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1.
Artículo en Inglés | MEDLINE | ID: mdl-38619791

RESUMEN

PURPOSE: Heart valve disease is commonly treated by minimally invasive procedures with guide wires and catheterization. The main purpose of this study is to find out whether an extension of the guide wire with a sensor can support the surgeon within the blood vessel to reduce X-ray necessity. METHODS: A smart guide wire is developed by an extension with a flex-bending sensor to evaluate the sensor signal with and without "blood" flow at a constant compression force. Various surgically relevant investigations are performed. For assessment, the mean temporal average of the moving averaged filtered ADC signal and a subsequent FFT are carried out. RESULTS: Results show that there is a smaller sensor signal when the applied force or bending at the sensor is higher. In all investigations, there was a different sensor signal. The flex-bending sensor can detect the effect of pulsatile flow. The smallest temporal averaged signal difference between reference and clamp in the front wire's tip is 1.09%. For example, the mean temporal average of the filtered ADC signal for different clinically relevant scenarios is between 2550 and 2900. CONCLUSIONS: The results show that the sensorized guide wire developed for catheterization can support aortic valve implementation. The sensor sensitivity is sufficient to detect even very small variations within the blood vessel and therefore is promising to support catheterization heart valve surgeries in future.

3.
Rev Neurol (Paris) ; 180(1-2): 42-52, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38176987

RESUMEN

The autonomic nervous system (ANS) harmoniously regulates all internal organic functions (heart rate, blood pressure, vasomotion, digestive tract motility, endocrinal secretions) and adapts them to the needs. It's the control of so-called vegetative functions, which allows homeostasis but also allostasis of our body. ANS is divided into two systems often understood as antagonistic and complementary: the sympathetic and the parasympathetic systems. However, we currently know of many situations of co-activation of the two systems. Long seen as acting through "reflex" control loops passing through the integration of peripheral information and the efferent response to the peripheral organ, more recent electrophysiological and brain functional imaging knowledge has been able to identify the essential role of the central autonomic network. This element complicates the understanding of the responses of the reflex loops classically used to identify and quantify dysautonomia. Finding the "ANS" tools best suited for the clinician in their daily practice is a challenge that we will attempt to address in this work.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Sistema Nervioso Autónomo , Humanos , Sistema Nervioso Autónomo/anatomía & histología , Sistema Nervioso Autónomo/fisiología , Frecuencia Cardíaca/fisiología
4.
West Afr J Med ; 40(12 Suppl 1): S38-S39, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38071469

RESUMEN

Introduction: A screening tool for obstructive sleep apnoea (OSA) is useful in low-income countries where it may be difficult to access sleep recordings. The objective of this study was to assess the performance of six screening scores compared with objective sleep recording in an African population sample. Methods: This analysis is based on the "Benin Sleep and Society" (BeSAS) populational study in which respiratory polygraphy (PG) was performed using a type III device and OSA screening questionnaires (STOP, STOP-Bang, Berlin, NOSAS [≥ 8 and ≥ 5), No-Apnea, GOAL) were administered to participants. PG-defined OSA severity categories were defined according to the apnoea-hypopnoea index (AHI): mild (AHI 5 to <15/h), moderate (AHI 15 to <30/h) or severe (AHI≥30/h), and these were compared to score findings. Results: A total of 1810 subjects (mean age 45.4±14.6 years; 57.3% women) were included. For moderate to severe OSA, the area under the receiving operating characteristic (ROC) curve was greatest for GOAL and No-Apnea (0.70), followed by NoSAS5 (0.69). The highest sensitivity values were for NoSAS5 (0.73), No-Apnea (0.72), and GOAL (0.69), while NoSAS8 had the highest specificity (0.91), followed by Berlin (0.88) and GOAL (0.71). All scores performed poorly with respect to the positive predictive value (PPV), which was highest with NoSAS8 (0.38). Conclusion: This study provides the first comparison of the performance of screening scores for OSA in an African population. Although still low, PPV was highest with NoSAS8. Hence, NoSAS8 would be the screening method of choice for OSA in resource-constrained settings where formal sleep recordings are not accessible.


