Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

Structural and Functional Results of Subscapularis and Conjoint Tendon After Latarjet Procedure at 8-Year Average Follow-up

BACKGROUND The Latarjet procedure involves initial dissection through a longitudinal split of the subscapularis tendon with only a final partial closure to accommodate the transferred coracoid bone. Furthermore, by transferring the coracoid bone block to the anterior glenoid, the surgeon completely alters the resting and dynamic route of the attached conjoint tendon. The eventual structural and functional integrity of the subscapularis and conjoint tendons is currently unknown. PURPOSE To examine the structural and functional integrity of the subscapularis and the conjoint tendon after the Latarjet procedure at an 8-year average follow-up. STUDY DESIGN Case series; Level of evidence, 4. METHODS Twenty patients with anterior shoulder instability at a mean age of 30 years (range, 19-50 years) underwent the open Latarjet procedure. Clinical examination at the final follow-up included quantitative isometric measurement of abduction and internal rotation strength compared with the nonoperative side. Patients were assessed via radiograph examination and preoperative computed tomography. Final position and healing of the transferred coracoid bone block were evaluated using standard radiographs. At follow-up, the subscapularis and conjoint tendon were evaluated via magnetic resonance imaging (MRI) with metal artifact reduction techniques and via ultrasound. RESULTS Nineteen of the 20 shoulders remained stable at the final follow-up; there was 1 redislocation (5%) after 14 months. The mean Rowe score was 83 points (SD, 17.9 points), the mean Constant score was 85 points (SD, 8.1 points), and the Subjective Shoulder Value was 80% (SD, 18%). The mean abduction strength of the operative shoulder was 7.41 ± 2.06 kg compared with 8.33 ± 2.53 kg for the nonoperative side (P = .02). The mean internal rotation strength at 0° for the operative shoulder was 8.82 ± 3.47 kg compared with 9.06 ± 3.01 kg for the nonoperative side (P = .36). The mean internal rotation strength in the belly-press position for the operative shoulder was 8.12 ± 2.89 kg compared with 8.50 ± 3.03 kg (P = .13). Four of 20 shoulders showed mild tendinopathic changes of the subscapularis tendon but no partial or complete tear. One patient exhibited fatty degeneration Goutallier stage 1. Conjoint tendon was in continuity in all 20 shoulders on MRI scans. CONCLUSION Abduction, but not internal rotation strength, was slightly reduced after the Latarjet procedure at a mean of 8 years of follow-up. The subscapularis tendon was intact based on ultrasound examination, and the conjoint tendon was intact based on MRI scans. Subscapularis muscle girth relative to the supraspinatus muscle remained intact from preoperative measurements based on MRI scans

Home blood pressure monitoring and e-Health: investigation of patients' experience with the Hy-Result system

International audienceBackground: Hy-Result is a validated system designed to help patients complying with the home blood pressure monitoring (HBPM) protocol and understanding their blood pressure (BP) readings. It is available as a standalone web application or within a wireless BP monitor app. Objective: The aim of the study was to explore patients' experience with Hy-Result. Methods: Online survey completed by 512 users of the Hy-Result web application or monitor app, and three focus groups with 24 hypertensive patients who monitor their BP at home and use the Hy-Result web application to record their data. We assessed the experience of patients with the functionalities and medical content of Hy-Result, their feelings and expectations, and the impact of Hy-Result on the physician-patient relationship. Results: (1) Functionalities: Over 90% of survey respondents and all focus group participants found Hy-Result easy to use. The main drawback of the web application is the need to manually enter all BP values at once. (2) Medical content: Hy-Result offers information on arterial hypertension and HBPM that most patients found useful. Users found that Hy-Result triggers appropriate reactions to BP readings, including adequately timed general practitioner visits. (3) Feelings and expectations: Over 90% of survey respondents trust Hy-Result and focus group participants understood that text messages are suggestions, not diagnoses. Hy-Result did not cause anxiety or excessive BP measurements. (4) Physician-patient relationship: Three-quarter of survey respondents agreed that Hy-Result may help when talking with their doctor about their BP values but only one-third of those have shown the report to their physician. For focus group participants, using Hy-Result should ideally be a physician prescription. They were aware that Hy-Result does not replace clinical judgment and that physicians still have a decisive role in BP management. Conclusion: Most of the users described Hy-Result as an easy-to-use and useful tool. Patients are willing to use it on physician request

Intake and digestibility of meat ewes belonging to two contrasting feed efficiency genetic lines, during their two first production cycles

