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BackgroundMET exon 14 skipping mutation (METex14) is observed in ~3% of non-small cell lung cancer (NSCLC) cases and has been shown to be an independent poor prognostic factor associated with shorter overall disease-specific survival. Broad molecular testing can identify this biomarker in patients with advanced NSCLC (aNSCLC) and allow patients to be matched with the appropriate targeted therapy. This study examines biomarker testing patterns and clinical outcomes of chemotherapy and immuno-oncology (IO) monotherapy in aNSCLC patients with METex14.MethodsA descriptive retrospective study was conducted using the Flatiron Health–Foundation Medicine Inc. (FMI) clinico-genomic database. Patients with METex14 aNSCLC treated with systemic therapies were included in the biomarker testing analysis. The duration from specimen collection to reported results was assessed for PD-L1– and METex14-tested patients. Clinical outcomes were assessed in patients treated with chemotherapy or IO monotherapy. First-line (1L) and second-line (2L) real-world progression-free survival (rw-PFS) were estimated using Kaplan-Meier analysis.ResultsOf 91 METex14 patients eligible for the biomarker testing analysis, 77% and 60% received PD-L1 and FMI next-generation sequencing (NGS) testing within 3 months post aNSCLC diagnosis. Of those assessed for both PD-L1 and METex14 (n=9), the median duration between specimen collection and reporting was 1 week shorter for PD-L1 than for FMI NGS. Median 1L rw-PFS was 5.7 months (95% CI, 4.6-7.1) and 2.4 months (95% CI, 1.4-3.2) in patients receiving 1L chemotherapy (n=59) and IO monotherapy (n=18), with 3-month 1L rw-PFS rates of 78% and 33%. Median 2L rw-PFS was 3.5 months (95% CI, 1.9-11.1) and 4.7 months (95% CI, 2.8-12.9) in patients receiving 2L chemotherapy (n=16) and IO monotherapy (n=23), with 3-month 2L rw-PFS rates of 54% and 67%.ConclusionsThe median time from biopsy to test results appears 1 week shorter for PD-L1 than for FMI NGS. Chemotherapy and IO monotherapy were the most common regimens utilized but with limited PFS.

IntroductionThe Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023.MethodsTwenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care.ResultsFive outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6.ConclusionsPR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.

An abdominal aortic aneurysm (AAA) in children is a rare clinical condition, with idiopathic AAAs even more atypical. We report a case of a 19-month-old girl with incidental findings of an infrarenal AAA and right common iliac artery aneurysm during workup for heart failure. Extensive genetic testing was unremarkable for connective tissue disorders. An aortic bi-iliac artery bypass with a Dacron graft from the infrarenal aorta to the right external iliac artery and left common iliac artery was performed. The patient achieved complete recovery and only required one oral hypertensive medication at 30 days of follow-up. Wide patency of the graft was observed on the 3-month follow-up computed tomography angiogram.

Background Adherence to pharmacotherapy and use of the correct inhaler technique are important basic principles of asthma management. Video- or remote-direct observation of therapy (v-DOT) could be a feasible approach to facilitate monitoring and supervising therapy, supporting the delivery of standard care.Objective To explore the utility and the feasibility of v-DOT to monitor inhaler technique and adherence to treatment in adults attending the asthma outpatient service in a tertiary hospital in Northern Ireland.Method The project evaluated use of the technology with 10 asthma patients. Patient and clinician feedback was obtained, in addition to measures of patient engagement and disease-specific clinical markers to assess the feasibility and utility of v-DOT technology in this group of patients.Results The engagement rate with v-DOT for participating patients averaged 78% (actual video uploads vs expected video uploads) over a median 7 week usage period. Although 50% of patients reported a technical issue at some stage during the usage period, all patients and clinicians reported that the technology was easy to use and that they were satisfied with the outcomes. A range of positive impacts were observed, including optimised inhaler technique and an observed improvement in lung function. An increase in asthma control test scores aligned with clinical aims to promote adherence and alleviate symptoms.Conclusion The v-DOT technology was shown to be a feasible method of assessing inhaler technique and monitoring adherence in this small group of adult asthma patients. A range of positive impacts for participating patients and clinicians were observed. Not all patients invited to join the project agreed to participate or engage with using the technology, highlighting that in this setting, digital modes of delivering care provide only one of the approaches in the necessary “tool kit” for clinicians and patients.

