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2.
Int J Pharm ; 647: 123530, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37858638

RESUMO

Posterior uveitis (PU), which often has an autoimmune origin, can be treated effectively with synthetic glucocorticoid triamcinolone acetonide (TAA). Due to the limitations of topical TAA administration reaching the posterior segment of the eye, the drug is injected directly into the eye through an intravitreal injection. In this study, we prepared TAA loaded poly(lactic-co-glycolic acid) phosphatidylcholine hybrid nanoparticles (TAA-PLHNPs) using the principles of design of experiments (DoE) for topical ocular administration. The mean particle size (nm) and drug loading efficiency (LE%) for the optimized formulations were 163 ± 2.8 nm and 39 ± 1.9%, respectively. The TAA-PLHNPs were then loaded into the dual responsive in situ gel that we reported in our previous work. In vitro assessments were done to show that the formulations are safe for ocular administration. Finally, in vivo ocular pharmacokinetic studies were performed to compare pharmacokinetic parameters of TAA-PLHNPs and TAA-PLHNPs loaded in situ gel with each other and with the previously reported conventional formulation of TAA (aqueous suspension of TAA with 20% hydroxypropyl ß-cyclodextrin (TAA-HP-ß-CD-Susp)). TAA-PLHNPs loaded dual responsive in situ gel (TAA-PLHNP-ISG) achieved higher concentrations of TAA in the vitreous humor (Cmax of 946.53 ng/mL) and sustained (MRT0-∞ of 16.26 h) the drug concentrations for longer period of time compared to aqueous suspension of TAA-PLHNPs (TAA-PLHNP-Susp) and TAA-HP-ß-CD-Susp.


Assuntos
Nanopartículas , Triancinolona Acetonida , 2-Hidroxipropil-beta-Ciclodextrina , Corpo Vítreo , Lecitinas , Tamanho da Partícula
3.
Quintessence Int ; 54(5): 428-437, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-36705489

RESUMO

OBJECTIVE: The objective was to evaluate oral health-related knowledge, and to compare the effectiveness of three different oral health education interventions (OHEI) on plaque removal in a cohort with Parkinson disease. METHOD AND MATERIALS: The three-arm, parallel-group, randomized controlled trial included 63 Parkinson disease stage 1 and 2 patients aged ≥ 40 years and scores ≥ 26 in both Montreal Cognitive Assessment test and Mini-Mental State Exam. These patients were allocated to three OHEI groups: lectures, presentation, and demonstration. The validated questionnaire assessed knowledge level at baseline (0), 1, 2, and 3 months. Oral hygiene at 0 and 3 months was assessed by the Plaque Index and the Patient Hygiene Performance Index (PHPI). Unstimulated whole saliva was collected to assess the salivary flow rate. RESULTS: Pairwise comparison using ANOVA showed a significant decrease in mean percentage knowledge 0, 1, 2, and 3 months in all three groups (P < .001). After Tukey post-hoc analysis the presentation group had significantly higher knowledge (P = .030). ANOVA showed that the percentage of knowledge decreased as time passed (P = .001). Comparison of means of Plaque Index and PHPI scores by MANOVA followed by Tukey post-hoc analysis showed significant decrease in Plaque Index scores from 0 to 3 months (P = .001). No significant change in the salivary flow rate was noted. CONCLUSION: Pictorial representation of OHEI is a better mode of intervention compared to lectures and demonstrations in Parkinson disease stage 1 and 2 patients. Despite the decline in knowledge with time, Plaque Index scores reduced significantly, implying that this form OHEI offers positive benefits.


Assuntos
Placa Dentária , Doença de Parkinson , Humanos , Higiene Bucal/educação , Assistência Odontológica , Índice de Placa Dentária
4.
Obes Surg ; 33(3): 750-760, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36698049

