Monitor Therapy Efficacy Research Articles

Circulating Tumor DNA as a Complementary Prognostic Biomarker during CAR-T Therapy in B-Cell Non-Hodgkin Lymphomas.

The emergence of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment paradigm for R/R B-cell NHLs. However, challenges persist in accurately evaluating treatment response and detecting early relapse, necessitating the exploration of novel biomarkers. Circulating tumor DNA (ctDNA) via liquid biopsy is a non-invasive tool for monitoring therapy efficacy and predicting treatment outcomes in B-NHL following CAR-T therapy. By overcoming the limitations of conventional imaging modalities, ctDNA assessments offer valuable insights into response dynamics, molecular mechanisms of resistance, and early detection of molecular relapse. Integration of ctDNA monitoring into clinical practice holds promise for personalized therapeutic strategies, guiding the development of novel targeted therapies, and enhancing patient outcomes. However, standardization of assay methodologies and consensus on clinical response metrics are imperative to unlock the full potential of ctDNA in the management of B-NHL. Prospective validation of ctDNA in clinical trials is necessary to establish its role as a complementary decision aid.

Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients.

Thoracic aortic aneurysm (TAA) is mainly sporadic and with higher incidence in the presence of a bicuspid aortic valve (BAV) for unknown reasons. The lack of drug therapy to delay TAA progression lies in the limited knowledge of pathophysiology. We aimed to identify the molecular hallmarks that differentiate the aortic dilatation associated with BAV and tricuspid aortic valve (TAV). Aortic vascular smooth muscle cells (VSMCs) isolated from sporadic TAA patients with BAV or TAV were analyzed by mass spectrometry. DNA oxidative damage assay and cell cycle profiling were performed in three independent cohorts supporting proteomics data. The alteration of secreted proteins was confirmed in plasma. Stress phenotype, oxidative stress, and enhanced DNA damage response (increased S-phase arrest and apoptosis) were found in BAV-TAA patients. The increased levels of plasma C1QTNF5, LAMA2, THSB3, and FAP confirm the enhanced stress in BAV-TAA. Plasma FAP and BGN point to an increased inflammatory condition in TAV. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA. The molecular pathways identified support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients, showing specific markers in plasma which may serve to monitor therapy efficacy.

Herbal Components for the Treatment of Various Kidney Disorders

Abstract:: Acute kidney injury is described as a loss of renal excretory function that occurs suddenly. AKI is one of several ailments grouped together as acute kidney diseases and disorders (AKD), in which progressive degradation of kidney function or persistent renal dysfunction is associated with irreversible loss of kidney cells and nephrons, potentially leading to chronic kidney disease (CKD). The prevalence and incidence of KDs are assessed in light of population disparities in the prevalence of risk factors such as diabetes, hypertension, and obesity. However, the presence of these associated illnesses does not fully explain the increased rate of progression of chronic renal disease in high-risk patients (CKD). The development of renal disease is accompanied by a decline in renal function, which eventually leads to renal failure. The current status of diagnostic testing does not allow for accurate early disease diagnosis, prognosis, or therapy efficacy monitoring. Despite significant advances in care and understanding of the causes of acute renal failure (ARF), many aspects of ARF remain controversial, confusing, and uncertain. Accurate information on the disease's prevalence, genesis, and clinical manifestations is required to successfully advocate for enough funding and resources to manage the disease. Herbal components for the treatment of a variety of kidney disorders, and the page includes a list of plants that are good for kidney treatment. This review focuses on several herbal products used to treat renal problems. It is clear from this study that medicinal plants play an important role in the fight against many different diseases. Several different plants and plant extracts have been shown to have beneficial effects in treating renal disease. These medications have great promise for use in treating kidney damage because of their nephroprotective, cytoprotective, immunomodulatory, antioxidant, anti-inflammatory, and reducing effects on oxidative stress, renal hypertension, and blood toxins such as urea, creatinine, and others. Therefore, India's traditional medicine offers a wide variety of medications that can be utilized in renal illnesses due to their effectiveness in both treating the ailment and restoring normal kidney function. Therefore, it is suggested that additional research be conducted to learn many aspects and mechanisms of medications.

