Notes

[HerediCaRe: Paperwork plus it Solution of your Specialized Computer registry with regard to Innate Breasts along with Ovarian Cancer].
NRG1 rearrangements are recurrent oncogenic drivers in solid tumors. NRG1 binds to HER3, leading to heterodimerization with other HER/ERBB kinases, increased downstream signaling, and tumorigenesis. Targeting ERBBs, therefore, represents a therapeutic strategy for these cancers. We investigated zenocutuzumab (Zeno; MCLA-128), an antibody-dependent cellular cytotoxicity-enhanced anti-HER2xHER3 bispecific antibody, in NRG1 fusion-positive isogenic and patient-derived cell lines and xenograft models. Zeno inhibited HER3 and AKT phosphorylation, induced expression of apoptosis markers, and inhibited growth. Three patients with chemotherapy-resistant NRG1 fusion-positive metastatic cancer were treated with Zeno. Two patients with ATP1B1-NRG1-positive pancreatic cancer achieved rapid symptomatic, biomarker, and radiographic responses and remained on treatment for over 12 months. A patient with CD74-NRG1-positive non-small cell lung cancer who had progressed on six prior lines of systemic therapy, including afatinib, responded rapidly to treatment with a partial response. Targeting HER2 and HER3 simultaneously with Zeno is a novel therapeutic paradigm for patients with NRG1 fusion-positive cancers.
NRG1 rearrangements encode chimeric ligands that activate the ERBB receptor tyrosine kinase family. Here we show that targeting HER2 and HER3 simultaneously with the bispecific antibody Zeno leads to durable clinical responses in patients with NRG1 fusion-positive cancers and is thus an effective therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1171.
NRG1 rearrangements encode chimeric ligands that activate the ERBB receptor tyrosine kinase family. Here we show that targeting HER2 and HER3 simultaneously with the bispecific antibody Zeno leads to durable clinical responses in patients with NRG1 fusion-positive cancers and is thus an effective therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1171.
Athletes train and compete at the elite level during their reproductive years, yet sport policies that support pregnant athletes are lacking. The experiences of elite athletes during pregnancy are vastly under-represented, and such voices are needed to support evidence-informed policy. Thus, the purpose of this qualitative study was to describe the experiences of elite female athletes as they navigate pregnancy, and to identify sport policy considerations regarding participation during pregnancy.

Twenty athletes (mean age 35±5 years) who, within the last 5 years, had trained or competed at the elite level immediately prior to becoming pregnant were included. Data were generated via one-on-one semistructured interviews that were audio-recorded, transcribed verbatim and analysed through a process of content analysis.

The findings of this study are represented by one overarching message mother versus athlete, and five main themes (1) pregnancy planning and fertility, (2) pregnancy disclosure and discrimination, (3) training pregnant athletic bodies, (4) safety concerns, and (5) supportive network and equitable funding.

In-depth stories shared by participants highlight the many significant decisions athletes must make as they navigate pregnancy alongside elite sport participation. The shared experiences of pregnant athletes highlight clear challenges that should be considered in the development of sport policy and practices that are inclusive and supportive of female athletes.
In-depth stories shared by participants highlight the many significant decisions athletes must make as they navigate pregnancy alongside elite sport participation. The shared experiences of pregnant athletes highlight clear challenges that should be considered in the development of sport policy and practices that are inclusive and supportive of female athletes.
To develop a core outcome set for lateral elbow tendinopathy (COS-LET) and to provide guidance for outcome evaluation in future studies.

We implemented a multi-stage mixed-methods design combining two systematic reviews, domain mapping of outcome measurement instruments to the core domains of tendinopathy, psychometric analysis of instruments, two patient focus groups and a Delphi study incorporating two surveys and an international consensus meeting. Following the OMERACT guidelines, we used a 70% threshold for consensus.

38 clinicians/researchers and 9 patients participated. 60 instruments were assessed for inclusion. CP-690550 JAK inhibitor The only instrument that was recommended for the COS-LET was Patient Rated Tennis Elbow Evaluation (PRTEE) for the disability domain. Interim recommendations were made to use the PRTEE function subscale for the function domain; PRTEE pain subscale items 1, 4 and 5 for the pain over a specified time domain; pain-free grip strength for the physical function capacity domain; a Numerical Rating Scale measuring pain on gripping for the pain on activity/loading domain; and time off work for the participation in life activities domain. No recommendations could be made for the quality-of-life, patient rating of condition and psychological factors domains.

