Measurement properties of the Body Awareness Scale Movement Quality (BAS MQ) in persons on the autism spectrum: A preliminary Rasch analysis.

BACKGROUND: Persons on the autism spectrum exhibit poorer body awareness than neurotypical persons. Since movement quality may be regarded as an expression of body awareness, assessment of movement quality is important. Sound assessments of measurement properties are essential if reliable decisions about body awareness interventions for persons on the autism spectrum are to be made, but there is insufficient research. OBJECTIVE: To assess measurement properties of the Body Awareness Scale Movement Quality (BAS MQ) in an autism and a neurotypical reference group. METHODS: Persons on the autism spectrum (n=108) and neurotypical references (n=32) were included. All were assessed with BAS MQ. Data were analyzed according to the Rasch model. RESULTS: BAS MQ was found to have acceptable unidimensionality, supported by the fit statistics. The hierarchical ordering showed that coordination ability was the most difficult, followed by stability and relating. Response category functioning worked as intended for 19 out of 23 items. There were few difficult items, which decreased targeting. Reliability measures were good. BAS MQ discriminated between the autism and the reference groups, with the autism group exhibiting poorer movement quality, reflecting clinical observations and previous research. CONCLUSIONS: BAS MQ was found to have acceptable measurement properties, though suffering from problems with targeting item difficulty to person ability for persons on the autism spectrum. The BAS MQ may, along with experienced movement quality, contribute to clinically relevant information of persons on the autism spectrum, although we encourage refinements and further analyses to improve its measurement properties.

Dynamic heterogeneity in COVID-19: Insights from a mathematical model.

Critical illness, such as severe COVID-19, is heterogenous in presentation and treatment response. However, it remains possible that clinical course may be influenced by dynamic and/or random events such that similar patients subject to similar injuries may yet follow different trajectories. We deployed a mechanistic mathematical model of COVID-19 to determine the range of possible clinical courses after SARS-CoV-2 infection, which may follow from specific changes in viral properties, immune properties, treatment modality and random external factors such as initial viral load. We find that treatment efficacy and baseline patient or viral features are not the sole determinant of outcome. We found patients with enhanced innate or adaptive immune responses can experience poor viral control, resolution of infection or non-infectious inflammatory injury depending on treatment efficacy and initial viral load. Hypoxemia may result from poor viral control or ongoing inflammation despite effective viral control. Adaptive immune responses may be inhibited by very early effective therapy, resulting in viral load rebound after cessation of therapy. Our model suggests individual disease course may be influenced by the interaction between external and patient-intrinsic factors. These data have implications for the reproducibility of clinical trial cohorts and timing of optimal treatment.

In silico clinical studies for optimal COVID-19 vaccination schedules in patients with cancer.

This study introduces a tailored COVID-19 model for patients with cancer, incorporating viral variants and immune-response dynamics. The model aims to optimize vaccination strategies, contributing to personalized healthcare for vulnerable groups.

Pneumonitis in Patients Receiving Thoracic Radiotherapy and Osimertinib: A Multi-Institutional Study.

Introduction: Thoracic radiotherapy (TRT) is increasingly used in patients receiving osimertinib for advanced NSCLC, and the risk of pneumonitis is not established. We investigated the risk of pneumonitis and potential risk factors in this population. Methods: We performed a multi-institutional retrospective analysis of patients under active treatment with osimertinib who received TRT between April 2016 and July 2022 at two institutions. Clinical characteristics, including whether osimertinib was held during TRT and pneumonitis incidence and grade (Common Terminology Criteria for Adverse Events version 5.0) were documented. Logistic regression analysis was performed to identify risk factors associated with grade 2 or higher (2+) pneumonitis. Results: The median follow-up was 10.2 months (range: 1.9-53.2). Of 102 patients, 14 (13.7%) developed grade 2+ pneumonitis, with a median time to pneumonitis of 3.2 months (range: 1.5-6.3). Pneumonitis risk was not significantly increased in patients who continued osimertinib during TRT compared with patients who held osimertinib during TRT (9.1% versus 15.0%, p = 0.729). Three patients (2.9%) had grade 3 pneumonitis, none had grade 4, and two patients had grade 5 events (2.0%, diagnosed 3.2 mo and 4.4 mo post-TRT). Mean lung dose was associated with the development of grade 2+ pneumonitis in multivariate analysis (OR = 1.19, p = 0.021). Conclusions: Although the overall rate of pneumonitis in patients receiving TRT and osimertinib was relatively low, there was a small risk of severe toxicity. The mean lung dose was associated with an increased risk of developing pneumonitis. These findings inform decision-making for patients and providers.

