Ethanol Ablation of Ranulas and Risk Factor Analysis for Recurrence.

Importance: Ethanol ablation (EA) was shown to be safe and effective for treating ranula, but few studies have assessed long-term outcomes and recurrence of ranula after EA. Objective: To evaluate the long-term outcomes and the risk factors for recurrence and receipt of subsequent surgery in patients who underwent treatment with EA for ranula. Design, Setting, and Participants: This case-series study was conducted at a single tertiary hospital and assessed patients who were treated with EA between July 2009 and March 2021. Among 70 consecutive patients, those with follow-up loss or who were followed up for less than 24 months were excluded. Exposures: EA for ranula. Main Outcomes and Measures: The primary outcome was recurrence at last follow-up after single or multiple EA sessions. Secondary outcomes included receipt of subsequent surgery and the recurrence-free survival (RFS) rate after initial EA. Factors possibly associated with outcomes included patient age and sex; ranula site, type, diameter, volume, and echogenicity; the presentation-to-EA interval; parapharyngeal space extension; and sublingual gland herniation. Risk factors were identified on logistic regression analyses. Two-year RFS rates were analyzed for the initial cohort using the Kaplan-Meier method and compared by log-rank tests. Results: A total of 57 patients (mean [SD] age, 26.4 [12.1] years; 24 female individuals [42%]) who were followed up for a median of 57 months (range, 24-167 months) were included. The recurrence rate was 33% (n = 19), and 11 (19%) underwent subsequent surgery. Among patients with recurrence, 86% (31 of 36) experienced first recurrence within 12 months after initial EA. A presentation-to-EA interval of 12 months or longer was associated with an increased risk of recurrence (adjusted odds ratio [OR], 3.74; 95% CI, 1.01-13.82). No risk factors were significantly associated with subsequent surgery (highest OR in parapharyngeal space extension: adjusted OR, 4.96; 95% CI, 0.94-26.35). Among the initial cohort of 70 patients, 2-year RFS was lower in a maximum diameter of ranula of 5 cm or greater than less than 5 cm (24% [95% CI, 7%-41%] vs 50% [95% CI, 34%-66%]; difference, 26% [95% CI, -4% to 56%]; log-rank test, P = .02). Conclusions and Relevance: This case-series study found that the recurrence rate of ranula after EA was 33%. A presentation-to-EA interval of 12 months or longer may be a risk factor for recurrence, suggesting that early intervention with EA might minimize recurrence. Most first recurrences occurred within 12 months after EA, with a maximum diameter of ranula of 5 cm or greater being a possible risk factor.

Enhanced Recovery After Surgery for Craniotomies: A Systematic Review and Meta-analysis.

The efficacy of the enhanced recovery after surgery (ERAS) protocols in neurosurgery has not yet been established. We performed a systematic review and meta-analysis of randomized controlled trials to compare the effects of ERAS protocols and conventional perioperative care on postoperative outcomes in patients undergoing craniotomy. The primary outcome was postoperative length of hospital stay. Secondary outcomes included postoperative pain visual analog pain scores, incidence of postoperative nausea and vomiting (PONV), postoperative complications, all-cause reoperation, readmission after discharge, and mortality. A literature search up to August 10, 2023, was conducted using PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. Five studies, including 871 patients, were identified for inclusion in this review. Compared with conventional perioperative care, ERAS protocols reduced the length of postoperative hospital stay (difference of medians, -1.52 days; 95% CI: -2.55 to -0.49); there was high heterogeneity across studies (I2, 74%). ERAS protocols were also associated with a lower risk of PONV (relative risk, 0.79; 95% CI: 0.69-0.90; I2, 99%) and postoperative pain with a visual analog scale score ≥4 at postoperative day 1 (relative risk, 0.37; 95% CI: 0.28-0.49; I2, 14%). Other outcomes, including postoperative complications, did not differ between ERAS and conventional care groups. ERAS protocols may be superior to conventional perioperative care in craniotomy patients in terms of lower length of hospital stay, lower incidence of PONV, and improved postoperative pain scores. Further randomized trials are required to identify the impact of ERAS protocols on the quality of recovery after craniotomy.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

Clinical implication of neck dissection for metastatic lymph nodes originating from non-head and neck regions.

