Effectiveness of microvascular flow imaging for radiofrequency ablation in recurrent thyroid cancer: comparison with power Doppler imaging.

OBJECTIVES: To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA). METHODS: This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard. RESULTS: MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity. CONCLUSION: MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer. CLINICAL RELEVANCE STATEMENT: Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer. KEY POINTS: The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity.

Chronic Inflammation as an Underlying Mechanism of Ageing and Ageing-Related Diseases.

Age-related chronic inflammation is characterized as the unresolved low-grade inflammatory process underlying the ageing process and various age-related diseases. In this chapter, we review the age-related changes in the oxidative stress-sensitive pro-inflammatory NF-κB signaling pathways causally linked with chronic inflammation during ageing based on senoinflammation schema. We describe various age-related dysregulated pro- and anti-inflammatory cytokines, chemokines, and senescence-associated secretory phenotype (SASP), and alterations of inflammasome, specialized pro-resolving lipid mediators (SPM), and autophagy as major players in the chronic inflammatory intracellular signaling network. A better understanding of the molecular, cellular, and systemic mechanisms involved in chronic inflammation in the ageing process would provide further insights into the potential anti-inflammatory strategies.

Compound Heterozygous Mutations of SACS in a Korean Cohort Study of Charcot-Marie-Tooth Disease Concurrent Cerebellar Ataxia and Spasticity.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

TLR7 activation by miR-21 promotes renal fibrosis by activating the pro-inflammatory signaling pathway in tubule epithelial cells.

BACKGROUND: Toll-like receptor 7 (TLR7) is an endosomal TLR activated by single-stranded RNA, including endogenous microRNAs. Although TLR7 is known to promote inflammatory responses in pathophysiological conditions, its role in renal fibrosis has not been investigated. Here, we aim to investigate the inflammatory roles of TLR7 in kidney inflammation and fibrosis. METHODS: TLR7 knockout mice (Tlr7 -/-) subjected to AD-induced kidney injury were utilized to examine the role of TLR7 in kidney fibrosis. To elucidate the role of TLR7 in renal epithelial cells, NRK52E rat renal tubule epithelial cells were employed. RESULTS: Under fibrotic conditions induced by an adenine diet (AD), TLR7 was significantly increased in damaged tubule epithelial cells, where macrophages were highly infiltrated. TLR7 deficiency protected against AD-induced tubular damage, inflammation, and renal fibrosis. Under in vitro conditions, TLR7 activation increased NF-κB activity and induced chemokine expression, whereas TLR7 inhibition effectively blocked NF-κB activation. Furthermore, among the known TLR7 endogenous ligands, miR-21 was significantly upregulated in the tubular epithelial regions. In NRK52E cells, miR-21 treatment induced pro-inflammatory responses, which could be blocked by a TLR7 inhibitor. When the TLR7 inhibitor, M5049, was administered to the AD-induced renal fibrosis model, TLR7 inhibition significantly attenuated AD-induced renal inflammation and fibrosis. CONCLUSIONS: Overall, activation of TLR7 by endogenous miR-21 in renal epithelial cells contributes to inflammatory responses in a renal fibrosis model, suggesting a possible therapeutic target for the treatment of renal fibrosis. Video Abstract.

INF2 mutations in patients with a broad phenotypic spectrum of Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis.

Mutations in INF2 are associated with the complex symptoms of Charcot-Marie-Tooth disease (CMT) and focal segmental glomerulosclerosis (FSGS). To date, more than 100 and 30 genes have been reported to cause these disorders, respectively. This study aimed to identify INF2 mutations in Korean patients with CMT. This study was conducted with 743 Korean families with CMT who were negative for PMP22 duplication. In addition, a family with FSGS was included in this study. INF2 mutations were screened using whole exome sequencing (WES) and filtering processes. As the results, four pathogenic INF2 mutations were identified in families with different clinical phenotypes: p.L78P and p.L132P in families with symptoms of both CMT and FSGS; p.C104Y in a family with CMT; and p.R218Q in a family with FSGS. Moreover, different CMT types were observed in families with CMT symptoms: CMT1 in two families and Int-CMT in another family. Hearing loss was observed in two families with CMT1. Pathogenicity was predicted by in silico analyses, and considerable conformational changes were predicted in the mutant proteins. Two mutations (p.L78P and p.C104Y) were unreported, and three families showed de novo mutations that were putatively occurred from fathers. This study suggests that patients with INF2 mutations show a broad phenotypic spectrum: CMT1, CMT1 + FSGS, CMTDIE + FSGS, and FSGS. Therefore, the genotype-phenotype correlation may be more complex than previously recognized. We believe that this study expands the clinical spectrum of patients with INF2 mutations and will be helpful in the molecular diagnosis of CMT and FSGS.