Traceability and comparability through crosswalks with the NeuroMET Memory Metric.

Accurate assessment of memory ability for persons on the continuum of Alzheimer's disease (AD) is vital for early diagnosis, monitoring of disease progression and evaluation of new therapies. However, currently available neuropsychological tests suffer from a lack of standardization and metrological quality assurance. Improved metrics of memory can be created by carefully combining selected items from legacy short-term memory tests, whilst at the same time retaining validity, and reducing patient burden. In psychometrics, this is known as "crosswalks" to link items empirically. The aim of this paper is to link items from different types of memory tests. Memory test data were collected from the European EMPIR NeuroMET and the SmartAge studies recruited at Charité Hospital (Healthy controls n = 92; Subjective cognitive decline n = 160; Mild cognitive impairment n = 50; and AD n = 58; age range 55-87). A bank of items (n = 57) was developed based on legacy short-term memory items (i.e., Corsi Block Test, Digit Span Test, Rey's Auditory Verbal Learning Test, Word Learning Lists from the CERAD test battery and Mini Mental State Examination; MMSE). The NeuroMET Memory Metric (NMM) is a composite metric that comprises 57 dichotomous items (right/wrong). We previously reported on a preliminary item bank to assess memory based on immediate recall, and have now demonstrated direct comparability of measurements generated from the different legacy tests. We created crosswalks between the NMM and the legacy tests and between the NMM and the full MMSE using Rasch analysis (RUMM2030) and produced two conversion tables. Measurement uncertainties for estimates of person memory ability with the NMM across the full span were smaller than all individual legacy tests, which demonstrates the added value of the NMM. Comparisons with one (MMSE) of the legacy tests showed however higher measurement uncertainties of the NMM for people with a very low memory ability (raw score ≤ 19). The conversion tables developed through crosswalks in this paper provide clinicians and researchers with a practical tool to: (i) compensate for ordinality in raw scores, (ii) ensure traceability to make reliable and valid comparisons when measuring person ability, and (iii) enable comparability between test results from different legacy tests.

Performance of a System for Rapid Phenotypic Antimicrobial Susceptibility Testing of Gram-Negative Bacteria Directly from Positive Blood Culture Bottles.

The rapid administration of optimal antimicrobial treatment is paramount for the treatment of bloodstream infections (BSIs), and rapid antimicrobial susceptibility testing (AST) results are essential. Q-linea has developed the ASTar system, a rapid phenotypic AST device. Here, we report the performance of the ASTar BC G- (Gram-negative) kit when assessed according to the ISO 20776-2:2007 standard for performance evaluation of in vitro diagnostic AST devices. The evaluated ASTar BC G- kit uses a broad panel of 23 antimicrobials for the treatment of BSIs caused by Gram-negative fastidious and nonfastidious bacteria across a range of 6 to 14 2-fold dilutions, including cefoxitin as a screening agent for AmpC-producing Enterobacterales. The ASTar system processes blood culture samples to generate data on MICs and susceptible, intermediate, or resistant (SIR) category. The automated protocol includes concentration determination and concentration adjustment to enable a controlled inoculum, followed by broth microdilution (BMD) and microscopy performed continuously to generate MIC values within approximately 6 h once the test is run on the ASTar system. The performance of the ASTar system was assessed against the ISO 20776-2:2007 standard BMD reference method. Testing was performed across three sites, with results from 412 contrived blood cultures and 74 fresh clinical blood cultures. The ASTar system was also tested for reproducibility, with triplicate testing of 11 strains. The accuracy study comprised 8,650 data points of bacterium-antimicrobial tests. The ASTar system demonstrated an overall essential agreement (EA) of 95.8% (8,283/8,650) and a categorical agreement (CA) of 97.6% (8,433/8,639) compared to the reference BMD method. The overall rate of major discrepancies (MDs) was 0.9% (62/6,845), and that of very major discrepancies (VMDs) was 2.4% (30/1,239). This study shows that the ASTar system delivers reproducible results with overall EA and CA of >95%.

Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.

SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it with available clinical data and use it to simulate the effectiveness of vaccines against viral variants with lower antigenicity, increased virulence, or enhanced cell binding for various vaccine platforms. The analysis includes the omicron variant as well as hypothetical future variants with even greater immune evasion of vaccine-induced antibodies and addresses the potential benefits of the new bivalent vaccines. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts ongoing booster requirements for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model suggests possible strategies for future vaccinations and suggests tailored strategies for high-risk groups.

Mechanistic model for booster doses effectiveness in healthy, cancer and immunosuppressed patients infected with SARS-CoV-2

SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, vaccines are based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity, validate it with available clinical data, and predict vaccine effectiveness for varied vaccine platforms in the setting of variants with ability to escape immunity, increased virulence, or enhanced transmissibility. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts at least one more booster dose is required for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model is useful for planning future vaccinations, and tailoring strategies to risk groups. Significance StatementCurrent SARS-CoV-2 vaccines are effective at preventing COVID-19 or limiting disease severity in healthy individuals, but effectiveness is lower among patients with cancer or immunosuppression. Here, we address the need for predictions of vaccine effectiveness over time by building on our mathematical framework to account for vaccination-induced immunity. A booster dose of both mRNA vaccines can induce a robust enhancement of both antibody levels and numbers of pertinent types of adaptive immune cells, which is predicted to provide sufficient protection for more than one year in healthy patients. However, our model suggests that for immunosuppressed people or patients with cancer receiving an immunosuppressive treatment, the booster effect may wane, and perhaps could be considered on a more frequent basis.

Utility of Noncancerous Chest CT Features for Predicting Overall Survival and Noncancer Death in Patients With Stage I Lung Cancer Treated With Stereotactic Body Radiotherapy.

BACKGROUND. Noncancerous imaging markers can be readily derived from pre-treatment diagnostic and radiotherapy planning chest CT examinations. OBJECTIVE. The purpose of this article was to explore the ability of noncancerous features on chest CT to predict overall survival (OS) and noncancer-related death in patients with stage I lung cancer treated with stereotactic body radiation therapy (SBRT). METHODS. This retrospective study included 282 patients (168 female, 114 male; median age, 75 years) with stage I lung cancer treated with SBRT between January 2009 and June 2017. Pretreatment chest CT was used to quantify coronary artery calcium (CAC) score, pulmonary artery (PA)-to-aorta ratio, emphysema, and body composition in terms of the cross-sectional area and attenuation of skeletal muscle and subcutaneous adipose tissue at the T5, T8, and T10 vertebral levels. Associations of clinical and imaging features with OS were quantified using a multivariable Cox proportional hazards (PH) model. Penalized multivariable Cox PH models to predict OS were constructed using clinical features only and using both clinical and imaging features. The models' discriminatory ability was assessed by constructing time-varying ROC curves and computing AUC at prespecified times. RESULTS. After a median OS of 60.8 months (95% CI, 55.8-68.0), 148 (52.5%) patients had died, including 83 (56.1%) with noncancer deaths. Higher CAC score (11-399: hazard ratio [HR], 1.83 [95% CI, 1.15-2.91], p = .01; ≥ 400: HR, 1.63 [95% CI, 1.01-2.63], p = .04), higher PA-to-aorta ratio (HR, 1.33 [95% CI, 1.16-1.52], p < .001, per 0.1-unit increase), and lower thoracic skeletal muscle index (HR, 0.88 [95% CI, 0.79-0.98], p = .02, per 10-cm2/m2 increase) were independently associated with shorter OS. Discriminatory ability for 5-year OS was greater for the model including clinical and imaging features than for the model including clinical features only (AUC, 0.75 [95% CI, 0.68-0.83] vs 0.61 [95% CI, 0.53-0.70]; p < .01). The model's most important clinical or imaging feature according to mean standardized regression coefficients was the PA-to-aorta ratio. CONCLUSION. In patients undergoing SBRT for stage I lung cancer, higher CAC score, higher PA-to-aorta ratio, and lower thoracic skeletal muscle index independently predicted worse OS. CLINICAL IMPACT. Noncancerous imaging features on chest CT performed before SBRT improve survival prediction compared with clinical features alone.