Reticulocyte Hemoglobin Content: Advancing the Frontiers in Iron-deficiency Anemia Diagnosis and Management

Iron-deficiency anemia (IDA) is a global health concern, and its widespread prevalence and multifaceted impact on various populations, particularly in developing countries, underscore the urgency for efficient diagnostic and management strategies. While traditional diagnostic methods such as ferritin and transferrin saturation are fundamental, their limitations in sensitivity and specificity lead to challenges in the early detection and effective management of IDA. This review provides a comprehensive analysis of IDA, focusing on the evolution of diagnostic methods culminating in the utilization of reticulocyte hemoglobin content (CHr) as a critical biomarker. The core of this review is the detailed examination of CHr as a biomarker. Its emergence has been pivotal due to its superior sensitivity and specificity in identifying iron deficiency and monitoring therapy efficacy. The review discusses the comparative advantages of CHr over conventional methods, including its ability to detect IDA at an earlier stage and its utility in varied demographic groups, such as children and pregnant women. Future research directions are proposed, including integration of CHr into routine clinical practice, cost-effectiveness analysis, and technological advancements for enhanced measurement and accessibility. In conclusion, CHr holds significant potential for revolutionizing IDA management, paving the way for more precise and personalized medical interventions, thereby improving patient outcomes in diverse populations.

Impact of Different Treatment Regimens and Timeframes in the Plasmatic Metabolic Profiling of Patients with Lung Adenocarcinoma.

In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) has suffered a variety of alterations. Chemotherapy (CTX), immunotherapy (IT) and tyrosine kinase inhibitors (TKI) have shown remarkable results. However, not all patients with NSCLC respond to these drug treatments or receive durable benefits. In this framework, metabolomics has been applied to improve the diagnosis, treatment, and prognosis of lung cancer and particularly lung adenocarcinoma (AdC). In our study, metabolomics was used to analyze plasma samples from 18 patients with AdC treated with CTX or IT via 1H-NMR spectroscopy. Relevant clinical information was gathered, and several biochemical parameters were also evaluated throughout the treatments. During the follow-up of patients undergoing CTX or IT, imaging control is recommended in order to assess the effectiveness of the therapy. This evaluation is usually performed every three treatments. Based on this procedure, all the samples were collected before the beginning of the treatment and after three and six treatments. The identified and quantified metabolites in the analyzed plasma samples were the following: isoleucine, valine, alanine, acetate, lactate, glucose, tyrosine, and formate. Multivariate/univariate statistical analyses were performed. Our data are in accordance with previous published results, suggesting that the plasma glucose levels of patients under CTX become higher throughout the course of treatment, which we hypothesize could be related to the tumor response to the therapy. It was also found that alanine levels become lower during treatment with CTX regimens, a fact that could be associated with frailty. NMR spectra of long responders' profiles also showed similar results. Based on the results of the study, metabolomics can represent a potential option for future studies, in order to facilitate patient selection and the monitoring of therapy efficacy in treated patients with AdC. Further studies are needed to improve the prospective identification of predictive markers, particularly glucose and alanine levels, as well as confer guidance to NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

Quality of life measurement in teledermatology. Position statement of the European Academy of Dermatology and Venereology TaskForces on Quality of Life and Patient Oriented Outcomes and Teledermatology.