Abstract Background Juvenile Idiopathic Arthritis (JIA) Associated Uveitis (JIA-U) remains one of the most serious complications of JIA in children. Historically, pediatric JIA is diagnosed by an Optometrist or Ophthalmologist; however, barriers to scheduling increase wait times that may delay diagnosis and treatment. The purpose of this study was to evaluate laser flare photometry (LFP) use to diagnose JIA-U in the Pediatric Rheumatology clinic for patients with JIA. Methods This prospective, observational study assessed pediatric patients diagnosed with JIA without a previous history of uveitis between January 2020 and September 2022. All patients underwent at least one evaluation of both eyes using a Kowa FM-600 laser flare photometer during a routine Rheumatology appointment, as well as a standard slit lamp examination (SLE) by optometry or ophthalmology during routine clinical care. Data collected at patient visits included demographics, JIA characteristics, treatment, LFP readings, and anterior chamber (AC) cell grade score utilizing the SUN grading system. Data were summarized using descriptive analyses and the uveitis false positive rate was calculated. Results The study cohort included 58 pediatric patients diagnosed with JIA. The mean age was 8.4 years (1.2–16.3 years) at diagnosis and 11.9 (4.8–16.5 years) at enrollment. The mean duration of disease at time of enrollment was 42 months (range; 0-157 months). Participants were predominantly female (n = 43, 74.1%) and white/Caucasian race (n = 37, 63.8%). The most common JIA subtypes included persistent oligoarticular JIA (n = 19, 32.8%), and RF negative polyarticular JIA (n = 12, 20.7%). There were 12 ANA positive patients (20.7%). At enrollment, 16 patients (27.6%) were not on medications, with 20 (34.5%) on methotrexate, 20 (34.5%) on adalimumab, 6 (10.3%) on tocilizumab, and 5 (8.6%) on etanercept. During the study period, no eye exams detected active uveitis based on SLE with a SUN grade over 0. However, of the 135 LFP readings, 131 (97.0%) were normal, yielding a false positive rate of 3% (95% CI: 0.8%, 7.4%). Conclusions LFP is a non-invasive tool that can be utilized in the pediatric rheumatology clinic to evaluate for JIA-U. There is a low false positive rate of LFP when compared with standard slit lamp exam.

In recent years, deep venous stenting has increasingly become a treatment strategy for post-thrombotic syndrome. Stent thrombosis can occur, resulting in symptom recurrence despite medical therapy, and there are few options available for durable stent patency restoration. We present a case of a 50-year-old male with prior iliocaval reconstruction that experienced recurrent left lower extremity swelling secondary to occlusion of left external iliac and common iliac vein stents during follow-up. Mechanical thrombectomy with the RevCore System and angioplasty was performed. One month later, the patient demonstrated widely patent bilateral iliac vein stents and complete symptomatic resolution. The RevCore System is a feasible alternative for treatment of chronic in-stent thrombosis.

Abstract As sea level rises, previously sequestered blue carbon can be exported offshore as particulate or dissolved organic matter where it may be re-mineralized or sequestered. The priming effect, or interactive effects of organic matter turnover with a mixed substrate, is well described in soils, but still debated in aquatic systems. Priming may contribute to enhanced blue carbon re-mineralization in coastal environments. Here we examined mangrove-derived dissolved organic matter turnover in a lab incubation, with leachates from mangrove peat, 13C-labeled algae, and peat+algae (primed). Particulate and dissolved organic matter were assessed; microbial metatranscriptomes were evaluated; and dissolved organic matter was characterized with high resolution mass spectrometry. Stable isotopes indicated rapid allocation of algal-derived dissolved organic matter into particulate organic matter. The algal treatment had the greatest increase in carbon dioxide, but primed and peat treatments had the greatest loss of dissolved organic carbon, greater RNA concentrations, and similar changes in total carbon dioxide. This suggests that, while total carbon dioxide did not increase under priming conditions, the addition of a peat substrate may promote microbial biomass production relative to carbon dioxide production. This work highlights that more targeted studies investigating the specific mechanisms of priming are necessary to address the molecular and microbial transformations associated with priming in aquatic systems.

