Αρχειοθήκη ιστολογίου

Τετάρτη 23 Νοεμβρίου 2022

Outcomes of Periodontal therapy in Rheumatoid Arthritis: the OPERA feasibility randomised trial

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Abstract

Background

Periodontitis is independently associated with rheumatoid arthritis (RA); however, there are limited data on whether periodontal treatment improves overall RA disease activity. We conducted a pilot feasibility randomised controlled clinical trial to test whether intensive periodontal therapy reduces RA disease activity in patients with active RA and periodontitis.

Methods

The following inclusion criteria were applied: patients with RA and periodontitis, aged 18+, stable on treatment with DMARDs for ≥ 3 months, disease activity score (DAS28) ≥3.2, and DAS28 >5.1 only if patient unwilling to take biologics. Participants meeting the inclusion criteria were randomised to immediate intensive periodontal therapy or to delayed therapy (control group) administered by a dental hygienist in a secondary care setting. Data were collected at baseline, 3 and 6 months of follow-up. Participants randomised to the control group (delayed therapy) received the standard of care for the duration of the trial, including oral hygiene instructions delivered by a dental hygienist, and the same periodontal therapy as the intervention group after study completion (i.e., 6 months after randomisation). The periodontal inflammation surface area (PISA) was calculated using clinical attachment loss, periodontal probing pocket depth and bleeding on probing. Cumulative pro bing depth was also measured. We examined the effect of periodontal therapy on periodontal outcomes and on clinical markers of disease activity in RA, as measured by the DAS28-CRP score and musculoskeletal ultrasound grey scale and power Doppler scores.

Results

A total of 649 patients with RA were invited to participate in the study. Of these, 296 (46%) RA patients consented to participate in the screening visit. A sample of 201 were assessed for eligibility, of whom 41 (20%) did not meet RA inclusion criteria and 100 (50%) did not meet periodontal disease (PD) criteria. Amongst 60 (30%) eligible participants, 30 were randomised to immediate periodontal therapy and 30 were allocated to the control group. The loss to follow-up was 18% at the end of the trial. There were no major differences with regards to baseline characteristics between groups. Periodontal therapy was associated with reduced periodontal inflamed surface area, cumulative probing depths, RA disease activity scores and ultrasound scores over the course of the trial. There was no change in clinical attachment loss.

Conclusions

Overall, the trial was feasible and acceptable to study participants. Recruitment and satisfactory retention into a randomised controlled trial on the effect of periodontal treatment on RA patients is possible, albeit challenging. In this feasibility study of patients with RA and periodontitis, periodontal treatment resulted in significant improvements in periodontal disease outcomes and overall RA disease activity, although complete resolution of periodontal inflammation was difficult to achieve in some cases.

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Implant deformation and implant–abutment fracture resistance after standardized artificial aging: An in vitro study

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Abstract

Background and purpose

Zirconia abutments have been widely adopted in clinical implant practice. The unique mechanical properties of zirconia may significantly affect the long-term prognosis of implant treatments. The purpose of this study was to investigate the influence of abutment material on implant deformation and fracture resistance of internal conical connection implant–abutment complexes of two diameters after standardized artificial aging.

Materials and methods

Thirty original abutments (one-piece titanium, one-piece zirconia, zirconia with alloy base) with two diameters (regular, narrow) were connected to internal conical connection implants and subjected to a standardized artificial aging process consisting of thermal cycling and mechanical cyclic loading. Microcomputed tomography (μCT) scans of implant bodies were performed before and after aging. 3-dimensional images of implant bodies were generated from the μCT scans and aligned for before and after aging to calculate the volumetric deformation amount. Finally, fracture resistance was measured using a mechanical static loading test for the surviving aged and 30 brand-new specimens.

Results

All specimens survived artificial aging. No significant difference in implant deformation was found in the regular groups (p = 0.095). In narrow groups, the one-piece zirconia group showed significantly less deformation (p < 0.0001). For fracture resistance, no significant decrease was observed after aging in any group (p > 0.05). One-piece zirconia abutments showed significantly lower strength than the other two materials for both diameters (p < 0.0001).

Conclusions

In the regular diameter system, abutment material had no significant influence on the tested mechanical property degradation after simulated long-term oral use. The mechanical performance of narrow diameter one-piece zirconia abutments differed from the other two materials. For optimal performance, one-piece zirconia abutments should be adopted only in anterior regions.

