The role of the ThyGeNEXT oncogene panel used in combination with the expanded miRNA panel ThyraMIRv2 in Indeterminate thyroid nodules: A large, blinded, real-world, observational study.

BACKGROUND: Molecular analysis of fine-needle aspiration biopsies (FNAB) improves the diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs). Recently, the use of MPTXv2 has been shown to further improve the accuracy of risk stratification of ITNs. METHODS: A total of 338 patient samples with atypia of undetermined significance (n = 260) or follicular neoplasm (n = 78) cytology diagnosis and corresponding surgical outcomes or clinical follow-up, collected between 2016 and 2020 were included. All samples underwent multiplatform testing (MPTXv1), which includes an oncogene panel (ThyGeNEXT®) plus a microRNA risk classifier (ThyraMIR®). A blinded, secondary analysis was performed to assess the added utility of MPTXv2 (ThyraMIR®v2). The average length of follow-up for the surveillance group (n = 248) was 30 months. RESULTS: Sensitivity at moderate threshold was 96% and specificity at positive threshold was 99% for MPTXv2. At 14% disease prevalence, the negative predictive value at the moderate threshold was 99% and the positive predictive value at the positive threshold was 89% for MPTXv2. MPTXv2 had fewer patients classified into the moderate-risk group than MPTXv1, which was statistically significant (p < .001). Using surgical resection, the gold standard for outcomes, MPTXv2 showed a statistically greater area under the curve (p = .028) than MPTXv1, demonstrating greater accuracy for MPTXv2. CONCLUSION: Both test versions demonstrated robust performance with low false-positive molecular results. Data suggest that incorporation of MPTXv1, and more recently MPTXv2, into clinical practice within our healthcare network resulted in improved accuracy of ITN risk stratification.

Molecular Genetic Profile of Myelofibrosis: Implications in the Diagnosis, Prognosis, and Treatment Advancements.

Myelofibrosis (MF) is an essential element of primary myelofibrosis, whereas secondary MF may develop in the advanced stages of other myeloid neoplasms, especially polycythemia vera and essential thrombocythemia. Over the last two decades, advances in molecular diagnostic techniques, particularly the integration of next-generation sequencing in clinical laboratories, have revolutionized the diagnosis, classification, and clinical decision making of myelofibrosis. Driver mutations involving JAK2, CALR, and MPL induce hyperactivity in the JAK-STAT signaling pathway, which plays a central role in cell survival and proliferation. Approximately 80% of myelofibrosis cases harbor additional mutations, frequently in the genes responsible for epigenetic regulation and RNA splicing. Detecting these mutations is crucial for diagnosing myeloproliferative neoplasms (MPNs), especially in cases where no mutations are present in the three driver genes (triple-negative MPNs). While fibrosis in the bone marrow results from the disturbance of inflammatory cytokines, it is fundamentally associated with mutation-driven hematopoiesis. The mutation profile and order of acquiring diverse mutations influence the MPN phenotype. Mutation profiling reveals clonal diversity in MF, offering insights into the clonal evolution of neoplastic progression. Prognostic prediction plays a pivotal role in guiding the treatment of myelofibrosis. Mutation profiles and cytogenetic abnormalities have been integrated into advanced prognostic scoring systems and personalized risk stratification for MF. Presently, JAK inhibitors are part of the standard of care for MF, with newer generations developed for enhanced efficacy and reduced adverse effects. However, only a minority of patients have achieved a significant molecular-level response. Clinical trials exploring innovative approaches, such as combining hypomethylation agents that target epigenetic regulators, drugs proven effective in myelodysplastic syndrome, or immune and inflammatory modulators with JAK inhibitors, have demonstrated promising results. These combinations may be more effective in patients with high-risk mutations and complex mutation profiles. Expanding mutation profiling studies with more sensitive and specific molecular methods, as well as sequencing a broader spectrum of genes in clinical patients, may reveal molecular mechanisms in cases currently lacking detectable driver mutations, provide a better understanding of the association between genetic alterations and clinical phenotypes, and offer valuable information to advance personalized treatment protocols to improve long-term survival and eradicate mutant clones with the hope of curing MF.

Privacy-preserving continual learning methods for medical image classification: a comparative analysis.

