this predicted histological grading with high accuracy. The future direction for imaging should explore a similar integrated layered approach of 2021 classification of central nervous system (CNS) tumours combining radio-phenotyping and grading from structural and multiparametric imaging.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Estudos Retrospectivos , Mutação/genética , Imageamento por Ressonância Magnética/métodos , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Organização Mundial da Saúde , Proteína Nuclear Ligada ao X/genética
4.
J Cyst Fibros ; 22(4): 656-664, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37121795

RESUMO

BACKGROUND: MRT5005, a codon-optimized CFTR mRNA, delivered by aerosol in lipid nanoparticles, was designed as a genotype-agnostic treatment for CF lung disease. METHODS: This was a randomized, double-blind, placebo-controlled Phase 1/2 study performed in the US. Adults with 2 severe class I and/or II CFTR mutations and baseline ppFEV1 values between 50 and 90% were randomized 3:1 (MRT5005: placebo). Six dose levels of MRT5005 (4, 8, 12, 16, 20, and 24 mg) or placebo (0.9% Sodium Chloride) were administered by nebulization. The single ascending dose cohort was treated over a range from 8 to 24 mg; the multiple ascending dose cohort received five weekly doses (range 8-20 mg); and the daily dosing cohort received five daily doses (4 mg). RESULTS: A total of 42 subjects were assigned to MRT5005 [31] or placebo [11]. A total of 14 febrile reactions were observed in 10 MRT5005-treated participants, which were mild [3] or moderate [11] in severity; two subjects discontinued related to these events. Additionally, two MRT5005-treated patients experienced hypersensitivity reactions, which were managed conservatively. The most common treatment emergent adverse events were cough and headache. No consistent effects on FEV1 were noted. CONCLUSIONS: MRT5005 was generally safe and well tolerated through 28 days of follow-up after the last dose, though febrile and hypersensitivity reactions were noted. The majority of these reactions resolved within 1-2 days with supportive care allowing continued treatment with MRT5005 and careful monitoring. In this small first-in-human study, FEV1 remained stable after treatment, but no beneficial effects on FEV1 were observed.


Assuntos
Fibrose Cística , Adulto , Humanos , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , RNA Mensageiro , Aerossóis e Gotículas Respiratórios , Mutação , Método Duplo-Cego
5.
Saudi J Kidney Dis Transpl ; 34(6): 514-519, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38725201

RESUMO

Rapidly progressive renal failure (RPRF) is not typical of diabetic nephropathy and suggests non-diabetic kidney disease (NDKD). We conducted an analysis of the data of RPRF patients (28 diabetic and 88 non-diabetic patients) with doubled creatinine over 2 weeks to 3 months and/or presented with >4 mg serum creatinine without prior renal disease to ascertain the types of lesions and compare the patients' histopathology. The primary outcome was dependence on dialysis at 1 year. Anti-neutrophilic cytoplasmic antibody-associated pauci-immune glomerulonephritis was the most common cause of RPRF in both groups. No particular lesion was more frequent in either group. Dependence on dialysis at 1 year was similar in both groups and was associated with dependence on dialysis at presentation but not diabetes. Crescentic glomerulonephritis was the most common in non-diabetic patients (57.9 vs. 25%, P = 0.002), and acute tubular necrosis (ATN) was seen in diabetic patients (21.4 vs. 11.4%, P = 0.179). Both factors were associated with adverse renal outcomes. Diffuse global glomerulosclerosis at presentation suggested a poor outcome in both groups. Diabetic nephropathy was seen in 14.29%, and its presence did not affect the outcome. The etiology of RPRF in diabetic patients has changed and is similar to that in non-diabetic patients, with no specific lesions predominating. Diabetic nephropathy does not alter the outcome for those with RPRF. Diffuse global glomerulosclerosis, being on dialysis at presentation, and ATN in a diabetic patient indicate a poor outcome and need close follow-up. Diabetic retinopathy should not prevent us from investigating for NDKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Progressão da Doença , Diálise Renal , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Índia/epidemiologia , Pessoa de Meia-Idade , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Fatores de Tempo , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Estudos Retrospectivos , Fatores de Risco , Creatinina/sangue , Resultado do Tratamento
6.
J Mol Model ; 28(12): 400, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434123