Safety and feasibility of single-port surgery for posterior retroperitoneal adrenalectomy using the da Vinci SP robotic system: a retrospective cohort study.

BACKGROUND: This study demonstrates our experience of single-port robotic posterior retroperitoneal adrenalectomy (RPRA) using the da Vinci SP robot system and evaluates its technical feasibility and surgical outcomes. METHODS: We conducted a retrospective analysis of 250 RPRAs, including 117 conventional 3-port RPRAs, 103 reduced 2-port RPRAs, and 30 single-port RPRAs. Each RPRA type was compared by analyzing 30 patients in the early phase of surgery. RESULTS: All patients who underwent single-port RPRA showed excellent surgical outcomes. Age, sex, BMI, and tumor location site did not significantly differ between the three groups. In the early phase, the size of the adrenal tumor was similar between three groups, and it tended to increase as the number of ports increased (p < 0.001). The mean operation time was shorter for patients who underwent single-port RPRA than those who underwent RPRA types (p < 0.001). The numeric rating scale score did not significantly differ between the groups on most days. No major complications were observed, and no patients were converted to open surgery or required additional port insertion. CONCLUSION: Single-port RPA using the da Vinci SP robotic system showed the effectiveness of the surgical procedure and improved cosmetic outcomes for patients, while also enabling surgeons to perform operations with greater ease and convenience. Therefore, single-port RPRA could be a good alternative option for the treatment of adrenal tumors in selected situations.

Association between birth-related factors and periodontitis in women: Korea National Health and Nutrition Examination Survey 2013-2018.

AIM: Adult women experience several changes in physiological status, such as pregnancy and childbirth, during their life cycle. This study analyses the association between birth-related factors (the number of childbirths, abortions and miscarriages) and periodontitis using data from the Korea National Health and Nutrition Examination Survey, which represents Korean adults. MATERIALS AND METHODS: The study used data from Korea National Health and Nutrition Examination Survey VI and VII (2013-2018) and included 10,072 women 19 years or older, with no missing data on the variables assessed. Periodontitis was defined according to the Community Periodontal Index (CPI) criteria. Multiple logistic regression analysis, adjusting for age, household income, education, alcohol consumption, smoking, stress, body mass index, waist circumference, hypertension, diabetes mellitus, an oral examination within 1 year, daily tooth brushing frequency, hygiene products and self-perceived oral health as identified via logistic regression analyses, was performed to determine the association between birth-related variables and periodontitis. RESULTS: In the crude model, the odds ratio (OR) showed a significantly increased risk of periodontitis (CPI ≥ 3) and severe periodontitis (CPI = 4) based on the number of childbirths, abortions and miscarriages (p < .05). After covariate adjustment, periodontitis (CPI ≥ 3) was associated with the number of childbirths (1: OR = 1.92; 95% confidence interval [CI]: 1.47-2.50; 2: OR = 2.03; 95% CI: 1.57-2.61; ≥3: OR = 2.11; 95% CI: 1.60-2.78). Furthermore, severe periodontitis (CPI = 4) was also associated with the number of childbirths (1: OR = 2.33; 95% CI: 1.24-4.38; 2: OR = 2.99; 95% CI: 1.62-5.52; ≥3: OR = 3.34; 95% CI: 1.79-6.21). CONCLUSIONS: The findings of this large-scale, nationally representative study suggest that the number of childbirths is associated with the severity of periodontitis. However, the relationship between the number of abortions and miscarriages and periodontitis (CPI ≥ 3) or severe periodontitis (CPI = 4) is not significant.

