Monitoring Treatment Effects Research Articles

Abstract P6-01-16: Circulating Tumour DNA (ctDNA) Detection and Dynamics in Patients with Early Breast Cancer (EBC): Results of the Neoadjuvant TRACER cohort

Abstract Background: ctDNA dynamics are associated with treatment response, and ctDNA detection following treatment is associated with disease recurrence in early breast cancer (EBC). Highly sensitive assays may permit effective risk stratification and guide interventional strategies. RaDaR, a bespoke assay using deep sequencing of tumour-specific variants, has been shown to detect recurrence in the postoperative setting. We quantified ctDNA using RaDaR in serial samples from a large prospective cohort of EBC patients who received standard neoadjuvant chemo- (+/- HER2- targeted) therapy. Methods: Patients with EBC of all receptor subtypes receiving neoadjuvant therapy were enrolled in the TRACER cohort from 2015. Plasma samples (Streck) were collected at baseline, during treatment, perioperatively, and during follow-up. RaDaR was performed on all available timepoints for patients with tissue available for exome sequencing (assay requirement). Clinical and pathologic characteristics, treatment, and recurrence outcomes were collected. Results: 145 patients were recruited as of April 2021, and over 700 plasma samples were collected through December 2021 (patient characteristics, Table 1). 115 (79%) tissue samples were retrieved for assay design. Data are presented for the initial 43 patients and 265 samples analyzed, including 82 post-surgical time points. Median time since diagnosis was 3.5 years (range, 1.5-5.0). Exome sequencing and assay generation were successful in all patients (n=43), yielding assays targeting a median of 48 (range 22-50) variants. 88% (38/43 patients) had ctDNA detected at baseline, with median variant allele frequency (eVAF) in positive patients of 0.15% (range, 0.0019-4.9%). ctDNA levels fell rapidly with treatment: 19/37 (51.3%; median eVAF in positive patients: 0.0098%, range 0.001-0.156%) had ctDNA detected prior to cycle 2, and 4/32 (12.5%) had ctDNA detected at cycle 4 or 5 (mid treatment; median eVAF in positive patients: 0.001%, range, 0.0007-0.011%). In the perioperative period, 17/18 (94%) of patients with available pre-operative specimens and 27/28 (96%) of patients with available post-operative samples had clearance of ctDNA. In adjuvant follow up, ctDNA was detected in 4 of the 43 analyzed patients, with ctDNA clearance observed following planned switch of endocrine therapy in one. Clinical follow-up continues, and analysis of the remaining samples (72 patients and over 425 samples) is underway. Conclusion: RaDaR demonstrated high sensitivity for ctDNA prior to treatment in patients receiving neoadjuvant therapy for EBC, permitted dynamic monitoring of treatment effect, and identified patients with persistent ctDNA after curative-intent therapy, as well as ctDNA emergence prior to clinical recurrence. Full results for the TRACER cohort and analysis of clinical covariates will be presented at the meeting. ClinicalTrials.gov NCT03702309. Table 1. Patient Baseline Characteristics Citation Format: Mitchell J. Elliott, Zachary Veitch, Philippe Bedard, Eitan Amir, Aaron Dou, Jesus Fuentes Antras, Michelle Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Helen Chow, Nathan Campbell, Samantha Terrell, Charlene Knape, Karen Howarth, Lillian Siu, Hal Berman, David W. Cescon. Circulating Tumour DNA (ctDNA) Detection and Dynamics in Patients with Early Breast Cancer (EBC): Results of the Neoadjuvant TRACER cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-16.

Tremor assessment scales before, during and after MRgFUS for essential tremor – results, recommendations and implications

