Clinical Reference Research Articles

Development and validation of nomograms based on the SEER database for the risk factors and prognosis of distant metastasis in gastric signet ring cell carcinoma.

Poor prognosis in patients with distant metastasis of gastric signet ring cell carcinoma (GSRC), and there are few studies on the development and validation of the diagnosis and prognosis of distant metastasis of GSRC. The Surveillance, Epidemiology, and End Results database was used to identify patients with GSRC from 2004 to 2019. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for distant metastasis of GSRC, while univariate and multivariate Cox proportional hazard regression analysis were used to determine independent prognostic factors for patients with distant metastasis of GSRC. Two nomograms were established, and model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. A total of 9703 cases with GSRC were enrolled, among which 2307 cases (23.78%) were diagnosed with distant metastasis at the time of diagnosis. Independent risk factors for distant metastasis included age, race, and T stage. Independent prognostic factors included T stage, chemotherapy, and surgery. The receiver operating characteristic curve, calibration curve, decision curve analysis curve, and Kaplan-Meier survival curve of the training set and validation set confirmed that the 2 nomograms could accurately predict the occurrence and prognosis of distant metastasis in GSRC. Two nomograms can serve as effective prediction tools for predicting distant metastasis in GSRC patients and the prognosis of patients with distant metastasis. They have a certain clinical reference value.

Clinical diagnostic reference levels and image quality metrics for CT in oncology patients

Background: In CT, the volumetric CT dose index (CTDIvol), dose-length product (DLP) and patient’s size-specific dose estimates (SSDE) are used as diagnostic reference level (DRL) metrics.Objectives: To develop clinical local DRL values for CT chest-abdomen-pelvis (CAP) examinations using the CTDIvol, DLP and SSDE, and to determine the image quality achieved.Method: In total, 201 cancer patients were included in the study. The scanning parameters, dose metrics from the CT unit and participants’ body mass index (BMI) were documented. The local CT DRL values for CAP examinations were defined as the median and 75th percentiles of the dose distribution.Results: The local DRL values given in terms of median CTDIvol ranged between 8.4 mGy and 12.7 mGy for the different types of cancers. The median DLPs ranged from 848 to 1173.4 mGy.cm for the various cancers. Generally, the radiation dose was directly proportional to the BMI and number of scan phases. Significant differences were observed between the DRLs for the various size-related parameters, number of scan phases and BMI classifications. The image quality was clinically satisfactory.Conclusion: No baseline data for clinical DRL values were available for this medical oncology department. The achieved DRLs were similar to published size-specific DRLs. The image quality was maintained during CT imaging. Dose optimisation and image quality assessment should be implemented to ensure optimal scanning parameters for different cancers in CT CAP examinations.Contribution: The first size-specific local DRL values for CT CAP investigations carried out on oncology patients in South Africa have been established.

Artificial intelligence-supported clear aligner orthodontic technology

With the advancement of digital healthcare and artificial intelligence (AI) technologies, the full automation of clear aligner orthodontic technology has become feasible. Significant research findings and commercial applications have emerged in areas such as intelligent diagnosis of multimodal orthodontic data, orthodontic treatment decision-making, automated generation of digital treatment plans, and remote intelligent monitoring. However, in the development and application of AI software, it is imperative to address issues related to clinical risks, target populations, and compliance with medical device software regulations. This article analyzes and summarizes the applications and challenges of AI in clear aligner orthodontic diagnosis, treatment, and production processes. Furthermore, it explores potential future trends in this field, providing valuable insights for clinical reference.

Clinical management model for impulse control disorders in Parkinson's disease.

