Diagnostic Paradigm Research Articles

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Long-Term Outcomes and Novel Observations from a Large BPDCN Cohort

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), is an ultra-rare, clinically aggressive, CD123-overexpressing hematologic malignancy now reclassified in the 5th edition WHO under dendritic cell and histiocytic neoplasms (Khoury J Leukemia 2022). BPDCN is characterized by involvement of 4 major compartments: skin, bone marrow, lymph nodes, and central nervous system (CNS). BPDCN has been historically associated with a lack of treatment options, dismal outcomes (median OS 8-16 months). Now, in the modern treatment era, with CD123-based and combination therapies, emerging data and a number of significant clinical/translational breakthroughs have led to progress in this rare disease field (Pemmaraju N JCO 2022; Pemmaraju N Blood Adv 2022). In this analysis, we aim to describe long-term patient characteristics and outcomes in one of the largest ongoing, single-institution, prospectively followed group of patients (pts) with BPDCN in the world. Patient Characteristics: All pts ages ≥ 18 years with a confirmed pathological diagnosis of BPDCN and treated at our institution were included in this analysis. During Oct 1998-July 2022, 118 pts with BPDCN were identified. Median age was 66 years [range 19-86 years]. 81% were male. At presentation to our institution: n=78 untreated; n=40 had prior therapy (median # prior therapies = 1 [1-5]). Bone marrow (BM) was involved in 75 (64%), skin-only in 41 (35%), lymph node-only in 2 (2%). In addition to CD4+ and CD56+ tumor immunophenotype demonstrated: TCL-1+ (77/77 tested) and CD123+ in 100%. Cytogenetics among 106 pts available: diploid (74%), complex (22%), del (12p) in 2%, miscellaneous (2%). Median BM blast count was 8% [0-95]. Historically, as there has been no standard of care therapeutic approach, a variety of frontline chemotherapy regimens were administered over time (including in this cohort: CD123-based; ALL-based; AML-based; CHOP/lymphoma-based; HMA+VEN based; other regimens). Results, overall cohort (n=118): The median follow-up time was 23 months [4.1 - 91 mo]. Median # of chemotherapy regimens was 1 [1-6]. Median overall survival (OS) was 23 mo [0.9 -158.0 mo]. 78 (66%) pts died, with the most common cause of death being multi-organ failure. Skin-only pts with BPDCN: Remarkably, in this long-term f/u, there was no statistically significant difference between skin (n=41) vs BM involved BPDCN (n=75) in terms of either OS (20 mo vs 23 mo) or CR1 (21 vs 38 mo). SCT: 40 pts (33%) received stem cell transplant (SCT) during CR1. The median OS for pts receiving SCT was statistically significantly superior at 66 mo [5.3-90.8 mo] vs a median OS for non-SCT group in CR1 (n=31) of 23 mo [4.1-158.0], p =0.003. CNS involvement BPDCN: Notably, in this longer f/u of our series, we found that a high rate, 33%, of our pts had CSF+ at any time during the course of their BPDCN, with the vast majority of cases detected on routine/asymptomatic lumbar punctures. Prior or concomitant hematologic malignancies (PCHM): The occurrence of PCHM remains quite common in BPDCN, making up 24% of our total BPDCN population, with MDS/CMML representing the most common PCHM. Next-generation Sequencing (NGS): A molecular gene panel via NGS on BM specimens was done in n=80; 60 (75%) had TET2 abnormality (standard mutation=36, standard+variant=2, variants=22), which was the most common molecular abnormality among our BPDCN cohort. There was no statistically significant difference in terms of OS or CR1 in pts with known TET2 mutations/variants vs all others/not done. The second most common mutation was ASXL1 in 38%, followed by RAS mutations in 19%. Conclusions: This longer-term analysis (med f/u ~ 2 years) of a large, ongoing cohort of pts with BPDCN reveals several important findings including continued overall similar long-term outcomes in skin-only vs BM-involved BPDCN; significant OS improvement in CR1 for younger/fit pts who are able to proceed to SCT when available; a strikingly high incidence of CSF+ in BPDCN which is a higher incidence than previously recognized, and has led to our practice-changing approach of standard incorporation of routine LP with IT chemo for all pts with BPDCN; and a notably common occurrence of PCHM in BPDCN to be aware of in both diagnostic and treatment paradigms. With median OS still only ~2 years, BPDCN remains a highly aggressive hematologic malignancy still in need of active clinical/translational research and novel therapeutic approaches.

