Assessment Of Treatment Efficacy Research Articles

Molecular subtype stratified outcomes according to adjuvant therapy in endometrial cancer

ObjectivesRecent data support the predictive implications of molecular subtype assignment in endometrial cancer (EC). Our objective was to retrospectively assess clinical outcomes according to adjuvant treatment received within EC molecular subtypes. MethodsClinical outcomes (disease-specific and progression-free survival DSS/PFS) of EC patients from a single institution and population-based cohorts that had undergone molecular classification were assessed with respect to adjuvant therapy received and 2016 ESMO risk group. Results2472 ECs were assessed; 184 (7.4%) POLEmut, 638 (25.8%) MMRd, 1223 (49.5%) NSMP and 427 (17.3%) p53abn. N = 774 (34.6%) of the cohort were ESMO 2016 high risk and 109 (4.8%) were advanced or metastatic. In patients with MMRd EC, assessed across and within stage, there was no observed benefit in DSS or PFS with the addition of chemotherapy +/− radiation compared to radiation alone in ESMO high risk (p = 0.694) or ESMO high, advanced, metastatic risk groups combined (p = 0.852). In patients with p53abn EC, adjuvant chemotherapy given with radiation was associated with significantly longer DSS compared to radiation alone in ESMO high risk (p = 0.007) and ESMO high, advanced and metastatic risk groups combined (p = 0.015), even when restricted to stage I disease (p < 0.001) and when compared in serous vs. non-serous histotypes (p = 0.009). ConclusionsAdjuvant chemotherapy is associated with more favorable outcomes for patients with p53abn EC, including stage I disease and non-serous histotypes, but does not appear to add benefit within MMRd ECs for any stage of disease, consistent with PORTEC-3 molecular subanalysis. Prospective trials, assessing treatment efficacy within molecular subtype are needed, however these ‘real-world’ data should be considered when discussing adjuvant treatment with patients.

Assessing the Increased Variability in Individual Lesion Kinetics During Immunotherapy: Does It Exist, and Does It Matter?

Several studies have raised the hypothesis that immunotherapy may exacerbate the variability in individual lesions, increasing the risk of observing divergent kinetic profiles within the same patient. This questions the use of the sum of the longest diameter to follow the response to immunotherapy. Here, we aimed to study this hypothesis by developing a model that estimates the different sources of variability in lesion kinetics, and we used this model to evaluate the impact of this variability on survival. We relied on a semimechanistic model to follow the nonlinear kinetics of lesions and their impact on the risk of death, adjusted on organ location. The model incorporated two levels of random effects to characterize both between- and within-patient variability in response to treatment. The model was estimated on 900 patients from a phase III randomized trial evaluating programmed death-ligand 1 checkpoint inhibitor atezolizumab versus chemotherapy in patients with second-line metastatic urothelial carcinoma (IMvigor211). The within-patient variability in the four parameters that characterize individual lesion kinetics represented between 12% and 78% of the total variability during chemotherapy. Similar results were obtained during atezolizumab, except for the durability of the treatment effects, for which the within-patient variability was markedly larger than during chemotherapy (40% v 12%, respectively). Accordingly, the occurrence of divergent profile consistently increased over time in patients treated with atezolizumab and was equal to about 20% after 1 year of treatment. Finally, we show that accounting for the within-patient variability provided a better prediction of most at-risk patients than a model relying solely on the sum of the longest diameter. Within-patient variability provides valuable information for the assessment of treatment efficacy and the detection of at-risk patients.

An international survey exploring the adoption and utility of diagnostic lung ultrasound by physiotherapists and respiratory therapists in intensive care.

