The Use of Wearable Devices in Oncology Patients: A Systematic Review.

INTRODUCTION: The aim of this systematic review was to summarize the current literature on wearable technologies in oncology patients for the purpose of prognostication, treatment monitoring, and rehabilitation planning. METHODS: A search was conducted in Medline ALL, Cochrane Central Register of Controlled Trials, Embase, Emcare, CINAHL, Scopus, and Web of Science, up until February 2022. Articles were included if they reported on consumer grade and/or non-commercial wearable devices in the setting of either prognostication, treatment monitoring or rehabilitation. RESULTS: We found 199 studies reporting on 18 513 patients suitable for inclusion. One hundred and eleven studies used wearable device data primarily for the purposes of rehabilitation, 68 for treatment monitoring, and 20 for prognostication. The most commonly-reported brands of wearable devices were ActiGraph (71 studies; 36%), Fitbit (37 studies; 19%), Garmin (13 studies; 7%), and ActivPAL (11 studies; 6%). Daily minutes of physical activity were measured in 121 studies (61%), and daily step counts were measured in 93 studies (47%). Adherence was reported in 86 studies, and ranged from 40% to 100%; of these, 63 (74%) reported adherence in excess of 80%. CONCLUSION: Wearable devices may provide valuable data for the purposes of treatment monitoring, prognostication, and rehabilitation. Future studies should investigate live-time monitoring of collected data, which may facilitate directed interventions.

Amino-acid PET as a prognostic tool after post Stupp protocol temozolomide therapy in high-grade glioma patients.

PURPOSE: This study aimed to evaluate the prognostic performance of amino-acid PET in high-grade gliomas (HGG) patients at the time of temozolomide (TMZ) treatment discontinuation, after the Stupp protocol. METHODS: The analysis included consecutive HGG patients with dynamic [18F]FDOPA PET imaging within 3 months of the end of TMZ therapy, post-Stupp protocol. Static and dynamic PET parameters, responses to RANO criteria for MRI and clinical and histo-molecular factors were correlated to progression-free (PFS). RESULTS: Thirty-two patients (59.4 [54.0;67.6] years old, 13 (41%) women) were included. Static PET parameters peak tumor-to-background ratio and metabolic tumor volume (respective thresholds of 1.9 and 1.5 mL) showed the best 84% accuracies for predicting PFS at 6 months (p = 0.02). These static PET parameters were also independent predictor of PFS in multivariate analysis (p ≤ 0.05). CONCLUSION: In HGG patients having undergone a Stupp protocol, the absence of significant PET uptake after TMZ constitutes a favorable prognostic factor.

Update on DWI for Breast Cancer Diagnosis and Treatment Monitoring.

DWI is a noncontrast MRI technique that measures the diffusion of water molecules within biologic tissue. DWI is increasingly incorporated into routine breast MRI examinations. Currently, the main applications of DWI are breast cancer detection and characterization, prognostication, and prediction of treatment response to neoadjuvant chemotherapy. In addition, DWI is promising as a noncontrast MRI alternative for breast cancer screening. Problems with suboptimal resolution and image quality have restricted the mainstream use of DWI for breast imaging, but these shortcomings are being addressed through several technologic advancements. In this review, we present an up-to-date assessment of the use of DWI for breast cancer imaging, including a summary of the clinical literature and recommendations for future use.

Sensor system for analysis of biofilm sensitivity to ampicillin.