Prone positioning reduces frontal and hippocampal neuronal dysfunction in a murine model of ventilator-induced lung injury.

Prone positioning is an established treatment for severe acute lung injury conditions. Neuronal dysfunction frequently occurs with mechanical ventilation-induced acute lung injury (VILI) and clinically manifests as delirium. We previously reported a pathological role for systemic interleukin 6 (IL-6) in mediating neuronal injury. However, currently no studies have investigated the relationship between prone or supine positioning and IL-6 mediated neuronal dysfunction. Here, we hypothesize that prone positioning mitigates neuronal injury, via decreased IL-6, in a model of VILI. VILI was induced by subjecting C57BL/6J mice to high tidal volume (35 cc/kg) mechanical ventilation. Neuronal injury markers [cleaved caspase-3 (CC3), c-fos, heat shock protein 90 (Hsp90)] and inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured in the frontal cortex and hippocampus. We found statistically significantly less neuronal injury (CC3, c-Fos, Hsp90) and inflammatory cytokines (IL-6, IL-1β, TNF-α) in the frontal cortex and hippocampus with prone compared to supine positioning (p < 0.001) despite no significant group differences in oxygen saturation or inflammatory infiltrates in the bronchoalveolar fluid (p > 0.05). Although there were no group differences in plasma IL-6 concentrations, there was significantly less cortical and hippocampal IL-6 in the prone position (p < 0.0001), indicating supine positioning may enhance brain susceptibility to systemic IL-6 during VILI via the IL-6 trans-signaling pathway. These findings call for future clinical studies to assess the relationship between prone positioning and delirium and for investigations into novel diagnostic or therapeutic paradigms to mitigate delirium by reducing expression of systemic and cerebral IL-6.

The Role of Contemporary Wearable and Handheld Devices in the Diagnosis and Management of Cardiac Arrhythmias.

Cardiac arrhythmias are associated with significant morbidity, mortality and economic burden on the health care system. Detection and surveillance of cardiac arrhythmias using medical grade non-invasive methods (electrocardiogram, Holter monitoring) is the accepted standard of care. Whilst their accuracy is excellent, significant limitations remain in terms of accessibility, ease of use, cost, and a suboptimal diagnostic yield (up to ∼50%) which is critically dependent on the duration of monitoring. Contemporary wearable and handheld devices that utilise photoplethysmography and the electrocardiogram present a novel opportunity for remote screening and diagnosis of arrhythmias. They have significant advantages in terms of accessibility and availability with the potential of enhancing the diagnostic yield of episodic arrhythmias. However, there is limited data on the accuracy and diagnostic utility of these devices and their role in therapeutic decision making in clinical practice remains unclear. Evidence is mounting that they may be useful in screening for atrial fibrillation, and anecdotally, for the diagnosis of other brady and tachyarrhythmias. Recently, there has been an explosion of patient uptake of such devices for self-monitoring of arrhythmias. Frequently, the clinician is presented such information for review and comment, which may influence clinical decisions about treatment. Further studies are needed before incorporation of such technologies in routine clinical practice, given the lack of systematic data on their accuracy and utility. Moreover, challenges with regulation of quality standards and privacy remain. This state-of-the-art review summarises the role of novel ambulatory, commercially available, heart rhythm monitors in the diagnosis and management of cardiac arrhythmias and their expanding role in the diagnostic and therapeutic paradigm in cardiology.