PurposeTo examine body weight change in women undergoing in vitro fertilization and embryo transfer (IVF-ET) using antagonist protocol after up to three treatment cycles.MethodsA prospective cohort study among IVF patients treated between 2018 and 2019. Each patient underwent weight measurement three times during the treatment cycle: before treatment, at the beginning of the hormonal stimulation, and at the completion of the cycle, on the day of the pregnancy test. Data were also analyzed according to the body mass index (BMI) groups for normal weight, overweight, and obese patients. Finally, weight changes were recorded following altogether 519 treatment cycles, 240, 131, and 148 cycles, for normal weight, overweight, and obese patients, respectively.ResultsThe change in the patient's weight was clinically non-significant either during the waiting period or during gonadotropin administration, and overall, during the first, second, or third treatment cycles. The recorded mean total weight change of 0.26 ± 1.85, 0.4 ± 1.81, and 0.17 ± 1.7, after the first, second, or third treatment cycles, represent a change of 0.36%, 0.56%, and 0.23% of their initial weights, respectively. This change of less than 1% of the body weight falls short of the clinically significant weight gain of 5%–7%. Analyzing the data for the various BMI groups, the changes observed in body weight were under 1%, hence with no clinical significance.ConclusionThe findings of the study reject the myth that hormone therapy involves clinically significant weight gain, and this can lower the concerns of many patients who are candidates for treatment of assisted reproductive technology.

Ventricular tachycardia and cardiac tumors are both extremely rare diagnoses in pediatric patients. We report a pediatric case of cardiac fibroma that was noted during the work up of ventricular tachycardia in a young patient concomitantly diagnosed with severe acute respiratory syndrome coronavirus 2.

Bullet embolism following a gunshot wound to the heart is a very unusual cause of acute limb ischemia. We report the case of a 3-year-old boy who sustained a penetrating cardiac trauma secondary to an accidental self-inflicted gunshot wound with a BB (ball bearing) gun. The BB pellet entered the left ventricle and embolized into the peripheral circulation, lodging at the bifurcation of the left common femoral artery. This resulted in acute left lower extremity ischemia. The patient was successfully treated by open common femoral artery exploration and foreign body removal.

Background: Q fever is a zoonotic disease produced by infection with Coxiella burnetii which can cause cardiovascular complications such as endocarditis, aneurysms, and vascular graft infections but is uncommon in the absence of exposure to animal reservoirs. Case summary: We present a case of a 64-year-old patient with chronic Q fever infection of an aortic endograft resulting in aorto-enteric fistula. Exposure history reported a recent travel to Mexico and no contact with animals during the stay. Vascular endograft explant was performed and intraoperative findings revealed an abscess cavity along the right anterior abdominal aorta and an aorto-enteric fistula. Extended course doxycycline and hydroxychloroquine were initiated. Due to the diagnostic challenge, we focused on preventing sepsis progression and exposure mitigation to the surgical team. Conclusion: We highlight the atypical presentation of a Q fever aneurysm, outcomes and possible delayed sequelae. A timely diagnosis and high clinical suspicion are paramount to reduce morbidity rate.

Endovascular treatment options for vascular injury in pediatric patients are quite limited owing to concerns regarding long-term durability and the lack of devices suitable for the pediatric anatomy. However, in rare circumstances, open surgical therapy will not be an option, and patients will require unconventional endovascular solutions for lifesaving or limb-saving therapies. In the present report, we describe an endovascular treatment of a pediatric patient for whom initial surgical management of a blunt abdominal aortic injury had failed, with subsequent development of an aortic pseudoaneurysm. A 10-year-old girl had presented after a high-speed motor vehicle accident with a seatbelt sign. Multiple abdominal injuries were identified, including blunt aortic injury, significant devitalization of the small bowel, colonic perforation with fecal contamination, multiple lumbar spine fractures, and pulmonary contusions. The patient developed bilateral lower extremity ischemia from the aortic injury and had initially undergone open repair. One month later, the patient had developed a pseudoaneurysm of the aorta near the aortic bifurcation. Because of the hostile abdomen and ensuing short gut syndrome, the pseudoaneurysm was managed using endovascular techniques. The limb of an Excluder internal iliac branch endoprosthesis (W.L. Gore & Associates, Flagstaff, AZ) was used as the endograft. The aortic bifurcation was raised and reconstructed using four Viabahn self-expanding stents (W.L. Gore & Associates). The completion angiogram showed complete resolution of the pseudoaneurysm. The follow-up computed tomography angiogram showed widely patent stent grafts with complete resolution of the pseudoaneurysm. Endovascular management of traumatic vascular injuries in pediatric patients is feasible. The likelihood of reintervention in the future is high with patient growth. However, it is a viable option in lifesaving or limb-saving situations in which open repair is high risk.