Many events, including the COVID-19 pandemic, have accelerated the implementation of teledermatology pathways within dermatology departments and across healthcare organizations. Quality of Life (QoL) assessment in dermatology is also a rapidly developing field with a gradual shift from theory to practice. The purpose of this paper organized jointly by the European Academy of Dermatology and Venereology (EADV) Task Force (TF) on QoL and patient-oriented outcomes and the EADV TF on teledermatology is to present current knowledge about QoL assessment during the use of teledermatology approaches, including data on health-related (HR) QoL instruments used in teledermatology, comparison of influence of different treatment methods on HRQoL after face-to-face and teledermatology consultations and to make practical recommendations concerning the assessment of QoL in teledermatology. The EADV TFs made the following position statements: HRQoL assessment may be an important part in most of teledermatology activities; HRQoL assessment may be easily and effectively performed during teledermatology consultations. It is especially important to monitor HRQoL of patients with chronic skin diseases during lockdowns or in areas where it is difficult to reach a hospital for face-to-face consultation; regular assessment of HRQoL of patients with skin diseases during teledermatology consultations may help to monitor therapy efficacy and visualize individual patient's needs; we recommend the use of the DLQI in teledermatology, including the use of the DLQI app which is available in seven languages; it is important to develop apps for dermatology-specific HRQoL instruments for use in children (for example the CDLQI and InToDermQoL) and for disease-specific instruments.

An Overview on Electrochemical Approaches for the Detection of Alpha-Fetoprotein

Cancer biomarkers have a remarkable role for not only early-stage detection of cancer but also in the monitoring therapy efficacy. Alpha-fetoprotein (AFP) is one of the biomarkers which is highly expressed in hepatocellular carcinoma (HCC) patients. Therefore, a high level of AFP can be considered for early diagnosis of HCC. Electrochemical assays can be used as the miniaturized biosensors for real-time detection of the analytes which are mostly categorized into three groups for AFP detection including immunosensors, aptasensors, and molecularly imprinted polymer-based sensors. All of these techniques provide beneficial detection features of fast and cost-effective compared with other analytical methods. This review describes the most recent electrochemical platforms for AFP detection to provide a perspective for future studies.

Quantitative real-time PCR analysis of bacterial biomarkers enable fast and accurate monitoring in inflammatory bowel disease.

Inflammatory bowel diseases (IBD) affect millions of people worldwide with increasing incidence. Ulcerative colitis (UC) and Crohn’s disease (CD) are the two most common IBDs. There is no definite cure for IBD, and response to treatment greatly vary among patients. Therefore, there is urgent need for biomarkers to monitor therapy efficacy, and disease prognosis. We aimed to test whether qPCR analysis of common candidate bacteria identified from a patient’s individual fecal microbiome can be used as a fast and reliable personalized microbial biomarker for efficient monitoring of disease course in IBD. Next generation sequencing (NGS) of 16S rRNA gene region identified species level microbiota profiles for a subset of UC, CD, and control samples. Common high abundance bacterial species observed in all three groups, and reported to be associated with IBD are chosen as candidate marker species. These species, and total bacteria amount are quantified in all samples with qPCR. Relative abundance of anti-inflammatory, beneficial Faecalibacterium prausnitzii, Akkermansia muciniphila, and Streptococcus thermophilus was significantly lower in IBD compared to control samples. Moreover, the relative abundance of the examined common species was correlated with the severity of IBD disease. The variance in qPCR data was much lower compared to NGS data, and showed much higher statistical power for clinical utility. The qPCR analysis of target common bacterial species can be a powerful, cost and time efficient approach for monitoring disease status and identify better personalized treatment options for IBD patients.

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study

BackgroundThe development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv.MethodsCalf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity.ResultsQuantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation.ConclusionsMuscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.

Skin Cancer Research Goes Digital: Looking for Biomarkers within the Droplets.

Skin cancer, which includes the most frequent malignant non-melanoma carcinomas (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC), along with the difficult to treat cutaneous melanoma (CM), pose important worldwide issues for the health care system. Despite the improved anti-cancer armamentarium and the latest scientific achievements, many skin cancer patients fail to respond to therapies, due to the remarkable heterogeneity of cutaneous tumors, calling for even more sophisticated biomarker discovery and patient monitoring approaches. Droplet digital polymerase chain reaction (ddPCR), a robust method for detecting and quantifying low-abundance nucleic acids, has recently emerged as a powerful technology for skin cancer analysis in tissue and liquid biopsies (LBs). The ddPCR method, being capable of analyzing various biological samples, has proved to be efficient in studying variations in gene sequences, including copy number variations (CNVs) and point mutations, DNA methylation, circulatory miRNome, and transcriptome dynamics. Moreover, ddPCR can be designed as a dynamic platform for individualized cancer detection and monitoring therapy efficacy. Here, we present the latest scientific studies applying ddPCR in dermato-oncology, highlighting the potential of this technology for skin cancer biomarker discovery and validation in the context of personalized medicine. The benefits and challenges associated with ddPCR implementation in the clinical setting, mainly when analyzing LBs, are also discussed.