Sensitivity of FEV1 and Clinical Parameters in Children With a Suspected Asthma Diagnosis

Asthma is the most common chronic disease in children and a robust diagnosis is crucial to optimize patient care and reduce its burden. To diagnose asthma in children, the Global Initiative for Asthma (GINA) recommendations propose a 12% improvement in forced expiratory volume in 1 second (FEV1) after a bronchodilation test. Nevertheless, such a criterion is rarely confirmed in these patients in clinical practice. The objective of this study was to evaluate the sensitivity of spirometric and clinical parameters in identifying children with possible asthma. The VERI-VEMS Study is a multicenter international retrospective cohort study. Data were collected, from January 2008 until January 2019, for all consecutive children (aged 5-18 years), with a diagnosis of asthma, who performed a spirometry at the time of the diagnosis. We compared the sensitivity of the reversibility criterion proposed by GINA guidelines, with other spirometric and clinical variables, using physician-diagnosed asthma and response to treatment as the standard. The study included 871 children. The reversibility criterion of 12% of FEV1 showed a sensitivity of 30.4%. The 3 best spirometric or clinical criteria were the presence of dry cough, or wheezing or atopy and dry cough, or wheezing or exercise-induced dyspnea, with a sensitivity reaching 99.5%, with no added value of the spirometric parameters in the calculation of the cumulated sensitivity for the diagnosis of pediatric asthma. Postbronchodilator reversibility of 12%, although essential for patients' follow-up, has an insufficient low sensitivity in reaching a diagnosis of asthma in pediatric patients, compared with a combination of clinical symptoms, that show a better sensitivity. Further studies on specificity will help clarify the role of this change in the diagnostic paradigm in formally diagnosing children with asthma.

Microbiome and metabolome dysbiosis of the gut-lung axis in pulmonary hypertension

Previous studies have suggested that dysbiosis of the gut microbiota is associated with the development of pulmonary hypertension (PH). In this study, we established a left pulmonary artery ligation (LPAL)-induced PH rat model due to high flow and hemodynamic stress and investigated the association between gut microbiota composition and host metabolome signatures (in both gut and lung tissues) by using multiomics and correlation analysis. The results showed that LPAL successfully induced PH, characterized by increased right ventricular systolic pressure, right ventricular hypertrophy and pulmonary vascular remodelling. Moreover, gut pathological abnormalities were observed in association with dramatic alterations in the gut microbiome and metabolome as well as the lung metabolome. The increased bacterial genus Sporobacter and decreased genera Eubacterium, Eubacteriaceae, Deltaproteobacteria and Desulfovibrio featured the altered gut microbiome in LPAL-PH versus SHAM rats. Moreover, imbalanced abundance of protective metabolites (e.g., butyrate, propionate) and pathogenic metabolites (e.g., proinflammatory mediators) were seen in the gut metabolome of LPAL-PH versus SHAM rats. In addition, the altered gut microbiome strongly correlated with the altered metabolome patterns in both the gut and lung of LPAL-PH rats. In conclusion, this study revealed significant gut dysbiosis in LPAL-PH rats, characterized by altered gut microbiota composition, in association with specific changes in gut and lung metabolome profiles. These findings enriched our understanding of the unique signature of the gut microbiome and the close association of the “gut-lung axis” in LPAL-PH induced by long-term high flow, leading to novel therapeutic, diagnostic or management paradigms for this subtype of PH.

Does Achalasia Subtype III Need to be Treated Differently Than Type I and II? Pro Argument

Type III achalasia, previously known as spastic achalasia, has been a rare but challenging diagnosis to treat. While it is included in the same diagnostic and treatment paradigm of types I and II achalasia, conventional therapies such as Botulinum Toxin A injection, pneumatic dilation, and Heller myotomy have yielded poor outcomes. Given the longer segment of spastic esophageal muscle, per oral endoscopic myotomy (POEM) is emerging as the dominant treatment paradigm. As such, it behooves us to treat type III achalasia as the unique entity that it is rather than the “garden variety” achalasia.

How Artificial Intelligence Aspires to Change the Diagnostic and Treatment Paradigm in Eyes With Age-Related Macular Degeneration.

How Artificial Intelligence Aspires to Change the Diagnostic and Treatment Paradigm in Eyes With Age-Related Macular Degeneration.

Artificial intelligence in dementia.