Lung ultrasound (LUS) is an emerging assessment tool for intensive care unit (ICU) therapists (physiotherapists, physical therapists and respiratory therapists) to aid pathology identification, intervention selection, clinical reasoning and as an outcome measure to assess intervention efficacy. However, the extent of LUS adoption and use by ICU therapists internationally has not been described in the literature. This survey explored the interest in LUS amongst ICU therapists internationally. In addition, LUS training, use in clinical practice and barriers to implementation were also explored. The survey findings were used to facilitate recommendations for future adoption. International ICU therapists were invited to answer a 37 question cross-sectional open e-survey, distributed using the online survey tool REDCap®. The exact sample size of eligible ICU therapists from around the world is unknown, therefore the participant responses received were a representative convenience sample of the international ICU therapist population. Survey links were posted on the relevant web pages and social media forums utilised by various ICU therapist associations and professional organisations worldwide. A snowballing technique was used to encourage survey participants to forward the survey link within their professional networks. The survey was open on REDCap® for an 8-week period between March and May 2021. Three hundred twenty ICU therapists from 30 countries responded with most respondents coming from either the United Kingdom (n = 94) or Australia (n = 87). Eighty-nine of the ICU therapist respondents (30%) reported being users of LUS, however, 40 of those 89 respondents reported having no formal accreditation. The top clinical indications to perform a LUS scan were changes on chest radiograph, altered findings on auscultation and a low partial pressure of arterial oxygen/fraction of inspired oxygen ratio. The 71% of LUS users reported that their ICU does not have a local policy in place to guide ICU therapists' use of LUS. Most LUS users (82%) only document their LUS findings in the patient's medical notes and (73%) only store the LUS clips on the ICU's ultrasound machine. The 85% of respondents perceive LUS becoming an increasing part of their objective assessment in the future and 96% report that they have other ICU therapist colleagues interested in adopting LUS. Main reasons why respondents believe that ICU therapists are not adopting LUS in their ICU are a difficulty in access to appropriate training, mentorship, and a lack of local governance policy guiding their use of LUS. To the authors' knowledge this is the first study to explore the international adoption and utility of LUS by ICU therapists. LUS is a growing technique with widespread interest from ICU therapists internationally with a desire to adopt LUS into their assessments and upskill their practice. ICU therapists' use of LUS could allow more targetted and appropriate treatment for patients on ICU. Barriers to LUS adoption could be mitigated by having access to quality training programmes and mentorship. Development of profession specific guidance and policies within local infrastructure should facilitate growth and ensure robust quality assurance and governance processes.

Developing a Bayesian hierarchical model for a prospective individual patient data meta-analysis with continuous monitoring

BackgroundNumerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques.MethodsWe provide a detailed look at the challenges and solutions for model development, describing the process that used extensive simulations to enable us to finalize the analysis plan. This includes establishing prior distribution assumptions, assessing and improving model convergence under different study composition scenarios, and assessing whether we can extend the model to accommodate multi-site RCTs and evaluate heterogeneous treatment effects. In addition, we recognized that we would need to assess our model for goodness-of-fit, so we explored an approach that used posterior predictive checking. Lastly, given the urgency of the research in the context of evolving pandemic, we were committed to frequent monitoring of the data to assess efficacy, and we set Bayesian monitoring rules calibrated for type 1 error rate and power.ResultsThe primary outcome is an 11-point ordinal scale. We present the operating characteristics of the proposed cumulative proportional odds model for estimating treatment effectiveness. The model can estimate the treatment’s effect under enormous uncertainties in study design. We investigate to what degree the proportional odds assumption has to be violated to render the model inaccurate. We demonstrate the flexibility of a Bayesian monitoring approach by performing frequent interim analyses without increasing the probability of erroneous conclusions.ConclusionThis paper describes a translatable framework using simulation to support the design of prospective IPD meta-analyses.

Optimization of the radiation dosimetry protocol in Lutetium-177-PSMA therapy: toward clinical implementation

BackgroundDosimetry in [177Lu]Lu-PSMA therapy is a valuable tool to assess treatment efficacy and toxicity. This study aims to develop a clinically implementable protocol to determine the absorbed dose in organs and tumor lesions after [177Lu]Lu-PSMA-617 therapy, by reducing the imaging time points and utilizing population-based kinetics with a single scan, with evaluation of its influence on the uncertainty in absorbed dose.MethodsTen patients with metastatic hormone-sensitive prostate cancer received two cycles of [177Lu]Lu-PSMA-617. Post-treatment imaging was performed at 1 h, 24 h, 48 h, 72 h and 168 h, consisting of three-bed positions SPECT/CT and a whole-body planar scan. Five-time point SPECT dosimetry was performed for lesions and organs with physiological uptake (kidneys, liver and salivary glands) and used as the reference standard. Absorbed dose values for various simplified protocols were compared to the reference standard.ResultsAccurate lesion dosimetry is possible using one-time point SPECT imaging at 168 h, with an increase in uncertainty (20% vs. 14% for the reference standard). By including a second time point, uncertainty was comparable to the reference standard (13%). Organ dosimetry can be performed using a single SPECT at 24 h or 48 h. Dosimetry based on planar scans did not provide accurate dose estimations.ConclusionAccurate lesion dosimetry in [177Lu]Lu-PSMA therapy can be performed using a one- or two-time point protocol, making dosimetry assessments more suitable for routine clinical implementation, although dosimetry based om multiple time points is more accurate.Clinical trial registration This study was approved by the Medical Review Ethics Committee Region Arnhem-Nijmegen on January 23, 2018 and was registered on clinicaltrials.gov (NCT03828838).

