Standard Clinical Criteria Research Articles

HepatoPredict Accurately Selects Hepatocellular Carcinoma Patients for Liver Transplantation Regardless of Tumor Heterogeneity

Background/Objectives: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths rising worldwide. This is leading to an increased demand for liver transplantation (LT), the most effective treatment for HCC in its initial stages. However, current patient selection criteria are limited in predicting recurrence and raise ethical concerns about equitable access to care. This study aims to enhance patient selection by refining the HepatoPredict (HP) tool, a machine learning-based model that combines molecular and clinical data to forecast LT outcomes. Methods: The updated HP algorithm was trained on a two-center dataset and assessed against standard clinical criteria. Its prognostic performance was evaluated through accuracy metrics, with additional analyses considering tumor heterogeneity and potential sampling bias. Results: HP outperformed all clinical criteria, particularly regarding negative predictive value, addressing critical limitations in existing selection strategies. It also demonstrated improved differentiation of recurrence-free and overall survival outcomes. Importantly, the prognostic accuracy of HP remained largely unaffected by intra-nodule and intra-patient heterogeneity, indicating its robustness even when biopsies were taken from smaller or non-dominant nodules. Conclusions: These findings support the usage of HP as a valuable tool for optimizing LT candidate selection, promoting fair organ allocation and enhancing patient outcomes through integrated analysis of molecular and clinical data.

Similar patient-reported satisfaction and professional appraisal of implant-supported fixed dental prosthesis fabricated by different workflows.

A triple-armed, double-blind randomized controlled trial with cross-over design investigated patient-reported satisfaction and objective dental evaluation of a 3-unit, monolithic zirconium dioxide (ZrO2), implant-supported fixed dental prosthesis (iFDP) fabricated with 2 completely digital workflows and 1 mixed analog-digital workflow. Participants enrolled required rehabilitation of 2 dental implants in posterior region of either of the arches with a 3-unit, ZrO2 iFDP. A total of 20 participants received the 3 types of ZrO2, iFDP fabricated by 3 different methods. Thus, a total of 60 iFDPs were fabricated in the study. 20 iFDP were fabricated by complete digital workflow by using 3Shape Trios 3 Intraoral scanner (IOS) and 3 Shape designing software (Test-1). In second group (Test-2) 20 iFDPs were fabricated by using Dental Wings Virtuo Vivo IOS and Dental Wings original software (DWOS) for CAD designing. 20 iFDPs (control) were fabricated by mixed analogue-digital workflow by using Polyether impression and Exocad Lab software. The primary clinical outcome was blinded, subjective evaluation on visual analogue scale (VAS) by the participant, and an objective evaluation on VAS by a dentist at the time of prosthetic try-in of each of the 3 types of prosthesis. Secondary outcome was patients' perception about the impression procedures in the 3 different workflows on VAS. The study was conducted at 2 instances during the prosthetic rehabilitation. The primary outcomes were assessed at the time of prosthetic try-in. The secondary outcome was observed after the impression session. Clinical parameters were measured on VAS from 0 to 100 score. For the primary outcome, VAS score was recorded for each iFDP as observed for patient perception (satisfaction) and dentist evaluation (objective). The perception about impression was also recorded on VAS. Descriptive analysis of all scores was done by mean and standard deviation. ANOVA test was used for comparisons among the 3 different types of iFDP. Tukey's HSD was used for pairwise comparisons within ANOVA. Linear regression analyses was done to compare overall satisfaction of the patients and the dentist within each group. The level of significance was set at α = 0.05. After the start of recruitment in January 2020, there were no losses and exclusions. VAS for patient satisfaction was higher than VAS for dentist evaluation. Patient satisfaction among Test-1, Test-2, and Control showed no significant difference (P = 0.876). Dentist satisfaction among workflows were also not significantly different (P = 0.22). The relationship between VAS scores of patients and dentists was weak for Test-1 (R-value = -0.424, P = 0.062), Test-2 (R-value = 0.116, P = 0.068), and Control (R-value = -0.183, P = 0.441). Significant differences for patients' perceptions related to the treatment time for impression procedure (P = 0.005), convenience of impression procedure (P < 0.001), bad oral taste with the impression procedure (P < 0.001), and nausea with the impression procedure (P < 0.001) were observed. Subjective patient satisfaction was similar when comparing iFDPs fabricated with 3 different workflows. Objective dentist evaluation was also similar when comparing the 3 types of iFDPs. However, patient satisfaction of the workflow was higher than dentist evaluation, although there was no correlation between the two. Lower VAS in dentist's evaluation has been attributed to strict standardized clinical criteria and critical expert view. The study also reveals that patients have a favorable perception and preference in favor of digital impressions as compared to use of elastomeric impression materials.

