Routine Clinical Evaluation Research Articles

Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-malignant disorder. The current standard of care is not to screen for MGUS, so it is often incidentally diagnosed in the clinic. It is unknown whether the outcomes of screened versus clinically detected MGUS differ. We compared the progression risk between screened versus clinical MGUS cohorts and assessed whether the MGUS detection method impacted risk prediction of established clinical factors (score). We included 379 screened MGUS from the Olmsted County population based study and 1384 MGUS patients diagnosed during routine clinical evaluation at Mayo Clinic. Median follow-up time for the screened versus clinical cohort was 26.6 and 40.1 years, respectively. Accounting for death as a competing risk, the cumulative incidence of progression at 25 years was similar in the screened (11.1% [95% CI 8.3-14.8]) versus clinical (10.1% [95% CI 8.6-11.8%]) MGUS cohorts, even when stratified by sex, age, or the baseline MGUS risk score. Overall, 0.9 (95% CI 0.6-1.2) screened versus 1.0 (95% CI 0.9-1.2) clinically detected MGUS patients experienced disease progression for every 100 person years of follow-up. MGUS detection method did not modify the association between MGUS risk score and progression risk (pinteraction=0.217) and did not add to known risk factors for progression (likelihood ratio test, p=0.839). Here we show that progression risk among patients with screened versus clinically detected heavy-chain MGUS was similar. Future studies are needed to assess if tailored follow-up of screened MGUS patients affects clinical outcomes.

Harnessing AI for Early Detection of Cardiovascular Diseases: Insights from Predictive Models Using Patient Data

Cardiovascular diseases (CVDs) continue to be the leading cause of death in the world, taking millions of lives every year. Early detection and treatment of these diseases are critical in preventing deaths and illnesses. Currently, traditional diagnostic methods like routine clinical examinations and other standard risk assessment tools fail to detect CVDs in early on set stages, posing numerous limitations for preventable interventions. This work explores incorporating artificial intelligence (AI) to catalyze early CVD diagnosis using AI models for patient data including electrocardiogram (ECG), wearable-generated metrics, and medical history. The research showcased the ability of AI to predict with high accuracy when CVD would start using machine learning methods such as Random Forest, Support Vector Machines (SVM) and Neural Networks. The powerful AI models were carefully constructed by training and testing them on an extensive dataset that contained measurements of diverse patient characteristics including many other readouts related to cardiovascular risk. Compared to traditional methods, the models outperformed, and Neural Networks had an accuracy of 92% in identifying high-risk patients. A hallmark of this work is that AI identifies subtle patterns and relationships within patient data ones that conventional approaches might not find. These AI-based predictive models might soon become part of the routine clinical evaluation for cardiovascular disease, providing a personalized and early health intervention to empower your cardiovascular care. Timely identification of these high-risk patients could allow for targeted interventions, leading to improved health and reductions in healthcare spending. Despite the promising potential that AI holds in healthcare, it also has brought up issues of data privacy, ethical use and the need for extensive clinical validation. This paper suggests a predictive strategy could be implemented using AI algorithms to lead early detection and management of CVD, which opens an opportunity for individualized care accompanied by big data era. Future studies should focus on improving such models with more diverse and larger datasets as well as overcoming logistical difficulties encountered in integrating AI into clinical workflows.

Multi-center improvement in screening for dystonia in young people with cerebral palsy.

Dystonia is a common, debilitating, and often treatment refractory motor symptom of cerebral palsy (CP), affecting 70-80% of this population based on research assessments. However, routine clinical evaluation for dystonia in CP has failed to match these expected numbers. Addressing this diagnostic gap is a medical imperative because the presence of dystonia rules in or out certain treatments for motor symptoms in CP. Therefore, our objective was to optimize rates of clinical dystonia screening to improve rates of clinical dystonia diagnosis. Using the quality improvement (QI) infrastructure of the Cerebral Palsy Research Network (CPRN), we developed and implemented interventions to increase the documentation percentage of five features of dystonia in young people with CP, aged 3-21 years old. This QI initiative was implemented by seven physiatry and pediatric movement disorders physicians at four tertiary-care pediatric hospitals between 10/10/21 and 7/1/23. We collected visit data cross-sectionally across all participating sites every 2 weeks and tracked our progress using control charts. We assessed 847 unique visits, mostly for established patients (719/847, 85%) who were 9.2 years old on average (95% CI 8.8-9.5). By 4/10/22, the mean percentage of dystonia screening elements documented across all sites rose from 39% to 90% and the mean percentage of visits explicitly documenting the presence or absence of dystonia rose from 65% to 94%. By 10/23/22, the percentage of visits diagnosing dystonia rose from 57% to 74%. These increases were all sustained through the end of the study period in 7/1/23. Using a rigorous QI-driven process across four member sites of a North American learning health network (CPRN), we demonstrated that we could increase screening for dystonia and that this was associated with increased clinical dystonia diagnosis, matching expected research-based rates. We propose that similar screening should take place across all sites caring for people with CP.

Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility.

Skeletal alterations and their complications can significantly impact the quality of life and overall prognosis of patients living with HIV (PLWHIV). Considering skeletal alterations are often asymptomatic and unapparent during routine clinical evaluation, these conditions are frequently overlooked in the clinical management of PLWHIV. However, since the use of combined antiretroviral therapy (cART) has increased life expectancy in PLWHIV effectively, osteopenia, osteoporosis, and bone fragility are now considered to have a major health impact, with a substantial increase in healthcare costs. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to bone changes in PLWHIV, focusing on the importance of taking a multi-scale approach in the assessment of bone hierarchical organization. Even though a low bone mineral density is frequently reported in PLWHIV, numerous ambiguities still remain to be solved. Recent data suggest that assessment of other bone properties (on various levels of the bone structure) could contribute to our understanding of bone fragility determinants in these individuals. Special attention is needed for women living with HIV/AIDS since a postmenopausal status was described as an important factor that contributes to skeletal alterations in this population. Further research on complex etiopathogenetic mechanisms underlying bone alterations in PLWHIV may lead to the development of new therapeutic approaches specifically designed to reduce the health burden associated with skeletal disorders in this population. A major challenge in the clinical management of PLWHIV lies in the adverse skeletal effects of some frequently prescribed cART regimens (e.g., regimens containing tenofovir disoproxil fumarate), which may require a switch to other pharmacological approaches for maintained HIV infection (e.g., regimens containing tenofovir alafenamide). Taken together, the findings are indicative that the HIV/AIDS status should be taken into consideration when designing new guidelines and strategies for individualized prevention, diagnosis, and treatment of increased bone fragility.

Real-World Evidence for Utility of Serum sFlt-1/PlGF Test for Routine Clinical Evaluation of Hospitalized Women with Hypertensive Disorders of Pregnancy

An imbalance of the anti-angiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1), and pro-angiogenic factor, placental growth factor (PlGF) in the circulation is a reliable predictor for development of preeclampsia with severe features and related adverse outcomes. In 2023, the United States (US) Food and Drug Administration approved a serum sFlt-1/PlGF test at a cut-off of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy (HDP) for the progression to preeclampsia with severe features between 23 and 35 weeks. The purpose of this study was to generate real-world evidence for clinical utility for serum sFlt-1/PlGF test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within two weeks of testing among hospitalized patients with HDP. Hospitalized patients with HDP between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to Jan 2024 following implementation of serum sFlt-1/PlGF testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (PlGF and sFlt-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines based on biomarkers but made pragmatic management decisions independently. Results of sFlt-1/PlGF tests were available to clinicians within 24 hours of venipuncture. The association between sFlt-1/PlGF ≥ 40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed. Of the 65 patient encounters, 36 had a sFlt-1/PlGF < 40 (55.4%). The rate of delivery for indications related to HDP within two weeks was significantly lower among encounters with a low ratio versus high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted HR 7.52, 95% CI: 3.05, 18.54; p < 0.001). A diagnosis of preeclampsia with severe features within two weeks of testing was also less likely among the encounters with sFlt-1/PlGF ratio < 40 when compared to sFlt-1/PlGF ratio ≥ 40 (2/36 [5.6%] versus 23/29 [79.3%], p<0.001; PPV 79% [95% CI: 0.65, 0.94] and NPV 0.94 [95% CI: 0.87, 1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within two weeks of testing were 6.13 and 0.09 respectively. Encounters with an sFlt-1/PlGF ratio <40 were less likely to experience a maternal or fetal adverse event as compared to encounters with sFlt-1/PlGF ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], p=0.01). Among 36 encounters involving low sFlt-1/PlGF values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed based on biomarkers and none developed preeclampsia with severe features or adverse outcomes at two weeks. The median latency defined as days between biomarker measurement and delivery in patients with low biomarker ratio was 33 (IQR 23, 47) versus 7 (IQR 4, 14) days among patients with a high ratio (p<0.001). Corticosteroid use within two weeks was also significantly reduced in the low biomarker group when compared to high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], p<0.001). In this study, incorporation of sFlt-1/PlGF ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with HDP in the US. Among patients with a low ratio, pregnancy may be prolonged which resulted in better neonatal outcomes without harm to the mother.

