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Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants., Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines., Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040)., Conclusion: The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, underscoring the urgent need for developing new therapies. The upregulation of TBK1 activity plays a crucial role in multiple pancreatic cancer-related signaling pathways, suggesting that inhibiting the kinase activity of TBK1 could be a promising strategy. Herein, we discovered a novel TBK1 inhibitor, LIB3S0280, using a structure-based virtual screening (SBVS) strategy. In the anti-proliferative and viability assays, LIB3S0280 showed significant inhibition against pancreatic cancer cell lines that highly express TBK1 with the GI 50 values of 2.24 and 4.71 μM and IC 50 values of 6.64 and 10.98 μM at 96 h. For the downstream targets, LIB3S0280 can inhibit TBK1 downstream signaling by decreasing the phosphorylation of IκBα and AKT better than a known TBK1 inhibitor, BX-795. Furthermore, PDAC cells were arrested in G 2 /M and underwent apoptosis or senescence with the treatment of LIB3S0280. These findings suggest that TBK1 inhibitor LIB3S0280 has great potential as a lead compound in the further development of a novel treatment for PDAC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Adrenocortical carcinoma (ACC) is a rare primary carcinoma originating in the adrenal gland with a poor prognosis and a high recurrence rate. This study evaluated the risk factors associated with recurrence in patients with early stage ACC after curative surgical resection., Methods: The present study retrospectively evaluated the risk factors for recurrence in 38 patients with stages 1 and 2 ACC who underwent curative resection between 1995 and 2020., Results: Recurrence was observed in 21 patients (55.3%), with no significant difference between stages 1 and 2 ACC (P = 0.640). The overall recurrence rate was higher in patients who underwent minimally invasive surgery than open adrenalectomy (71.4% vs. 51.6%). Of the 33 patients with gross tumor margins negative for malignancy, 16 (48.5%) experienced tumor recurrence, and all 5 patients with positive and unknown gross resection margins had recurrence. Recurrences were observed in 14 of the 30 patients (46.7%) negative for pathologic resection margins, 6 of the 7 patients (85.7%) with pathologically indeterminate margins, and 1 patient with pathologically positive margins., Conclusion: The recurrence rates are high even in patients with early stage ACC, being higher in patients who undergo minimally invasive surgery than open adrenalectomy. Obtaining clear resection margins during surgery may reduce tumor recurrence; however, gross or pathologic margin safety was not a secure factor in preventing recurrence. None of the factors analyzed was a definitive predictor of poor prognosis., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Backgruound: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients., Methods: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0-1, 2-3, 4-5, and 6-9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell's concordance index (C-index), and the Kaplan-Meier method., Results: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13)., Conclusion: mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Background: Adrenal incidentalomas (AI) are predominantly nonfunctional and benign, and their detection and differential diagnosis are aided by computed tomography (CT). A nonfunctioning adrenal incidentaloma (NFAI) usually requires regular follow-up; however, adrenalectomy may be necessary in certain patients. This study aimed to evaluate prognostic predictors to guide the treatment approach for AIs., Methods: This retrospective, single-center study involved patients diagnosed with NFAI from January 2000 to December 2020. Patients were divided into surgery and observation groups. A subgroup analysis compared malignant and benign adenoma within the surgery group., Results: A total of 307 patients were included, with 127 in the surgery group and 180 in the observation group. The surgery group displayed distinct morphological and malignant potential features in CT scans more frequently than the observational group did. The malignant subgroup exhibited more irregular borders on CT, and a higher number of patients with absolute washout under 60 % and relative washout under 40 % compared with the benign adenoma subgroup. Interestingly, within the surgery group, the mean tumor size was <4 cm for the both malignant and benign adenoma subgroups., Conclusions: Characterizing NFAI is important for appropriate treatment, as not all AIs have a favorable prognosis. CT findings associated with malignant potential, such as Hounsfield unit and washout values, were useful in determining the need for surgical treatment. However, the conventional criterion of a 4-cm size threshold for surgery was not a reliable malignancy predictor. Surgical resection should be considered for specific patient groups to ensure proper treatment over mere observation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Remimazolam is an ultrashort-acting benzodiazepine that is increasingly used for its efficacy in anesthesia induction and maintenance. However, limited research has explored its impact on intraoperative hypothermia compared to that of traditional inhalation anesthetics. This study aimed to compare the incidence of hypothermia during endoscopic nasal surgery when using remimazolam for maintenance anesthesia versus using inhalation anesthetics., Methods: This prospective study included 70 patients who underwent endoscopic nasal surgery under general anesthesia. The patients were randomly assigned to one of two groups: the inhalation anesthetic (IA) group (n=35), in which desflurane and nitrous oxide were administered, and the remimazolam (R) group (n=35), in which remimazolam and remifentanil were administered for anesthesia maintenance. The primary outcome was the incidence of intraoperative hypothermia, defined as an esophageal temperature below 36 °C during anesthesia., Results: The incidence of intraoperative hypothermia was significantly higher in the R group than in the IA group (P = 0.014). Furthermore, the temperature at the end of the surgery was significantly lower in the R group than in the IA group (P = 0.006). Additionally, the use of warming devices after surgery was more frequent in the R group than in the IA group (P = 0.047)., Conclusions: These findings suggest that the use of remimazolam for maintenance anesthesia during endoscopic nasal surgery increases the risk of intraoperative hypothermia compared to the use of inhalation anesthetics. This highlights the importance of temperature monitoring in patients receiving remimazolam to minimize the adverse outcomes associated with hypothermia during surgery., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background and Objective: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients., Methods: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed. We analyzed baseline characteristics and postoperative complications at discharge, 90 d, and 1 yr. We conducted propensity score matching (PSM; 1:1 ratio) and multivariable analyses to evaluate outcomes and risk factors for the occurrence of complications and higher Comprehensive Complication Index (CCI)., Key Findings and Limitations: Of 1755 patients, 1613 (91.9%) underwent LA and 142 (8.1%) underwent RA. Estimated blood loss, conversion rate, complication rate, and CCI at discharge, 90 d, and 1 yr were similar between the groups. However, RA was associated with a longer operative time in comparison to LA (100 vs 123 min; p < 0.001), but not after PSM (p = 0.120). Multivariable analysis revealed that Charlson comorbidity index (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.29; p = 0.001), and tumor size per 1-cm increment (OR 1.13, 95% CI 1.07-1.21; p < 0.001) were independently associated with the incidence of complications, but there was no significant difference in complication rates between the LA and RA groups (OR 1.09, 95% CI 0.63-1.87; p = 0.767). After PSM, RA was associated with a lower rate of severe (grade ≥3a) complications in comparison to LA (p = 0.023)., Conclusions and Clinical Implications: RA is a safe alternative to LA and yields similar outcomes for patients with pheochromocytoma. RA may be associated with a lower likelihood of severe complications. Further studies are warranted to determine the role of robotic surgery in pheochromocytoma., Patient Summary: Pheochromocytoma is a rare tumor in the adrenal gland and the gold-standard treatment is surgical removal. We assessed patient outcomes after robot-assisted surgery compared with laparoscopic surgery and found that outcomes are similar, but the rate of severe complications may be lower if a surgical robot is used., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Remimazolam is an ultrashort-acting benzodiazepine. Few studies have evaluated the effects of remimazolam-based total intravenous anesthesia (TIVA) on emergence agitation (EA). This study aimed to compare the incidence and severity of EA between TIVA using remimazolam and desflurane., Methods: This prospective randomized controlled study enrolled 76 patients who underwent nasal surgery under general anesthesia. Patients were randomized into two groups of 38 each: desflurane-nitrous oxide (N2O) (DN) and remimazolam-remifentanil (RR) groups. The same protocol was used for each group from induction to emergence, except for the use of different anesthetics during maintenance of anesthesia according to the assigned group: desflurane and nitrous oxide for the DN group and remimazolam and remifentanil for the RR group. The incidence of EA as the primary outcome was evaluated using three scales: Ricker Sedation-Agitation Scale, Richmond Agitation-Sedation Scale, and Aono's four-point agitation scale. Additionally, hemodynamic changes during emergence and postoperative sense of suffocation were compared., Results: The incidence of EA was significantly lower in the RR group than in the DN group in all three types of EA assessment scales (all P < 0.001). During emergence, the change in heart rate differed between the two groups (P = 0.002). The sense of suffocation was lower in the RR group than in the DN group (P = 0.027)., Conclusions: RR reduced the incidence and severity of EA in patients undergoing nasal surgery under general anesthesia. In addition, RR was favorable for managing hemodynamics and postoperative sense of suffocation.