Breast Cancer MRI Screening of Patients After Multiplex Gene Panel Testing

Enhanced breast cancer screening with magnetic resonance imaging (MRI) is recommended to women with elevated risk of breast cancer, yet uptake of screening remains unclear after genetic testing. To evaluate uptake of MRI after genetic results disclosure and counseling. This multicenter cohort study was conducted at the University of Southern California Norris Cancer Hospital, the Los Angeles General Medical Center, and the Stanford University Cancer Institute. Patients were recruited from July 1, 2014, through November 30, 2016. Following multiplex gene panel testing and genetic counseling, patients responded to surveys about breast MRI screening at 3, 6, 12, and 24 months and to a final survey between 3 and 4 years after counseling. Participants met standard clinical criteria for genetic testing or had a 2.5% or greater probability of inherited cancer susceptibility. Patients were categorized based on breast cancer risk from genetic testing results and Tyrer-Cuzick model-calculated risk as having (1) a BRCA or other high-risk pathogenic variant (PV), (2) a moderate-risk PV, (3) a higher lifetime breast cancer risk (≥20%), or (4) a lower lifetime breast cancer risk (<20%). Analysis was conducted from September 28 to November 9, 2023. Genetic testing with a 25- or 28-gene panel, and pretest and posttest genetic counseling by a genetic counselor or an advanced practice genetics nurse practitioner, which included cancer-specific screening recommendations. MRI screening adherence over time across risk groups was estimated using Cox proportional hazards regression modeling. Likelihood of screening adherence (odds ratios [ORs] with 95% CIs), controlling for potential confounders, was estimated using logistic regression. This study included 638 patients, with a mean (SD) age of 50.7 (13.3) years at testing. There were 43 patients (6.7%) with a BRCA or other high-risk PV, 16 (2.5%) with a moderate-risk PV, 146 (22.9%) with higher lifetime breast cancer risk, and 433 (67.9%) with lower lifetime breast cancer risk. A total of 52 patients (8.2%) identified as Asian, 21 (3.3%) as Black, 271 (42.5%) as Hispanic, and 255 (40.0) as White. Compared with patients with lower lifetime breast cancer risk, patients with a BRCA or other high-risk PV and those with a moderate-risk PV were approximately 10 times (OR, 9.81 [95% CI, 4.05-23.86]; P < .001) and 4 times (OR, 4.12 [95% CI, 1.10-14.35]; P = .03) as likely to undergo MRI, respectively. Patients with a BRCA or other high-risk PV were nearly 16 times (OR, 15.81 [95% CI, 5.17-48.31]) as likely to report consistent yearly MRI screening compared with patients with lower lifetime risk. In this study, women with inherited PVs conferring increased breast cancer risk had higher and more consistent MRI uptake than women with lower estimated risk. These findings emphasize the importance of genetic cancer risk assessment for effective enhanced breast cancer screening.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD. To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk. We analyzed data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Mean follow-up was 2.9 (SD, 0.8) years. Baseline assessment was from 11/2009 to 11/2016, and cognitive follow-up from 01/2013 to 07/2019. Associations of interest were also examined in the UK Biobank (UKB) for replication purposes (mean follow-up was 12.9 (SD, 2.4) years; baseline assessment was from 12/2006 to 10/2010). Population-based study. The HELIAD sample included 622 participants ≥65 years of age without baseline dementia or amnestic mild cognitive impairment (aMCI-the prodromal stage of AD). The UKB sample included 142,637 participants ≥60 years of age without prevalent dementia. Genetic predisposition to elevated circulating levels of IL-6 was estimated using a polygenic risk score (PRS), calculated based on the summary statistics of a current GWAS meta-analysis. AD and MCI diagnoses were based on standard clinical criteria [HELIAD], or hospital records and death registry data [UKB]. Associations with AD or aMCI incidence [HELIAD] and AD incidence [UKB] were examined with Cox regression models. In HELIAD, mean age was 73.4 (SD, 5.0) years; 363 (58%) women. An increase in IL-6 PRS by 1 standard deviation unit (SDU) was associated with up to a 43% increase in the risk for incident AD/aMCI (HRGWAS significance threshold of 0.01, 1.43 [95%CI, 1.14 - 1.80]). In UKBB, mean age was 64.2 (SD, 2.8) years; 73,707 (52%) women. A 1 SDU increase in IL-6 PRS was associated with up to an 8% increase in the risk for incident AD (HRGWAS significance threshold of 0.2, 1.08 [95%CI, 1.04 - 1.12]). Genetic predisposition to higher circulating levels of IL-6 was associated with an increased risk for AD, supporting the role of IL-6-related pathways in AD pathogenesis, and suggesting that genetic predisposition to proinflammatory states might trigger or accelerate AD-related neuropathology.