Artificial intelligence tools are being rapidly integrated into clinical environments and may soon be incorporated into dementia diagnostic paradigms. A comprehensive review of emerging trends will allow physicians and other healthcare providers to better anticipate and understand these powerful tools. Machine learning models that utilize cerebral biomarkers are demonstrably effective for dementia identification and prediction; however, cerebral biomarkers are relatively expensive and not widely available. As eye images harbor several ophthalmic biomarkers that mirror the state of the brain and can be clinically observed with routine imaging, eye-based machine learning models are an emerging area, with efficacy comparable with cerebral-based machine learning models. Emerging machine learning architectures like recurrent, convolutional, and partially pretrained neural networks have proven to be promising frontiers for feature extraction and classification with ocular biomarkers. Machine learning models that can accurately distinguish those with symptomatic Alzheimer's dementia from those with mild cognitive impairment and normal cognition as well as predict progressive disease using relatively inexpensive and accessible ocular imaging inputs are impactful tools for the diagnosis and risk stratification of Alzheimer's dementia continuum. If these machine learning models can be incorporated into clinical care, they may simplify diagnostic efforts. Recent advancements in ocular-based machine learning efforts are promising steps forward.

Median Arcuate Ligament Syndrome: A 10-year Review of Management at a Tertiary Medical Center

Median arcuate ligament syndrome (MALS) was described decades ago; however, its diagnostic criteria and treatment paradigms remain unclear. Ligament release and celiac ganglionectomy can relieve symptoms, however only certain patients benefit. We sought to characterize the factors leading to operative management and its influence on outcomes at our institution.

Efficacy and utilization of intravascular ultrasound in office-based lower extremity endovascular interventions for peripheral arterial disease.

Intravascular ultrasound (IVUS) is a uniquely objective but underutilized imaging modality in the interventional treatment of peripheral arterial disease treatment. IVUS has been shown to improve device size selection and diagnose occult pathology difficult to see with routine angiography. We hypothesize that the use of IVUS in lower extremity endovascular intervention improves accuracy in stent and balloon size selection and minimizes contrast use. This is a retrospective case series performed at a single-institution outpatient center by two vascular surgeons from July 2016 through July 2017. We identified 94 total IVUS-assisted procedures. We collected data regarding demographics, balloon and stent size, IVUS-determined vessel diameter, pre-procedure and post-procedure ABI values, and contrast used during the procedure. An independent core laboratory was further utilized to characterize all IVUS and angiographic size vessel measurements. For the 94 lower extremity IVUS-assisted interventions, the average patient age was 70±9 years old, with an average contrast use of 37.1mL of Omnipaque 300. There was substantial improvement in pre- and post-procedure ABI (0.7±0.23 to 0.94±0.21). On analysis of average intraluminal IVUS vessel diameter to balloon angioplasty used, we had a correlation in size of 0.96±0.16 in our series. Additionally, in eight instances IVUS allowed for identification of a flow-limiting dissection with subsequent stenting. Routine use of IVUS offers a powerful diagnostic paradigm that has the potential to significantly decrease contrast use and to improve objectivity in choosing appropriate vascular tools to maximize intra-procedural efficacy. The discovery of adverse findings not initially noticed on angiography further reinforces the value of IVUS utilization.

The Use of Modern Technologies in Post-COVID-19 Cardiopulmonary Rehabilitation

Managing cardiopulmonary rehabilitation in patients with COVID-19 remains a global challenge due to the facets of this virus. The technologies used in the rehabilitation of post-COVID-19 patients fail to keep pace with the global epidemiological developments. The purpose of this article is to review the medical technologies used in post-COVID-19 cardiopulmonary rehabilitation and the innovations that have allowed us to adapt and care for our patients. The pandemic highlighted the need for seismic changes in diagnostic and rehabilitation paradigms. We discuss advances in telemedicine and telemedicine-based rehabilitation, remote patient monitoring and emerging technologies used in cardiopulmonary rehabilitation. The rapid adoption of modern technologies in the practice of post-COVID-19 cardiopulmonary rehabilitation is promising and can improve patients’ access to complex rehabilitation programs with outstanding results.

Developmental Coordination Disorder and Most Prevalent Comorbidities: A Narrative Review.

