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Chi-Han Lin,1,2,&ast; Yung-Chia Kuo,1– 3,&ast; Hsuan-Chih Kuo,1– 3,&ast; Ching-Ting Wang,4 Shi-Ming Lin,1,5 Alan Chao-Wei Lee,1,6 Ming-Chin Yu,1,6,7 Wei-Chen Lee,1,6 Cherry Chiao-Erh Chen,2,3 Jason Chia-Hsun Hsieh1– 3 1College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 2Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan; 3Division of Hematology-Oncology, Department of Internal Medicine, New Taipei City Municipal TuCheng Hospital, New Taipei City, 236, Taiwan; 4Registered Nurse, Case Manager of Nursing Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 6Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan; 7Department of Surgery, New Taipei City Municipal TuCheng Hospital, New Taipei City, 236, Taiwan&ast;These authors contributed equally to this workCorrespondence: Jason Chia-Hsun Hsieh, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, No. 5, Fu-Hsin Street, Gueishan District, Taoyuan City, 333, Taiwan, Tel +886-3-3281200 Ext 8825, Email wisdom5000@gmail.comBackground: Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear.Methods: In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns.Results: One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses.Conclusion: Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.Keywords: hepatitis, immune checkpoint inhibitor, advanced hepatocellular carcinoma, liver enzymes, overall survival

Yu-Chieh Ho,1,&ast; Chia-Ti Wang,1,&ast; Tzu-Chieh Weng,2 Chung-Han Ho,3,4 Kang-Ting Tsai,5,6 Chien-Chin Hsu,1,7 Hung-Jung Lin,1,7,8 Hsiu-Chin Chen,5,9 Chien-Cheng Huang1,7,10 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 4Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 5Department of Senior Welfare and Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 6Division of Geriatrics and Gerontology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 7School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; 8Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan; 10Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chien-Cheng Huang, Department of Emergency Medicine, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email jasonhuang0803@gmail.com Hsiu-Chin Chen, Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email 300006@mail.chimei.org.twPurpose: The home-based medical integrated program (HMIP) is a novel model for home healthcare (HHC) in Taiwan, initiated in 2016 to enhance care quality. However, the outcomes of this program on health outcomes and medical resource utilization in HHC patients remain unclear. Thus, we conducted this study to clarify it.Patients and Methods: The authors utilized the Taiwan National Health Insurance Research Database to identify HHC patients who received HMIP and those who did not between January 2015 and December 2017. A retrospective cohort study design was used. Convenience sampling was employed to select patients who met the inclusion criteria: being part of the HHC program and having complete data for analysis.Results: A total of 4982 HHC patients in the HMIP group and 10,447 patients in the non-HMIP group were identified for this study. The mean age in the HMIP group and non-HMIP group was 77.6 years and 76.1 years, respectively. Compared with the non-HMIP group, the HMIP group had lower total medical costs for HHC, fewer outpatient department visits and lower medical costs, lower medical costs for emergency department visits, fewer hospitalizations, and a lower mortality rate (34.6% vs 41.2%, p< 0.001).Conclusion: The HMIP is a promising model for improving care quality and reducing medical resource utilization in HHC patients. While this suggests that the non-HMIP model should be replaced, it’s important to note that both non-HMIP and HMIP models currently coexist. The HMIP may serve as an important reference for other nations seeking to improve care quality and reduce medical resource utilization in their own HHC systems.Keywords: home-based medical integrated plan, health outcomes, medical resource utilization, Taiwan

Kun-Ming Chan,1 Yin Lai,1 Hao-Chien Hung,1 Jin-Chiao Lee,1 Chih-Hsien Cheng,1 Yu-Chao Wang,1 Tsung-Han Wu,1 Chen-Fang Lee,1 Ting-Jung Wu,1 Hong-Shiue Chou,1 Ching-Ting Wang,2 Pei-Mei Chai,2 Hsin-Yi Lien,3 Wei-Chen Lee1 1Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Nursing, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Graduate School of Education, Ming Chuan University, Taoyuan, TaiwanCorrespondence: Kun-Ming Chan, Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, No. 5 Fu-Hsing Street, Gui-Shan District, Taoyuan City, 33305, Taiwan, Tel +886-3-3281200 Ext 3366, Fax +886-3-3285818, Email chankunming@cgmh.org.twBackground: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment.Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed.Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55– 3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20– 3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32– 0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21– 0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients.Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.Keywords: hepatocellular carcinoma, advanced-stage, tyrosine kinase inhibitor, lenvatinib, outcome