Prospective Trial of a Passive Diversion Device to Reduce Blood Culture Contamination.

Blood culture contaminants can lead to inappropriate antibiotic use, prolonged length of stay, and additional hospital costs. Several devices have been developed to reduce the risk of blood culture contamination by diverting a portion of the initial blood sample from the blood culture bottle. We assessed the effectiveness of 1 blood diversion device (BDD) in a prospective trial performed at the 2 separate emergency departments (EDs) of an academic medical center. A multiphase prospective crossover trial was performed with the BDD in use at 1 ED and standard equipment at the other ED for 10 weeks, and a second 10-week study phase was conducted with the use of the BDD and standard equipment in the EDs reversed. Contaminants were identified both by standard clinical microbiology lab criteria and by independent retrospective review by 3 infectious disease (ID) physicians. The primary analysis was performed based on intention-to-use data using the physician review of positive blood cultures. A total of 5637 blood samples were obtained, with 5625 samples analyzed after 12 blood culture results were deemed inconclusive by the ID physician review. The University ED had a higher blood culture contamination rate of 2.9% compared with the Memorial ED at 1.4%. In an intention-to-use analysis, the overall contamination rates were 2.0% and 2.9% in the BDD and standard equipment periods, respectively (P = .03), and in an actual-use analysis the contamination rates were 1.2% and 3.0% for the BDD and standard equipment, respectively (P < .001). The BDD was associated with significantly lower blood culture contamination rates at the institution's 2 EDs, with a stronger effect noted at the campus caring for higher acuity patients.

Evaluating the relationship between obstructive sleep apnea and all-cause and cause-specific mortality in adults with and without metabolic syndrome using real-world data.

Obstructive Sleep Apnea (OSA) is a prevalent sleep disorder linked to increased risks of cardiovascular and metabolic disorders, significantly raising overall mortality rates. This study explores the associations between OSA and mortality in adults with and without Metabolic Syndrome (MetS) using data from the National Health and Nutrition Examination Survey (NHANES). Data from NHANES (2005-2008) were analyzed, including 11,759 participants. OSA and MetS were identified based on survey responses and standard clinical criteria. Cox proportional hazards regression models were used to assess the relationship between OSA and mortality, adjusting for covariates. OSA was associated with significantly higher all-cause and cardiovascular mortality in the general population. In individuals without MetS, OSA was linked to higher all-cause and cardiovascular mortality. However, in individuals with MetS, OSA did not significantly affect mortality rates after adjusting for covariates. OSA increases the risk of all-cause and cardiovascular mortality in individuals without MetS, emphasizing the need for early identification and management, particularly in those without metabolic comorbidities. In contrast, the impact of OSA on mortality in individuals with MetS may be mitigated by medical monitoring and treatment. These findings highlight the importance of individualized clinical strategies and call for further research to explore the underlying mechanisms of OSA-MetS interactions.