This narrative review describes, in detail, the relationships between Developmental Coordination Disorder (DCD) and most prevalent associated comorbidities in their complexity, heterogeneity and multifactoriality. The research has been conducted on the main scientific databases, excluding single case papers. Blurred borders between the different nosographic entities have been described and advances in this field have been highlighted. In this multifaceted framework a specific profiling for co-occurring DCD, ADHD and ASD signs and symptoms is proposed, confirming the need for a multidisciplinary approach to define new diagnostic paradigms in early childhood.

Debate: Conduct disorder, like all psychiatric diagnoses, is not a diagnosis.

Like all psychiatric diagnoses, conduct disorder (CD) relies on entirely subjective foundations. Without empirical anchors, we are left with descriptors that cannot help us identify cases that share universalisable commonalities beyond those imposed on them by the subjectivity of the diagnoser. This article highlights how mistaking a descriptive category for a diagnosis has resulted in, including for CD, a failure to improve scientific knowledge or clinical outcomes. For progress to occur the dominance of a technical diagnostic paradigm in psychiatry must be over-turned and CD will then lie on the slag heap of history alongside the other consumable brands mis-labelled as a psychiatric diagnosis.

Inflammatory Microenvironment in Early Non-Small Cell Lung Cancer: Exploring the Predictive Value of Radiomics.

Simple SummaryDespite therapeutic advances in treatments and translational research, patient prognosis for non-small cell lung cancer (NSCLC) remains unsatisfactory. Although stage I NSCLC has a relatively favorable prognosis than more advanced stage disease, almost 40% of patients diagnosed with a localized NSCLC are predicted to have a poor prognosis after surgery. The reasons why patients diagnosed with the same NSCLC traits will experience good or bad outcomes are far from being known. Therefore, new diagnostic paradigms are needed to predict treatment response and inform clinical decision-making. The tumor microenvironment is widely orchestrated by inflammatory cells and is an essential participant in carcinogenesis, contributing to the patient’s prognosis. This retrospective study explored the value use of computed tomography (CT) images as a “virtual biopsy”, in assessing the biomarkers CD68 and IL-1β that we have identified on a biological scale to be related to NSCLC patients’ overall survival (OS).Patient prognosis is a critical consideration in the treatment decision-making process. Conventionally, patient outcome is related to tumor characteristics, the cancer spread, and the patients’ conditions. However, unexplained differences in survival time are often observed, even among patients with similar clinical and molecular tumor traits. This study investigated how inflammatory radiomic features can correlate with evidence-based biological analyses to provide translated value in assessing clinical outcomes in patients with NSCLC. We analyzed a group of 15 patients with stage I NSCLC who showed extremely different OS outcomes despite apparently harboring the same tumor characteristics. We thus analyzed the inflammatory levels in their tumor microenvironment (TME) either biologically or radiologically, focusing our attention on the NLRP3 cancer-dependent inflammasome pathway. We determined an NLRP3-dependent peritumoral inflammatory status correlated with the outcome of NSCLC patients, with markedly increased OS in those patients with a low rate of NLRP3 activation. We consistently extracted specific radiomic signatures that perfectly discriminated patients’ inflammatory levels and, therefore, their clinical outcomes. We developed and validated a radiomic model unleashing quantitative inflammatory features from CT images with an excellent performance to predict the evolution pattern of NSCLC tumors for a personalized and accelerated patient management in a non-invasive way.

ECG diagnosis of left ventricular hypertrophy: The need for changing the diagnostic paradigm

ECG diagnosis of left ventricular hypertrophy: The need for changing the diagnostic paradigm

Hematological, Biochemical Properties, and Clinical Correlates of Hemoglobin S Variant Disorder: A New Insight Into Sickle Cell Trait