Incidence of Radiation Therapy Among Patients Enrolled in a Multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic.

Importance: The number of pulmonary nodules discovered incidentally or through screening programs has increased markedly. Multidisciplinary review and management are recommended, but the involvement of radiation oncologists in this context has not been defined. Objective: To assess the role of stereotactic body radiation therapy among patients enrolled in a lung cancer screening program. Design, Setting, and Participants: This prospective cohort study was performed at a pulmonary nodule and lung cancer screening clinic from October 1, 2012, to September 31, 2019. Referrals were based on chest computed tomography with Lung Imaging Reporting and Data System category 4 finding or an incidental nodule 6 mm or larger. A multidisciplinary team of practitioners from radiology, thoracic surgery, pulmonology, medical oncology, and radiation oncology reviewed all nodules and coordinated workup and treatment as indicated. Exposures: Patients referred to the pulmonary nodule and lung cancer screening clinic with an incidental or screen-detected pulmonary nodule. Main Outcomes and Measures: The primary outcome was the proportion of patients undergoing therapeutic intervention with radiation therapy, stratified by the route of detection of their pulmonary nodules (incidental vs screen detected). Secondary outcomes were 2-year local control and metastasis-free survival. Results: Among 1150 total patients (median [IQR] age, 66.5 [59.3-73.7] years; 665 [57.8%] female; 1024 [89.0%] non-Hispanic White; 841 [73.1%] current or former smokers), 234 (20.3%) presented with screen-detected nodules and 916 (79.7%) with incidental nodules. For patients with screen-detected nodules requiring treatment, 41 (17.5%) received treatment, with 31 (75.6%) undergoing surgery and 10 (24.4%) receiving radiation therapy. Patients treated with radiation therapy were older (median [IQR] age, 73.8 [67.1 to 82.1] vs 67.6 [61.0 to 72.9] years; P < .001) and more likely to have history of tobacco use (67 [95.7%] vs 128 [76.6%]; P = .001) than those treated with surgery. Fifty-eight patients treated with radiation therapy (82.9%) were considered high risk for biopsy, and treatment recommendations were based on a clinical diagnosis of lung cancer after multidisciplinary review. All screened patients who received radiation therapy had stage I disease and were treated with stereotactic body radiation therapy. For all patients receiving stereotactic body radiation therapy, 2-year local control was 96.3% (95% CI, 91.1%-100%) and metastasis-free survival was 94.2% (95% CI, 87.7%-100%). Conclusions and Relevance: In this unique prospective cohort, 1 in 4 patients with screen-detected pulmonary nodules requiring intervention were treated with stereotactic body radiation therapy. This finding highlights the role of radiation therapy in a lung cancer screening population and the importance of including radiation oncologists in the multidisciplinary management of pulmonary nodules.

Strategies to minimize heterogeneity and optimize clinical trials in Acute Respiratory Distress Syndrome (ARDS): Insights from mathematical modelling.

BACKGROUND: Mathematical modelling may aid in understanding the complex interactions between injury and immune response in critical illness. METHODS: We utilize a system biology model of COVID-19 to analyze the effect of altering baseline patient characteristics on the outcome of immunomodulatory therapies. We create example parameter sets meant to mimic diverse patient types. For each patient type, we define the optimal treatment, identify biologic programs responsible for clinical responses, and predict biomarkers of those programs. FINDINGS: Model states representing older and hyperinflamed patients respond better to immunomodulation than those representing obese and diabetic patients. The disparate clinical responses are driven by distinct biologic programs. Optimal treatment initiation time is determined by neutrophil recruitment, systemic cytokine expression, systemic microthrombosis and the renin-angiotensin system (RAS) in older patients, and by RAS, systemic microthrombosis and trans IL6 signalling for hyperinflamed patients. For older and hyperinflamed patients, IL6 modulating therapy is predicted to be optimal when initiated very early (<4th day of infection) and broad immunosuppression therapy (corticosteroids) is predicted to be optimally initiated later in the disease (7th - 9th day of infection). We show that markers of biologic programs identified by the model correspond to clinically identified markers of disease severity. INTERPRETATION: We demonstrate that modelling of COVID-19 pathobiology can suggest biomarkers that predict optimal response to a given immunomodulatory treatment. Mathematical modelling thus constitutes a novel adjunct to predictive enrichment and may aid in the reduction of heterogeneity in critical care trials. FUNDING: C.V. received a Marie Sklodowska Curie Actions Individual Fellowship (MSCA-IF-GF-2020-101028945). R.K.J.'s research is supported by R01-CA208205, and U01-CA 224348, R35-CA197743 and grants from the National Foundation for Cancer Research, Jane's Trust Foundation, Advanced Medical Research Foundation and Harvard Ludwig Cancer Center. No funder had a role in production or approval of this manuscript.