A prospective clinical study of the influence of oral protein intake on [18F]FET-PET uptake and test–retest repeatability in glioma

BackgroundO-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography ([18F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test–retest variation of [18F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [18F]FET-PET metrics and to assess the impact of protein-intake prior to [18F]FET PET scanning of gliomas.ResultsTest–retest variability in the non-protein group was good with absolute (and relative) upper and lower limits of agreement of + 0.15 and − 0.13 (+ 9.7% and − 9.0%) for mean tumour-to-background ratio (TBRmean), + 0.43 and − 0.28 (+ 19.6% and − 11.8%) for maximal tumour-to-background ratio (TBRmax), and + 2.14 cm3 and − 1.53 ml (+ 219.8% and − 57.3%) for biological tumour volume (BTV). Variation was lower for uptake ratios than for BTV. Protein intake was associated with a 27% increase in the total sum of plasma concentration of the l-type amino acid transporter 1 (LAT1) relevant amino acids and with decreased standardized uptake value (SUV) in both healthy appearing background brain tissue (mean SUV − 25%) and in tumour (maximal SUV − 14%). Oral intake of 24 g of protein 1 h prior to injection of tracer tended to increase variability, but the effects on derived tumour metrics TBRmean and TBRmax were only borderline significant, and changes generally within the variability observed in the group with no protein intake.ConclusionThe test–retest repeatability was found to be good, and better for TBRmax and TBRmean than BTV, with the methodological limitation that tumour growth may have influenced results. Oral intake of 24 g of protein one hour before a [18F]FET PET scan decreases uptake of [18F]FET in both tumour and in healthy appearing brain, with no clinically significant difference on the most commonly used tumour metrics.

Role of dynamic ctDNA monitoring in cervical and anal epidermoid carcinomas under curative chemoradiation.

3141 Background: Cervical and anal canal squamous cell carcinoma (SSC) are a significant health problem in underdevelopment countries. Definitive chemoradiation (CRT) is the standard-of-care (SOC) approach for curative treatment in locally advanced disease. Due to the common substantial local inflammation during CRT, the conventional clinical image cannot identify non-responders early. In this scenario, the evaluation of circulating tumor DNA (ctDNA) is a promising tool for real-time tumor response monitoring. Methods: We performed a prospective multicentric cohort study of patients treated between 2020 and 2023 in tertiary oncologic centers in Brazil to evaluate the role of ctDNA dynamic monitoring in epidermoid cervical (CC) and anal cancer (AC) T1-4, N0-1, M0 by AJCC 8th edition and candidates to complete curative CRT. The cDNA was assessed by Signatera test at D1, D29, immediately post-treatment, 8 weeks (w) post-CRT, 24w post-CRT, every 6 months (m) in the first 1-2 years(y), and yearly at 3-5y of follow-up (FUP). The primary endpoint was to estimate the correlation of ctDNA with a tumoral response assessed by conventional routine image and clinical evaluation at 8w. Secondary endpoints included a correlation between ctDNA results at different time points with progression-free survival (PFS) and overall survival (OS). The predictive potential of the biomarker was evaluated using receiving operating characteristic (ROC) curve analysis. Results: We included 33 patients, and 27 were evaluable with ctDNA, with a median FUP of 10m. The majority were female (n=23, 85.1%), and 3 (11%) were HIV-positive(+). Most patients presented with positive nodes and stage III disease (n=18, 66.6%). In the AC group (n=15), the majority received CRT with capecitabine and cisplatin (n=12, 55.5%); in the CC group (n=12), all pts received cisplatin. All pts tested expressed ctDNA+ before treatment. At 8w, images had a sensitivity of 42.8% and specificity of 100% for disease progression (area under the curve [AUC] 0.714), while ctDNA yielded a sensitivity of 85.7% and specificity of 89.4% (AUC 0.875). The ctDNA+ immediately after CRT ended (32%) was consistent with ctDNA+ at 8w (30.7%) and 24w (30%). Pts with ctDNA+ immediately post CRT have a higher risk of disease progression with PFS of 8.2m in ctDNA+ and not reached in ctDNA- group (HR:17.5; IC95%:1.9-157.3; p=0.01). Data are immature for OS analysis. Conclusions: CtDNA immediately post-CRT has a high predictive value in patients with anal and cervical tumors in early access CRT non-responders, who are at a high risk of disease progression. This biomarker should be considered for tailoring strategies of treatment escalation in this population.