Over the last decade, we have gained a better understanding of impulse control disorder in Parkinson's disease (PD-ICD), a medication complication in PD. Researchers were aware of its complexity and took efforts to learn more about its diagnostic and treatment possibilities. Nevertheless, clinical management for it is currently neglected. We conducted a narrative overview of literature published from 2012 to October 2023 on various aspects of clinical management for PD-ICD. A potential "susceptibility-catalytic-stress" model in the development of PD-ICD was proposed and a profile encoding predictors for PD-ICD was created. Based on these predictors, some methods for prediction were recently developed for better prediction, such as the polymorphic dopamine genetic risk score and the clinic-genetic ICD-risk score. A variety of treatment options, including dose reduction of dopamine receptor agonists (DAs), DAs removal, DAs switch, and add-on therapy, are investigated with inconsistent reports. Based on current findings, we developed a clinical management model prototype centered on prevention, consisting of prediction, prevention, follow-up and monitoring, therapy, and recurrence prevention, for clinical reference, and further proposed 4 key clinical management principles, including standardization, prediction centered, persistence, and whole course.

Genomic evaluation of the probiotic and pathogenic features of Enterococcus faecalis from human breast milk and comparison with the isolates from animal milk and clinical specimens.

Enterococcus faecalis is considered a probiotic, commensal lactic acid bacterium in human breast milk (HBM), but there are circulating antibiotic resistant and virulence determinants that could pose a risk in some strains. The study aimed to conduct genomic analysis of E. faecalis isolates recovered from HBM and animal milk and to evaluate their probiotic and pathogenic features through comparative genomics with isolates from clinical specimens (e.g., urine, wound, and blood). Genomic analysis of 61 isolates was performed, including E. faecalis isolates recovered from HBM in Saudi Arabia. Genome sequencing was conducted using the MiSeq system. The fewest antibiotic resistance genes (lsaA, tetM, ermB) were identified in isolates from HBM and animal milk compared to clinical isolates. Several known and unknown mutations in the gyrA and parC genes were observed in clinical isolates. However, 11 virulence genes were commonly found in more than 95% of isolates, and 13 virulence genes were consistently present in the HBM isolates. Phylogenetically, the HBM isolates from China clustered with the probiotic reference strain Symbioflor 1, but all isolates from HBM and animal milk clustered separately from the clinical reference strain V583. Subsystem functions 188 of 263 were common in all analyzed genome assemblies. Regardless of the source of isolation, genes associated with carbohydrate metabolism, fatty acid, and vitamin biosynthesis were commonly found in E. faecalis isolates. In conclusion, comparative genomic analysis can help distinguish the probiotic or pathogenic potential of E. faecalis based on genomic features.

Tofacitinib for ulcerative colitis: A promising treatment option

A single center retrospective clinical study revealed the efficacy and safety of tofacitinib in the treatment of ulcerative colitis (UC). This study has clinical reference value but also has some limitations. Previous studies, including this clinical trial, have shown that tofacitinib could be a promising treatment option for UC, but further clinical research is required to prove this point.

Pilot deployment of a machine-learning enhanced prediction of need for hemorrhage resuscitation after trauma – the ShockMatrix pilot study

ImportanceDecision-making in trauma patients remains challenging and often results in deviation from guidelines. Machine-Learning (ML) enhanced decision-support could improve hemorrhage resuscitation.AimTo develop a ML enhanced decision support tool to predict Need for Hemorrhage Resuscitation (NHR) (part I) and test the collection of the predictor variables in real time in a smartphone app (part II).Design, setting, and participantsDevelopment of a ML model from a registry to predict NHR relying exclusively on prehospital predictors. Several models and imputation techniques were tested. Assess the feasibility to collect the predictors of the model in a customized smartphone app during prealert and generate a prediction in four level-1 trauma centers to compare the predictions to the gestalt of the trauma leader.Main outcomes and measuresPart 1: Model output was NHR defined by 1) at least one RBC transfusion in resuscitation, 2) transfusion ≥ 4 RBC within 6 h, 3) any hemorrhage control procedure within 6 h or 4) death from hemorrhage within 24 h. The performance metric was the F4-score and compared to reference scores (RED FLAG, ABC). In part 2, the model and clinician prediction were compared with Likelihood Ratios (LR).ResultsFrom 36,325 eligible patients in the registry (Nov 2010—May 2022), 28,614 were included in the model development (Part 1). Median age was 36 [25–52], median ISS 13 [5–22], 3249/28614 (11%) corresponded to the definition of NHR. A XGBoost model with nine prehospital variables generated the best predictive performance for NHR according to the F4-score with a score of 0.76 [0.73–0.78]. Over a 3-month period (Aug—Oct 2022), 139 of 391 eligible patients were included in part II (38.5%), 22/139 with NHR. Clinician satisfaction was high, no workflow disruption observed and LRs comparable between the model and the clinicians.Conclusions and relevanceThe ShockMatrix pilot study developed a simple ML-enhanced NHR prediction tool demonstrating a comparable performance to clinical reference scores and clinicians. Collecting the predictor variables in real-time on prealert was feasible and caused no workflow disruption.