Feature importance explanation of prosthetic valve endocarditis through machine learning via SHAP

Abstract Introduction Diagnosing prosthetic valve endocarditis poses a significant challenge in daily clinical practice. Accurately identifying these patients is vital due to its treatment implications. Clinical and imaging assessment of suspected cases yields a substantial number of interrelated variables, which can be analyzed through machine learning techniques in order to improve diagnostic accuracy. Feature ranking facilitates identification and interpretability of relevant clinical and imaging variables in this task. Purpose To utilize machine learning feature ranking and modeling in order to improve interpretable identification of patients with prosthetic valve endocarditis. Methods 89 cases defined by the endocarditis team and 173 controls were analyzed. We implemented the SHapley Additive exPlanations (SHAP) method to evaluate feature importance. 5-fold cross-validated Xgboost models were trained and independently tested with additive clinical, echocardiographic and 18F-FDG PET/CT data. Performance was evaluated through confusion matrices, F1-scores and AUCs. These were compared against conventional logistic regression of the Duke Criteria classification. Results Mean age was 59.6 ± 15.7, with 29.7% women. 14 clinical (demographic, laboratory and cultures), 2 echocardiographic, and 5 PET/CT features were included. The XGBoost model trained with all additive features demonstrated an AUC of 0.91±0.1 and outperformed simpler models as well as the Duke classification model (AUC=0.85). The clinical variables alone achieved an AUC of 0.85±0.11, while integration with echocardiography enhanced its performance to 0.90±0.04 (Fig. 1). Feature ranking demonstrated that antibiotic treatment duration, positive blood cultures, valve type, weight and CRP were the most relevant clinical variables, while the presence of vegetation or abscess, and abnormal uptake and uptake focality on PET/CT represented the most relevant imaging variables (Fig. 2). Conclusion Machine learning-based feature ranking and modeling may significantly enhance identification of patients with prosthetic valve endocarditis beyond standard clinical criteria. Feature selection offers interpretable performance in identifying these cases, model testing in clinical decision support may be warranted.Fig. 1:Comparative AUC Analysis.Fig. 2:SHAP feature importance.

The Efficacy, Safety, and Persistence of Therapy after Non-Medical Switching from an Originator Adalimumab in Inflammatory Bowel Disease: Real-Life Experience from Two Tertiary Centres.

During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. Materials and Methods: This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. Aims: The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. Results: No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. Conclusions: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD.

Assessment of the Effect of COPD on Intraocular Pressure in Ain Shams University Hospitals Patients

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is a group of diseases that cause airflow blockage and breathing-related problems. It includes emphysema and chronic bronchitis. COPD is a preventable and treatable disease. COPD is one of the main reasons of morbidity and mortality in all over the world, and its prevalence is generally associated with the prevalence of direct tobacco use. Aim of the Work To assess the effect of COPD on intraocular pressure in Ain Shams University Hospitals patients. Patients and Methods This is a controlled cross sectional study which recruited from clinical chest department at Ain Shams University Hospitals. The study was done on 50 diagnosed chronic obstructive pulmonary disease with age more than 40 years old included in the study diagnosed using standard clinical and diagnostic criteria to assess intra ocular pressure and 50 age and sex- matched healthy control subjects included in the study. Results Study results showed that there was a statistically significant Relation between severity of COPD and IOP measurement in right and left eye and also there was significant positive correlation between IOP in right and left eye with smoke pack and duration of smoking. Conclusion COPD as a disease had many effects on eye structures and cause increase in IOP which will lead to Glaucoma. The more the severity of COPD the more the increase in IOP.

