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Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer.
Get PDFBACKGROUND
Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing.
METHODS
Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS.
RESULTS
A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Advanced diseases and metastases to other organs would be fit for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS.
CONCLUSION
ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC
Different trajectories of post-concussive symptom subscales after pediatric mild traumatic brain injury:: Data from a prospective longitudinal study
No full textPurpose: The aim of this study was to investigate the trajectory of parent-rated post-concussive symptoms (PCS), attentional performance and participation within 6 months in children after mild traumatic brain injury (mTBI).
Methods: For this prospective longitudinal study, we included data on 64 children after mTBI and 57 healthy control children (age 8–16 years). Parents rated PCS using the Post-Concussion Symptom Inventory (PCSI) immediately (T0), 1 week (T1), and 3–6 months after injury (T2). Attentional performance (alertness, selective and divided attention) was measured using the Test of Attentional Performance (TAP) at T1 and T2 and participation was measured using the Child and Adolescent Scale of Participation (CASP) at T2.
Results: Friedman tests showed different trajectories of PCS subscales over time: Compared to pre-injury level, the amount of somatic and cognitive PCS was still elevated at T1, while emotional PCS at T1 were already comparable to pre-injury level. The rating of sleep-related PCS at T2 was significantly elevated compared to the preinjury rating. Quade ANCOVAs indicated group differences in PCS subscales between patients and controls at T1, but not at T2. Patients and controls showed a similar performance in tests of attention at T1 and T2, but parental rating of participation at school was significantly reduced. Although cognitive PCS and attention were not correlated, there were significantly negative Spearman correlations between participation at home and preinjury and concurrent PCS at T2.
Conclusions: Our data imply that sleep-related PCS are still elevated weeks after injury and are thus a target for interventions after mTBI
Beyond Feminism? Jineolojî and the Kurdish Women’s Freedom Movement.
No full textJineolojî, the women's science proposed and developed by the Kurdish Women's Freedom Movement, has become central to its transnational organizing both in the Middle East and in Europe and the Americas. Activists in the Kurdish women's movement critique positivist and androcentric forms of knowledge production as well as liberal feminism. They instead propose Jineolojî, which aims to rediscover women's histories and restore women's central place in society. Based on a series of interviews with Kurdish women involved in developing Jineolojî, this article first situates Jineolojî within wider transnational and decolonial feminist approaches and then draws out the main ideas constituting Jineolojî. We focus on the ways Jineolojî speaks to ongoing discussions within transnational feminist knowledge production. Our article critically assesses the claim of Kurdish women activists who present Jineolojî as a new science and paradigm that goes beyond feminism while developing our argument that Jineolojî represents an important continuation of critical interventions made by marginalized women activists and academics transnationally. Moreover, our article illustrates that Jineolojî provides a helpful ideological underpinning for and epistemology of Kurdish women's political struggle for gender-based equality and justice
Surface roughness, optical properties, and microhardness of additively and subtractively manufactured CAD-CAM materials after brushing and coffee thermal cycling.
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To evaluate the surface roughness, optical properties, and microhardness of additively or subtractively manufactured CAD-CAM materials after simulated brushing and coffee thermal cycling.
MATERIAL AND METHODS
Two additively manufactured resins (Crowntec, CT and VarseoSmile Crown Plus, VS) and 3 subtractively manufactured materials (a reinforced composite (Brilliant Crios, BC), a polymer-infiltrated ceramic network (Enamic, VE), and a feldspathic ceramic (Mark II, VM)) were used to fabricate disk-shaped specimens (Ø10×1-mm) (n = 10). Surface roughness, Vickers microhardness, and color coordinates were measured after polishing, while surface roughness was also measured before polishing. Specimens were then subjected to 25000 cycles of brushing and 10000 cycles of coffee thermal cycling, and measurements were repeated after each time interval. Color difference (ΔE00 ) and relative translucency parameter (RTP) were calculated. Robust analysis of variance test was used to evaluate surface roughness, ΔE00 , and RTP data, while generalized linear model analysis was used for microhardness data (α = .05).