Effects of Dupilumab on Itch-Related Events in Atopic Dermatitis: Implications for Assessing Treatment Efficacy in Clinical Practice.

Dupilumab attenuates itch and skin inflammation in patients with atopic dermatitis (AD). However, itch-related events that are improved by dupilumab remain unclear. Therefore, the present study investigated changes in clinical scores, serum biomarkers, and the number of intraepidermal nerve fibers (IENFs) using skin biopsies and blood samples from 12 patients with moderate to severe AD before and after treatment with dupilumab. Clinical manifestations were assessed using eczema area and severity index (EASI) and visual analogue scale (VAS) scores at baseline and after 8 and 16 weeks of treatment. Serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), interleukin (IL)-4, IL-13, IL-22, and IL-31 were examined by electrochemiluminescence, chemiluminescent enzyme immunoassays, ProQuantum immunoassays, and enzyme-linked immunosorbent assays (ELISA) at baseline and after 8 and 16 weeks of treatment. In skin biopsies from AD patients at baseline and after 16 weeks of treatment, IENFs were examined immunohistochemically with the anti-protein gene product (PGP) 9.5 antibody. The dupilumab treatment significantly improved EASI and VAS scores and decreased serum levels of TARC, IgE, and IL-22, whereas those of IL-13 and IL-31, and the number of IENFs remained unchanged and those of IL-4 increased. VAS scores were positively correlated with serum TARC, IL-22, and IgE levels and the degree of epidermal thickening. Serum IL-31 levels were positively correlated with the number of IENFs. These results suggest that serum TARC, IL-22, and IgE levels and epidermal thickness are itch-related events associated with dupilumab treatment and that serum IL-31 levels may reflect the degree of IENF density in AD patients. Therefore, dynamic changes may be used to assess the efficacy of dupilumab treatment to treat itching and inflammation in patients with AD.

Integrated Visual Assessment Method for Infestation by Lebbek Borer (Xystrocera globosa) in Rain Trees of Singapore

"Background: In Singapore, determining the level of infestation by lebbek borer (Xystrocera globosa)(Olivier, 1795)[Coleoptera: Cerambycidae] is the crucial first step in control of this pestra in rain tree (Albizia saman [Jacq.] Merr.)[Fabales: Fabaceae]. Current assessment methods rely on symptoms such as canopy colour, defoliation, dieback, and actual estimation of borer population via counting of larvae or exit holes created by adults. Currently, there is a lack of systematic approach to integrate different tree health indicators and symptoms to quantify infestation level. This gap poses challenges in assessment of treatment efficacy as managers could not quantitatively determine whether infestation level has changed following treatment. Thus, this study aimed to develop a visual assessment method that can integrate all mentioned symptoms to quantify infestation level. Methods: We surveyed a total of 388 rain trees and used principal component analysis (PCA) to investigate the correlation between X. globosa infestation and different borer infestation symptoms. Borer Infestation Score (BIS) formula was developed based on the linear combinations of the statistically significant principal component. Results: Infestation level was strongly associated with bark peeling, exit holes, and proximity of bark peeling and/or exit holes to trunk base and weakly associated with defoliation, dieback, and canopy colour. Developed BIS formula generated numerical values that distinguished between noninfested and infested trees, reflected infestation level in surveyed areas and temporal progression of infestation. Conclusions: Described integrated visual assessment method can be executed quickly on field. BIS formula generates quantitative scores easy to be interpreted, tracked, and compared.

Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy

The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.

High dose intravenous vitamin C for lyme disease: a safety and tolerability study with an exploratory assessment of treatment efficacy.