Asunto(s)
Apnea Obstructiva del Sueño , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Encuestas y Cuestionarios , Apnea Obstructiva del Sueño/diagnóstico , Tamizaje Masivo/métodos , Valor Predictivo de las Pruebas , Polisomnografía
5.
West Afr J Med ; 40(12 Suppl 1): S39-S40, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38071478

RESUMEN

Background: The Epworth Sleepiness Scale (ESS) is a tool widely used to assess excessive daytime sleepiness. Unfortunately, it is not reliable in low-income countries where situations such as reading a book, watching TV or driving a car are not common. The aim of this study was thus to assess the performance of a modified version of the Epworth scale in a low-income country. Methods: We used data from the Benin Society and Sleep (BeSAS) study where the ESS and a modified ESS (mESS) were administered to participants. In the mESS, questions four questions over eight were redesigned to reflect common living situations in Benin. The internal coherence of the mESS was assessed using the Cronbach alpha coefficient (CAC). The discriminatory ability of the scale was assessed by comparing the mean scores according to reported sleep quality, insomnia complaints and apnea-hypopnea index (AHI). Results: A total of 2909 participants were recruited, 1129 were male (38.9%) with a mean age (SD) of 44.7 (14.5) y. Overall, 52.4% (1526) completed all the mESS questions while 453 (15.6%) completed the standard ESS. The CAC of the mES was 0.86 showing good internal coherence. Concerning the discriminatory ability, mean scores for mESS were 7.8 for participants with ISI < 8 vs 9.2 for participants with ISI≥8 (p<0.001), 7.8 for participants withPSQI<5 vs 8.3 for participants with PSQI≥5 (p=0.03). No difference was found when comparing the participants participants using different cut-offs of AHI (15 and 30). Conclusion: The mES is more reliable than ES in the Beninese population. mESS shows good internal coherence and differentiates between insomniacs vs non-insomniacs and between good and poor sleepers. Although the mES is not a perfect score, it appears more relevant in the Benin population than the original Epworth scale but needs further validation/improvement in other low-income countries.


Asunto(s)
Trastornos de Somnolencia Excesiva , Somnolencia , Humanos , Masculino , Femenino , Benin , Encuestas y Cuestionarios , Sueño , Trastornos de Somnolencia Excesiva/diagnóstico
6.
Braz J Biol ; 83: e275688, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37970904

RESUMEN

Paclitaxel (PTX) is a potent anticancer drug. In the present study, PTX was loaded in poly-3-hydroxybutyrate-co-3-hydroxyvalarate (PHBV) to fabricate the PTX/PHBV (drug-loaded) nanoparticles via the nanoprecipitation method. Blank PHBV nanoparticles were also prepared. The drug-encapsulation efficiency of PTX/PHBV nanoparticles was 45±0.4%. The PTX/PHBV nanoparticles exhibited a pH-sensitive release profile and followed a quasi-Fickian diffusion mechanism. Cytotoxic properties of PHBV and PTX/PHBV nanoparticles were checked against the MCF-7 and Caco-2 cell lines. The PHBV nanoparticle did not inhibit the proliferation of MCF-7 and Caco-2 cell lines, thus depicting their non-toxic and biocompatible nature. On the other hand, the PTX/PHBV nanoparticles demonstrated 1.03-fold higher cytotoxicity and 1.61-fold enhanced apoptosis after treatment with the PTX/PHBV nanoparticles versus free PTX. In summary, the PHBV nanoparticles could be a potential candidate for the delivery of PTX for cancer treatment.


Asunto(s)
Antineoplásicos , Nanopartículas , Humanos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Células CACO-2 , Poliésteres/farmacología , Línea Celular Tumoral
7.
Allergy ; 78(10): 2756-2766, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37366581

RESUMEN

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

8.
Expert Rev Pharmacoecon Outcomes Res ; 23(4): 383-389, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36880336

RESUMEN

BACKGROUND: The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent's perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap. METHODS: Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A 'before the interview' (including translation, recruitment, training), Part B 'during the interview' (including setting, opening, completing the instrument, open-ended questions, closing), and part C 'after the interview' (including transcription and data analysis, trustworthiness). CONCLUSIONS: This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.