Telomerase reverse transcriptase (TERT) promoter mutation is associated with an aggressive clinical course in thyroid carcinomas. Therefore, detection of TERT promoter mutation is essential for proper patient management. 5-Hydroxymethylcytosine (5hmC) is an epigenetic marker involved in the DNA demethylation pathway, and its loss has been observed in various tumors. Loss of 5hmC has also been reported in thyroid carcinomas and is presented as a possible predictive biomarker for TERT promoter mutation and worse prognosis. This study evaluated the expression of TERT and 5hmC by immunohistochemistry (IHC) in 105 patients (44 in the TERT mutant group and 61 in the TERT wild group) with various thyroid carcinomas. H-scores were calculated using an image analyzer. The median H-scores of TERT IHC were significantly higher in the TERT mutant group than in the TERT wild group (47.15 vs. 9.80). The sensitivity and specificity of TERT IHC for predicting TERT promoter mutations were 65.9 and 65.7 %, respectively. Regardless of TERT promoter mutation status, the 5hmC H-scores were markedly lower in all subtypes of thyroid carcinomas compared to those in their normal counterparts. Significant differences in 5hmC H-scores were observed between N0 and N1 in total thyroid carcinomas, but not within the papillary thyroid carcinoma subgroup. In conclusion, TERT and 5hmC IHC have limitations in predicting the presence of TERT promoter mutations. The expression of 5hmC was downregulated in various thyroid carcinomas compared to that in normal and benign lesions, but comprehensive further studies are required to elucidate the role of 5hmC in thyroid carcinomas., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest. This study was supported by a grant (2023IL0006) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. Methods: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan-Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. Results: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24-143 months). The mean VRR was 81% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA ( n = 33) or surgery ( n = 4) or left under observation ( n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared with nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183-4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms ( n = 4) or newly detected thyroid tumors ( n = 22), one benign and 21 malignant. The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. Conclusion: RFA is safe and effective for treating benign thyroid nodules, with a high VRR at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients.

Background: This systematic review and meta-analysis aimed to compare the effects of using phenylephrine or norepinephrine on the pH and base excess (BE) of the umbilical artery and vein in parturients undergoing cesarean section., Methods: The study protocol was registered in INPLASY. Independent researchers searched Ovid-Medline, Ovid-EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases and Google Scholar for relevant randomized controlled trials (RCTs). The primary outcome of this study was the umbilical artery (UA) or umbilical vein (UV) pH as neonatal condition at birth, and the secondary outcome was the UA or UV BE as an additional prognostic value over the measurement of umbilical pH., Results: There was no evidence of a difference between phenylephrine and norepinephrine for overall, UA, and UV pH (mean difference (MD) -0.001, 95% confidence interval (CI) -0.004 to 0.007; MD 0.000, 95%CI -0.004 to 0.004; and MD 0.002, 95%CI -0.013 to 0.017). There was also no evidence of a difference between phenylephrine and norepinephrine for overall, UA, and UV BE (MD 0.096, 95% CI -0.258 to 0.451; MD 0.076, 95%CI -0.141 to 0.294; and MD 0.121, 95%CI; -0.569 to 0.811). A meta-regression showed that factors such as umbilical artery or vein, infusion method, single or twin, and the number of parturients per study had no effect on the UA pH, UV pH, UA BE, or UV BE. No evidence of publication bias was detected., Conclusions: There was no evidence of a difference between phenylephrine and norepinephrine for umbilical pH and BE. A subgroup analysis and meta-regression also did not show evidence of differences.

