A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma.

BACKGROUND: S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). METHODS: This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights. RESULTS: A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity. CONCLUSIONS: S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.

Interdisciplinary treatment of a mutilated dentition with multiple missing teeth and horizontal impaction of a mandibular third molar using an orthodontic skeletal anchorage and dental implants-Case report.

OBJECTIVE: This case report presents a female adult patient who exhibits poor oral hygiene, a mutilated dentition with multiple missing teeth, and skeletal asymmetry. CLINICAL CONSIDERATIONS: Interdisciplinary treatment was necessary to maintain oral hygiene, treat caries, extract residual roots, and upright a horizontally impacted third molar using a miniplate. Additionally, orthodontic mini-implants were utilized as anchorage to improve sagittal relationship and space closing. Space management was completed with orthodontic treatment, followed by restoration of the multiple missing teeth with dental implants. CONCLUSION: Consequently, an esthetic smile and functional occlusion were achieved by interdisciplinary treatment using orthodontic skeletal anchorage devices and dental implants. CLINICAL SIGNIFICANCE: Missing mandibular first molar spaces were closed with retraction of the anterior teeth and protraction of the mandibular second molars using orthodontic mini-implants. The mandibular right third molar, which should have erupted, was protracted with the second molar, while the horizontally impacted mandibular left third molar was uprighted using a miniplate and was protracted with an orthodontic mini-implant. The missing maxillary lateral incisors were replaced with the maxillary canines, and the maxillary canines were replaced with the maxillary first premolars. The missing maxillary right second premolar and first molar and left first and second molars were successfully restored with dental implants.

Revision for unsatisfactory outcomes of scalp micropigmentation.

BACKGROUND: Scalp micropigmentation (SMP) is becoming increasingly popular. Accordingly, complications of the procedure are on the rise. However, the results of improperly performed SMP are exceedingly challenging to rectify and ultimately lead to severe mental stress and feelings of inferiority in patients. AIMS: This retrospective study aimed to explore various aspects of unsatisfactory SMP outcomes and examine corrective measures available after the procedure. MATERIALS AND METHODS: A total of 120 patients who underwent corrective surgery or procedures due to unsatisfactory outcomes after SMP were enrolled in the study. Their photographs and medical charts were reviewed retrospectively. RESULTS: Out of 120 participants, 76 were women and 43 men. In total, 107 patients (89.2%) had been treated at a tattooing or cosmetic facility at a beauty salon performing permanent makeup, 12 (10.0%) at another clinic, and one (0.8%) at an oriental medicine clinic. Of 120 patients, hair transplant surgery was performed on 74 patients (61.7%). Twenty-five (20.8%) underwent both hair transplant surgery and complementary SMP. Sixteen (13.3%) patients received laser tattoo removal and underwent SMP anew. Five patients (4.2%) had a previous tattoo removed without additional treatment. Patients' subjective satisfaction scores averaged 4.5/5. The physician's objective satisfaction score was 4.6/5. CONCLUSION: In cases where SMP is inadequately performed, satisfactory results can be achieved through appropriate revisions, such as tattoo removal, repeated SMP, or hair transplant surgery to conceal the tattoo by highly experienced medical professionals. LEVEL OF EVIDENCE: IV.

Hair transplantation versus scalp micropigmentation: A retrospective study of treatment selection in persons with female pattern hair loss.

BACKGROUND: Hair transplant (HT) is the standard treatment for female pattern hair loss (FPHL), but scalp micropigmentation (SMP) is an alternative. Currently, there are no criteria to help choose between HT and SMP. METHODS: Forty female patients with FPHL who had successfully undergone HT and SMP, were reviewed to identify factors that might help decide between treatments. Hair density (HD) and hair caliber were measured at the part line and mid-occipital region by a Folliscope. The sensitivity and specificity of HT and SMP were determined by area under the curve (AUC) and receiver operating characteristic curve. RESULTS: Patients were divided into HT (n = 23) and SMP (n = 17) groups. The follicular unit density (FUD) (HT: 62.06 ± 4.8551/cm2; SMP: 66.59 ± 3.4971/cm2) and HD (HT: 96.16 ± 16.6954/cm2; SMP: 116.08 ± 17.0520/cm2) were significantly different (p < 0.01) between groups. The AUC for FUD was 77.6% with a cutoff value of 66.83 and 87.0% (1-0.412) sensitivity. The AUC for HD was 82.4% with a cutoff value of 96.17 and 69.6% (1-0.118) sensitivity. CONCLUSIONS: HD was the most important factor when deciding between HT surgery and SMP. SMP is recommended when the HD is ≥104.6 hairs/cm2 and HT surgery is strongly recommended when the HD is ≤96.17 hairs/cm2.