BACKGROUND: Cervical lymph node metastasis (CLNM) from remote primary sites is rare in head and neck cancer. The efficacy of neck dissection is still being investigated for therapeutic benefits of local management in oligometastasis from non-head and neck cancer. OBJECTIVES: To evaluate the clinical efficacy of neck dissection (ND) in CLNM from distant primary cancers and identify factors contributing to improved survival. MATERIALS AND METHODS: This retrospective case-control study enrolled patients who underwent ND for CLNM from distant primary cancer at Asan Medical Centre between January 2010 and December 2020. We analysed overall survival and association between clinical covariate and survival. RESULTS: The study included 31 (14 males, 17 females) among 114 patients. Ovarian cancer was the most common primary malignancy (32.3%). Patients with fewer than three metastatic lymph nodes, without extranodal extension and with adjuvant therapy after surgery had better survival rates. CONCLUSION AND SIGNIFICANCE: In patients with CLNM from a distant primary cancer, ND is beneficial as local treatment. And adequate selection of patients for ND is pivotal to improve prognosis.

Impact of clonal haematopoiesis on atherosclerotic cardiovascular disease according to low-density lipoprotein cholesterol levels in general population.

AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the precise role of CHIP in the development of atherosclerotic cardiovascular disease (ASCVD) remains unclear. METHODS: Among 4,300 asymptomatic Korean participants aged 40-79 years, we investigated the risk of ASCVD by CHIP and the interplay between CHIP and conventional risk factors in ASCVD development. Additionally, we assessed changes in coronary arteries based on the presence of CHIP using coronary computed tomography angiography (CCTA). RESULTS: CHIP was present in 363 participants (8.4%), and its prevalence increased with age. Commonly mutated genes were DNMT3A, TET2 and ASXL1, in order. During follow-up (median, 4.7 years), 18 ASCVD cases (5.0%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (p < 0.001), indicating an elevated risk of ASCVD associated with CHIP (adjusted HR 2.49, 95% CI 1.45-4.29, p < 0.001). Notably, with high levels of low-density lipoprotein (LDL) cholesterol, CHIP enhanced the risk of ASCVD (adjusted HR 6.20, 95% CI 3.14-12.23, p < 0.001), demonstrating synergism between CHIP and LDL cholesterol levels (S-index, 4.94; 95% CI 1.08-22.53, p = 0.039). Serial CCTAs confirmed that CHIP, in conjunction with high LDL cholesterol levels, had significant early impact on coronary arteries, revealing new measurable coronary atherosclerosis, mainly with unstable plaque, in proximal lesions. CONCLUSIONS: The presence of CHIP was significantly associated with the risk of ASCVD, promoting the early stage of atherosclerosis through synergy with high LDL cholesterol in the general population.

In this cohort study of 4,300 asymptomatic community-dwelling Korean adults, we demonstrated a detailed interplay between clonal haematopoiesis of indeterminate potential (CHIP) and conventional risk factors in the development of atherosclerotic cardiovascular disease (ASCVD).The presence of CHIP significantly increased the risk of ASCVD in the general population, displaying a notable synergistic effect with high levels of low-density lipoprotein (LDL) cholesterol.Analyses of serial coronary computed tomography angiography scans revealed that CHIP, in conjunction with high LDL cholesterol levels, may contribute to the promotion of "early" stage in coronary atherosclerosis, providing new insights into CHIP-associated atherosclerosis in the primary prevention.

Genome-wide association study implicates the role of TBXAS1 in the pathogenesis of depressive symptoms among the Korean population.

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6474 (1484 cases and 4990 controls) and 1654 (557 cases and 1097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10-8; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15-1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (12,455 cases and 85,548 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.

A novel approach of kinship determination based on the physical length of genetically shared regions of chromosomes.