Examining the toxicity of peptides is essential for therapeutic peptide-based drug design. Machine learning approaches are frequently used to develop highly accurate predictors for peptide toxicity prediction. In this paper, we present ToxTeller, which provides four predictors using logistic regression, support vector machines, random forests, and XGBoost, respectively. For prediction model development, we construct a data set of toxic and nontoxic peptides from SwissProt and ConoServer databases with existence evidence levels checked. We also fully utilize the protein annotation in SwissProt to collect more toxic peptides than using keyword search alone. From this data set, we construct an independent test data set that shares at most 40% sequence similarity within itself and with the training data set. From a quite comprehensive list of 28 feature combinations, we conduct 10-fold cross-validation on the training data set to determine the optimized feature combination for model development. ToxTeller's performance is evaluated and compared with existing predictors on the independent test data set. Since toxic peptides must be avoided for drug design, we analyze strategies for reducing false-negative predictions of toxic peptides and suggest selecting models by top sensitivity instead of the widely used Matthews correlation coefficient, and also suggest using a meta -predictor approach with multiple predictors., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience., Materials and Methods: This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LN A ) and venous phase (LN V ), LN A normalized to the common carotid artery (NAV CCA ), internal jugular vein (NAV IJV ), and sternocleidomastoid muscle (NAV SCM ), attenuation difference [AD; (LN A  - MAV SCM )], and relative washout ratio [((LN A  - LN V )/LN A ) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated., Results: Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83-0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LN V showed good diagnostic performance for metastatic LNs (AUC, 0.81-0.85). NAV CCA (0.85, 95% CI: 0.8-0.9) and AD (0.85, 95% CI: 0.81-0.89) had the highest AUCs. All quantitative parameters except for NAV IJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist., Conclusion: Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement., Clinical Relevance Statement: When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary., Key Points: Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%-20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL., Methods: In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114)., Results: In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738-0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567-0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65-111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival., Conclusion: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL., (© 2024 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Objective: To assess the metabolic effects of adrenalectomy in patients with mild autonomous cortisol secretion (MACS)., Background: Despite retrospective studies showing the association of adrenalectomy for MACS with beneficial metabolic effects, there have been only 2 randomized prospective studies with some limitations to date., Methods: A prospective, multicenter study randomized 132 patients with adrenal incidentaloma without any features of Cushing syndrome but with serum cortisol >50 nmol/L after a 1 mg overnight dexamethasone suppression test into an adrenalectomy group (n = 66) or control group (n = 66). The primary outcomes were changes in body weight, glucose, and blood pressure (BP)., Results: Among the 118 participants who completed the study with a median follow-up duration of 48 months (range: 3-66), the adrenalectomy group (n = 46) exhibited a significantly higher frequency of improved weight control, glucose control, and BP control (32.6%, 45.7%, and 45.7%, respectively) compared with the control group (n = 46; 6.5%, P = 0.002; 15.2%, P = 0.002; and 23.9%, P = 0.029, respectively) after matching for age and sex. Adrenalectomy [odds ratio (OR) = 10.38, 95% CI = 2.09-51.52, P = 0.004], body mass index (OR = 1.39, 95% CI = 1.08-1.79, P = 0.010), and cortisol after a 1 mg overnight dexamethasone suppression test levels (OR = 92.21, 95% CI = 5.30-1604.07, P = 0.002) were identified as independent factors associated with improved weight control. Adrenalectomy (OR = 5.30, 95% CI = 1.63-17.25, P = 0.006) and diabetes (OR = 8.05, 95% CI = 2.34-27.65, P = 0.001) were independently associated with improved glucose control. Adrenalectomy (OR = 2.27, 95% CI = 0.87-5.94, P = 0.095) and hypertension (OR = 10.77, 95% CI = 3.65-31.81, P < 0.001) demonstrated associations with improved BP control., Conclusions: adrenalectomy improved weight, glucose, and BP control in patients with MACS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The identification of an effective inhibitor is an important starting step in drug development. Unfortunately, many issues such as the characterization of protein binding sites, the screening library, materials for assays, etc., make drug screening a difficult proposition. As the size of screening libraries increases, more resources will be inefficiently consumed. Thus, new strategies are needed to preprocess and focus a screening library towards a targeted protein. Herein, we report an ensemble machine learning (ML) model to generate a CDK8-focused screening library. The ensemble model consists of six different algorithms optimized for CDK8 inhibitor classification. The models were trained using a CDK8-specific fragment library along with molecules containing CDK8 activity. The optimized ensemble model processed a commercial library containing 1.6 million molecules. This resulted in a CDK8-focused screening library containing 1,672 molecules, a reduction of more than 99.90%. The CDK8-focused library was then subjected to molecular docking, and 25 candidate compounds were selected. Enzymatic assays confirmed six CDK8 inhibitors, with one compound producing an IC 50 value of ≤100 nM. Analysis of the ensemble ML model reveals the role of the CDK8 fragment library during training. Structural analysis of molecules reveals the hit compounds to be structurally novel CDK8 inhibitors. Together, the results highlight a pipeline for curating a focused library for a specific protein target, such as CDK8., (© 2024 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Digital pathology uses digitized images for cancer research. We aimed to assess morphometric parameters using digital pathology for predicting recurrence in patients with papillary thyroid carcinoma (PTC) and lateral cervical lymph node (LN) metastasis. We analyzed 316 PTC patients and assessed the longest diameter and largest area of metastatic focus in LNs using a whole slide imaging scanner. In digital pathology assessment, the longest diameters and largest areas of metastatic foci in LNs were positively correlated with traditional optically measured diameters (R = 0.928 and R 2  = 0.727, p < 0.001 and p < 0.001, respectively). The optimal cutoff diameter was 8.0 mm in both traditional microscopic (p = 0.009) and digital pathology (p = 0.016) evaluations, with significant differences in progression-free survival (PFS) observed at this cutoff (p = 0.006 and p = 0.002, respectively). The predictive area's cutoff was 35.6 mm 2 (p = 0.005), which significantly affected PFS (p = 0.015). Using an 8.0-mm cutoff in traditional microscopic evaluation and a 35.6-mm 2 cutoff in digital pathology showed comparable predictive results using the proportion of variation explained (PVE) methods (2.6% vs. 2.4%). Excluding cases with predominant cystic changes in LNs, the largest metastatic areas by digital pathology had the highest PVE at 3.9%. Furthermore, high volume of LN metastasis (p = 0.001), extranodal extension (p = 0.047), and high ratio of metastatic LNs (p = 0.006) were associated with poor prognosis. Both traditional microscopic and digital pathology evaluations effectively measured the longest diameter of metastatic foci in LNs. Moreover, digital pathology offers limited advantages in predicting PFS of patients with lateral cervical LN metastasis of PTC, especially those without predominant cystic changes in LNs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Backgruound: We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB)., Methods: This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy., Results: Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system., Conclusion: Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.

The overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), commonly observed in neurodegenerative diseases like Alzheimer's disease (AD) and Down syndrome (DS), can induce the formation of neurofibrillary tangles (NFTs) and amyloid plaques. Hence, designing a selective DYRK1A inhibitor would result in a promising small molecule for treating neurodegenerative diseases. Developing selective inhibitors for DYRK1A has been a difficult challenge due to the highly preserved ATP-binding site of protein kinases. In this study, we employed a structure-based virtual screening (SBVS) campaign targeting DYRK1A from a database containing 1.6 million compounds. Enzymatic assays were utilized to verify inhibitory properties, confirming that Y020-3945 and Y020-3957 showed inhibitory activity towards DYRK1A. In particular, the compounds exhibited high selectivity for DYRK1A over a panel of 120 kinases, reduced the phosphorylation of tau, and reversed the tubulin polymerization for microtubule stability. Additionally, treatment with the compounds significantly reduced the secretion of inflammatory cytokines IL-6 and TNF-α activated by DYRK1A-assisted NFTs and Aβ oligomers. These identified inhibitors possess promising therapeutic potential for conditions associated with DYRK1A in neurodegenerative diseases. The results showed that Y020-3945 and Y020-3957 demonstrated structural novelty compared to known DYRK1A inhibitors, making them a valuable addition to developing potential treatments for neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Surgery for irreversible hyperparathyroidism is the preferred management for kidney transplant patients. The authors analyzed the factors associated with persistent hypercalcemia after parathyroidectomy in kidney transplant patients and evaluated the appropriate extent of surgery., Materials and Methods: The authors retrospectively analyzed 100 patients who underwent parathyroidectomy because of persistent hyperparathyroidism after kidney transplantation at a tertiary medical center between June 2011 and February 2022. Patients were divided into two groups: 22 with persistent hypercalcemia after parathyroidectomy and 78 who achieved normocalcemia after parathyroidectomy. Persistent hypercalcemia was defined as having sustained hypercalcemia (≥10.3 mg/dl) 6 months after kidney transplantation. The authors compared the biochemical and clinicopathological features between the two groups. Multivariate logistic regression analysis was used to identify potential risk factors associated with persistent hypercalcemia following parathyroidectomy., Results: The proportion of patients with serum intact parathyroid hormone (PTH) level is greater than 65 pg/ml was significantly high in the hypercalcemia group (40.9 vs. 7.7%). The proportion of patients who underwent less than subtotal parathyroidectomy was significantly high in the persistent hypercalcemia group (17.9 vs. 54.5%). Patients with a large remaining size of the preserved parathyroid gland (≥0.8 cm) had a high incidence of persistent hypercalcemia (29.7 vs. 52.6%). In the multivariate logistic regression analysis, the drop rate of intact PTH is less than 88% on postoperative day 1 (odds ratio 10.3, 95% CI: 2.7-39.1, P =0.001) and the removal of less than or equal to 2 parathyroid glands (odds ratio 6.8, 95% CI: 1.8-26.7, P =0.001) were identified as risk factors for persistent hypercalcemia., Conclusion: The drop rate of intact PTH is less than 88% on postoperative day 1 and appropriate extent of surgery for controlling the autonomic function were independently associated with persistent hypercalcemia. Confirmation of parathyroid lesions through frozen section biopsy or intraoperative PTH monitoring can be helpful in preventing the inadvertent removal of a parathyroid gland and achieving normocalcemia after parathyroidectomy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Robotic adrenalectomy has become a surgical treatment option for benign and selected malignant adrenal diseases. We aimed to evaluate the eligibility of two-port robotic posterior retroperitoneoscopic adrenalectomy (PRA) as an alternative to the conventional three-port technique by comparing their surgical outcomes. Materials and Methods: This retrospective cohort study compared the clinicopathological factors and surgical outcomes among 197 patients who underwent two-port or three-port robotic adrenalectomy between 2016 and 2020 in a single tertiary center. For further evaluation, propensity score matching was performed to reduce the selection bias in population characteristics. Results: Patients were categorized by the number of ports (two-port group, 87; and three-port group, 110). The two-port group compared with the three-port group was significantly older ( P  = .006) and had a smaller mean tumor size ( P  = .003) and shorter mean operation time ( P  = .001). Upon comparing clinicopathologic characteristics according to adrenal disorders, for pheochromocytoma, the three-port group had a larger tumor size and a longer operation time. For Cushing's syndrome, the operation time was short and numeric rating scale pain score was significantly low in the two-port group. After propensity score matching, the two-port group had a short operation time and a significantly low postoperative pain score ( P  < .05). Predictive factors associated with prolonged operation time included male gender, an increased number of ports, and large tumor size. Conclusions: The two-port technique resulted in a shorter operation time and lower pain score compared with the three-port technique. The two-port technique may be a safe alternative to the conventional three-port technique for robotic PRA.

