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1.
Br J Dermatol ; 189(5): 540-552, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37488811

RESUMO

BACKGROUND: Treatment of psoriasis with risankizumab has demonstrated superior efficacy to other treatments, such as adalimumab, ustekinumab and secukinumab. OBJECTIVES: This study compared the efficacy and safety of risankizumab and apremilast in adults with moderate plaque psoriasis eligible for systemic therapy. It also evaluated the efficacy and safety of switching to risankizumab vs. continuing apremilast in patients who did not achieve ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75 nonresponders) after 16 weeks of treatment with apremilast. METHODS: This 52-week, phase IV, multicentre, randomized, open-label, efficacy assessor-blinded study (NCT04908475) enrolled patients (aged ≥ 18 years) with a diagnosis of moderate chronic plaque psoriasis (≥ 6 months) and who were candidates for systemic therapy. The enrolled patients (randomized 1 : 2) received subcutaneous risankizumab (150 mg at weeks 0 and 4) or oral apremilast (30 mg twice daily). At week 16, all patients treated with apremilast were re-randomized (1 : 1) to risankizumab or apremilast, stratified by week-16 PASI 75 response. The co-primary outcomes in period A at week 16 were the achievement of ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) and static Physician's Global Assessment (sPGA) 0/1 with a two-grade or better improvement from baseline. At week 52, the primary endpoint in period B was the achievement of PASI 90 in PASI 75 nonresponders with apremilast at week 16. Safety was monitored throughout the study. All patients who received one dose of treatment were included in the efficacy and safety analysis. RESULTS: At baseline, 118 and 234 patients were assigned to receive risankizumab and apremilast, respectively. At week 16, PASI 90 was achieved by 55.9% [95% confidence interval (CI) 47.0-64.9] and 5.1% (95% CI 2.3-8.0), and sPGA 0/1 by 75.4% (95% CI 67.7-83.2) and 18.4% (95% CI 13.4-23.3), respectively. In period B, among PASI 75 nonresponders with apremilast at week 16, 83 switched to risankizumab and 78 continued apremilast. At week 52, 72.3% (95% CI 62.7-81.9) who switched to risankizumab achieved PASI 90 vs. 2.6% (95% CI 0.0-6.1) who continued apremilast. The most frequent adverse events (reported in ≥ 5%) in risankizumab-treated patients were COVID-19 infection and nasopharyngitis. Diarrhoea, nausea and headache were most frequent among apremilast-treated patients. CONCLUSIONS: For patients with moderate psoriasis, treatment with risankizumab demonstrated superior efficacy to those treated with apremilast, including those who did not benefit from prior treatment with apremilast. The safety profile of risankizumab was similar to prior studies, and no new safety signals were identified. These results show that, compared with apremilast, risankizumab treatment can significantly improve clinical outcomes in systemic-eligible patients with moderate psoriasis.


Assuntos
Psoríase , Humanos , Adulto , Resultado do Tratamento , Método Duplo-Cego , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença
2.
Sensors (Basel) ; 21(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066256

RESUMO

Accurately estimating the current state of local traffic scenes is one of the key problems in the development of software components for automated vehicles. In addition to details on free space and drivability, static and dynamic traffic participants and information on the semantics may also be included in the desired representation. Multi-layer grid maps allow the inclusion of all of this information in a common representation. However, most existing grid mapping approaches only process range sensor measurements such as Lidar and Radar and solely model occupancy without semantic states. In order to add sensor redundancy and diversity, it is desired to add vision-based sensor setups in a common grid map representation. In this work, we present a semantic evidential grid mapping pipeline, including estimates for eight semantic classes, that is designed for straightforward fusion with range sensor data. Unlike other publications, our representation explicitly models uncertainties in the evidential model. We present results of our grid mapping pipeline based on a monocular vision setup and a stereo vision setup. Our mapping results are accurate and dense mapping due to the incorporation of a disparity- or depth-based ground surface estimation in the inverse perspective mapping. We conclude this paper by providing a detailed quantitative evaluation based on real traffic scenarios in the KITTI odometry benchmark dataset and demonstrating the advantages compared to other semantic grid mapping approaches.