An immersive virtual reality shopping task detects declines in instrumental activities of daily living in individuals with Parkinson's disease

IntroductionDeclines in instrumental activities of daily living (IADLs) have been proposed as a prodromal marker of Parkinson's disease (PD). The Cleveland Clinic Virtual Reality Shopping (CC-VRS) platform combines an omnidirectional treadmill with a virtual reality headset to create a virtual grocery store that a user physically walks through and completes a shopping task. The primary aim of this project was to determine the known-group validity of the CC-VRS platform in discriminating IADL performance and to characterize specific motor and cognitive declines responsible for PD-related IADL impairments. MethodsSixteen individuals with PD and 15 healthy adults completed traditional motor, cognitive, and IADL assessments and the CC-VRS task. Group differences were evaluated using Welch's t-test. ResultsThere were no between-group differences in traditional performance measures of motor, cognitive, or IADL function. Regarding CC-VRS performance, participants in the PD group completed the task significantly slower than controls (690 vs. 523 sec, respectively). Participants with PD spent 25 % more time walking and turning and were stopped 46 % longer than controls. Average gait speed when viewing the shopping list, a measure of dual-task performance, was significantly slower in the PD group compared to controls (0.26 vs. 0.17 m/s, respectively). ConclusionUnlike traditional performance measures of motor, cognitive, and IADL function, the CC-VRS discriminated participants with PD from healthy older adults. For the PD group, motor and dual-task declines contributed to diminished CC-VRS performance. Identifying underlying contributors to IADL declines supports using ecological assessments, such as the CC-VRS, for the routine clinical evaluation of IADLs.

Lower Extremity Muscle Tendon Interaction Around Knee During Gait Among Adolescent Children with Cerebral Palsy with Varying Crouch Angle.

Optimal management and surgical planning of severe bony deformities and muscle tendon unit contractures demands comprehensive evaluation of all structures including the dynamic muscle tendon length of all muscles around the joint during gait. Present study aimed to explore dynamic muscle-tendon length for all muscles around the knee joint along with pelvis, hip, and ankle joint kinematics among adolescent children with varying crouch angle. Muscle-tendon length of 29 adolescent children with cerebral palsy with varying crouch angles was computed using a full-body musculo-skeletal model and expressed as a percentage of muscle-tendon length during walking compared to resting condition. Children with knee flexion angle greater than 25° demonstrated lower anterior pelvic tilt and 11% greater muscle-tendon length of semimembranosus and biceps femoris during stance phase of gait compared to children with knee flexion angle less than 25° and typically developing children (p < 0.01). The findings of present study reported that routine bedside clinical evaluation in adolescent children with knee flexion angle greater than 25° revealed moderate shortening of hamstring muscle in supine position. Whereas instrumented objective evaluation of gait demonstrated lengthened hamstring muscle and reduced hip extension and relatively lower anterior pelvic tilt. Therefore, it may be valuable to add objective assessment of dynamic muscle-tendon length to kinematics of all lower-extremity joint motion during gait, in order to understand the muscle-joint interactions; particularly in children with severe crouch and plan specific, tailor-made surgical and non-surgical interventions.

Application of boosted trees to the prognosis prediction of COVID-19.

