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A human meniscus explant model for studying early events in osteoarthritis development by proteomics

J Orthop Res. 2023 May 23. doi: 10.1002/jor.25633. Online ahead of print.

ABSTRACT

Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We therefore sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee-healthy donors. The meniscal body was cut into vertical slices, and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every three days up to day 21 and liquid chromatography-mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed-effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1ß increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM)+tumor necrosis factor (TNF) and TNF+interleukin-6 (IL6)+sIL6R treatments, and analysis of semi-tryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development. This article is protected by copyright. All rights reserved.

PMID:37218349 | DOI:10.1002/jor.25633

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Efficacy and safety of montelukast adjuvant therapy in adults with cough variant asthma: A systematic review and meta-analysis

Clin Respir J. 2023 May 22. doi: 10.1111/crj.13629. Online ahead of print.

ABSTRACT

BACKGROUND: Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can significantly and safely treat adults with cough variant asthma (CVA) remains inconclusive.

AIMS: This meta-analysis systematically evaluated the efficacy and safety of montelukast as an adjuvant treatment for adults with CVA.

MATERIALS AND METHODS: Randomized controlled trials (RCTs) on montelukast combined with inhaled corticosteroids (ICS) and long-acting β2 agonists (LABAs) to treat CVA in adults, from inception to March 6, 2023, were retrieved from the CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, and Web of Science databases and Clinical Trials website. Review Manager (version 5.4) and Stata (version 15.0) were used to conduct the meta-analysis.

RESULTS: A total of 15 RCTs were ultimately included in the meta-analysis. It was established that montelukast as adjuvant therapy raised the total effective rate (RR = 1.20, 95% confidence interval [CI] [1.13, 1.27], P < 0.01) and improved the FEV1% (SMD = 0.91, 95% CI [0.40, 1.41], P < 0.01), PEF% (SMD = 0.63, 95% CI [0.38, 0.88], P < 0.01), FEV1 (SMD = 1.15, 95% CI [0.53, 1.77], P < 0.01), PEF (SMD = 0.64, 95% CI [0.42, 0.86], P < 0.01), and FEV1/FVC% (SMD = 0.76, 95% CI [0.51, 1.01], P < 0.01) and reduced the recurrence rate (RR = 0.28, 95% CI [0.15, 0.53], P < 0.01). The incidence of adverse reactions was higher in the montelukast auxiliary group compared to the control group but with no statistical difference (RR = 1.32, 95% CI [0.89, 1.96], P = 0.17).

CONCLUSION: Existing evidence indicated that the use of montelukast as an adjuvant therapy had therapeutic efficacy superior to ICS + LABA alone for the treatment of adult patients with CVA. However, further research is needed, especially a combination of high-quality long-term prospective studies and carefully designed RCTs.

PMID:37218346 | DOI:10.1111/crj.13629

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Impact of erosion and aging simulation on chairside materials

Microsc Res Tech. 2023 May 22. doi: 10.1002/jemt.24361. Online ahead of print.

ABSTRACT

This study investigates the influence of acid exposure and thermocycling simulating erosion tooth wear, on the optical properties and surface roughness of chairside materials. Resin-ceramic, lithium disilicate, premium zirconium oxide and resin composite material comprise the materials tested. To simulate the dental erosion and aging, specimens from each material were immersed in hydrochloric acid, while the thermocycling procedure included 10,000 cycles. The translucency, the color differences and the surface roughness were calculated. The materials phase composition was tested using X-ray diffraction analysis to evaluate T-M phase transformation. The CIEDE2000 color difference and the translucency parameter were tested different significantly among groups. Data were statistically analyzed via independent samples t-test, and paired samples t-test. The thermocycling procedure and the exposure to the acid solution had different effect on the surface roughness of CAD/CAM materials. The present result demonstrated the negative effect the acid exposure has on the zirconia material in terms of color difference. However, no color differences over the threshold of acceptability were recorded after the thermocycling procedure. Both polymer materials exhibit an increase of the surface roughness when they were immersed in acid but they did not display an increase in roughness when they were thermocycled.

PMID:37218339 | DOI:10.1002/jemt.24361

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Effectiveness of technology-based interventions compared with other non-pharmacological interventions for relieving procedural pain in hospitalized neonates: a systematic review

JBI Evid Synth. 2023 May 23. doi: 10.11124/JBIES-22-00179. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this review was to evaluate the effectiveness of technology-based interventions for relieving procedural pain among hospitalized neonates compared with other non-pharmacological interventions.