3.
J Am Chem Soc ; 141(2): 831-839, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30501178

RESUMO

Cubosomes are bicontinuous cubic-phase particles generated by amphiphile self-assembly with bicontinuous cubic phases, which creates an intricate network of interconnected nanochannels that endow these materials with special functions for advanced applications. On the other hand, clusters are an attractive class of molecules that exhibit intriguing functions and properties that differ from those of atoms and nanoparticles. Inspired by lipid self-assembly and attracted to the new functionalities of clusters, we prepared special heterocluster Janus dumbbells (HCJDs) composed of dissimilar nanoclusters: namely, a polyoxometalate and a polyhedral oligomeric silsesquioxane. HCJDs resemble conventional amphiphiles and, as such, they self-assemble in solution into faceted hybrid cubosomes via the transformation of vesicles into spongelike aggregates. Multiple mechanisms that lead to equilibrium, including molecular self-assembly, vesicle accumulation, membrane fusion, inner-structure reorganization, and cubic crystal growth, contributed to the overall process. On the basis of these results, we proposed a strategy for self-assembly-from basic molecular design that goes beyond traditional amphiphiles to the construction of micro- or nanomaterials with hierarchical structures and advanced functions.


Assuntos
Nanoestruturas/química , Compostos de Organossilício/química , Compostos de Tungstênio/química , Estrutura Molecular , Compostos de Organossilício/síntese química , Compostos de Tungstênio/síntese química
4.
Chemistry ; 25(36): 8508-8512, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31066944

RESUMO

A sequence of a Baeyer-Villiger oxidation and a Lewis acid-promoted reduction of the resulting formate with Et3 SiH enabled the metal-free formal decarbonylation of tertiary and secondary aliphatic aldehydes. The new methodology mimics the biosynthetic decarbonylation pathway through oxidative C-C bond cleavage rather than the C(O)-H bond activation known from conventional Tsuji-Wilkinson-type reactions. The substrate scope is complementary to existing transition-metal-catalyzed protocols.

5.
Protein Expr Purif ; 133: 199-204, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27157442

RESUMO

The reductive amination is one of the most important reactions in the synthesis of chiral amines. Imine reductases (IREDs) are novel enzymes that catalyze the asymmetric reduction of imines and reductive aminations using NADPH as hydride donor. In this study, we have developed a simple method to produce two enantiocomplementary IREDs from Streptosporangium roseum DSM 43021 (R-IRED-Sr) and Paenibacillus elgii (S-IRED-Pe). The proteins were expressed efficiently in Escherichia coli (E. coli) JW5510 at the 4-L-cultivation scale and were purified to 95% homogeneity in two steps by immobilized metal ion affinity and anion-exchange chromatography. The total protein yield was about 9 g per liter of E. coli culture and resulted in 150-220 mg purified IRED per liter of E. coli culture. The bioactivity of both IREDs was measured by the depletion of the NADPH cofactor in the reduction of model substrates 2-methylpyrroline (R-IRED-Sr) and 3,4-dihydroisoquinoline (S-IRED-Pe). High level reducing activity was found demonstrating the production of correctly folded and active IRED proteins. Specific activities of about 2.58 U/mg and 0.24 U/mg for the R- and S-selective IREDs were obtained, being in agreement with activities reported in the literature.


Assuntos
Actinobacteria/genética , Proteínas de Bactérias , Escherichia coli/metabolismo , Oxirredutases , Paenibacillus/genética , Actinobacteria/enzimologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Escherichia coli/química , Escherichia coli/genética , Oxirredutases/biossíntese , Oxirredutases/química , Oxirredutases/genética , Oxirredutases/isolamento & purificação , Paenibacillus/enzimologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação
6.
Chemistry ; 22(50): 17958-17961, 2016 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-27786397

RESUMO

The manganese-catalyzed cyanation of inert C-H bonds was achieved within a heterobimetallic catalysis regime. The manganese(I) catalysis proved widely applicable and enabled C-H cyanations on indoles, pyrroles and thiophenes by facile C-H manganesation. The robustness of the manganese catalyst set the stage for the racemization-free C-H cyanation of amino acids with excellent levels of positional and chemo selectivity by the new cyanating agent NCFS. Experimental and computational mechanistic studies provided strong support for a synergistic heterobimetallic activation mode, facilitating the key C-C formation.