BackgroundThe sickle cell trait (SCT) disorder possesses a clinical heterogeneity ranging from a symptomless condition to sudden death. This study aimed to develop a diagnostic approach that helps the characterization and identification of SCT from normal subjects and sickle cell disease (SCD) patients, and to assess its severity.MethodsSixty controls, 24 SCD patients and 31 SCT subjects were assessed clinically, radiologically and by laboratory investigations.ResultsOf the SCT subjects, 12.8% were symptomatic (3.2% anemic, 6.4% hemolytic crisis, and 3.2% painful crises). Anemia was normocytic in 66.6%, and normochromic and polychromatic in 33.4%. Significantly lower red blood cells (RBCs), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hematocrit (Hct), Shine and Lal index (SL), and hemoglobin A (Hb A), and higher mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), Ricerca index (RI), and Huber-Herklotz index (HH) were found in SCT subjects compared with the controls. Hb A and hemoglobin S (Hb S) were excellent in discriminating SCT from SCD (cut-off for SCT > 50% and < 40%) followed by Hct, MCHC, Hb, Green and King index (GK), and England and Fraser index (EF) (cut-off for SCT > 33%, > 32, > 11, < 71, and < 10, respectively). Radiologically normal findings were detected in 87% of SCT subjects; they had nearly normal liver and renal function tests (except one case each). A schematic diagnostic paradigm for SCT was proposed.ConclusionThis study allowed understanding of SCT in various aspects, i.e., clinical, hematological, biochemical and radiological. Thus, it could help prevention of the Hb S variant disorder and proper management of carriers. This might be applied in pre-marital screening, particularly in those with family history of Hb S disorder.

Newborn screening research sponsored by the NIH: From diagnostic paradigms to precision therapeutics.

Newborn screening (NBS) is a successful public health initiative that effectively identifies pre-symptomatic neonates so that treatment can be initiated before the onset of irreversible morbidity and mortality. Legislation passed in 2008 has supported a system of state screening programs, educational resources, and an evidence-based review process to add conditions to a recommended universal newborn screening panel (RUSP). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, has promoted NBS research to advance legislative goals by supporting research that will uncover fundamental mechanisms of disease, develop treatments for NBS disorders, and promote pilot studies to test implementation of new conditions. NICHD's partnerships with other federal agencies have contributed to activities that support nominations of new conditions to the RUSP. The NIH's Newborn Sequencing In Genomic Medicine and Public Health (NSIGHT) initiative funded research projects that considered how genomic sequencing could be integrated into NBS and its ethical ramifications. Recently, the workshop, "Gene Targeted Therapies: Early Diagnosis and Equitable Delivery," has explored the possibility of expanding NBS to include genetic diagnosis and precision, gene-based therapies. Although hurdles remain to realize such a vision, broad engagement of multiple stakeholders is essential to advance genomic medicine within NBS.

0863 A Unique case of sleep state misperception in an elderly patient

Abstract Introduction Insomnia is a widespread condition, especially in the elderly population. While the International Classification of Sleep Disorders (ICSD) third edition appropriately removed primary insomnia subtypes from the classification, our case illustrates the importance of these factors in considering a chronic insomnia disorder diagnosis. We present a case of severe subjective insomnia with no apparent objective findings, instead with evidence of excellent sleep efficiency on the contrary. Report of Cases: A 76-year-old male with a past medical history of anxiety and a recent diagnosis of early Parkinson's disease presented to the Sleep medicine clinic with two years of insomnia which started after his retirement. The patient felt difficulty with falling asleep every night. He underwent a sleep study and was found to have sleep-disordered breathing, which responded well to Bilevel positive airway pressure (BiPAP) therapy. However, insomnia symptoms persisted and were resistant to multiple medications, including Mirtazapine, Melatonin, and Suvorexant. He was referred for Cognitive Behavioral Therapy with minimal to no improvement in his symptoms. Conversely, a one-week Actigraphy recording on Bipap therapy surprisingly revealed an excellent sleep efficiency with near-continuous seven to eight hours of sleep every night. The etiology of chronic insomnia is poorly understood but is typically multifactorial, as described in the second edition of ICSD. In this case, paradoxical insomnia played a significant role in the patient's clinical presentation. Paradoxical insomnia is defined as thoughts or perceptions of time asleep as wakefulness, with objective measures documenting normative amounts of sleep. Previous work suggests that alterations in the sleep/arousal system may contribute to this apparent mismatch between conventional objective sleep measures and subjective reports. Conclusion This case demonstrates the challenge of effectively diagnosing and managing chronic insomnia. While the new classification guidelines from the ICSD appropriately remove insomnia subtypes from the diagnostic paradigm, familiarity with these previously described subtypes may aid clinical decisions. Crucial to this discussion is that previously described "secondary" or "subtypes" of primary insomnia may develop an independent clinical course that may require further attention. Support (If Any) ICSD 2nd,3rd editions.