BACKGROUND: Determination of genetic relatedness between individuals plays a crucial role in resolving numerous civil cases involving familial relationships and in forensic investigation concerning missing persons. Short tandem repeats (STRs), known for their high degree of DNA polymorphism, have traditionally been the primary choice of DNA markers in genetic testing, but their application for kinships testing is limited to cases involving close kinship. SNPs have emerged as promising supplementary markers for kinship determination. Nevertheless, the challenging remains in discriminating between third-degree or more distant relatives, such as first cousins, using SNPs. OBJECTIVE: To investigate a kinship analysis method for distant degree of familial relationships using high-density SNP data. METHODS: A high-density SNP data from 337 individuals of Korean families using Affymetrix Axiom KORV1.0-96 Array was obtained for this study. SNPs were aligned by chromosomal positions, and identity-by-state (IBS) was determined, and then shared regions as consecutive SNPs with IBS of 1 or 2 were investigated. The physical lengths of these IBS segments were measured and summed them to create an Index, as a measure of kinship. RESULTS: The kinship was determined by the physical length of shared chromosomal regions that are distinguished by each kinship. Using this method, the relationship was able be distinguished up to the fourth degree of kinship, and non-relatives were clearly distinguished from true relatives. We also found a potential for this approach to be used universally, regardless of microarray platforms for SNP genotyping and populations. CONCLUSION: This method has a potential to determine the different degree of kinship between individuals and to distinguish non-relatives from true relatives, which can be of great help for practical applications in kinship determination.

Genetic and Metabolic Characteristics of Lean Nonalcoholic Fatty Liver Disease in a Korean Health Examinee Cohort.

Background/Aims: The pathophysiology of lean nonalcoholic fatty liver disease (NAFLD) is unclear but has been shown to be associated with more diverse pathogenic mechanisms than that of obese NAFLD. We investigated the characteristics of genetic or metabolic lean NAFLD in a health checkup cohort. Methods: This retrospective cross-sectional study analyzed single nucleotide polymorphism data for 6,939 health examinees. Lean individuals were categorized according to a body mass index cutoff of 23 kg/m2. Single nucleotide polymorphisms were analyzed using genotyping arrays. Results: The prevalence of lean NAFLD was 21.6% among all participants with NAFLD, and the proportion of lean NAFLD was 18.5% among lean participants. The prevalence of metabolic syndrome and diabetes among lean patients with NAFLD was 12.4% and 10.4%, respectively. Lean NAFLD appeared to be metabolic-associated in approximately 20.1% of patients. The homozygous minor allele (GG) of PNPLA3 (rs738409) and heterozygous minor alleles (CT, TT) of TM6SF2 (rs58542926) were associated with lean NAFLD. However, the prevalence of fatty liver was not associated with the genetic variants MBOAT7 (rs641738), HSD17B13 (rs72613567), MARC1 (rs2642438), or AGXT2 (rs2291702) in lean individuals. Lean NAFLD appeared to be associated with PNPLA3 or TM6SF2 genetic variation in approximately 32.1% of cases. Multivariate risk factor analysis showed that metabolic risk factors, genetic risk variants, and waist circumference were independent risk factors for lean NAFLD. Conclusions: In a considerable number of patients, lean NAFLD did not appear to be associated with known genetic or metabolic risk factors. Further studies are required to investigate additional risk factors and gain a more comprehensive understanding of lean NAFLD.

Customized Integrating-Sphere System for Absolute Color Measurement of Silk Cocoon with Corrugated Microstructure.

Silk fiber, recognized as a versatile bioresource, holds wide-ranging significance in agriculture and the textile industry. During the breeding of silkworms to yield new varieties, optical sensing techniques have been employed to distinguish the colors of silk cocoons, aiming to assess their improved suitability across diverse industries. Despite visual comparison retaining its primary role in differentiating colors among a range of silk fibers, the presence of uneven surface texture leads to color distortion and inconsistent color perception at varying viewing angles. As a result, these distorted and inconsistent visual assessments contribute to unnecessary fiber wastage within the textile industry. To solve these issues, we have devised an optical system employing an integrating sphere to deliver consistent and uniform illumination from all orientations. Utilizing a ColorChecker, we calibrated the RGB values of silk cocoon images taken within the integrating sphere setup. This process accurately extracts the authentic RGB values of the silk cocoons. Our study not only helps in unraveling the intricate color of silk cocoons but also presents a unique approach applicable to various specimens with uneven surface textures.