Abstract P2-02-05: Dynamic circulating tumor cell changes in enumeration and HER2 expression during systemic therapy for metastatic breast cancer

Abstract Introduction: CTCs are tumor cells that circulate in the blood of patient with primary and MBC and, are responsible for seeing of metastasis. The monitoring of CTCs in MBC emerged as strong prognostic and possible predictive biomarker in oncology over the past couple of decades. Meanwhile, overexpression of HER2 protein has been associated with rapid cell division and worse prognosis of MBC. Here we report a significant correlation between dynamic CTCs enumeration and CTCs-HER2 expression during the systemic therapies, with potential implication to understand treatment resistance. Methods: A total of 298 whole blood samples (7.5ml/each) were collected from 149 patients with stage IV breast cancer (2016-2020) at the Northwestern University Robert H Lurie Comprehensive Cancer Center, before (Baseline) and 3 months after (Time point 2) initiation of systemic treatment. CTC enumerations were performed using the FDA approved CellSearch™ system (Menarini) which is specific for the intracellular protein cytokeratin (CK) in epithelial cells, DAPI stains the cell nucleus, anti-CD45-APC is specific for leukocytes, and anti-HER-2/neu-FLU is specific for HER-2/neu antigen. The CTCs were classified as CK+, EpCAM+, DAPI+ and CD45-. We developed a criteria for evaluation of HER2 expression by 4 different categories (0,1+,2+,3+) based on expression intensity in our lab (present in 2021 ASCO). In this study we included CTCs with all intensities of HER2 expression (1+ to 3+) which was standardized in our lab. Mann-Whitney U test was used for statistics. Results: Of the 149 baseline samples, CTC≥1 were found in 101 patients (67.8%). A change in CTCs between baseline and time point 2 for these 101 patients: Three groups were identified: Group 1: 33patients (33%) with increase CTCs; Group 2: 64 patients (63%) with decreased CTC; Group 3: 4 patients (4%) with no change The median increase of total CTCs and HER2+ CTCs in Group 1 were 7.0 and 2.0, respectively; the median decrease of total CTCs and HER2+ CTCs in Group 2 were 9.5 and 2.0, respectively. The change of HER2+ CTCs was significantly correlated with the change of total CTCs after systemic therapy, with the correlation coefficient as rs=0.662 (p<0.001) for these 101 patients. A significant positive correlation between HER2+ CTCs and total CTCs were found in both Group 1 and Group 2, rs=0.717 (p<0.001) and rs=0.604 (p<0.001) respectively. Furthermore, the ratio of HER2+ CTCs (HER2+ CTCs/total CTCs) in both Group 1 and Group 2 was also significantly correlated with total CTCs after therapy with the corresponding correlation coefficient as rs=0.536 (p<0.001) and rs=0.388 (p<0.001) in Group 1 and Group 2, respectively. Conclusion: Our study demonstrated that dynamic changes of CTCs after systemic therapies, are positively correlated with the HER2 expression in CTCs in different levels of baseline CTCs amounts. Observation of HER2 expression and ratio in CTCs during the course of systemic therapy is useful in monitoring therapy efficacy and potential disease progress. Citation Format: Qiang Zhang, Weijun Qin, Paolo D'Amico, Andrew A. Davis, Jianhua Jiao, Lorenzo Gerratana, Saya L. Jacob, Youbin Zhang, Jeannine Donahue, Wenan Qiang, Ami N Shah, Amir Behdad, Lisa Flaum, William Gradishar, Leonidas C Platanias, Massimo Cristofanilli. Dynamic circulating tumor cell changes in enumeration and HER2 expression during systemic therapy for metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-02-05.