Sex-Mediated Differences in TNF Signaling- and ECM-Related Gene Expression in Aged Rat Kidney.

Aging leads to the functional decline of an organism, which is associated with age and sex. To understand the functional change of kidneys depending on age and sex, we carried out a transcriptome analysis using RNA sequencing (RNA-Seq) data from rat kidneys. Four differentially expressed gene (DEG) sets were generated according to age and sex, and Gene Ontology analysis and overlapping analysis of Kyoto Encyclopedia of Genes and Genomes pathways were performed for the DEG sets. Through the analysis, we revealed that inflammation- and extracellular matrix (ECM)-related genes and pathways were upregulated in both males and females during aging, which was more prominent in old males than in old females. Furthermore, quantitative real-time PCR analysis confirmed that the expression of tumor necrosis factor (TNF) signaling-related genes, Birc3, Socs3, and Tnfrsf1b, and ECM-related genes, Cd44, Col3a1, and Col5a2, which showed that the genes were markedly upregulated in males and not females during aging. Also, hematoxylin-eosin (H&E) staining for histological analysis showed that renal damage was highly shown in old males rather than old females. In conclusion, in the rat kidney, the genes involved in TNF signaling and ECM accumulation are upregulated in males more than in females during aging. These results suggest that the upregulation of the genes may have a higher contribution to age-related kidney inflammation and fibrosis in males than in females.

Identification of potential biomarkers associated with meat tenderness in Hanwoo (Korean cattle): An expression quantitative trait loci analysis.

Meat tenderness is considered the most important trait contributing to beef quality, level of consumer satisfaction, willingness to pay premium prices and industry profit. Genomic selection method would be helpful for genetic improvement of traits with low heritability and that are difficult to measure. The identification of core genes can aid genomic selection for complex traits with low heritability that are difficult to measure. We performed statistical analysis of associations between longissimus dorsi muscle tenderness and gene expression in 20 Hanwoo cattle, using Warner-Bratzler shear force and RNAseq data, respectively. We found a total of 166 core genes, from which six (ASAP1, CAPN5, ELN, SUMF2, TTC8 and MGAT4A) were regulated by 16 cis-expression quantitative trait loci (eQTL) SNPs. Notably, we found that a cis-eQTL SNP of the ELN gene contained an MFZ-1 binding site in its putative promoter region. These findings provide useful information for genomic prediction of beef tenderness in Hanwoo cattle.

PPAR Pan Agonist MHY2013 Alleviates Renal Fibrosis in a Mouse Model by Reducing Fibroblast Activation and Epithelial Inflammation.

The peroxisome proliferator-activated receptor (PPAR) nuclear receptor has been an interesting target for the treatment of chronic diseases. Although the efficacy of PPAR pan agonists in several metabolic diseases has been well studied, the effect of PPAR pan agonists on kidney fibrosis development has not been demonstrated. To evaluate the effect of the PPAR pan agonist MHY2013, a folic acid (FA)-induced in vivo kidney fibrosis model was used. MHY2013 treatment significantly controlled decline in kidney function, tubule dilation, and FA-induced kidney damage. The extent of fibrosis determined using biochemical and histological methods showed that MHY2013 effectively blocked the development of fibrosis. Pro-inflammatory responses, including cytokine and chemokine expression, inflammatory cell infiltration, and NF-κB activation, were all reduced with MHY2013 treatment. To demonstrate the anti-fibrotic and anti-inflammatory mechanisms of MHY2013, in vitro studies were conducted using NRK49F kidney fibroblasts and NRK52E kidney epithelial cells. In the NRK49F kidney fibroblasts, MHY2013 treatment significantly reduced TGF-ß-induced fibroblast activation. The gene and protein expressions of collagen I and α-smooth muscle actin were significantly reduced with MHY2013 treatment. Using PPAR transfection, we found that PPARγ played a major role in blocking fibroblast activation. In addition, MHY2013 significantly reduced LPS-induced NF-κB activation and chemokine expression mainly through PPARß activation. Taken together, our results suggest that administration of the PPAR pan agonist effectively prevented renal fibrosis in both in vitro and in vivo models of kidney fibrosis, implicating the therapeutic potential of PPAR agonists against chronic kidney diseases.