RESUMO

Nutritional deficiencies following malabsorptive surgeries are a major concern. PURPOSE: To present clinical-based, mid-term nutritional outcomes in single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) patients using a nutritional supplement based on the American Society for Metabolic & Bariatric Surgery (ASMBS) guidelines. SETTING: Single private institute, Australia. MATERIALS AND METHODS: Data from 196 patients who underwent a primary SADI-S by a single surgeon from January 2017 through March 2022 were retrospectively analysed. All patients received either original or altered formulated nutritional supplementation throughout the study. In total, three formulae, slightly different from each other, were used at three different time points to formulate the supplement. RESULTS: In total, 196 patients were included. The average age and preoperative body mass index were 44.9 ± 6.7 years and 43.6 ± 22.5 kg/m2, respectively. Nutritional follow-up was available on 77.5%, 73.2%, 73.4%, and 59.7% of patients at 12, 24, 36, and 48 months, respectively. At baseline, 48.3%, 30%, 14.9%, 13.3%, 12.4%, 3.8%, 2.3%, and 0.5% of the patients had vitamin D, calcium, folic acid, total protein, iron, vitamin B12, copper, and vitamin A deficiencies, respectively. Postoperatively, mild to moderate vitamin deficiencies were noted in 14.2% of the patients in the first 18 months; however, at 4 years, the cohort had zero nutritional deficiencies. There were no long-term complications, revisions/conversions, or mortalities related to nutritional deficiencies. CONCLUSION: Factors, like preoperative and postoperative early, aggressive correction of nutritional deficiencies, regular laboratory monitoring and follow-ups with the multidisciplinary team, and adherence to our formulated nutritional supplement, have contributed to favourable nutritional outcomes at 4 years.


Assuntos
Derivação Gástrica , Desnutrição , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Austrália/epidemiologia , Desnutrição/epidemiologia , Desnutrição/etiologia , Anastomose Cirúrgica/efeitos adversos , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos
5.
J Periodontol ; 94(6): 785-792, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36542371

RESUMO

BACKGROUND: The delicate balance between oxidative stress and its antioxidant system can be disrupted in diabetes mellitus (DM), making the tissue susceptible to injury. Hence, this case-control study aims to estimate and correlate the gingival tissue sulfiredoxin and crevicular total oxidative stress (TOS) levels in generalized periodontitis Stage II individuals Grade C (PSII) with and without type II DM. MATERIAL AND METHODS: A total of 72 individuals were grouped based on their glycosylated hemoglobin (HbA1c) levels and clinical parameters: group I, periodontally healthy non-diabetic (HbA1c < 5.7%) (n = 24); group II, non-diabetic with PSII (n = 24); and group III, diabetic individuals (HbA1c > 6.5%) with PSII (n = 24). Gingival tissues and crevicular fluid samples were collected. The samples with adequate protein concentrations (n = 72) were further estimated for sulfiredoxin and TOS levels by enzyme-linked immunosorbent assay (ELISA) and calorimetric method, respectively. RESULTS: Tissue sulfiredoxin and crevicular TOS levels are increased significantly in the periodontitis group compared to the non-periodontitis group (p < 0.001).The tissue sulfiredoxin levels did not vary significantly between the two periodontitis groups (p < 0.179). The TOS levels are significantly higher in the diabetic compared to non-diabetic periodontitis group (p < 0.001). Correlation statistics showed a significant positive correlation (r = 0.65 and p < 0.005) between sulfiredoxin and TOS levels in diabetes with PSII group, however, no such significant correlation was observed in the non-diabetic PSII group (r = 0.255 and p < 0.422). CONCLUSION: Diabetic individuals showed inadequate sulfiredoxin-mediated antioxidant response to an increase in oxidative stress levels in periodontitis Stage II Grade C individuals.


Assuntos
Periodontite Crônica , Diabetes Mellitus Tipo 2 , Periodontite , Humanos , Hemoglobinas Glicadas , Estudos de Casos e Controles , Antioxidantes/análise , Antioxidantes/metabolismo , Líquido do Sulco Gengival/química , Periodontite/metabolismo , Diabetes Mellitus Tipo 2/complicações , Estresse Oxidativo , Periodontite Crônica/metabolismo
6.
Quintessence Int ; 53(10): 840-849, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36169271

RESUMO

OBJECTIVE: Clinical research in the field of regeneration presents challenges for regulating inflammation and speeding up healing and regenerative processes, which are lacking in individuals with diabetes. Platelet-rich fibrin (PRF) has shown promising results in regeneration. Variations in its properties are attributed mainly to the centrifugation method and other parameters. Hence, the present in vitro study on leukocyte-PRF (L-PRF) and advanced-PRF (A-PRF) membranes, with varying protocols amongst diabetes, was conducted. METHOD AND MATERIALS: Sixty-four PRF membranes from 30 individual's venous blood samples (16 nondiabetic and 16 diabetic) were assessed for platelet parameters, tensile strength, strain, and growth factor release. The resulting data were statistically analyzed. RESULTS: The A-PRF membrane had better tensile strength, strain, and growth factor level in comparison with the L-PRF membrane in healthy individuals. Significantly (P < .05) higher strain and growth factor levels in the A-PRF membrane and marginally higher tensile strength in the L-PRF membrane were seen in diabetic individuals. CONCLUSIONS: The nondiabetic A-PRF membrane had better tensile strength, strain, and growth factor release. Well-controlled diabetic individuals had higher growth factor release, suggesting the use of A-PRF membrane as a suitable autogenous regenerative material.