INTRODUCTION: Neonates who require hospital care often experience acute pain during medical procedures. The current best practice for relieving pain in neonates is the use of non-pharmacological interventions, such as oral solutions or intervention-based human touch. Technological solutions (eg, games, eHealth applications, mechanical vibrators) have become more commonplace in pediatric pain management over recent years. However, there is a sizeable knowledge gap concerning how effective technology-based interventions are for relieving pain in neonates.

INCLUSION CRITERIA: This review considered experimental trials that include technology-based, non-pharmacological interventions for relieving procedural pain among hospitalized neonates. The primary outcomes of interest include pain response to a procedure measured by a pain assessment scale validated for neonates, behavioral indicators, and changes in physiological indicators.

METHODS: The search strategy aimed to identify both published and unpublished studies. PubMed MEDLINE (PubMed), CINAHL (EBSCOhost), Scopus, Cochrane Central Register of Controlled Trials, MedNar, and EBSCO Open Dissertations databases were searched for studies published in English, Finnish, or Swedish. Critical appraisal and data extraction were conducted by 2 independent researchers who adhered to JBI methodology. Meta-analysis could not be performed due to considerable heterogeneity in the studies; as a result, the findings are presented narratively.

RESULTS: A total of 10 randomized controlled trials involving 618 children were included in the review. The staff members delivering the interventions and the outcome assessors were not blinded in all of the studies, which introduced a potential risk of bias. The presented technology-based interventions were diverse, including laser acupuncture, noninvasive electrical stimulation of acupuncture points, robot platform, vibratory stimulation, recorded maternal voice, and recorded intrauterine voice. In the studies, pain was measured using validated pain scales, behavioral indicators, and physiological variables. In the studies in which pain was assessed with a validated pain measure (N=8), technology-based pain relief was significantly more effective than the comparator in 2 studies, whereas no statistically significant differences were observed in 4 studies and the technology-based intervention was less effective than the comparator in 2 studies.

CONCLUSIONS: The effectiveness of technology-based interventions in relieving neonatal pain, either as a standalone method or in combination with another non-pharmacological method, was mixed. Further research is needed to provide reliable evidence on which technology-based, non-pharmacological pain relief intervention is most effective for hospitalized neonates.

A FINNISHLANGUAGE VERSION OF THE ABSTRACT OF THIS REVIEW IS AVAILABLE AS SUPPLEMENTAL DIGITAL CONTENT: [http://links.lww.com/SRX/A19].

PMID:37218335 | DOI:10.11124/JBIES-22-00179

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Efficacy and Safety of Trastuzumab Biosimilars in Combination with Pertuzumab

Gan To Kagaku Ryoho. 2023 May;50(5):615-618.

ABSTRACT

Although trastuzumab biosimilars have been approved based on clinical studies on their use as monotherapy or in combination with chemotherapy, clinical studies on their combination with pertuzumab are lacking. Data on the efficacy and safety of this combination are scarce. We evaluated the efficacy and safety of trastuzumab biosimilars in combination with pertuzumab. Progression-free survival was 10.5 months(95% confidence interval[CI]: 3.3-16.3)for a reference biological product and 8.7 months(2.1-not applicable)for biosimilars with a hazard ratio of 0.96(95%CI: 0.29-3.13, p=0.94); however, no statistically significant difference was observed. The incidence of adverse events was not significantly different between the reference biological product and biosimilars, and no increase was observed for any adverse events after switching to the biosimilars. The results of this study verify that a combination of trastuzumab biosimilars with pertuzumab is sufficiently effective and safe in clinical practice.

PMID:37218323

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Development of CAR-T Cells Effective against Solid Tumors

Gan To Kagaku Ryoho. 2023 May;50(5):577-583.

ABSTRACT

Traditionally, the 3 major standard treatments for cancers-surgery, chemotherapy, and radiation therapy-have been applied and have saved many lives. However, malignancies have been the leading cause of death in Japan for more than 40 years since 1981, and the trend is still accelerating. According to the statistics report from the Ministry of Health, Labour and Welfare, cancers accounted for 26.5% of all deaths in 2021, which means that about 1 in 3.5 of all deaths in Japan was due to cancers. Additionally, medical expenditure spent on the diagnosis and treatments for cancer patients have significantly increased, contributing to the pressure on the Japanese economy. Therefore, there is a demand to develop the novel technologies concerning diagnostic methods, effective treatment, and recurrence prevention of cancers. Chimeric antigen receptor(CAR)-T cell therapy has attracted much attention as the next generation of cancer immunotherapy following immune checkpoint blockade therapy, which was the subject of the 2018 Nobel Prize in Physiology or Medicine. CAR-T cell therapy was first approved in the United States in 2017, followed by the EU in 2018 and Japan in March 2019, after having demonstrated significant therapeutic efficacies against B-cell malignancies in clinical trials. However, current CAR-T cell therapies are not yet complete, and there still remain challenges to be overcome. In particular, it is one of the most important issues that current CAR-T cell therapies do not work effectively against solid cancers, which make up the majority of malignant tumors. This review provides an overview of the development toward establishing the next generation CAR-T cell therapy with therapeutic potential against solid cancers.