Background: Adrenal computed tomography (CT) is a useful tool for locating adrenal lesion in primary aldosteronism (PA) patients. However, adrenal vein sampling (AVS) is considered as a gold standard for subtype diagnosis of PA. The aim of this study was to investigate the consistency of CT and AVS for the diagnosis of PA subtypes and evaluate the concordance of surgical outcomes., Materials and Methods: This retrospective study included 264 PA patients having both CT and AVS. Diagnostic consistency between CT and AVS was accessed, and clinical and biochemical outcomes were evaluated at 6 months after adrenalectomy., Results: Of all, 207 (78%) had a CT unilateral lesion, 31 (12%) CT bilateral lesion, and 26 (10%) CT bilateral normal findings. Among the CT unilateral lesion group, 138 (67%) had ipsilateral AVS lateralization. For CT bilateral lesion and bilateral normal, AVS unilateral lateralization was found in 17 (55%) and 2 (8%), respectively. The consistency between CT lesion and AVS lateralization including CT unilateral with AVS ipsilateral, and CT bilateral lesion with AVS bilateral patients was 63.8% (152/238). Of 77 patients with available data out of 138 patients who underwent adrenalectomy with consistency between CT and AVS, the clinical success rate was 96%, for 17 inconsistency patients out of 22 patients who underwent adrenalectomy, the clinical success rate was 94% after adrenalectomy following the lateralization result of AVS., Conclusion: CT is a useful tool to diagnose the adrenal lesion in PA patients. However, AVS is more sufficient to detect the unilateral PA subtype, which could provide curable treatment to surgical candidates of PA such that AVS can identify patients with contralateral PA in CT unilateral lesion and unilateral PA in CT bilateral lesion. The surgical outcome was successful when an adrenalectomy was performed according to the AVS lateralization result., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Silent pheochromocytoma refers to tumors without signs and symptoms of catecholamine excess. This study aimed to clarify the clinical, radiological characteristics, and perioperative features of silent pheochromocytomas diagnosed after adrenalectomy for adrenal incidentaloma., Methods: Medical records of patients who underwent adrenalectomy for adrenal incidentaloma and were subsequently diagnosed with silent pheochromocytoma between January 2000 and December 2020 were retrospectively reviewed for demographic, diagnostic, surgical, and pathological findings., Results: Of the 130 patients who underwent adrenalectomy for incidentaloma, 8 (6.1%) were diagnosed with silent pheochromocytoma. Almost all patients had no hypertensive symptoms and their baseline hormonal levels remained within normal ranges. All patients exhibited tumor size >4 cm, precontrast Hounsfield unit >10, and absolute washout <60%. Intraoperative hypertensive events were noted in 2 patients (25.0%) in whom antiadrenergic medications were not administered. All patients in the intraoperative hypertensive event group exhibited atypical features on CT, whereas 83.3% of patients in the non-intraoperative hypertensive event group showed atypical features on CT imaging., Conclusion: Silent pheochromocytomas share radiological traits with malignant adrenal tumors. Suspicious features on CT scans warrant surgical consideration for appropriate treatment. Administering alpha-blockers can enhance hemodynamic stability during adrenalectomy in suspected silent pheochromocytoma cases., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Background/purpose: Vertical root fracture (VRF) is a prevalent reason for tooth extraction following root canal treatment and even after crown placement. Predicting fractures is challenging due to multifactorial nature. The current study aimed to predict the likelihood of fracture following root canal treatment and crown placement by developing a deep learning (DL) model., Materials and Methods: DL techniques were employed to analyze a dataset comprising 145 clinical cases consisting of 97 fractured teeth and 48 non-fractured teeth. This dataset spanned a five-year period and encompassed cases involving root canal therapy and crown installation. The analysis identified several root fracture-related parameters, which were incorporated into the DL system. The dataset consisted of 17 features presented in a mixed-type tabular format., Results: The deep neural network (DNN) model surpassed the support vector machine (SVM) model with a higher accuracy (80.7 % vs. 71.7 %) and F1-score value (0.857 vs. 0.817) for predicting root fracture. Furthermore, in determining root fracture occurrence, it was observed that 17 significant characteristics in the DNN model outperformed the 7 features by 11.7 % in accuracy and 10 % in F1-score., Conclusion: DL shows promise in predicting root fracture post root canal therapy and prosthesis, and it may have the potential to aid clinicians in assessing fracture risk and improving decision-making., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Purpose: This study aimed to compare the diagnostic performances of 18 F-FDOPA PET/CT and 123 I-MIBG scintigraphy with SPECT/CT for detection of pheochromocytoma and paraganglioma (PPGL)., Patients and Methods: We conducted a prospective, single-institution comparative study. Patients suspected of having PPGL or those showing recurrence and/or distant metastasis of PPGL were enrolled. The primary objective was to affirm the noninferiority of 18 F-FDOPA PET/CT for diagnostic sensitivity. Both 123 I-MIBG scintigraphy with SPECT/CT (at 4 and 24 hours) and 18 F-FDOPA PET/CT (at 5 and 60 minutes after radiotracer administration) were performed. The final diagnosis was established either pathologically or via clinical follow-up. Nuclear physicians, unaware of the clinical data, undertook image analysis., Results: Thirty-two patients were evaluated: 14 of 21 with an initial diagnosis and 9 of 11 with recurrence/metastasis had PPGLs in their final diagnoses. In patient-based analyses, 18 F-FDOPA PET/CT (95.7%) exhibited noninferior sensitivity compared with 123 I-MIBG SPECT/CT (91.3%), within the predetermined noninferiority margin of -12% by a 95% confidence interval lower limit of -10%. Both modalities showed no significant difference in specificity (88.9% vs 88.9%). In the region-based analysis for the recurrence/metastasis group, 18 F-FDOPA PET/CT demonstrated significantly higher sensitivity compared with 123 I-MIBG SPECT/CT (86.2% vs 65.5%, P = 0.031) and superior interobserver agreement (κ = 0.94 vs 0.85). The inclusion of an early phase in dual-phase 18 F-FDOPA PET/CT slightly improved diagnostic performance, albeit not to a statistically significant degree., Conclusions: 18 F-FDOPA PET/CT demonstrated noninferior sensitivity and comparable specificity to 123 I-MIBG SPECT/CT in the diagnosing PPGL. Notably, in the assessment of PPGL recurrence and metastasis, 18 F-FDOPA PET/CT outperformed 123 I-MIBG SPECT/CT in terms of both sensitivity and interobserver agreement., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflict of interest. This research was partly supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea (grant number HR18C0016)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We investigated the impacts of computed tomography (CT) added to ultrasound (US) for preoperative evaluation of patients with papillary thyroid carcinoma (PTC) on staging, surgical extent, and postsurgical survival., Materials and Methods: Consecutive patients who underwent surgery for PTC between January 2015 and December 2015 were retrospectively identified. Of them, 584 had undergone preoperative additional thyroid CT imaging (CT + US group), and 859 had not (US group). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for 14 variables and balance the two groups. Changes in nodal staging and surgical extent caused by CT were recorded. The recurrence-free survival and distant metastasis-free survival after surgery were compared between the two groups., Results: In the CT + US group, discordant nodal staging results between CT and US were observed in 94 of 584 patients (16.1%). Of them, CT accurately diagnosed nodal staging in 54 patients (57.4%), while the US provided incorrect nodal staging. Ten patients (1.7%) had a change in the extent of surgery based on CT findings. Postsurgical recurrence developed in 3.6% (31 of 859) of the CT + US group and 2.9% (17 of 584) of the US group during the median follow-up of 59 months. After adjustment using IPTW (580 vs. 861 patients), the CT + US group showed significantly higher recurrence-free survival rates than the US group (hazard ratio [HR], 0.52 [95% confidence interval {CI}, 0.29-0.96]; P = 0.037). PSM analysis (535 patients in each group) showed similar HR without statistical significance (HR, 0.60 [95% CI, 0.31-1.17]; P = 0.134). For distant metastasis-free survival, HRs after IPTW and PSM were 0.75 (95% CI, 0.17-3.36; P = 0.71) and 0.87 (95% CI, 0.20-3.80; P = 0.851), respectively., Conclusion: The addition of CT imaging for preoperative evaluation changed nodal staging and surgical extent and might improve recurrence-free survival in patients with PTC., Competing Interests: Jeong Hyun Lee, the section editor, and Jung Hwan Baek, the editor board member of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. All authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Inhibiting a specific target in cancer cells and reducing unwanted side effects has become a promising strategy in pancreatic cancer treatment. MAP4K4 is associated with pancreatic cancer development and correlates with poor clinical outcomes. By phosphorylating MKK4, proteins associated with cell apoptosis and survival are translated. Therefore, inhibiting MAP4K4 activity in pancreatic tumours is a new therapeutic strategy. Herein, we performed a structure-based virtual screening to identify MAP4K4 inhibitors and discovered the compound F389-0746 with a potent inhibition (IC 50 120.7 nM). The results of kinase profiling revealed that F389-0746 was highly selective to MAP4K4 and less likely to cause side effects. Results of in vitro experiments showed that F389-0746 significantly suppressed cancer cell growth and viability. Results of in vivo experiments showed that F389-0746 displayed comparable tumour growth inhibition with the group treated with gemcitabine. These findings suggest that F389-0746 has promising potential to be further developed as a novel pancreatic cancer treatment.