RESUMO

TKX-50 (dihydroxylammonium 5,5'-bistetrazolate-1,1'-dioxide) is a recent time invention by Klapotke et. al. in the field of high energy materials, and it outperforms all the existing materials by means of performance parameters. It is rising as potential energetic material due to favorable thermal insensitivity, low toxicity and safe handling. The decomposition temperature (Tmax) values of precursors such as glyoxime (I), 1,2-dichloroglyoxime (II), 1,2-diazidoglyoxime (III), and bistetrazoledihydroxide (IV) and ending products TKX-50 (V) and ABTOX (VI) have been attempted to correlate with the results obtained from molecular electrostatic potentials and band gaps calculated from the difference of ionization potential and electron affinity. The molecular electrostatic potential values of azido attached -NO group of III are much less than that of hydro/chloro attached -NO group of I/II and that of tetrazole groups IV, V, and VI. The band gaps calculated from stability trend in the increasing order of III < II < I < IV < V < VI are well corroborated with stability trend drawn from experimentally determined decomposition temperatures. Further, employing conceptual density functional theory (DFT) molecular descriptors, band gap values were calculated via the difference of ionization potential and electron affinity to understand the thermal stability of TKX-50, ABTOX, and its precursors.

7.
Anesth Essays Res ; 16(2): 203-207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36447913

RESUMO

Background and Objectives: The study sought to compare the postoperative analgesia after ultrasonography (USG)-guided bilateral transversus abdominis plane (TAP) block versus quadratus lumborum (QL) 1 block with lower concentration of bupivacaine in patients undergoing lower-segment cesarean section (LSCS). Materials and Methods: A randomized controlled trial was conducted at a tertiary hospital, Bengaluru, from 2019 to 2021. Fifty-six patients belonging to the American Society of Anesthesiologists physical status Class I and II aged 20-40 years posted for LSCS under subarachnoid block were divided into two groups. Patients in Group I were given bilateral TAP block and patients in Group II were given bilateral QL1 block under USG guidance at the end of surgery using 0.125% bupivacaine (20 ml) and 4 mg dexamethasone. Patients were monitored for postoperative pain with Numerical Pain Intensity Scale (NPIS) at 0, 1, 4, 8, 12, and 24 h. Rescue analgesic was given if NPIS score was 6 or more. Time to first dose of rescue analgesic was noted. NPIS scores and time to rescue analgesic were compared using independent t test. P < 5% was considered statistically significant. Results: Average NPIS scores were less at 0, 1, and 4 h (<6) and higher at 8, 12, and 24 h in both the groups postoperatively. NPIS scores at 8 h were significantly higher in Group I compared to Group II (P = 0.02). Time to first dose of rescue analgesic was 7.32 h in Group I and 9.07 h in Group II (P < 0.001). Conclusions: Postoperative analgesia was better with USG-guided QL1 block versus USG-guided TAP block with 0.125% bupivacaine and 4 mg dexamethasone in patients undergoing LSCS.