Lyme disease is the most common vector-borne disease in the United States with an estimated 476,000 new cases per year. Delays in diagnosis and treatment are common and there is a lack of consensus on the antibiotic therapy protocols to ensure successful outcomes. Much of this discord is due to the observation that more than 50 percent of people treated with conventional antibiotic protocols, which have changed little in the last 30 years, report persistent and/or recurring symptoms within 6 months of completing treatment. Labeled as chronic Lyme or post-treatment Lyme disease, it is a syndrome that afflicts more than 2 million people in the United States and can have a devastating impact on both quality of life and socioeconomic capacity. Despite these known treatment failures, the research community has lacked the funding necessary to advance our understanding of this syndrome or to explore innovative options to improve success. In this regard, complementary and alternative therapies, which are generally not patentable and have little potential for producing large economic gain, are generally disregarded in favor of new designer drugs or old reworked protocols. Intravenous vitamin C is one such example that has research validated effectiveness for a wide range of clinical conditions ranging from infection to cancer care. Achieving serum levels much higher than could be obtained orally, high dose intravenous vitamin C has the capacity to generate a concentration of intracellular peroxide that exerts both cytotoxic and immune stimulating effects. Unfortunately, these high doses of intravenous vitamin C have never been evaluated to establish safety and tolerability in Lyme positive patients. This study’s primary aim is to examine this question with the unique additions of DMSO and calcium EDTA into the formula to enhance tissue penetration and address biofilm formation respectively, both of which are known barriers to antibiotic success. The secondary aim of the study is to determine whether subjects gain relief from Lyme-associated symptoms by tracking changes in both the PROMIS-29 and the Horowitz-Lyme-MSIDS questionnaires. The exploratory objective is to assess changes in Lyme specific labs including the standard immunoblot and the T-cell based Elispot as well as the CD57+ lymphocyte immune marker. Administered at a 75-gram dose twice weekly over 12 weeks, high dose intravenous vitamin C was shown to be both well tolerated and safe. The secondary and exploratory aims of the study provide insight into the potential efficacy of this protocol, as both subjective measures of symptom severity and objective assessment of Lyme biomarkers showed marked improvement. Ultimately, this study paves the way for future research using high dose intravenous vitamin C in Lyme patents either as a stand-alone treatment or in synergy with other therapies. It is this author’s hope that employing an integrative medical approach such as this will eventually see chronic Lyme disease as a rare rather than common occurrence.

Роль гленополярного угла в оценке эффективности лечения переломов лопатки

Relevance: Scapula fractures are a rare musculoskeletal system injury, accounting for only 0.4–1% of all fractures and approximately 3–5% of all shoulder girdle injuries. Proper visualization plays a key role in determining the severity of a scapula fracture and the choice of further treatment tactics. It allows not only to fully assess the integrity of the body and neck of the scapula, but also to analyze various radiologic parameters, the most important of which is the glenopolar angle (GPA). Aim. To review the values of GPA in patients with different extra-articular types of scapula fractures before and after treatment, and to analyze the correlation of the assessment of treatment efficacy with the values of GPA. Material and methods. We selected 35 patients with extra-articular fractures of the scapula, with damage to the neck and body, including 9 (26%) women and 26 (74%) men. Constant Shoulder Score (CSS) questionnaire scale was used to evaluate the effectiveness of the treatment performed. A value in the range of 30 to 45º was accepted as a normal value of the GPA. Results. After analyzing the radiographs, several groups of patients were formed. After evaluating the treatment efficacy of all patients in the sample, an average CSS score of 81 (good result) was obtained. Group 1 patients achieved on average a good treatment result (μ=84 points), group 2 — good result (μ=82 points), group 3 patients — satisfactory result (μ=75 points). Conclusion. Based on the results of this study, we can conclude that there is a correlation between the value of the GPA and the overall effectiveness of the treatment of scapula fracture. Ignoring the GPA may lead to unsatisfactory results of treatment in the long-term period.

PREP Plus combined postrehabilitation programme to support upper limb recovery in community-dwelling stroke survivors: protocol for a mixed-methods, cluster-assigned feasibility study

IntroductionPoor recovery of the upper limb following a stroke has been recognised as a significant problem in the UK. Although there is good evidence that early, intense rehabilitation can lead...

Individual behavioral profiling as a translational approach to assess treatment efficacy in an animal model of post-traumatic stress disorder.