Guidelines for the Use of Botulinum Toxin in Otolaryngology From the Korean Society of Laryngology, Phoniatrics and Logopedics Guideline Task Force.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

P16 expression and presence of lymphoid stroma are correlated with good prognosis in mucoepidermoid carcinoma of the head and neck.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. This study was designed to identify valuable prognosticator in MEC. METHODS: Histopathologic analysis, immunohistochemistry, and in situ hybridization were performed on 128 carcinomas diagnosed as MEC of the head and neck. RESULTS: Expression of p16 was found in 96 cases (76%) of MEC. Lymphoid stroma was identified in 63 cases (49%). There was a significant correlation between loss of p16 expression and absence of lymphoid stroma. Expression of p16 was significantly associated with better clinicopathologic features. Lymphoid stroma was significantly associated with lower histologic grade. Overall survival (OS) was significantly longer in cases expressing p16 (P = 0.00096) and lymphoid stroma cases (P = 0.0023). Multivariate analysis revealed loss of p16 expression as negative prognosticators for OS. CONCLUSION: Our data showed p16 expression and the presence of lymphoid stroma were significantly associated with good clinical outcomes. Testing for these factors could lead to better prognostication and treatment of patients with MEC.

Role of reduction gastrectomy in patients with gastric cancer with a single non-curable factor: Supplementary analysis of REGATTA trial.

Background: REGATTA trial failed to demonstrate the survival benefit of reduction gastrectomy in patients with advanced gastric cancer with a single non-curable factor. However, a significant interaction was found between the treatment effect and tumor location in the subset analysis. Additionally, the treatment effect appeared to be different between Japan and Korea. This supplementary analysis aimed to elucidate the effect of reduction surgery based on tumor location and country. Methods: Multivariable Cox regression analyses in each subgroup were performed to estimate the hazard ratio (HRadj), including the following variables as explanatory variables: country, age, sex, incurable factor, cT, cN, primary tumor, performance status, histological type, and macroscopic type. Results: Patients (95 in Japan and 80 in Korea) were randomized to chemotherapy alone (86 patients) or gastrectomy plus chemotherapy (89 patients). The subgroup analysis according to the country revealed a worse overall survival in gastrectomy plus chemotherapy arm in Japan (hazard ratio: 1.32, 95% confidence interval: 0.85-2.05), but not in Korea (hazard ratio: 0.85.95% confidence interval: 0.52-1.40). Overall survival was better in distal gastrectomy plus chemotherapy compared with chemotherapy alone (hazard ratio = 0.69, 95% confidence interval: 0.42-1.13), and worse in total gastrectomy plus chemotherapy compared with chemotherapy alone (hazard ratio = 1.34, 95% CI: 0.93-1.94), which was more remarkable in Korea than in Japan. Conclusions: Primary chemotherapy is a standard of care for advanced gastric cancer; however, the survival benefits from reduction by distal gastrectomy remained controversial.

Characteristics Analysis of Plasticized Polyvinyl Chloride Gel-Based Microlens at Different Temperatures.

Temperature plays a crucial role in the preparation of polyvinyl chloride (PVC) gels for optical applications. Incorrect temperature selection can lead to various issues such as poor surface roughness, inadequate light transmission, and insufficient solution for optical devices. To address this challenge, this study focuses on the preparation of PVC gel samples by combining PVC powder (n = 3000), eco-friendly dibutyl adipate, and tetrahydrofuran at different stirring temperatures ranging from 40 to 70 °C. The PVC gel preparation process is categorized into four groups (T40, T50, T60, and T70) based on the mixing temperatures, employing a controlled test method with specific temperature conditions. The prepared PVC gel samples are then subjected to analysis to evaluate various properties including surface morphology, tensile strength, light transmittance, and electrical response time. Among the samples, the PVC gel prepared at 60 °C (referred to as T60) exhibits excellent optical properties, with a transmittance of 91.2% and a tensile strength of 2.07 MPa. These results indicate that 60 °C is an optimal reaction temperature. Notably, the PVC gel microlenses produced at this temperature achieve their maximum focal length (ranging from -8 to -20 mm) within approximately 60 s, and they recover their initial state within around 80 s after the power is switched off. This focal length achievement is twice as fast as reported in previous studies on microlenses. It is observed that the reaction temperature significantly influences the solubility of the resin-based raw materials and the homogeneity of the gel. Consequently, these findings open up possibilities for utilizing PVC gel microlenses in novel commercial optics applications, thanks to their desirable properties.