Prognosis of Patients with 1-4 cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles.

BACKGROUND: This study was designed to evaluate the prognostic implication of gross extrathyroidal extension (ETE) invading the strap muscles after thyroid lobectomy in patients with 1-4 cm papillary thyroid cancer (PTC). METHODS: This retrospective cohort study included patients with 1-4 cm PTC who underwent thyroid lobectomy from 2005 to 2012. Overall, 595 patients were enrolled after excluding patients with aggressive variants of PTC, gross ETE into a major neck structure, and lateral cervical lymph node (LN) metastasis. We evaluated the risk factors for structural recurrence after lobectomy in 1-4 cm PTC. RESULTS: Seventy-eight patients (13.1%) had gross ETE invading only the strap muscles. During the median follow-up period of 7.7 years, structural recurrence was confirmed in 35 patients (5.9%). The presence of gross ETE was an independent risk factor for structural recurrence (hazard ratio 2.54, 95% confidence interval 1.19-5.44; p = 0.016). Subgroup analysis of patients with gross ETE showed that 11 and 47 patients had low- and intermediate-risk LN metastasis, respectively. A significant difference in recurrence-free survival was observed according to the degree of cervical LN metastasis (p = 0.03). Those without LN metastasis or low-risk LNs had a 75% lower risk of recurrence when compared with those with both gross ETE and intermediate-risk LNs. CONCLUSION: Gross ETE and intermediate-risk cervical LN metastasis were associated with a significantly high risk of recurrence after lobectomy in patients with 1-4 cm PTC. Completion thyroidectomy would be considered in this subgroup of patients but not in all patients with gross ETE invading only the strap muscles.

Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors.

Pevonedistat (TAK-924/MLN4924) is an investigational small molecule inhibitor of the NEDD8-activating enzyme that has demonstrated clinical activity across solid tumors and hematological malignancies. Here we report the results of a phase 1 study evaluating the effect of rifampin, a strong CYP3A inducer, on the pharmacokinetics (PK) of pevonedistat in patients with advanced solid tumors (NCT03486314). Patients received a single 50 mg/m2 pevonedistat dose via a 1-h infusion on Days 1 (in the absence of rifampin) and 10 (in the presence of rifampin), and daily oral dosing of rifampin 600 mg on Days 3-11. Twenty patients were enrolled and were evaluable for PK and safety. Following a single dose of pevonedistat at 50 mg/m2, the mean terminal half-life of pevonedistat was 5.7 and 7.4 h in the presence and in the absence of rifampin, respectively. The geometric mean AUC0-inf of pevonedistat in the presence of rifampin was 79% of that without rifampin (90% CI: 69.2%-90.2%). The geometric mean Cmax of pevonedistat in the presence of rifampin was similar to that in the absence of rifampin (96.2%; 90% CI: 79.2%-117%). Coadministration of pevonedistat with rifampin, a strong metabolic enzyme inducer, did not result in clinically meaningful decreases in systemic exposures of pevonedistat. The study results support the recommendation that no pevonedistat dose adjustment is needed for patients receiving concomitant CYP3A inducers. CLINICALTRIALS.GOV IDENTIFIER: NCT03486314.

Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype.

OBJECTIVE: Neurofilaments are the major scaffolding proteins for the neuronal cytoskeleton, and variants in NEFH have recently been described to cause axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC). METHODS: In this large observational study, we present phenotype-genotype correlations on 30 affected and 3 asymptomatic mutation carriers from eight families. RESULTS: The majority of patients presented in adulthood with motor-predominant and lower limb-predominant symptoms and the average age of onset was 31.0±15.1 years. A prominent feature was the development of proximal weakness early in the course of the disease. The disease progressed rapidly, unlike other Charcot-Marie-Tooth disease (CMT) subtypes, and half of the patients (53%) needed to use a wheelchair on average 24.1 years after symptom onset. Furthermore, 40% of patients had evidence of early ankle plantarflexion weakness, a feature which is observed in only a handful of CMT subtypes. Neurophysiological studies and MRI of the lower limbs confirmed the presence of a non-length-dependent neuropathy in the majority of patients.All families harboured heterozygous frameshift variants in the last exon of NEFH, resulting in a reading frameshift to an alternate open reading frame and the translation of approximately 42 additional amino acids from the 3' untranslated region (3'-UTR). CONCLUSIONS: This phenotype-genotype study highlights the unusual phenotype of CMT2CC, which is more akin to spinal muscular atrophy rather than classic CMT. Furthermore, the study will enable more informative discussions on the natural history of the disease and will aid in NEFH variant interpretation in the context of the disease's unique molecular genetics.