Assuntos
Produtos Biológicos , Diabetes Mellitus , Fibrina Rica em Plaquetas , Humanos , Leucócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Cicatrização , Produtos Biológicos/metabolismo , Diabetes Mellitus/metabolismo
7.
Quintessence Int ; 53(10): 850-857, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36169273

RESUMO

OBJECTIVE: To evaluate the association of Fusobacterium nucleatum and Capnocytophaga species in dental plaque, cord blood, pericrevicular vaginal samples, and adverse pregnancy outcomes in gestational diabetic mellitus (GDM) women with and without periodontitis stage II. METHOD AND MATERIALS: In this prospective cohort study, 415 pregnant women were screened and 60 primigravidae with diagnosis of GDM were recruited. Glycosylated hemoglobin (HbA1c) was recorded at weeks 24, 28, and 32, and at parturition. Subgingival plaque sample, cord blood, and pericrevicular vaginal swab were taken immediately postpartum from both the groups. Identification of F nucelatum and Capnocytophaga species was done using polymerase chain reaction. Adverse pregnancy outcomes such as preterm birth, low birth weight, and macrosomia were prospectively checked in all the recruited individuals. RESULTS: Incidence of adverse pregnancy outcomes was significantly higher in the GDM with periodontitis group (48%) than the nonperiodontitis GDM group (14%) with P < .07. There was a moderate positive correlation (r = 0.429) between Gingival Index and HbA1c and microorganisms in the three samples at parturition. Macrosomia was seen in equal percentages in both groups. CONCLUSION: Concomitant existence of F nucleatum and Capnocytophaga species in all three samples was shown to be associated with increased incidence of adverse pregnancy outcomes in the GDM with periodontitis group. Of the adverse outcomes, preterm birth and low birth weight were more closely related to the periodontitis group than macrosomia.


Assuntos
Diabetes Gestacional , Periodontite , Nascimento Prematuro , Humanos , Recém-Nascido , Feminino , Gravidez , Resultado da Gravidez , Hemoglobinas Glicadas , Macrossomia Fetal/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Estudos Prospectivos , Periodontite/complicações , Periodontite/microbiologia
8.
World Neurosurg ; 162: e131-e140, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35257953

RESUMO

BACKGROUND: Mucormycosis infection of the maxillofacial region and brain has been associated with coronavirus disease 2019 (COVID-19) infection. Mucormycosis was relatively a rare infection before COVID-19, and imaging findings are not very well described. MATERIALS AND METHODS: A retrospective imaging study of 101 patients diagnosed with COVID-19-associated mucormycosis by histopathology and/or culture was performed. All patients underwent computed tomography and/or magnetic resonance imaging based on the clinical condition of the patient and on consensus decision by the team of treating physicians. A simple 3-stage classification system based on imaging findings was adopted. RESULTS: One hundred one cases were included in the final analysis (mean age = 55.1 years; male/female ratio = 67:34). The affected patients had diabetes in 94% of the instances (n = 95), 80.1% (n = 81) received steroids), whereas 59.4% (n = 60) patients received supplemental oxygen. The majority underwent surgical intervention, whereas in 6 cases, patients were treated with antibiotic regimens. Sixty subjects improved following therapy, whereas 18 eventually succumbed to the illness. We noted a significant positive correlation between the imaging stage and outcomes. No association was seen between other clinical parameters and final clinical outcomes. Salient imaging findings include lack of normal sinonasal mucosal enhancement, perisinus inflammation, ischemic optic neuropathy, perineural spread, pachymeningeal enhancement, and presence of strokes. CONCLUSIONS: We describe the imaging findings in the largest cohort of patients with rhino-orbito-cerebral mucormycosis in the context of the current COVID-19 pandemic. A simplified staging system described here is helpful for standardized reporting and carries prognostic information.