Salivary Gland Neoplasms With a Unique Trabecular Histology and MAML2 Translocation : A Trabecular Variant of a Mucoepidermoid Carcinoma.

Mucoepidermoid carcinomas (MECs) are the most common salivary gland malignancy and have a diverse histology. Many histologic variants of MEC have now been confirmed with characteristic molecular alterations involving CRTC1::MAML2 or CRTC1::MAML3 translocations. We here report a series of 7 trabecular variants of MEC which showed a predominant trabecular or nested pattern with either focal glandular differentiation or clear cell change and keloid-like fibrosis in the background. In addition, these tumors were either negative or showed only focal positivity for p63. Such features are not characteristic of known disease entities and resulted in an initial misdiagnosis of adenocarcinoma, not otherwise specified, or low-grade to intermediate-grade MEC with uncertainty. The patients' ages in our cohort ranged from 26 to 55 years with a female predominance (5/7). The tumors were located in the parotid gland (n=3), base of tongue (n=2), hard palate (n=1), and parapharyngeal space (n=1), with a median size of 1.5 cm. All 7 cases showed an MAML2 split pattern on fluorescence in situ hybridization analysis, and both RNA and whole-genome sequencing presented CRTC1::MAML2 translocation. All 7 cases showed a solid-predominant histology, and 3 cases displayed extracapsular extension. There were no other signs of high-grade histology and no recurrences or deaths occurred over a follow-up period of up to 79 months. We thus propose a unique trabecular variant of MEC that has atypical histologic and immunohistochemical features.

Parkinson's Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson's Disease Progression.

BACKGROUND: Identifying a meaningful progression metric for Parkinson's disease (PD) that reflects heterogeneity remains a challenge. OBJECTIVE: To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. METHODS: Using data from the Parkinson's Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains ("walking and balance"; "motor complications"; "cognition"; "autonomic dysfunction"; "functional dependence"; "activities of daily living"). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression. RESULTS: Half of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639). CONCLUSION: Clinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma.

BACKGROUND: The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA). METHODS: Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody. RESULTS: Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression. CONCLUSIONS: Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Risk of Bacterial Exposure to the Anesthesiologist's Face During Intubation and Extubation.

Introduction: Anesthesiologists are exposed to the risk of infection from various secretions or droplets from the respiratory tract of patients. We aimed to determine bacterial exposure to anesthesiologists' faces during endotracheal intubation and extubation. Methods: Six resident anesthesiologists performed 66 intubation and 66 extubation procedures in patients undergoing elective otorhinolaryngology surgeries. Sampling was performed by swabbing the face shields twice in an overlapping slalom pattern, before and after each procedure. Samples for pre-intubation and pre-extubation were collected immediately after wearing the face shield at the time of anesthesia induction and at the end of the surgery, respectively. Post-intubation samples were collected after the injection of anesthetic drugs, positive pressure mask ventilation, endotracheal intubation, and confirmation of intubation success. Post-extubation samples were collected after endotracheal tube suction, oral suction, extubation, and confirmation of spontaneous breathing and stable vital signs. All swabs were cultured for 48 h, and bacterial growth was confirmed by colony forming unit (CFU) count. Results: There was no bacterial growth in either pre- or post-intubation bacterial cultures. In contrast, while there was no bacterial growth in pre-extubation samples, 15.2% of post-extubation samples were CFU+ (0/66 [0%] vs 10/66 [15.2%], p=0.001). All the CFU+ samples belonged to 47 patients with post-extubation coughing, and the CFU count was correlated with the number of coughing episodes during the process of extubation (P < 0.01, correlation coefficient= 0.403). Conclusion: The current study shows the actual chance of bacterial exposure to the anesthesiologist's face during the patient awakening process after general anesthesia. Given the correlation between the CFU count and the number of coughing episodes, we recommend anesthesiologists to use appropriate facial protection equipment during this procedure.

Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study.

BACKGROUND: Emerging evidence shows that α-synuclein seed amplification assays (SAAs) have the potential to differentiate people with Parkinson's disease from healthy controls. We used the well characterised, multicentre Parkinson's Progression Markers Initiative (PPMI) cohort to further assess the diagnostic performance of the α-synuclein SAA and to examine whether the assay identifies heterogeneity among patients and enables the early identification of at-risk groups. METHODS: This cross-sectional analysis is based on assessments done at enrolment for PPMI participants (including people with sporadic Parkinson's disease from LRRK2 and GBA variants, healthy controls, prodromal individuals with either rapid eye movement sleep behaviour disorder (RBD) or hyposmia, and non-manifesting carriers of LRRK2 and GBA variants) from 33 participating academic neurology outpatient practices worldwide (in Austria, Canada, France, Germany, Greece, Israel, Italy, the Netherlands, Norway, Spain, the UK, and the USA). α-synuclein SAA analysis of CSF was performed using previously described methods. We assessed the sensitivity and specificity of the α-synuclein SAA in participants with Parkinson's disease and healthy controls, including subgroups based on genetic and clinical features. We established the frequency of positive α-synuclein SAA results in prodromal participants (RBD and hyposmia) and non-manifesting carriers of genetic variants associated with Parkinson's disease, and compared α-synuclein SAA to clinical measures and other biomarkers. We used odds ratio estimates with 95% CIs to measure the association between α-synuclein SAA status and categorical measures, and two-sample 95% CIs from the resampling method to assess differences in medians between α-synuclein SAA positive and negative participants for continuous measures. A linear regression model was used to control for potential confounders such as age and sex. FINDINGS: This analysis included 1123 participants who were enrolled between July 7, 2010, and July 4, 2019. Of these, 545 had Parkinson's disease, 163 were healthy controls, 54 were participants with scans without evidence of dopaminergic deficit, 51 were prodromal participants, and 310 were non-manifesting carriers. Sensitivity for Parkinson's disease was 87·7% (95% CI 84·9-90·5), and specificity for healthy controls was 96·3% (93·4-99·2). The sensitivity of the α-synuclein SAA in sporadic Parkinson's disease with the typical olfactory deficit was 98·6% (96·4-99·4). The proportion of positive α-synuclein SAA was lower than this figure in subgroups including LRRK2 Parkinson's disease (67·5% [59·2-75·8]) and participants with sporadic Parkinson's disease without olfactory deficit (78·3% [69·8-86·7]). Participants with LRRK2 variant and normal olfaction had an even lower α-synuclein SAA positivity rate (34·7% [21·4-48·0]). Among prodromal and at-risk groups, 44 (86%) of 51 of participants with RBD or hyposmia had positive α-synuclein SAA (16 of 18 with hyposmia, and 28 of 33 with RBD). 25 (8%) of 310 non-manifesting carriers (14 of 159 [9%] LRRK2 and 11 of 151 [7%] GBA) were positive. INTERPRETATION: This study represents the largest analysis so far of the α-synuclein SAA for the biochemical diagnosis of Parkinson's disease. Our results show that the assay classifies people with Parkinson's disease with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals before diagnosis. These findings suggest a crucial role for the α-synuclein SAA in therapeutic development, both to identify pathologically defined subgroups of people with Parkinson's disease and to establish biomarker-defined at-risk cohorts. FUNDING: PPMI is funded by the Michael J Fox Foundation for Parkinson's Research and funding partners, including: Abbvie, AcureX, Aligning Science Across Parkinson's, Amathus Therapeutics, Avid Radiopharmaceuticals, Bial Biotech, Biohaven, Biogen, BioLegend, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel, Coave, DaCapo Brainscience, 4D Pharma, Denali, Edmond J Safra Foundation, Eli Lilly, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, VanquaBio, Verily, Voyager Therapeutics, and Yumanity.

High visceral fat attenuation and long-term mortality in a health check-up population.