The precise prediction of COVID-19 prognosis remains a clinical challenge. In this regard, early identification of severe cases facilitates the triage and management of COVID-19 cases. The present paper aims to explore the prognosis of COVID-19 patients based on routine laboratory tests taken when patients are admitted. A data set including 1455 COVID-19 patients (727 male, 728 female) and their routine laboratory tests conducted upon hospital admission, age, Intensive Care Unit (ICU) admission, and outcome were gathered. The data set was randomly split into the train (75% of the data) and test data set (25% of the data). The explainable boosting machine (EBM) and extreme gradient boosting (XGBoost) were used for predicting the mortality and ICU admission of COVID-19 cases. Also, feature importance was extracted using EBM and XGBoost. The EBM and XGBoost achieved 86.38% and 88.56% accuracy in the test data set, respectively. In addition, EBM and XGBoost predicted the ICU admission with an accuracy of 89.37%, and 79.29% in the test data set for COVID-19 patients, respectively. Also, obtained models indicated that aspartate transaminase (AST), lymphocyte, blood urea nitrogen (BUN), and age are the most significant predictors of COVID-19 mortality. Furthermore, the lymphocyte count, AST, and BUN level were the most significant ICU admission predictors of COVID-19 patients. The current study indicated that both EBM and XGBoost could predict the ICU admission and mortality of COVID-19 cases based on routine hematological and clinical chemistry evaluation at the time of admission. Also, based on the results, AST, lymphocyte count, and BUN levels could be used as early predictors of COVID-19 prognosis.

Frequency of sarcopenia in Turkish women with systemic lupus erythematosus

ObjectiveThis study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity.MethodsA...

Abstract 1273: Tumor progression and tumor microenvironment of pancreas cancer ascites revealed by scRNA-seq and spatial transcriptomics

Abstract Peritoneal metastasis of pancreas cancer is one of the ultimate modes of spread in the cancer. Little is known about how cancer cells spread into abdominal cavity and what is different from hematogenous metastasis. It is also not well characterized how tumor microenvironment prevent cancer cells from spreading in abdominal cavity. We performed single-cell RNA-seq analysis and special transcriptomic analysis to clarify the progression and environment of the cancer. We collected and processed ascites samples of 20 PDAC samples from 19 patients. Sixteen ascites samples were obtained from abdominal paracentesis and two cases in the postmortem period. For one patient ascites was collected both pre and postmortem. All but one patient received chemotherapy prior to ascites collection. Routine clinical cytology evaluation of ascites samples from 17 patients indicated it was malignant in 11 patients and nonmalignant in six patients. All ascites samples were purified by gradient centrifuge using Ficoll-Paque Plus to remove erythrocytes and necrotic debris. For the platform, we adopted the 10x Genomics Chromium Single Cell Gene Expression platform for single-cell RNA-seq library preparation. Spatial transcriptomics was performed for eight FFPE samples from the two autopsy patients with paired cancer ascites using 10x Visium. The CytAssist was used to transfer transcripts of pre-sectioned and pre-stained tissues with 11 × 11 mm Visium Capture Area slides. The sample locations were metastatic tumors to bowel wall, rib bone, mesentery, iliac nerve, diaphragm, peritoneum, pelvis, and primary pancreas tumor. A total of 248,263 cells were analyzed in single-cell RNA-seq. Cell population in pancreas cancer ascites consisted of macrophages, lymphocytes, dendritic cells, plasma cells, plasmacytoid dendritic cells, mesothelial cells, and cancer cells. Cancer cells were detected in twelve samples whereas no cancer cells were detected in eight samples. Gene ontology and gene set enrichment analyses showed macrophages in ascites with cancer cells involved neutrophil activation while those in ascites without cancer cells retained antigen presentation capacity and inducing interferon gamma pathway. Mesothelial cells in ascites with cancer cells showed more apoptosis and lymphocyte proliferation while those in ascites without cancers cells triggered fibrosis and mitosis. These data suggest that macrophage and mesothelial cells could be categorized into anti-tumor cells and tumor associated cells. Ongoing investigations are exploring ligand-receptor relationships. We are going to compare the expression profile of tumor cells in ascites fluid and in tissue from various organs by integrating single cell RNA-seq data and special transcriptomics data. Citation Format: Shigeaki Umeda, Elias-Ramzey Karnoub, Fiyinfolu Balogun, Alejandro Jiménez-Sánchez, Christine A. Iacobuzio-Donahue. Tumor progression and tumor microenvironment of pancreas cancer ascites revealed by scRNA-seq and spatial transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1273.