Background neurosurgical interventions such as MR-guided focused ultrasound (MRgFUS) are increasingly deployed for treatment of essential tremor. Objective to make recommendations for monitoring treatment effects during and after MRgFUS based on our investigation of correlations between different scales of tremor severity. Methods twenty-five clinical assessments were collected from thirteen patients before and after unilateral MRgFUS sequential lesioning of the thalamus and posterior subthalamic area for alleviating essential tremor. Scales included Bain Findley Spirography (BFS), Clinical Rating Scale for Tremor (CRST), Upper Extremity Total Tremor Score (UETTS) and Quality of Life of Essential Tremor (QUEST), and were documented at baseline, while lying in the scanner with stereotactic frame attached (BFS), and at 24-month follow-up. Results the four different scales of tremor severity all correlated significantly. BFS and CRST showed a strong correlation of 0.833 (p < 0.001). BFS, UETTS and CRST correlated moderately with QUEST (ρ = 0.575–0.721, p < 0.001). BFS and UETTS correlated significantly with all CRST subparts, with the strongest correlation between UETTS and CRST part C (ρ = 0.831, p < 0.001). Moreover, BFS drawn sitting upright in an outpatient setting correlated with spirals drawn in a supine position on the scanner bed with the stereotactic frame attached. Conclusion we recommend a combination of BFS & UETTS for intraoperative assessment of awake essential tremor patients and BFS & QUEST for pre-operative and follow-up assessments, as these scale sets are quick and simple to collect and provide meaningful information whilst meeting the practical constraints of intraoperative assessment.

Reliability and validity of the incremental shuttle walk test in patients with fully ambulatory multiple sclerosis.

Functional exercise capacity evaluation is crucial to monitor treatment effects and disease progression in people with multiple sclerosis (pwMS). Compared to other tests, the incremental shuttle walking test (ISWT), which more accurately reflects cardiovascular responses, may be more useful for assessing exercise capacity. The aim of the study is to investigate the reliability and validity of the ISWT. Thirty-six pwMS with an Expanded Disability Status Scale (EDSS) score<4.5 between the ages of 25 and 65 were included in the study. The subjects underwent practice (ISWT-p) before undergoing the test-retest protocol in order to rule out the ISWT learning effect (ISWT-1 - ISWT-2). ISWT-1 and ISWT-2 were administered with a 3-7 day interval for test-retest reliability. Six-minutes walking test (6MWT) were applied for concurrent validity. The EDSS, pulmonary function tests, Fatigue Impact Scale (FIS), respiratory muscle strength [maximum inspiratory and expiratory pressure (MIP-MEP)] measurements were made for convergent validity. ISWT was found to have excellent test-retest reliability with an ICC value of 0.97. The area under the curve value was 0.904 indicating that ISWT has a good performance for predicting disease severity. The moderate correlation between ISWT and 6MWT (rho: 0.68, p<0,001) proved concurrent validity. It was also moderately correlated with EDSS, MEP (rho: -0.58 and 0.47 respectively), weakly correlated with MIP and FIS (rho:0.37 and -0.36, respectively) while not correlated with pulmonary function tests. The ISWT had excellent test-retest reliability, acceptable criterion and construct validity in ambulatory MS patients.

Application of deep learning for bronchial asthma diagnostics using respiratory sound recordings.

Methods of computer-assisted diagnostics that utilize deep learning techniques on recordings of respiratory sounds have been developed to diagnose bronchial asthma. In the course of the study an anonymous database containing audio files of respiratory sound recordings of patients suffering from different respiratory diseases and healthy volunteers has been accumulated and used to train the software and control its operation. The database consists of 1,238 records of respiratory sounds of patients and 133 records of volunteers. The age of tested persons was from 18 months to 47 years. The sound recordings were captured during calm breathing at four points: in the oral cavity, above the trachea, at the chest, the second intercostal space on the right side, and at the point on the back. The developed software provides binary classifications (diagnostics) of the type: "sick/healthy" and "asthmatic patient/non-asthmatic patient and healthy". For small test samples of 50 (control group) to 50 records (comparison group), the diagnostic sensitivity metric of the first classifier was 88%, its specificity metric -86% and accuracy metric -87%. The metrics for the classifier "asthmatic patient/non-asthmatic patient and healthy" were 92%, 82%, and 87%, respectively. The last model applied to analyze 941 records in asthmatic patients indicated the correct asthma diagnosis in 93% of cases. The proposed method is distinguished by the fact that the trained model enables diagnostics of bronchial asthma (including differential diagnostics) with high accuracy irrespective of the patient gender and age, stage of the disease, as well as the point of sound recording. The proposed method can be used as an additional screening method for preclinical bronchial asthma diagnostics and serve as a basis for developing methods of computer assisted patient condition monitoring including remote monitoring and real-time estimation of treatment effectiveness.