International audienceFeed is the largest cost in animal production, therefore improving feed efficiency (FE) is one of the main priorities when redesigning farming systems. The objective of this work was to evaluate the effects of a divergent genetic selection for FE in Romane rams [i.e. efficient (RFI-) or inefficient (RFI+)] on the feed intake and nutrient digestibility of their daughters (ewes), reared in different conditions. Different to their sires, which were fed high concentrate-diets, the ewes were fed ad libitum total mixed ration (TMR) composed of silage (65%), hay (25%) and barley (10%). A series of in vivo digestibility trials were conducted using Romane ewes (n =20; 10 RFI- and 10 RFI+) during their 2 first production cycles. The BW, metabolic BW (MBW), body condition score (BCS), DM intake (DMI) and nutrient intake and digestibility were individually monitored. All parameters were significantly affected (P < 0.05) by the production cycle. The BW, MBW, BCS as well as the feed intake and nutrient digestibility were higher in the cycle 2 compared to cycle 1. The exception was the CP digestibility, which was higher in younger ewes (cycle 1). The BW and MBW was, as expected, higher in older ewes thus increasing the feed intake capacity in cycle 2 compared with cycle 1. Slight differences in TMR nutritive composition between the years of the study were also probably responsible of differences in CP digestibility. The RFI+ ewes showed a better BCS than RFI- ewes (3.0 vs. 2.7; P < 0.0001). In the conditions used in this study, we could not demonstrate any differences in intake and digestive efficiency between the two ewe FE lines, probably because the selected rams were tested with one diet (concentrate-based diet) whereas their daughters (ewes) with another (forage-based diet). Further research is warranted to evaluate RFI testing in animals fed a more fibrous diet closer to that of ewes under range conditions whereas also assessing responses to multiple-generation divergent selection on RFI

Angiotensin-Converting Enzyme N-Terminal Inactivation Alleviates Bleomycin-Induced Lung Injury

Bleomycin has potent anti-oncogenic properties for several neoplasms, but drug administration is limited by bleomycin-induced lung fibrosis. Inhibition of the renin-angiotensin system has been suggested to decrease bleomycin toxicity, but the efficacy of such strategies remains uncertain and somewhat contradictory. Our hypothesis is that, besides angiotensin II, other substrates of angiotensin-converting enzyme (ACE), such as the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), play a significant role in controlling fibrosis. We studied bleomycin-induced lung injury in normotensive mice, termed N-KO and C-KO, which have point mutations inactivating either the N- or C-terminal catalytic sites of ACE, respectively. N-KO, but not C-KO mice, have a marked resistance to bleomycin lung injury as assessed by lung histology and hydroxyproline content. To determine the importance of the ACE N-terminal peptide substrate AcSDKP in the resistance to bleomycin injury, N-KO mice were treated with S-17092, a prolyl-oligopeptidase inhibitor that inhibits the formation of AcSDKP. In response to bleomycin injection, S-17092-treated N-KO mice developed lung fibrosis similar to wild-type mice. In contrast, the administration of AcSDKP to wild-type mice reduced lung fibrosis due to bleomycin administration. This study shows that the inactivation of the N-terminal catalytic site of ACE significantly reduced bleomycin-induced lung fibrosis and implicates AcSDKP in the mechanism of protection. These data suggest a possible means to increase tolerance to bleomycin and to treat fibrosing lung diseases

Robust and Efficient Medical Imaging with Self-Supervision

Recent progress in Medical Artificial Intelligence (AI) has delivered systems that can reach clinical expert level performance. However, such systems tend to demonstrate sub-optimal "out-of-distribution" performance when evaluated in clinical settings different from the training environment. A common mitigation strategy is to develop separate systems for each clinical setting using site-specific data [1]. However, this quickly becomes impractical as medical data is time-consuming to acquire and expensive to annotate [2]. Thus, the problem of "data-efficient generalization" presents an ongoing difficulty for Medical AI development. Although progress in representation learning shows promise, their benefits have not been rigorously studied, specifically for out-of-distribution settings. To meet these challenges, we present REMEDIS, a unified representation learning strategy to improve robustness and data-efficiency of medical imaging AI. REMEDIS uses a generic combination of large-scale supervised transfer learning with self-supervised learning and requires little task-specific customization. We study a diverse range of medical imaging tasks and simulate three realistic application scenarios using retrospective data. REMEDIS exhibits significantly improved in-distribution performance with up to 11.5% relative improvement in diagnostic accuracy over a strong supervised baseline. More importantly, our strategy leads to strong data-efficient generalization of medical imaging AI, matching strong supervised baselines using between 1% to 33% of retraining data across tasks. These results suggest that REMEDIS can significantly accelerate the life-cycle of medical imaging AI development thereby presenting an important step forward for medical imaging AI to deliver broad impact

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation (vol 21, pg 764, 2019)

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