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1. Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry

   https://doi.org/10.3389/fphys.2023.1287416  

   Nieman, Gary F.; Herrmann, Jacob; Satalin, Joshua; Kollisch-Singule, Michaela; Andrews, Penny L.; Habashi, Nader M.; Tingay, David G.; Gaver, Donald P.; Bates, Jason H.; Kaczka, David W. (November 2023, Frontiers in Physiology)

   Alysson Roncally Silva Carvalho (Ed.)

   Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS. The immediate goal of mechanical ventilation in ARDS should be to prevent atelectrauma resulting from repetitive alveolar collapse and reopening. However, a long-term goal should be to re-open collapsed and edematous regions of the lung and reduce regions of high mechanical stress that lead to regional volutrauma. In this paper, we consider the proposed strategy used by the full-term newborn to open the fluid-filled lung during the initial breaths of life, by ratcheting tissues opened over a series of initial breaths with brief expirations. The newborn’s cry after birth shares key similarities with the Airway Pressure Release Ventilation (APRV) modality, in which the expiratory duration is sufficiently short to minimize end-expiratory derecruitment. Using a simple computational model of the injured lung, we demonstrate that APRV can slowly open even the most recalcitrant alveoli with extended periods of high inspiratory pressure, while reducing alveolar re-collapse with brief expirations. These processes together comprise a ratchet mechanism by which the lung is progressively recruited, similar to the manner in which the newborn lung is aerated during a series of cries, albeit over longer time scales. 

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2. Improving Prediction of Late Symptoms using LSTM and Patient-reported Outcomes for Head and Neck Cancer Patients

   https://doi.org/10.1109/ICHI57859.2023.00047  

   Wang, Yaohua; Dijk, Lisanne Van; Mohamed, Abdallah_S R; Naser, Mohamed; Fuller, Clifton David; Zhang, Xinhua; Marai, G Elisabeta; Canahuate, Guadalupe (June 2023, IEEE Xplore)

   Patient-Reported Outcomes (PRO) are collected directly from the patients using symptom questionnaires. In the case of head and neck cancer patients, PRO surveys are recorded every week during treatment with each patient’s visit to the clinic and at different follow-up times after the treatment has concluded. PRO surveys can be very informative regarding the patient’s status and the effect of treatment on the patient’s quality of life (QoL). Processing PRO data is challenging for several reasons. First, missing data is frequent as patients might skip a question or a questionnaire altogether. Second, PROs are patient-dependent, a rating of 5 for one patient might be a rating of 10 for another patient. Finally, most patients experience severe symptoms during treatment which usually subside over time. However, for some patients, late toxicities persist negatively affecting the patient’s QoL. These long-term severe symptoms are hard to predict and are the focus of this study. In this work, we model PRO data collected from head and neck cancer patients treated at the MD Anderson Cancer Center using the MD Anderson Symptom Inventory (MDASI) questionnaire as time series. We impute missing values with a combination of K nearest neighbor (KNN) and Long Short-Term Memory (LSTM) neural networks, and finally, apply LSTM to predict late symptom severity 12 months after treatment. We compare performance against clinical and ARIMA models. We show that the LSTM model combined with KNN imputation is effective in predicting late-stage symptom ratings for occurrence and severity under the AUC and F1 score metrics. 

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3. Early Diagnosis and Real-Time Monitoring of Regional Lung Function Changes to Prevent Chronic Obstructive Pulmonary Disease Progression to Severe Emphysema

   https://doi.org/10.3390/jcm10245811  

   Jung, Tony; Vij, Neeraj (December 2021, Journal of Clinical Medicine)

   First- and second-hand exposure to smoke or air pollutants is the primary cause of chronic obstructive pulmonary disease (COPD) pathogenesis, where genetic and age-related factors predispose the subject to the initiation and progression of obstructive lung disease. Briefly, airway inflammation, specifically bronchitis, initiates the lung disease, leading to difficulty in breathing (dyspnea) and coughing as initial symptoms, followed by air trapping and inhibition of the flow of air into the lungs due to damage to the alveoli (emphysema). In addition, mucus obstruction and impaired lung clearance mechanisms lead to recurring acute exacerbations causing progressive decline in lung function, eventually requiring lung transplant and other lifesaving interventions to prevent mortality. It is noteworthy that COPD is much more common in the population than currently diagnosed, as only 16 million adult Americans were reported to be diagnosed with COPD as of 2018, although an additional 14 million American adults were estimated to be suffering from COPD but undiagnosed by the current standard of care (SOC) diagnostic, namely the spirometry-based pulmonary function test (PFT). Thus, the main issue driving the adverse disease outcome and significant mortality for COPD is lack of timely diagnosis in the early stages of the disease. The current treatment regime for COPD emphysema is most effective when implemented early, on COPD onset, where alleviating symptoms and exacerbations with timely intervention(s) can prevent steep lung function decline(s) and disease progression to severe emphysema. Therefore, the key to efficiently combatting COPD relies on early detection. Thus, it is important to detect early regional pulmonary function and structural changes to monitor modest disease progression for implementing timely interventions and effectively eliminating emphysema progression. Currently, COPD diagnosis involves using techniques such as COPD screening questionnaires, PFT, arterial blood gas analysis, and/or lung imaging, but these modalities are limited in their capability for early diagnosis and real-time disease monitoring of regional lung function changes. Hence, promising emerging techniques, such as X-ray phase contrast, photoacoustic tomography, ultrasound computed tomography, electrical impedance tomography, the forced oscillation technique, and the impulse oscillometry system powered by robust artificial intelligence and machine learning analysis capability are emerging as novel solutions for early detection and real time monitoring of COPD progression for timely intervention. We discuss here the scope, risks, and limitations of current SOC and emerging COPD diagnostics, with perspective on novel diagnostics providing real time regional lung function monitoring, and predicting exacerbation and/or disease onset for prognosis-based timely intervention(s) to limit COPD–emphysema progression. 