Assuntos
COVID-19 , Mucormicose , Doenças Orbitárias , Antifúngicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/diagnóstico por imagem , Doenças Orbitárias/complicações , Doenças Orbitárias/diagnóstico por imagem , Pandemias , Estudos Retrospectivos , SARS-CoV-2
9.
Photodiagnosis Photodyn Ther ; 36: 102617, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34740837

RESUMO

INTRODUCTION: This study compares and evaluates the efficacy of tetracycline, laser and photodynamic therapy on bacterial counts, cell damage, cell viability and neutralization of gingipains. MATERIAL AND METHODS: P.gingivalis (ATCC 33,277) was cultured anaerobically. The minimal inhibitory concentration (MIC) for 50% inhibition of P.gingivalis by tetracycline, laser, and toluidine blue (TB) was determined using spectrophotometry. The antibacterial effects, cell viability, cell damage and neutralization of gingipains of the treated groups was evaluated by microbial culture and counting, 2,3 Bis 2 Methyloxy-4 Nitro-5 Sulphophenyl 2 H tetrazolium-5-Carboxaanilide (MTT) assay, lactate dehydrogenase (LDH) assay, and gingipain assay (BAPNA). RESULTS: The MIC of tetracycline, toulidine, diode laser (810nmm; 0.5 Watts) is 1 µg/mL, 50 µg/mL and 15 s respectively. Comparative analysis for bacterial colony reduction was highest in tetracycline followed by PDT and then laser group at p < 0.01. MTT assay shows a significantly lesser number of viable cells in the tetracycline and PDT group when compared to laser group p < 0.01. Comparative analysis for cell damage using LDH shows the highest results for PDT followed by tetracycline and laser at p < 0.01. The highest neutralization of the gingipains is seen in the PDT group followed by tetracycline and laser groups at p < 0.01. CONCLUSION: PDT shows highest antibacterial activity, gingipain neutralization, cell damage, and least number of viable cells in comparison with tetracycline and laser.


Assuntos
Fotoquimioterapia , Porphyromonas gingivalis , Antibacterianos/farmacologia , Sobrevivência Celular , Lasers , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Tetraciclinas , Virulência
10.
Int J Periodontics Restorative Dent ; 41(6): e213-e221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34818382

RESUMO

Smoking has a profound effect on platelet morphology and activation and has also been shown to affect hemostasis, coagulation, and healing cascade. To date, no previous reports are available to assess the impact of cigarette smoke on leukocyte- and platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) membranes. Therefore, this study aims to analyze the impact of cigarette smoking on the mechanical and biologic properties of L-PRF and A-PRF membranes. Sixty blood samples from both smokers (n = 34) and nonsmokers (n = 26) who were matched for age and other factors were collected and subjected to complete blood count and platelet indices (mean platelet volume, platelet distribution width, platelet large cell ratio, and plateletcrit). The L-PRF membrane (2,700 rpm; 12 minutes) and A-PRF membrane (1,500 rpm; 14 minutes) were prepared using a standard protocol. A total of 64 experimental L-PRF and A-PRF membranes from 16 individuals selected randomly from the two groups were subjected to tensile strength evaluation using a micro universal testing machine and growth factor release analysis (platelet-derived growth factor [PDGF-AB], vascular endothelial growth factor [VEGF], and bone morphogenic protein-2 [BMP-2]) using ELISA (enzyme-linked immune sorbent assay). Results were tabulated, and statistical analysis was done using Mann-Whitney, Kruskal-Wallis, and Spearman correlation tests. Tensile strengths of L-PRF and A-PRF did not show a statistical difference between groups (P = .47). BMP-2 was not detected in any of the groups. A high initial release of PDGF-AB and VEGF was noticed in A-PRF samples from smokers. Although statistically insignificant, cigarette smoking does affect platelet activation and influences the tensile strength of L-PRF membranes as well as growth factor release in A-PRF membranes in smokers.


Assuntos
Produtos Biológicos , Fumar Cigarros , Fibrina Rica em Plaquetas , Plaquetas , Fumar Cigarros/efeitos adversos , Humanos , Leucócitos , Fator A de Crescimento do Endotélio Vascular
11.
Cureus ; 13(4): e14782, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-34094746

RESUMO

We report the finding of a rare diagnosis of a duodenal duplication cyst (DDC) resulting in malignancy. Duplication cysts are rare entities in itself but less than 5% arise from duodenum. Our case represents a rare case, but high suspicion and early resection may have prevented associated complications.