Sha-Sha He,1,* Cheng-Tao Wang,1,* Zhen-Wei Peng,1,* Yu-Feng Ren,1 Li-Xia Lu,2 Rui-Wan Chen,1 Shao-Bo Liang,2,3 Yan Wang,1 Yong Chen11Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510080, People’s Republic of China; 3Department of Radiation Oncology, The First People’s Hospital of Foshan, Foshan, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workObjective: To facilitate decision-making support for individual patients, development and external validation of a nomogram was undertaken to reveal prognostic factors and predict the value of concurrent chemoradiotherapy (CCRT) compared with radiotherapy (RT) for stage-II nasopharyngeal carcinoma (NPC) patients.Methods: Clinical data of 419 and 309 patients with American Joint Committee on Cancer (2017) stage-II NPC in two institutions in China were collected retrospectively. Overall survival (OS) and progression-free survival were compared using Kaplan–Meier estimates. Cox regression analysis was used to identify the prognostic factors for building the nomogram. Predictive accuracy and discriminative ability were measured using the Concordance Index.Results: Finally, there were 24 and 20 deaths in the development and validation group, respectively. Patients with stage T2N1, N1 stage, involvement of retropharyngeal and unilateral cervical lymph nodes, and who had RT alone had worse OS (P=0.019, 0.035, 0.003 and 0.010, respectively; log-rank test) than patients with stage T1N1 and T2N0, N0 stage, involvement of retropharyngeal or unilateral cervical lymph nodes, and CCRT, respectively. After multivariate analysis of the training set, age, neutrophil-to-lymphocyte ratio, therapy type, and pretreatment plasma concentration of Epstein–Barr virus DNA were independent prognostic factors of OS. A nomogram was established externally by involving all the factors stated above. The Concordance Index for the established nomogram to predict the OS of the training set was 0.793 (95% CI 0.689–0.897), and 0.803 (95% CI 0.696–0.910) in the validation set.Conclusion: These data suggest that the nomogram was validated externally, could predict long-term outcome accurately, and enable accurate stratification of risk groups for stage-II NPC. Our model facilitated individualized care of NPC patients.Keywords: chemotherapy, nasopharyngeal carcinoma, nomogram, prognosis, radiotherapy

Objective: This study aimed to investigate whether adding low-molecular-weight dextran to oral steroids in patients with idiopathic sudden sensorineural hearing loss resulted in better hearing outcomes than those in patients receiving oral corticosteroids alone.Study Design: Historical cohort study.Setting: Tertiary teaching hospital.Subjects and Methods: The authors reviewed the clinical records of 166 patients with idiopathic sudden sensorineural hearing loss. Therapeutic effectiveness was measured by the gain of pure-tone averages and 4 categories of hearing outcome (complete recovery, marked recovery, mild improvement, or no improvement). To manage potential confounding factors associated with treatment allocation, the authors matched the subjects from each group according to the propensity score (ie, the predicted probability that they would receive a specific treatment).Results: The authors identified 50 pairs of propensity score-matched subjects (n = 100) without significant difference of all clinical factors (P > .05). Subsequent analyses demonstrated that the average hearing gain in subjects receiving additional dextran to oral steroid was 31.7 ± 21.5 dB, which did not differ from 33.0 ± 21.8 dB in subjects receiving steroids alone (P = .76). Difference of hearing outcomes between the 2 groups was also nonsignificant (P = .92).Conclusion: Matching propensity scores successfully balanced the heterogeneity between the dextran and steroid groups. Analytical results demonstrated that adding low-molecular-weight dextran to oral corticosteroids was not associated with greater hearing gain or better hearing outcome in idiopathic sudden sensorineural hearing loss. [ABSTRACT FROM AUTHOR]

Background: There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion.Methods: From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed.Results: The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 +/- 2.3 months compared with 23.4 +/- 14.9, 12.2 +/- 8.5, and 6.6 +/- 4.3 months in Groups 1, 2, and 3, respectively.Conclusions: This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts. [ABSTRACT FROM AUTHOR]

