Radiotherapy in breast cancer: current standards of treatment, prediction of local recurrence and open questions

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A Narrative Review of Patient-Reported Outcome Measures and Their Application in Recent Pediatric Surgical Research:Advancing Knowledge and Offering New Perspectives to the Field

Introduction Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This narrative review aims to describe PROM use in recent pediatric surgical research, identify and describe psychometrically robust PROMs, providing an overview of those derived from pediatric patient input, and make recommendations for future research. Materials and Methods A search was conducted to identify articles published from 2021 to August 2023 describing the availability and/or use of at least one valid or reliable PROM in children with conditions including anorectal malformations, biliary atresia, congenital diaphragmatic hernia, duodenal atresia, esophageal atresia, abdominal wall defects, Hirschsprung's disease, sacrococcygeal teratoma, and short bowel syndrome. Articles were categorized based on their objectives in applying PROMs. Psychometrically robust PROMs were identified and described. Results Out of the 345 articles identified, 49 met the inclusion criteria. Seventeen focused on esophageal atresia and 14 on Hirschsprung's disease. Twenty-nine PROMs were identified, with 12 deemed psychometrically robust. Seven psychometrically robust PROMs were developed using patient input in the primary item generation. Most PROMs were applied to advance understanding of conditions and/or treatment and fewer were developed or psychometrically evaluated. No PROMs were assessed for their impact or incorporated into an implementation study. Conclusions This review reveals gaps in the application of PROMs in recent pediatric surgical research. Emphasis should be placed on the development and utilization of psychometrically robust PROMs, broadening the scope of covered diseases, conducting impact assessments, and evaluating implementation strategies

A Narrative Review of Patient-Reported Outcome Measures and Their Application in Recent Pediatric Surgical Research:Advancing Knowledge and Offering New Perspectives to the Field

Introduction Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This narrative review aims to describe PROM use in recent pediatric surgical research, identify and describe psychometrically robust PROMs, providing an overview of those derived from pediatric patient input, and make recommendations for future research. Materials and Methods A search was conducted to identify articles published from 2021 to August 2023 describing the availability and/or use of at least one valid or reliable PROM in children with conditions including anorectal malformations, biliary atresia, congenital diaphragmatic hernia, duodenal atresia, esophageal atresia, abdominal wall defects, Hirschsprung's disease, sacrococcygeal teratoma, and short bowel syndrome. Articles were categorized based on their objectives in applying PROMs. Psychometrically robust PROMs were identified and described. Results Out of the 345 articles identified, 49 met the inclusion criteria. Seventeen focused on esophageal atresia and 14 on Hirschsprung's disease. Twenty-nine PROMs were identified, with 12 deemed psychometrically robust. Seven psychometrically robust PROMs were developed using patient input in the primary item generation. Most PROMs were applied to advance understanding of conditions and/or treatment and fewer were developed or psychometrically evaluated. No PROMs were assessed for their impact or incorporated into an implementation study. Conclusions This review reveals gaps in the application of PROMs in recent pediatric surgical research. Emphasis should be placed on the development and utilization of psychometrically robust PROMs, broadening the scope of covered diseases, conducting impact assessments, and evaluating implementation strategies

De pandemie als mogelijke katalysator van emancipatie

Tijdens de coronapandemie moesten veel ouders thuiswerken en tegelijkertijd voor de kinderen zorgen en hen ondersteunen bij thuisonderwijs. Zorgtaken worden traditioneel vaker door vrouwen gedaan. Tijdens de pandemie zagen we echter dat ook vaders meer gingen zorgen. Hoewel de pandemie aanvankelijk een mogelijke katalysator van emancipatie leek, zijn oude patronen hardnekkig. Na verloop van tijd keerden veel ouders terug naar hun oorspronkelijke, traditionele verdeling van arbeid en zorg. We reflecteren op de beleidsimplicaties

Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

<p>Abstract</p> <p>Background</p> <p>The genus <it>Flavivirus </it>encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle.</p> <p>Results</p> <p>We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation.</p> <p>Conclusions</p> <p>We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.</p

Hematopoietic Stem Cell Transplant for the Treatment of X-MAID

We report outcomes after hematopoietic stem cell transplant for three patients with X-MAID, including 1 patient from the originally described cohort and two brothers with positive TREC newborn screening for SCID who were found to have a T-B-NK+ SCID phenotype attributable to X-linked moesin associated immunodeficiency (X-MAID). A c.511C&gt;T variant in moesin was identified via exome sequencing in the older of these siblings in the setting of low lymphocyte counts and poor proliferative responses consistent with SCID. He received reduced intensity conditioning due to CMV, and was transplanted with a T-depleted haploidentical (maternal) donor. His post-transplant course was complicated by hemolytic anemia, neutropenia, and sepsis. He had poor engraftment, requiring a 2nd transplant. His younger brother presented with the same clinical phenotype and was treated with umbilical cord blood transplant following myeloablative conditioning, has engrafted and is doing well. The third case also presented with severe lymphopenia in infancy, received a matched related bone marrow transplant following myeloablative conditioning, has engrafted and is doing well. These cases represent a novel manifestation of non-radiosensitive X-linked form of T-B-NK+ SCID that is able to be detected by TREC based newborn screening and effectively treated with HCT

White matter microstructural changes using ultra-strong diffusion gradient MRI in adult-onset idiopathic focal cervical dystonia