12.
Forensic Sci Int ; 324: 110850, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082395

RESUMO

Thanatochemistry also known as chemistry of death and is used to determine post mortem interval (PMI). It is arguably one of the critical steps in forensic investigation. Recent addition of analyzing biochemical changes along with the traditional methods have gained importance, as they help us to record very early changes in the tissue specimens. In this view, our study aimed to correlate both histological changes and enzymatic changes in gingival tissue samples at intervals of immediate, 1 h, 5 h, 24 h and 48 h after death. Histologic changes noted were loss of epithelial architecture, chromatin clumping, nuclear vacuolation, karryopyknosis, eosinophilia and wide intercellular junctions. Two enzymes which differentiate between the autolytic phase (acid phosphatase) and putrefactive phase (ammonia) of decomposition were evaluated using UV spectrometer. Results in our study demonstrated there were variations as in gradual increase in ammonia levels (1.13±0.24-26.6±2.09) and gradual decrease in acid phosphatase levels (5.61±0.67-1.25±0.53) at different time intervals till 48 h. The cellular changes in gingival tissue could also be related to time. The result of our study helps us to identify potential of enzymatic changes which when correlated with histological reports helps us to predict the time of death accurately. Replicating this experiment in various known taphonomic conditions and other enzymes could highlight the usefulness of gingival tissue samples in determining time of death.


Assuntos
Gengiva/enzimologia , Gengiva/patologia , Mudanças Depois da Morte , Fosfatase Ácida/metabolismo , Adulto , Amônia/metabolismo , Apoptose , Núcleo Celular/patologia , Cromatina/patologia , Eosinofilia/patologia , Células Epiteliais/patologia , Feminino , Patologia Legal/métodos , Humanos , Junções Intercelulares/patologia , Masculino , Necrose , Espectrofotometria Ultravioleta , Vacúolos , Adulto Jovem
13.
Int J Angiol ; 30(1): 40-47, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34025094

RESUMO

Angiography is inaccurate in assessing functional significance of coronary lesions, and often stenoses deemed severe on angiographic assessment do not restrict coronary blood flow at rest or with maximal dilatation. Angiography-guided revascularization has not shown improvement in hard clinical outcomes in stable ischemic heart disease (SIHD). Most current guidelines for SIHD recommend invasive functional assessment of lesions to guide revascularization if prior evidence of ischemia is not available. There has been several recent advances and development of novel methods in this arena. Various contemporary clinical trials have been undertaken for validation of these indices. Here we review the physiological basis, tools, techniques, and evidence base for various invasive (resting as well as hyperemic) and noninvasive methods for functional assessment of coronary lesions. Left main stenosis, bifurcation lesions, serial stenosis, and acute coronary syndrome each causes unique disequilibrium that may affect measurements and require special considerations for accurate functional assessment.

14.
J Int Acad Periodontol ; 23(2): 106-114, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929811

RESUMO

Aims: To test the hypothesis that higher periodontal inflamed surface area (PISA) positively correlates with the coefficient of variation of red cell distribution width (RDW-CV) in non-obese hypertensive patients. Materials and methods: Hypertensive subjects aged between 40-60 years with and without periodontitis were enrolled for the study. They completed a structured questionnaire that included gender, height, weight, and other variables. Body mass index was calculated to exclude obese individuals. Clinical periodontal parameters were recorded. PISA was calculated, and participants were divided into four groups: Group 1: Non-hypertension without periodontitis, Group 2: Non-hypertensive with periodontitis, Group 3: Hypertensive without periodontitis, and Group 4: Hypertensive with periodontitis. The hematologic evaluation included red cell distribution width analysis. Results: ANOVA showed age and diastolic blood pressure were significantly related to RDW-CV at p < 0.001. Periodontal parameters showed significant association with RDW-CV in both hypertensive and non-hypertensive groups at p < 0.001. Pearson correlation test showed a significant association between RDW-CV and PISA. Multivariate regression models showed PISA to be a significant predictor for RDW-CV in the periodontitis group compared to a non-periodontitis group. Conclusions: The increase in the RDW-CV in the periodontitis group in both hypertensive and non-hypertensive indicates the independent role of increased inflammation on pathogenic alteration of red cell morphology.


