Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling.

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by declines in cognitive and functional severities. This research utilized the Clinical Dementia Rating (CDR) to assess the influence of tilavonemab on these deteriorations. METHODS: Longitudinal Item Response Theory (IRT) models were employed to analyze CDR domains in early-stage AD patients. Both unidimensional and multidimensional models were contrasted to elucidate the trajectories of cognitive and functional severities. RESULTS: We observed significant temporal increases in both cognitive and functional severities, with the cognitive severity deteriorating at a quicker rate. Tilavonemab did not demonstrate a statistically significant effect on the progression in either severity. Furthermore, a significant positive association was identified between the baselines and progression rates of both severities. DISCUSSION: While tilavonemab failed to mitigate impairment progression, our multidimensional IRT analysis illuminated the interconnected progression of cognitive and functional declines in AD, suggesting a comprehensive perspective on disease trajectories. Highlights: Utilized longitudinal Item Response Theory (IRT) models to analyze the Clinical Dementia Rating (CDR) domains in early-stage Alzheimer's disease (AD) patients, comparing unidimensional and multidimensional models.Observed significant temporal increases in both cognitive and functional severities, with cognitive severity deteriorating at a faster rate, while tilavonemab showed no statistically significant effect on either domain's progression.Found a significant positive association between the baseline severities and their progression rates, indicating interconnected progression patterns of cognitive and functional declines in AD.Introduced the application of multidimensional longitudinal IRT models to provide a comprehensive perspective on the trajectories of cognitive and functional severities in early AD, suggesting new avenues for future research including the inclusion of time-dependent random effects and data-driven IRT models.

Three-Dimensional Location of the Facial Artery in Relation to the Nasolabial Fold in Asian People: A Cadaveric CTA Study.

BACKGROUND: Injection cosmetics have become popular in recent years. The nasolabial fold is one of the most important and dangerous regions in the midface, and its three-dimensional relationship with the facial artery remains unclear. METHODS: Fifty-two cadavers infused with lead oxide contrast medium via the external carotid arteries were scanned by computed tomography (CT). The three-dimensional model was reconstructed using Mimics and Origin software, and the relevant data were calculated using validated algorithms. RESULTS: There were three facial artery types according to its course in relation to the nasolabial fold. In the most common type, accounting for 83.7% of specimens, the facial artery evolves into an angular artery, with a horizontal distance between facial artery and nasolabial fold of - 1.90 ± 2.40, - 3.90 ± 2.95, - 5.18 ± 3.42, - 5.59 ± 3.53, - 5.59 ± 3.83, - 6.07 ± 4.10, - 6.92 ± 3.70, - 6.79 ± 3.37, - 4.52 ± 3.20, and - 2.76 ± 3.60 (mm) from the nasal ala to the oral commissure and a vertical distance of - 4.03 ± 2.56, - 3.27 ± 2.27, - 2.81 ± 2.57, - 2.1 ± 2.64, - 1.5 ± 3.32, - 0.71 ± 3.99, 0.92 ± 4.43, 0.4 ± 5.31, - 4.14 ± 5.14, - 7.05 ± 4.74 (mm). CONCLUSIONS: The facial artery is vulnerable to damage when injecting filler in the nasolabial fold. For the upper 1/3 of the nasolabial fold, the supraperiosteal layer is recommended for injection, while for the lower 2/3 of the nasolabial fold, the dermal layer along the nasolabial fold is recommended. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC. METHODS: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan-Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135. FINDINGS: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48-1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41-0.66, p < 0.0001). The PALOMA-3 study analysed 520 patients with MBC. Within the 153 HER2-0 patients, the palbociclib-fulvestrant group showed a significantly longer PFS than the placebo-fulvestrant group (hazard ratio = 0.54, 95% CI 0.30-0.95, p = 0.034). Among the 367 HER2-low-positive patients, palbociclib-fulvestrant improved PFS (hazard ratio = 0.39, 95% CI 0.28-0.54, p < 0.0001). INTERPRETATION: The combination of a CDK4/6 inhibitor with ET significantly improved PFS in HER2-low-positive patients, while for HER2-0 patients, benefits were primarily observed in patients who had progressed on previous ET. Furthermore, HER2-0 patients may derive limited benefits from first-line CDK4/6 inhibitor treatment. Further work is needed to validate these findings and to delineate patient subsets that are most likely to benefit from the combination of CDK4/6 inhibitors and ET as first-line treatments. FUNDING: None.