Background: The optimal extent of surgery for unilateral papillary thyroid carcinoma (PTC) with contralateral nodules remains unclear. This study evaluated the long-term outcomes in a large cohort of patients with unilateral PTC and contralateral low-to-intermediate suspicious nodules who underwent lobectomy. Methods: This retrospective cohort study included patients with unilateral PTC who underwent lobectomy between January 2016 and December 2017 at Asan Medical Center in Korea. Patients were divided into two groups, those with and without contralateral nodules at the time of lobectomy: the Present group and the Absent group. All contralateral nodules observed at the time of surgery and during follow-up were evaluated. Results: The study cohort consisted of 1761 patients (1879 nodules), including 700 (39.8%) with and 1061 (60.2%) without contralateral nodules. The median size of the contralateral nodules was 0.5 cm. After a median follow-up of 59 months, the median growth of the contralateral nodules in the Present group was 0.1 cm (range, -3.4 to 4.7 cm). Of the contralateral nodules present at the time of lobectomy, 54.7% remained unchanged, decreased in size, or disappeared; whereas 14.8% increased ≥0.3 cm. Of the 700 patients with contralateral nodules, 20 (2.9%) were diagnosed with contralateral PTC. The 5-year contralateral PTC disease-free survival rates in patients with and without contralateral nodules were 98.2% and 99.3% ( p  = 0.003), respectively, whereas the 5-year recurrence-free survival rates did not differ significantly in these two groups. Of the 39 patients who underwent completion thyroidectomy, 2 (5.1%) experienced permanent hypocalcemia. Conclusions: Lobectomy may be a safe and feasible initial treatment option for patients with unilateral low-risk PTC and contralateral low-to-intermediate suspicious nodules.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hypothermia is common in patients undergoing urological surgery; however, no single preventative modality is completely effective. This study evaluated the effects of combining prewarming with intraoperative phenylephrine infusion for the prevention of hypothermia in patients undergoing urological surgery. Methods: This prospective study enrolled 58 patients scheduled for urological surgery under general anesthesia. The patients were randomized into two groups (n = 29). Patients in the experimental (prewarming and phenylephrine infusion) group (PP group) received prewarming for 20 min and intraoperative phenylephrine infusion, whereas those in the control group (C group) received no active prewarming with only intermittent administration of vasoactive agents. The patient's sublingual temperatures before and after anesthesia and nasopharyngeal temperature during anesthesia were recorded as core temperatures. Results: The incidence of intraoperative hypothermia was higher in the C group than in the PP group (57.7% [15/26] vs. 23.1% [6/26], P = 0.01). The severity of intraoperative hypothermia was higher in the C group than in the PP group ( P = 0.004). The nasopharyngeal temperature at the end of surgery was lower in the C group than in the PP group (35.8 ± 0.6°C vs. 36.3 ± 0.4°C, P = 0.002). The trend of core temperature decline during the first hour after anesthesia induction differed between the two groups ( P = 0.003; its decline was more gradual in the PP group). Conclusions: The combination of prewarming for 20 min and intraoperative phenylephrine infusion reduced the incidence and severity of intraoperative hypothermia and modified the trend of decreasing core temperatures in patients undergoing urological surgery., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Remifentanil and sufentanil are potent short-acting synthetic opioid analgesics. The administration of remifentanil has been associated with the incidence of opioid-induced hyperalgesia. Opioid-induced hyperalgesia may be alleviated when opioids, such as morphine, are switched to sufentanil. Therefore, this retrospective observational study aimed to compare the effects of remifentanil and sufentanil on postoperative pain in patients undergoing robotic gynecological surgery., Methods: We retrospectively analyzed the electronic medical records of patients who underwent elective robotic gynecological surgery between January 2016 and February 2021. The patients were classified into sufentanil (n = 159) or remifentanil (n = 359) groups according to the opioids administered continuously during anesthesia. The primary outcome assessed in this study was the postoperative pain score measured using the numeric rating scale (NRS). The secondary outcomes assessed included the recovery time (from discontinuation of opioid infusion to extubation) and frequency of rescue analgesic administration in the post-anesthesia care unit (PACU)., Results: The recovery time did not differ significantly between the two groups. The NRS score for pain (median [1Q, 3Q]) in the PACU was significantly lower in the sufentanil group than in the remifentanil group (2 [2, 3] vs. 4 [3, 7], P < 0.001). The frequency of rescue analgesic administration in the PACU was 6.3% and 35.4% in the sufentanil and remifentanil groups, respectively (P < 0.001)., Conclusions: Sufentanil, as an adjunct to sevoflurane anesthesia is more advantageous than remifentanil in terms of postoperative pain control during robotic gynecological surgery.