The resistance of biofilms to antibiotics is a key factor that makes bacterial infections unsusceptible to antimicrobial therapy. The results of classical tests of cell sensitivity to antibiotics cannot be used to predict therapeutic success in infections associated with biofilm formation. We describe a simple and rapid method for the real-time evaluation of bacterial biofilm sensitivity to antibiotics, with Pseudomonas putida and ampicillin as examples. The method uses an electric biosensor to detect the difference between changes in the biofilm electric polarizability, thereby evaluating antibiotic sensitivity. The electric signals showed that P. putida biofilms were susceptible to ampicillin and that at high antibiotic concentrations, the biofilms differed markedly in their susceptibility (dose-dependent effect). The sensor also detected differences between biofilms before and after ampicillin treatment. The electric-signal changes enabled us to describe the physical picture of the processes occurring in bacterial biofilms in the presence of ampicillin. The approach used in this study is promising for evaluating the activity of various compounds against biofilms, because it permits a conclusion about the antibiotic sensitivity of biofilm bacteria to be made in real time and in a short period (analysis time, not longer than 20 min). An added strong point is that analysis can be done directly in liquid, without preliminary sample preparation. KEY POINTS: • Sensor system to analyze biofilm antimicrobial susceptibility is described. • The signal change depended on the ampicillin concentration (dose-dependent effect). • The sensor allows real-time determination of the antibiofilm effect of ampicillin.

Hydradermabrasion through the lens of Line-Field Confocal Optical Coherence Tomography.

BACKGROUND: Hydradermabrasion, also known as "HydraFacial," is an exfoliative cosmetic procedure for skin rejuvenation that has gained popularity. Despite its increasing popularity, clinical studies validating its efficacy with non-invasive assessment of histological changes to the skin, are scarce. In this study, we used Line-Field Confocal Optical Coherence Tomography (LC-OCT), an optical imaging device, to non-invasively visualize microscopic changes to skin anatomy after hydradermabrasion treatment. MATERIALS/METHODS: Eight volunteers (Fitzpatrick skin types II-V) were recruited for this study. Images, using LC-OCT (DeepLive, DAMAE medical) were obtained before and after hydradermabrasion and at 2 weeks post-treatment. A commercially available hydradermabrasion device was utilized to perform the dermabrasion. RESULTS: In the epidermis, initially, a decrease in the average thickness of the stratum corneum, from 9.42 to 6.67 µm was visualized in LC-OCT images after hydradermabrasion. However, at 2 weeks of follow-up, the average stratum corneum thickness was 9.75 µm, resulting in an overall increase in the average thickness after treatment. Improved homogenization of the stratum corneum and decreased number of undulations in the epidermis post-treatment were also visualized. In all the subjects, the superficial dermis appeared stretched, which returned to baseline by the 2-week follow-up. At the 2-week follow-up, there were no visible differences in the quality and quantity of collagen fibers in the dermis. CONCLUSION: In our study, LC-OCT images of the epidermis and dermis demonstrated microscopic features of skin rejuvenation when treated with hydradermabrasion. Thus, not only highlighting the efficacy of hydradermabrasion but also the potential of LC-OCT to serve as a tool for visualizing the microscopic effects of cosmetic procedures on skin anatomy.

A review of non-invasive samples and tools in kala-azar diagnosis and test of cure.

The recurrence of visceral leishmaniasis (VL), also called kala-azar (KA), in endemic regions of tropical countries like India, is primarily attributed to asymptomatic VL, post-kala azar dermal leishmaniasis (PKDL), and human immunodeficiency virus (HIV) co-infection. To effectively manage VL cases and elimination targets, an early and rapid diagnosis as well as accurate field surveillance is highly essential. The traditional sampling methods like bone marrow (BM), spleen, and lymph node (LN) tissue aspirations are invasive, painful, tedious, and prone to nosocomial infections, require skilled persons and hospital facilities, and are not feasible in rural areas. Therefore, there is an urgent requirement for the adoption of a patient-friendly, non-invasive, non-hospitalized sampling procedure that ensures an effective VL diagnosis. This review aims to meticulously evaluate the most recent scientific research that focuses on the precision, feasibility, and applicability of non-invasive sampling (NIS) and techniques for the diagnosis and test of cure of VL, particularly in resource-limited settings. Apart from that, the non-invasive techniques (NIT) that have shown promising results while monitoring VL treatment response and relapse are also reviewed. The limitations associated with NIT and possible improvements in this regard are discussed as well to improve the diagnosis and management of VL.