Prevalence of Thyroid Dysfunction among Patients with Type II diabetes Mellitus in Tertiary Care Center: A Descriptive Cross-sectional Study

Introduction: Diabetes mellitus (DM) and thyroid dysfunction (TD) are two of the most prevalent endocrine disorders globally. Both conditions have significant effects on metabolism and are known to influence each other. Thyroid hormones play a crucial role in glucose homeostasis by affecting insulin secretion, sensitivity, and glucose metabolism.Conversely, altered glucose metabolism in diabetes can impact thyroid function, leading to a higher prevalence of thyroid disorders in diabetic patients. Understanding this relationship is important for improving the clinical management of patients with Type II DM. However, there is limited data on the prevalence of thyroid dysfunction in diabetic populations within specific regions. Methods: A cross-sectional descriptive study was conducted from February to September 2023 among 209 patients diagnosed with Type II DM at a tertiary care center after obtaining ethical approval from Institutional Review Committee(Reference No: 367 (6-11) E2). Thyroid function was assessed using thyroid-stimulating hormone (TSH), free T3 (FT3), and free T4 (FT4) levels. Thyroid dysfunction was classified into hypothyroidism and hyperthyroidism based on standard clinical and laboratory criteria. Data management involved entry into Microsoft Excel, verification for accuracy, and subsequent analysis using SPSS version 29.Results: The study included 209 patients (61% female, 39% male), with a mean age of 65.87 ± 13.7 years. The prevalence of thyroid disorders was 77(36.8%): 53(25.3%) hypothyroidism,24 (11.4%) hyperthyroidism among patient with type II diabetes mellitus.Conclusions: Our study shows a high prevalence of thyroid disorders, especially subclinical hypothyroidism, in individuals with type 2 diabetes. Poorly controlled blood glucose (HbA1c ≥ 7.5) significantly increases the risk, underscoring the need for routine thyroid screening in T2DM management

Magnetic resonance spectroscopy as a diagnostic model for assessment of liver steatosis in metabolic dysfunction-associated steatotic liver disease in non-diabetic patients

BackgroundMetabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt.ResultsThis study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades.ConclusionMRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials.

Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

Restauración volumétrica autóloga en pacientes con hemiatrofia adiposa facial

IntroductionFacial lipoatrophy lacks standard clinical criteria for its diagnosis and treatment; however, patients with hemifacial atrophy increase, affecting the mental health of patients who suffer from it. Lipografting has been rescued as an effective and safe treatment option. ObjectiveTo show the results of autologous volumetric restoration in patients with facial adipose hemiatrophy. MethodMulticenter, descriptive, longitudinal and prospective study carried out on 29 patients treated at the Hermanos Ameijeiras Hospital, Cuba and the EIMEC clinic, Spain in the period from July 2018 to July 2023. Both sexes were included, between 19 and 75 years old, with facial asymmetry due to unilateral decrease in subcutaneous cellular tissue. ResultsThe average age was 47.9 years. Women predominated with 79.3%. The most common etiologies were idiopathic, autoimmune and orbital trauma, each accounting for 17.2%. According to the degree of severity, grade II was the highest, with 65.5%, and grade III represented 34.5% of the total. Regarding the amount of grafted adipose tissue, 62.1% of the cases were 31 to 60ml, and 27.6% more than 60ml. According to the number of graft applications, 72.4% required one and 27.6% two applications. 93.1% had no complications and 6.9% reported 50% reabsorption of the graft. Patient satisfaction reached 100% and the results were classified as good in 86.21%; when there was improvement, without complications as well as patient satisfaction. ConclusionAutologous lipotransfer assisted with adipose tissue stem cells is a safe treatment option that offers good results in correcting asymmetry caused by hemifacial lipoatrophy.