P357 Automated assessment of histological disease activity in Ulcerative Colitis using a deep learning algorithm

Abstract Background Assessment of histological disease activity in patients with ulcerative colitis (UC) is becoming more important. Therefore, the DCA score was developed for use in clinical practice. Distribution (D), chronicity (C) and activity (A) are each scored on a three-point scale with distribution being dependent on the percentage of biopsy area affected by inflammatory changes. A major problem for implementation of any score is interobserver heterogeneity. To overcome this hurdle, we developed a deep learning algorithm to automatically compute the DCA score. Methods A retrospective cohort was created consisting of 117 adult patients with ulcerative colitis from which biopsies were taken during a colonoscopy performed in the setting of routine clinical evaluation (training set of 537 slides). From 75 cohort patients, an additional set of biopsies was available (test set of 299 slides). An expert gastrointestinal pathologist performed the DCA score. The model was trained on H&amp;E-stained whole slide images scanned at 40x (0.243-μm pixel) resolution. Training was performed in a weakly supervised multiple-instance learning setup, using slide-level labels without region of interest annotations. The features from the convolutional neural network-based model trained at 2.5x, 5x, and 10x magnification were incorporated using a random forest classifier for final prediction. Model accuracy was evaluated using the test set. Results The algorithm differentiates between normal and inflamed with an accuracy of 90.9% (Table 1). Model performance from features aggregated across all magnification levels (i.e., 2.5x, 5x, and 10x) was superior to features from individual levels. This can be explained with the help of GradCam heatmaps (Figure 1), where we show that features learned at different magnification levels correspond to different aspects of histological changes in UC. The multiple instance approach did not appear to detect crypt abscesses, which may have resulted in a relatively poor performance in differentiating A1 from A2. The model accuracy for the 9-class DCA was 64.8%. Conclusion The algorithm first appears to assess architectural distortions at lower magnification and then the presence of cellular elements like neutrophils at higher magnification. This closely mirrors the approach of pathologists. The present model automates the scoring process and by supporting the daily diagnostic practice highlights the potential of deep learning technologies in assessment of histological disease activity in UC.

Patients' perspective on the medical pathway from first symptoms to diagnosis in genetic lipodystrophy.

Underdiagnosis is an important issue in genetic lipodystrophies, which are rare diseases with metabolic, cardiovascular, gynecological, and psychological complications. We aimed to characterize the diagnostic pathway in these diseases from the patients' perspective. Cross-sectional study conducted through a self-reported patient questionnaire. Patients with genetic lipodystrophy were recruited throughout the French national reference network for rare diseases of insulin secretion and insulin sensitivity. Patients completed a self-reported questionnaire on disease symptoms, steps leading to the diagnosis, and healthcare professionals involved. Descriptive analyses were conducted. Out of 175 eligible patients, 109 patients (84% women) were included; 93 had partial familial lipodystrophy and 16 congenital generalized lipodystrophy. Metabolic comorbidities (diabetes 68%, hypertriglyceridemia 66%, hepatic steatosis 57%), cardiovascular (hypertension 54%), and gynecologic complications (irregular menstruation 60%) were frequently reported. Median age at diagnosis was 30 years (interquartile range [IQR] 23-47). The overall diagnostic process was perceived as "very difficult" for many patients. It extended over 12 years (IQR 5-25) with more than five different physicians consulted by 36% of respondents, before diagnosis, for lipodystrophy-related symptoms. The endocrinologist made the diagnosis for 77% of the patients. Changes in morphotype were reported as the first symptoms by the majority of respondents. Diagnostic pathway in patients with genetic lipodystrophy is rendered difficult by the multisystemic features of the disease and the lack of knowledge of non-specialized physicians. Training physicians to systematically include adipose tissue examination in routine clinical evaluation should improve diagnosis and management of lipodystrophy and lipodystrophy-associated comorbidities.