8.
J Eur Acad Dermatol Venereol ; 36(11): 2051-2054, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35729732

RESUMO

BACKGROUND: Cutaneous metastases (CM) diagnosis is clinically challenging, requiring an invasive biopsy for confirmation. A novel, RCM-OCT device combines the advantage of horizontal high-resolution reflectance confocal microscopy (RCM) images and vertical deeper optical coherence tomography (OCT) images to aid in non-invasive diagnosis of CM from breast cancers. OBJECTIVE: Characterize CM from breast cancers using RCM-OCT device. METHODS: Seven patients suffering from breast cancers with suspicious CM were consented and imaged with RCM-OCT device. CM features were defined by comparing with histopathology. Tumour depths were measured on OCT and on H&E-images and correlated using statistical analysis Pearson test. 3D-OCT images were reconstructed to enhance tumour visualization. RESULTS: 6/7 lesions were CM from breast cancers, and one was vascular ectasia, on histopathology. CM appeared as greyish-darkish oval to round structures within the dermis on RCM and OCT-images. On RCM, individual tumour cells were seen, enabling identification of even small tumour foci; while, on OCT deeper tumours were detected. Inflammatory cells, dilated vessels and coarse collagen were identified in the dermis. Pearson correlation had an r2 of 0.38 and a significant P-value <0.004 for depth measurements. CM from breast cancers could be differentiated from ecstatic vessels on 3D-reconstructed OCT image. LIMITATION: Small sample size and lack of clinical mimickers. CONCLUSION: RCM-OCT can detect CM and has potential in aiding non-invasive diagnosis and management.


Assuntos
Neoplasias Cutâneas , Tomografia de Coerência Óptica , Biópsia , Humanos , Microscopia Confocal/métodos , Pele/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia
10.
Eur J Ophthalmol ; 32(1): NP125-NP129, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33092398

RESUMO

AIM: To describe the multimodal imaging findings of pigmented paravenous retinochoroidal atrophy. METHODS: A 23-year-old female presented to us for a routine ocular examination. She had a best-corrected visual acuity of 6/6 in both eyes. Anterior segment examination was unremarkable. Fundus examination showed pigmentary changes along the retinal vasculature extending from mid periphery to post-equatorial retina suggesting a diagnosis of pigmented paravenous retinochoroidal atrophy. Swept-source optical coherence tomography of the macula showed choriocapillaris thinning at the mid periphery whereas coherence tomography angiography at the mid periphery showed a relatively normal choriocapillaris vasculature in the early stage of the disease. CONCLUSION: A relatively normal choriocapillaris structure was seen on ocular coherence tomography angiography which could have been due to a milder form of the disease in a young patient.


Assuntos
Degeneração Retiniana , Adulto , Atrofia/patologia , Corioide/patologia , Feminino , Angiofluoresceinografia , Humanos , Imagem Multimodal , Degeneração Retiniana/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto Jovem
12.
Indian J Anaesth ; 66(12): 854-860, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36654893

RESUMO

Background and Aims: The COVID-19 pandemic led to significant infections among healthcare workers and deaths warranting the need for personal protective equipment. This study aimed to estimate the proportion of anaesthesiologists adhering to safety precautions and to evaluate their adherence patterns, difficulties faced and coping mechanisms in the operation theatre during the pandemic. Methods: This was a multicentric mixed methods study conducted among anaesthesiologists from two tertiary care hospitals. A paper-based questionnaire was given to all participants. The first part consisted of 21 questions regarding safety measures and extent of adherence. The second part was a response sheet regarding the various difficulties faced and coping mechanisms adopted. Following this, an in-depth interview was conducted to understand the same. The proportion of anaesthesiologists in different categories of adherence, patterns of adherence, difficulties faced, and coping mechanisms were computed and compared. Thematic framework analysis was done for in-depth interview. Results: Sixty participants were included. The adherence levels for N95 masks and face shields were higher. Most participants practised frequent handwashing and took showers after work. Fogging, difficulty in communication, marks on the face were the commonly faced difficulties. Self reassurance, adjusting the fit of masks/face shields, or taking breaks were the coping mechanisms mostly followed. Themes generated from in-depth interview include waning of caution, adaptation through innovative methods and stress due to uncertainty. Conclusion: The N95 mask was the most preferred safety precaution. Ease of use and safety were important considerations for adherence. Physical and mental acclimatisation and improved knowledge of disease played a vital role.