Driving improvement of diagnosis and awareness of heavy menstrual bleeding in women among physicians.

A number of barriers in care exist for women/girls with bleeding disorders. Little progress has been made to overcome them, particularly regarding levels of awareness of healthcare professionals (HCPs) and women/girls. To evaluate awareness and perception of heavy menstrual bleeding (HMB) and bleeding disorders among HCPs and women/girls. A three-part qualitative study was conducted, including HCPs and women/girls from over seven countries. Part 1 included eleven 60-min interviews with experts discussing HMB diagnostic barriers, which were further assessed in surveys among 6099 women/girls, 353 general practitioners (GPs), and 426 obstetricians and gynaecologists (OB/GYNs) during Part 2. Part 3 included three 1.5-2-h workshops with 20 clinicians and patient representatives covering HMB knowledge, criteria defining HMB and HCP resourcing for diagnosis. Many HCPs do not conduct certain investigations for women/girls presenting with HMB, and 22% of GPs lack confidence in the management of HMB. Only 8% of GPs use screening tools to evaluate menstrual blood loss, and 13% of GPs and 15% of OB/GYNs assess underlying bleeding disorders. Seventy-six percent of menstruating women/girls believed they could recognise HMB symptoms 'well'. However, 23% of these women/girls would not seek medical advice for abnormal/prolonged menstruation disrupting their lives. Disruptions were reported in 34% of women/girls from the general population and 61% of women with at-risk symptoms of HMB. Many women/girls and HCPs have limited awareness of important HMB indicators. There is a need for standardized clinical criteria to promote efficient diagnoses and management.

OTHR-20. MINIMALLY-INVASIVE MOLECULAR DIAGNOSIS OF INFILTRATING BRAINSTEM GLIOMAS THROUGH CEREBROSPINAL FLUID CELL-FREE DNA SEQUENCING

Abstract BACKGROUND Accurate molecular diagnosis of infiltrating brainstem tumors, including diffuse midline gliomas and IDH mutant astrocytomas, is essential for prognostication and optimal therapy. Surgical biopsy of the brainstem carries risk of permanent neurological deficits and may yield insufficient or non-diagnostic tissue. We hypothesized that minimally invasive “liquid biopsy” analyzing circulating tumor cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) could represent an alternative molecular diagnostic modality. METHODS We performed MSK-IMPACT, a New York State Department of Health authorized hybridization capture-based next-generation panel DNA sequencing clinical assay on 44 CSF samples from 37 unique patients with brainstem tumors. Ages at time of CSF collection ranged from 1–47 years (median: 29 years). For samples in which diagnostic alterations could not be detected, we performed a series of secondary analyses for known hotspot mutations such as H3F3A, IDH1/2, and BRAF, including manual review for mutant reads below the official clinical reporting threshold, as well as droplet digital PCR (ddPCR). RESULTS Among 44 samples included in this study, 10/44 (23%) samples had mutations detected by MSK-IMPACT using standard clinical calling criteria and 14 of the remaining 34 samples (41%) had supporting evidence of a diagnostically relevant mutation based on manual review. Testing by ddPCR was performed on 11 samples (based on DNA availability), uncovering 4 additional mutations. Overall positive diagnostic yield was 64% (28/44). In biopsied patients, CSF confirmed disease-defining mutations in 80% (16/20) of CSF samples, including H3F3A K28M (9/10; 90%) and IDH1/2 (5/6; 83%). Among 24 unbiopsied patients, a disease-defining mutation was identified in 60% (15/25) of CSF samples. CONCLUSIONS Analysis of CSF cfDNA in patients with brainstem tumors has a high diagnostic yield and obviates the need for tissue biopsy in a majority of patients. A tiered testing approach using next-generation sequencing and ddPCR assays helps maximize diagnostic information and sensitivity.