Assuntos
Hipertensão , Periodontite , Adulto , Índices de Eritrócitos , Humanos , Hipertensão/complicações , Inflamação , Pessoa de Meia-Idade , Obesidade/complicações , Periodontite/complicações
15.
Cureus ; 13(2): e13515, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33786223

RESUMO

Hepatic involvement with space-occupying lesions seen in patients with multiple myeloma (MM) is a rare phenomenon. We present two cases of extramedullary multiple myeloma (EMM), with different presentations to highlight the diversity of clinical presentation. Clinically relevant hepatic involvement of myeloma is uncommon and can pose management problems. Hepatic involvement of EMM is indicative of a poor prognosis. Early recognition can help stage and prognosticate the disease.

16.
Cureus ; 13(2): e13082, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33680622

RESUMO

Members of the SWItch/sucrose nonfermentable (SWI-SNF) family, including SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1)/integrase interactor 1 (INI-1) are known tumor suppressor genes. Interactions between SMARCB1/INI-1 and key protein components in various cellular pathways are related to tumor progression and proliferation.SMARCB1/INI-1 protein was undetectable in rhabdoid tumor cells, whereas non-tumorous cells express the SMARCB1/INI-1 genes. Germline and sporadic mutations of several genes encoding for proteins in this complex are known to cause a spectrum of cancers, usually with sarcomatoid features which include a very aggressive renal medullary carcinoma. We report a case of a 29-year-old male who presented with SMARCA4 deficient renal tumor with a very aggressive clinical behavior which ultimately led to his death.

17.
RMD Open ; 7(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526709

RESUMO

OBJECTIVE: Interleukin (IL)-6 is a pleiotropic cytokine involved in the pathophysiology of rheumatoid arthritis (RA). Sirukumab is a human monoclonal antibody that binds to IL-6 with high affinity and specificity. METHODS: This long-term extension (LTE) study of the SIRROUND-D and SIRROUND-T studies assessed long-term safety and efficacy of sirukumab in adults with moderate-to-severe RA refractory to conventional disease-modifying antirheumatic drug therapy or antitumor necrosis factor agents. Patients received sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) or sirukumab 50 mg SC every 4 weeks (q4w). RESULTS: 1820 patients enrolled in the LTE; median exposure was 2.34 and 2.07 years in sirukumab 50 mg q4w and 100 mg q2w groups, respectively. Adverse events (AEs) occurred in similar proportions between groups, with the exception of major adverse cardiovascular events (MACE), which were more common in the 50 mg q4w versus 100 mg q2w group (2.2% vs 1.0%), and injection-site reactions, more common in the 100 mg q2w group versus 50 mg q4w group (7.5% vs 3.7%). The most common serious AEs were infections (10% of the patients); 32 (1.8%) patients died during the study (primarily from serious infection and MACE). Malignancies were reported in 24 (1.3%) patients. Gastrointestinal perforations, hepatobiliary abnormalities and changes in laboratory parameters were rare. Reductions in RA signs and symptoms and improvements in physical function were maintained throughout the LTE. CONCLUSIONS: The safety profile of sirukumab in the LTE remained consistent with that reported in SIRROUND-D and SIRROUND-T and efficacy was maintained. TRIAL REGISTRATION NUMBER: NCT01856309.


Assuntos
Antirreumáticos , Artrite Reumatoide , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Método Duplo-Cego , Humanos
18.
Cardiovasc Revasc Med ; 30: 20-25, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33077394