Porous Ti-6Al-4V alloy was fabricated using the electron beam melting (EBM) process. The phases of the as-received powder and fabricated samples were characterized using X-ray diffraction (XRD) analysis. The XRD peaks of both diffraction patterns agree well, which indicated that the EBM process has not changed the composition of Ti-6Al-4V. The fabricated samples exhibited a Vickers microhardness value of around 428 HV. The compression and three-point bending tests were performed to evaluate the mechanical properties of the porous Ti-6Al-4V implant with a porosity of around 60 per cent. The compressive yield strength, Young's modulus, and ultimate compressive strength were 194.6 MPa, 4.25 GPa, and 222.6 MPa respectively. The bending stiffness and bending strength were 3.7 GPa and 126.3 MPa respectively. These results demonstrated that the porous Ti-6Al-4V implant with a low stiffness and high porosity could be a promising biomaterial for biomedical applications. [ABSTRACT FROM AUTHOR]

Background. Previously, we reported that there was an outbreak of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The objectives of the present study were to conduct a molecular epidemiological analysis and to characterize the full-length genome of the Taiwanese CRF07_BC.Methods. Three hundred and fifty-eight patients with HIV-1/AIDS from hospitals and 133 HIV-1-infected inmates from detention centers were recruited. DNA sequencing and phylogenetic analysis were conducted to determine subtypes and evolutionary relationships. Recombination breakpoints of 2 full-length CRF07_BC strains were elucidated using a bootscanning method.Results. Of 206 HIV-1-infected patients who received a diagnosis in 2004, 44.7% were infected with subtype B, 53.4% with CRF07_BC, and 1.5% with CRF01_AE. Ninety-eight percent (109/111) of IDUs were infected with CRF07_BC. Deletions of 7-11 amino acids in both p6(gag) and p6(pol) proteins were noted among the Taiwanese CRF07_BC strains. The CRF_07BC strains belonged to 2 phylogenetic clusters, and the first cluster contained only CRF07_BC strains from the southern part of Taiwan.Conclusions. The Taiwanese CRF07_BC strains had 97% full-length sequence homology with the prototype from mainland China. CRF07_BC was first introduced into the southern region in 2002 and then spread to other regions in Taiwan in 2004. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Background: Herein, we evaluated, retrospectively, the effect of posterior capsular repair upon postoperative hip dislocation subsequent to total hip arthroplasty (THA) incorporating a posterolateral approach.Methods: A total of 181 patients undergoing 204 primary non-complicated THA surgical procedures in the period from January 2000 to October 2005 inclusively were included in this study. The patients were separated into two groups by whether the posterior capsular repair had been incorporated in the surgical procedure. For the surgeon did not commence repairing the posterior capsule until July, 2003, all members in the group that did not undergo posterior capsular repair (142 hips from 131 patients) were collected since January, 2000 to July, 2003, while the members in the group that underwent posterior capsular repair (62 hips from 52 patients) were followed since July, 2003, to October, 2005. With a minimum follow-up period of 12 months, we evaluated the early post-operative dislocation rate.Results: The early postoperative hip-dislocation rate for the group who did not undergo posterior capsular repair appeared to be substantially greater (6.38% versus 0%) than the corresponding figure for the group the members of which underwent posterior capsular repair. In addition, patient demographics and the orientation of acetabular components for the replaced hip joints, as presented in postoperative radiographs, did not differ between the two groups.Conclusion: Thus, surgeons should include posterior capsular repair as an important step in the surgical procedures of posterolateral approach for all THA in order to reduce the likelihood of early hip dislocation subsequent to THA. [ABSTRACT FROM AUTHOR]

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty.Methods: This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed.Results: Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 +/- 1.68 vs. 3.43 +/- 1.50, p = 0.03) and 72 hrs (1.78 +/- 1.66 vs. 3.17 +/- 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8 degrees +/- 17.3 degrees vs. 25.8 degrees +/- 11.5 degrees , p = 0.01 (day 1); 60.7 degrees +/- 18.1 degrees vs. 45.0 degrees +/- 17.3 degrees , p = 0.004 (day 2); 77.7 degrees +/- 15.1 degrees vs. 64.3 degrees +/- 16.9 degrees , p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions.Conclusion: Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding.Trial Registration: Clinicaltrials.gov NCT00598234. [ABSTRACT FROM AUTHOR]