A major challenge in treating post-traumatic stress disorder (PTSD) continues to be the large variability in responsiveness to pharmacotherapy. Only 20-30% of patients experience total remission to a specific treatment, while others demonstrate either partial remission or no response. However, this heterogeneity in response to pharmacotherapy has not been adequately addressed in animal models, since these analyze the averaged group effects, ignoring the individual variability to treatment response, which seriously compromises the translation power of such models. Here we examined the possibility of employing an "individual behavioral profiling" approach, originally developed to differentiate between "affected" and "exposed-unaffected" individuals in an animal model of PTSD, to also enable dissociating "responders" or "non-responders" after SSRI (fluoxetine) treatment. Importantly, this approach does not rely on a group averaged response to a single behavioral parameter, but considers a cluster of behavioral parameters, to individually characterize an animal as either "responder" or "non-responder" to the treatment. The main variable to assess drug efficacy thus being the proportion of "responders" following treatment. Alteration in excitatory/inhibitory (E/I) balance has been proposed as being associated with stress-related psychopathology. Toward a functional proof of concept for our behaviorally-based characterization approach, we examined the expression patterns of α1 and α2 subunits of GABAA receptor, and GluN1 and GluN2A subunits of the NMDAR receptor in the ventral hippocampus, as well as electrophysiologically local circuit activity in the dorsal dentate gyrus (DG). We demonstrate that with both parameters, treatment "responders" differed from treatment "non-responders," confirming the functional validity of the behavior-based categorization. The results suggest that the ability to respond to fluoxetine treatment may be linked to the ability to modulate excitation-inhibition balance in the hippocampus. We propose that employing the "individual behavioral profiling" approach, and the resultant novel variable of the proportion of "recovered" individuals following treatment, offers an effective translational tool to assess pharmacotherapy treatment efficacy in animal models of stress and trauma-related psychopathology.

Corneal Densitometry to Assess the Corneal Cystine Deposits in Patients With Cystinosis.

The purpose of this study was to assess the suitability of corneal densitometry measurements obtained with Scheimpflug imaging in estimating the corneal changes caused by cystine deposits in the cornea in patients with cystinosis. Scheimpflug imaging (Pentacam) was performed for 14 patients with cystinosis and 16 age-matched controls. Pentacam data were used for analysis of the corneal densitometry at different zones in the cornea for patients with cystinosis and controls. Densitometry measurements were compared with the corneal crystal scores obtained from the slitlamp images for patients with cystinosis. There was no statistically significant difference in keratometry measurements between the 2 groups ( P > 0.05). Corneal thickness was found to be significantly higher in the control group when compared with the cystinosis group ( P = 0.0004). The mean corneal densitometry was significantly higher in patients with cystinosis when compared with controls at most of the corneal layers and zones. The corneal densitometry readings for the right and left eyes showed moderate positive correlation with the corneal crystal score with a ceiling effect being reached at the maximum corneal crystal score of 3. Corneal densitometry obtained through Pentacam can be used as an objective estimate of the level of cystine crystals present in patients with cystinosis. The clinical estimate of corneal crystal score, although effective at low levels of crystal deposition, does not allow for accurate estimates of change when the level of crystal deposition is high leading to limited utility when assessing treatment effects. Hence, densitometry measurements can potentially be used to assess treatment efficacy of cystinosis treatments in clinical settings.

Quantifying Rheumatoid Arthritis Disease Activity Using a Multimodal Sensing Knee Brace.

Rheumatoid arthritis (RA) is a chronic inflammatory syndrome that features painful and destructive joint disease. Aggressive disease-modifying treatment can result in reduced symptoms and protection from irreversible joint damage; however, assessment of treatment efficacy is currently based largely on subjective measures of patient and physician impressions. In this work, we address this compelling need to provide an accurate and quantitative capability for monitoring joint health in patients with RA. Joint acoustic emissions (JAEs), electrical bioimpedance (EBI), and kinematics were measured noninvasively from 11 patients with RA over the course of three weeks using a custom multimodal sensing brace, resulting in 49 visits with JAE recordings and 43 with EBI recordings. Features derived from all sensing modalities were fed into a linear discriminant analysis (LDA) model to predict disease activity according to the validated disease activity index (the DAS28-ESR). Erythrocyte sedimentation rate (ESR) was predicted using ridge regression and classified into a high or low class using LDA. DAS28-ESR level was predicted with an area under the receiver operating characteristic curve (AUC) of 0.82. With JAEs alone, we were able to track intrasubject differences in the disease activity score as well as classify ESR level with an AUC of 0.93. The majority of patients reported both an interest and ability to use the brace at home for longitudinal monitoring. This work demonstrates the ability to detect RA disease activity using noninvasive sensing. This system has the potential to improve RA disease activity monitoring by giving treating clinicians objective data that can be acquired independent of a face-to-face clinic visit.