Bacteria of healthy periodontal tissues as candidates of probiotics: a systematic review

ObjectivesThe use of probiotics could promote the balance of the subgingival microbiota to contribute to periodontal health. This study aimed to identify the potential of bacteria commonly associated with healthy periodontal tissues as probiotic candidates.Material and methodsA systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Scopus, Science Direct, ProQuest, and Ovid databases as well as the combination of Medical Subject Headings (MeSH) and non-MeSH terms. Based on the selection criteria, original studies published in English and identifying the microorganisms present in the periodontium of healthy individuals and patients with periodontitis using the high-throughput 16S ribosomal gene sequencing technique were included.ResultsOut of 659 articles, 12 met the criteria for this review. These articles were published from 2012 to 2020 and mainly originated from the United States, China, and Spain. Most of these studies reported adequate criteria for selecting participants, using standardized clinical criteria, and compliance with quality based on the tools used. In periodontal healthy tissue were identified species like Actinomyces viscosus, Actinomyces naeslundii, Haemophilus parainfluenzae, Rothia dentocariosa, Streptococcus sanguinis, Streptococcus mitis, Streptococcus oralis, Streptococcus gordonii, Streptococcus intermedius, and Prevotella nigrescens which have recognized strains with a capacity to inhibit periodontopathogens.ConclusionsS. sanguinis, S. oralis, S. mitis, and S. gordonii are among the bacterial species proposed as potential probiotics because some strains can inhibit periodontopathogens and have been reported as safe for humans.

Comparing clinical measures of near point of convergence and accommodation from the lateral canthus and browline in a paediatric and adolescent population.

Clinicians measure the near point of convergence (NPC) and the amplitude of accommodation (AA) from the spectacle plane, the bridge of the nose or the lateral canthus when assessing visual function. These values are compared to standard clinical criteria to diagnose vergence and accommodation deficits, despite varying reference points. This prospective study explored measuring relative to the spectacle plane and from the lateral canthus for NPC and monocular AA, and the resulting clinical implications of diagnosing visual deficits. Participants were seen by a single clinician for an eye examination. NPC was measured from the forehead and the lateral canthus of the right eye. Monocular AA was measured from the brow and the lateral canthus. Differences between measurements were analysed using non-parametric statistical tests including Wilcoxon Signed Rank, as well as linear regression and a linear mixed effects model to adjust for inter-eye correlation and repeated measures. Chi-square tests were used to assess differences in rates of abnormal findings. Data were collected from 70 participants (53% female, median age 13 [11-15] years). On average, measuring NPC from the lateral canthus yielded a value 1.8 cm higher than measuring from the forehead. Measuring AA from the lateral canthus resulted in an average difference of 1.5 cm compared to measuring from the brow. A total of 39% and 76% of subjects failed NPC compared to clinical norms when measured from the forehead or the lateral canthus, respectively, while 7% and 40% failed AA when measured from the brow or the lateral canthus, respectively. With the variable anatomy of the eye, it is imperative to account for the measurement point when assessing visual function. Measuring from the lateral canthus greatly increased the failure rates for NPC and AA compared with measuring from the forehead and brow, respectively.

An Automated Vertebrae Localization, Segmentation, and Osteoporotic Compression Fracture Detection Pipeline for Computed Tomographic Imaging.