Perianal Fistula: An Overview

Perianal fistula is a common inflammatory condition in the general population and affects the area around the anal canal. Although most cases are benign, they cause serious morbidity and require surgical treatment due to a high risk of recurrence. MR imaging is a gold standard technique for the evaluation of perianal fistulas and provides accurate information on the anatomy of the anal canal, its relationship to the anal sphincter complex, accurate identification of secondary tracts or abscesses, and reporting associated complications. MR imaging can help monitor treatment effects and determine treatment methods. Crohn's disease-related fistulas often require medical rather than surgical treatment. The radiologist is required to know the anatomy and MR imaging findings of the perianal fistula to present an accurate diagnosis to the clinician.

Evaluation of Intra-Aneurysmal Residual Blood Flow with the iMSDE T1-Black Blood Imaging after Flow Diverter Treatment.

We aimed to evaluate the efficacy of the "improved motion-sensitized driven-equilibrium (iMSDE)"-prepared T1-weighted black blood (T1-BB) MRI for monitoring treatment effect with a flow diverter (FD) for cerebral aneurysms. Following the exclusion of concomitant coiling and retreatment cases from 60 consecutive cases of cerebral aneurysms treated with FDs at our institution, 32 with imaging data were included in the analysis. Detectability of residual blood flow within the aneurysms was validated as follows: 1) comparison of MRI sequences (iMSDE-prepared T1-BB images, T1-weighted images [ T1WI], and time-of-flight [ TOF]-MRA) in cases of incompletely occluded aneurysms and 2) comparison of angiography and MRI sequences in the same period. 1) The probability of diagnosing intra-aneurysmal blood flow was significantly higher with iMSDE-prepared T1-BB (iMSDE-prepared T1-BB vs. T1WI, p <0.001; iMSDE-prepared T1-BB vs. TOF-MRA, p <0.001). 2) The diagnostic accuracy of residual aneurysmal blood flow was significantly higher with iMSDE-prepared T1-BB than that with T1WI (p = 0.032). Furthermore, in cases of incomplete occlusion, the probability of detecting intra-aneurysmal blood flow was significantly higher with iMSDE-prepared T1-BB (iMSDE-prepared T1-BB vs. T1WI, p <0.001; iMSDE-prepared T1-BB vs. TOF-MRA, p = 0.023). Our results demonstrated that iMSDE-prepared T1-BB could help distinguish between blood flow and thrombus within the aneurysms after FD treatment, especially in the early stages of FD treatment.

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders.

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects. To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders. Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 =51, n2 =101), corticobasal degeneration (CBD) (n1 =11, n2 =3), progressive supranuclear palsy (PSP) (n1 =22, n2 =21), multiple system atrophy (MSA) (n1 =31, n2 =26), and healthy control (HC) (n1 =48, n2 =30) participants, as well as Alzheimer's disease (AD) (n2 =23) patients in the second cohort. Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho=0.25-0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho=0.29, P=0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate=-0.025 to -0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate=0.32, P=0.021). These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exploring Application in Lung Cancer Treatment Evaluation via Construction of Exosomes/CTCs Isolation and Identification System and Determination of Hypoxia-Inducible Factor-1α/FGFR

This study aims to realize efficient enrichment of lung cancer exosomes/CTCs and identified by immunofluorescence technique. The multi-site immunolipid magnetic ball were designed using CD63 (for exosomes) and EGFR (for CTCs). Patient’s peripheral blood sample patients with lung cancer were collected (n = 42) before and after treatment with apatinib. The exosomes/CTCs it was it was isolated and identified by transmission electron microscopy, concentration, particle tracer, immunofluorescence check. In addition, the number and identification of CTCs in the included samples were also tested. The results showed that the peripheral blood exosomes increased and the plasma extracellular vesicle concentration decreased significantly after lung cancer treatment. Through detecting genes in the exosomes, Studies have shown that protein expression levels HIF and FGFR gene decreased after apatinib treatment. The decrease of exosomes level and the increase of recurrence after lung cancer may be helpful for tumor monitoring and evaluation of treatment effect. The EGFR-based CTC identification system has high detection ratio and good stability. This exosomal/CTC isolation system is a promising integrated analysis tool and a potential non-invasive diagnostic platform.

Integrative Approaches to the Treatment of Cancer.