Low-Field MRI for Dental Imaging in Pediatric Patients With Supernumerary and Ectopic Teeth: A Comparative Study of 0.55 T and Ultra-Low-Dose CT.

This study sought to elucidate the diagnostic performance of 0.55 T magnetic resonance imaging (MRI) for pediatric dental imaging, specifically in terms of the image quality (IQ) for detecting ectopic and/or supernumerary teeth, compared with routine ultra-low-dose computed tomography (ULD-CT) of the jaw. A total of 16 pediatric patients (mean age: 12.4 ± 2.6 years, range: 9-17 years) with ectopic and/or supernumerary teeth screened from January 2023 to January 2024 were enrolled in this prospective, single-center study. All patients underwent ULD-CT as the clinical reference standard and 0.55 T MRI as the study scan on the same day. A 0.6-mm isotropic 3-dimensional T1w FLASH sequence was developed with a dedicated field of view of the upper and lower jaws. ULD-CT was performed using a new single-source computed tomography (CT) scanner equipped with a tin filter (Sn100, slice thickness: 1 mm, quality reference mAs: 24). The IQ for the tooth axis, the tooth length, the tooth root, root resorptions, cysts, the periodontal ligament space, and the mandibular canal was evaluated twice by 3 senior readers using a 5-point Likert scale (LS) (LS score of 1: insufficient, 3: reduced IQ but sufficient for clinical use, and 5: perfect) and compared between both methods. Subsequently, the results were dichotomized into nonvalid (LS score of ≤2) and valid (LS score of ≥3) for clinical use. A total of 49 ectopic and/or supernumerary teeth in 16 pediatric patients were investigated using ULD-CT (CTDI: 0.43 ± 0.09 mGy) and 0.55 T MRI. The mean MRI acquisition time was 9:45 minutes. Motion artifacts were nonsignificantly different between 0.55 T MRI and ULD-CT (P = 0.126). The IQ for the tooth axis, the tooth root, root resorptions, and cysts was similar between the methods. The IQ for the periodontal ligament space and tooth length favored ULD-CT by 14% (confidence interval [CI]: 4.3%-24%) and 7.5% (CI: 1.8%-13%), respectively, whereas that for the mandibular canal favored 0.55 T MRI by -35% (CI: -54%-16%). Sufficient IQ was found especially for cystic lesions (CT: 100% sufficient, MRI: 95% sufficient), the tooth root (CT: 100%, MRI: 98%), root resorptions (CT: 94%; MRI: 85%), the tooth axis (CT: 100%; MRI: 98%), and the tooth length (CT: 99%; MRI: 91%). The findings indicate that 0.55 T MRI is a feasible, radiation-free technique for delineating ectopic and/or supernumerary teeth in pediatric patients. Nevertheless, to date, 0.55 T MRI has not yet been able to provide an optimal IQ for all anatomical tooth and jaw structures. In cases of advanced clinical indications that require optimal spatial resolution, high-resolution CT or cone-beam CT may still be necessary.