Background: The implementation of deep learning models for medical image classification poses significant challenges, including gradual performance degradation and limited adaptability to new diseases. However, frequent retraining of models is unfeasible and raises concerns about healthcare privacy due to the retention of prior patient data. To address these issues, this study investigated privacy-preserving continual learning methods as an alternative solution. Methods: We evaluated twelve privacy-preserving non-storage continual learning algorithms based deep learning models for classifying retinal diseases from public optical coherence tomography (OCT) images, in a class-incremental learning scenario. The OCT dataset comprises 108,309 OCT images. Its classes include normal (47.21%), drusen (7.96%), choroidal neovascularization (CNV) (34.35%), and diabetic macular edema (DME) (10.48%). Each class consisted of 250 testing images. For continuous training, the first task involved CNV and normal classes, the second task focused on DME class, and the third task included drusen class. All selected algorithms were further experimented with different training sequence combinations. The final model's average class accuracy was measured. The performance of the joint model obtained through retraining and the original finetune model without continual learning algorithms were compared. Additionally, a publicly available medical dataset for colon cancer detection based on histology slides was selected as a proof of concept, while the CIFAR10 dataset was included as the continual learning benchmark. Results: Among the continual learning algorithms, Brain-inspired-replay (BIR) outperformed the others in the continual learning-based classification of retinal diseases from OCT images, achieving an accuracy of 62.00% (95% confidence interval: 59.36-64.64%), with consistent top performance observed in different training sequences. For colon cancer histology classification, Efficient Feature Transformations (EFT) attained the highest accuracy of 66.82% (95% confidence interval: 64.23-69.42%). In comparison, the joint model achieved accuracies of 90.76% and 89.28%, respectively. The finetune model demonstrated catastrophic forgetting in both datasets. Conclusion: Although the joint retraining model exhibited superior performance, continual learning holds promise in mitigating catastrophic forgetting and facilitating continual model updates while preserving privacy in healthcare deep learning models. Thus, it presents a highly promising solution for the long-term clinical deployment of such models.

Optimizing transition from pediatric to adult care in short bowel syndrome and intestinal failure.

As the majority of children with short bowel syndrome (SBS) and intestinal failure (IF) are now surviving into adulthood, there is a paradigm shift from short-term management to long-term outcomes and a growing need to focus on healthcare transition (HCT). It is imperative that adolescents and young adults with SBS and IF receive disease education, empowerment, and support as they navigate the transition from pediatric to adult care. Furthermore, both pediatric and adult healthcare providers who manage these patients should be aware of the challenges faced by this population, barriers to their HCT, and strategies to overcome them. This article reviews the literature on HCT in children with chronic illnesses, discusses barriers to HCT in SBS/IF, identifies the important constituents of the transition process in SBS/IF, and provides recommendations for the successful and smooth transition of the pediatric patient to the adult healthcare environment. Structured and multicomponent HCT programs should become the standard of care to ensure uninterrupted high-quality care across the life span for patients with SBS/IF.

Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1.

BACKGROUND: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer. METHODS: We accessed archival tissue from rectal cancer patients treated with neoadjuvant cCRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients. RESULTS: We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant cCRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression. CONCLUSIONS: This provides a glimpse into the TME before and after neoadjuvant cCRT. We suggest that the biomarkers noted to be upregulated could be used for designing appropriate clinical trials and development of therapeutic targeted drug therapy in an effort to achieve better response to neoadjuvant therapy, increasing clinical and pathological complete response rates and improved overall outcomes.

Examination of Transition Readiness, Medication Adherence, and Resilience in Pediatric Chronic Illness Populations: A Pilot Study.

The present study assessed the relationship between resilience, adherence, and transition readiness in adolescents/young adults with chronic illness. Participants included 50 patients (Mean age, Mage = 17.3 ± 2.1 years) diagnosed with an oncology disorder (n = 7; 12.1%), hematology disorder (n = 5; 8.6%), nephrology disorder (n = 31; 53.4%), or rheumatology disorder (n = 7; 12.1%). Patients were administered questionnaires assessing resilience (Conner-Davidson Resilience Scale 25-item questionnaire, CD-RISC-25), transition readiness (Self-Management and Transition to Adulthood with Rx=Treatment, STARx), and self-reported medication adherence (Medication Adherence Module, MAM). Medical chart reviews were conducted to determine objective medication adherence rates based on pharmacy refill history (medication adherence ratios). A multivariate correlation analysis was used to examine the relationship between resilience, transition readiness, and adherence. There was a moderate relationship (r = 0.34, p ≤ 0.05) between resilience (M = 74.67 ± 13.95) and transition readiness (M = 67.55 ± 8.20), such that more resilient patients reported increased readiness to transition to adult care. There also was a strong relationship (r = 0.80, p ≤ 0.01) between self-reported medication adherence (M = 86.27% ± 15.98) and pharmacy refill history (Mean Medication Adherence Ratio, MMAR = 0.75 ± 0.27), which indicated that self-reported adherence was consistent with prescription refill history across pediatric illness cohorts. Our findings underscore the importance of assessing resilience, transition readiness, and adherence years before transitioning pediatric patients to adult providers to ensure an easier transition to adult care.

Evaluation of antimicrobial property of modified acrylic resin-containing cetylpyridinium chloride.

