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At least 19 records

Tracing and Forecasting Metabolic Indices of Cancer Patients Using Patient-Specific Deep Learning Models

We develop a patient-specific dynamical system model from the time series data of the cancer patient’s metabolic panel taken during the period of cancer treatment and recovery. The model consists of a pair of stacked long short-term memory (LSTM) recurrent neural networks and a fully connected neural network in each unit. It is intended to be used by physicians to trace back and look forward at the patient’s metabolic indices, to identify potential adverse events, and to make short-term predictions. When the model is used in making short-term predictions, the relative error in every index is less than 10% in the L ∞ norm and less than 6.3% in the L 1 norm in the validation process. Once a master model is built, the patient-specific model can be calibrated through transfer learning. As an example, we obtain patient-specific models for four more cancer patients through transfer learning, which all exhibit reduced training time and a comparable level of accuracy. This study demonstrates that this modeling approach is reliable and can deliver clinically acceptable physiological models for tracking and forecasting patients’ metabolic indices.

60 APPLIED LIFE SCIENCES↗

Patient-Reported Toxicity and Quality-of-Life Profiles in Patients With Head and Neck Cancer Treated With Definitive Radiation Therapy or Chemoradiation

Radiation therapy is an effective but burdensome treatment for head and neck cancer (HNC). We aimed to characterize the severity and time pattern of patient-reported symptoms and quality of life in a large cohort of patients with HNC treated with definitive radiation therapy, with or without systemic treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Association of Short-term Patient-reported Outcomes With Long-term Oncologic Outcomes in Localized Prostate Cancer Patients Treated With Radiation Therapy and Androgen Deprivation Therapy in a Randomized Controlled Trial

Both oncologic outcomes and patient-reported outcomes are pivotal in prostate cancer (PCa). However, it remains unknown if there is any association between these 2 outcomes. In this secondary analysis of a randomized controlled trial, we investigated the association of short-term changes in patient-reported outcome with long-term event-free survival (EFS) and metastasis-free survival (MFS) in localized PCa.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M + M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up, whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

60 APPLIED LIFE SCIENCES↗

Floor and ceiling effects in the EORTC QLQ-C30 Physical Functioning subscale among patients with advanced or metastatic breast cancer

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 Physical Functioning subscale is a widely used patient-reported outcome measure that quantifies cancer patients' physical functioning. Strong floor/ceiling effects can affect a scale's sensitivity to change. The aim of this study was to characterize floor/ceiling effects of the physical functioning domain in patients with advanced/metastatic breast cancer enrolled in commercial clinical trials and a community-based trial. The clinical trial cohort comprised patients from 5 registrational trials submitted to the Food and Drug Administration for review (2010-2017). The community cohort comprised a subgroup of patients from the Alliance Patient Reported Outcomes to Enhance Cancer Treatment (PRO-TECT) trial. The distribution of patient responses to Physical Functioning items and the summed score were assessed at the baseline and 3-month follow-up for both cohorts. Descriptive statistics were used to determine floor/ceiling effects at the item and scale levels. The clinical trial cohort and the community cohort consisted of 2407 and 178 patients, respectively. Twenty-four percent or more of the respondents reported “not at all” for having trouble/needing help with each Physical Functioning item across both cohorts and measurement time points. Fourteen to twenty percent of the patients scored perfectly (100 of 100) on the Physical Functioning subscale summary measure (where higher scores indicated better physical functioning) across both cohorts and time points. Minor floor effects and notable ceiling effects were found at the item and scale levels of the Physical Functioning subscale, regardless of cohort, and this creates some uncertainty about its ability to detect changes in physical functioning among high-functioning patients. In conclusion, investigators may consider adding additional high-functioning items from the EORTC's item library to more accurately describe the impact of anticancer treatment on patients' physical functioning.

60 APPLIED LIFE SCIENCES↗

Urban relatives ameliorate survival disparities for genitourinary cancer in rural patients

Patients living in rural areas have worse cancer-specific outcomes. This study examines the effect of family-based social capital on genitourinary cancer survival. We hypothesized that rural patients with urban relatives have improved survival relative to rural patients without urban family. We examined rural and urban based Utah individuals diagnosed with genitourinary cancers between 1968 and 2018. Familial networks were determined using the Utah Population Database. Patients and relatives were classified as rural or urban based on 2010 rural–urban commuting area codes. Overall survival was analyzed using Cox proportional hazards models. We identified 24,746 patients with genitourinary cancer with a median follow-up of 8.72 years. Rural cancer patients without an urban relative had the worst outcomes with cancer-specific survival hazard ratios (HRs) at 5 and 10 years of 1.33 (95% CI 1.10–1.62) and 1.46 (95% CI 1.24–1.73), respectively relative to urban patients. Rural patients with urban first-degree relatives had improved survival with 5- and 10-year survival HRs of 1.21 (95% CI 1.06–1.40) and 1.16 (95% CI 1.03–1.31), respectively. Our findings suggest rural patients who have been diagnosed with a genitourinary cancer have improved survival when having relatives in urban centers relative to rural patients without urban relatives. Further research is needed to better understand the mechanisms through which having an urban family member contributes to improved cancer outcomes for rural patients. Better characterization of this affect may help inform policies to reduce urban–rural cancer disparities.