Accurate estimation of atmospheric chemical concentrations from multiple observations is crucial for assessing the health effects of air pollution. However, existing methods are limited by imbalanced samples from observations. Here, we introduce a novel deep-learning model-measurement fusion method (DeepMMF) constrained by physical laws inferred from a chemical transport model (CTM) to estimate NO 2 concentrations over the Continental United States (CONUS). By pretraining with spatiotemporally complete CTM simulations, fine-tuning with satellite and ground measurements, and employing a novel optimization strategy for selecting proper prior emission, DeepMMF delivers improved NO 2 estimates, showing greater consistency and daily variation alignment with observations (with NMB reduced from -0.3 to -0.1 compared to original CTM simulations). More importantly, DeepMMF effectively addressed the sample imbalance issue that causes overestimation (by over 100%) of downwind or rural concentrations in other methods. It achieves a higher R 2 of 0.98 and a lower RMSE of 1.45 ppb compared to surface NO 2 observations, overperforming other approaches, which show R 2 values of 0.4-0.7 and RMSEs of 3-6 ppb. The method also offers a synergistic advantage by adjusting corresponding emissions, in agreement with changes (-10% to -20%) reported in the NEI between 2019 and 2020. Our results demonstrate the great potential of DeepMMF in data fusion to better support air pollution exposure estimation and forecasting.

Aims: One effective clinical strategy to combat obesity is intragastric botulinum toxin (BTX) injection, which increases gastric emptying time and regulates appetite. However, it remains unknown if and how BTX affects ghrelin levels., Materials and Methods: An obese animal model was established by feeding male mice with high-fat diet (HFD). BTX was administered by subserosal injection in the antrum via an upper midline laparotomy. The mice were monitored in terms of body weight and blood biochemical parameters. Glucose utility and insulin sensitivity were measured by intraperitoneal glucose and insulin tolerance tests. Additionally, stomach and liver were histologically examined after BTX treatment. AGS gastric adenocarcinoma cells were used to investigate the molecular mechanism by which BTX affects ghrelin expression., Key Findings: In HFD-fed mice, BTX injection significantly decreased both food intake and body weight over a 3-week monitoring period. Moreover, HFD-induced hyperglycemia, hyperinsulinemia, dyslipidemia and obesity readouts were improved after BTX injection. Importantly, mice also exhibited decreased plasma and gastric ghrelin levels after BTX injection. In cultured AGS cells, BTX significantly increased reactive oxygen species (ROS) levels and activated nuclear factor-κB (NF-κB), which led to decreased ghrelin expression. Pre-treatment with inhibitors of either ROS or NF-κB reversed the effects of BTX on ghrelin expression in the cultured cells., Significance: BTX decreases ghrelin expression in HFD-fed animals and in AGS cells through an ROS/NF-κB-dependent pathway. This mechanism may contribute to decreased food intake in obese subjects receiving intragastric BTX injection for weight control., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study investigated whether artificial intelligence (AI) models combining voice signals, demographics, and structured medical records can detect glottic neoplasm from benign voice disorders., Methods: We used a primary dataset containing 2-3 s of vowel "ah", demographics, and 26 items of structured medical records (e.g., symptoms, comorbidity, smoking and alcohol consumption, vocal demand) from 60 patients with pathology-proved glottic neoplasm (i.e., squamous cell carcinoma, carcinoma in situ, and dysplasia) and 1940 patients with benign voice disorders. The validation dataset comprised data from 23 patients with glottic neoplasm and 1331 patients with benign disorders. The AI model combined convolutional neural networks, gated recurrent units, and attention layers. We used 10-fold cross-validation (training-validation-testing: 8-1-1) and preserved the percentage between neoplasm and benign disorders in each fold., Results: Results from the AI model using voice signals reached an area under the ROC curve (AUC) value of 0.631, and additional demographics increased this to 0.807. The highest AUC of 0.878 was achieved when combining voice, demographics, and medical records (sensitivity: 0.783, specificity: 0.816, accuracy: 0.815). External validation yielded an AUC value of 0.785 (voice plus demographics; sensitivity: 0.739, specificity: 0.745, accuracy: 0.745). Subanalysis showed that AI had higher sensitivity but lower specificity than human assessment (p < 0.01). The accuracy of AI detection with additional medical records was comparable with human assessment (82% vs. 83%, p = 0.78)., Conclusions: Voice signal alone was insufficient for AI differentiation between glottic neoplasm and benign voice disorders, but additional demographics and medical records notably improved AI performance and approximated the prediction accuracy of humans., Level of Evidence: NA Laryngoscope, 134:4585-4592, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Vocal process granuloma (VPG) is a chronic condition resulting from a mucoperichondrial injury of vocal process. Initial conservative treatment typically involves vocal hygiene education and antireflux medication. Treatment challenges arise with refractory cases. Outcomes of second-line treatments such as surgical excision and botulinum toxin injections remain inconsistent. Thus, we propose this study to investigate the effectiveness of intralesional steroid injections for refractory VPG., Methods: We conducted a retrospective review of 23 patients with VPG who showed no improvement after 3 months of proton pump inhibitors. These patients underwent one to three courses of monthly in-office intralesional steroid injections as a second-line therapy. Treatment outcomes were evaluated by measuring the size of the VPG relative to the length of the vocal folds before and after the final injection procedure., Results: Results showed a significant reduction in VPG size from baseline of 27.74 ± 15.06 to 5.48 ± 8.95 (p < .001). 15 out of 23 patients were responsive (size reduction ≥ 75%) to intralesional steroid injection. Alcohol consumption and longer symptom duration were associated with a poor response (size reduction <75%), whereas prior intubation was associated with better response., Conclusions: For refractory VPG not responding to conservative treatment, intralesional steroid injection appears to be a promising alternative option without significant adverse effects., (© 2024 John Wiley & Sons Ltd.)