A significant proportion of cancer patients use forms of complementary medicine or therapies. An integrative approach to cancer management combines conventional medicine with evidence-based complementary medicines/therapies and lifestyle interventions, for the treatment and prevention of disease and the optimisation of health. Its basis is a holistic one; to treat the whole person, not just the disease. It makes use of adjunct technologies which may assist the clinician in diagnosis of early carcinogenesis and monitoring of treatment effectiveness. Many factors contribute to the development of cancer including some which are largely modifiable by the patient and which oncologists may be in a position to advise on, such as stress, poor nutrition, lack of physical activity, poor sleep, and Vitamin D deficiency. An integrative approach to addressing these factors may contribute to better overall health of the patient and better outcomes. Evidence-based complementary medicine approaches include the use of supplements, herbal medicine, various practices that reduce stress, and physical therapies. Individualised to the patient, these can also help address the symptoms and signs associated with cancer and its orthodox treatment.

Potential biomarkers of atopic dermatitis.

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease with a wide range of heterogeneity. Accurate biomarkers or predictors are the keys to instructing personalized tailored precise treatment. The development of technology such as transcriptomics, genomics, and proteomics provides novel insights into the possibility to find potential biomarkers. Meanwhile, emerging minimally invasive methods such as tape stripping were used to reveal different profiles of patients' skin without biopsy. Several potential biomarkers or predictors have been found. In this review, we summarized the current development of potential biomarkers of AD. Nitric oxide synthase 2/inducible nitric oxide synthase (NOS2/iNOS), human beta-defensin-2 (hBD-2), and matrix metalloproteinases 8/9 (MMP8/9) may be the candidate biomarkers for AD diagnosis. Filaggrin (FLG) gene mutation increased the occurrence risk of AD. Fatty-acid-binding protein 5 (FABP5) may serve as an effective biomarker for the atopic march (AM). Squamous cell carcinoma antigen 2 (SCCA2), serum thymus and activation-regulated chemokine (TARC), cutaneous T-cell-attracting chemokine (CTACK), eosinophil-derived neurotoxin (EDN), macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH), and interleukin (IL)-18 can be the candidate biomarkers for disease severity monitoring. IL-17, IL-23, IL-33, and indoleamine 2,3-dioxygenase (IDO1) can be used as predictive biomarkers for AD comorbidities. LDH, TARC, pulmonary and activation-regulated chemokine (PARC), periostin, IL-22, eotaxin-1/3, and IL-8 may be the candidate biomarkers for monitoring treatment effects. There are still unmet needs and a long way to go for more convenient, non-invasive, and effective predictors and biomarkers to better guide personalized precise treatment.

Estimation of blood-based biomarkers of glial activation related to neuroinflammation

BackgroundNeuroinflammation is a well-known feature of Alzheimer’s disease (AD), and a blood-based test for estimating the levels of neuroinflammation would be expected. In this study, we examined and validated a model using blood-based biomarkers to predict the level of glial activation due to neuroinflammation, as estimated by 11C-DPA-713 positron emission tomography (PET) imaging. MethodsWe included 15 patients with AD and 10 cognitively normal (CN) subjects. Stepwise backward deletion multiple regression analysis was used to determine the predictors of the TSPO-binding potential (BPND) estimated by PET imaging. The independent variables were age, sex, diagnosis, apolipoprotein E4 positivity, body mass index and the serum concentration of blood-based biomarkers, including monocyte chemotactic protein 1 (MCP-1), fractalkine, chitinase 3-like protein-1 (CHI3L1), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and clusterin. ResultsSex, diagnosis, and serum concentrations of MCP1 and sTREM2 were determined as predictors of TSPO-BPND in the Braak1-3 area. The serum concentrations of MCP1 and sTREM2 correlated positively with TSPO-BPND. In a leave one out (LOO) cross-validation (CV) analysis, the model gave a LOO CV R2 of 0.424, which indicated that this model can account for approximately 42.4% of the variance of brain TSPO-BPND. ConclusionsWe found that the model including serum MCP-1 and sTREM2 concentration and covariates of sex and diagnosis was the best for predicting brain TSPO-BPND. The detection of neuroinflammation in AD patients by blood-based biomarkers should be a sensitive and useful tool for making an early diagnosis and monitoring disease progression and treatment effectiveness.