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Characterization of FA1654: a putative DPS protein in Filifactor alocis

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Abstract

The survival/adaptation of Fillifactor alocis, a fastidious gram positive asaccharolytic anaerobe, to the inflammatory environment of the periodontal pocket requires an ability to overcome oxidative stress. Moreover, its pathogenic characteristics are highlighted by its capacity to survive in the oxidative-stress microenvironment of the periodontal pocket and a likely ability to modulate the microbial community dynamics. There is still a significant gap in our understanding of its mechanism of oxidative stress resistance and its impact on the virulence and pathogenicity of the microbial biofilm. Coinfection of epithelial cells with F.alocis and P.gingivalis, resulted in the upregulation of several genes including HMPREF0389_01654(FA1654). Bioinformatics analysis indicates that FA1654 has a "di-iron binding domain", and could function as a DNA Starvation and Stationary Phase Protection (DPS) protein. We have further characterized the FA1654 protein to deter mine its role in oxidative stress resistance in F.alocis. In the presence of hydrogen peroxide induced oxidative stress there was a ∼1.3 fold upregulation of the FA1654 gene in F.alocis. Incubation of the purified FA1654 protein with DNA in the presence of hydrogen peroxide and iron resulted in the protection of the DNA from Fenton-mediated degradation. Circular Dichroism (CD) and Differential Scanning Flourimetry (DSF) studies have documented the intrinsic ability of rFA1654 protein to bind iron, however the rFA1654 protein is missing the intrinsic ability to reduce hydrogen peroxide. Collectively, the data may suggest that FA1654 in F.alocis is involved in oxidative stress resistance via an ability to protect against Fenton-mediated oxidative stress-induced damage.

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Study on the Use of Ozone Water as a Chemical Decontamination Agent for Antineoplastic Drugs in Clinical Settings

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Abstract
The exposure of healthcare workers to antineoplastic drugs in hospitals has been recognized to be harmful. To minimize the risk of exposure, the removal of these drugs from work environments, such as compounding facilities, has been recommended. In our previous paper, the degradation and inactivation efficacy of ozone water, which is being introduced into Japanese hospitals as a chemical decontamination agent, was reported for its effects on typical antineoplastic drugs (gemcitabine, irinotecan, paclitaxel). This article aims to further investigate the efficacy of ozone water for eight antineoplastic drugs to clarify its application limitations. A small amount (medicinal ingredient: typically ca. 1.5 μmol) of formulation containing 5-fluorouracil, pemetrexed, cisplatin, oxaliplatin, cyclophosphamide, ifosfamide, doxorubicin, or docetaxel was mixed with 50 mL of ozone water (~8 mg/L), and the resulting solu tions were analyzed by high-performance liquid chromatography over time to observe the degradation. Consequently, the ozonation was overall effective for the degradation of the drugs, however this varied depending on the chemical structures of the drugs and additives in their formulations. In addition, after the parent drugs were completely degraded by the ozonation, the degradation mixtures were subjected to 1H nuclear magnetic resonance spectroscopy and evaluated for mutagenicity against Salmonella typhimurium strains and cytotoxicity against human cancer cells. The degradation mixtures of cisplatin and ifosfamide were mutagenic while those of the other drugs were non-mutagenic. Further, the ozonation resulted in clear decreases of cytotoxicity for 5-fluorouracil, oxaliplatin, and doxorubicin, but increases of cytotoxicity for pemetrexed, cisplatin, cyclophosphamide, and ifosfamide. These results suggest that the ozone water shoul d be restrictedly used according to the situation of contamination in clinical settings because the ozonation enhances toxicity depending on the drug even if degradation is achieved.
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An HPV-Vaccinated Patient With Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

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This case report describes an extremely early-onset case of hu man papillomavirus–positive oropharyngeal squamous cell carcinoma in a Norwegian woman in her early 20s.
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Use of the Toxicity Index in Evaluating Adverse Events in Anal Cancer Trials: Analysis of RTOG 9811 and RTOG 0529

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imageNovel toxicity metrics that account for all adverse event (AE) grades and the frequency of may enhance toxicity reporting in clinical trials. The Toxicity Index (TI) accounts for all AE grades and frequencies for categories of interest. We evaluate the feasibility of using the TI methodology in 2 prospective anal cancer trials and to evaluate whether more conformal radiation (using Intensity Modulated Radiation Therapy) results in improved toxicity as measured by the TI. Patients enrolled on NRG/RTOG 0529 or nonconformal RT enrolled on the 5-Fluorouracil/Mitomycin arm of NRG/RTOG 9811 were compared using the TI. Patients treated on NRG/RTOG 0529 had lower median TI compared with patients treated with nonconformal RT on NRG/RTOG 9811 for combined GI/GU/Heme/Derm events (3.935 vs 3.996, P=0.014). The TI methodology is a feasible method to assess all AEs of interest and may be useful as a composite metric for future efforts aimed at treatment de-escalation or escalation
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Predicting Factors for a Favorable Pathologic Response to Neoadjuvant Therapy in Esophageal Cancer

