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It was assumed that only autogenous bone had appropriate osteoconductive and osteoindutive properties for bone regeneration, but this assumption has been challenged. Many studies have shown that synthetic biomaterials must be considered as the best choice for guided bone regeneration. The objective of this work is to compare the performances of nanohydroxyapatite/β-tricalcium phosphate (n-HA/β-TCP) composite and autogenous bone grafting in bone regeneration applications. The composite was characterized by scanning electron microscopy (SEM) and used as an allograft in bone defects formed in adult Wistar rats. The bone defects in the dorsal cranium were grafted with autogenous bone on one side and the n-HA/β-TCP composite on the other. Histomorphometry evaluation via different staining methods (Goldner trichrome, PAS, and Sirius red) and TRAP histochemistry were performed. Immunohistomorphometries of OPN, Cathepsin K, TRAP, acid phosphatase, VEGF, NFκ-β, MMP-2, MMP-9, and TGF-β were carried out. The RT-PCR method was also applied to to RANK-L , Osteocalcine , Alcaline Phosphatase , Osterix , and Runx2 . The results showed that for all morphometric evaluations with the different staining methods, histochemistry, and immunohistochemistry, VEGF and NFκ-β were higher in the n-HA/β-TCP composite group than in the autogenous bone graft group. The RT-PCR markers were higher in the autogenous bone group than in the n-HA/β-TCP composite group. The n-HA/β-TCP composite exhibited enhanced cell-matrix interactions in bone remodeling, higher adhesion, proliferation, and differentiation, and increased vascularization. These results suggest that the n-HA/β-TCP composite induces faster bone formation than autogenous bone grafting.

High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992)., Competing Interests: Declaration of interests X.L. reported personal/consulting fees from EMD Serono during the conduct of the study; personal or consulting fees from AstraZeneca, Spectrum Pharmaceuticals, Novartis, Eli Lilly, Boehringer Ingelheim, Janssen, Blueprint Medicines, Bayer, and Albion; grants from ArriVent, Eli Lilly, Boehringer Ingelheim, and Regeneron; and personal fees from AbbVie outside the submitted work. L.G.P.-A. reported consulting roles with AstraZeneca, Lilly, EMD Serono, Spectrum Pharmaceuticals, and Daiichi Sankyo/Eli Lilly; research funding from Lilly and Boehringer Ingelheim; leadership roles from Genomica and ALTUM Sequencing; speakers bureau from Merck & Co., Kenilworth, NJ, Bristol-Myers Squibb, Roche, Pfizer, Lilly, AstraZeneca, and the healthcare business of Merck KGaA, Darmstadt, Germany; travel/accommodations/expenses from Roche, AstraZeneca, Merck & Co., Kenilworth, NJ, Bristol-Myers Squibb, Pfizer, and Takeda; and honoraria from Roche, Lilly, Pfizer, Bristol-Myers Squibb, Merck & Co., Kenilworth, NJ, AstraZeneca, the healthcare business of Merck KGaA, Darmstadt, Germany, PharmaMar, Novartis, Celgene, Amgen, Sanofi, Ipsen, Servier, Bayer, Blueprint Medicines, Mirati Therapeutics, and Takeda outside the submitted work. J.V.M. reported an advisory role with Amgen outside the submitted work. S.V. reported consulting or advisory role from the healthcare business of Merck KGaA, Darmstadt, Germany, AbbVie, Bristol-Myers Squibb, AstraZeneca, Merck & Co., Kenilworth, NJ, and Roche; non-financial support from OSE Immunotherapeutics; and personal fees from Janssen and Puma Biotechnology outside the submitted work. C.C.G. reported a consulting/advisory role with Boehringer Ingelheim and travel/accommodations/expenses from Roche and Merck & Co., Kenilworth, NJ, outside the submitted work. E.F.S. reported an advisory/consultancy role (institution) with Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol-Myers Squibb, the healthcare business of Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, and Seattle Genetics; and research funding (institution) from Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca, and Bristol-Myers Squibb outside the submitted work. M.G. reported personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study; grants and personal