Objective: To evaluate the computed tomography (CT) features for diagnosing metastatic cervical lymph nodes (LNs) in patients with differentiated thyroid cancer (DTC) and validate the CT-based risk stratification system suggested by the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) guidelines., Materials and Methods: A total of 463 LNs from 399 patients with DTC who underwent preoperative CT staging and ultrasound-guided fine-needle aspiration were included. The following CT features for each LN were evaluated: absence of hilum, cystic changes, calcification, strong enhancement, and heterogeneous enhancement. Multivariable logistic regression analysis was performed to identify independent CT features associated with metastatic LNs, and their diagnostic performances were evaluated. LNs were classified into probably benign, indeterminate, and suspicious categories according to the K-TIRADS and the modified LN classification proposed in our study. The diagnostic performance of both classification systems was compared using the exact McNemar and Kosinski tests., Results: The absence of hilum (odds ratio [OR], 4.859; 95% confidence interval [CI], 1.593-14.823; P = 0.005), strong enhancement (OR, 28.755; 95% CI, 12.719-65.007; P < 0.001), and cystic changes (OR, 46.157; 95% CI, 5.07-420.234; P = 0.001) were independently associated with metastatic LNs. All LNs showing calcification were diagnosed as metastases. Heterogeneous enhancement did not show a significant independent association with metastatic LNs. Strong enhancement, calcification, and cystic changes showed moderate to high specificity (70.1%-100%) and positive predictive value (PPV) (91.8%-100%). The absence of the hilum showed high sensitivity (97.8%) but low specificity (34.0%). The modified LN classification, which excluded heterogeneous enhancement from the K-TIRADS, demonstrated higher specificity (70.1% vs. 62.9%, P = 0.016) and PPV (92.5% vs. 90.9%, P = 0.011) than the K-TIRADS., Conclusion: Excluding heterogeneous enhancement as a suspicious feature resulted in a higher specificity and PPV for diagnosing metastatic LNs than the K-TIRADS. Our research results may provide a basis for revising the LN classification in future guidelines., Competing Interests: Jeong Hyun Lee, the section editor, and Jung Hwan Baek, the editor board member of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. All authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Background: Femoral fracture repair surgery under general anesthesia is associated with postoperative pulmonary complications (PPCs). However, information on PPCs caused by residual neuromuscular blockade following perioperative use of neuromuscular blockers is limited. This study aimed to identify the differences in the incidence of PPCs according to the type of neuromuscular blockade reversal agent used in femoral fracture repair surgery, as well as the risk factors for PPCs., Methods: We retrospectively analyzed the electronic medical records of 604 patients aged >18 years who underwent general anesthesia for femoral fracture repair surgery at a single university hospital between March 2017 and March 2022. Patients in whom sugammadex or anticholinesterase was used to reverse the neuromuscular block were subjected to propensity score matching. Multivariate logistic regression analysis was performed to identify risk factors for PPCs., Results: Among the 604 patients, 108 were matched in each group. The incidence rates of PPCs overall and in the anticholinesterase and sugammadex groups were 7.0%, 8.3%, and 5.6%, respectively, with no significant differences between the groups. Older age, higher ASA (American Society of Anesthesiologists) physical status, and lower preoperative oxygen saturation were risk factors, whereas emergency surgery was a preventive factor., Conclusions: Our results demonstrated that the incidence of PPC did not differ significantly between sugammadex and anticholinesterase in patients undergoing femur fracture repair under general anesthesia. Identifying the risk factors and confirming complete recovery from neuromuscular blockade might be more important.

Isobaric labeling relative quantitation is one of the dominating proteomic quantitation technologies. Traditional quantitation pipelines for isobaric-labeled mass spectrometry data are based on sequence database searching. In this study, we present a novel quantitation pipeline that integrates sequence database searching, spectral library searching, and a feature-based peptide-spectrum-match (PSM) filter using various spectral features for filtering. The combined database and spectral library searching results in larger quantitation coverage, and the filter removes PSMs with larger quantitation errors, retaining those with higher quantitation accuracy. Quantitation results show that the proposed pipeline can improve the overall quantitation accuracy at the PSM and protein levels. To our knowledge, this is the first study that utilizes spectral library searching to improve isobaric labeling-based quantitation. For users to conveniently perform the proposed pipeline, we have implemented the feature-based filter being executable on both Windows and Linux platforms; its executable files, user manual, and sample data sets are freely available at https://ms.iis.sinica.edu.tw/comics/Software&#95;FPF.html . Furthermore, with the developed filter, the proposed pipeline is fully compatible with the Trans-Proteomic Pipeline., (© 2023. Springer Nature Limited.)

Background: The role of measuring serum thyroglobulin (Tg) levels in patients who have undergone lobectomy has not been proven. The goal of this research is to see if serum Tg levels can predict the recurrence of papillary thyroid carcinoma (PTC) after lobectomy., Methods: The 463 patients with 1-4 cm PTC who underwent lobectomy between January 2005 and December 2012, were included in this retrospective cohort study. Postoperative serum Tg levels and neck ultrasound were evaluated every 6-12 months after lobectomy during a median 7.8-year follow-up period. The receiver operating characteristic (ROC) curve and its area under the ROC curve (AUC) was used to assess the diagnostic performance of serum Tg levels., Results: During the follow-up, the structural recurrent disease was confirmed in 30 patients (6.5%). The serum Tg levels measured by initial Tg, maximal Tg, and last Tg did not differ statistically between the recurrence and non-recurrence groups. According to our findings, serial patterns of serum maximal Tg variations in 30 patients with recurrence showed no obvious trend and no rising trend toward recurrence before detecting recurrence. The AUC was 54.5% (IQR 43.1%-65.9%) in the ROC curve analysis, indicating that it was not significantly different from the random classifier., Conclusion: Serum Tg levels did not differ significantly between the recurrence and non-recurrence groups, and there was no tendency for the recurrence group to increase Tg levels. In patients with PTC who underwent lobectomy, monitoring Tg levels regularly provides little benefit in predicting recurrence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dantrolene sodium (DS) was first introduced as an oral antispasmodic drug. However, in 1975, DS was demonstrated to be effective for managing malignant hyperthermia (MH) and was adopted as the primary therapeutic drug after intravenous administration. However, it is difficult to administer DS intravenously to manage MH. MH is life-threatening, pharmacogenomically related, and induced by depolarizing neuromuscular blocking agents or inhalational anesthetics. All anesthesiologists should know the pharmacology of DS. DS suppresses Ca2+ release from ryanodine receptors (RyRs). RyRs are expressed in various tissues, although their distribution differs among subtypes. The anatomical and physiological functions of RyRs have also been demonstrated as effective therapeutic drugs for cardiac arrhythmias, Alzheimer's disease, and other RyR-related diseases. Recently, a new formulation was introduced that enhanced the hydrophilicity of the lipophilic DS. The authors summarize the pharmacological properties of DS and comment on its indications, contraindications, adverse effects, and interactions with other drugs by reviewing reference articles.