Efficacy of vital pulp therapy for carious pulp injury in permanent teeth: a study protocol for an open-label randomized controlled noninferiority trial.

Vital pulp therapy (VPT) has recently been reported as an effective approach for preventing and treating carious pulp injury in permanent teeth. Compared with root canal treatment (RCT), which involves complete removal of the pulp tissue, VPT effectively maintains pulp vitality and retains the physiological functions of the pulp. In the research pool, large-scale randomized controlled trials evaluating the treatment outcome of VPT using calcium silicate cements and RCT in cariously exposed permanent teeth are lacking. Here, we present a monocentric clinical protocol to compare the effects of VPT using iRoot BP Plus (Innovative Bioceramix, Vancouver, BC, Canada) as a pulp-capping material with RCT. The proposed trial is an open-label, single-centre, randomized, controlled, noninferiority trial. In total, 462 patients will be included in this trial according to the following criteria: adult patients (18-50years old), pulp exposure during the treatment of deep caries in mature permanent teeth, a diagnosis of reversible or partially irreversible pulpitis without apical translucency on X-ray, without periodontitis or systemic disease. Patients with signed informed consent forms will be enrolled and randomly divided into two groups (VPT and RCT) with a balanced treatment allocation (1:1). Clinical evaluations will be conducted at baseline and at 3, 6, 12, and 24months after treatment, with the potential for extension. The primary outcome measure will be the duration of success. The secondary outcomes will include the success rate at the 1-year follow-up and any adverse reactions. The Kaplan‒Meier method and log-rank test will be used to compare the duration of success of both treatments. For other outcomes, the χ2 test or Fisher's exact test will be used for categorical variables, and the t test or Mann‒Whitney U test will be used for continuous variables to assess the differences between groups. The results of this trial will provide a clinical reference for selecting treatments for carious pulp injuries in permanent teeth. ClinicalTrials.gov ChiCTR2100051369. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ). Registered on 21 September 2021.

Comparing the effects of Swiss-ball training and virtual reality training on balance, mobility, and cortical activation in individuals with chronic stroke: study protocol for a multi-center randomized controlled trial

BackgroundBalance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke.MethodsA prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30–80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up.DiscussionThis trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke.Trial registrationChinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024.

Establishment and verification of reference intervals for blood cell analysis in extremely high altitude.

This study aimed to establish the reference intervals for complete blood count (CBC) in healthy adults at very high altitudes. This study recruited 4,863 healthy adults (3,598 males and 1,265 females) who received routine health check-ups at Ali District People's Hospital from January 2019 to December 2021 through the LIS system. CBC was detected by the XT-4000i automatic cell analyzer and statistically analyzed by SPSS 23.0 software (between-groups comparison, diagnostic concordance comparison). In addition, 20 health check samples were collected in 2022 to validate the established reference intervals. The CBC count showed a non-normal distribution in each item separately. The white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH), monocyte (MONO), eosinophil (EO), basophil (BASO), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean hemoglobin content (MCH), and mean erythrocyte hemoglobin concentration (MCHC) levels of healthy adults were significantly different from the national clinical reference range (p < 0.05). There were significant differences between males and females in RBC, HGB, and HCT levels (p < 0.05). The new reference intervals were less consistent with the expert consensus CBC reference intervals (p < 0.05). Compared with the other reference intervals, the diagnostic value of the reference screening interval established was significantly higher in this study (p < 0.05). The reference range established is verified by 20 independent samples from 2022, and the results are acceptable. This study preliminarily established reference intervals for complete blood counts of healthy adults at high altitudes in the Ali region of Tibet to provide a reference point for understanding routine blood markers in permanent residents of high-altitude environments and illustrate the need for regular establishment of laboratory reference intervals on a regular basis.