fees from AstraZeneca; and personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, Bayer, Bristol-Myers Squibb, AbbVie, Takeda, Janssen, Roche, Sanofi, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novartis, and Blueprint outside the submitted work. R.V. reported research funding from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study; personal consulting fees from Janssen; personal speaker fees from Bristol-Myers Squibb and Takeda; personal speaker bureau fees from Amgen, Sanofi, Roche, and AstraZeneca; and travel fees from Pfizer Travel and Janssen outside the submitted work. D.V.B. reported advisory/consultancy honoraria from Roche, the healthcare business of Merck KGaA, Darmstadt, Germany, Bristol-Myers Squibb, AstraZeneca, Pfizer, Boehringer Ingelheim, and Takeda; and speaker honoraria from Roche, the healthcare business of Merck, KGaA, Darmstadt, Germany, Bristol-Myers Squibb, AstraZeneca, Pfizer, and Boehringer Ingelheim outside the submitted work. J.F.P. reported consulting/advisory roles with Roche, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck & Co., Kenilworth, NJ, and GlaxoSmithKline outside the submitted work. M.S. reported an advisory/consulting role with Roche, AstraZeneca, Bristol-Myers Squibb, and Merck & Co., Kenilworth, NJ, outside the submitted work. T.K. reported grants and personal fees from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Merck & Co., Kenilworth, NJ, and Kyowa Hakko Kirin; personal fees from Ono Pharmaceutical, Pfizer Japan, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, and Daiichi-Sankyo; and grants from the healthcare business of Merck KGaA, Darmstadt, Germany, outside the submitted work. Y.-C.K. reported honoraria from AstraZeneca, Roche, Boehringer Ingelheim, Merck & Co., Kenilworth, NJ, Pfizer, Ono, Bristol-Myers Squibb, Daiichi Sankyo, and Yuhan; and research funding from AstraZeneca, Roche, and Boehringer Ingelheim outside the submitted work. S.S.Y. reported honoraria from AstraZeneca, Roche, Boehringer Ingelheim, Merck & Co., Kenilworth, NJ, Pfizer, Ono Pharmaceutical, Bristol-Myers Squibb, Daiichi Sankyo, and Yuhan; and research funding from AstraZeneca, Roche, and Boehringer Ingelheim outside the submitted work. J.-Y.H. reported research funding from Hoffmann-La Roche, Ltd., Ono Pharmaceutical, Pfizer, and Takeda outside the submitted work. J.-H.K. reported honoraria from Roche, Boehringer Ingelheim, Merck & Co., Kenilworth, NJ, and Bristol-Myers Squibb; consulting roles with Roche, Boehringer Ingelheim, Merck & Co., Kenilworth, NJ, AstraZeneca, and Yuhan; speakers bureau for Pfizer, Merck & Co., Kenilworth, NJ, and Roche; and research funding from Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, and Yuhan outside the submitted work. Y.J.C. reported consulting/advisory role with Astella, Yuhan, Merck & Co., Kenilworth, NJ, Roche, and Chong Kun Dang outside the submitted work. C.S. is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany. D.J. is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, and holds stock in Merck KGaA, Darmstadt, Germany. H.V. is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany. R.B. is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, and holds stock in Merck KGaA, Darmstadt, Germany. G.O. was an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, at the time of the study and holds stock in Novartis. A.J. is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, and holds stock in Merck KGaA, Darmstadt, Germany. P.K.P. reported an advisory/consulting role from Takeda, Xencor, Janssen, CrownBio, Bicara, Mirati, and EMD Serono; and research funding (institution) from Bicara, Boehringer Ingelheim, and EMD Serono outside the submitted work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO 2 ) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group., Methods/design: In this study, 668 spontaneously-breathing preterm infants, born at 25 +0 to 29 +6  weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group., Discussion: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores., Trial Registration: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022., (© 2023. The Author(s).)