PET imaging in animal models of Parkinson’s disease

Alpha-synucleinopathies, such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy, are characterized by aberrant accumulation of alpha-synuclein and synaptic dysfunction leading to motor and cognitive deficits. Animal models of alpha-synucleinopathy have greatly facilitated the mechanistic understanding of the disease and the development of therapeutics. Various transgenic, alpha-synuclein fibril-injected, and toxin-injected animal models of Parkinson’s disease and multiple system atrophy that recapitulate the disease pathology have been developed and widely used. Recent advances in positron emission tomography have allowed the noninvasive visualization of molecular alterations, underpinning behavioral dysfunctions in the brains of animal models and the longitudinal monitoring of treatment effects. Imaging studies in these disease animal models have employed multi-tracer PET designs to reveal dopaminergic deficits together with other molecular alterations. This review focuses on the development of new positron emission tomography tracers and studies of alpha-synuclein, synaptic vesicle glycoprotein 2A neurotransmitter receptor deficits such as dopaminergic receptor, dopaminergic transporter, serotonergic receptor, vesicular monoamine transporter 2, hypometabolism, neuroinflammation, mitochondrial dysfunction and leucine rich repeat kinase 2 in animal models of Parkinson’s disease. The outstanding challenges and emerging applications are outlined, such as investigating the gut-brain-axis by using positron emission tomography in animal models, and provide a future outlook.

Mathematical Estimation of Axial Length Increment in the Control of Myopia Progression.

This study aims to evaluate the existing mathematical approach for the theoretical estimation of axial length (AL) in a cross-sectional study, developing a new mathematical model and testing it in a longitudinal sample. Many professionals do not have a device to measure the AL due to clinic space and cost of equipment. However, this parameter plays an important role in the assessment of myopia progression to monitor treatment effects with myopia control strategies. First, a cross-sectional study based on the mathematical equation proposed by Morgan was performed. The AL was estimated based on the mean values of keratometry and spherical equivalent in 1783 subjects (52% female), aged 14.6 ± 4.6 years (6 to 25 years), of whom 738 were myopic, 770 emmetropic and 275 hyperopic. On average, the AL estimated with the Morgan formula was 0.25 ± 0.48 mm larger than the real AL value (95% limits of agreement: +0.70 to −1.20 mm). The study by gender, ametropia, type of astigmatism and age showed statistically significant differences between the real AL and predicted AL_Morgan (r > 0.750, spearman). Based on the previous sample, a multiple linear regression was applied, and a new mathematical model was proposed. The model was tested on a longitudinal sample of 152 subjects whose mean age was 13.3 ± 3.1 years (9 to 24 years) and of whom 96 were female (64%). The sample consisted of 46 myopes, 82 emmetropes and 24 hyperopes. The longitudinal study of the differences in axial length at one year between the models showed no statistically significant differences and that the mathematical equations are valid for estimating differences in axial increment for ages between 9 and 24 years, despite errors in the predicted value for axial length.

Complex Neuropsychiatric and Laboratory-Instrumental Diagnostics in Determination of Tactics of Therapeutic Management of Patients with Spinal Muscular Atrophy: Regional Experience