Post-irradiation dysbiosis in patients with nasopharyngeal carcinoma having received radiotherapy - A pilot study.

OBJECTIVE: To compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis. STUDY DESIGN: Prospective cohort study. SETTING: Unicenter, Tertiary referral hospital. METHODS: Included patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy) RESULTS: Total of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT). CONCLUSIONS: This is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.

Evaluation of the Reproducibility of Auricular Subunit Markers Based on Three-Dimensional Computed Tomography.

BACKGROUND: As a facial feature, the auricle plays an important role in the integrity and aesthetics of the whole face. Auricular subunits are associated with patient satisfaction in auricular reconstruction, but there are few studies on auricular subunits. We want to evaluate the reproducibility of auricular subunits by measuring the coordinates of the marker points of auricular subunits, accordingly provide a reference for the improvement of auricular reconstruction and the aesthetics of auricular injection. METHODS: Mimics 19.0 was used to carry out three-dimensional (3D) reconstruction of the computed tomography (CT) scan data of patients' brains; measure the three-dimensional coordinates of the 13 auricular subunit markers, the morphological auricle length and width, and the physiological auricle length and width; and analyze the reproducibility as well as the differences between group. RESULTS: Reproducibility of auricle subunit markers: There are 1124 (58.82%) high reproducibility, 580 (30.35%) moderate reproducibility, and 207 (10.83%) low reproducibility. The superior tragus notch, tragus, and antitragus had the highest reproducibility. There was no significant difference between the groups in the marking points on the helix, and there were no statistically significant differences in the measurement values of the auricles on the two sides. The physiological ear length and width and the morphological ear length of males were larger than those of females. These showed significant differences between the age groups. CONCLUSION: Most auricular subunit markers have high reproducibility. The subunits with higher reproducibility are the structures that need to be optimized during auricle reconstruction surgery or auricle injection in the future. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multiple coherent amplitude modes and exciton-phonon coupling in quasi-one-dimensional excitonic insulator Ta2NiSe5.

An excitonic insulator (EI) is an intriguing correlated electronic phase of condensed excitons. Ta2NiSe5 is a model material for investigating condensed excitonic states. Herein, femtosecond pump-probe spectroscopy is used to study the coherent phonon dynamics and associated exciton-phonon coupling in single-crystal Ta2NiSe5. The reflectivity time series consists of exponential decay due to hot carriers and damped oscillations due to the Ag phonon vibration. Given the in-plane anisotropic thermal conductivity of Ta2NiSe5, coherent phonon oscillations are stronger with perpendicular polarization to its quasi-one-dimensional chains. The 1-, 2-, and 4-THz vibration modes show coherent amplitude responses in the EI phase of Ta2NiSe5 with increasing temperature, totally different from those of normal coherent phonons (the 3- and 3.7-THz modes). The amplitude modes at higher frequencies decouple with the EI order parameter at lower temperatures, as supported by theoretical analysis with a model Hamiltonian of the exciton-phonon coupling system. Our work provides valuable insights into the character of the EI order parameter and its coupling to multiple coherent amplitude modes.

Supplementing Best Care with Specialized Rehabilitation Treatment in Parkinson's Disease: A Retrospective Study by Different Expert Centers.

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson's disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson's Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson's Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions.

VLST: Virtual Lung Screening Trial for Lung Cancer Detection Using Virtual Imaging Trial.

Importance: The efficacy of lung cancer screening can be significantly impacted by the imaging modality used. This Virtual Lung Screening Trial (VLST) addresses the critical need for precision in lung cancer diagnostics and the potential for reducing unnecessary radiation exposure in clinical settings. Objectives: To establish a virtual imaging trial (VIT) platform that accurately simulates real-world lung screening trials (LSTs) to assess the diagnostic accuracy of CT and CXR modalities. Design Setting and Participants: Utilizing computational models and machine learning algorithms, we created a diverse virtual patient population. The cohort, designed to mirror real-world demographics, was assessed using virtual imaging techniques that reflect historical imaging technologies. Main Outcomes and Measures: The primary outcome was the difference in the Area Under the Curve (AUC) for CT and CXR modalities across lesion types and sizes. Results: The study analyzed 298 CT and 313 CXR simulated images from 313 virtual patients, with a lesion-level AUC of 0.81 (95% CI: 0.78-0.84) for CT and 0.55 (95% CI: 0.53-0.56) for CXR. At the patient level, CT demonstrated an AUC of 0.85 (95% CI: 0.80-0.89), compared to 0.53 (95% CI: 0.47-0.60) for CXR. Subgroup analyses indicated CT's superior performance in detecting homogeneous lesions (AUC of 0.97 for lesion-level) and heterogeneous lesions (AUC of 0.71 for lesion-level) as well as in identifying larger nodules (AUC of 0.98 for nodules > 8 mm). Conclusion and Relevance: The VIT platform validated the superior diagnostic accuracy of CT over CXR, especially for smaller nodules, underscoring its potential to replicate real clinical imaging trials. These findings advocate for the integration of virtual trials in the evaluation and improvement of imaging-based diagnostic tools.

Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

OsPRMT6a-mediated arginine methylation of OsJAZ1 regulates jasmonate signaling and spikelet development in rice.

Although both protein arginine methylation (PRMT) and jasmonate (JA) signaling are crucial for regulating plant development, the relationship between these processes in the control of spikelet development remains unclear. In this study, we used the CRISPR/Cas9 technology to generate two OsPRMT6a loss-of-function mutants that exhibit various abnormal spikelet structures. Interestingly, we found that OsPRMT6a can methylate arginine residues in JA signal repressors OsJAZ1 and OsJAZ7. We showed that arginine methylation of OsJAZ1 enhances the binding affinity of OsJAZ1 with the JA receptors OsCOI1a and OsCOI1b in the presence of JAs, thereby promoting the ubiquitination of OsJAZ1 by the SCFOsCOI1a/OsCOI1b complex and degradation via the 26S proteasome. This process ultimately releases OsMYC2, a core transcriptional regulator in the JA signaling pathway, to activate or repress JA-responsive genes, thereby maintaining normal plant (spikelet) development. However, in the osprmt6a-1 mutant, reduced arginine methylation of OsJAZ1 impaires the interaction between OsJAZ1 and OsCOI1a/OsCOI1b in the presence of JAs. As a result, OsJAZ1 proteins become more stable, repressing JA responses, thus causing the formation of abnormal spikelet structures. Moreover, we discovered that JA signaling reduces the OsPRMT6a mRNA level in an OsMYC2-dependent manner, thereby establishing a negative feedback loop to balance JA signaling. We further found that OsPRMT6a-mediated arginine methylation of OsJAZ1 likely serves as a switch to tune JA signaling to maintain normal spikelet development under harsh environmental conditions such as high temperatures. Collectively, our study establishes a direct molecular link between arginine methylation and JA signaling in rice.

The risk of free flap revision and subsequent medical costs in patients with hypopharyngeal cancer.

BACKGROUND: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. METHODS: A 20-year retrospective case-control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. RESULTS: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12-5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. CONCLUSIONS: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population.

Effective evaluations of community nursing on rehabilitation for stroke survivors: A meta-analysis.

BACKGROUND: Long-term rehabilitation of stroke survivors is often difficult and new tools to improve quality of life should be proposed. Community nursing can be a cost-effective tool to positively impact the lives of stroke survivors. This meta-analysis aimed to comprehensively evaluate the effects of community nursing on rehabilitation for stroke survivors. METHODS: The Cochrane Library, PubMed, Web of Science, CINAHL Plus, Embase, PEDro, China Knowledge Resource Integrated Database (CNKI), WANFANG, and WEIPU databases were comprehensively searched from their inception to April 18, 2023. The revised Cochrane risk-of-bias tool for RCTs(RoB 2 tool) was used to assess the quality of the included studies. Meta-analysis was conducted using the Stata 12.0 software package and Review Manager v5.3 software. RESULTS: A total of 25 randomized controlled trials with 2537 participants were included in the meta-analysis. Compared with the control group, community nursing combined with routine nursing had a significantly superior effect on the Barthel Index(BI), Fugl-Meyer(FMA), National Institutes of Health Stroke Scale(NIHSS), Self-rating Anxiety Scale(SAS), and Self-rating Depression Scale(SDS) scores for stroke survivors (BI: MD: 18.48, 95 % CI [16.87, 20.08], P < 0.00001; FMA: MD: 12.61, 95 % CI [10.44, 14.78], P < 0.00001; NIHSS: MD: -2.94, 95 % CI [-3.50, -2.37], P < 0.00001; SAS: MD: -8.19; 95 % CI: [-9.46, -6.92], P < 0.00001; SDS: MD: -6.46 95 % CI [-7.23, -5.70], P < 0.00001). Subgroup analysis demonstrated that routine nursing, health education, exercise rehabilitation nursing and psychological nursing combined with different community nursing measures were significant in rehabilitation for stroke survivors and there was no heterogeneous in the studies of each subgroup(P > 0.1, I2 < 50 %). CONCLUSION: This meta-analysis demonstrated that community nursing combined with routine nursing might improve activities of daily living, motor function and nerve function, and relieve anxiety and depression in stroke survivors. Overall, community nursing had a significant effect on rehabilitation of stroke survivors. However, this study still has limitations such as the overestimation effects caused by the sample size and the risk of bias caused by interventions. Future research will attempt to overcome these limitations and comprehensively assess the effect of community nursing on the rehabilitation of stroke survivors.