Background and Objectives Adult-onset idiopathic focal cervical dystonia (AOIFCD) involves abnormal posturing of the cervical musculature and, in some individuals, an associated head tremor. Existing neuroimaging studies have implicated key motor networks. However, measures used to date lack specificity toward underlying pathophysiologic differences. We aim to assess white matter motor pathways for localized, microstructural differences, which may aid in understanding underlying mechanisms. Methods Individuals diagnosed with AOIFCD and an age- and sex-matched control group were prospectively recruited through the Welsh Movement Disorders Research Network. All participants underwent in-depth clinical phenotyping and MRI (structural and diffusion sequences) using ultra-strong diffusion gradients. Tractography (whole-tract median values) and tractometry (along tract profiling) were performed for key white matter motor pathways assessing diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and standard model parameters. Groups were compared using linear model analysis with Bonferroni multiple comparison correction. Results Fifty participants with AOIFCD and 30 healthy control participants were recruited, with 46 with AOIFCD and 30 healthy controls included for analysis (33 without head tremor, 13 with head tremor). Significant differences were observed in the anterior thalamic radiations (lower mid-tract fractional anisotropy [estimate = −0.046, p = 3.07 × 10−3], radial kurtosis [estimate = −0.165, p = 1.42 × 10−4], f–intra-axonal signal fraction [estimate = −0.044, p = 2.78 × 10−3], p2 orientation coherence [estimate = −0.043, p = 1.64 × 10−3], higher Orientation Dispersion Index [ODI, estimate = 0.023, p = 2.22 × 10−3]) and thalamopremotor tracts (higher mid-tract mean kurtosis [estimate = 0.064, p = 7.56 × 10−4], lower Neurite Density Index [estimate = 0.062, p = 2.1 × 10−3], higher distal tract ODI [estimate = 0.062, p = 3.1 × 10−3], lower f [estimate = −0.1, p = 2.3 × 10−3], and striatopremotor tracts [proximal lower f: estimate = −0.075, p = 1.06 × 10−3]). These measures correlated with clinical measures: dystonia duration (right thalamopremotor distal ODI: r = −0.9, p = 1.29 × 10−14), psychiatric symptoms (obsessive compulsive symptoms: left anterior thalamic radiation p2 r = 0.92, p = 2.797 × 10−11), sleep quality (Sleep Disorders Questionnaire Score: left anterior thalamic radiation ODI: r = −0.84, p = 4.84 × 10−11), pain (left anterior thalamic radiation ODI: r = −0.89, p = 1.4 × 10−13), and cognitive functioning (paired associated learning task p2, r = 0.94, p = 6.68 × 10−20)

Live imaging of targeted cell ablation in Xenopus:a new model to study demyelination and repair

Live imaging studies of the processes of demyelination and remyelination have so far been technically limited in mammals. We have thus generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the central nervous system (CNS). In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein (MBP) regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the E. coli nitroreductase (NTR) selection enzyme. This enzyme converts the innocuous pro-drug metronidazole (MTZ) to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR tadpoles display a graded oligodendrocyte ablation in response to MTZ, which depends on the exposure time to MTZ. MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage. After cessation of MTZ treatment, remyelination proceeded spontaneously, but was strongly accelerated by retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR line as a novel in vivo model for the study of demyelination/remyelination processes and for large-scale screens of therapeutic agents promoting myelin repair

White Matter Microstructural Changes Using Ultra-Strong Diffusion Gradient MRI in Adult-Onset Idiopathic Focal Cervical Dystonia

Background and Objectives Adult-onset idiopathic focal cervical dystonia (AOIFCD) involves abnormal posturing of the cervical musculature and, in some individuals, an associated head tremor. Existing neuroimaging studies have implicated key motor networks. However, measures used to date lack specificity toward underlying pathophysiologic differences. We aim to assess white matter motor pathways for localized, microstructural differences, which may aid in understanding underlying mechanisms. Methods Individuals diagnosed with AOIFCD and an age- and sex-matched control group were prospectively recruited through the Welsh Movement Disorders Research Network. All participants underwent in-depth clinical phenotyping and MRI (structural and diffusion sequences) using ultra-strong diffusion gradients. Tractography (whole-tract median values) and tractometry (along tract profiling) were performed for key white matter motor pathways assessing diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and standard model parameters. Groups were compared using linear model analysis with Bonferroni multiple comparison correction. Results Fifty participants with AOIFCD and 30 healthy control participants were recruited, with 46 with AOIFCD and 30 healthy controls included for analysis (33 without head tremor, 13 with head tremor). Significant differences were observed in the anterior thalamic radiations (lower mid-tract fractional anisotropy [estimate = −0.046, p = 3.07 × 10−3], radial kurtosis [estimate = −0.165, p = 1.42 × 10−4], f–intra-axonal signal fraction [estimate = −0.044, p = 2.78 × 10−3], p2 orientation coherence [estimate = −0.043, p = 1.64 × 10−3], higher Orientation Dispersion Index [ODI, estimate = 0.023, p = 2.22 × 10−3]) and thalamopremotor tracts (higher mid-tract mean kurtosis [estimate = 0.064, p = 7.56 × 10−4], lower Neurite Density Index [estimate = 0.062, p = 2.1 × 10−3], higher distal tract ODI [estimate = 0.062, p = 3.1 × 10−3], lower f [estimate = −0.1, p = 2.3 × 10−3], and striatopremotor tracts [proximal lower f: estimate = −0.075, p = 1.06 × 10−3]). These measures correlated with clinical measures: dystonia duration (right thalamopremotor distal ODI: r = −0.9, p = 1.29 × 10−14), psychiatric symptoms (obsessive compulsive symptoms: left anterior thalamic radiation p2 r = 0.92, p = 2.797 × 10−11), sleep quality (Sleep Disorders Questionnaire Score: left anterior thalamic radiation ODI: r = −0.84, p = 4.84 × 10−11), pain (left anterior thalamic radiation ODI: r = −0.89, p = 1.4 × 10−13), and cognitive functioning (paired associated learning task p2, r = 0.94, p = 6.68 × 10−20)