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imageBackground: Favorable pathologic response(FPR) is a significant predictor for improved survival following Neoadjuvant therapy(NAT) in esophageal and gastroesophageal cancer(GEJ). Preoperative prediction of FPR could modify treatment plans. No reliable method for predicting FPR exists. We sought to identify preoperative predicting factors for FPR. Materials and Methods: Retrospective analysis of patients with esophageal and GEJ cancer who underwent esophagectomy following (NAT). Univariate and multivariate analysis was used to identify preoperative predicting factors for FPR. A comparison of Tumor Regression Grade(TRG) was used to assess treatment response on overall survival(OS). Results: Out of 121 patients, 82(67.8%) had neoadjuvant chemoradiation. FPR was observed in 60(49.6%). Female sex, Radiation therapy(RT), squamous cell carcinoma(SCC), lack of signet ring feature, and FDG avidity posttreatment were associated with FPR on univariate analysis. RT and SCC were associated with FPR (OR=3.9 and 4.0, respectively) on multivariate analysis. OS was lower among patients who did not achieve FPR to NAT(P=0.027). Conclusions: FPR is a predictor of improved OS. SCC and radiation therapy-based protocol were identified as major prediction factors of FPR in patients with esophageal and GEJ cancers.
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Preoperative Computed Tomography Radiomics Analysis for Predicting Receptors Status and Ki-67 Levels in Breast Cancer

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imageBackground: To assess the prediction performance of preoperative chest computed tomography (CT) based radiomics features for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2+), and Ki-67 status of breast cancer. Materials and Methods: This study enrolled 108 breast cancer patients who received preoperative chest CT examinations in our institution from July 2018 to January 2020. Radiomics features were separately extracted from nonenhanced, arterial, and portal-venous phases CT images. The least absolute shrinkage and selection operator logistic regression was used for feature selection. Then the radiomics signatures for each phase and a combined model of 3 phases were built. Finally, the receiver operating characteristic curves and calibration curves were used to confirm the performance of the radiomics signatures and combined model. In addition, the decision curves were performed to estimate the clinical usefulness of the combined model. Results: The 20 most predictive features were finally selected to build radiomics signatures for each phase. The combined model achieved the overall best performance than using either of the nonenhanced, arterial and portal-venous phases alone, achieving an area under the receiver operating characteristic curve of 0.870 for ER+ versus ER−, 0.797 for PR+ versus PR−, 0.881 for HER2+ versus HER2−, and 0.726 for Ki-67. The decision curve demonstrated that the CT-based radiomics features were clinically useful. Conclusion: This study indicated preopreative chest CT radiomics analysis might be able to assess ER, PR, HER2+, and Ki-67 status of breast cancer. The findings need further to be verified in future larger studies.
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Identifying vulnerable populations with symptomatic cholelithiasis at risk for increased health care utilization

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imageBACKGROUND Gallstones are a common problem in the United States with many patients suffering from symptomatic cholelithiasis (SC). Patients with SC may first present to the emergency department ED) and are often discharged for elective follow-up; however, it is unknown what system and patient factors are associated with increased risk for ED revisits. This study aimed to assess longitudinal ED utilization and cholecystectomy for patients with SC and identify patient, geographic, and hospital characteristics associated with ED revisits, specifically race/ethnicity and insurance status. METHODS Patients discharged from the ED with SC between July 1, 2016, and December 31, 2017, were identified from California administrative databases and followed for 1 year. Emergency department revisits and cholecystectomy after discharge were examined using logistic regression, clustering standard errors by hospital. Models adjusted for patient, geographic, and hospital variables using census and hospital administrative data. RESULTS Cohort included 34,427 patients who presented to the ED with SC and were discharged. There were 18.8% of the patients that had one or more biliary-related ED revisits within 1 year. In fully adjusted models, non-Hispanic Black patients had higher odds for any ED revisit (adjusted odds ratio 1.23; 95% confidence interval, 1.09–1.39) and for two more ED revisits (adjusted odds ratio 1.48; 95% confidence interval, 1.20–1.82). Insurance type was also associated with ED revisits. CONCLUSION Non-Hispanic Black patients experienced higher utilization of health care resources for SC after adjusting for other patient, geographic and hospital variables. Strategies to mitigate these disparities may include the development of standardized protocols regarding the follow-up and education for SC. Implementation of such strategies can ensure equitable treatment for all patients. LEVEL OF EVIDENCE Prognostic and Epidemiological; Level III.
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Epidemiology and outcomes of multiple organ dysfunction syndrome following pediatric trauma

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imageBACKGROUND Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database. METHODS We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status. RESULTS Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1–43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4–5.3). CONCLUSION Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma. LEVEL OF EVIDENCE Prognostic and Epidemiological; Level III.
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