Exploring mean platelet volume and neutrophil-to-albumin ratio as surrogate markers for monitoring tuberculosis treatment: a prospective longitudinal study.

BACKGROUND: Tuberculosis (TB) remains a global health challenge, with India bearing a significant burden. Despite advancements in TB diagnosis and treatment, monitoring TB treatment is challenging, particularly in resource-limited settings. This study aimed to explore the mean platelet volume (MPV) as a potential surrogate marker for monitoring TB treatment and assessing if the neutrophil-to-albumin ratio (NAR) enhances treatment monitoring. METHODS: Patients diagnosed with TB following NTEP guidelines were recruited. Participants underwent routine blood tests during the six-month Anti-Tubercular therapy course at the start, end of the intensive phase, and end of the continuous phase. Statistical analyses included Spearman correlation, Friedman test, linear mixed effects (LME) models, and multiple linear regression. RESULTS: 150 individuals were included for analysis. Deviations from normality were noted. Significant associations were found between CRP and sputum grade. MPV mediated between CRP and sputum grade. Significant differences were observed across the three-time points. LME models showed changes in MPV and CRP levels over time. Including NAR enhanced predictive capability. CONCLUSIONS: MPV may serve as a promising surrogate marker for monitoring ATT. Personalized approaches are crucial in TB treatment monitoring. LME models revealed MPV and CRP level trends. Future research should explore MPV's treatment response mechanisms and cost-effectiveness.

Treatment Monitoring of a Patient with Synchronous Metastatic Angiosarcoma and Breast Cancer Using ctDNA.

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy. Consequently, there is a need for improved methods and biomarkers for treatment monitoring. Quantification of circulating tumor-DNA (ctDNA) is a promising approach for patient-specific monitoring of treatment response. In this case report, we demonstrate that quantification of ctDNA using SiMSen-Seq was successfully utilized to monitor a patient with metastatic angiosarcoma. By quantifying ctDNA levels using 25 patient-specific mutations in blood plasma throughout surgery and palliative chemotherapy, we predicted the outcome and monitored the clinical response to treatment. This was accomplished despite the additional complexity of the patient having a synchronous breast cancer. The levels of ctDNA showed a superior correlation to the clinical outcome compared with the radiological evaluations. Our data propose a promising approach for personalized biomarker analysis to monitor treatment in angiosarcomas, with potential applicability to other cancers and for patients with synchronous malignancies.

FLT3-TKD Measurable Residual Disease Detection Using Droplet Digital PCR and Clinical Applications in Acute Myeloid Leukemia.

The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common FLT3-TKD mutations (D835Y, D835H, D835V, D835E). Twenty-two diagnostic samples, six donor controls, and a commercial D835Y positive control were tested using a commercial Bio-rad® ddPCR assay. All known variants were identified, and no false positives were detected in the wild-type control (100% specificity and sensitivity). The assays achieved a limit of detection suitable for MRD testing at 0.01% variant allelic fraction. Serial samples from seven intensively-treated patients with FLT3-TKD variants at diagnosis were tested. Five patients demonstrated clearance of FLT3-TKD clones, but two patients had FLT3-TKD persistence in the context of primary refractory disease. In conclusion, ddPCR is suitable for the detection and quantification of FLT3-TKD mutations in the MRD setting; however, the clinical significance and optimal management of MRD positivity require further exploration.

Tuberculosis Treatment Monitoring and Outcome Measures: New Interest and New Strategies.

Despite the advent of new diagnostics, drugs and regimens, tuberculosis (TB) remains a global public health threat. A significant challenge for TB control efforts has been the monitoring of TB therapy and determination of TB treatment success. Current recommendations for TB treatment monitoring rely on sputum and culture conversion, which have low sensitivity and long turnaround times, present biohazard risk, and are prone to contamination, undermining their usefulness as clinical treatment monitoring tools and for drug development. We review the pipeline of molecular technologies and assays that serve as suitable substitutes for current culture-based readouts for treatment response and outcome with the potential to change TB therapy monitoring and accelerate drug development.

Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application.

Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.

Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment. METHODS: A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease. RESULTS: In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression. CONCLUSION: Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.

Integration of longitudinal deep-radiomics and clinical data improves the prediction of durable benefits to anti-PD-1/PD-L1 immunotherapy in advanced NSCLC patients.

BACKGROUND: Identifying predictive non-invasive biomarkers of immunotherapy response is crucial to avoid premature treatment interruptions or ineffective prolongation. Our aim was to develop a non-invasive biomarker for predicting immunotherapy clinical durable benefit, based on the integration of radiomics and clinical data monitored through early anti-PD-1/PD-L1 monoclonal antibodies treatment in patients with advanced non-small cell lung cancer (NSCLC). METHODS: In this study, 264 patients with pathologically confirmed stage IV NSCLC treated with immunotherapy were retrospectively collected from two institutions. The cohort was randomly divided into a training (n = 221) and an independent test set (n = 43), ensuring the balanced availability of baseline and follow-up data for each patient. Clinical data corresponding to the start of treatment was retrieved from electronic patient records, and blood test variables after the first and third cycles of immunotherapy were also collected. Additionally, traditional radiomics and deep-radiomics features were extracted from the primary tumors of the computed tomography (CT) scans before treatment and during patient follow-up. Random Forest was used to implementing baseline and longitudinal models using clinical and radiomics data separately, and then an ensemble model was built integrating both sources of information. RESULTS: The integration of longitudinal clinical and deep-radiomics data significantly improved clinical durable benefit prediction at 6 and 9 months after treatment in the independent test set, achieving an area under the receiver operating characteristic curve of 0.824 (95% CI: [0.658,0.953]) and 0.753 (95% CI: [0.549,0.931]). The Kaplan-Meier survival analysis showed that, for both endpoints, the signatures significantly stratified high- and low-risk patients (p-value< 0.05) and were significantly correlated with progression-free survival (PFS6 model: C-index 0.723, p-value = 0.004; PFS9 model: C-index 0.685, p-value = 0.030) and overall survival (PFS6 models: C-index 0.768, p-value = 0.002; PFS9 model: C-index 0.736, p-value = 0.023). CONCLUSIONS: Integrating multidimensional and longitudinal data improved clinical durable benefit prediction to immunotherapy treatment of advanced non-small cell lung cancer patients. The selection of effective treatment and the appropriate evaluation of clinical benefit are important for better managing cancer patients with prolonged survival and preserving quality of life.

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Tyrosine kinase inhibitor therapy in pediatric sarcoma: Prognostic implications of pulmonary metastatic cavitation.

PURPOSES: This study aims to ascertain the prevalence of cavitations in pulmonary metastases among pediatric and young adult patients with sarcoma undergoing tyrosine kinase inhibitor (TKI) therapy, and assess whether cavitation can predict clinical response and survival outcomes. METHODS: In a single-center retrospective analysis, we examined chest computed tomography (CT) scans of 17 patients (median age 16 years; age range: 4-25 years) with histopathologically confirmed bone (n = 10) or soft tissue (n = 7) sarcoma who underwent TKI treatment for lung metastases. The interval between TKI initiation and the onset of lung nodule cavitation and tumor regrowth were assessed. The combination of all imaging studies and clinical data served as the reference standard for clinical responses. Progression-free survival (PFS) was compared between patients with cavitating and solid nodules using Kaplan-Meier survival analysis and log-rank test. RESULTS: Five out of 17 patients (29%) exhibited cavitation of pulmonary nodules during TKI therapy. The median time from TKI initiation to the first observed cavitation was 79 days (range: 46-261 days). At the time of cavitation, all patients demonstrated stable disease. When the cavities began to fill with solid tumor, 60% (3/5) of patients exhibited progression in other pulmonary nodules. The median PFS for patients with cavitated pulmonary nodules after TKI treatment (6.7 months) was significantly longer compared to patients without cavitated nodules (3.8 months; log-rank p-value = .03). CONCLUSIONS: Cavitation of metastatic pulmonary nodules in sarcoma patients undergoing TKI treatment is indicative of non-progressive disease, and significantly correlates with PFS.