60 APPLIED LIFE SCIENCES↗

The Prediction Model of Risk Factors for COVID-19 Developing into Severe Illness Based on 1046 Patients with COVID-19

This study analyzed the risk factors for patients with COVID-19 developing severe illnesses and explored the value of applying the logistic model combined with ROC curve analysis to predict the risk of severe illnesses at COVID-19 patients’ admissions. The clinical data of 1046 COVID-19 patients admitted to a designated hospital in a certain city from July to September 2020 were retrospectively analyzed, the clinical characteristics of the patients were collected, and a multivariate unconditional logistic regression analysis was used to determine the risk factors for severe illnesses in COVID-19 patients during hospitalization. Based on the analysis results, a prediction model for severe conditions and the ROC curve were constructed, and the predictive value of the model was assessed. Logistic regression analysis showed that age (OR = 3.257, 95% CI 10.466–18.584), complications with chronic obstructive pulmonary disease (OR = 7.337, 95% CI 0.227–87.021), cough (OR = 5517, 95% CI 0.258–65.024), and venous thrombosis (OR = 7322, 95% CI 0.278–95.020) were risk factors for COVID-19 patients developing severe conditions during hospitalization. When complications were not taken into consideration, COVID-19 patients’ ages, number of diseases, and underlying diseases were risk factors influencing the development of severe illnesses. The ROC curve analysis results showed that the AUC that predicted the severity of COVID-19 patients at admission was 0.943, the optimal threshold was −3.24, and the specificity was 0.824, while the sensitivity was 0.827. The changes in the condition of severe COVID-19 patients are related to many factors such as age, clinical symptoms, and underlying diseases. This study has a certain value in predicting COVID-19 patients that develop from mild to severe conditions, and this prediction model is a useful tool in the quick prediction of the changes in patients’ conditions and providing early intervention for those with risk factors.

Lian, Zhichuang↗

Image analysis reveals differences in tumor multinucleations in Black and White patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma

Background Understanding biological differences between different racial groups of human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies. Methods This study evaluated whether there were morphologic differences between HPV‐associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis‐derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin–eosin images and previously has been prognostic in HPV‐associated OPSCC patients. In this study, the authors specifically evaluated whether the same MuNI cutoff that was prognostic of overall survival (OS) and disease‐free survival in their previous study, T TR , is valid for Black and White patients, separately. We also evaluated population‐specific cutoffs, T B for Blacks and T W for Whites, for risk stratification. Results MuNI was statistically significantly different between Black (mean, 3.88e–4; median, 3.67e–04) and White patients (mean, 3.36e–04; median, 2.99e–04), with p = .0078. Using T TR , MuNI was prognostic of OS in the entire population with hazard ratio (HR) of 1.71 ( p = .002; 95% confidence interval [CI], 1.21–2.43) and in White patients with HR of 1.72 ( p = .005; 95% CI, 1.18–2.51). Population‐specific cutoff, T W , yielded improved HR of 1.77 ( p = .003; 95% CI, 1.21–2.58) for White patients, whereas T B did not improve risk‐stratification in Black patients with HR of 0.6 ( p = .3; HR, 0.6; 95% CI, 0.2–1.80). Conclusions Histological difference between White and Black patient tumors in terms of multinucleated tumor cells suggests the need for considering population‐specific prognostic biomarkers for personalized risk stratification strategies for HPV‐associated OPSCC patients.

Koyuncu, Can F.↗

Factors associated with treatment limitations in two Swedish intensive care units: Prevalence and patient involvement