ANCA Testing in Clinical Practice: From Implementation to Quality Control and Harmonization.

Analyses for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) are important in the diagnostic work-up of patients with small vessel vasculitis. Since current immuno-assays are predominantly designed for diagnosis of patients with ANCA-associated vasculitis (AAV), implementation in routine clinical practice, internal and external quality control, and harmonization are focused on this particular use. However, ANCA testing may also be relevant for monitoring therapy efficacy and for predicting a clinical relapse in AAV patients, and even for diagnostic purposes in other clinical situations. In the current review, the topics of implementation, quality control, and standardization vs. harmonization are discussed while taking into account the different applications of the ANCA assays in the context of AAV.

RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies.

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples. In contrast, the transcriptome contains information on signaling pathway activity and can complement genomic analyses. Here we present the validation and clinical application of a new knowledge-based mRNA-based diagnostic assay platform (OncoSignal) for measuring activity of relevant signaling pathways simultaneously and quantitatively with high resolution in tissue samples and circulating tumor cells, specifically with very small specimen quantities. The approach uses mRNA levels of a pathway’s direct target genes, selected based on literature for multiple proof points, and used as evidence that a pathway is functionally activated. Using these validated target genes, a Bayesian network model has been built and calibrated on mRNA measurements of samples with known pathway status, which is used next to calculate a pathway activity score on individual test samples. Translation to RT-qPCR assays enables broad clinical diagnostic applications, including small analytes. A large number of cancer samples have been analyzed across a variety of cancer histologies and benchmarked across normal controls. Assays have been used to characterize cell types in the cancer cell microenvironment, including immune cells in which activated and immunotolerant states can be distinguished. Results support the expectation that the assays provide information on cancer driving signaling pathways which is difficult to derive from next generation DNA sequencing analysis. Current clinical oncology applications have been complementary to genomic mutation analysis to improve precision medicine: (1) prediction of response and resistance to various therapies, especially targeted therapy and immunotherapy; (2) assessment and monitoring of therapy efficacy; (3) prediction of invasive cancer cell behavior and prognosis; (4) measurement of circulating tumor cells. Preclinical oncology applications lie in a better understanding of cancer behavior across cancer types, and in development of a pathophysiology-based cancer classification for development of novel therapies and precision medicine.

Digital Image Analysis Applied to Tumor Cell Proliferation, Aggressiveness, and Migration-Related Protein Synthesis in Neuroblastoma 3D Models.

Patient-derived cancer 3D models are a promising tool that will revolutionize personalized cancer therapy but that require previous knowledge of optimal cell growth conditions and the most advantageous parameters to evaluate biomimetic relevance and monitor therapy efficacy. This study aims to establish general guidelines on 3D model characterization phenomena, focusing on neuroblastoma. We generated gelatin-based scaffolds with different stiffness and performed SK-N-BE(2) and SH-SY5Y aggressive neuroblastoma cell cultures, also performing co-cultures with mouse stromal Schwann cell line (SW10). Model characterization by digital image analysis at different time points revealed that cell proliferation, vitronectin production, and migration-related gene expression depend on growing conditions and are specific to the tumor cell line. Morphometric data show that 3D in vitro models can help generate optimal patient-derived cancer models, by creating, identifying, and choosing patterns of clinically relevant artificial microenvironments to predict patient tumor cell behavior and therapeutic responses.

Perfluorocarbons-Based 19F Magnetic Resonance Imaging in Biomedicine.