7.
Angew Chem Int Ed Engl ; 55(27): 7747-50, 2016 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-27095021

RESUMO

The first manganese(I)-catalyzed C-H allylations with ample scope were achieved by carboxylate assistance. The highly selective C-H/C-O functionalizations proved viable with densely substituted allyl carbonates, and the organometallic C-H allylation strategy set the stage for expedient late-stage diversification with excellent levels of positional selectivity.

8.
Angew Chem Int Ed Engl ; 54(21): 6352-5, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25864965

RESUMO

Inexpensive cobalt catalysts with N-heterocyclic carbene ligands enable direct arene alkenylations with easily accessible alkenyl acetates through regioselective C-H/C-O functionalizations in a stereoconvergent fashion. The versatile cobalt catalyst was broadly applicable and thus also allowed for the efficient conversion of alkenyl phosphates, carbonates, and carbamates at ambient temperature.

9.
Angew Chem Int Ed Engl ; 54(19): 5744-7, 2015 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-25782604

RESUMO

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction.


Assuntos
Acetatos/química , Furanos/síntese química , Furanos/química , Estrutura Molecular
10.
Hepatogastroenterology ; 61(129): 192-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24895819

RESUMO

BACKGROUND/AIMS: Although liver resection is the gold standard for patients with colorectal liver metastases (CRLM), only 15-20% of the patients are candidates for surgery. As ablative therapies may extend this low rate of curative option, the aim of the present study was to analyze the impact of cryosurgery (cryo) on survival of patients with CRLM compared to liver resection (Phx). METHODOLOGY: In a matched-pair analysis, patients undergoing Phx or cryo were compared (n = 39 each). Analysis included pre-, peri-and postoperative data and follow-up for tumor-free and overall survival. Survival was estimated by Kaplan-Meier method. RESULTS: Out of 124 patients undergoing 143 cryosurgical procedures, 39 patients could be identified undergoing single liver cryo procedure for CRLM with a curative approach. Matching of these patients with a Phx cohort, patients undergoing Phx revealed better overall (20 vs. 46 months) and tumor-free survival (7.8 vs. 33.6 months) than patients with cryo. CONCLUSIONS: Liver resection is strongly recommended for patients with CRLM compared to cryosurgery.


Assuntos
Neoplasias Colorretais/patologia , Criocirurgia/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de Sobrevida
11.
Neurophotonics ; 11(Suppl 1): S11505, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38298866

RESUMO

Significance: Deep learning enables label-free all-optical biopsies and automated tissue classification. Endoscopic systems provide intraoperative diagnostics to deep tissue and speed up treatment without harmful tissue removal. However, conventional multi-core fiber (MCF) endoscopes suffer from low resolution and artifacts, which hinder tumor diagnostics. Aim: We introduce a method to enable unpixelated, high-resolution tumor imaging through a given MCF with a diameter of around 0.65 mm and arbitrary core arrangement and inhomogeneous transmissivity. Approach: Image reconstruction is based on deep learning and the digital twin concept of the single-reference-based simulation with inhomogeneous optical properties of MCF and transfer learning on a small experimental dataset of biological tissue. The reference provided physical information about the MCF during the training processes. Results: For the simulated data, hallucination caused by the MCF inhomogeneity was eliminated, and the averaged peak signal-to-noise ratio and structural similarity were increased from 11.2 dB and 0.20 to 23.4 dB and 0.74, respectively. By transfer learning, the metrics of independent test images experimentally acquired on glioblastoma tissue ex vivo can reach up to 31.6 dB and 0.97 with 14 fps computing speed. Conclusions: With the proposed approach, a single reference image was required in the pre-training stage and laborious acquisition of training data was bypassed. Validation on glioblastoma cryosections with transfer learning on only 50 image pairs showed the capability for high-resolution deep tissue retrieval and high clinical feasibility.