Management of Cowlick in Female Hairline Correction Surgery.

PURPOSE: To investigate the results of two grafting methods to manage CLs in the FHL of women. BACKGROUND: The present study was performed to investigate the results of two grafting methods to manage cowlicks (CLs) in the frontal hairline of women. METHODS: Patients were categorized into two groups based on the grafting method: the matching with the original hair direction (MOD) group and the matching with the CL hair direction (MCD) group. Satisfaction ratings were compared between the two groups. RESULTS: Among 80 patients, 77 had a single CL and 3 had a double CL. In the MOD group, 7 of 12 (58.3%) patients underwent a touch-up procedure for density enhancement with an average of 123 follicular units; the average patient and physician satisfaction ratings were 4.84 and 4.60, respectively. In the MCD group, 7 of 68 (10.3%) patients underwent a touch-up procedure for density enhancement around the CL; the average patient and physician satisfaction ratings were 4.64 and 4.50, respectively. CONCLUSION: In female hairline correction surgery, the surgeon must choose between MOD and MCD by considering the location, shape, and pattern of the CL; the facial shape; and the patient's preference. Delicate graft placement is required to obtain natural-looking results. 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 .

Uprighting a mesially impacted mandibular second molar with scissor bite using simple tubes.

Orthodontic uprighting or traction of an impacted mandibular second molar often necessitates invasive interventions. This report aims to illustrate the utilization of nickel-titanium wire segments inserted into small, simple tubes for uprighting mesially impacted mandibular second molars and also for scissor bite correction. The term "simple tube" refers to a tube without a bonding base attached to a tooth surface by covering it with flowable composite resin. Due to the absence of a bonding base, the simple tube is characterized by its diminutive size and minimal profile height, facilitating placement on partially exposed second molars and unconventional positioning to adjust the force geometry. In this case study, mesially-impacted mandibular second molars with scissor bite were uprighted in a 21-year-old male utilizing simple tubes. Simple tubes can be used for molar uprighting and scissor bite correction buccally and lingually.

Long-term skeletodental changes with early and late treatment using modified C-palatal plates in hyperdivergent Class II adolescents.

OBJECTIVES: To compare skeletodental changes between early and late treatment groups using modified C-palatal plates (MCPP) and long-term retention outcomes in hyperdivergent Class II adolescents. MATERIALS AND METHODS: Seventy-one hyperdivergent Class II patients were divided into four groups according to treatment modality and treatment timing: group 1, early treatment with MCPP (n = 16; 9.9 ± 0.9 years); group 2, late treatment with MCPP (n = 19; 12.3 ± 0.8 years); group 3, early treatment with headgear (HG; n = 18; 9.6 ± 0.8 years); and group 4, late treatment with HG (n = 18; 12.1 ± 1.2 years). Lateral cephalograms were taken and skeletal and dental variables were measured. For statistical analysis, paired t-tests, independent t-tests, and multiple regression were performed. RESULTS: The early MCPP group showed a more significant decrease in mandibular plane angle than the late MCPP group did, and vertical control was more efficient in the early group than in the late group. In the MCPP groups, both FMA and SN-GoGn were increased with late treatment but decreased with early treatment, and the difference was statistically significant (P < .01). The early-treatment MCPP group had a significant decrease in SN-GoGn of 0.6° compared with an increase of 1.7° in the early treatment HG group (P < .01). Posttreatment stability of both the early and late MCPP groups was maintained in long-term retention. CONCLUSIONS: Early MCPP showed more significant vertical control than late MCPP. However, there was no difference in long-term stability between early and late groups.

Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct.

BACKGROUND: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. RESULTS: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-ß1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. CONCLUSIONS: Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart.

Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications.

Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.

Reliability of Artificial Intelligence-based Cone Beam Computed Tomography Integration with Digital Dental Images.

This study aimed to introduce cone-beam computed tomography (CBCT) digitization and integration of digital dental images (DDI) based on artificial intelligence (AI)-based registration (ABR) and to evaluate the reliability and reproducibility using this method compared with those of surface-based registration (SBR). This retrospective study consisted of CBCT images and DDI of 17 patients who had undergone computer-aided bimaxillary orthognathic surgery. The digitization of CBCT images and their integration with DDI were repeated using an AI-based program. CBCT images and DDI were integrated using a point-to-point registration. In contrast, with the SBR method, the three landmarks were identified manually on the CBCT and DDI, which were integrated with the iterative closest points method. After two repeated integrations of each method, the three-dimensional coordinate values of the first maxillary molars and central incisors and their differences were obtained. Intraclass coefficient (ICC) testing was performed to evaluate intra-observer reliability with each method's coordinates and compare their reliability between the ABR and SBR. The intra-observer reliability showed significant and almost perfect ICC in each method. There was no significance in the mean difference between the first and second registrations in each ABR and SBR and between both methods; however, their ranges were narrower with ABR than with the SBR method. This study shows that AI-based digitization and integration are reliable and reproducible.

Optimization of Acetabular Cup Abduction by Adjusting Pelvic Pitch.

Background: The purposes of this study were to determine the accuracy of our cup positioning method and to evaluate the dislocation rate after total hip arthroplasty (THA). Methods: After positioning the patient in the lateral decubitus position on the operation table, an anteroposterior view of the hip was taken. The pelvic pitch was measured on the X-ray. A positive pitch was defined as the caudal rotation of the upper hemipelvis. Our target abduction of the cup was 43°. We used the cup holder to guesstimate the cup abduction. In a preliminary study, we found that the weight of the cup holder increased the pelvic pitch by 5°. Thus, the target abduction of the cup holder was calculated by a formula: 43° - pelvic pitch - 5°. During the cup insertion, the cup holder was anteverted to the calculated target according to the concept of combined anteversion. We evaluated 478 THAs (429 patients), which were done with the use of the method. Results: The mean cup abduction was 43.9° (range, 32.0°-53.0°) and the mean error of cup abduction was 2.4° (standard deviation [SD], 2.0°; range, 0.0°-11.0°). The mean cup anteversion was 28.5° (range, 10.0°-42.0°) and the mean error of cup anteversion was 6.7° (SD, 5.2°; range, 0.0°-27.6°). Of all, 82.4% of the cups (394 / 478) were within the safe zone: 30°-50° abduction and 10°-35° anteversion. During 2- to 5-year follow-up, no hip dislocated. Conclusions: Our adjusting method according to the pelvic pitch can be a reliable option for optimizing the cup abduction in THA.

Huge Pseudoaneurysm at the Aortic Bifurcation Misdiagnosed as a Mesenchymal Tumor: A Case Report.

Aortic pseudoaneurysms (PA) vary in size and may remain asymptomatic. PAs may be caused by vascular injury, such as trauma or surgery, or other non-traumatic causes, such as Bechet disease, infection, or penetrating atherosclerotic ulcers. The diagnosis of PAs may have been delayed for decades. We present a case of a PA detected incidentally in a male patient who experienced traumatic bowel perforation due to blunt abdominal trauma 30 years before presentation. Computed tomography (CT) displayed a 9.2 cm mass in the pelvis, initially considered a neoplasm of small bowel origin. Further analysis of the CT images suggested a thrombosed PA at the aortic bifurcation, which was confirmed via surgical exploration. Graft interposition was performed using a Dacron 16-8 mm graft and the patient recovered without any complications. This case highlights the importance of a high index of suspicion for the diagnosis of a thrombosed aortic PA.

One-year Outcomes of Ultrathin Descemet Stripping Automated Endothelial Keratoplasty Combined with Cataract Surgery in the Korean Population.