Background and Objective: A long-term tracheostomy can have significant negative effects on quality of life because it causes physical, functional, sensory, psychological, social, economic, and work impairments to the life of the individual. The objective of this study was to validate in Spanish a quality-of-life questionnaire for these patients., Materials and Methods: A psychometric validation study of a questionnaire in 45 patients over 18 years of age, with tracheostomy for six months, who understand Spanish and have a good understanding of the questions of the SF-36 questionnaire and a specific quality of life questionnaire for the patient with tracheostomy (TQOL-versión española). This Vquestionnaire is a modification and cultural adaptation into Spanish of the original English instrument named Tracheostomy Specific Quality of Life Questionnaire (TQOL). The two questionnaires (TQOL-versión española) and the SF-36 were completed 6 months after the tracheostomy and between 30 and 50 days after the first administration. The reliability, repeatability, and construct validity of the TQOL-versión española were evaluated. The construct validity was assessed by the correlation between the results of the TQOL-versión española and the dimensions of the SF-36 questionnaire., Results: The reliability of the TQOL-versión española measured by Cronbach's alpha coefficient was .814, with variation between items from .783 to .817 in the sample at 6 months and from .794 in the validation sample, with variation between items from .758 to .813. There was intraclass correlation for the total score of the scale using the concordance analysis of Bland-Altman and agreement for the individual questions with the McNemar symmetry test. There was also a good correlation between the scales of the TQOL-versión española and the dimensions of the S-F36., Conclusions: The TQOL-versión española showed good reliability, repeatability, and construct validity, therefore it is a useful tool to assess the impact on individual patients with a tracheostomy in place for more than 6 months, and to establish strategies at the healthcare and social levels to improve the quality of daily life., (Copyright © 2022 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Clostridioides difficile causes diarrhea and pseudomembranous colitis. Its diagnosis is made with glutamate dehydrogenase (GDH) or toxins A and B detection and is confirmed with nucleic acid amplification tests., Objective: To define if GDH determination is redundant to that of toxins., Methods: Retrospective, observational study in diarrheal stools of patients with suspected Clostridioides difficile infection. Toxins and GDH were determined by immunochromatography. Bayesian simulation was performed with likelihood ratios; a p-value < 0.05 was regarded as significant., Results: 329 GDH and toxin A and B results were analyzed. Clostridioides difficile infection prevalence was 18.2 %. Sensitivity and specificity of the GDH test were 0.90 and 0.89, respectively. Positive likelihood ratio was 8.9, and negative was 0.11., Conclusions: A negative GDH result considerably reduces the probability of infection but does not rule it out. Clostridioides difficile toxins detection may be necessary in institutions where nucleic acid amplification is not affordable or accessible., (Copyright: © 2020 Permanyer.)

Background: There is a need to examine the psychological traits that impact the "personal quality of life" and "personal well-being" of caregivers in the workplace., Purpose: This research proposes the resource-based reflective risk assessment model using a "at risk" framework to integrate mental health traits, producing a "portrait" of nursing quality of life and well-being., Methods: Cross-sectional surveys on the quality of work life of nurses in Australia and Mexico were used to collect data., Findings: Significant differences based on the ProQOL "at-risk" categories were found in all the 10 constructs with a similar pattern between the 2 countries. The proposed model was shown to be a useful framework for integrating mental health constructs that have a "draining" and "gaining" effect on nurses' well-being., Discussion: The proposed model provides framework for understanding nursing well-being as well an integrating structure to add additional constructs to construct a comprehensive portrait of nurses' quality work life and personal well-being., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Identification of membrane proteins expressed exclusively on tumor cells is a goal for cancer drug development. The receptor tyrosine kinase-like orphan receptor type 1 and 2 (ROR1/2), are type-I transmembrane proteins expressed in cancer but not in adult normal tissue. Here, we explore the prognostic role ROR1/2 expression on patient outcome., Methods: A systematic search of electronic databases identified publications exploring the effect of ROR1/2 on overall survival (OS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site or tumor type., Results: Twenty five studies met the inclusion criteria. ROR1 was associated with worse overall survival (HR 2.13, 95% confidence interval (CI) 1.62-2.80; P < 0.001) with subgroup analysis showing the strongest association between ROR1 and OS was in lung cancer. There was no significant difference between solid tumors and hematological malignancies (HR 2.15, 95% CI 1.52-3.06 vs. HR 2.02, 95% CI 