Protocol of clinical population pharmacokinetics/pharmacodynamics analysis of alkaloids from the leaves of alstonia scholaris in acute bronchitis patients

Objective: To validate whether orally administered Alkaloid Capsules from the leaves of Alstonia scholaris (CALAS) can improve the clinical indices of acute bronchitis and to investigate the alterations in the relationship between its composition and pharmacodynamic (PD) markers, thereby providing a clinical reference for the administration of this medication. Methods: This is a prospectively planned, blinded, placebo-controlled, parallel-grouped clinical trial with aggregated population pharmacokinetics/PD (PPK/PPD) data. A total of 55 subjects will be randomly allocated into four arms; specifically, 10 of the 55 subjects will be selected randomly for the placebo arm, and will be orally administered placebo (Tid), and 45 subjects will be randomly assigned to CALAS treatment groups (20 mg, 40 mg, and 80 mg Tid, at 15 subjects per group). The medication, presence of cough and phlegm, as well as body temperature of every subject will be recorded daily during treatment. About 3–4 blood samples will be collected from each subject at the following points for PPK/PPD parameters analysis: at pre-dose (0 h) and post-dose at 15 min, 40 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 30 h, and 48 h after last dosing. All the subjects will be subjected to a laboratory examination and efficacy evaluation on day 8. Discussion: A new integrating strategy to explore the relationship among drug components, action pathways, and clinical efficacy will be established through this study. We aim to explore the mechanism of action of CALAS in the treatment of acute bronchitis on the premise of definite active ingredients and reliable clinical efficacy. It is difficult to enrol patients in classical PK research because it adopts an intensive sampling method, and it cannot quantify the variability of PK parameters (Intra-individual variation, inter-individual variation and weekly variation). Moreover, the extrapolation and prediction of dosage regimens in different species and populations cannot be achieved. Therefore, the PPK/PPD method, which takes advantage of sparse data (3–5 time points sampling per patient), is adopted to determine the measurable pathological and physiological factors that can influence dose concentration to guide reasonable dose adjustment towards achieving optimal clinical effects.

Outer Membrane Vesicles Formed by Clinical Proteus mirabilis Strains May Be Incorporated into the Outer Membrane of Other P. mirabilis Cells and Demonstrate Lytic Properties.

Outer membrane vesicles (OMVs) are extracellular structures, ranging in size from 10 to 300 nm, produced by Gram-negative bacteria. They can be incorporated into the outer membrane of a recipient's cells, which may enable the transfer of substances with lytic properties. Due to the scarce information regarding the OMVs produced by Proteus mirabilis, the aim of this study was to test the blebbing abilities of the clinical P. mirabilis O77 and O78 strains and to determine the blebs' interactions with bacterial cells, including their possible bactericidal activities. The production of OMVs was visualised by Transmission electron microscopy (TEM). The presence of OMVs in the obtained samples as well as the phenomenon of OMV fusion to recipient cells were confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA) and Western blotting assays. The bacteriolytic activity of the OMVs was examined against P. mirabilis clinical strains and reference Staphylococcus aureus and Escherichia coli strains. It was shown that each of the two tested P. mirabilis strains could produce OMVs which were able to fuse into the cells of the other strain. The lytic properties of the O78 OMVs against another P. mirabilis O78 strain were also demonstrated. This promising result may help in the future to better understand the mechanisms of the pathogenesis and to treat the infections caused by P. mirabilis.

Clinician-Ordered Peripheral Smear Review by a Pathologist Has Low Clinical Utility-A Reference Laboratory Perspective.