Unmasking the sky: high-resolution PM2.5 prediction in Texas using machine learning techniques.

BACKGROUND: Although PM2.5 (fine particulate matter with an aerodynamic diameter less than 2.5 µm) is an air pollutant of great concern in Texas, limited regulatory monitors pose a significant challenge for decision-making and environmental studies. OBJECTIVE: This study aimed to predict PM2.5 concentrations at a fine spatial scale on a daily basis by using novel machine learning approaches and incorporating satellite-derived Aerosol Optical Depth (AOD) and a variety of weather and land use variables. METHODS: We compiled a comprehensive dataset in Texas from 2013 to 2017, including ground-level PM2.5 concentrations from regulatory monitors; AOD values at 1-km resolution based on images retrieved from the MODIS satellite; and weather, land-use, population density, among others. We built predictive models for each year separately to estimate PM2.5 concentrations using two machine learning approaches called gradient boosted trees and random forest. We evaluated the model prediction performance using in-sample and out-of-sample validations. RESULTS: Our predictive models demonstrate excellent in-sample model performance, as indicated by high R2 values generated from the gradient boosting models (0.94-0.97) and random forest models (0.81-0.90). However, the out-of-sample R2 values fall within a range of 0.52-0.75 for gradient boosting models and 0.44-0.69 for random forest models. Model performance varies slightly across years. A generally decreasing trend in predicted PM2.5 concentrations over time is observed in Eastern Texas. IMPACT STATEMENT: We utilized machine learning approaches to predict PM2.5 levels in Texas. Both gradient boosting and random forest models perform well. Gradient boosting models perform slightly better than random forest models. Our models showed excellent in-sample prediction performance (R2 > 0.9).

Clinical Relevance of the Variability of the Infraorbital Arterial Anatomy Evaluated by Three-Dimensional Computed Tomography.

BACKGROUND: Knowledge of the anatomy of the infraorbital artery (IOA) is crucial for the rejuvenation of the anterior medial aspect of the midface; however, studies adequately describing the anatomy of the IOA branches are lacking, and their connection with the ophthalmic artery branches remains unclear. OBJECTIVES: This study aims to elucidate the anatomical characteristics of the IOA in its deployment within the lower eyelid using three-dimensional (3D) technology, thereby offering an anatomical foundation for clinical surgical procedures. METHODS: An analysis was conducted on computed tomography scans of 132 cadaveric head sides post-contrast injection, utilizing the Mimics software for reconstruction. The study focused on examining the anastomosis of the IOA, its principal branches, and the branches emanating from the ophthalmic artery. RESULTS: The prevalence of type I IOA was observed at 38.6% (51/132), while Type II IOA was found in 61.4% (81/132) of cases. A 7.6% incidence (10/132) of IOA directly anastomosing with the angular artery was noted. The presence of palpebral branches (PIOA) was identified in 57.6% (76/132) of instances. In the lower eyelid, four distinct distribution patterns of IOA were discerned: The likelihood of Type I PIOA was 5.3%, whereas for Types IIA, IIB, and IIC PIOA, the probabilities were 8.3%, 32.6%, and 11.4%, respectively. The occurrence of the orbital branch of IOA was recorded at 41.7% (55/132). CONCLUSIONS: 3D technology can map IOA variants and identify the deployment patterns of IOA branches in the lower eyelid vascular vesicles at high resolution as a guide in clinical practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Value of the Nutritional Indicators in Predicting Free Flap Failure From a Multicentre Database.