OBJECTIVE: To evaluate the antimicrobial property of cetylpyridinium chloride (CPC) when polymerized with cold cure acrylic and to assess the duration of its release from modified acrylic. MATERIALS AND METHODS: CPC was added in different concentrations (0%, 2.5%, 5%, and 10%) to cold cure acrylic resin and 180 acrylic discs were prepared. These were divided into four groups of 45 each depending on the concentration of CPC. The antimicrobial property of the modified acrylic for Streptococcus mutans was tested using disc diffusion assay in agar. The duration of release of CPC from self-cure acrylic was tested with optical density reading of solutions by ultraviolet spectrophotometer. The effect of addition of CPC on diametral tensile strength (DTS) of acrylic was tested using UTM (Instron) and the effect of water aging on modified acrylic was compared with unaged specimens. RESULTS AND CONCLUSION: The normality of the data was checked by Shapiro-Wilktest, and as the data failed to show normal distribution, inferential statistics were performed using nonparametric tests of significance. Antimicrobial activity of modified acrylic increased with increase in CPC concentration. Greatest CPC release was observed on the seventh day with a decrease in release from 7 to 180 days. There was a decrease in the diametral strength of the modified resin and water aging had a significant effect on the DTS of the modified resin.

When Multiple Objective Measures of Medication Adherence Indicate Incongruent Adherence Results: An Example with Pediatric Cancer.

Previous research suggests that children and adolescents with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) often have difficulty adhering to complex treatment regimens during the maintenance phase of therapy. Measurement of treatment adherence can be done via objective (e.g., electronic monitoring (EM), pharmacological assays) or subjective methods (patient, parent, or physician reports). This paper provides an illustration of recommended strategies for comparing discrepancies between two objective measures of medication adherence (e.g., behavioral adherence using electronic monitoring versus pharmacological adherence using 6-mercaptopurine (6MP) metabolite data) within a relatively large cohort of pediatric patients with ALL or LBL (N = 139) who had longitudinal data for both measures of medication adherence over a 15-month period. Additionally, individual- and family-level factors such as gender, socioeconomic status, household environment, and dose intensity will be examined to identify possible sources of discrepancies between adherence measures. This information will provide practical advice for physicians, healthcare providers, and psychologists in identifying nonadherence and the caveats therein so patients achieve the best possible health outcomes.

Psychological Considerations in Pediatric Chronic Illness: Case Examples.

Abstract: Despite significant gains in survival rates for pediatric patients and adolescents/young adults (AYA) with chronic illness, patients in this vulnerable age group are also at an increased risk for developing one or more adverse effects related to their disease, treatment, or maladaptive health behaviors. Maladaptive health behaviors ultimately increase the risk for developing adverse effects, including: increased rates of morbidity and mortality, impaired physical functioning, increased fatigue, obesity, increased psychological distress, and poor quality of life. With close attention including participation in preventive and therapeutic health promotion interventions, problematic health behaviors can be mitigated and ultimately prevented over time. It is well known that improved psychological functioning and adaptive coping can result in improved health status. The present paper provides four case examples illustrating various psychological interventions in pediatric chronic illness. As evidenced in the four case examples, pediatric psychologists provide comprehensive interventions for patients with acute and chronic medical conditions through the use of health promotion interventions, adherence and self-management promotion, cognitive behavioral therapy, behavioral therapy, medical coping, parent training, and motivational interviewing. Our case series demonstrates that for the most impactful behavior change to occur, a combination of interventions is often the most effective.

The Study of Coagulation Parameters in Polytrauma Patients and Their Effects on Outcome.

BACKGROUND: Mortality from trauma remains a major public health issue as it is the leading cause of death in persons aged 5 - 44 years. There is a dearth of information on polytrauma from developing countries such as ours. Hence, this topic was studied at our institute. The objective is to study the coagulation parameters in polytrauma patients at our institute and to correlate the findings with the prognosis. METHODS: A prospective study was carried out in the department of pathology in a tertiary care center, during a period of 20 months from December 2012 to July 2014. All the polytrauma patients (injury severity score (ISS) ≥ 15) with injuries to head and neck, face, thorax, abdomen, extremities and external (skin) were included. Sampling was done within 20 min of arrival during primary survey of the patient. Screening tests like bleeding time (BT) and clotting time (CT) were carried out bedside. Other tests carried out were complete blood count (CBC), prothrombin time (PT), activated thromboplastin time (aPTT), thrombin time (TT) and D-dimer assay. Tests were carried out on fresh samples within 2 h of collection. RESULTS: The incidence of coagulopathy was 59.86%. There was significant prolongation of PT, aPTT and TT in those patients who developed coagulopathy. PT was found to be a stronger predictor of mortality among polytrauma patients. CONCLUSION: A significant proportion of polytrauma patients were coagulopathic. Initial coagulation profile is very useful in predicting outcomes for major polytrauma patients. This study emphasizes the importance of early suspicion and basic screening for coagulopathy in polytrauma patients in developing countries.