BACKGROUND: The prognostic role of increased visceral fat attenuation (VFA) remains underexplored. We investigated the long-term prognostic implications of computed tomography (CT)-derived VFA in a health check-up population. METHODS: This study included consecutive individuals who had positron-emission tomography/CT scans for health check-ups between January 2004 and December 2010. The primary outcome was overall survival (OS), and the secondary outcomes were cancer-specific survival (CSS) and non-cancer-specific survival (NCS). Commercially available body composition analysis software was used to obtain abdominal waist VFA, visceral fat volume index (VFI) and skeletal muscle index (SMI) at the L3 level. Sarcopenia was determined using sex-specific SMI references. VFA and VFI were dichotomized using the thresholds for the highest quartiles. The relationship between CT-derived body composition parameters and body mass index (BMI) was evaluated with Pearson correlation coefficients. The prognostic implications of VFA and sarcopenic obesity (SO) defined by VFA were assessed by multivariable Cox regression analysis and Kaplan-Meier plots with log-rank tests. RESULTS: A total of 2720 individuals (1530 men [56.3%] and 1190 women [43.7%]; median age: 53 years, inter-quartile range: 47-60 years) were included. During the median follow-up of 138 months, 128 individuals (5%) died (cancer mortality: 2%; non-cancer mortality: 3%), with 0.2% (5 of 2720) and 1.1% (30 of 2720) of 1- and 5-year mortality rates. VFA was negatively correlated with BMI (r = -0.62; P < 0.001) and VFI (r = -0.69; P < 0.001). After adjusting for clinical variables, sarcopenia and VFI, high VFA was a negative prognostic factor for OS (hazard ratio [HR]: 1.05 per Hounsfield unit; 95% confidence interval [CI]: 1.02, 1.08; P = 0.001), CSS (HR: 1.07 per Hounsfield unit; 95% CI: 1.02, 1.12; P = 0.006) and NCS (HR: 1.03 per Hounsfield unit; 95% CI: 1.01, 1.06; P = 0.009). Individuals with high VFA had higher high-sensitivity C-reactive protein levels than those with low VFA (0.11 vs. 0.03 mg/dL; P < 0.001). Individuals with SO defined by VFA had worse OS (9% vs. 4%; P < 0.001), CSS (3% vs. 2%; P = 0.02) and NCS (6% vs. 3%; P < 0.001) than those without SO, even in the same BMI (underweight-to-normal BMI, OS: 8% vs. 4%; overweight-to-obese BMI, OS: 38% vs. 4%; P < 0.001 in both) or VFI category (high VFI, OS: 43% vs. 6%; low VFI, OS: 8% vs. 3%; P < 0.001 in both). CONCLUSIONS: High VFA was associated with long-term mortality and low-grade inflammation. VFA can further stratify the current SO by BMI or VFI, and SO defined by VFA can identify individuals who are most vulnerable to long-term mortality.

Pulse Oximetry Imaging System Using Spatially Uniform Dual Wavelength Illumination.

Pulse oximetry is a non-invasive method for measuring blood oxygen saturation. However, its detection scheme heavily relies on single-point measurements. If the oxygen saturation is measured at a single location, the measurements are influenced by the profile of illumination, spatial variations in blood flow, and skin pigment. To overcome these issues, imaging systems that measure the distribution of oxygen saturation have been demonstrated. However, previous imaging systems have relied on red and near-infrared illuminations with different profiles, resulting in inconsistent ratios between transmitted red and near-infrared light over space. Such inconsistent ratios can introduce fundamental errors when calculating the spatial distribution of oxygen saturation. In this study, we developed a novel illumination system specifically designed for a pulse oximetry imaging system. For the illumination system, we customized the integrating sphere by coating a mixture of barium sulfate and white paint inside it and by coupling eight red and eight near-infrared LEDs. The illumination system created identical patterns of red and near-infrared illuminations that were spatially uniform. This allowed the ratio between transmitted red and near-infrared light to be consistent over space, enabling the calculation of the spatial distribution of oxygen saturation. We believe our developed pulse oximetry imaging system can be used to obtain spatial information on blood oxygen saturation that provides insight into the oxygenation of the blood contained within the peripheral region of the tissue.