RESULTS
Material type and time interval interaction affected tested parameters (P≤.002). In addition, material type affected all parameters (P<.001) other than surface roughness (P = .051), and time interval affected surface roughness and microhardness values (P<.001). Tested materials mostly had their highest surface roughness before polishing (P≤.026); however, there was no clear trend regarding the roughness of materials within different time intervals along with ΔE00 and RTP values within materials or time intervals. VS and CT had the lowest microhardness regardless of the time interval, while the remaining materials were listed as VM, VE, and BC in decreasing order (P<.001). Coffee thermal cycling only reduced the microhardness of VM (P<.001).
CONCLUSIONS
Tested additively manufactured resins can be considered more susceptible to simulated brushing and coffee thermal cycling than the other materials, given the fact that their surface roughness and ΔE00 values were higher than previously reported acceptability thresholds and because they had the lowest microhardness after all procedures were complete. This article is protected by copyright. All rights reserved
Disease resolution following treatment of peri-implant diseases: A systematic review.
No full textThe aim of this PRISMA-compliant systematic review was to analyze the evidence pertaining to disease resolution after treatment of peri-implant diseases (PROSPERO: CRD42022306999) with the following PICO question: what is the rate of disease resolution following non-surgical and surgical therapy for peri-implant diseases in adult human subjects? A literature search to identify studies that fulfilled a pre-established eligibility criteria was conducted. Data on primary therapeutic outcomes, including treatment success, rate of disease resolution and/or recurrence, as well as a variety of secondary outcomes was extracted and categorized. Fifty-five articles were included. Few studies investigated the efficacy of different non-surgical and surgical therapies to treat peri-implant diseases using a set of pre-defined criteria and with follow-up periods of at least one year. The definition of treatment success and outcomes of disease resolution differed considerably among the included studies. Treatment of peri-implant mucositis was most commonly reported to be successful in arresting disease progression for ≤60% of the cases, whereas most studies on peri-implantitis treatment reported disease resolution occurring in <50% of the fixtures. In conclusion, disease resolution is generally unpredictable and infrequently achieved after the treatment of peri-implant diseases. A great variety of definitions have been used to define treatment success. Notably, percentages of treatment success and disease resolution were generally underreported. The use of standardized parameters to evaluate disease resolution should be considered an integral component in future clinical studies
Influence of the sintering atmosphere on the physico-chemical properties and the osteoclastic resorption of β-tricalcium phosphate cylinders.
No full textOne of the most widely used materials for bone graft substitution is β-Tricalcium phosphate (β-TCP; β-Ca3(PO4)2). β-TCP is typically produced by sintering in air or vacuum. During this process evaporation of phosphor (P) species occurs, leading to the formation of a calcium-rich alkaline layer. It was recently shown that the evaporation of P species could be prevented by co-sintering β-TCP with dicalcium phosphate (DCPA; CaHPO4; mineral name: monetite). The aim of this study was to see how a change of sintering atmosphere could affect the physico-chemical and biological properties of β-TCP. For this purpose, three experimental groups were considered: β-TCP cylinders sintered in air and subsequently polished to remove the surface layer (control group); the same polished cylinders after subsequent annealing at 500°C in air to generate a calcium-rich alkaline layer (annealed group); and finally, β-TCP cylinders sintered in a monetite-rich atmosphere and subsequently polished (monetite group). XPS analysis confirmed that cylinders from the annealed group had a significantly higher Ca/P molar ratio at their surface than that of the control group while this ratio was significantly lower for the cylinders from the monetite group. Sintering β-TCP in the monetite-rich atmosphere significantly reduced the grain size and increased the density. Changes of surface composition affected the activity of osteoclasts seeded onto the surfaces, since annealed β-TCP cylinders were significantly less resorbed than β-TCP cylinders sintered in the monetite-rich atmosphere. This suggests that an increase of the surface Ca/P molar ratio leads to a decrease of osteoclastic resorption. STATEMENT OF SIGNIFICANCE: Minimal changes of surface and bulk (< 1%) composition have major effects on the ability of osteoclasts to resorb β-tricalcium phosphate (β-TCP), one of the most widely used ceramic for bone substitution. The results presented in this study are thus important for the calcium phosphate community because (i) β-TCP may have up to 5% impurities according to ISO and ASTM standards and still be considered to be "pure β-TCP", (ii) β-TCP surface properties are generally not considered during biocompatibility assessment and (iii) a rationale can be proposed to explain the various inconsistencies reported in the literature on the biological properties of β-TCP
Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study.