Prostate cancer is a prevalent malignancy among men globally, and androgen deprivation therapy is the conventional first-line treatment for metastatic prostate cancer. While androgen deprivation therapy is efficacious in castration-sensitive prostate cancer, it remains less effective in castration-resistant cases. Transcriptional dysregulation is a well-established hallmark of cancer, and targeting proteins involved in transcriptional regulation, such as cyclin-dependent kinase 8 (CDK8), has become an attractive therapeutic strategy. CDK8, a nuclear serine-threonine kinase, is a key component of the mediator complex and plays a critical role in transcriptional regulation. Recent studies have highlighted the promising role of CDK8 as a target in the treatment of metastatic prostate cancer. Our study assessed the efficacy of a novel CDK8 inhibitor, E966-0530-45418, which exhibited potent CDK8 inhibition (IC 50 of 129 nM) and high CDK8 selectivity. Treatment with E966-0530-45418 significantly inhibited prostate cancer cell migration and epithelial-to-mesenchymal transition (EMT) at both the RNA and protein levels. Further mechanistic analysis indicated that E966-0530-45418 suppresses prostate cancer metastasis by decreasing CDK8 activity and inhibiting TGF-β1-mediated Smad3/RNA polymerase II linker phosphorylation and Akt/GSK3β/β-catenin signaling. The results in animal model also showed that E966-0530-45418 exhibited anti-metastatic properties in vivo. Our study demonstrated that E966-0530-45418 has great therapeutic potential in the treatment of metastatic prostate cancer., Competing Interests: Conflict of interest statement The authors declare no competing financial interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Identifying hit compounds is an important step in drug development. Unfortunately, this process continues to be a challenging task. Several machine learning models have been generated to aid in simplifying and improving the prediction of candidate compounds. Models tuned for predicting kinase inhibitors have been established. However, an effective model can be limited by the size of the chosen training dataset. In this study, we tested several machine learning models to predict potential kinase inhibitors. A dataset was curated from a number of publicly available repositories. This resulted in a comprehensive dataset covering more than half of the human kinome. More than 2,000 kinase models were established using different model approaches. The performances of the models were compared, and the Keras-MLP model was determined to be the best performing model. The model was then used to screen a chemical library for potential inhibitors targeting platelet-derived growth factor receptor-β (PDGFRB). Several PDGFRB candidates were selected, and in vitro assays confirmed four compounds with PDGFRB inhibitory activity and IC 50 values in the nanomolar range. These results show the effectiveness of machine learning models trained on the reported dataset. This report would aid in the establishment of machine learning models as well as in the discovery of novel kinase inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cyclin-dependent protein kinase 8 (CDK8) plays important roles in regulating fibrotic growth factors and inflammatory signaling pathways. Long-term chronic inflammation of the lungs can lead to idiopathic pulmonary fibrosis (IPF). Abnormal alveolar epithelial regeneration leads to the release of various fibrotic growth factors and the activation of inflammatory cells. CDK8 regulates profibrotic cytokines broadly implicated in the pathogenesis of fibrosis. Therefore, inhibition of CDK8 is considered a promising strategy for treating IPF. Here, CDK8 inhibitors were designed and optimized using a fragment-based drug design strategy. Testing results revealed that 71% of the synthesized compounds inhibited CDK8 activity better than the original compound E966-0530. Of these compounds, compound 4k exhibited the strongest CDK8 enzyme-inhibiting activity (IC 50 =129 nM). Notably, it displayed a 13-fold increase in potency when compared to E966-0530. Experiments on toxicity and inhibition of epithelial-mesenchymal transition (EMT) protein expressions showed that compound 4k can inhibit EMT protein expressions, but with no significant cytotoxicity for alveolar epithelial cells. Compound 4k showed a potent inhibitory effect in cell migration assays. Furthermore, compound 4k significantly inhibited the phosphorylation of p-Smad3 and RNA Pol II, which are critical mediators in the fibrotic response signaling pathway. Compound 4k remarkably reduced TGF-β1-induced oxidative stress. The above results reveal optimized CDK8 inhibitors with potential use for IPF therapeutic treatment., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Percutaneous thermal ablation is a minimally invasive treatment for liver, kidney, lung, bone, and thyroid tumors. This treatment also has been used to treat adrenal tumors in patients, but there is no evidence for the efficacy of thermal ablation of adrenal cysts. The present study was performed to analyze the experience of a single center with percutaneous radiofrequency ablation (RFA) of adrenal cysts and to evaluate its efficacy. The present study enrolled all patients who underwent percutaneous RFA for unilateral adrenal cysts from 2019 to 2021. All patients underwent USG-guided percutaneous aspiration of cystic fluid, followed by RFA. A total nine patients with adrenal cysts were included in this study. All of them underwent technically successful percutaneous RFA, with no immediate complication. Follow-up CT 3 months after RFA showed that six of the nine adrenal cysts showed good responses, with reductions in cyst volume ranging from 86.4 to 97.9%. One patient had poor response in the cyst size (volume reduction rate 11.2%). She underwent secondary RFA with resulting that the cyst volume reduced by 91.1%. After a median follow-up period of 17.2 months, eight patients showed no evidence of regrowth. The patient, who showed evidence of regrowth, declined any other treatment and has been under regular surveillance. None of the nine patients developed adrenal insufficiency during the follow-up period. In conclusion, percutaneous RFA is a safe and effective minimally invasive treatment for adrenal cysts, suggesting that percutaneous RFA may be a good alternative option in selected patients., (© 2023. The Author(s).)

Cor triatriatum sinister is a rare congenital heart disease in which the left atrium is divided into two compartments by a fibromuscular membrane. In most cases, its symptoms appear in childhood, and it is rarely diagnosed in adulthood. Patients with cor triatriatum sinister are more prone to neurological diseases, such as cerebral infarction. Herein, we report the case of a patient whose cor triatriatum sinister went undiagnosed in the preoperative evaluation, but was diagnosed whilst investigating a cerebral infarction that occurred following a surgery in the beach chair position. It highlights the potential complications in otherwise healthy asymptomatic patients undergoing surgery in the beach chair position. Additionally, in high-risk patients, the provision of clear communication, in advance, regarding potential complications and their management, may reduce the patient's morbidity., (© 2022 Wiley Periodicals LLC.)

Purpose: The aim of this study was to assess the diagnostic role of fine-needle aspiration cytology (FNAC) and analyze factors associated with false-negative FNAC results in patients with parathyroid incidentaloma who were referred for ultrasonography (US)-guided fine-needle aspiration (FNA) of thyroid nodules., Methods: In this study, 121 patients with suspected parathyroid lesions were enrolled. The patients underwent US-guided FNAC with measurements of washout parathyroid hormone (PTH) between January 2015 and May 2020. The diagnostic performance of FNAC for the diagnosis of parathyroid lesions was assessed using surgical results and elevated washout PTH as a reference standard. The clinical and radiologic features associated with false-negative results on FNAC for the diagnosis of parathyroid lesions were evaluated., Results: Among the 121 nodules assessed, 38 were parathyroid lesions (31.4%), and 83 were non-parathyroid lesions (68.6%). The diagnostic performance of FNAC for parathyroid incidentaloma showed a sensitivity of 31.6% (12/38), specificity of 100% (83/83), positive predictive values of 100% (12/12), negative predictive values of 76.1% (83/109), and accuracy of 78.5% (95/121). The FNAC results of non-parathyroid lesions included thyroid nodules, lymph nodes, neurogenic tumors, and fat tissue. True-positive results on FNAC were significantly associated with performing FNA twice (58.3% vs. 23.1%, P=0.043)., Conclusion: Considering the low sensitivity of FNAC, measuring washout PTH in addition to FNAC may help accurately diagnose parathyroid incidentaloma on thyroid US. Further, the falsenegative rate for FNAC can be reduced by obtaining two or more FNA samples.