Abstract The aim was to study the prevalence, documentation, and patient involvement in treatment limitations (TLs) in two Swedish intensive care units (ICUs). All patients admitted to the ICUs of two Swedish regional hospitals in 2019 were screened for inclusion. Exclusion criteria included postanesthesia care <24 h. Patients were identified using the Swedish Intensive Care Registry (SIR) and data were extracted from SIR and hospital charts. Uni‐ and multivariable logistic analysis was performed to investigate associations with the presence of TLs. A total of 3090 patients were admitted to the two ICUs in 2019. After exclusion, 1019 patients were included in the study. 45.5% were women and the mean age was 62.9 years. 26.5% of the patients had one or several TLs. Age (OR 1.04 per one year increase 95% confidence interval (CI) 1.02–1.05), SAPS3‐score (OR 1.08 per one unit increase 95% CI 1.06–1.09) and ICU length of stay (OR 1.11 per one day increase 95% CI 1.05–1.17) were independently associated with an increased likelihood of receiving a TL. 17% of the patients were involved in the decision‐making process and in >30% of cases neither the patient nor next‐of‐kin were informed. Women were to a larger extent involved in the decision process than men (24.5 vs. 12.5% p < .05). When the intensivist documented why a TL was established, patient autonomy was four times more commonly stated as the motivation for the TL among women compared to men (15.5% vs. 3.8% p < .05). TLs were common in two Swedish ICUs but a substantial number of patients and next‐of‐kin were not involved in the decision‐making process or informed of the decision. Women were more often than men engaged in the decision to establish a TL.

Jönsson, Nino↗

Copy number variation in pituitary stalk interruption syndrome: A large case series of sporadic non‐syndromic patients and literature review

Abstract Abnormal hypothalamic/posterior pituitary development appears to be a major determinant of pituitary stalk interruption syndrome (PSIS). The observation of familial cases and associated congenital abnormalities suggests a genetic basis. Single‐gene mutations explain less than 5% of the cases, and whole exome sequencing has shown heterogeneous results. The present study aimed to assess copy number variation (CNV) using array‐based comparative genomic hybridization (aCGH) in patients with non‐syndromic PSIS and comprehensively review data from the literature on CNV analysis in congenital hypopituitarism (CH) patients. Twenty‐one patients with sporadic CH from our outpatient clinics presented with ectopic posterior pituitary (EPP) and no central nervous system abnormalities on magnetic resonance image (MRI) or any other malformations on physical examination at presentation were enrolled in the study. aCGH using a whole‐genome customized 400K oligonucleotide platform was performed in our patients. For the literature review, we searched for case reports of patients with CH and CNV detected by either karyotype or aCGH reported in PubMed up to November 2021. Thirty‐five distinct rare CNVs were observed in 18 patients (86%) and two of them (6%) were classified as pathogenic: one deletion of 1.8 Mb in chromosome 17 (17q12) and one deletion of 15 Mb in chromosome 18 (18p11.32p11.21), each one in a distinct patient. In the literature review, 67 pathogenic CNVs were published in 83 patients with CH, including the present study. Most of these patients had EPP (78% out of the 45 evaluated by sellar MRI) and were syndromic (70%). The most frequently affected chromosomes were X, 18, 20 and 1. Our study has found that CNV can be a mechanism of genetic abnormality in non‐syndromic patients with CH and EPP. In future studies, one or more genes in those CNVs, both pathogenic and variant of uncertain significance, may be considered as good candidate genes.

Correa‐Silva, Silvia R.↗

The effects of exercise training interventions on depression in hemodialysis patients

Purpose Depression considerably influences the clinical outcomes, treatment compliance, quality of life, and mortality of hemodialysis patients. Exercise plays a beneficial role in depressive patients, but its quantitative effects remain elusive. This study aimed to summarize the effects of exercise training on depression in patients with end-stage renal disease undergoing hemodialysis. Methods The PUBMED, EMBASE, and Cochrane Library databases were systematically searched from inception to April 2023 to identify published articles reporting the effect of exercise training on the depression level of patients with End-Stage Renal Disease undergoing hemodialysis. Data were extracted from the included studies using predefined data fields by two independent researchers. The Cochrane Handbook for Systematic Reviews of Interventions and Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies were employed for quality evaluation. Results A total of 22 studies enrolling 1,059 patients who participated in exercise interventions were included. Hemodialysis patients exhibited superior outcomes with intradialytic exercise (SMD = −0.80, 95% CI: −1.10 to −0.49) and lower levels of depression following aerobic exercise (SMD = −0.93, 95%CI: −1.32 to −0.55) compared to combined exercise (c − 0.85, 95% CI: −1.29 to −0.41) and resistance exercise (SMD = −0.40, 95%CI: −0.96 to 0.17). Regarding exercise duration, patients manifested lower depression levels when engaging in exercise activities for a duration exceeding 6 months (SMD = −0.92, 95% CI: −1.67 to −0.17). Concerning the duration of a single exercise session, the most significant improvement was noted when the exercise duration exceeded 60 min (SMD = −1.47, 95% CI: −1.87 to −1.06). Conclusion Our study determined that exercise can alleviate depression symptoms in hemodialysis patients. This study established the varying impacts of different exercise parameters on the reduction of depression levels in hemodialysis patients and is anticipated to lay a theoretical reference for clinicians and nurses to devise tailored exercise strategies for interventions in patients with depression. Systematic review registration https://www.crd.york.ac.uk/prospero/ , This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database, with registration number CRD42023434181.