CEP41-mediated ciliary tubulin glutamylation drives angiogenesis through AURKA-dependent deciliation.

The endothelial cilium is a microtubule-based organelle responsible for blood flow-induced mechanosensation and signal transduction during angiogenesis. The precise function and mechanisms by which ciliary mechanosensation occurs, however, are poorly understood. Although posttranslational modifications (PTMs) of cytoplasmic tubulin are known to be important in angiogenesis, the specific roles of ciliary tubulin PTMs play remain unclear. Here, we report that loss of centrosomal protein 41 (CEP41) results in vascular impairment in human cell lines and zebrafish, implying a previously unknown pro-angiogenic role for CEP41. We show that proper control of tubulin glutamylation by CEP41 is necessary for cilia disassembly and that is involved in endothelial cell (EC) dynamics such as migration and tubulogenesis. We show that in ECs responding to shear stress or hypoxia, CEP41 activates Aurora kinase A (AURKA) and upregulates expression of VEGFA and VEGFR2 through ciliary tubulin glutamylation, as well as leads to the deciliation. We further show that in hypoxia-induced angiogenesis, CEP41 is responsible for the activation of HIF1α to trigger the AURKA-VEGF pathway. Overall, our results suggest the CEP41-HIF1α-AURKA-VEGF axis as a key molecular mechanism of angiogenesis and demonstrate how important ciliary tubulin glutamylation is in mechanosense-responded EC dynamics.

Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: A National Population-Based Cohort Study.

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.

Variants of aminoacyl-tRNA synthetase genes in Charcot-Marie-Tooth disease: A Korean cohort study.

Charcot-Marie-Tooth disease (CMT) and related diseases are a genetically and clinically heterogeneous group of peripheral neuropathies. Particularly, mutations in several aminoacyl-tRNA synthetase (ARS) genes have been reported to cause axonal CMT (CMT2) or distal hereditary motor neuropathy (dHMN). However, the common pathogenesis among CMT subtypes by different ARS gene defects is not well understood. This study was performed to investigate ARS gene mutations in a CMT cohort of 710 Korean families. Whole-exome sequencing was applied to 710 CMT patients who were negative for PMP22 duplication. We identified 12 disease-causing variants (from 13 families) in GARS1, AARS1, HARS1, WARS1, and YARS1 genes. Seven variants were determined to be novel. The frequency of overall ARS gene mutations was 1.22% among all independent patients diagnosed with CMT and 1.83% in patients negative for PMP22 duplication. WARS1 mutations have been reported to cause dHMN; however, in our patients with WARS1 variants, CMT was associated with sensory involvement. We analyzed genotype-phenotype correlations and expanded the phenotypic spectrum of patients with CMT possessing ARS gene variants. We also characterized clinical phenotypes according to ARS genes. This study will be useful for performing exact molecular and clinical diagnoses and providing reference data for other population studies.

The association between the type of anesthesia and hemodynamic instability during pheochromocytoma surgery: a retrospective cohort study.