Fluorine-19 (19F) magnetic resonance (MR) molecular imaging is a promising noninvasive and quantitative molecular imaging approach with intensive research due to the high sensitivity and low endogenous background signal of the 19F atom in vivo. Perfluorocarbons (PFCs) have been used as blood substitutes since 1970s. More recently, a variety of PFC nanoparticles have been designed for the detection and imaging of physiological and pathological changes. These molecular imaging probes have been developed to label cells, target specific epitopes in tumors, monitor the prognosis and therapy efficacy and quantitate characterization of tumors and changes in tumor microenvironment noninvasively, therefore, significantly improving the prognosis and therapy efficacy. Herein, we discuss the recent development and applications of 19F MR techniques with PFC nanoparticles in biomedicine, with particular emphasis on ligand-targeted and quantitative 19F MR imaging approaches for tumor detection, oxygenation measurement, smart stimulus response and therapy efficacy monitoring, et al.

Expanding and validating the biomarkers for mitochondrial diseases

Mitochondrial diseases are highly heterogeneous metabolic disorders caused by genetic alterations in the mitochondrial DNA (mtDNA) or in the nuclear genome. In this study, we investigated a panel of blood biomarkers in a cohort of 123 mitochondrial patients, with prominent neurological and muscular manifestations. These biomarkers included creatine, fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF-15), and the novel cell free circulating-mtDNA (ccf-mtDNA). All biomarkers were significantly increased in the patient group. After stratification by the specific phenotypes, ccf-mtDNA was significantly increased in the Mitochondrial Encephalomyopathy Lactic Acidosis Stroke-like episodes syndrome (MELAS) group, and FGF21 and GDF-15 were significantly elevated in patients with MELAS and Myoclonic Epilepsy Ragged Red Fibers syndrome. On the contrary, in our cohort, creatine was not associated to a specific clinical phenotype. Longitudinal assessment in four MELAS patients showed increased levels of ccf-mtDNA in relation to acute events (stroke-like episodes/status epilepticus) or progression of neurodegeneration. Our results confirm the association of FGF21 and GDF-15 with mitochondrial translation defects due to tRNA mutations. Most notably, the novel ccf-mtDNA was strongly associated with MELAS and may be used for monitoring the disease course or to evaluate the efficacy of therapies, especially in the acute phase.Key messages• FGF21/GDF15 efficiently identifies mitochondrial diseases due to mutations in tRNA genes.• The novel ccf-mtDNA is associated with MELAS and increases during acute events.• Creatine only discriminates severe mitochondrial patients.• FGF21, GDF-15, and ccf-mtDNA are possibly useful for monitoring therapy efficacy.

Off-axis loads cause failure of the distal radius at lower magnitudes than axial loads: A side-to-side experimental study.

Off-axis loading associated with a fall onto the outstretched hand has been hypothesized to induce distal radius failure at lower magnitudes than axially directed loading commonly used in biomechanical models for estimating fracture risk. However, this hypothesis has not been tested with side-to-side experimental testing. The objective of this study was to compare distal radius failure loads between forearm pairs experimentally tested in an axial or off-axis loading configuration. We acquired 18 pairs of cadaveric forearms from 18 female donors (mean age (standard deviation): 84.4 (7.9) years). Each forearm pair was tested to failure using either an axial compression test (vertical orientation with 0° dorsal inclination, 3°-6° radial inclination) or an off-axis test corresponding to the hand position during a fall (15° dorsal inclination, 3°-6° radial inclination). Failure testing was performed at 3 mm/s onto the palm of the hand until fracture occurred. Of the 18 pairs, 11 sustained a distal radius fracture. We compared failure loads between the two groups using a paired t test. Results indicated that failure load under off-axis loading was 29% lower than failure load under axial compressive loading (mean difference: -0.31 kN; 95% confidence interval: -0.47 to -0.16 kN, P = .001). In conclusion, off-axis loading associated with a fall onto the outstretched hand resulted in a 29% lower failure load. Integrating an off-axis loading configuration into current biomechanical models of distal radius bone strength may prevent overestimating of failure load and may offer a clinically relevant option to estimate distal radius fracture risk and monitor therapy efficacy.

The new horizon of liquid biopsy in sarcoma: the potential utility of circulating tumor nucleic acids.