Heterogeneous immunogenicity of SARS-CoV-2 vaccines in cancer patients receiving radiotherapy.

The immunogenicity of SARS-CoV-2 vaccines in cancer patients receiving radiotherapy is unknown. This prospective cohort study demonstrates that anti-SARS-CoV-2 spike antibody and neutralization titers are reduced in a subset of thoracic radiotherapy patients, possibly due to immunosuppressive conditions. Antibody testing may be useful to identify candidates for additional vaccine doses.

An off-target scale limits the utility of Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) as a measure of well-being in public health surveys.

OBJECTIVES: To assess the utility and measurement properties for the well-being scale Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) in a Swedish general population survey. STUDY DESIGN: A cross-sectional survey study. METHODS: Data were retrieved from the 2018 public health survey in Stockholm County, containing a random sample of 22 856 persons stratified to be representative for the municipalities and districts within the region. The data were analyzed according to Rasch Measurement Theory. RESULTS: Person attribute values are positively skewed (mean 2.32, SD 1.85), with wide gaps in the item threshold attribute values. Overall item fit statistics were acceptable, and person measurement separation reliability was 0.83, indicating three statistically distinct ranges in the estimated well-being values. CONCLUSION: While the SWEMWBS items indicated acceptable fit to the Rasch measurement model, targeting of items to sample is skewed toward lower levels of well-being, and there is a ceiling effect. Thus, we suggest a careful reconsideration of SWEMWBS as a tool for use in general public health surveys, especially for assessing change over time and group differences, as there are large measurement uncertainties for the majority of cases when the population as a whole is sampled. We encourage revisions applying a coherent and comprehensive ordinal construct theory for well-being to fill the gaps in the upper end of the SWEMWBS scales' item thresholds. The addition of more challenging items would improve targeting for population-based surveys, increase reliability, and provide more actionable information that could be useful in improving individuals' well-being.

Automated clinical target volume delineation using deep 3D neural networks in radiation therapy of Non-small Cell Lung Cancer.

BACKGROUND AND PURPOSE: Clinical targeted volume (CTV) delineation accounting for the patient-specific microscopic tumor spread can be a difficult step in defining the treatment volume. We developed an intelligent and automated CTV delineation system for locally advanced non-small cell lung carcinoma (NSCLC) to cover the microscopic tumor spread while avoiding organs-at-risk (OAR). MATERIALS AND METHODS: A 3D UNet with a customized loss function was used, which takes both the patients' respiration-correlated ("4D") CT scan and the physician contoured internal gross target volume (iGTV) as inputs, and outputs the CTV delineation. Among the 84 identified patients, 60 were randomly selected to train the network, and the remaining as testing. The model performance was evaluated and compared with cropped expansions using the shape similarities to the physicians' contours (the ground-truth) and the avoidance of critical OARs. RESULTS: On the testing datasets, all model-predicted CTV contours followed closely to the ground truth, and were acceptable by physicians. The average dice score was 0.86. Our model-generated contours demonstrated better agreement with the ground-truth than the cropped 5 mm/8 mm expansion method (median of median surface distance of 1.0 mm vs 1.9 mm/2.0 mm), with a small overlap volume with OARs (0.4 cm3 for the esophagus and 1.2 cm3 for the heart). CONCLUSIONS: The CTVs generated by our CTV delineation system agree with the physician's contours. This approach demonstrates the capability of intelligent volumetric expansions with the potential to be used in clinical practice.

Probability of live birth after IVF/ICSI treatments in female early onset cancer survivors: a Finnish population-based registry study.