12.
Appl Microbiol Biotechnol ; 97(16): 7215-27, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23188459

RESUMO

Phenoxy radical coupling reactions are involved in the biosynthesis of lignans in planta. Interestingly, the reaction can be guided by dirigent proteins, which mediate the stereoselective formation of either (+) or (-)-pinoresinol from coniferyl alcohol. So far, the mechanism is poorly understood, and for detailed mechanistic studies, a heterologous expression platform which allows the cost-effective, fast, and robust expression in high yields is needed. We established a reliable, high-yield fed-batch fermentation process with Pichia pastoris resulting in 47 mg L⁻¹ of the dirigent protein AtDIR6, which represents a more than 250-fold increase compared to previous studies. Biochemical characterization of AtDIR6 produced with P. pastoris showed an overall agreement in protein structure, N-glycosylation sites, and dirigent activity compared to AtDIR6 produced by plant cell cultures of Solanum peruvianum. CD spectroscopy verified the ß-barrel structure proposed by earlier studies and bioconversion experiments revealed similar activities to plant-derived protein, validating P. pastoris as a suitable expression system for dirigent proteins. Compared to the complex glycan structures of most plant cells, proteins produced with P. pastoris have the advantage that they can be enzymatically deglycosylated under non-denaturating conditions. With this study, we demonstrate that the glycan structures of AtDIR6 are essential for structure, solubility, and function of the protein as deglycosylation induced conformational changes leading to the complete loss in dirigent activity and subsequent protein aggregation.


Assuntos
Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Furanos/metabolismo , Lignanas/metabolismo , Fenóis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/isolamento & purificação , Dicroísmo Circular , Expressão Gênica , Glicosilação , Pichia/enzimologia , Pichia/genética , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
13.
J Surg Res ; 178(1): 268-79, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22482753

RESUMO

INTRODUCTION: The aim of the present study was to analyze the impact of cryosurgery (CRYO) on liver metastases compared to other thermoablative techniques. In a rat liver metastases model, evidence for tumor cell spread was analyzed comparing CRYO, radiofrequency ablation (RFA), and laser-induced thermotherapy (LITT). METHODS: In an experimental study, we compared cell spillage in the washout of isolated perfused rat livers undergoing thermal ablation. Within the same model, CC531-GFP rat liver tumors were treated with CRYO, RFA, or LITT and the number of vital tumor cells within the perfusate was measured. Matrix metalloproteinases (MMP-2, MMP-9) were analyzed after in vivo ablation of rat colorectal liver metastases in the third experimental model. RESULTS: Our data showed pronounced washout of cells after CRYO with a higher amount of intravascular cells and cell detritus compared to RFA and LITT. Only the effluent fluid of cryosurgery-treated livers revealed GFP-stained tumor cells. MMP-2 and MMP-9 expression was significantly higher after cryosurgery than after RFA and LITT. CONCLUSION: When using thermoablative techniques, intravascular metastatic cell spillage is highest in CRYO, and increased expression of matrix metalloproteinases may further facilitate tumor cell spread. Therefore, RFA and LITT may be preferable whenever surgical resection of liver tumors is impossible.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Células Neoplásicas Circulantes/patologia , Animais , Líquidos Corporais/citologia , Líquidos Corporais/metabolismo , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Criocirurgia/efeitos adversos , Criocirurgia/métodos , Feminino , Proteínas de Fluorescência Verde/genética , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/métodos , Neoplasias Hepáticas/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Transplante de Neoplasias , Ratos , Ratos Sprague-Dawley
14.
Int J Colorectal Dis ; 27(9): 1199-205, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22614682

RESUMO

PURPOSE: The aims of this study were to obtain normative values in resting/squeeze pressure and surface electromyography (s-EMG) in anorectal manometry using microtip technology and to determine the relationship between objective measurable values, gender and age in a cohort with no anorectal disorders. METHODS: One hundred seventy-two white central European subjects (106 males/66 females) were recruited prior to left colonic or upper rectal surgery and studied by anorectal rapid pull-through manometry with a microtip transducer system and endoanal s-EMG using a bipolar plug electrode. s-EMG patterns were determined as plateau, peak and decrease by a blinded co-investigator. Objective measurable sphincter pressures and s-EMG values were correlated with gender, age and s-EMG patterns. RESULTS: Squeeze pressure, voluntary pressure as well as s-EMG amplitude and its area under the curve were significantly lower in women compared to men (p < 0.001 each), whereas resting pressure showed no gender differences. s-EMG patterns were strongly influenced by gender. Male patients showed significantly more plateau pattern whereas peak pattern was significantly more often in women. In both genders, the peak pattern was associated with significant higher squeeze pressures. In all measurements, we found considerable inter-individual variations being higher in elder patients. There was no manometric parameter correlating with age. CONCLUSIONS: Gender is the strongest factor influencing objective measurable manometric data for healthy men and women. There are significant gender differences concerning squeeze patterns. All manometric values should be interpreted in the context of gender and of methodology used. Large prospective cohort studies matched for gender are necessary to clarify the effect of ageing on anal sphincter strength.