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Theranostics is a breakthrough paradigm of personalized and precision medicine for treatment of visual disorders. In this work, accuracy and precision of this therapeutic approach for achieving predictable strengthening of corneal tissue biomechanics were assessed on eye bank human donor tissues. Theranostic UV‐A light mediated imaging and photo‐activation of the tissues enriched with riboflavin demonstrated highly precise and predictable real time assessment of treatment efficacy on individual corneas.Further details can be found in the article by Giuseppe Lombardo, Giuseppe Massimo Bernava, Sebastiano Serrao, and Marco Lombardo (e202200218). image

The place of laser fluorescence spectroscopy, doppler flowmetry and ultrasound in the diagnosis and assessment of treatment efficacy for plaque scleroderma

According to modern ideas, a reasonable choice of an effective method of treating plaque scleroderma is based on the diagnosis of the pathological process prevailing in the tissues (inflammation-sclerosis). Therefore, an urgent problem of a personalized approach to dermatosis therapy is the possibility of an objective assessment of the prevailing process using non-invasive diagnostic methods. The article presents a clinical case of widespread plaque scleroderma in a 66-year-old patient, demonstrating the possibility of using laser fluorescence spectroscopy and laser Doppler flowmetry to determine the degree of activity of the focus and determine the leading pathological process.&#x0D; We selected three pathological skin foci localized in the abdomen and characterizing three clinical stages of the disease (inflammation, induration, sclerosis). The analysis of fluorescence and laser Doppler flowmetry data showed that in areas clinically defined as inflammation, there is an increase in the average values of the indices of tissue content of porphyrins, lipofuscin and microcirculation index compared with intact skin, while the intensity of collagen fluorescence does not differ significantly. In the induration zone, along with an increase in the fluorescence indices of lipofuscin and porphyrins, there is an increase in the average values of collagen fluorescence indices at effective registration waves. The data obtained by us indicate an active inflammatory process in these foci and the process of fibrosis in the induration zone. In the sclerosis zone, there is an increase in the average values of collagen fluorescence indices compared with intact skin, and the fluorescence of optical markers of inflammation (lipofuscin and porphyrins) do not differ significantly in comparison with the control intact skin. When analyzing the fluorescence spectra and laser Doppler flowmetry data after treatment, we found that in the zones of induration and inflammation, the average values of the fluorescence indices of porphyrins, lipofuscin, collagen and microcirculation index are reduced relative to the initial values (before treatment), but remain higher in comparison with intact skin. The data obtained may indicate that active inflammation in these foci persists at the time of the study. In the study of the focus of sclerosis, the obtained autofluorescence and microcirculation data in dynamics do not differ significantly from the initial values. The data for laser Doppler flowmetry and laser fluorescence spectroscopy are consistent with ultrasound examination of the skin.&#x0D; In our study, the potential possibility of using laser fluorescence spectroscopy and laser Doppler flowmetry methods to establish the degree of activity of the focus, determine the leading pathological process, as well as to evaluate the effectiveness of therapy was demonstrated for the first time.

ImageJ assessment of double-frequency YAG laser efficacy in treatment of mild lower eyelid ectropion with punctal eversion

PurposeTo describe a simple and minimally invasive technique using double-frequency YAG laser for correction of mild medial lower eyelid ectropion with punctal eversion and assess the efficacy of the technique by measuring the tear film meniscus pre- and post-laser treatment using imageJ software.MethodsThis study included 23 eyes of 19 patients with lower eyelid ectropion with punctal eversion. All patients were treated by double-frequency YAG laser applied to lower medial conjunctiva. Tear film thickness was assessed using imageJ software pre- and post-argon laser treatment.ResultsThere was a highly significant change detected after argon laser treatment as regarding the mean of the height of tear film which was found to be significantly lower after argon laser treatment compared to before it (81.1 pixels versus 193.1 pixels, respectively) (P < 0.001).ConclusionDouble-frequency YAG laser applied to lower medial palpebral conjunctiva is a simple, easy, safe, and effective procedure which can be used as a solo treatment in early cases of punctal eversion with no or mild medial canthal tendon laxity.

Novel neuroelectrophysiological age index associated with imaging features of brain aging and sleep disorders.