Asunto(s)
Proyectos de Investigación , Humanos , Encuestas y Cuestionarios
9.
ESMO Open ; 8(2): 100884, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36863095

RESUMEN

BACKGROUND: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. METHODS: In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs. RESULTS: Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable. CONCLUSIONS: The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Melanoma , Viroterapia Oncolítica , Neoplasias de la Mama Triple Negativas , Adulto , Humanos , Melanoma/terapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/etiología , Estudios de Cohortes , Viroterapia Oncolítica/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Colorrectales/terapia
10.
Arch Pediatr ; 30(3): 179-186, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36804355

RESUMEN

BACKGROUND: The coronavirus pandemic created an unprecedented deployment of health professionals. The objective of this study was to describe the experiences of pediatric nurses transferred to adult COVID-19 wards during the first wave of the pandemic. METHODS: We performed a qualitative study using a phenomenological approach. Nurses were recruited on a voluntary basis. All participants moved from a pediatric ward and were redeployed to an adult COVID-19 ward in another hospital. Interviews were carried out face to face in line with social-distancing guidelines. We used a script of open-end questions. The interviews were recorded and transcribed in full and qualitative data were analyzed using NVivo software. RESULTS AND CONCLUSIONS: In total, 23 nurses were interviewed. Our analysis revealed positive and negative experiences given the different types of support the nurses received, individual attitudes that promoted resilience in a crisis situation, ethical conflicts linked to end-of-life care, and their perspectives on the next wave of the pandemic. The main difficulties encountered by the transferred nurses were related to their working conditions and safety, communication about working practices, and end-of-life patient care. In most cases, the individual resilience strategies put in place and the different forms of social support enabled them to cope with stress and maintain their commitment. However, some interviewees would have benefited from improved managerial support. For all participants, their perception of this support and the benefits of their experience influenced their willingness to be transferred to an adult ward again during a future wave of the pandemic.


Asunto(s)
COVID-19 , Enfermeras Pediátricas , Adulto , Humanos , Niño , COVID-19/epidemiología , Hospitales , Pandemias , Personal de Salud , Investigación Cualitativa
11.
Ann Oncol ; 34(3): 215-227, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36529447

RESUMEN

BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers. METHODS: We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and 'on-tumour' status (established tumour-gene association). RESULTS: Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%. CONCLUSION: Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven 'most actionable' cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type.


Asunto(s)
Neoplasias , Medicina de Precisión , Humanos , Frecuencia de los Genes , Mutación de Línea Germinal , Genes BRCA2 , Predisposición Genética a la Enfermedad
12.
Ann Pharm Fr ; 81(4): 710-719, 2023 Jun.
Artículo en Francés | MEDLINE | ID: mdl-36513152

RESUMEN

The development of Oral Cancer Therapies (OAT) raises the question of the therapeutic adherence of patients, put in difficulty by the isolation of the patient in the management of treatment and adverse reactions. Accompanying processes are developing, such as Pharmaceutical Consultations (PC), whose monitoring and education objectives are multiple. The PCs and their implementation are presented here, as well as the first results at 15months. The scope of the PCs was first defined, as well as their organization and supporting documents. A patient's medication history is carried out before the PC, then analyzed. The initial PC incorporates a discussion about patient's health habits, followed by information on the OAT, which is closed by the delivery of a follow-up diary. The follow-up PCs, distributed over the course of the first year following the initiation, allow to correct the erroneous knowledge of the patient, to support him in his difficulties and to detect any adverse effects. From May 2019 to August 2020, 81.2% of the 32 patients who initiated OAT took part in CP. A pharmacotherapeutic problem is encountered in 65.4% of them and a drug interaction with alternative or complementary medicines in 62.5% of patients which consuming. The PCs developed provide new elements compared to the recommendations and provide support for patients with toxicities that weaken their medical care throughout their care pathway.


Asunto(s)
Farmacia , Humanos , Masculino , Preparaciones Farmacéuticas , Derivación y Consulta , Atención al Paciente , Hospitales de Enseñanza
13.
Expert Rev Pharmacoecon Outcomes Res ; 23(1): 135-141, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36472303

RESUMEN

BACKGROUND: Health problems can lead to costs in the education sector. However, these costs are rarely incorporated in health economic evaluations due to the lack of reference unit costs (RUCs), cost per unit of service, of education services and of validated methods to obtain them. In this study, a standardized unit cost calculation tool developed in the PECUNIA project, the PECUNIA RUC Template for services, was applied to calculate the RUCs of selected education services in five European countries. METHODS: The RUCs of special education services and of educational therapy were calculated using the information collected via an exploratory gray literature search and contact with service providers. RESULTS: The RUCs of special education services ranged from €55 to €189 per school day. The RUCs of educational therapy ranged from €6 to €25 per contact and from €5 to €35 per day. Variation was observed in the type of input data and measurement unit, among other. DISCUSSION: The tool helped reduce variability in the RUCs related to costing methodology and gain insights into other aspects that contribute to the variability (e.g. data availability). Further research and efforts to generate high quality input data are required to reduce the variability of the RUCs.