13.
Sci Total Environ ; 793: 148518, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34171804

RESUMO

Ozone plays an important role in the thermal structure and chemical composition of the atmosphere. The present study compares the temporal and spatial distributions of Total Column Ozone (TCO) over the Indian sub-continent retrieved from a geostationary Indian National Satellite (INSAT-3D) and Atmospheric Infrared Sounder (AIRS). The INSAT-3D TCO values are also evaluated against the Dobson spectrophotometer observations at two locations. The inter-comparison results reveal a good correlation of 0.8, the bias of -5 DU, and Root Mean Square Error (RMSE) of 15 DU approximately between the TCO retrieved from INSAT-3D and AIRS. The lowest RMSE and highest correlation coefficient were found in the pre-monsoon season. The INSAT-3D and AIRS show reasonable agreement with the RMSE varying between 10 and 30 DU. On the other hand, evaluation of the INSAT-3D TCO with the ground-based observations from Dobson spectrophotometers located at New Delhi and Varanasi showed fair agreement with a maximum monthly mean correlation coefficient of 0.68 and 0.76, respectively, and RMSE varying from 11 to 16 DU for both the stations. The seasonal distribution of TCO and its variation over the Indian region has also been studied using INSAT-3D and AIRS data. The analysis exhibits strong seasonal variations, with higher values in pre-monsoon season and minimum values in winter season. The noticeable seasonal variability of TCO can be attributed to complex combination of photochemical and dynamical processes in the troposphere and stratosphere. The main objectives of the study are to compare the INSAT-3D TCO with two independent ground-based Dobson spectrophotometer observations and Atmospheric Infrared Sounder (AIRS) aboard NASA's Aqua satellite.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/análise , Atmosfera , Monitoramento Ambiental , Índia , Ozônio/análise
14.
J Clin Orthop Trauma ; 16: 168-175, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33717953

RESUMO

INTRODUCTION: In the last decade, there has been a renewed interest in anterior cruciate ligament (ACL) preservation surgeries in the younger patients. Several ACL preservation techniques such as primary repair, augmented repair, and scaffold repair have been described based on the particular tear type and pattern. The purpose of this study was to determine the distribution of tear patterns in young patients presenting with an acute ACL injury. METHODS: A prospective observational study was performed at two tertiary children's hospitals. Patients under 18 years undergoing ACL reconstruction within 8 weeks of initial injury were included from 2017 to 2019. Tear patterns were classified by two orthopedic surgeons from each of the two centers during arthroscopic ACL reconstruction into 4 types: I. Avulsion off the femur, II. <10% of total ACL length tear from femoral end, III. Mid-substance tear and IV. Single bundle tear. For reliability, the four surgeons classified ACL injury (2 rounds each) based on de-identified intraoperative videos of 33 randomly selected surgical ACL cases. Inter and intra-rater reliability studies were calculated using Kappa statistics. RESULTS: 224 patients (123 males, 101 females) with mean age of 16 (range: 9-18) years were enrolled in this study. Fifty-seven (25%) patients reported contact injury while 167 (75%) reported non-contact. Isolated ACL injury was recorded in 70 (31%) patients, while concomitant injuries were recorded in 154 patients (69%). The most common associated injury was lateral meniscus tear (35%), followed by lateral and medial meniscus tears (20%). According to our classification, 31 (14%) patients were Type I, 30 (13%) were Type II, 139 (62%) were Type III, 18 (8%) were Type IV. The intra-rater reliability was excellent for 2 reviewers, good for 1 and marginal for another. The overall inter-rater reliability for all 4 reviewers was marginal for both readings. There was no statistical difference in the occurrence of type of tear based on the mechanism of injury (contact vs non-contact) or age of the patients. CONCLUSIONS: This is the first multicenter study using an arthroscopic assessment to classify the location of ACL tear in the young population. It gives us further insight on the possible application for surgeries to preserve the ACL in this group. Larger studies incorporating these findings with MRI evaluation and ACL repair techniques are needed to confirm the utility of this information to decide the eligibility for repair in pediatric patients.