Osteoporosis is the most common chronic metabolic bone disease worldwide. Vertebral compression fracture (VCF) is the most common type of osteoporotic fracture. Approximately 700,000 osteoporotic VCFs are diagnosed annually in the USA alone, resulting in an annual economic burden of ~$13.8B. With an aging population, the rate of osteoporotic VCFs and their associated burdens are expected to rise. Those burdens include pain, functional impairment, and increased medical expenditure. Therefore, it is of utmost importance to develop an analytical tool to aid in the identification of VCFs. Computed Tomography (CT) imaging is commonly used to detect occult injuries. Unlike the existing VCF detection approaches based on CT, the standard clinical criteria for determining VCF relies on the shape of vertebrae, such as loss of vertebral body height. We developed a novel automated vertebrae localization, segmentation, and osteoporotic VCF detection pipeline for CT scans using state-of-the-art deep learning models to bridge this gap. To do so, we employed a publicly available dataset of spine CT scans with 325 scans annotated for segmentation, 126 of which also graded for VCF (81 with VCFs and 45 without VCFs). Our approach attained 96% sensitivity and 81% specificity in detecting VCF at the vertebral-level, and 100% accuracy at the subject-level, outperforming deep learning counterparts tested for VCF detection without segmentation. Crucially, we showed that adding predicted vertebrae segments as inputs significantly improved VCF detection at both vertebral and subject levels by up to 14% Sensitivity and 20% Specificity (p-value = 0.028).

Validating Risk Prediction Models for Multiple Primaries and Competing Cancer Outcomes in Families With Li-Fraumeni Syndrome Using Clinically Ascertained Data.

There exists a barrier between developing and disseminating risk prediction models in clinical settings. We hypothesize that this barrier may be lifted by demonstrating the utility of these models using incomplete data that are collected in real clinical sessions, as compared with the commonly used research cohorts that are meticulously collected. Genetic counselors (GCs) collect family history when patients (ie, probands) come to MD Anderson Cancer Center for risk assessment of Li-Fraumeni syndrome, a genetic disorder characterized by deleterious germline mutations in the TP53 gene. Our clinical counseling-based (CCB) cohort consists of 3,297 individuals across 124 families (522 cases of single primary cancer and 125 cases of multiple primary cancers). We applied our software suite LFSPRO to make risk predictions and assessed performance in discrimination using AUC and in calibration using observed/expected (O/E) ratio. For prediction of deleterious TP53 mutations, we achieved an AUC of 0.78 (95% CI, 0.71 to 0.85) and an O/E ratio of 1.66 (95% CI, 1.53 to 1.80). Using the LFSPRO.MPC model to predict the onset of the second cancer, we obtained an AUC of 0.70 (95% CI, 0.58 to 0.82). Using the LFSPRO.CS model to predict the onset of different cancer types as the first primary, we achieved AUCs between 0.70 and 0.83 for sarcoma, breast cancer, or other cancers combined. We describe a study that fills in the critical gap in knowledge for the utility of risk prediction models. Using a CCB cohort, our previously validated models have demonstrated good performance and outperformed the standard clinical criteria. Our study suggests that better risk counseling may be achieved by GCs using these already-developed mathematical models.

Encephalocraniocutaneous Lipomatosis: A Case Report.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome and subclassification of oculoectodermal syndrome. Encephalocraniocutaneous lipomatosis may be associated with postzygotic mutations. However, absence of an identifiable mutation does not preclude a diagnosis of ECCL. Encephalocraniocutaneous lipomatosis commonly causes skin, eye, and central nervous system anomalies. Diagnosis can be made through genetic sequencing or standardized clinical criteria. One clinically apparent major criterion for the diagnosis of ECCL is nevus psiloliparus (NP), a fatty nevus with overlying nonscarring alopecia. In this case, a 50-day-old female infant with uncomplicated birth history presented to dermatology clinic for evaluation of 2 superficial cranial masses that had been present since birth without regression or evolution. One of the masses was located within the hairline and demonstrated overlying nonscarring alopecia, suspicious of NP. Because of concern for ECCL, brain magnetic resonance imaging was ordered and revealed 2 intracranial lipomas. Genetic testing was inconclusive. Excision of the masses was performed at the request of the parents for cosmetic purposes. Histologic evaluation of the surgical specimens confirmed the diagnosis of NP and ECCL. A suspected NP should raise concern for ECCL and prompt further evaluation for systemic involvement. In particular, patients with suspected ECCL should be screened for ocular and CNS involvement. Early identification and diagnosis are important for prognostication because patients with ECCL are at increased risk of developing neoplasms of the head and neck and may require more frequent screening examinations.