The role of preoperative ultrasound in the management of peripheral nerve injuries

BackgroundPeripheral nerve injury refers to any damage or trauma to the nerves located outside the central nervous system. Ultrasonography is a reliable, cheap, and minimally invasive method in clinical practice to give physicians useful information about nerve injury. Objectivesto assess the power of ultrasound in determining the presence, localization, and extent of neural damage in patients with clinical evidence of peripheral nerve lesions before surgery. MethodsThis cross-sectional study was conducted on 78 patients (56 females and 22 males, aged from 9 to 52 years) who had different pathologies including entrapment, tumoral, post-traumatic, and post-surgical nerve injuries at the Neurosurgery and Physical Medicine, Rheumatology, and Rehabilitation Departments, Tanta University Hospitals. All studied patients had preoperative evaluation; neurological examination, electrodiagnostic studies, and sonographic examinations with linear array transducers (frequencies ranging from 7.5 to 16 MHz). ResultsThe most common pathological condition was entrapment neuropathy (39 patients) (50%). Ultrasound complemented the electrodiagnostic studies by determining the site of entrapment manifested by increased mean maximum cross-sectional area of the nerve proximal to the site of entrapment and nerve hypoechogenicity. In post-traumatic and iatrogenic neuropathies (35 patients) (44.9%), the ultrasound finding revealed neuroma in continuity in nine cases (11.5%), complete neurotmesis with stump neuroma in eighteen patients (23.1%), and eight cases (10.3%) showed perineural adhesion. In all cases, the nerve was hypoechoic at the site of injury. The presence of hyperechoic fibrous tissue could indicate perineural adhesion and the necessity for neurolysis. This study also included three (3.8%) cases had schwannoma, and one case (1.3%) had neurofibroma. Ultrasound was used to confirm the diagnosis by determining the tumor's size and vascular supply. ConclusionsUltrasonography is a diagnostic and surgical planning tool that is becoming more and more useful for the management of peripheral nerve injuries. Its high resolution and real-time capability provide safe and cost-effective scans that aid in determining the extent of injuries. For patients with peripheral nerve injuries, ultrasound is advised to be added to the routine clinical and neurophysiological evaluation. It is also advised to use ultrasound as a first-line imaging modality for tumors thought to be of nerve origin.

Effect on Kidney Function Recovery Guiding Decongestion with VExUS in Patients with Cardiorenal Syndrome 1: A Randomized Control Trial

Plain Language SummaryDuring cardiorenal syndrome type 1 (CRS1), congestion is a major contributor to worsening renal function, but promoting decongestion with routine clinical evaluation is ineffective in some patients. The venous evaluation by ultrasound (VExUS) may optimize its management when evaluating for improvement in kidney function and other metrics related to decongestion. In this randomized clinical trial conducted in patients with CRS1, guiding decongestion with VExUS compared to the usual evaluation did not improve kidney function recovery, but decongestion was achieved more effectively.

The Role of Early Warning System in Predicting Severe Maternal MorbidityTaking Intensive Care Unit Admission as the Reference Standard

Objective: To determine the diagnostic accuracy of a modified early warning system (MEOWS) for predicting severe maternal morbidity, taking intensive care unit admission as the reference standard. Study Design: Cross-sectional study. Setting and Duration of Study: Combined Military Hospital, Abbottabad Pakistan, from Nov 2019 to Apr 2020. Methodology: After getting approval from the Institutional Ethical Committee, pregnant women fulfilling the inclusion criteria were included from the Labour Room of Department of Obstetrics &amp; Gynecology. A modified early obstetric warning system chart was used to assess all women, labelling them positive or negative as per the criteria. In case of a fatal outcome or development of severe morbidity warranting intensive care unit admission, the patient was labelled as positive. Women who developed severe morbidity were managed as per standard protocols. Results: The early warning chart showed sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy as 69.44%, 90.97%, 64.10%, 92.76% and 86.91%, respectively, for predicting severe obstetric morbidity considering intensive care unit admission as gold standard. Conclusion: Modified early obstetric warning system chart effectively predicts severe obstetric morbidity. It could lead to better patient care, thus preventing severe obstetric morbidity in our local population if implemented as part of routine clinical evaluation.