PURPOSE: To evaluate the refractive outcomes after ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) combined with phacoemulsification and intraocular lens implantation (triple procedure) in the South Korean population. METHODS: This retrospective observational study included 37 eyes of 36 patients who underwent the UT-DSAEK triple procedure between 2012 and 2021 in a single tertiary hospital. Preoperative and postoperative refractive outcomes and endothelial parameters at 1, 3, 6, and 12 months were observed. RESULTS: At the final postoperative 12-month period, the average best-corrected visual acuity was 0.4 ± 0.5 in logarithm of the minimum angle of resolution. The mean endothelial cell density at 12 months was 1,841.92 ± 731.24 cells/mm2, indicating no significant endothelial cell loss compared to the baseline (p = 0.128). The mean postoperative central corneal thickness at 12 months was 597.41 ± 86.26 µm. The postoperative mean absolute error at 12 months was 0.96 ± 0.89 diopters (D) and mean error was 0.89 ± 0.97 D. CONCLUSIONS: The results of our South Korean cohort study on UT-DSAEK triple surgery showed favorable and safe outcomes. Regardless of graft thickness, it should be noted that a hyperopic shift of 1.00 to 2.00 D needs to be considered in the case of UT-DSAEK triple surgery.

2023-2024 American Board of Orthodontics practice analysis study: Part 1.

As a specialty board, the American Board of Orthodontics (ABO) serves to protect the public and the orthodontic specialty by certifying orthodontists. The demonstration of commitment to lifelong learning and self-improvement is critical to achieving the highest level of patient care. The ABO completed a practice analysis study in 2023 to ensure all examinations represent current assessments of proficiency in orthodontics at a level of quality that satisfies professional expectations. The practice analysis is essential to providing a demonstrable relationship between the examination content and orthodontic practice and provides a critical foundation for ABO's examination programs.

Comparison of posttreatment stability after total mandibular arch distalization with mini-implants and mandibular setback surgery.

OBJECTIVES: To compare posttreatment stability in skeletal Class III patients between those treated by total mandibular arch distalization (TMAD) with buccal mini-implants and those by mandibular setback surgery (MSS). MATERIALS AND METHODS: The samples included 40 Class III adults, 20 treated by TMAD using buccal interradicular mini-implants and 20 treated with MSS. Lateral cephalograms were taken at pretreatment, posttreatment, and at least 1-year follow-up, and 24 variables were compared using statistical analysis. RESULTS: Mandibular first molars moved distally 1.9 mm with intrusion of 1.1 mm after treatment in the TMAD group. The mandibular incisors moved distally by 2.3 mm. The MSS group exhibited a significant skeletal change of the mandible, whereas the TMAD group did not. During retention, there were no skeletal or dental changes other than 0.6 mm labial movement of the mandibular incisors (P < .05) in the MSS group. There was 1.4° of mesial tipping (P < .01) and 0.4 mm of mesial movement of the mandibular molars and 1.9° of labial tipping (P < .001) and 0.8 mm of mesial movement of the mandibular incisors in the TMAD group. These dental changes were not significantly different between the two groups. CONCLUSIONS: The TMAD group showed a slightly decreased overjet with labial tipping of the mandibular incisors and mesial tipping of the first molars during retention. Posttreatment stability of the mandibular dentition was not significantly different between the groups. It can be useful to plan camouflage treatment by TMAD with mini-implants in mild-to-moderate Class III patients.

Structural basis of hepatitis B virus receptor binding.

Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2-48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus-host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.

Orthodontic considerations in hypodivergent craniofacial patterns.

This article examines the characteristics of hypodivergent craniofacial patterns and explores treatment modalities in response to these features. It discusses the impact of robust masticatory muscles, which produce heavy occlusal forces. In addition, it examines the use of Botox or splints to reduce gonial angles in individuals with a square face. A nonextraction treatment approach supported by temporary skeletal anchorage devices is recommended; however, if anatomical limitations persist, extraction may be necessary when arch expansion, molar distalization, incisor proclination, or interproximal reduction cannot create the necessary space. In hypodivergent cases where a nonextraction approach is impractical, a single-arch extraction strategy may be considered to prevent a reduction in the vertical dimension. Emphasizing esthetics, particularly maxillary incisor display, a protocol of total arch extrusion of the maxillary dentition assisted with temporary skeletal anchorage device, bite raisers, and interarch elastics is suggested.