Clinician-ordered peripheral smear review by pathologist (CPSR) is commonly ordered and has been recommended for decades. However, the clinical utility of this labor-intensive test in the reference laboratory has not been examined. The objective of this study is to assess hematologic abnormalities identified in CPSR orders and to correlate them with complete blood count (CBC) and laboratory-derived smear review (LDSR) in the reference laboratory. Two hundred consecutive CPSRs with corresponding CBCs from April 2023 were run by Sysmex® XN-11 analyzers, and their peripheral smears were examined by a board-certified hematopathologist. Hematologic abnormalities of CPSRs were assessed, and the correlation between CPSR and CBC/LDSR was reviewed. Nearly one-third of CPSRs (29%) had normal peripheral smears and CBCs. The majority of CPSRs showed nonspecific quantitative abnormalities. When compared against CPSR results, LDSR criteria identified 100% of hematologic abnormalities appropriately. Samples that were not flagged for review by LDSR rules were also reviewed (n = 174) to rule out clinically meaningful false negatives. One minor discrepancy (0.6% of cases) of small platelet aggregates was observed in a patient with a reported platelet count of 139 K/uL that was missed by the LDSR process. In the reference laboratory setting, our findings demonstrate that LDSR adequately detects significant hematologic abnormalities and, therefore, CPSR should be discontinued.

The impact of preoperative fasting time on patients undergoing partial nephrectomy and analysis of risk factors for postoperative hemorrhage.

This study investigates the impact of preoperative fasting time on patients undergoing partial nephrectomy and analyzes the risk factors for postoperative hemorrhage to provide clinical reference for physicians treating patients undergoing partial nephrectomy. A retrospective analysis was conducted on 74 patients who underwent partial nephrectomy for renal tumors between January 2022 and March 2024. Baseline and perioperative data were collected. The effects of long-term and short-term preoperative fasting on patients undergoing partial nephrectomy were compared. Additionally, univariate and multivariate logistic regression analyses were performed to identify risk factors for hemorrhagic complications following partial nephrectomy. Among the patients in this study, 26 (35.14%) underwent short-term preoperative fasting, while 48 (64.86%) underwent long-term preoperative fasting. The hemoglobin difference in the short-term fasting group was 21.08 ± 12.44 ml, compared to 13.65 ± 11.69 ml in the long-term fasting group, showing a statistically significant difference (p = 0.020). Differences in serum calcium (p = 0.003), serum magnesium (p = 0.031), and serum phosphorus (p = 0.001) between the short-term and long-term fasting groups were also statistically significant. Univariate and multivariate regression analyses identified the type of surgery (p = 0.050) and preoperative fasting time (p < 0.001) as independent risk factors for postoperative hemorrhage following partial nephrectomy. Patients undergoing partial nephrectomy with short-term preoperative fasting experience a more significant decrease in hemoglobin compared to those with long-term fasting. The type of surgery and preoperative fasting time are independent risk factors for postoperative hemorrhage in patients undergoing partial nephrectomy.

Automated orofacial virtual patient creation: A proof of concept

ObjectivesTo (1) construct a virtual patient (VP) using facial scan, intraoral scan, and low-dose computed tomography scab based on an Artificial intelligence (AI)-approach, (2) quantitatively compare it with AI-refined and semi-automatic registration, and (3) qualitatively evaluate user satisfaction when using virtual patient as a communication tool in clinical practice. Materials and methodsA dataset of 20 facial scans, intraoral scans, and low-dose computed tomography scans was imported into the Virtual Patient Creator platform to create an automated virtual patient. The accuracy of the virtual patients created using different approaches was further analyzed in the Mimics software. The accuracy (% of corrections required), consistency, and time efficiency of the AI-driven virtual patient registration were then compared with the AI-refined and semi-automatic registration (clinical reference). User satisfaction was assessed through a survey of 35 dentists and 25 laypersons who rated the virtual patient's realism and usefulness for treatment planning and communication on a 5-point scale. ResultsThe accuracy for AI-driven, AI-refined, and semi-automatic registration virtual patient was 85 %, 85 %, and 100 % for the upper and middle thirds of the face, and 30 %, 30 %, and 35 % for the lower third. Registration consistency was 1, 1 and 0.99, and the average time was 26.5, 30.8, and 385 s, respectively (18-fold time reduction with AI). The inferior facial third exhibited the highest registration mismatch between facial scan and computed tomography. User satisfaction with the virtual patient was consistently high among both dentists and laypersons, with most responses indicating very high satisfaction regarding realism and usefulness as a communication tool. ConclusionThe AI-driven registration can provide clinically accurate, fast, and consistent virtual patient creation using facial scans, intraoral scans, and low-dose computed tomography scans, enabling interpersonal communication. Clinical significanceUsing AI for automated segmentation and registration of maxillofacial structures leads to clinically efficient and accurate VP creation, opening the doors for its widespread use in diagnosis, treatment planning, and interprofessional and professional-patient communication.