RESUMO

BACKGROUND/PURPOSE: There is limited data available on atherectomy usage in hospitals or centers without on-site surgical backup. The purpose of this retrospective analysis was to gain further knowledge by analyzing the in-hospital and 30-day outcomes of complex PCI patients (including diabetics) treated with coronary orbital atherectomy (OA) at centers without on-site surgical back-up. METHODS/MATERIALS: All comers treated with OA at two centers without on-site surgical backup were included. Baseline, procedure, and outcome data were compared in diabetic and non-diabetic patients. The impact of transfemoral (TFA) versus transradial (TRA) vascular access was also assessed. RESULTS: Of the 221 patients treated with OA, 43% were diabetics. The diabetes and no-diabetes groups had similar baseline demographic and lesion characteristics, except for the higher rate of chronic kidney disease seen in the diabetics. Overall, there was a high freedom from major adverse cardiac events (MACE; in-hospital: 99.5%; 30-day: 98.6%), as well as a high success in stent delivery (99.5%) and procedural success (97.3%). The rate of angiographic complications was low in both the diabetes and no-diabetes groups (3.1% vs. 1.6%, p = 0.450). TFA and TRA were used in 36% and 64% of the patients, respectively-resulting in low angiographic complications in both groups (3.8% vs. 1.4%, p = 0.263). CONCLUSIONS: Despite the complexity of patient co-morbidities and the presence of heavily calcified lesions, the results indicate that coronary OA can be used safely and effectively without on-site surgical back-up. OA treatment resulted in a high rate of successful stent delivery and procedural success, as well as low rates of angiographic complications and MACE, in diabetic and non-diabetic patients, regardless of access site. TABLE OF CONTENTS SUMMARY: There is limited data available on atherectomy usage in centers without on-site surgical backup. The purpose of this retrospective analysis was to gain further knowledge by analyzing the outcomes of complex PCI patients (including diabetics) treated with coronary orbital atherectomy (OA) at centers without on-site surgical back-up. The impact of transfemoral (TFA) versus transradial (TRA) vascular access was also assessed. Despite the complexity of patient co-morbidities and the presence of heavily calcified lesions, the results indicate that coronary OA can be used safely and effectively without on-site surgical back-up. OA treatment resulted in a high rate of successful stent delivery and procedural success, as well as low rates of angiographic complications and major adverse cardiac events, in diabetic and non-diabetic patients, regardless of access site (TFA or TRA).


Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Calcificação Vascular , Aterectomia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/terapia
19.
J Periodontol ; 92(7): 968-974, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33151545

RESUMO

BACKGROUND: The aim of the present study is to assess the ability of procalcitonin (PCT) to differentiate between periodontal health and Stage II and III periodontitis. We further assessed, if PCT can reflect early bacteremia induced by non-surgical periodontal treatment (NSPT). METHODS: Sixty-four systemically healthy individuals were divided into Group I, periodontally healthy, and Group II, Stage II and III periodontitis. NSPT was done for both the groups. Standardized serum and salivary samples were obtained and analyzed for PCT levels using highly sensitive double antibody sandwich enzyme-linked immunosorbent assay at baseline and 2 weeks. In addition, the serum levels of PCT were recorded at immediate and 1-hour post-NSPT. RESULTS: Mean PCT levels (saliva = 0.03 ng/mL and serum = 0.05 ng/mL) in periodontally healthy group were considerably lower than that in the periodontitis group (saliva = 0.22 ng/mL and serum = 1.85 ng/mL) with significant intergroup comparison at P < 0.001. Post NSPT the mean serum PCT values increased from 1.854 ng/mL to 1.871 ng/mL at the immediate interval and remained at 0.879 ng/mL after 2 weeks at P < 0.001. Spearman correlation showed highly significant positive correlation between serum and salivary PCT values to clinical attachment level (CAL) at P < 0.001 and rho = 0.78 and 0.75, respectively. Linear regression model showed serum PCT to be a significant predictor for CAL. CONCLUSION: Screening for serum PCT levels in patients with periodontitis could act not only as a guide to assess the bacterial load and use of antibiotics but also as a predictor for CAL loss in patients with periodontitis.


Assuntos
Bacteriemia , Periodontite , Bacteriemia/diagnóstico , Humanos , Periodontite/diagnóstico , Pró-Calcitonina , Saliva
20.
Int J Infect Dis ; 102: 566-570, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33160064

RESUMO

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a source of significant morbidity and death worldwide, and effective treatments are urgently needed. Clinical trials have focused largely on direct antiviral therapies or on immunomodulation in patients with severe manifestations of COVID-19. One therapeutic approach that remains to be clinically investigated is disruption of the host-virus relationship through amino acid restriction, a strategy used successfully in the setting of cancer treatment. Arginine is an amino acid that has been shown in nonclinical studies to be essential in the life cycle of many viruses. Therefore, arginine depletion may be an effective therapeutic approach against SARS-CoV-2. Several arginine-metabolizing enzymes in clinical development may be a viable approach to induce a low arginine environment to treat COVID-19 and other viral diseases. Herein, we explore the rationale for arginine depletion as a therapeutic approach for COVID-19.


Assuntos
Arginina/deficiência , COVID-19/metabolismo , COVID-19/terapia , SARS-CoV-2/metabolismo , Animais , COVID-19/virologia , Humanos , SARS-CoV-2/genética
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