Assuntos
Canal Anal/fisiopatologia , Manometria/instrumentação , Manometria/métodos , Reto/fisiopatologia , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Comorbidade , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Valores de Referência , Adulto Jovem
15.
Langenbecks Arch Surg ; 397(5): 763-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22426638

RESUMO

PURPOSE: Surgeons frequently describe the shape of intraoperative findings using visual judgement and their own sense of proportion or describing these findings in comparison to commonly used or metaphoric subjects. The aim of the study was to analyse the reliability of surgeon's estimations of dimensions. METHODS: The study was performed in two phases. First, physicians had to estimate the metric proportions of four well-known objects. Second, surgeons were asked intraoperatively to estimate the liver resection surface after partial hepatectomy. The exact surface of the resection plane was measured using computed tomography-guided planimetry of the resection specimen. Physician's estimations and the exact measurements of the well-known objects and the liver resection surface were compared. Systematic error was defined by the natural logarithm of estimated/real size. RESULTS: We found a large individual discrepancy in estimating the metric proportions of commonly used objects and a tendency to underestimate both commonly used objects and liver resection surface. Experienced liver surgeons were more accurate in estimating liver resection surface compared with younger staff members. CONCLUSIONS: We found a large bias in estimating the dimension of both commonly used objects and the surface area of liver parenchyma transection. Obviously, estimating errors are more influenced by the individual subject who estimates than by the object itself. In clinical routine, surgeons should rely more on simple measuring devices than on their own sense of proportion. Education in how to estimate more correctly human liver resection surfaces can be achieved by ex vivo studies using porcine livers.


Assuntos
Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Fígado/diagnóstico por imagem , Fígado/patologia , Competência Clínica , Estudos de Coortes , Tomada de Decisões , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/normas , Feminino , Hepatectomia/normas , Humanos , Período Intraoperatório , Neoplasias Hepáticas/patologia , Masculino , Erros Médicos , Tamanho do Órgão , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Propriedades de Superfície , Inquéritos e Questionários , Carga Tumoral
16.
Langenbecks Arch Surg ; 397(3): 383-95, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22089696

RESUMO

BACKGROUND: Hepatic resection of colorectal liver metastases is the only curative treatment option. As clinical and experimental data indicate that the extent of liver resection correlates with growth of residual metastases, the present study analyzes the potential benefit of a parenchyma-preserving liver surgery approach. METHODS: Data from a prospectively maintained database of patients undergoing liver resection for colorectal metastases were reviewed. Evaluation of outcome was performed using the Kaplan-Meier method. Correlations were calculated between clinical-pathological variables. RESULTS: One hundred sixty-three patients underwent 198 liver resections for colorectal metastases: 26 major hepatectomies, 65 minor anatomical resections, 78 non-anatomical resections, as well as 29 combinations of minor anatomical and non-anatomical procedures. Overall 1-, 3-, and 5-year survival was 93%, 62%, and 40%, respectively. Patients with repeated liver resections had a 5-year survival of 27%. Interestingly, large dissection areas were associated with a significant reduction of the 5-year survival rate (33%). Five-year survival after major hepatectomy was not significantly reduced. CONCLUSION: For colorectal liver metastases, minor resections offer a prolonged survival compared to major hepatectomies. As patients with stage IV colorectal disease are candidates for repeat resections, preservation of hepatic parenchyma is of increasing importance in the setting of multi-modal and repeated therapy approaches.