PMID:37218315

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Surgical Site Infection After Polymethyl Methacrylate Pedicle Screw Augmentation in Osteoporotic Spinal Vertebrae: A Series of 537 Cases

Int J Spine Surg. 2023 May 22:8474. doi: 10.14444/8474. Online ahead of print.

ABSTRACT

BACKGROUND: Retrospective observational study of prospectively collected outcomes.

OBJECTIVE: The use of transpedicular screws augmented with polymethyl methacrylate (PMMA) is an alternative for patients with osteoporotic vertebrae. To investigate whether using PMMA-augmented screws in patients undergoing elective instrumented spinal fusion (ISF) is correlated with an increased risk of infection and the long-term survival of these spinal implants after surgical site infection (SSI).

METHODS: We studied 537 consecutive patients who underwent ISF at some point within a 9-year period, involving a total of 2930 PMMA-augmented screws. Patients were classified into groups: (1) those whose infection was cured with irrigation, surgical debridement, and antibiotic treatment; (2) those whose infection was cured by hardware removal or replacement; and (3) those in whom treatment failed.

RESULTS: Twenty eight of the 537 patients (5.2%) developed SSI after ISF. An SSI developed after primary surgery in 19 patients (4.6%) and after revision surgery in 9 (7.25%). Eleven patients (39.3%) were infected with gram-positive bacteria, 7 (25%) with gram-negative bacteria, and 10 (35.7%) with multiple pathogens. By 2 years after surgery, infection had been cured in 23 patients (82.15%). Although there were no statistically significant differences in infection incidence between preoperative diagnoses (P = 0.178), the need to remove hardware for infection control was almost 80% lower in patients with degenerative disease. All screws were safely explanted while vertebral integrity was maintained. PMMA was not removed, and no recementing was done for new screws.

CONCLUSIONS: The success rate for treatment of deep infection after cemented spinal arthrodesis is high. Infection rate findings and the most commonly found pathogens do not differ between cemented and noncemented fusion. It does not appear that the use of PMMA in cementing vertebrae plays a pivotal role in the development of SSIs.

PMID:37217274 | DOI:10.14444/8474

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Does knowledge have a half-life? An observational study analyzing the use of older citations in medical and scientific publications

BMJ Open. 2023 May 22;13(5):e072374. doi: 10.1136/bmjopen-2023-072374.

ABSTRACT

OBJECTIVES: In the process of scientific progress, prior evidence is both relied on and supplanted by new discoveries. We use the term ‘knowledge half-life’ to refer to the phenomenon in which older knowledge is discounted in favour of newer research. By quantifying the knowledge half-life, we sought to determine whether research published in more recent years is preferentially cited over older research in medical and scientific articles.

DESIGN: An observational study employing a directed, systematic search of current literature.

DATA SOURCES: BMJ, PNAS, JAMA, NEJM, The Annals of Internal Medicine, The Lancet, Science and Nature were searched.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eight high-impact medical and scientific journals were sampled examining original research articles from the first issue of every year over a 25-year span (1996-2020). The outcome of interest was the difference between the publication year of the article and references cited, termed ‘citation lag’.

DATA EXTRACTION AND SYNTHESIS: Analysis of variance was used to identify significant differences in citation lag.

RESULTS: A total of 726 articles and 17 895 references were included with a mean citation lag of 7.5±8.4 years. Across all journals, >70% of references had been published within 10 years of the citing article. Approximately 15%-20% of referenced articles were 10-19 years old, and articles more than 20 years old were cited infrequently. Medical journals articles had references with significantly shorter citation lags compared with general science journals (p≤0.01). Articles published before 2009 had references with significantly shorter citation lags compared with those published in 2010-2020 (p<0.001).

CONCLUSIONS: This study found evidence of a small increase in the citation of older research in medical and scientific literature over the past decade. This phenomenon deserves further characterisation and scrutiny to ensure that ‘old knowledge’ is not being lost.