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare hereditary disabling disease and the most common hereditary cause of infant deaths. The timely comprehensive diagnosis of SMA permits to plan therapeutic tactics and preserve the quality of patients life. One of the objectives of the given work is a review of the actual literature data on etiopathogenesis, clinical presentation, valid diagnosis and modern effective tactics of SMA management.&#x0D; AIM: To evaluate the management tactics of patients with SMA taking into account neuropsychiatric symptoms, to analyze problems of proposal and organization of measures aimed at improvement of the quality of medical care, on the basis of the practical experience of the Samara region and with consideration of the current state of the problem.&#x0D; MATERIALS AND METHODS: In the work, the data of the archive of Seredavin Samara Regional Clinical Hospital were analyzed, 132 medical histories of 77 patients were processed with discharge dates from January 2008 to February 2022 with the following diagnoses (according to the code of the International Classification of Diseases and Health Related Problem, 10th revision (ICD-10)): G12.0 (spinal muscular atrophy, type I [WerdnigHoffmann disease], G12.1 (other hereditary SMA), G12.8 (other SMA and related syndromes) and G12.9 (unspecified SMA). The analysis of the results of clinical, laboratory, instrumental and neuropsychiatric diagnostic methods was performed in comparison with the tactics of therapeutic management of these patients. For statistical processing of the data, methods of descriptive statistics were used.&#x0D; RESULTS: Socio-demographic data. As of February 2022, 58 patients were registered (mean age 38.4 (41.3) years, of them 32 (55.2%) were individuals of female gender including 21 children (mean age 12.3 (7.4) years, 14 (24.1%) girls), with the following diagnoses according to ICD-10: G12.0 (n = 7; 12.0%; only children), G12.1 (children: n = 14; 24.1%; adults: n = 29; 50.0%), G12.8 (n = 6; 10.3%; only adults), G12.9 (n = 2; 3.4%; only adults). Clinical data. Motor disorders from a mild proximal lower paraparesis (n = 13; 22.4%) to pronounced tetraparesis (n = 7; 12.0%). The study of mental status was limited to evaluation of the state of consciousness and effectiveness of contact. Data on therapy. Until 2021, symptomatic therapy of SMA was conducted in the region, since March 2021, 8 children (13.8% of the total sample) aged 7.3 (8.8) years received nusinersen, another 8 children (13.8%) aged 9.5 (6.9) years received risdiplam; parents of 3 more children (5.2%) refused taking drugs. Of adult patients (n = 37; 63.8%; 35.3 (23.6) years) with confirmed SMA 5q (n = 10; 17.2%, 35.3 (19.0) years), 1 patient received nusinersen, the rest 9 patients (15.5%) did not receive therapy, 3 (5.2%) were achieving the right to receive drugs (at the moment of the analysis).&#x0D; CONCLUSION: The data analysis revealed deficit of early SMA diagnosis (at the moment of the diagnosis, all the patients were already having pronounced symptoms), of assessment of affective and cognitive disorders, monitoring of treatment effectiveness (absence of validated scales for motor skills assessment), and also showed low availability of treatment for adult patients, which requires reorganization of care of patients with SMA in the region taking into account the revealed factors).

The Impact of Carbohydrate Antigen 19-9 on Survival in Patients with Clinical Stage I and II Pancreatic Cancer.

Carbohydrate antigen (CA)19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB). The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I-II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98U/mL and CA19-9 ≥ 98U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported. Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1%) and II (60%) patients had CA19-9 ≥ 98U/mL. Stage I-II patients with CA19-9 < 98U/mL had improved OS rates (stage I: 67.5%, 42.6%; stage II: 59.8%, 32.8%) compared with stage I and II patients with CA19-9 ≥ 98U/mL (stage I: 50.7%, 26.9%; stage II: 48.1%, 22%). Among resected stage I patients, CA19-9 <98U/mL was associated with improved OS (< 98: 80.5%, 56%; ≥ 98: 70.2%, 42.8%), and a similar trend was seen in resected stage II patients (< 98: 77.6%, 49.9%; ≥ 98: 71%, 39.2%). Unresected stage I patients with lower CA19-9 had improved OS (< 98: 42.1%, 17.5; ≥ 98: 29.9%, 10%), with similar findings in unresected stage II patients (< 98: 41.1%, 15.3%; ≥ 98: 33.4%, 10.6%). Our study demonstrated the prognostic value of CA19-9 in patients with clinical stage I-II PC, with a value < 98 U/mL demonstrating improved survival. Surgery significantly improved survival at 12 and 24 months irrespective of CA19-9.

Cardiac magnetic resonance imaging before and after therapeutic interventions for systemic sclerosis-associated myocarditis.