Assuntos
Neoplasias do Colo/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Retais/patologia , Idoso , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Humanos , Tempo de Internação , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Adjuvante , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Análise de Sobrevida
17.
J Comp Eff Res ; 11(8): 575-582, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35514324

RESUMO

Aim: To compare rates of biologic initiation after commencing treatment with apremilast (APR) versus methotrexate (MTX) in systemic-naive patients with psoriasis (PsO). Methods: This was a retrospective cohort study of systemic-naive patients with PsO who initiated treatment with APR or MTX between 1 January 2015 and 31 March 2018. Outcomes: Adjusted rates of biologic initiation during follow-up were compared by logistic and Cox regressions. Results: APR initiators had 58% lower likelihood of biologic initiation (odds ratio: 0.42; 95% CI: 0.37-0.48; p < 0.001), lower adjusted biologic initiation rate (14.4% [95% CI: 13.2-15.7%] vs 28.6% [95% CI: 26.8-30.5%]), lower risk of biologic initiation (hazard ratio: 0.45; 95% CI: 0.40-0.51; p < 0.001) compared with MTX initiators. Conclusion: Systemic-naive patients with PsO have a lower rate of biologic initiation over 1 year following APR initiation.


Assuntos
Produtos Biológicos , Psoríase , Humanos , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Talidomida/análogos & derivados
18.
J Rheumatol ; 49(7): 694-699, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35428720

RESUMO

OBJECTIVE: The probability of achieving Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) treatment targets (remission [REM], low disease activity [LDA]) was evaluated following apremilast monotherapy in disease-modifying antirheumatic drug (DMARD)-naïve patients with psoriatic arthritis (PsA) based on baseline disease activity. METHODS: This post hoc probability analysis of PALACE 4, a phase III, multicenter, randomized, placebo-controlled study, evaluated shifting across cDAPSA categories from baseline to week 52 and included DMARD-naïve patients receiving apremilast 30 mg BID with available baseline cDAPSA data. Changes in articular/extraarticular manifestations were evaluated in patients with week 52 cDAPSA components. cDAPSA treatment target achievement was assessed in a subgroup with baseline extraarticular PsA manifestations (skin involvement, enthesitis, dactylitis). RESULTS: Of 175 apremilast-treated patients in the probability analysis, 66.3% were in high disease activity (HDA) and 31.4% in moderate disease activity (ModDA) at baseline. Approximately twice as many patients in ModDA at baseline reached REM/LDA at week 52 vs those in HDA (61.7% vs 28.2%). Achieving cDAPSA treatment targets was associated with reductions in articular (swollen/tender joints) and extraarticular (skin involvement, enthesitis, dactylitis, functional disability) disease activity. Similar treatment target achievement rates were observed in the subgroup with ≥ 1 extraarticular PsA manifestation (n = 126; ModDA: 66.7%, HDA: 32.2%). CONCLUSION: Apremilast-treated patients with baseline ModDA had higher probability of achieving cDAPSA treatment targets than patients with HDA. Resolution and/or near resolution of articular and/or extraarticular PsA manifestations was achieved by patients in REM/LDA at week 52. Consistent treatment target achievement was observed in patients with 1 or multiple extraarticular manifestations of active PsA.


Assuntos
Antirreumáticos , Artrite Psoriásica , Entesopatia , Artropatias , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Entesopatia/tratamento farmacológico , Humanos , Índice de Gravidade de Doença , Talidomida/análogos & derivados , Resultado do Tratamento
19.
Dermatol Ther (Heidelb) ; 12(1): 61-78, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34704231