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4. Multi-organ spatial stratification of 3-D dose distributions improves risk prediction of long-term self-reported severe symptoms in oropharyngeal cancer patients receiving radiotherapy: development of a pre-treatment decision support tool

   https://doi.org/10.3389/fonc.2023.1210087  

   Wentzel, Andrew; Mohamed, Abdallah_S R; Naser, Mohamed A; van_Dijk, Lisanne V; Hutcheson, Katherine; Moreno, Amy M; Fuller, Clifton D; Canahuate, Guadalupe; Marai, G Elisabeta (August 2023, Frontiers in Oncology)

   PURPOSE: Identify Oropharyngeal cancer (OPC) patients at high-risk of developing long-term severe radiation-associated symptoms using dose volume histograms for organs-at-risk, via unsupervised clustering. MATERIAL AND METHODS: All patients were treated using radiation therapy for OPC. Dose-volume histograms of organs-at-risk were extracted from patients’ treatment plans. Symptom ratings were collected via the MD Anderson Symptom Inventory (MDASI) given weekly during, and 6 months post-treatment. Drymouth, trouble swallowing, mucus, and vocal dysfunction were selected for analysis in this study. Patient stratifications were obtained by applying Bayesian Mixture Models with three components to patient’s dose histograms for relevant organs. The clusters with the highest total mean doses were translated into dose thresholds using rule mining. Patient stratifications were compared against Tumor staging information using multivariate likelihood ratio tests. Model performance for prediction of moderate/severe symptoms at 6 months was compared against normal tissue complication probability (NTCP) models using cross-validation. RESULTS: A total of 349 patients were included for long-term symptom prediction. High-risk clusters were significantly correlated with outcomes for severe late drymouth (p <.0001, OR = 2.94), swallow (p = .002, OR = 5.13), mucus (p = .001, OR = 3.18), and voice (p = .009, OR = 8.99). Simplified clusters were also correlated with late severe symptoms for drymouth (p <.001, OR = 2.77), swallow (p = .01, OR = 3.63), mucus (p = .01, OR = 2.37), and voice (p <.001, OR = 19.75). Proposed cluster stratifications show better performance than NTCP models for severe drymouth (AUC.598 vs.559, MCC.143 vs.062), swallow (AUC.631 vs.561, MCC.20 vs -.030), mucus (AUC.596 vs.492, MCC.164 vs -.041), and voice (AUC.681 vs.555, MCC.181 vs -.019). Simplified dose thresholds also show better performance than baseline models for predicting late severe ratings for all symptoms. CONCLUSION: Our results show that leveraging the 3-D dose histograms from radiation therapy plan improves stratification of patients according to their risk of experiencing long-term severe radiation associated symptoms, beyond existing NTPC models. Our rule-based method can approximate our stratifications with minimal loss of accuracy and can proactively identify risk factors for radiation-associated toxicity. 

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5. Partially observable collaborative model for optimizing personalized treatment selection

   https://doi.org/10.1016/j.ejor.2023.03.014  

   Gong, Jue; Liu, Shan (September 2023, European Journal of Operational Research)

   Precision medicine that enables personalized treatment decision support has become an increasingly important research topic in chronic disease care. The main challenges in designing a treatment algorithm include modeling individual disease progression dynamics and designing adaptive treatment selection strategy. This study aims to develop an adaptive treatment selection framework tailored to an individual patient’s disease progression pattern and treatment response. We propose a Partially Observable Collaborative Model (POCM) to capture the individual variations in a heterogeneous population and optimize treatment outcomes in three stages. The POCM first infers the disease progression models by subgroup patterns using population data in stage one and then fine-tunes the models for individual patients with a small number of treatment trials in stage two. In stage three, we show how the treatment policies based on the Partially Observable Markov Decision Process (POMDP) can be tailored to individual patients by utilizing the disease models learned from the POCM. Using a simulated population of chronic depression patients, we show that the POCM can more accurately estimate the personal disease progression than the traditional method of solving a hidden Markov model. We also compare the POMDP treatment policies with other heuristic policies and demonstrate that the POCM-based policies give the highest net monetary benefits in majority of parameter settings. To conclude, the POCM method is a promising approach to model the chronic disease progression process and recommend a personalized treatment plan for individual patients in a heterogeneous population. 

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