Cardiac magnetic resonance imaging (CMRI) is increasingly used to evaluate cardiac involvement in SSc. We assessed changes, including inflammatory and/or fibrotic myocardial lesions detected by CMRI, following therapeutic interventions for SSc-associated symptomatic myocarditis. In this retrospective study, myocarditis was diagnosed by CMRI (2018 revised Lake Louise criteria) in 14 diffuse and 4 limited SSc patients [16/18 women, age 56 years (s.d. 11), disease duration 8 years (s.d. 11), 17/18 with lung involvement] with cardiac symptoms and abnormal findings on echocardiography (4/18) and/or in 24-hour Holter monitoring (12/14). CMRI was repeated after 8 months (s.d. 3) following administration of cyclophosphamide (n = 11, combined with corticosteroids in 3 and rituximab in 1), mycophenolate (n = 1), tocilizumab (n = 1), methotrexate/corticosteroids (n = 2), corticosteroids (n = 1) or autologous stem cell transplantation (n = 2). Functional cardiac improvement was evident by increases in left [by 5.8% (s.d. 7.8), P = 0.006] and right ventricular ejection fraction [by 4.5% (s.d. 11.4), P = 0.085] in the second CMRI compared with the first. Notably, late gadolinium enhancement, currently considered to denote replacement fibrosis, decreased by 3.1% (s.d. 3.8; P = 0.003), resolving in six patients. Markers of myocardial oedema, namely T2 ratio and T2 mapping, decreased by 0.27 (s.d. 0.40; P = 0.013) and 6.0 (s.d. 7; P = 0.025), respectively. Conversely, both T1 mapping, considered to reflect acute oedema and diffuse fibrosis, and extracellular volume fraction, reflecting diffuse fibrosis, remained unchanged. CMRI may distinguish between reversible inflammatory/fibrotic and irreversible fibrotic lesions in SSc patients with active myocarditis, confirming the unique nature of primary cardiac involvement in SSc. Whether, and how, CMRI should be used to monitor treatment effects in SSc-associated myocarditis warrants further study.

Integrating molecular biomarkers in breast cancer rehabilitation. What is the current evidence? A systematic review of randomized controlled trials.

Background: Quality of life issues is a crucial burden in breast cancer (BC) survivors with relevant implications in terms of survivorship and health-care costs. The increasing long-term survival of these patients provides new challenges, with translational research now focusing on innovative and tailored approaches to improve their complex management. In this scenario, several emerging biomarkers have the potential to improve the clinical rehabilitative management of patients with BC. However, to date, guidelines supporting biomarker implementation in this area are still lacking. Therefore, the aim of this systematic review was to summarize the currently available biomarkers that might be potentially integrated into rehabilitation practice to promote a precision medicine approach to BC survivorship issues. Methods: On 9th March 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for randomized controlled trials (RCTs) assessing rehabilitation interventions in BC patients. Molecular biomarker modifications induced by physical exercise have been assessed through the review of the study protocols and published results. The Jadad scale was used to assess the quality of the studies included. Results: Out of 2,224 records, 22 studies were included in the present systematic review. Exercise therapy showed significant results in 15 RCTs, in terms of metabolic biomarkers, including glycemic and insulin profile, and lipid profile (p ≤ 0.05). Similarly, 12 studies underlined significant effects in inflammation and immune response biomarkers, including TNF-α, IL-6, IL-10, C-reactive protein, leptin, and adiponectin (p ≤ 0.05). On the other hand, cardiac biomarkers were assessed in three studies without reporting significant differences after exercise therapy (p = NS). The quality assessment identified 19 RCTs as high-quality studies and three RCTs of low quality. Conclusion: Our findings reveal significant biochemical perturbations in key molecules induced by physical exercise in patients with BC, suggesting room for the implementation of actionable biomarkers. Future research might clarify the role of biomarkers on treatment effectiveness monitoring, to optimize rehabilitative strategies tailored to patient’s needs.

Analysis of clinical and endoscopic characteristics of colorectal polyps in children