RESUMO

INTRODUCTION: Since the 2012 Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, several systemic treatments for psoriasis (PsO) and/or psoriatic arthritis (PsA) have been approved. The population-based UPLIFT survey was conducted to understand how perceptions of treatment-related outcomes have evolved, particularly for patients with mild to moderate PsO and/or PsA and their dermatologists. METHODS: This population- and web-based survey was conducted from 2 March to 3 June 2020, in North America, Europe, and Japan. Adults with self-reported healthcare practitioner (HCP)-diagnosed PsO and/or PsA and dermatologists who spent > 50% of time treating patients and treated ≥ 20 patients with PsO, including plaque PsO, per month were included. Patient participants were recruited at random from online panels; dermatologists were recruited randomly from representative physician panels. RESULTS: Of 264,054 patient responses, 3806 who self-reported an HCP diagnosis of PsO and/or PsA were included in the final sample; 67% had PsO alone, 28% had PsO and PsA, and 5% had PsA alone. The estimated population prevalence of psoriatic disease was 7% (PsO only: 4%; PsO and PsA: 2%; PsA only: 1%). Most patients (78%) reported PsO-involved body surface area (BSA) ≤ 3 palms, and ~ 90% or more reported itching, redness, flaking, and scales. Many PsO patients without diagnosed PsA reported musculoskeletal symptoms suggestive of PsA (63%). Across BSA categories, approximately one in four patients was not currently receiving treatment and > 50% had Dermatology Life Quality Index score > 5. Patients and dermatologists had different perceptions of PsO severity, office visit discussions, treatment goals, and treatment satisfaction. The survey was conducted during the coronavirus disease 2019 (COVID-19) pandemic, which could have affected assessments of patient-reported outcomes and ability to have in-person HCP visits. CONCLUSIONS: Patients with PsO and PsA in UPLIFT reported high disease burden, including patients with limited skin involvement. An opportunity exists to align patient and dermatologist perceptions to optimize management of PsO and PsA. INFOGRAPHIC: DIGITAL FEATURE: This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article go to https://doi.org/10.6084/m9.figshare.17104586 .


In recent years, several new treatments for psoriasis and psoriatic arthritis have become available. The UPLIFT survey was conducted to understand how viewpoints on psoriatic disease outcomes have changed, especially for patients whose disease is mild or moderate. UPLIFT was a large, online, population-based survey conducted in North America, Europe, and Japan. Adults with psoriasis and/or psoriatic arthritis and dermatologists who treated at least 20 patients with psoriasis per month were included. There were 3806 patients who participated; of these, most had psoriasis and few had psoriatic arthritis. Most patients (78%) with mild to moderate psoriasis had a limited area of skin affected by psoriasis. Psoriasis symptoms were common and included itching, redness, flaking, and scales. Many patients without a diagnosis of psoriatic arthritis reported symptoms that could be related to this disease (such as joint discomfort). Although many patients had psoriasis symptoms, approximately one in four was not currently receiving treatment and more than half reported psoriasis impacted their quality of life. Patients and dermatologists had different perceptions of psoriasis severity, office visit discussions, treatment goals, and treatment satisfaction. There is an opportunity to improve treatment of psoriasis and psoriatic arthritis and to better align patient and physician perceptions of psoriasis. This survey was conducted during the COVID-19 pandemic, which could have partially affected some assessments and the ability to have in-person doctor visits.

20.
World J Surg ; 35(9): 1945-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21713579

RESUMO

BACKGROUND: The influence of superstition, moon calendars, and popular belief on evidence-based medicine is stunning. More than 40% of medical staff is convinced that lunar phases can affect human behavior. The idea that Friday the 13th is associated with adverse events and bad luck is deep-rooted in the population of Western industrial countries. The aim of the present study was to test the hypothesis that these myths are transferable to real-life surgery. METHODS: We analyzed the extent to which moon phases, zodiac signs, and Friday the 13th influence blood loss, emergency frequency, and intestinal perforations by evaluating the operation records of all 27,914 consecutive patients of our institution undergoing general, visceral, or vascular surgery between August 2001 and August 2010. Dates of surgery were allocated to lunar phases and to zodiac signs, as well as to Friday the 13th. RESULTS: A total of 111 lunar cycles and 15 Fridays the 13th occurred within the 3,281-day observation period. Patients' characteristics did not differ in lunar phases, zodiac signs, or Fridays the 13th. Full moon phases, the presence of Friday the 13th, and zodiac signs influenced neither intraoperative blood loss nor emergency frequency. No statistical peaks regarding perforated aortic aneurysms and gastrointestinal perforations were found on full moon or Friday the 13th. CONCLUSIONS: Scientific analysis of our data does not support the belief that moon phases, zodiac signs, or Friday 13th influence surgical blood loss and emergency frequency. Our data indicate that such beliefs are myths far beyond reality.


Assuntos
Perda Sanguínea Cirúrgica , Cultura , Lua , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Emergências/epidemiologia , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Teste de Realidade , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/métodos , Adulto Jovem
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