STUDY QUESTION: Does the probability of a live birth after fresh IVF/ICSI cycles with autologous oocytes differ in early onset female cancer survivors compared to their siblings? SUMMARY ANSWER: The probability of a live birth was similar in female cancer survivors and siblings after four fresh IVF/ICSI cycles. WHAT IS KNOWN ALREADY: Fertility preservation strategies are rapidly being developed to help female cancer patients who wish to have children later. However, there are only a few studies available on fertility treatments and following live births in female cancer survivors before fertility preservation strategies became available. In one of them, the probability of a live birth was reduced after assisted reproductive technology with autologous oocytes in cancer survivors compared to siblings. STUDY DESIGN, SIZE, DURATION: In this retrospective, register-based study, data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8944 female cancer survivors (diagnosed with cancer between 1953 and 2012 at the age of 0-40 years) and 9848 female siblings of survivors eligible for IVF/ICSI treatments between January 1993 and December 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fresh IVF/ICSI cycles and following live birth rates (LBRs) within 22-48 weeks in cancer survivors and siblings at the age of 20-41 years were identified. A binomial regression model with log-link function was used to calculate risk ratio (RR) for live births after fresh IVF/ICSI cycles in survivors compared to siblings, adjusting for attained age and calendar time. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for an IVF/ICSI treatment, as well as overall live births, including both pregnancies after fertility treatments and spontaneous pregnancies, in survivors compared to siblings. MAIN RESULTS AND THE ROLE OF CHANCE: We observed an overall decreased LBR, irrespective of IVF/ICSI treatments, in cancer survivors compared to siblings (IRR 0.68, 95% CI 0.64-0.71). All in all, 179 (2.0%) survivors and 230 (2.3%) siblings were prescribed fertility drugs for IVF/ICSI treatments (IRR 0.72, 95% CI 0.62-0.84). For the first fresh IVF/ICSI cycle, the LBR was 17.2% among survivors and 15.7% among siblings (RR 1.13, 95% CI 0.72-1.87). The mean LBR after four fresh IVF/ICSI cycles was not statistically different in survivors compared to siblings. LIMITATIONS, REASONS FOR CAUTION: In this study, only IVF/ICSI treatments with autologous oocytes were included. The probability of a live birth after a frozen embryo transfer or oocyte donation could not be evaluated in this study. Information on miscarriages, extrauterine pregnancies or termination of pregnancies was not available. WIDER IMPLICATIONS OF THE FINDINGS: For those early onset cancer survivors, who received IVF/ICSI treatments, the probability of live birth was not different from siblings who received IVF/ICSI treatments. However, an overall decreased LBR, irrespective of IVF/ICSI treatments, was observed in cancer survivors compared to siblings, indicating that cancer survivors receiving IVF/ICSI treatments in our study consisted of a selected group with at least a moderate ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Cancer Foundation (Finland) (grant number 130079) and by a grant from LähiTapiola. The authors have no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Results and Molecular Correlates from a Pilot Study of Neoadjuvant Induction FOLFIRINOX Followed by Chemoradiation and Surgery for Gastroesophageal Adenocarcinomas.

PURPOSE: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer. PATIENTS AND METHODS: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response. RESULTS: From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-chemoradiation ctDNA (P = 0.004) and/or postoperative ctDNA (P = 0.045) were associated with disease recurrence. CONCLUSIONS: Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.See related commentary by Catenacci, p. 6281.

Comparing machine learning algorithms for predicting ICU admission and mortality in COVID-19.

As predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and mortality among COVID-19 patients. Using COVID-19 patient data from the Mass General Brigham (MGB) Healthcare database, we developed and internally validated models using patients presenting to the Emergency Department (ED) between March-April 2020 (n = 3597) and further validated them using temporally distinct individuals who presented to the ED between May-August 2020 (n = 1711). We show that ensemble-based models perform better than other model types at predicting both 5-day ICU admission and 28-day mortality from COVID-19. CRP, LDH, and O2 saturation were important for ICU admission models whereas eGFR <60 ml/min/1.73 m2, and neutrophil and lymphocyte percentages were the most important variables for predicting mortality. Implementing such models could help in clinical decision-making for future infectious disease outbreaks including COVID-19.