Foot/Ankle Prostheses Design Approach Based on Scientometric and Patentometric Analyses

There are different alternatives when selecting removable prostheses for below the knee amputated patients. The designs of these prostheses vary according to their different functions. These prostheses designs can be classified into Energy Storing and Return (ESAR), Controlled Energy Storing and Return (CESR), active, and hybrid. This paper aims to identify the state of the art related to the design of these prostheses of which ESAR prostheses are grouped into five types, and active and CESR are categorized into four groups. Regarding patent analysis, 324 were analyzed over the last six years. For scientific communications, a bibliometric analysis was performed using 104 scientific reports from the Web of Science in the same period. The results show a tendency of ESAR prostheses designs for patents (68%) and active prostheses designs for scientific documentation (40%).Beca Conacyt Doctorad

Ivacaftor Reduces Inflammatory Mediators in Upper Airway Lining Fluid From Cystic Fibrosis Patients With a G551D Mutation: Serial Non- Invasive Home-Based Collection of Upper Airway Lining Fluid

In cystic fibrosis (CF) therapy, the recent approval of CF-transmembrane conductance regulator (CFTR) channel modulators is considered to be the major breakthrough. However, the current first-line approach based mainly on pulmonary function to measure effects of the novel therapy, tested by forced expiratory volumes in one second (FEV1), provides restricted sensitivity to detect early structural damages. Accordingly, there is a need for new sensitive surrogate parameters. Most interestingly, these should quantify inflammation that precedes a decline of pulmonary function. We present a novel method assessing inflammatory markers in the upper airways’ epithelial lining fluid (ELF) obtained by nasal lavage (NL). In contrast to broncho-alveolar lavage, ELF sampling by NL is an attractive method due to its limited invasiveness which allows repeated analyses, even performed in a home-based setting. In a longitudinal cohort study (ClinicalTrials.gov, Identifier: NCT02311140), we assessed changes of inflammatory mediators in 259 serially obtained nasal lavages taken up to every second day before and during therapy with ivacaftor from ten CF patients carrying a G551D mutation. Patients were trained to sample NL-fluid at home, to immediately freeze and transfer chilled secretions to centers. Neutrophil Elastase, Interleukins IL-1b, IL-6 and IL-8 in NL were quantified. During 8-12 weeks of ivacaftor-treatment, median values of IL-1b and IL-6 significantly declined 2.29-fold (2.97!1.30 pg/mL), and 1.13-fold (6.48!5.72 pg/mL), respectively. In parallel, sweat tests and pulmonary function improved considerably. This is the first study assessing changes of airway inflammation on a day-to-day basis in CF patients receiving a newly administered CFTR-modulator therapy. It proves a decline of airway inflammation during ivacaftor-therapy

Divergent dynamics of inflammatory mediators and multiplex PCRs during airway infection in cystic fibrosis patients and healthy controls: Serial upper airway sampling by nasal lavage

Background In cystic fibrosis (CF), acute respiratory exacerbations critically enhance pulmonary destruction. Since these mainly occur outside regular appointments, they remain unexplored. We previously elaborated a protocol for home-based upper airway (UAW) sampling obtaining nasal-lavage fluid (NLF), which, in contrast to sputum, does not require immediate processing. The aim of this study was to compare UAW inflammation and pathogen colonization during stable phases and exacerbations in CF patients and healthy controls. Methods Initially, we obtained NLF by rinsing 10 ml of isotonic saline/nostril during stable phases. During exacerbations, subjects regularly collected NLF at home. CF patients directly submitted one aliquot for microbiological cultures. The remaining samples were immediately frozen until transfer on ice to our clinic, where PCR analyses were performed and interleukin (IL)-1β/IL-6/IL-8, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were assessed. Results Altogether, 49 CF patients and 38 healthy controls (HCs) completed the study, and 214 NLF samples were analyzed. Of the 49 CF patients, 20 were at least intermittently colonized with P. aeruginosa and received azithromycin and/or inhaled antibiotics as standard therapy. At baseline, IL-6 and IL-8 tended to be elevated in CF compared to controls. During infection, inflammatory mediators increased in both cohorts, reaching significance only for IL-6 in controls (p=0.047). Inflammatory responses tended to be higher in controls [1.6-fold (NE) to 4.4-fold (MMP-9)], while in CF, mediators increased only moderately [1.2-1.5-fold (IL-6/IL-8/NE/TIMP-1/MMP-9)]. Patients receiving inhalative antibiotics or azithromycin (n=20 and n=15, respectively) revealed lower levels of IL-1β/IL-6/IL-8 and NE during exacerbation compared to CF patients not receiving those antibiotics. In addition, CF patients receiving azithromycin showed MMP-9 levels significantly lower than CF patients not receiving azithromycin at stable phase and exacerbation. Altogether, rhinoviruses were the most frequently detected virus, detected at least once in n=24 (49.0%) of the 49 included pwCF and in n=26 (68.4%) of the 38 healthy controls over the 13-month duration of the study. Remarkably, during exacerbation, rhinovirus detection rates were significantly higher in the HC group compared to those in CF patients (65.8% vs. 22.4%; p<0.0001). Conclusion Non-invasive and partially home-based UAW sampling opens new windows for the assessment of inflammation and pathogen colonization in the unified airway system