A-042 Assessment of Known and Newly Discovered IGF-1 Variants by a High-throughput Clinical Reference Laboratory

Abstract Background The top-down approach to quantitate intact insulin-like growth factor 1 (IGF-1) by liquid chromatography coupled to high-resolution, accurate-mass, mass spectrometry (LC-HRAM-MS) is a highly specific and robust technique. The method also provides a unique opportunity to study point mutations represented as amino acid sequence variants in IGF-1. While physical consequences of most variants remain unknown, those in or close to the binding region of the IGF-1 protein (positions 30-62) may be pathogenic, while those at the C-terminus are likely benign. In addition, information about the presence of IGF-1 variants is critical for accurate estimation of growth hormone levels. In the current study, our goal was to assess the presence of new and known variants by targeted screening of a clinical population. Methods LC-HRAM-MS was used for the detection of the wild type (WT) IGF-1 and its variants in specimens submitted for IGF-1 testing. In total, 2,013,503 specimens were screened. A novel variant detection and identification (NVDI) approach was employed that uses variant group m/z, isotopic peak index (IPi), and relative retention time (rRT) to characterize IGF-1 variants. Deidentified specimens were analyzed with tandem mass spectrometry (MS/MS) and DNA sequencing to confirm variants. Results In the specimens that were analyzed, 0.44% had IGF-1 variants and 98% of these had amino acid substitutions in the C-terminal region. We identified 8 variants represented in the Exome Aggregation Consortium (ExAC) database (A67T, A70T, P66A, A67S, S34N, A38V, R36Q, and T4M), 2 previously reported variants (V44M and A67V), and 11 new variants (Y31H, S33P, R50Q, R56K, T41I, A62T, S34G, N26K, V44L, G7A, and R36W). The underlined variants listed were discovered in the current study and are first reported here. In total, 16 variants had amino acid substitutions in or close to the binding region of the IGF-1 protein, and these were found in 0.4% of patients with variants in the clinical population. Conclusions In the study population, almost all patients with IGF-1 variants had point mutations affecting the C-terminal amino acid sequence. Although these variants are likely benign, they could affect patient care if IGF-1 levels were underestimated by being based purely on WT concentrations. Pathogenic or possibly pathogenic variants occurred in a small but important fraction of the study population. The discovery of novel variants further validates this platform as a discovery engine for IGF-1 variants. We expect more variants to be discovered with more patients and broader criteria. Information about the presence of IGF-1 variants is critical for proper estimation of growth hormone levels. Patients with variants should have their physician informed to properly assess the patient’s condition. This collaboration between clinical laboratories and attending physicians may result in the characterization and better understanding of the role and effect of IGF-1 variants on growth disorders.