The COS-LET comprises the PRTEE for the disability domain. Interim-use recommendations included PRTEE subscales, time off work, pain-free grip strength and a Numerical Rating Scale measuring pain on gripping. Further work is required to validate these interim measures and develop suitable measures to capture the other domains.
The COS-LET comprises the PRTEE for the disability domain. Interim-use recommendations included PRTEE subscales, time off work, pain-free grip strength and a Numerical Rating Scale measuring pain on gripping. Further work is required to validate these interim measures and develop suitable measures to capture the other domains.
Vertical jump performance (height) is a more representative metric for knee function than horizontal hop performance (distance) in healthy individuals. It is not known what the biomechanical status of athletes after anterior cruciate ligament (ACL) reconstruction (ACLR) is at the time they are cleared to return to sport (RTS) or whether vertical performance metrics better evaluate knee function.

Standard marker-based motion capture and electromyography (EMG) were collected from 26 male athletes cleared to RTS after ACLR and 22 control healthy subjects during single leg vertical jumps (SLJ) and single leg drop jumps (SLDJ). Performance outcomes, jump height and the Reactive Strength Index, were calculated. Sagittal plane kinematics, joint moments and joint work were obtained using inverse dynamics and lower limb muscle forces were computed using an EMG-constrained musculoskeletal model. Muscle contribution was calculated as a percentage of the impulse of all muscle forces in the model. Between-limb and bet interlimb asymmetries than the more commonly used hop distance and should be included in the testing battery for the RTS.
During vertical jumps, male athletes after ACLR at RTS still exhibit knee biomechanical deficits, despite symmetry in horizontal functional performance and strength tests. Vertical performance metrics like jump height and RSI can better identify interlimb asymmetries than the more commonly used hop distance and should be included in the testing battery for the RTS.
Cannabis-related emergency department visits can be an entry point for youths to mental health and substance use care systems. We aimed to examine trends in cannabis-related emergency department visits as a function of youths' age and sex.

Using administrative data, we examined all visits to emergency departments in Ontario, Canada, from 2003 to 2017, by youth aged 10-24 years (grouped as 10-13, 14-18 and 19-24 yr) to determine trends in cannabis-related emergency department visits. Cannabis-related visits were identified using
codes for cannabis poisoning and mental disorders due to cannabinoids. We categorized presentations as "less severe" versus "more severe" using scores assigned by nurses at triage.

We examined 14 697 778 emergency department visits. link2 Cannabis-related visits increased from 3.8 per 10 000 youths (95% confidence interval [CI] 3.5-4.0) in 2003 to 17.9 (95% CI 17.4-18.4) in 2017, a 4.8-fold increase (95% CI 4.4-5.1). Rates increased for both sexes and each age group. Males were more health and social consequences of cannabis-related visits for these youths.
Rates of cannabis-related emergency department visit by youths aged 10-24 years increased almost fivefold from 2003 to 2017, with increases in visit severity and hospital admissions. These trends describe an emerging public health problem, and research is needed to identify the causes of this increase and the health and social consequences of cannabis-related visits for these youths.
Predicting mortality from COVID-19 using information available when patients present to the emergency department can inform goals-of-care decisions and assist with ethical allocation of critical care resources. The study objective was to develop and validate a clinical score to predict emergency department and in-hospital mortality among consecutive nonpalliative patients with COVID-19; in this study, we define palliative patients as those who do not want resuscitative measures, such as intubation, intensive care unit care or cardiopulmonary resuscitation.

This derivation and validation study used observational cohort data recruited from 46 hospitals in 8 Canadian provinces participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN). We included adult (age ≥ 18 yr) nonpalliative patients with confirmed COVID-19 who presented to the emergency department of a participating site between Mar. 1, 2020, and Jan. 31, 2021. We randomly assigned hospitals to derivation or validatiod for level-of-care discussions with patients and in situations of critical care resource constraints to accurately predict death using variables available on emergency department arrival. The score was derived and validated mostly in unvaccinated patients, and before variants of concern were circulating widely and newer treatment regimens implemented in Canada.

ClinicalTrials.gov, no. NCT04702945.
ClinicalTrials.gov, no. NCT04702945.
Hospital-based food insecurity is defined as the inability of caregivers to obtain adequate food during their child's hospital admission. link3 We aimed to measure the prevalence of household and hospital-based food insecurity, and to explore the associations with caregiver distress in an academic pediatric hospital setting.

We conducted a cross-sectional survey of caregivers of children admitted to the general pediatric ward of an academic pediatric hospital in Toronto, Ontario, from April to October 2020. We measured household food insecurity using the 18-item Household Food Security Survey Module, and included 3 adapted questions about hospital-based food insecurity. We measured caregiver distress with the Distress Thermometer for Parents. We used descriptive statistics to assess the proportion of respondents with food insecurity, and linear regression models to explore the relation of household (adult and child) and hospital-based food insecurity with caregiver distress. We used thematic analysis to explore caregivers' feedback.
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