Non-Invasive Assessment of Skin Surface Proteins of Psoriasis Vulgaris Patients in Response to Biological Therapy.

Measurements of skin surface biomarkers have enormous value for the detailed assessment of skin conditions, both for clinical application and in skin care. The main goals of the current study were to assess whether expression patterns of skin surface hBD-1, hBD-2, IL-1α, CXCL-1, and CXCL-8, examples of proteins known to be involved in psoriasis pathology, are associated with disease severity and whether expression patterns of these proteins on the skin surface can be used to measure pharmacodynamic effects of biological therapy. In this observational study using transdermal analysis patch (TAP), levels of skin surface IL-1α, hBD-1, hBD-2, CXCL-1/2, and CXCL-8 of psoriasis vulgaris (PV) patients over biological therapy were assessed. The Psoriasis Area Severity Index (PASI) and local score for erythema, induration, and desquamation were determined from the exact same skin area as FibroTx TAP measurements. Thirty-seven adult PV patients were included, of which twenty-three were subjected to anti-TNF-α, seven to anti-IL-17A, and seven to anti-IL12/IL-23 therapy. Significantly higher levels of hBD-1, hBD-2, CXCL-1/2, and CXCL-8 were detected on lesional skin compared to the non-lesional skin of the PV patients. In contrast, lower levels of IL-1α were found in lesional skin compared to non-lesional skin. In addition, we observed that the biomarker expression levels correlate with disease severity. Further, we confirmed that changes in the expression levels of skin surface biomarkers during biological therapy correlate with treatment response. Biomarker expression patterns in response to treatment differed somewhat between treatment subtypes. We observed that, in the case of anti-TNF-α therapy, an increase after a steady decrease in the expression levels of CXCL-1/2 and CXCL-8 occurred before the change in clinical scores. Moreover, response kinetics of skin surface proteins differs between the applied therapies-hBD2 expression responds quickly to anti-IL-17A therapy, CXCL-1/2 to anti-IL-12/23, and levels of CXCL-8 are rapidly down-regulated by IL-17A and IL-12/23 therapy. Our findings confirm that the skin surface hBD-2, IL-1α, CXCL-1/2, and CXCL-8 are markers for the psoriasis severity. Further, data obtained during this study give the basis for the conclusion that skin surface proteins CXCL-1/2 and CXCL-8 may have value as therapeutic biomarkers, thus confirming that measuring the 'molecular root' of inflammation appears to have value in scoring disease severity on its own.

Detection and clinical significance of circulating tumour cells in patients with colorectal carcinoma.

Circulating tumour cells (CTCs) are tumour cells identified in the peripheral blood of patients with malignant disease. CTCs present a very interesting biomarker with promising potential for use in the treatment management of patients with colorectal cancer. Unlike other tumour biomarkers, CTCs are living tumour cells that carry molecular and biological information about the tumour as a whole and reflect ongoing mutational changes. Detection of CTCs from peripheral blood presents a simple and easily repeatable method of liquid biopsy. However, various techniques of CTC selection and detection render clinical use of CTC as a clinical biomarker difficult. The presence/amount of CTCs correlates very well with prognosis and patients ́ survival. Since CTCs have metastatic potential, knowledge of the effect of different treatment modalities on the amount of CTCs in the blood appears to be very important. It can be expected that a more effective treatment regimen will be associated with a reduction in blood CTC levels, and also with a better prognosis. Conversely, an increase or persistence of CTC levels will be associated with resistance to the applied treatment. Routine use of CTCs in clinical practice is limited predominantly by price and very high variability of available scientific evidence. Recently published studies demonstrated the promising potential of CTCs; however, further research will be required for their routine use in clinical practice.