OBJECTIVE: Nutritional and inflammatory statuses have been associated with complications in microvascular-free flaps during head and neck surgeries. This study aimed to evaluate the potential of nutritional indicators in predicting postoperative free flap complications. STUDY DESIGN: We conducted a 20-year retrospective, case-control study within a defined cohort. SETTING: The study involved head and neck cancer patients from the Chang Gung Research Database who underwent simultaneous tumor ablation and free flap wound reconstruction between January 1, 2001, and December 31, 2019. METHODS: We employed logistic regression and stratified analysis to assess the risk of free flap complications and the subsequent need for flap revision or redo in relation to nutritional indicators and other clinical variables. RESULTS: Of the 8066 patients analyzed, 687 (8.5%) experienced free flap complications. Among these, 197 (2.4%) had free flap failures necessitating a redo of either a free flap or a pedicled flap. Beyond comorbidities such as chronic obstructive pulmonary disease, end-stage renal disease, and a history of prior radiotherapy, every 10-unit decrease in the preoperative prognostic nutritional index (PNI) was consistently associated with an increased risk of both free flap complications and failure. The covariate-adjusted odds ratios were 1.90 (95% confidence interval [CI]: 1.42-2.54) and 1.89 (95% CI: 1.13-3.17), respectively. CONCLUSION: A lower preoperative PNI suggests a higher likelihood of microvascular free flap complications in head and neck surgeries. Further randomized controlled trial designs are required to establish causality.

Ribonucleic Acid Sequencing Reveals the Upregulation and Resolution of Inflammation and Extracellular Matrix Remodeling in Lidocaine-Treated Human Acute Monocytic Leukemia Cell Line THP-1.

Lidocaine, a local anesthetic widely used in dentistry, is esteemed for its efficacy and safety. Recent research reveals its additional role in modulating the immune system, and particularly in reducing inflammation crucial for protecting tooth-supporting tissues. Notably, monocytes and macrophages, essential cellular components overseeing various physiological and pathological processes, stand as potential mediators of lidocaine's effects. Therefore, this study aimed to investigate how lidocaine influences cell behavior using RNA sequencing. To investigate the effect of lidocaine on THP-1 cells' behavior, we performed an MTT assay and RNA-Seq along with qPCR analyses to evaluate the transcriptomic and proteomic changes in THP-1 cells. Our results showed that a high dose of lidocaine (>1 mM) had a significant cytotoxic effect on THP-1 cells. However, a lidocaine dose lower than 0.5 mM induced a mixed anti-inflammatory profile by significantly upregulating tissue remodeling (GDF15, FGF7, HGF, COL4A3, COL8A2, LAMB2, LAMC2, PDGFRA, and VEGFA) and through the resolution of inflammation (Cpeb4, Socs1, Socs2, Socs3, Dusp1, Tnfaip3, and Gata3) gene cassettes. This study explores the effect of lidocaine on the THP-1 in the M2-like healing phenotype and provides potential applications of lidocaine's therapeutic effectiveness in dental tissue repair.

The Safety of Injections in the Infraorbital Region.

BACKGROUND:  Infraorbital filler injection is a commonly used minimally invasive cosmetic procedure on the face, which can cause vascular complications. OBJECTIVE:  In this study, we aimed to explore the anatomical structure of the infraorbital vasculature and to establish an accurate protocol for infraorbital filler injection. METHODS:  The vascular structure of the infraorbital region was evaluated in 84 hemifacial specimens using computed tomography. Four segments (P1-P4) and five sections (C1-C5) were considered. We recorded the number of identified arteries in each slice and at each location and the number of deep arteries. Furthermore, we also measured the infraorbital artery (IOA) distribution. RESULTS:  At P1-P4, the lowest number of arteries was detected in segment P4, with a 317/1727 (18.4%) and 65/338 (2.3%) probability of total and deep arterial identification, respectively. The probabilities of encountering an identified artery at the five designated locations (C1-C5) were 277/1727 (16%), 318/1727 (18.4%), 410/1727 (23.7%), 397/1727 (23%), and 325/1727 (18.8%), respectively. The probability of an IOA being identified at C2 was 68/84 (81%). CONCLUSION:  We described an effective filler injection technique in the infraorbital region to minimize the associated risks. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.