Measurement(s) Neighborhood context Technology Type(s) Naturally-occurring data Sample Characteristic - Environment City neighborhoods Sample Characteristic - Location Boston, MA, USA

Since 2020, hundreds of thousands of more deaths than expected have been observed across the globe. Amid the coronavirus 2019 (COVID-19) pandemic, current research priorities are to control the spread of infection and minimise loss of life. However, there may be future opportunities to learn from the pandemic to build a better healthcare system that delivers maximum health benefits with minimum harm. So far, much research has focused on foregone benefits of healthcare services such as cancer screening during the pandemic. A more balanced approach is to recognise that all healthcare services have potential harms as well as benefits. In this way, we may be able to use pandemic ‘natural experiments’ to identify cases where a reduction in a healthcare service has not been harmful to the population and some instances where this may have even been beneficial.

We report the case of a 23-year-old female pedestrian who had been struck by a car and had presented with axillary artery transection in the setting of scapulothoracic dissociation. The initial endovascular repair was compromised by her shoulder instability and had required the addition of bridging stent placement. Caution is advised with endovascular repair in this clinical scenario because of possible stent separation.

This study aimed to assess whether the Teslasuit, a wearable motion-sensing technology, could detect subtle changes in gait following slip perturbations comparable to an infrared motion capture system. A total of 12 participants wore Teslasuits equipped with inertial measurement units (IMUs) and reflective markers. The experiments were conducted using the Motek GRAIL system, which allowed for accurate timing of slip perturbations during heel strikes. The data from Teslasuit and camera systems were analyzed using statistical parameter mapping (SPM) to compare gait patterns from the two systems and before and after slip. We found significant changes in ankle angles and moments before and after slip perturbations. We also found that step width significantly increased after slip perturbations (p = 0.03) and total double support time significantly decreased after slip (p = 0.01). However, we found that initial double support time significantly increased after slip (p = 0.01). However, there were no significant differences observed between the Teslasuit and motion capture systems in terms of kinematic curves for ankle, knee, and hip movements. The Teslasuit showed promise as an alternative to camera-based motion capture systems for assessing ankle, knee, and hip kinematics during slips. However, some limitations were noted, including kinematics magnitude differences between the two systems. The findings of this study contribute to the understanding of gait adaptations due to sequential slips and potential use of Teslasuit for fall prevention strategies, such as perturbation training.

Introduction The COVID-19 pandemic has a significant spill-over effect on people with non-communicable diseases (NCDs) over the long term, beyond the direct effect of COVID-19 infection. Evaluating changes in health outcomes, health service use and costs can provide evidence to optimise care for people with NCDs during and after the pandemic, and to better prepare outbreak responses in the future.Methods and analysis This is a population-based cohort study using electronic health records of the Hong Kong Hospital Authority (HA) CMS, economic modelling and serial cross-sectional surveys on health service use. This study includes people aged ≥18 years who have a documented diagnosis of diabetes mellitus, hypertension, cardiovascular disease, cancer, chronic respiratory disease or chronic kidney disease with at least one attendance at the HA hospital or clinic between 1 January 2010 and 31 December 2019, and without COVID-19 infection. Changes in all-cause mortality, disease-specific outcomes, and health services use rates and costs will be assessed between pre-COVID-19 and-post-COVID-19 pandemic or during each wave using an interrupted time series analysis. The long-term health economic impact of healthcare disruptions during the COVID-19 pandemic will be studied using microsimulation modelling. Multivariable Cox proportional hazards regression and Poisson/negative binomial regression will be used to evaluate the effect of different modes of supplementary care on health outcomes.Ethics and dissemination The study was approved by the institutional review board of the University of Hong Kong, the HA Hong Kong West Cluster (reference number UW 21–297). The study findings will be disseminated through peer-reviewed publications and international conferences.