No full textAIMS
Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multi-centre cohort of contemporary ACS patients.
METHODS AND RESULTS
SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Secondary endpoints were defined as any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p<0.001) and thrombus (60% vs 35%, p<0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE (PSM adjusted HR 0.70, 95% CI 0.49-0.99), but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups.
CONCLUSION
In patients with ACS undergoing PCI and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks
European Respiratory Society Clinical Practice Guideline on symptom management for adults with serious respiratory illness.
No full textRespiratory symptoms are ubiquitous and impair health-related quality of life in people with respiratory disease. This European Respiratory Society (ERS) task force aimed to provide recommendations for symptomatic treatment in people with serious respiratory illness.The ERS task force comprised 16 members, including representatives of people with serious respiratory illness and informal caregivers. Seven questions were formulated, six in the "Population, Intervention, Comparison, Outcome" (PICO) format, which were addressed with full systematic reviews and evidence assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). One question was addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations.To treat symptoms in people with serious respiratory illness, the task force suggests the use of graded exercise therapy (conditional recommendation, low certainty of evidence); and suggests the use of a multicomponent services, handheld fan and breathing techniques (conditional recommendations, very low certainty of evidence). The task force suggests not to use opioids (conditional recommendation, very low certainty of evidence); and suggests either administering or not administering supplemental oxygen therapy (conditional recommendation, low certainty of evidence). The task force suggests that needs assessment tools may be used as part of a comprehensive needs assessment, but do not replace patient centred care and shared decision making (conditional recommendation, low certainty of evidence). The low certainty of evidence, modest impact of interventions on patient-centred outcomes, and absence of effective strategies to ameliorate cough highlight the need for new approaches to reduce symptoms and enhance wellbeing for individuals who live with serious respiratory illness
Effect of preparation design and endodontic access on fracture resistance of zirconia overlays in mandibular molars: An in vitro study.
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To evaluate the fracture resistance of zirconia overlays, considering various preparation designs and the presence of endodontic access.
MATERIALS AND METHODS
Ninety translucent zirconia (5Y-PSZ) overlay restorations were divided into six groups (n = 15/group) based on different preparation designs, with and without endodontic access: chamfer margin 4 mm above the gingival level without (group 1) and with endodontic access (group 2); margin 2 mm above the gingival level without (group 3) and with endodontic access (group 4); overlay with no chamfer margin without (group 5) and with endodontic access (group 6). Restorations were bonded to mandibular first molar resin dies, and the groups with endodontic access were sealed with flowable resin composite. All restorations underwent 100,000 cycles of thermal cycling between 5°C and 55°C, followed by loading until fracture. Maximum load and fracture resistance were recorded. ANOVA with Tukey post-hoc tests were used for statistical comparison (α < 0.05).
RESULTS
Fracture resistance significantly varied among overlay designs with and without endodontic access (p < 0.001), except for the no-margin overlays (groups 5 and 6). Overlays with a 2 mm margin above the gingival margin with endodontic access (group 4) exhibited significantly higher fracture resistance compared to both the 4-mm supragingival (group 2) and no-margin (group 6) designs, even when compared to their respective intact groups (groups 1 and 5). There were no significant differences between the no-margin and 4-mm supragingival overlays.
CONCLUSION
The more extensive zirconia overlay for mandibular molars is the first choice since the 2 mm margin above the gingival level design withstood considerable loads even after undergoing endodontic access. A no-margin overlay is preferred over the 4-mm supragingival design as it preserves more tooth structure and there was no outcome difference, irrespective of endodontic access. Caution is warranted in interpreting these findings due to the in vitro nature of the study
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