Elexacaftor-Tezacaftor-Ivacaftor treatment reduces abdominal symptoms in cystic fibrosis -Early results obtained with the CF-specific CFAbd-Score

BACKGROUND: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score. METHODES: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations. RESULTS: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2→10.6 ± 1.4; p &lt; 0.01). Also EMMs of all five domains significantly declined (“pain” 16.3 ± 1.6→10.2 ± 2.3, “GERD” 15.8 ± 1.8→8.2 ± 1.9, “disorders of bowel movement” 20.9 ± 1.5→16.0 ± 1.7, “disorders of appetite” 7.9 ± 1.1→2.6 ± 1.1 and “quality of life impairment” 10.1 ± 1.92→3.9 ± 1.9). However, during 24 weeks, CF participants’ symptoms mostly still did not reach the reference levels of HCs. DISCUSSION: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI. KEYWORDS: gastrointestinal, patient reported outcome measure, CFTR modulators, elexacaftor, symptom scor

MODELO INDUSTRIAL DE PRÓTESIS PARA PIERNA MX/f/2021/001244

Modelo Industrial. Se presenta una prótesis para pierna, constituida de elementos mecánicos

Ivacaftor Reduces Inflammatory Mediators in Upper Airway Lining Fluid From Cystic Fibrosis Patients With a G551D Mutation: Serial Non- Invasive Home-Based Collection of Upper Airway Lining Fluid

In cystic fibrosis (CF) therapy, the recent approval of CF-transmembrane conductance regulator (CFTR) channel modulators is considered to be the major breakthrough. However, the current first-line approach based mainly on pulmonary function to measure effects of the novel therapy, tested by forced expiratory volumes in one second (FEV1), provides restricted sensitivity to detect early structural damages. Accordingly, there is a need for new sensitive surrogate parameters. Most interestingly, these should quantify inflammation that precedes a decline of pulmonary function. We present a novel method assessing inflammatory markers in the upper airways’ epithelial lining fluid (ELF) obtained by nasal lavage (NL). In contrast to broncho-alveolar lavage, ELF sampling by NL is an attractive method due to its limited invasiveness which allows repeated analyses, even performed in a home-based setting. In a longitudinal cohort study (ClinicalTrials.gov, Identifier: NCT02311140), we assessed changes of inflammatory mediators in 259 serially obtained nasal lavages taken up to every second day before and during therapy with ivacaftor from ten CF patients carrying a G551D mutation. Patients were trained to sample NL-fluid at home, to immediately freeze and transfer chilled secretions to centers. Neutrophil Elastase, Interleukins IL-1b, IL-6 and IL-8 in NL were quantified. During 8-12 weeks of ivacaftor-treatment, median values of IL-1b and IL-6 significantly declined 2.29-fold (2.97!1.30 pg/mL), and 1.13-fold (6.48!5.72 pg/mL), respectively. In parallel, sweat tests and pulmonary function improved considerably. This is the first study assessing changes of airway inflammation on a day-to-day basis in CF patients receiving a newly administered CFTR-modulator therapy. It proves a decline of airway inflammation during ivacaftor-therapy

Ivacaftor Reduces Inflammatory Mediators in Upper Airway Lining Fluid From Cystic Fibrosis Patients With a G551D Mutation: Serial Non- Invasive Home-Based Collection of Upper Airway Lining Fluid

In cystic fibrosis (CF) therapy, the recent approval of CF-transmembrane conductance regulator (CFTR) channel modulators is considered to be the major breakthrough. However, the current first-line approach based mainly on pulmonary function to measure effects of the novel therapy, tested by forced expiratory volumes in one second (FEV1), provides restricted sensitivity to detect early structural damages. Accordingly, there is a need for new sensitive surrogate parameters. Most interestingly, these should quantify inflammation that precedes a decline of pulmonary function. We present a novel method assessing inflammatory markers in the upper airways’ epithelial lining fluid (ELF) obtained by nasal lavage (NL). In contrast to broncho-alveolar lavage, ELF sampling by NL is an attractive method due to its limited invasiveness which allows repeated analyses, even performed in a home-based setting. In a longitudinal cohort study (ClinicalTrials.gov, Identifier: NCT02311140), we assessed changes of inflammatory mediators in 259 serially obtained nasal lavages taken up to every second day before and during therapy with ivacaftor from ten CF patients carrying a G551D mutation. Patients were trained to sample NL-fluid at home, to immediately freeze and transfer chilled secretions to centers. Neutrophil Elastase, Interleukins IL-1b, IL-6 and IL-8 in NL were quantified. During 8-12 weeks of ivacaftor-treatment, median values of IL-1b and IL-6 significantly declined 2.29-fold (2.97!1.30 pg/mL), and 1.13-fold (6.48!5.72 pg/mL), respectively. In parallel, sweat tests and pulmonary function improved considerably. This is the first study assessing changes of airway inflammation on a day-to-day basis in CF patients receiving a newly administered CFTR-modulator therapy. It proves a decline of airway inflammation during ivacaftor-therapy