Yu, Huihui↗

A multiscale model of immune surveillance in micrometastases gives insights on cancer patient digital twins

Abstract Metastasis is the leading cause of death in patients with cancer, driving considerable scientific and clinical interest in immunosurveillance of micrometastases. We investigated this process by creating a multiscale mathematical model to study the interactions between the immune system and the progression of micrometastases in general epithelial tissue. We analyzed the parameter space of the model using high-throughput computing resources to generate over 100,000 virtual patient trajectories. We demonstrated that the model could recapitulate a wide variety of virtual patient trajectories, including uncontrolled growth, partial response, and complete immune response to tumor growth. We classified the virtual patients and identified key patient parameters with the greatest effect on the simulated immunosurveillance. We highlight the lessons derived from this analysis and their impact on the nascent field of cancer patient digital twins (CPDTs). While CPDTs could enable clinicians to systematically dissect the complexity of cancer in each individual patient and inform treatment choices, our work shows that key challenges remain before we can reach this vision. In particular, we show that there remain considerable uncertainties in immune responses, unreliable patient stratification, and unpredictable personalized treatment. Nonetheless, we also show that in spite of these challenges, patient-specific models suggest strategies to increase control of clinically undetectable micrometastases even without complete parameter certainty.

Mathematical & Computational Biology↗

Survival outcomes of patients with head and neck squamous cell cancer with hepatitis B virus infection: An analysis from an endemic tertiary center

Abstract Background Hepatitis B virus (HBV) affects the occurrence and survival outcome of various malignant disorders. The study aimed to evaluate the survival outcome of head and neck squamous cell cancer (HNSCC) patients with or without HBV infection. Methods This study included patients with HNSCC who visited Taichung Veterans General Hospital from 2007 to 2015. HBV infection was defined by hepatitis B surface antigen (HBsAg) seropositivity. By propensity score matching, we compared survival outcomes, including progression‐free survival (PFS) and overall survival (OS), among patients with or without HBV infection. Results The prevalence of HBV infection in our cohort was 12.3%. Among the 1,015 patients included in the matched analysis, a higher risk of baseline liver cirrhosis (11.3% vs. 3.4%, p < 0.001) and initial hepatic dysfunction (10.8% vs. 5.4%, p = 0.005) rates were observed than those without HBV infection at baseline. The 5‐year OS was 43.1% and 53.2% ( p < 0.001) and the 5‐year PFS was 37.4% and 42.3% ( p = 0.007) in patients with and without HBV infection, respectively. The incidence of subsequent hepatic dysfunction showed no difference between patients with and without HBV infection (29.6% vs. 26.8%, p = 0.439). Conclusions Patients with HNSCC and HBV infection were younger and had a higher risk of cirrhosis compared to those without HBV infection. Moreover, HBV infection significantly influenced the OS and PFS outcomes but not subsequent hepatic dysfunction in patients with HNSCC.

Lai, Cheng‐Lun↗

Gut microbiome dynamics and associations with mortality in critically ill patients

Abstract Background Critical illness and care within the intensive care unit (ICU) leads to profound changes in the composition of the gut microbiome. The impact of such changes on the patients and their subsequent disease course remains uncertain. We hypothesized that specific changes in the gut microbiome would be more harmful than others, leading to increased mortality in critically ill patients. Methods This was a prospective cohort study of critically ill adults in the ICU. We obtained rectal swabs from 52 patients and assessed the composition the gut microbiome using 16 S rRNA gene sequencing. We followed patients throughout their ICU course and evaluated their mortality rate at 28 days following admission to the ICU. We used selbal, a machine learning method, to identify the balance of microbial taxa most closely associated with 28-day mortality. Results We found that a proportional ratio of four taxa could be used to distinguish patients with a higher risk of mortality from patients with a lower risk of mortality (p = .02). We named this binarized ratio our microbiome mortality index (MMI). Patients with a high MMI had a higher 28-day mortality compared to those with a low MMI (hazard ratio, 2.2, 95% confidence interval 1.1–4.3), and remained significant after adjustment for other ICU mortality predictors, including the presence of the acute respiratory distress syndrome (ARDS) and the Acute Physiology and Chronic Health Evaluation (APACHE II) score (hazard ratio, 2.5, 95% confidence interval 1.4–4.7). High mortality was driven by taxa from theAnaerococcus(genus) andEnterobacteriaceae(family), while lower mortality was driven byParasutterellaandCampylobacter(genera). Conclusions Dysbiosis in the gut of critically ill patients is an independent risk factor for increased mortality at 28 days after adjustment for clinically significant confounders. Gut dysbiosis may represent a potential therapeutic target for future ICU interventions.

Gastroenterology & Hepatology↗