Uzak metastazlı kanser hastalarında iskelet kası kütlesinin prediktif ve prognostik değeri

Aim:Skeletal muscle loss is an indicator of cachexia and a strong prognostic factor for some types of cancer. After strict standardization, we aim to evaluate both the predictive and prognostic value of low muscle mass (LMM) in common cancer types for first-line chemotherapy. Methods: This retrospective single-center study was conducted in a regional hospital between 2015 and 2020. Patients diagnosed with distant metastatic cancer were screened and included in the study if they had abdominal computed tomography 45 days prior to first-line chemotherapy. The relationship between LMM and progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) was evaluated. Results: Initially, 289 patients with metastatic cancer were included. The median duration of follow-up was 17 months, with a mean age of 61.09±13.03 years (range 25 to 95), and 45.9% of patients were female. In total, 50.5% of patients had LMM, which was adjusted for gender. LMM was associated with worse OS and PFS in univariate analysis (HR:1.598;1.216-2.100; p=0.001 for OS and HR:1.583;1.216-2.059; p=0.001 for PFS), and this positive association was maintained after adjusted for diagnosis and age. Better ORRs were obtained in respiratory and gastrointestinal tract cancers, breast, prostate and gynecological cancer in non-LMM groups. Conclusion:LMM has not only prognostic value but also predictive value for many types of cancer. Therefore, the assessment of muscle loss should be incorporated as part of the initial routine clinical evaluation.

The MyJump App is a Valid Method of Assessing and Classifying Limb Symmetry During Recovery from Anterior Cruciate Ligament Reconstruction.

Jump testing performance and limb symmetry measures are important metrics for clinicians to monitor during rehabilitation after Anterior Cruciate Ligament (ACL) reconstruction, however they require hardware and software which is not commonly available in clinical practice. Video-based solutions may present a feasible alternative, but their veracity in classifying patients using limb-symmetry of 90% has not been established, nor have the clinimetric values for the performance measures been reported in this population. To describe the diagnostic accuracy (pass/fail using 90% LSI) and clinimetrics of an iPad-based app ("MyJump") compared to reference force plate analyses for limb symmetry, jump/hop height, contact time, flight time, and reactive strength index. Prospective cohort, diagnostic accuracy. Fifty-one consecutive patients recovering from ACL reconstruction undertaking routine independent clinical evaluation of their hop and jump performance were concurrently and independently examined using force plates and the MyJump app. Diagnostic accuracy of MyJump was compared to reference force plate analyses using a criterion of 90% limb symmetry. Diagnostic accuracy of the MyJump app was very good: positive predictive value for jump height was 0.83 and 1.0 for reactive strength index, and negative predictive value was 0.95 and 1.0 for the same metrics, respectively. Of the 131 classifications made using the MyJump app, there were five false positives and three false negatives - all of these were in classification of jump height with no misclassifications of RSI. Irrespective of jump type, the MyJump app displayed excellent reliability (ICC>0.95) for both height and reactive strength index. Minimum detectable changes were approximately 1cm for height, 0.1 for reactive strength index, 0.02s for contact time, and 0.3s for flight time. Where force plates are unavailable, the MyJump app is a valid and reliable substitute for criteria assessment of jump/hop height and reactive strength index in those recovering from ACL surgery using a 90% limb symmetry threshold. The minimum detectable changes vary by metric but are likely sufficiently accurate to detect clinical changes. Level 3.

Dosimetric Quality of Artificial Intelligence Based Organ at Risk Segmentation

to compare dosimetric parameters between Artificial intelligence (AI) generated organ at risks (OAR) and Radiation Oncologist approved OARs and evaluation of appropriateness unedited AI- OARs in routine clinical plan optimization and evaluation. The OARs (lung, spinal cord and heart) for twenty SBRT (stereotactic body radiotherapy) lung CT simulation datasets were derived by AI based segmentation algorithms. These AI- OARs were edited by a staff Radiation Oncologist and then subjected to our SBRT peer-review process at our institution. A SBRT plan based on the approved contours was created. Dosimetric parameters for the unedited AI-OARs and edited physician-approved OARs were then compared. Lung V20 differences between AI- OAR and physician- OAR varied from 0.01% - 0.7% with a mean value of 0.1% difference (p-value 0.004). Spinal cord D0.03cc varied from 0.02 Gy - 0.9 Gy with a mean value of 0.3 Gy difference (p-value 0.002). Heart D0.03cc varied from 0.01 Gy - 4.3 Gy with mean value 0.9 Gy difference (p-value 0.02). Dosimetric parameters for AI-based lung, spinal cord and heart OARs vs physician approved OARs were different, overall, the differences were generally small. These differences are likely on par with inter-observer differences seen between individual radiation oncologists. Unedited OARs have the promise for routine use in plan optimization and evaluation to further improve efficiency.