Objective: To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC). Methods: The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan-Meier method was used for survival analysis. Results: We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4-112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2-21.8) months. Conclusion: The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Objective: Ambulatory phonation monitoring (APM) has a long evolving history. Current devices mostly use a contact microphone or accelerometer over the anterior neck, limiting its general acceptance outside of academic purposes. This study applied wireless Bluetooth earphones to receive voice signals. We also designed a mobile App with personalized AI model to identify phonation segments., Study Design: Proof of concept study., Setting: Acoustic laboratory., Methods: The materials comprised 1-hour audio files from seven teachers recorded in the classroom. The first 5minutes were used to train the personalized SpeechDetection models using deep neural networks. Another six segments (30 seconds each) were selected for assessing the accuracy of this APM system using two parameters: (1) speech intensity, which was compared to the gold standard measured by CLIO 12, a professional system for voice recording, and (2) phonation segments, which was compared with manual labeling., Results: The training accuracy of the SpeechDetection model ranged from 91.2% to 98.5%, with a mean of 95.4%. The testing accuracy for detecting phonation segments ranged from 88.4% to 97.0% (mean: 91.5%). The Kappa value of consistency ranged from 0.710 to 0.931 (mean: 0.813, P < 0.001 for all seven participants). After linear calibration, the accuracy of measuring speech intensity ranged from 0.846 to 0.927 (mean: 0.885, P < 0.001, Pearson correlation coefficient)., Conclusions: The study results demonstrated that a novel APM system using wireless earphones with mobile apps can accurately measure phonation segments and speech intensity for teachers in the classrooms. Further experiments under different environments with more participants are mandatory before extrapolating this system to real-world use cases., Level of Evidence: N/A., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chi-Te Wang reports financial support was provided by Far Eastern Memorial Hospital. Chi-Te Wang and Ying-Hui Lai have patent #METHOD FOR MONITORING PHONATION AND SYSTEM THEREOF (I-749663) licensed to Taiwan Intellectual Property Office. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The combination of anti-angiogenic therapy and immune checkpoint inhibitors has revolutionized the management of unresectable hepatocellular carcinoma (uHCC). While an early-phase study demonstrated promising outcomes for lenvatinib plus pembrolizumab (L+P) in treating uHCC, the LEAP-002 trial did not meet its primary endpoint. However, the comparative efficacy between L+P and atezolizumab plus bevacizumab (A+B) as first-line treatment remains a topic of uncertainty. This study aimed to assess the effectiveness and safety of L+P in contrast to A+B among patients diagnosed with uHCC., Methods: We conducted a retrospective analysis of enrolled patients with uHCC who received L+P or A+B as initial systemic treatment at Chang Gung Memorial Hospital from June 2019 to December 2022. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by modified RECIST were compared., Results: 121 patients were recruited, with 37 receiving L+P and 84 receiving A+B. Among them, 95 (78.5%) patients were BCLC stage C, and 99 (81.8%) patients had viral etiology for HCC, predominantly chronic HBV (68.6%). Both the L+P and the A+B groups demonstrated comparable OS (18.2 months versus 14.6 months, p = 0.35) and PFS (7.3 months versus 8.9 months, p = 0.75). The ORR and DCR were similar. After propensity score matching, the results remained consistent between the matched patients. Treatment-related adverse events of any grade occurred in 30 (81.1%) in the L+P group and 62 (73.8%) in the A+B group., Conclusions: Our findings suggest that L+P and A+B exhibit comparable efficacy and safety profiles in real-world settings.