Asunto(s)
Costos de la Atención en Salud , Humanos , Análisis Costo-Beneficio , Europa (Continente) , Escolaridad
14.
Rheumatol Int ; 43(5): 803-824, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36454326

RESUMEN

To assess the reporting quality of interventions aiming at promoting physical activity (PA) using a wearable activity tracker (WAT) in patients with inflammatory arthritis (IA) or hip/knee osteoarthritis (OA). A systematic search was performed in eight databases (including PubMed, Embase and Cochrane Library) for studies published between 2000 and 2022. Two reviewers independently selected studies and extracted data on study characteristics and the reporting of the PA intervention using a WAT using the Consensus on Exercise Reporting Template (CERT) (12 items) and Consolidated Standards of Reporting Trials (CONSORT) E-Health checklist (16 items). The reporting quality of each study was expressed as a percentage of reported items of the total CERT and CONSORT E-Health (50% or less = poor; 51-79% = moderate; and 80-100% = good reporting quality). Sixteen studies were included; three involved patients with IA and 13 with OA. Reporting quality was poor in 6/16 studies and moderate in 10/16 studies, according to the CERT and poor in 8/16 and moderate in 8/16 studies following the CONSORT E-Health checklist. Poorly reported checklist items included: the description of decision rule(s) for determining progression and the starting level, the number of adverse events and how adherence or fidelity was assessed. In clinical trials on PA interventions using a WAT in patients with IA or OA, the reporting quality of delivery process is moderate to poor. The poor reporting quality of the progression and tailoring of the PA programs makes replication difficult. Improvements in reporting quality are necessary.


Asunto(s)
Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Monitores de Ejercicio , Ejercicio Físico , Osteoartritis de la Rodilla/terapia , Osteoartritis de la Cadera/terapia , Extremidad Inferior
15.
J Craniomaxillofac Surg ; 50(11): 817-824, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36376159

RESUMEN

The aim of this study was the development of a statistical model for reliable prediction of Posterior Airway Space (PAS) changes in lateral cephalograms (LCR) of patients after bimaxillary orthognathic surgery. The LCRs of patients who underwent bimaxillary orthognathic surgery were retrospectively analyzed. The anteroposterior dimension of the PAS was measured at three levels in the pre-operative and postoperative LCR: On the nasopharyngeal (SPAS), oropharyngeal (MAS), and hypopharyngeal level (IAS). The data of 139 patients were collected. The following changes of the PAS were measured: in class II patients SPAS: 0.291 mm (SD = 2.570 mm); MAS: 2.444 mm (SD = 2.986 mm); IAS: 0.750 mm (SD = 3.017 mm); in class III patients SPAS: 1.377 mm (SD 3.212 mm); MAS: 0.962 (SD: = 3.135 mm); IAS: 0.370 mm (SD = 3.468 mm). Linear regression analysis showed for class II patients, a significant influence of mandibular movement on MAS (p = 0.049) and a significant effect of maxillary and mandibular movements on SPAS (p = 0.001) and MAS (p = 0.022) in class III patients. The other jaw displacements had no significant impact on the investigated PAS levels. While the presented method does not permit exact prediction of the dimension of the PAS, it is still an easily accessible method of orientation for the surgeon. The surgeon can initiate three-dimensional examinations to provide exact three-dimensional prediction based on this calculation.


Asunto(s)
Maloclusión de Angle Clase III , Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Humanos , Estudios Retrospectivos , Procedimientos Quirúrgicos Ortognáticos/métodos , Maloclusión de Angle Clase III/cirugía , Cefalometría/métodos , Faringe/diagnóstico por imagen , Modelos Teóricos
16.
Ann Oncol ; 33(12): 1284-1295, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36089134