PMID:37217270 | DOI:10.1136/bmjopen-2023-072374

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Validating the InterVA-5 cause of death analytical tool: using mortality data from the Comprehensive Health and Epidemiological Surveillance System in Papua New Guinea

BMJ Open. 2023 May 22;13(5):e066560. doi: 10.1136/bmjopen-2022-066560.

ABSTRACT

OBJECTIVE: InterVA-5 is a new version of an analytical tool for cause of death (COD) analysis at the population level. This study validates the InterVA-5 against the medical review method, using mortality data in Papua New Guinea (PNG).

DESIGN AND SETTING: This study used mortality data collected from January 2018 to December 2020 in eight surveillance sites of the Comprehensive Health and Epidemiological Surveillance System (CHESS), established by the PNG Institute of Medical Research in six major provinces.

METHODS: The CHESS demographic team conducted verbal autopsy (VA) interviews with close relatives of the deceased, who died in communities within the catchment areas of CHESS, using the WHO 2016 VA instrument. COD of the deceased was assigned by InterVA-5 tool, and independently certified by the medical team. Consistency, difference and agreement between the InterVA-5 model and medical review were assessed. Sensitivity and positive predictive value (PPV) of the InterVA-5 tool were calculated with reference to the medical review method.

RESULTS: Specific COD of 926 deceased people was included in the validation. Agreement between the InterVA-5 tool and medical review was high (kappa test: 0.72; p<0.01). Sensitivity and PPV of the InterVA-5 were 93% and 72% for cardiovascular diseases, 84% and 86% for neoplasms, 65% and 100% for other chronic non-communicable diseases (NCDs), and 78% and 64% for maternal deaths, respectively. For infectious diseases and external CODs, sensitivity and PPV of the InterVA-5 were 94% and 90%, respectively, while the sensitivity and PPV of the medical review method were both 54% for classifying neonatal CODs.

CONCLUSION: The InterVA-5 tool works well in the PNG context to assign specific CODs of infectious diseases, cardiovascular diseases, neoplasms and injuries. Further improvements with respect to chronic NCDs, maternal deaths and neonatal deaths are needed.

PMID:37217264 | DOI:10.1136/bmjopen-2022-066560

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Prevalence of undiagnosed stage 3 chronic kidney disease in France, Germany, Italy, Japan and the USA: results from the multinational observational REVEAL-CKD study

BMJ Open. 2023 May 22;13(5):e067386. doi: 10.1136/bmjopen-2022-067386.

ABSTRACT

OBJECTIVES: REVEAL-CKD aims to estimate the prevalence of, and factors associated with, undiagnosed stage 3 chronic kidney disease (CKD).

DESIGN: Multinational, observational study.

SETTING: Data from six country-specific electronic medical records and/or insurance claims databases from five countries (France, Germany, Italy, Japan and the USA [two databases]).

PARTICIPANTS: Eligible participants (≥18 years old) had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements (calculated from serum creatinine values, sex and age) taken from 2015 onwards that were indicative of stage 3 CKD (≥30 and <60 mL/min/1.73 m2). Undiagnosed cases lacked an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before, and up to 6 months after, the second qualifying eGFR measurement (study index).

MAIN OUTCOME MEASURES: The primary outcome was point prevalence of undiagnosed stage 3 CKD. Time to diagnosis was assessed using the Kaplan-Meier approach. Factors associated with lacking a CKD diagnosis and risk of diagnostic delay were assessed using logistic regression adjusted for baseline covariates.

RESULTS: The prevalence of undiagnosed stage 3 CKD was 95.5% (19 120/20 012 patients) in France, 84.3% (22 557/26 767) in Germany, 77.0% (50 547/65 676) in Italy, 92.1% (83 693/90 902) in Japan, 61.6% (13 845/22 470) in the US Explorys Linked Claims and Electronic Medical Records Data database and 64.3% (161 254/250 879) in the US TriNetX database. The prevalence of undiagnosed CKD increased with age. Factors associated with undiagnosed CKD were female sex (vs male, range of odds ratios across countries: 1.29-1.77), stage 3a CKD (vs 3b, 1.81-3.66), no medical history (vs a history) of diabetes (1.26-2.77) or hypertension (1.35-1.78).

CONCLUSIONS: There are substantial opportunities to improve stage 3 CKD diagnosis, particularly in female patients and older patients. The low diagnosis rates in patients with comorbidities that put them at risk of disease progression and complications require attention.

TRIAL REGISTRATION: NCT04847531.

PMID:37217263 | DOI:10.1136/bmjopen-2022-067386