16.
J Cyst Fibros ; 20(2): 213-219, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33249004

RESUMO

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor, was first approved for people with CF and the G551D CFTR mutation. This study describes the long-term clinical effectiveness of ivacaftor in this population. METHODS: We conducted a multicenter, prospective, longitudinal, observational study of people with CF ages ≥6 years with at least one copy of the G551D CFTR mutation. Measurements of lung function, growth, quality of life, and sweat chloride were performed after ivacaftor initiation (baseline, 1 month, 3 months, 6 months, and annually thereafter until 5.5 years). RESULTS: Ninety-six participants were enrolled, with 81% completing all study measures through 5.5 years. This cohort experienced significant improvements in percent predicted forced expiratory volume in 1 second (ppFEV1) of 4.8 [2.6, 7.1] (p < 0.001) at 1.5 years, that diminished to 0.8 [-2.0, 3.6] (p = 0.57) at 5.5 years. Adults experienced larger improvements in ppFEV1 (7.4 [3.6, 11.3], p < 0.001 at 1.5 years and 4.3 [0.6, 8.1], p = 0.02 at 5.5 years) than children (2.8 [0.1, 5.6], p = 0.04 at 1.5 years and -2.0 [-5.9, 2.0], p = 0.32 at 5.5 years). Rate of lung function decline for the overall study cohort from 1 month after ivacaftor initiation through 5.5 years was estimated to be -1.22 pp/year [-1.70, -0.73]. Significant improvements in growth, quality of life measures, sweat chloride, Pseudomonas aeruginosa detection, and pulmonary exacerbation rates requiring antimicrobial therapy persisted through five years of therapy. CONCLUSIONS: These findings demonstrate the long-term benefits and disease modifying effects of ivacaftor in children and adults with CF and the G551D mutation.


Assuntos
Aminofenóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Quinolonas/uso terapêutico , Adolescente , Adulto , Criança , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Proteínas Mutantes/genética , Mutação , Estudos Prospectivos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Qualidade de Vida , Testes de Função Respiratória , Estados Unidos
17.
J Eur Acad Dermatol Venereol ; 35(4): 928-937, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33030755

RESUMO

BACKGROUND: The efficacy of biologic therapies is greater among biologic-naïve vs. biologic-experienced psoriasis patients. However, little is known as to whether prior use of other systemic therapies impacts secukinumab efficacy in patients with moderate-to-severe psoriasis. OBJECTIVE: To investigate the impact of prior exposure to systemic therapies upon the efficacy and safety of secukinumab 300 mg for moderate-to-severe psoriasis. METHODS: Post hoc analysis of six randomised controlled trials (RCTs) comparing secukinumab with placebo, ustekinumab or etanercept at 12 weeks of treatment. Data comparing secukinumab with placebo and ustekinumab were meta-analysed, while comparisons between secukinumab and etanercept were from a single RCT. Four subgroups of patients were assessed: (i) naïve to non-biologic systemics (NBS) and biologics; (ii) exposed to NBS but naïve to biologics; (iii) naïve to NBS but exposed to biologics; and (iv) exposed to NBS and biologics. Outcomes of interest included the following: investigator's global assessment (IGA) score, absolute psoriasis area and severity index (PASI) response, PASI 75, PASI 90 and PASI 100 responses, and dermatology life quality index (DLQI). Safety was also assessed. RESULTS: One thousand three hundred and eighty-three patients were included in the secukinumab vs. placebo meta-analysis: 1776 in the secukinumab vs. ustekinumab meta-analysis and 653 in the within-trial analyses of secukinumab vs. etanercept. For all subgroups, secukinumab was significantly more efficacious than placebo for all outcomes measured. Secukinumab generated greater responses in biologic-naïve patients, while prior NBS had a negligible impact on treatment response. Furthermore, secukinumab was more efficacious than both ustekinumab and etanercept on many outcomes, with an even greater difference for biologic-naïve than biologic-exposed patients. Safety results were consistent with individual clinical trial results. CONCLUSIONS: Twelve-week treatment with secukinumab 300 mg is consistently more efficacious than placebo, etanercept and ustekinumab in patients with moderate-to-severe psoriasis, regardless of prior exposure to biologics or NBS. Secukinumab had a comparable safety profile to both etanercept and ustekinumab.