RESUMEN

BACKGROUND: Studies of targeted therapy resistance in lung cancer have primarily focused on single-gene alterations. Based on prior work implicating apolipoprotein b mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, we hypothesized that mutational signature analysis may help elucidate acquired resistance to targeted therapies. PATIENTS AND METHODS: APOBEC mutational signatures derived from an Food and Drug Administration-cleared multigene panel [Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)] using the Signature Multivariate Analysis (SigMA) algorithm were validated against the gold standard of mutational signatures derived from whole-exome sequencing. Mutational signatures were decomposed in 3276 unique lung adenocarcinomas (LUADs), including 93 paired osimertinib-naïve and -resistant EGFR-mutant tumors. Associations between APOBEC and mechanisms of resistance to osimertinib were investigated. Whole-genome sequencing was carried out on available EGFR-mutant lung cancer samples (10 paired, 17 unpaired) to investigate large-scale genomic alterations potentially contributing to osimertinib resistance. RESULTS: APOBEC mutational signatures were more frequent in receptor tyrosine kinase (RTK)-driven lung cancers (EGFR, ALK, RET, and ROS1; 25%) compared to LUADs at large (20%, P < 0.001); across all subtypes, APOBEC mutational signatures were enriched in subclonal mutations (P < 0.001). In EGFR-mutant lung cancers, osimertinib-resistant samples more frequently displayed an APOBEC-dominant mutational signature compared to osimertinib-naïve samples (28% versus 14%, P = 0.03). Specifically, mutations detected in osimertinib-resistant tumors but not in pre-treatment samples significantly more frequently displayed an APOBEC-dominant mutational signature (44% versus 23%, P < 0.001). EGFR-mutant samples with APOBEC-dominant signatures had enrichment of large-scale genomic rearrangements (P = 0.01) and kataegis (P = 0.03) in areas of APOBEC mutagenesis. CONCLUSIONS: APOBEC mutational signatures are frequent in RTK-driven LUADs and increase under the selective pressure of osimertinib in EGFR-mutant lung cancer. APOBEC mutational signature enrichment in subclonal mutations, private mutations acquired after osimertinib treatment, and areas of large-scale genomic rearrangements highlights a potentially fundamental role for APOBEC mutagenesis in the development of resistance to targeted therapies, which may be potentially exploited to overcome such resistance.


Asunto(s)
Adenocarcinoma del Pulmón , Cromotripsis , Neoplasias Pulmonares , Humanos , Proteínas Tirosina Quinasas/genética , Resistencia a Antineoplásicos/genética , Proteínas Proto-Oncogénicas/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Proteínas Tirosina Quinasas Receptoras/genética , Mutagénesis , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico
17.
Eur Rev Med Pharmacol Sci ; 26(13): 4770-4773, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35856369

RESUMEN

OBJECTIVE: Botulism is a very rare disease in Switzerland, with less than one case per year, an incidence of 0.01 cases for 100,000 inhabitants. Indeed, over the past ten years, 9 cases have been reported to Public Health registry. Foodborne botulism (FB) is caused by ingestion of preformed botulinum neurotoxin. Characteristic features should be rapidly recognized, and prompt treatment should be administered to avoid further progression towards respiratory failure and death. CASE REPORT: We report the case of a patient who developed gastrointestinal symptoms just after a sandwich consumption followed by rapidly progressive cranial nerve impairment, truncal muscle weakness in a descending pattern and respiratory failure requiring mechanical ventilation. The diagnosis of foodborne botulism was delayed due to differential diagnosis considerations. Specific antitoxin therapy was administered immediately after firm clinical conviction of botulism, without waiting for serologic results that later confirmed the diagnosis. As expected, muscle weakness recovery was slow, with persistent chronic deficits nine years later. CONCLUSIONS: This case highlights differential diagnosis issues of botulism. These include acute neuromuscular disorders such as myasthenia gravis, Guillain-Barré syndrome, or tick-borne encephalitis. The importance of careful medical history and repeated clinical evaluation to avoid misdiagnosis can be lifesaving. Our case highlights the typical warning signs.


Asunto(s)
Toxinas Botulínicas , Botulismo , Insuficiencia Respiratoria , Enfermedad Aguda , Toxinas Botulínicas/uso terapéutico , Botulismo/diagnóstico , Botulismo/epidemiología , Botulismo/terapia , Humanos , Debilidad Muscular/etiología , Respiración Artificial/efectos adversos
18.
Sleep Med ; 98: 106-113, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35816789