Purpose: The aim of this pilot study was to explore the efficacy of an intensive 3 week water resistance phonation (WRP) therapy program for people with presbyphonia. Method: Participants included 13 people with presbyphonia who received intensive WRP therapy. All participants completed eight sessions of therapy over 3 weeks. Auditory perceptual ratings, and acoustic and aerodynamic assessments were performed before and after treatment. Participants also completed the voice-related quality of life questionnaire before and after the treatment. Result: After 3 weeks of intensive voice therapy, significant improvements were demonstrated in acoustic, aerodynamic, and auditory perceptual parameters, as well as patient perceptions of voice-related quality of life. Acoustically, it was found there were significant decreases in shimmer ( p  = 0.019), noise-to-harmonic ratio ( p  = 0.016), and smoothed cepstral peak prominence ( p  = 0.001). Perceptually, the clients with presbyphonia showed significant reductions in the ratings of the overall grade, roughness, asthenia, and strain. Moreover, there was a significant increase in the total score of the Mandarin version of the Voice-Related Quality of Life measure post-therapy. Conclusion: The investigation provides preliminary evidence that people with presbyphonia can improve their vocal function and voice-related quality of life through intensive WRP therapy within a short period of time.

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells' vulnerabilities, potentially marking a significant advancement in managing this deadly disease.

Background: 3-Hydroxybutyrate, also called β-hydroxybutyrate, is a significant constituent of ketone bodies. Previous observational and experimental studies have suggested that ketogenic diet, especially 3-hydroxybutyrate, may have a protective effect against cardiovascular disease. However, the relationship between ketone bodies, especially 3-hydroxybutyrate, and aortic dissection remains uncertain., Materials and Methods: Publicly accessible data from genome-wide association study (GWAS) was utilized to obtain information on ketone bodies, including 3-hydroxybutyrate, acetoacetate and acetone as exposure respectively, while GWAS data on aortic dissection was used as outcome. Subsequently, two-sample Mendelian randomization (MR) analysis was conducted to examine the potential relationship between ketone bodies and aortic dissection. Then, reverse and multivariate Mendelian randomization analyses were performed. Additionally, sensitivity tests were conducted to assess the robustness of MR study., Results: The inverse-variance weighted (IVW) method of Mendelian randomization analysis of gene prediction observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection (OR 0.147, 95% CI 0.053-0.410). Furthermore, consistent findings were obtained through the implementation of the weighted median, simple mode, Mendelian randomization-Egger (MR-Egger), and weighted mode methods. After adjusting acetoacetate (OR 0.143, 95% CI 0.023-0.900) or acetone (OR 0.100, 95% CI 0.025-0.398), MR analysis of gene prediction still observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection. No indications of heterogeneity or pleiotropy among the SNPs were detected., Conclusion: The findings from the MR analysis demonstrated that genetically predicted 3-hydroxybutyrate exhibits a protective effect against aortic dissection., (© 2024. The Author(s).)

Type 2 diabetes mellitus (T2DM) is a prevalent health challenge faced by countries worldwide. In this study, we propose a novel large language multimodal models (LLMMs) framework incorporating multimodal data from clinical notes and laboratory results for diabetes risk prediction. We collected five years of electronic health records (EHRs) dating from 2017 to 2021 from a Taiwan hospital database. This dataset included 1,420,596 clinical notes, 387,392 laboratory results, and more than 1505 laboratory test items. Our method combined a text embedding encoder and multi-head attention layer to learn laboratory values, and utilized a deep neural network (DNN) module to merge blood features with chronic disease semantics into a latent space. In our experiments, we observed that integrating clinical notes with predictions based on textual laboratory values significantly enhanced the predictive capability of the unimodal model in the early detection of T2DM. Moreover, we achieved an area greater than 0.70 under the receiver operating characteristic curve (AUC) for new-onset T2DM prediction, demonstrating the effectiveness of leveraging textual laboratory data for training and inference in LLMs and improving the accuracy of new-onset diabetes prediction., (© 2024. The Author(s).)