Assuntos
Produtos Biológicos , Psoríase , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Humanos , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab
18.
Ann Dermatol Venereol ; 147(12): 868-872, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-33139060

RESUMO

INTRODUCTION: CDAGS syndrome (craniosynostosis, deafness, anal and genitourinary abnormality with rash) has been reported in 8 families of different geographical origins since 1981. No genes have been identified to date. PATIENTS AND METHODS: The patient is a girl born at 40 weeks of amenorrhea after a normal pregnancy. She was born to non-consanguineous parents and there was no significant family history. At birth, she presented craniosynostosis with a form of premature coronal suture. When she was 3 months old, she presented an eczematous facial rash. At 11 months, a skin biopsy showed lichenoid dermatosis with epidermal atrophy associated with ortho- and para-keratotic hyperkeratosis. She had sparse hair, eyelashes and eyebrows. Her initial psychomotor development was normal. No other malformations were observed. At 6 years, she presented pale pink, reticulated, erythematous plaques around healthy bands of skin on her throat and chin. Lesions on the elbows, knees and buttocks were linear and keratotic with no atrophy or telangiectasia. At 7 years, she had learning difficulties and delayed speech. Genetic assessment revealed no abnormalities. DISCUSSION: The specific dermatologic aspect combined with craniosynostosis suggested a possible diagnosis of CDAGS syndrome, even in the absence of urogenital or anal lesions. This syndrome may take numerous different forms. The appearance of porokeratosis previously noted was not found here. The underlying genetic substratum of this syndrome is not known as yet and additional genetic studies should be considered.


Assuntos
Craniossinostoses , Surdez , Exantema , Poroceratose , Anormalidades Urogenitais , Canal Anal/anormalidades , Anormalidades do Sistema Digestório , Feminino , Humanos , Recém-Nascido
20.
Sci Rep ; 10(1): 15650, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973232

RESUMO

Metastable states created by electron or hole capture in crystal defects are widely used in dosimetry and photonic applications. Feldspar, the most abundant mineral in the Earth's crust (> 50%), generates metastable states with lifetimes of millions of years upon exposure to ionizing radiation. Although feldspar is widely used in dosimetry and geochronometry, the creation of metastable states and charge transfer across them is poorly understood. Understanding such phenomena requires next-generation methods based on high-resolution, site-selective probing of the metastable states. Recent studies using site-selective techniques such as photoluminescence (PL), and radioluminescence (RL) at 7 K have revealed that feldspar exhibits two near-infrared (NIR) emission bands peaking at 880 nm and 955 nm, which are believed to arise from the principal electron-trapping states. Here, we map for the first time the electron-trapping states in potassium-rich feldspar using spectrally-resolved cathodoluminescence microscopy at a spatial resolution of ~ 6 to 22 µm. Each pixel probed by a scanning electron microscope provides us a cathodoluminescence spectrum (SEM-CL) in the range 600-1000 nm, and elemental data from energy-dispersive x-ray (EDX) spectroscopy. We conclude that the two NIR emissions are spatially variable and, therefore, originate from different sites. This conclusion contradicts the existing model that the two emissions arise from two different excited states of a principal trap. Moreover, we are able to link the individual NIR emission peaks with the geochemical variations (K, Na and Fe concentration), and propose a model that explains the quenching of the NIR emission by Fe4+. Our study contributes to an improved understanding of charge storage in feldspathic minerals, with implications for developing sub-single grain (micrometer scale) measurement techniques in radiation dosimetry.

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