RESUMEN

OBJECTIVE: Changes in sleep architecture following ischemic stroke have been poorly investigated. Our objective was to explore changes of sleep structure in patients with ischemic stroke or transient ischemic attack in order to verify a possible predictive value of sleep with respect to clinical outcome. METHODS: Patients recruited in the prospective SAS-CARE study received two polysomnographies (PSG) in the acute and chronic phases after stroke/TIA. Sleep parameters were compared between the two time-points and matched with a non-stroke population randomly selected from the HypnoLaus cohort. RESULTS: Of the 169 patients investigated with PSG in the acute phase, 104 were again studied 3 months after stroke symptom onset and compared with 162 controls. The acute phase of stroke/TIA was associated with sleep disruption, which significantly improved in the chronic phase, but remained worse than controls (total sleep time improve from 318.8 ± 90.8 to 348.4 ± 81.5 min, compared to 388.2 ± 71.3 in controls, sleep latency from 49.9 ± 58.4 to 27.9 min, compared to 20.2 ± 22 in controls, sleep efficiency from 58.2 ± 18.1% to 27.9 ± 36.4 min, compared to 83.4 ± 10.3% in controls, wakefulness after sleep onset percentage from 36.5 ± 17.3 to 29.3 ± 15.6, compared to 13.2 ± 9.2 in controls). The percentage of REM sleep was negatively associated with stroke severity, whereas stroke topography did not correlate with sleep parameters. CONCLUSIONS: This study confirmed a severe sleep disruption in the acute phase of stroke. Although a significant improvement of sleep quality was observed during the three months after stroke, sleep architecture did not normalize. In particular, sleep efficiency and REM sleep seem to be particularly affected by stroke in the acute phase, with a relative preservation of NREM sleep. We suggest that these sleep architecture changes represent a persistent marker of brain damage due to stroke. Further studies are needed to assess the relationship with stroke topographic and outcome.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Ataque Isquémico Transitorio/complicaciones , Polisomnografía , Estudios Prospectivos , Sueño , Accidente Cerebrovascular/epidemiología
19.
Eur J Paediatr Dent ; 23(2): 131-136, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35722839

RESUMEN

AIM: To investigate the effects of anticancer therapy on dental development and caries formation in Italian childhood cancer survivors compared to healthy controls. METHODS: A total of 52 children treated with chemotherapy and/or radiotherapy when younger than 10 years and in remission from at least 2 years, and 52 healthy age- and gender-matched children were consecutively enrolled in this cross-sectional study. All participants were examined for dental caries and enamel defects according to the decayed-missing-filled teeth (dmft/DMFT) index and the Aine rating scale. Panoramic radiographs were taken to estimate dental age and to assess dental abnormalities using the Höltta Defect Index. CONCLUSION: These children are at high risk for tooth developmental abnormalities and poor dental health and should be closely monitored by a specialist dentist.


Asunto(s)
Anodoncia , Caries Dental , Anomalías Dentarias , Niño , Estudios Transversales , Índice CPO , Dentición , Humanos , Prevalencia
20.
BMC Pregnancy Childbirth ; 22(1): 479, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35698051

RESUMEN

BACKGROUND: Women who smoke during pregnancy make less use of prenatal care; the relation of smoking behavior with the use of other forms of maternal healthcare is unknown. The objective of this study is to investigate the association between women's smoking behavior and their use of healthcare during pregnancy, birth and six weeks postpartum. METHODS: We analyzed data from the Dutch Midwifery Case Registration System (VeCaS), period 2012-2019. We included women with a known smoking status, singleton pregnancies, and who had their first appointment before 24 weeks of gestation with the primary care midwife. We compared three groups: non-smokers, early stoppers (stopped smoking in the first trimester), and late- or non-stoppers (stopped smoking after the first trimester or continued smoking). Descriptive statistics were used to report maternal healthcare utilization (during pregnancy, birth and six weeks postpartum), statistical differences between the groups were calculated with Kruskal-Wallis tests. Multivariable logistic regression was conducted to assess the association between smoking behavior and referrals to primary, secondary or tertiary care. RESULTS: We included 41 088 pregnant women. The groups differed significantly on maternal healthcare utilization. The late- or non-stoppers initiated prenatal care later and had less face-to-face consultations with primary care midwives during pregnancy. Compared to the non-smokers, the early- and late- or non-stoppers were statistically signficiantly more likely to be referred to the obstetrician during pregnancy and birth. Postpartum, the early- and late- or non-stoppers were statistically signficantly less likely to be referred to the obstetrician compared to the non-smokers. CONCLUSIONS: Although the early- and late- or non-stoppers initiated prenatal care later than the non-smokers, they did receive adequate prenatal care (according to the recommendations). The results suggest that not smoking during pregnancy may decrease the likelihood of referral to secondary or tertiary care. The large population of smokers being referred during pregnancy underlines the important role of the collaboration between healthcare professionals in primary and secondary or tertiary care. They need to be more aware of the importance of smoking as a medical and as a non-medical risk factor.


Asunto(s)
Parto , Atención Prenatal , Estudios de Cohortes , Femenino , Humanos , Embarazo , Derivación y Consulta , Fumar/epidemiología
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