1.46-2.84; subgroup difference P = 0.80). ROR2 was also associated with worse OS (HR 1.84, 95% CI 1.43-2.38; P < 0.001). There was no significant difference between disease sites although the highest association seen was in head and neck cancers (HR 3.19, 95% CI 1.13-8.97) and the lowest in gynecological cancers (HR 1.19, 95% CI 0.71-2.00; subgroup difference P = 0.10)., Conclusions: ROR1 and ROR2 expression is associated with adverse outcome in several tumors. ROR1/2 warrants study as a target for developmental therapeutics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A systematic review/meta-analysis of literature addressing a possible association between traumatic injury and onset of multiple sclerosis was conducted. Medline, Embase, Cochrane DSR, Ovid HealthStar, CINAHL, ISI Web of Science and Scopus were searched for analytical studies from 1950 to 2011. Two investigators independently reviewed articles for inclusion, assessing their quality using the Newcastle-Ottawa Scale. Of the 13 case-control studies included, 8 were moderate quality and 5 low; of the 3 cohort studies 2 were high and 1 moderate. Meta-analysis including moderate and low quality case-control studies produced a modest but significant odds ratio: 1.41 (95% confidence interval: 1.03, 1.93). However, when low quality studies were excluded, the resulting odds ratio was non-significant. Cohort studies produced a non-significant standardized incidence ratio of 1.00 (95% confidence interval: 0.86, 1.16). These findings support the conclusion that there is no association between traumatic injury and multiple sclerosis onset; more high quality cohort studies would help to confirm this observation.

Posterior glottic stenosis or interarytenoid fibrous adhesion is uncommon and has sometimes been misdiagnosed as cord paralysis. Laryngoscopy and laryngeal electromyography studies are the two main diagnostic aids. We present the case of a 63-year-old man under endotracheal intubation during 10 days after a cardiac procedure who was evaluated in our department for persistent dysphonia. The laryngoscopy showed a granuloma-like lesion in the posterior glottic space. During the microlaryngoscopy procedure, the osseous consistence of the interarytenoid lesion was observed. Laser surgery excision of the lesion was performed with good results. According to our review of the literature, this corresponds to the second case reported., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

When otologic procedures that involve tympanic membrane repairs are performed, biomaterials or biological tissues as normal as grafts are used. At the moment, biological material from the own patient is used with varying success rates. The procedure used and the patient's tissue repair capabilities tend to determine the outcome. We present a preliminary study on tympanic membrane perforation repairs using an autograft obtained by manipulating platelet degranulation and the coagulation cascade and reinforced with a seal using platelet growth factors. We present three cases in which we used this procedure. The results will be valued based on the tympanic perforation closure index. With this study, we want to assess the effectiveness of tympanic perforation repairs with this technically simple method. If this method was objectively proved to be effective, it would lead to lower patient morbidity and sanitary costs.

This paper describes Peru's experiences with its National Blood Banking Program. Until the mid-1990s, the country faced a host of problems, including the lack of a legal framework to regulate blood banks, a high maternal mortality rate due to a shortage of blood, virtually no voluntary donations, a high risk of infection from transfusions, the use of only whole blood for transfusion, serious disorganization in the blood banks, deficiencies in blood bank supervision and control, no training programs, indifference on the part of health officials, frequent selling of blood, and limited community awareness. Subsequently, a strategic plan was prepared that made it possible to solve many of those problems. Legal instruments were prepared; the rate of voluntary donations rose from 0% to 19.5%; the safety of the blood was improved through compulsory screening of all donated blood units for seven markers of infectious diseases, as well as by placing a national seal of quality on all screened units. The availability of blood doubled, thus meeting 70% of the need; sales of blood decreased; and the use of blood components was improved, with 80% of the blood being fractionated. In addition, supervisory control of 100% of the blood banks in the country was achieved, a national registry was established, the cost-benefit relationship for blood units was improved through centralized screening, internal and external quality control was made mandatory, and pro-donation campaigns led to commitments from civil society. While important, all these achievements represent just a first step. This is especially true given that developing the National Blood Banking Program required the participation of outside organizations, such as the Pan American Health Organization, whose support, together with the experience provided by other countries, was key. The Program is facing a number of new challenges, and the progress that has been achieved could be threatened if current activities stagnate or if officials become complacent.