Abstract Ornithine transcarbamylase (OTC) catalyses the reaction from ornithine to citrulline in the urea cycle. Ornithine transcarbamylase deficiency (OTCD) results in episodes of hyperammonemia. Arcturus Therapeutics developed a lipid nanoparticle (LNP)‐encapsulated OTC‐mRNA (LUNAR‐OTC) that results in a replacement enzyme and is currently undergoing clinical trials. In this study, the efficacy of LUNAR OTC‐mRNA drug in the spfash mouse model was examined by measuring the OTC enzyme activity and protein expression in the liver and plasma of OTC‐mRNA‐treated mice. Using purified citrulline‐D4 as the substrate improved the sensitivity of the OTC activity assay and allowed us to quantify the ornithine‐D4 product from the mouse plasma samples. OTC activity in the liver showed a clear dose response: The lowest dose, 0.3 mg/kg, resulted in higher activity than that of the untreated group, and the highest dose, 3 mg/kg, resulted in completely restored OTC activity in the liver. OTC activity in plasma was also dose‐dependent. A clear positive correlation between the OTC activity in the liver and that in the plasma suggests that the plasma OTC activity assay may serve as a surrogate for measuring OTC activity in liver biopsy samples. In addition, the OTC protein expression levels correlated well with the OTC activity in liver samples, but there was no quantifiable OTC protein in the plasma samples. This finding suggests that the sensitivity of the OTC activity assay is superior to that of the protein expression assay. Overall, the results of this study suggest that the OTC activity assay described here can be used as a clinical pharmacodynamic endpoint to measure the effectiveness of OTCD treatment.

The assessment of movement reaction time (RT) as a sideline assessment is a valuable biomarker for mild TBI or concussion. However, such assessments require controlled laboratory environments, which may not be feasible for sideline testing during a game. Body-worn wearable devices are advantageous as being cost-effective, easy to don and use, wirelessly transmit data, and ensure unhindered movement performance. This study aimed to develop a Drop-stick Test System (DTS) with a wireless inertial sensor and confirm its reliability for different standing conditions (Foam versus No Foam) and task types (Single versus Dual), and postures (Standing versus sitting). Fourteen healthy young participants (seven females, seven males; age 24.7 ± 2.6 years) participated in this study. The participants were asked to catch a falling stick attached to the sensor during a drop test. Reaction Times (RTs) were calculated from data for each trial from DTS and laboratory camera system (gold standard). Intraclass correlation coefficients (ICC 3,k) were computed to determine inter-instrument reliability. The RT measurements from participants using the camera system and sensor-based DTS showed moderate to good inter-instrument reliability with an overall ICC of 0.82 (95% CI 0.78–0.85). Bland–Altman plots and 95% levels of agreement revealed a bias where the DTS underestimated RT by approximately 50 ms.

Background: A stroke often bequeaths surviving patients with impaired neuromusculoskeletal systems subjecting them to increased risk of injury (e.g., due to falls) even during activities of daily living. The risk of injuries to such individuals can be related to alterations in their movement. Using inertial sensors to record the digital biomarkers during turning could reveal the relevant turning alterations. Objectives: In this study, movement alterations in stroke survivors (SS) were studied and compared to healthy individuals (HI) in the entire turning task due to its requirement of synergistic application of multiple bodily systems. Methods: The motion of 28 participants (14 SS, 14 HI) during turning was captured using a set of four Inertial Measurement Units, placed on their sternum, sacrum, and both shanks. The motion signals were segmented using the temporal and spatial segmentation of the data from the leading and trailing shanks. Several kinematic parameters, including the range of motion and angular velocity of the four body segments, turning time, the number of cycles involved in the turning task, and portion of the stance phase while turning, were extracted for each participant. Results: The results of temporal processing of the data and comparison between the SS and HI showed that SS had more cycles involved in turning, turn duration, stance phase, range of motion in flexion–extension, and lateral bending for sternum and sacrum (p-value < 0.035). However, HI exhibited larger angular velocity in flexion–extension for all four segments. The results of the spatial processing, in agreement with the prior method, showed no difference between the range of motion in flexion–extension of both shanks (p-value > 0.08). However, it revealed that the angular velocity of the shanks of leading and trailing legs in the direction of turn was more extensive in the HI (p-value < 0.01). Conclusions: The changes in upper/lower body segments of SS could be adequately identified and quantified by IMU sensors. The identified kinematic changes in SS, such as the lower flexion–extension angular velocity of the four body segments and larger lateral bending range of motion in sternum and sacrum compared to HI in turning, could be due to the lack of proper core stability and effect of turning on vestibular system of the participants. This research could facilitate the development of a targeted and efficient rehabilitation program focusing on the affected aspects of turning movement for the stroke community.