Biocompatible magnetic hydroxyapatite Fe3O4-HAp nanocomposites for T1-magnetic resonance imaging guided photothermal therapy of breast cancer

Theranostic nanomedicine designs integrating diagnostic and therapeutic paradigms have been achieving considerable success at clinics. However, the toxicity of nanocomposites in these designs remains a major obstacle to the success of personalized medicine. Herein, highly biocompatible iron and hydroxyapatite materials were selected to design a Fe3O4-HAp nano-theranostic system with controlled dimensions using simple solvothermal synthesis. The biocompatibility of Fe3O4-HAp magnetic hydroxyapatite nanocomposites (MHNCs) was further enhanced by Food and Drug Administration- (FDA-) approved triblock copolymers, namely, Pluronic® F-127. Indeed, polymer modification improved the drug encapsulation capacity of HAp, and 70% anti-TROP 2 was loaded onto the surface of MHNCs for intracellular targeting of breast cancer. The Fe3O4 component of MHNCs possessed a high T1-MR imaging enhancement feature with an excellent r1 value, demonstrating these MHNCs as capable substitutes for Gd-based toxic contrast agents. Moreover, indocyanine green (ICG-) coupled-MHNCs revealed strong absorption in the near-infrared region and produced enough temperature (75 °C), even at low (50 ug/mL) concentrations, to ablate cancerous cells upon 808 laser irradiation to induce cell toxicity and apoptosis. The promising diagnostic and photothermal therapeutic performance of these designed MHNCs make them an ideal nano-theranostic agent.

0641 Automated Detection of Isolated REM Sleep Behavior Disorder (iRBD) During Single Night In-Lab Video-Polysomnography (PSG) Using Computer Vision

Abstract Introduction At least 1% of adults aged 45 and above have isolated REM sleep behavior disorder (iRBD), a prodromal stage of a synucleinopathy, however a majority remains undiagnosed until they develop irreversible neuropathology. The gold-standard diagnostic procedure, the in-lab video-polysomnography (PSG), relies on complex rules for sleep staging and electromyography quantification which potentially lead to incorrect diagnoses. We tested a computer vision classifier for RBD versus other sleep conditions based on automated video analysis of body movements during a single-night in-lab PSG. Methods Raw PSG video recordings of 60 iRBD patients (mean 67 years, 78% males) and 100 controls (mean 65, 65% males) were selected from the Stanford Sleep Center database. Our pipeline involved three main steps: movement detection, feature extraction, and RBD recognition. The recordings between lights off and lights on were 7 to X hours in duration with some interspersed short movements. For every recording, short video segments that contain movements were first extracted using background subtraction. Additional features, such as sleep-onset time and wake-up time, were used to filter out noisy segments that did not involve patients being asleep. Next, I3D, a state-of-the-art method for action recognition, was used to derive a feature vector of 2048 features from every extracted segment. RBD diagnosis could be considered as an action recognition task in which ‘RBD’ was the action category to be classified. For every recording, the feature vectors for every segments were averaged, resulting in one feature vector per subject. With 160 PSG video recordings, this resulted in a dataset of 160 feature vectors that were used to train a multi-layer perceptron (MLP) for RBD recognition. Results Leave-one-out cross-validation (LOOC) procedure was used for evaluation achieving 91.9% accuracy, with a 78.3% sensitivity and 100% precision. Conclusion We tested the feasibility and performance of a new diagnostic paradigm for RBD solely based on single-night video analysis of PSG. Our results suggest that a machine learning model can detect and distinguish the characteristics of movements related to RBD versus other sleep disorders and normal sleep. Larger studies in heterogeneous datasets are needed to validate these findings. Support (If Any) Google