The diagnosis, treatment and prognosis of sarcoma are mainly dependent on tissue biopsy, which is limited in its ability to provide a panoramic view into the dynamics of tumor progression. In addition, effective biomarkers to monitor the progression and therapeutic response of sarcoma are lacking. Liquid biopsy, a recent technological breakthrough, has gained great attention in the last few decades. Nucleic acids (such as DNA, mRNAs, microRNAs, and long non-coding RNAs) that are released from tumors circulate in the blood of cancer patients and can be evaluated through liquid biopsy. Circulating tumor nucleic acids reflect the intertumoral and intratumoral heterogeneity, and thus liquid biopsy provides a noninvasive strategy to examine these molecules compared with traditional tissue biopsy. Over the past decade, a great deal of information on the potential utilization of circulating tumor nucleic acids in sarcoma screening, prognosis and therapy efficacy monitoring has emerged. Several specific gene mutations in sarcoma can be detected in peripheral blood samples from patients and can be found in circulating tumor DNA to monitor sarcoma. In addition, circulating tumor non-coding RNA may also be a promising biomarker in sarcoma. In this review, we discuss the clinical application of circulating tumor nucleic acids as blood-borne biomarkers in sarcoma.

Liver function trends after biliary decompression in obstructive jaundice: a clinico-pathological-biochemical study

Background: Liver functions tests suggest the underlying cause, estimate the severity, assess prognosis and monitor efficacy of therapy. Severity of liver dysfunction when performed serially may predict prognosis and may be helpful in assessing response to medical therapy or a surgical intervention.Methods: The data was collected in thirty cases of surgical obstructive jaundice in terms of age, sex, etiology, clinical presentation, surgical intervention for biliary drainage and the laboratory liver biochemical and coagulation profiles on a day prior to surgical intervention and post-operatively on 1st week and 4th week were recorded.Results: Of total 30 patients 56.66% were females. Patients with 73.68% of benign disease and 100% of malignant disease were of age more than 40 years. 63.33% of patients had benign cause for biliary obstruction. Choledochoithiasis and periampullary carcinoma were two most common causes of obstructive jaundice. The commonest complaints were; yellowish discolouration of sclera and skin, high colored urine (100%) and acholic stool (70%). Hepatomegaly, palpable gallbladder and ascites were observed in only malignant conditions. Serum bilirubin and transaminases were significantly higher in patients with malignant lesions on pre-operative and postoperative assessment. After decompression the rate of fall of serum bilirubin, serum glutamic-oxaloacetic transaminase and SGPT were almost identical in both benign and malignant biliary obstructions. However, a better biochemical recovery profile was observed in patients with benign lesions, as they returned to normal by 4 weeks but remained at 2 to 3 times of the normal in malignant lesions.Conclusions: Sequential biochemical assessment of liver functions has diagnostic as well as prognostic value in surgical obstructive jaundice.

A Self-Managed System for Automated Assessment of UPDRS Upper Limb Tasks in Parkinson's Disease.

A home-based, reliable, objective and automated assessment of motor performance of patients affected by Parkinson’s Disease (PD) is important in disease management, both to monitor therapy efficacy and to reduce costs and discomforts. In this context, we have developed a self-managed system for the automated assessment of the PD upper limb motor tasks as specified by the Unified Parkinson’s Disease Rating Scale (UPDRS). The system is built around a Human Computer Interface (HCI) based on an optical RGB-Depth device and a replicable software. The HCI accuracy and reliability of the hand tracking compares favorably against consumer hand tracking devices as verified by an optoelectronic system as reference. The interface allows gestural interactions with visual feedback, providing a system management suitable for motor impaired users. The system software characterizes hand movements by kinematic parameters of their trajectories. The correlation between selected parameters and clinical UPDRS scores of patient performance is used to assess new task instances by a machine learning approach based on supervised classifiers. The classifiers have been trained by an experimental campaign on cohorts of PD patients. Experimental results show that automated assessments of the system replicate clinical ones, demonstrating its effectiveness in home monitoring of PD.