To analyze the clinical and endoscopic characteristics of colorectal polyps in children, and to explore the detection rate, age and gender distribution characteristics, endoscopic treatment effect and follow-up monitoring of colorectal polyps in children, so as to provide reference for disease management of colorectal polyps in children. The clinical and endoscopic characteristics of children with colorectal polyps in Xi 'an Children's Hospital from January 2019 to December 2019 were retrospectively analyzed. The patients were divided into 5 groups according to age (y): 0<y<1 years, 1≤ y<4 years, 4≤ y<7 years, 7≤ y<12 years, and 12≤ y ≤18 years. Independent sample t test, Pearson Chi-square test (χ2) were used to compare groups' differences. The results showed that a total of 724 colonoscopies were completed in 2019, and 160 colorectal polyps were diagnosed, with a detection rate of 22.10%. Among the children with colorectal polyps, 105 were males, accounting for 65.62%, and 55 were females, accounting for 34.38%. The detection rate of male colorectal polyps was 22.68%, and the detection rate of female colorectal polyps was 21.08%. There was no significant difference in the detection rate of colorectal polyps between males and females (χ2 = 0.25, P =0.617). Children with colorectal polyps were most common in the age group of 1≤ y<4 years, 72 cases, accounting for 41.14%(72/175). The detection rate of colorectal polyps in different age groups was statistically significant (χ2=73.929, P<0.05). The main symptom of children with colorectal polyps was hematochezia, accounting for 87.5% (140/160). Colorectal polyps were mainly single polyps in 140 patients, accounting for 87.50%, 15 patients had 2-4 polyps, accounting for 9.38%, and 5 patients had 5 or more polyps, accounting for 3.12%. A total of 210 polyps were removed, and the most common site of polyps was rectum, 123 polyps, accounting for 58.57% (123/210). 111 (52.86%, 111/210) of them were 1 cm to 2 cm in diameter. The Yamada classification was mainly type Ⅲ, 114 pieces, accounting for 54.29% (114/210). Among the 210 polyps with diameter ≥0.5 cm, 165 were removed by endoscopic mucosal resection, accounting for 78.57% (165/210). There were 23 patients with postoperative complications, including hematochezia, abdominal pain, fever, vomiting, diarrhea, dizziness, and no gastrointestinal perforation. Juvenile polyps were the main pathological type, accounting for 88.13% (141/160). The children with juvenile polyps were followed up for 3-30 months, and recurrence was considered in 2 of them. In conclusion, the detection rate of colorectal polyps in children aged 1≤ y<4 years is high, and hematochezia is the main clinical manifestation. Standardized endoscopic treatment and follow-up monitoring are very important for children with colorectal polyps.

Research advances in the application of bone metabolic markers in children's diseases associated with growth and development

The incidence of children's growth and development diseases such as rickets, obesity, dwarfism and precocious puberty has increased year by year recently. The occurrence and development of these diseases are often closely related to children's malnutrition and endocrine disorders. Plenty of studies have indicated that bone is not only the structural scaffold of human body, but also an important endocrine and hormone target organ. As a series of substances closely related to bone formation and bone resorption, the levels of bone metabolic markers have been confirmed to change in the course of many children's growth and development diseases. The characteristics, classification and application of bone metabolism markers in children's growth and development related diseases was summarized and commented in this article in order to provide reference for the prevention, early diagnosis and treatment effect monitoring of children's growth and development diseases.

Compartmental model describing the physiological basis for the HepQuant SHUNT test

The HepQuant SHUNT test quantifies hepatic functional impairment from the simultaneous clearance of cholate from the systemic and portal circulations for the purpose of monitoring treatment effects or for predicting risk for clinical outcome. Compartmental models are defined by distribution volumes and transfer rates between volumes to estimate parameters not defined by noncompartmental analyses. Previously, a noncompartmental analysis method, called the minimal model (MM), demonstrated reproducible and reliable measures of liver function (Translational Research 2021). The aim of this study was to compare the reproducibility and reliability of a new physiologically based compartmental model (CM) vs the MM. Data were analyzed from 16 control, 16 nonalcoholic steatohepatitis (NASH), and 16 hepatitis C virus (HCV) subjects, each with 3 replicate tests conducted on 3 separate days. The CM describes transfer of cholates between systemic, portal, and liver compartments with assumptions from measured or literature-derived values and unknown parameters estimated by nonlinear least-squares regression. The CM was compared to the MM for 6 key indices of hepatic disease in terms of intraclass correlation coefficient (ICC) with a lower acceptable limit of 0.7. The CM correlated well with the MM for disease severity index (DSI) with R2 (95% confidence interval) of 0.96 (0.94–0.98, P < 0.001). Acceptable reproducibility (ICC > 0.7) was observed for 6/6 and 5/6 hepatic disease indices for CM and MM, respectively. SHUNT, a measure of the absolute bioavailability, had ICC of 0.73 (0.60–0.83, P = 0.3095) for MM and 0.84 (0.76–0.90, P = 0.0012) for CM. The CM, but not the MM, allowed determination of anatomic shunt and hepatic extraction and improved the within individual reproducibility.