Assessment of Lefamulin 20 µg Disk versus Broth Microdilution When Tested against Common Respiratory Pathogens

ObjectiveTo evaluate the performance of the disk diffusion test with lefamulin 20 µg compared with the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. Methods572 clinical stains, including 240 Staphylococcus aureus, 211 Streptococcus pneumoniae and 121 Haemophilus influenzae, isolated from 71 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2020. Broth microdilution method and disk diffusion methods were performed according to CLSI. Categorical agreement (CA), major error (ME), and very major error (VME) were calculated. ResultsLefamulin showed potent activity against S. aureus, S. pneumoniae, and H. influenzae. Using the broth microdilution method, lefamulin inhibited 97.1% of S. aureus isolates at 0.25 mg/L; seven isolates were not susceptible. For S. pneumoniae and H. influenzae, the percentage of susceptibility to lefamulin was 100% and no non-susceptible strains were found in this study. Compared with the reference broth microdilution method, the CA of the lefamulin 20 µg disk testing was 99.8% (571/572), with 14.3% (1/7) VME and no ME. In our study, VME was determined in S. aureus. For S. pneumoniae and H. influenzae, the VME was not determined due to the lack of lefamulin non-susceptible strains. ConclusionThe lefamulin 20 µg disk diffusion testing showed excellent CA and ME with the reference broth microdilution method for S. aureus, S. pneumoniae, and H. influenzae. The VME exceeding CLSI recommendations may be a bias due to fewer lefamulin non-susceptible isolates. Our results suggest that lefamulin non-susceptible isolates detected by disk diffusion should be confirmed by the reference BMD.

Strategies for prevention and treatment of vascular and nerve injuries in mandibular anterior implant surgery

Important anatomical structures such as mandibular incisive canal, tongue foramen, and mouth floor vessels may be damaged during implant surgery in the mandibular anterior region, which may lead to mouth floor hematoma, asphyxia, pain, paresthesia and other symptoms. In severe cases, this can be life-threatening. The insufficient alveolar bone space and the anatomical variation of blood vessels and nerves in the mandibular anterior region increase the risk of blood vessel and nerve injury during implant surgery. In case of vascular injury, airway control and hemostasis should be performed, and in case of nerve injury, implant removal and early medical treatment should be performed. To avoid vascular and nerve injury during implant surgery in the mandibular anterior region, it is necessary to be familiar with the anatomical structure, take cone-beam computed tomography, design properly before surgery, and use digital technology during surgery to achieve accurate implant placement. This article summarizes the anatomical structure of the mandibular anterior region, discusses the prevention strategies of vascular and nerve injuries in this region, and discusses the treatment methods after the occurrence of vascular and nerve injuries, to provide clinical reference.

Reference ranges and test-retest reliability of subject visual horizontal from different head-tilt angles in young healthy adults

Objective:To establish the normal values of subjective visual horizontal（SVH） under different head tilt angles, analyze the test-retest reliability, and provide a normal value reference for the refined diagnosis and functional assessment of SVH in clinical vestibular disorders. Methods:Thirty-one healthy young people were selected to wear visual reality glasses to test SVH data in five different head tilt angles: upright head position 0°, head tilted 45°to the left（L45°）, head tilted 45° to the right（R45°）, head tilted 90° to the left（L90°）, and head tilted 90° to the right（R90°）, and were re-tested 2 weeks later. Results:①The normal values of SVH at 0°, L45°, R45°, L90°, and R90°were 0.30±1.32, 5.94±5.54, -11.44±5.32, -0.87±8.63, -2.70±8.02, respectively. ②The 95% confidence intervals of SVH at 0°, L45°, R45°, L90°, and R90° were: （-2.34,2.94）,（-5.14,17.02）,（-22.08,-0.80）,（-18.13,16.39）,（-18.74，13.34）, respectively. The ratio of asymmetry in the absolute value of bilateral 45° deviation was 26.4% and the ratio of asymmetry in the absolute value of bilateral 90° deviation was 1.3%. ③The intra-class correlation coefficient（ICC） for 0°, L45°, R45°, L90° and R90° was 0.625, 0.641, 0.564, 0.769, 0.656, respectively. Conclusion:SVH has good test-retest reliability and high clinical test stability and stability. The data on normal values of SVH at different head tilt angles established in this study can provide clinical references for the refined diagnosis and functional assessment of vestibular system disorders.