BACKGROUND: Pheochromocytoma often carries a risk for perioperative hemodynamic instability (HDI). The aim of this study is to evaluate the risk factors of intraoperative HDI during minimally invasive posterior retroperitoneal adrenalectomy (PRA) for pheochromocytoma. MATERIALS AND METHODS: This retrospective study analyzed the prospectively collected data of 172 patients who underwent laparoscopic PRA or robotic PRA for pheochromocytoma between January 2014 and December 2020 at a single tertiary center. The patients were divided into two groups according to the intraoperative hypertensive event of systolic blood pressure (> 160 mmHg). The clinical manifestations and perioperative hemodynamic conditions were analysed. RESULTS: In the multivariate logistic regression analysis, the tumor size (> 3.4 cm) [OR 3.14, 95% confidence intervals (CI) (1.48-6.64), p = 0.003], type of preoperative alpha-blocker (selective type) [OR 3.9, 95% CI (1.52-10.02), p = 0.005], preoperative use of beta-blockers [OR 3.94, 95% CI (1.07-14.49), p = 0.039] and type of anesthesia [total intravenous anesthesia (TIVA) vs. balanced anesthesia (BA)] [OR 2.57, 95% CI (1.23-5.38), p = 0.012] were determined as independent risk factors of intraoperative hypertensive events during minimally invasive adrenalectomy. CONCLUSIONS: The type of anesthesia was independently associated with intraoperative HDI along with larger tumor size, type of preoperative alpha-blocker and the use of preoperative beta-blockers. TIVA increased the risk of intraoperative hypertensive events compared with BA. Thus, the consideration of the type of anesthesia prior to adrenal surgery for pheochromocytoma along with the use of preoperative non-selective alpha-blockers may be beneficial in minimizing the risk of intraoperative HDI.

Thyroid-dedicated internally-cooled wet electrode for benign thyroid nodules: experimental and clinical study.

BACKGROUND: To assess the effects of radiofrequency ablation (RFA) using an internally-cooled wet (ICW) electrode in ex vivo bovine liver and evaluate the feasibility of the ICW electrode for benign thyroid nodules. METHODS: We developed an 18-gauge ICW electrode with a microhole at the distal tip for tissue infusion of chilled (0 - 4 °C) isotonic saline (rate = 1.5 ml/min). RFA using ICW and IC electrodes were performed in bovine livers (40 pairs, 1-cm active tip, 50 W, 1-min). We compared the morphological characteristics of ablation zones and presence of carbonization. Twenty patients with benign thyroid nodules larger than 5 ml were prospectively enrolled in a clinical study and underwent ultrasound-guided RFA with ICW electrodes. Ultrasound examinations, laboratory data, and symptom and cosmetic scores were evaluated preprocedure and 1 and 6 months after the procedure. RESULTS: In the ex vivo study, the ICW achieved significantly larger ablation zones than the IC (p<.001). In the clinical study, ICW electrodes were tolerable in all patients. At last follow-up, nodule volume had decreased from 15.6 ± 12.1 ml to 4.1 ± 4.3 ml (p<.001), and the mean volume reduction ratio (VRR) was 73.3 ± 13.7% at 6.0 months follow-up. Cosmetic and symptom scores were reduced from 3.52 ± 1.03 to 2.65 ± 0.88 and 3.10 ± 2.17 to 0.85 ± 0.99 (both p<.001), respectively. After RFA, thyroid function was well preserved in all patients, and mean thyroglobulin level decreased from 36.6 ± 52.1 ng/ml to 26.9 ± 62.2 ng/ml. One patient experienced a temporary voice change that recovered within a week. CONCLUSIONS: We developed a thyroid-dedicated ICW electrode that we showed to be feasible and effective in patients with benign thyroid nodules.

Clinical Characteristics of 40 Patients Infected With the SARS-CoV-2 Omicron Variant in Korea.

Since severe acute respiratory syndrome-coronavirus-2 variant B.1.1.529 (omicron) was first reported to the World Health Organization on November 24, 2021, the cases of the omicron variant have been detected in more than 90 countries over the last month. We investigated the clinical and epidemiological characteristics of the first 40 patients with the omicron variant who had been isolated at the National Medical Center in South Korea during December 4-17, 2021. The median age of the patients was 39.5 years. Twenty-two patients (55%) were women. Seventeen patients (42.5%) were fully vaccinated, and none were reinfected with the omicron. Eighteen (45%) had recent international travel history. Half of the patients (19, 47.5%) were asymptomatic, while the others had mild symptoms. Six patients (15%) showed lung infiltrations on chest image; however, none required supplemental oxygen. These mild clinical features are consistent with recent case reports on the omicron variant from other countries.

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults.

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND50) titers in serum samples. ND50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0-12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7-294.0]) and delta (24.3 [14.3-81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.