Sleep architecture and microstructures alter with aging and sleep disorder-led accelerated aging. We proposed a sleep EEG based brain age prediction model using convolutional neural networks. We then associated the estimated brain age index with brain structural aging features, sleep disorders and various sleep parameters. Our model also showed a higher BAI (predicted brain age minus chronological age) is associated with cortical thinning in various functional areas. We found a higher BAI for sleep disorder groups compared to healthy sleepers, as well as significant differences in the spectral pattern of EEG among different sleep disorders (lower power in slow and ϑ waves for sleep apnea vs. higher power in β and σ for insomnia), suggesting sleep disorder-dependent pathomechanisms of aging. Our results demonstrate that the new EEG-BAI can be a biomarker reflecting brain health in normal and various sleep disorder subjects, and may be used to assess treatment efficacy.

BIOM-14. SYSTEMIC BIOMARKERS OF TUMOR BURDEN IN GLIOBLASTOMA PATIENTS

Abstract Glioblastomas (GBM) are Grade IV gliomas that are highly aggressive, lethal primary brain tumors. They are extremely heterogenous tumors both at a cellular and molecular level, harboring diverse oncogenes and mutated tumor suppressor genes with both inter- and intra-tumor variability in expression patterns. Currently, the presence of GBM cannot be predicted and they are diagnosed post-surgical resection by histologic evaluation of tumor tissue. There is an urgent, unmet need for the discovery of GBM-specific biomarkers that could precisely predict and monitor the presence of tumors in GBM patients. Over the last seven years we have carried out a prospective, multi-center, clinical study to longitudinally analyze tumor and plasma samples from GBM patients. We have characterized expression levels of microRNAs, mRNAs and proteins isolated from plasma samples collected from GBM patients throughout their treatment and compared these data to clinical and pathological reports for each patient. Our research has identified a set of systemic microRNAs and their targets that can be correlated to tumor burden in GBM patients. Data will be presented to demonstrate how specific sets of molecular markers and secreted proteins can track disease in GBM patients. This study provides insights into how systemically expressed biomarkers in GBM patients can be used in the development of methods for the precise assessment of disease progression and treatment efficacy while being minimally invasive and cost-effective. Combining clinicopathological findings and biomarker profiling will predict treatment outcomes and provide oncologists precise readouts for tumor burden and response to treatment. Furthermore, this research will also provide critically needed criteria for rigorous monitoring of efficacy of all new therapeutic trials for GBM.

NIMG-14. RADIOLOGIC ASSESSMENT OF BRAIN METASTASES UNDERGOING LASER INTERSTITIAL THERMAL THERAPY (LITT)

Abstract BACKGROUND Laser Interstitial Thermal Therapy (LITT) is a novel treatment for brain metastases (BMs), and data regarding radiologic changes and long-term efficacy is sparse. This study explored volumetric changes in responding and non-responding BMs and their associations with lesion-specific progression-free survival (PFS-L). METHODS Patients with BMs treated with LITT were retrospectively enrolled. 3D volumes-of-interest of the contrast-enhancing BM tissue (CE) on pre-, post-LITT, and follow-up MRI scans were obtained. BMs were followed until progression or censoring. PFS-L was determined using the modified RANO criteria to assess treatment efficacy on each lesion. RESULTS Thirty-one BMs (from 30 patients) were preliminarily analyzed. 2 BMs had no follow-up scans. Median follow-up for 29 BMs was 248 days (range 28-2200). Median time to response was 430 days (responders n=7/29), median time to progression was 176 days (progressive disease n=7/29). Pre-LITT CE volume was a predictor of PFS-L (p=0.001), with BMs&amp;gt; 2.5 cc being 14 times more likely to undergo progression. Differences in age and primary tumor site did not impact PFS-L, whereas PFS-L tended to be longer in females (p=0.059), and in frontal and deep grey matter BMs (p=0.11). Post-LITT CE volume was higher than pre-LITT (p&amp;lt; 0.0001, median increase 59%), with no significant differences among responders, stable disease, and progressive disease. In each responding BM, the CE volume shrinkage over time was described by an exponential decay (R2 ranging 0.92-1.0 and half-life ranging 16.55-204 days). All responding BMs showed a pooled exponential decay with R2=0.88 and half-life=75.6 days. CONCLUSIONS Our data suggest that smaller BMs may have improved outcomes from LITT treatment. CE volumes may increase in the early post-procedural scans, possibly due to both inflammatory changes and thermal damage. The characterization of the volumetric changes across time for responding lesions may be useful for an early detection of BMs at risk for progression.