Biomarkers That Correlate with Active Pulmonary Tuberculosis Treatment Response: a Systematic Review and Meta-analysis.

Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of the intensive phase of treatment. These methods either have suboptimal accuracy or a long turnaround time. There is a need to identify alternative biomarkers to monitor TB treatment response. We conducted a systematic review of active pulmonary TB treatment monitoring biomarkers. We screened 9,739 articles published between 1 January 2008 and 31 December 2020, of which 77 met the inclusion criteria. When studies quantitatively reported biomarker levels, we meta-analyzed the average fold change in biomarkers from pretreatment to week 8 of treatment. We also performed a meta-analysis pooling the fold change since the previous time point collected. A total of 81 biomarkers were identified from 77 studies. Overall, these studies exhibited extensive heterogeneity with regard to TB treatment monitoring study design and data reporting. Among the biomarkers identified, C-reactive protein (CRP), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), and tumor necrosis factor alpha (TNF-α) had sufficient data to analyze fold changes. All four biomarker levels decreased during the first 8 weeks of treatment relative to baseline and relative to previous time points collected. Based on limited data available, CRP, IL-6, IP-10, and TNF-α have been identified as biomarkers that should be further explored in the context of TB treatment monitoring. The extensive heterogeneity in TB treatment monitoring study design and reporting is a major barrier to evaluating the performance of novel biomarkers and tools for this use case. Guidance for designing and reporting treatment monitoring studies is urgently needed.

Serum Neurofilament Light Chain in Wilson's Disease: A Promising Indicator but Unparallel to Real-Time Treatment Response.

BACKGROUND: Wilson's disease (WD) currently lacks a promising indicator that could reflect neurological impairment and monitor treatment outcome. We aimed to investigate whether serum neurofilament light chain (sNfL) functions as a candidate for disease assessment and treatment monitoring of WD. METHODS: We assessed preclinical and manifested WD patients' sNfL levels compared to controls and analyzed the differences between patients with various clinical symptoms. We then explored the correlation between clinical scales and sNfL levels. And repeated measurements were performed in 34 patients before and after treatment. RESULTS: WD patients with neurological involvement had significantly higher sNfL levels than both hepatic patients and controls. Positive correlations were found between Unified Wilson's Disease Rating Scale scores and sNfL and between semiquantitative magnetic resonance imaging scales and sNfL levels in WD patients. However, in the treatment follow-up analysis, the trend of sNfL before and after treatment disaccorded with clinical response. CONCLUSION: These findings suggest that sNfL levels can be an ideal indicator for the severity of neurological involvement but fail to evaluate change in disease condition after treatment. © 2022 International Parkinson and Movement Disorder Society.

A Novel Detection Method of Breast Cancer through a Simple Panel of Biomarkers.

Circulating tumor cells (CTCs) have been identified as responsible for the spread of tumors to other organs of the body. In this sense, the development of sensitive and specific assays for their detection is important to reduce the number of deaths due to metastases. Here, we assessed whether the detection of CTCs in peripheral blood can serve in the construction of a panel of diagnosis and monitoring treatments of breast cancer (BC), focusing on the expression of markers of epithelial-mesenchymal transition. Through analyzing the blood from women without breast alterations (control), women with benign alterations, women with breast cancer without chemotherapy, and women with breast cancer with chemotherapy, we identified the best markers by transcriptional levels and determined three profiles of CTCs (mesenchymal, intermediate, and epithelial) by flow cytometry which, combined, can be used for diagnosis and therapy monitoring with sensitivity and specificity between 80% and 100%. Therefore, we have developed a method for detecting breast cancer based on the analysis of CTC profiles by epithelial-mesenchymal transition markers which, combined, can be used for the diagnosis and monitoring of therapy.