Bruton tyrosine kinase (BTK) is linked to multiple signalling pathways that regulate cellular survival, activation, and proliferation. A covalent BTK inhibitor has shown favourable outcomes for treating B cell malignant leukaemia. However, covalent inhibitors require a high reactive warhead that may contribute to unexpected toxicity, poor selectivity, or reduced effectiveness in solid tumours. Herein, we report the identification of a novel noncovalent BTK inhibitor. The binding interactions (i.e. interactions from known BTK inhibitors) for the BTK binding site were identified and incorporated into a structure-based virtual screening (SBVS). Top-rank compounds were selected and testing revealed a BTK inhibitor with >50% inhibition at 10 µM concentration. Examining analogues revealed further BTK inhibitors. When tested across solid tumour cell lines, one inhibitor showed favourable inhibitory activity, suggesting its potential for targeting BTK malignant tumours. This inhibitor could serve as a basis for developing an effective BTK inhibitor targeting solid cancers.

Objective: To evaluate the ultrasonography (US) features for diagnosing metastasis in cervical lymph nodes (LNs) in patients with thyroid cancer and compare the US classification of risk of LN metastasis between European and Korean guidelines., Materials and Methods: From January 2014 to December 2018, US-guided fine-needle aspiration was performed on 836 LNs from 714 patients for the preoperative nodal staging of thyroid cancer. The US features of LNs were retrospectively reviewed for the following features: size, presence of hilum, margin, orientation, cystic change, punctate echogenic foci (PEF), large echogenic foci, eccentric cortical thickening, abnormal vascularity, and cortical hyperechogenicity. A multiple logistic regression analysis was performed to identify the independent US features for the diagnosis of metastatic LNs. The diagnostic performance of independent US features was subsequently evaluated. LNs were categorized according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and European Thyroid Association (ETA) guidelines, and the correlation between the two sets of classifications was assessed., Results: Absence of the hilum, presence of cystic changes, PEF, abnormal vascularity, and cortical hyperechogenicity were independent US features of metastatic LNs. Cystic changes, PEF, abnormal vascularity, and cortical hyperechogenicity showed high specificity (86.8%-99.6%). The absence of the hilum had the highest sensitivity yet low specificity (66.4%). When LNs were classified according to the ETA guidelines and K-TIRADS, they yielded similar categorizations of malignancy risks and were strongly correlated (Spearman coefficient, 0.9766 [95% confidence interval, 0.973-0.979]). According to the ETA guidelines, 9.8% (82/836) of LNs were classified as "not specified.", Conclusion: Absence of hilum, cystic changes, PEF, abnormal vascularity, and cortical hyperechogenicity were independent US features suggestive of metastatic LNs in thyroid cancer. Both K-TIRADS and the ETA guidelines provided similar risk stratification for metastatic LNs with a high correlation; however, the ETA guidelines failed to classify 9.8% of LNs into a specific risk stratum. These results may provide a basis for revising LN classification in future guidelines., Competing Interests: Jung Hwan Baek and Jeong Hyun Lee who is on the editorial board of the Korean Journal of Radiology was not involved in the editorial evaluation or decision to publish this article. Financial activities not related to the present article. Consultant of two radiofrequency companies, STARmed and RF medical since 2017. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Korean Society of Radiology.)

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., (© 2022. Society of Surgical Oncology.)

Background: Adrenocortical carcinoma, a rare malignancy, has a poor prognosis, and the treatment modalities have not been well established. This study aimed to analyze the trend of treatment modalities and outcomes of patients with adrenocortical carcinoma., Methods: We retrospectively analyzed 94 patients with adrenocortical carcinoma between January 1995 and June 2020 for distributions according to the American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging, the yearly trend of demographic features, differences in multidisciplinary treatment, and prognostic outcomes. Multidisciplinary treatment included any combination of treatment including surgery, mitotane, chemotherapy or radiation., Results: The mean age and tumor size were 48.9 years and 11.7 cm, respectively. Fifteen patients (16.0%) underwent surgery only, and 56 (59.6%) underwent surgery with additional multidisciplinary treatments. Initial curative treatment was performed in all patients with stage 1 (n=5), 33 patients with stage 2 (n=34, 97.1%), 12 patients with stage 3 (n=19, 63.2%), and 11 patients with stage 4 (n=36, 30.6%) (P<0.0001). Two patients (40.0%) with stage 1 presented recurrence. In stages 2, 3, and 4, 57.6%, 58.3%, and 90.9% of patients who received curative treatment had recurrences, respectively. The annual trend presented statistical differences in mitotane use that have been increasing recently (P<0.0001)., Conclusions: Overall distribution of adrenocortical carcinoma stage was similar throughout the years. Although the rate of mitotane use in the treatment of patients with Adrenocortical carcinoma has increased over time, recurrences were common even after multidisciplinary curative treatment in all stages. The treatment effect and prognostic outcomes presented no promising progression even with adjuvant chemotherapy and mitotane use in addition to surgical treatment. Adrenocortical carcinoma still presented an extremely poor prognosis, and further prospective studies are needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-274/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Background: Short-term prewarming effectively reduces intraoperative hypothermia in adult patients. However, few data exist regarding its efficacy in elderly patients. Elderly people have a reduced ability to regulate their body temperature, which affects the efficacy of prewarming. This study aimed to compare the clinical efficacy of short-term pre-warming in elderly patients with that in adult patients. Methods: We enrolled 25 adult (20-50 years) and 25 elderly (> 65 years) patients scheduled for ureteroscopic stone surgery under general anaesthesia. All patients received preanaesthetic forced-air warming for 20 min. The core temperature was measured using an infrared tympanic thermometer during awakening and nasopharyngeal thermistors during anaesthesia. Incidence and severity of intraoperative hypothermia (< 36°C) was compared. Postoperative shivering and number of patients requiring active warming in the post-anaesthesia care unit were also assessed. Results: Intraoperative hypothermia was more frequent in elderly than in adult patients (58.3% vs . 12.0%; relative risk 2.6; 95% confidence interval 1.5 to 4.6; effect size h = 1.010; p = 0.001). The severity of intraoperative hypothermia showed a significant intergroup difference ( p = 0.002). Postoperative shivering was more frequent in elderly than in adult patients (33.3% vs . 8.0%, p = 0.037). A greater number of elderly patients in the post-anaesthesia care unit required active warming (33.3% vs . 8.0%, p = 0.037). Conclusions: The effects of short-term prewarming on the prevention of hypothermia and maintenance of perioperative normothermia are not the same in the elderly and adult patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: This study aimed to determine sonographic features and clinical significance of minor extrathyroidal extension (ETE) to the posterior thyroid capsule in papillary thyroid microcarcinoma (PTMC) patients., Methods: We retrospectively reviewed the records of 506 PTMC patients consisting of 151 patients with minor ETE and 355 patients without ETE. Significant clinicoradiologic features associated with ETE were identified by logistic regression analyses. The diagnostic performance of sonographic features, including the presence of capsular abutment, capsular abutment degree (< 25%, 25-50%, ≥ 50%), and protrusion, were assessed for the diagnosis of posterior minor ETE. Interobserver agreement was calculated., Results: PTMC patients with posterior minor ETE were more likely to have lymphovascular invasion and lateral neck lymph node metastasis (OR = 2.636, 95%CI: 1.754, 3.963 and OR = 2.897, 95%CI: 1.069, 7.848). Regarding the diagnostic performance, the capsular abutment yielded the highest sensitivity (81.5%), followed by ≥ 25% abutment, protrusion, and ≥ 50% abutment (57.0%, 21.9%, and 4.6%, respectively), with similar levels of diagnostic accuracy (71.3-75.1%). The specificity was highest for the sonographic feature of ≥ 50% abutment (99.7%), followed by protrusion, ≥ 25% abutment, and capsular abutment (97.8%, 82.0%, and 68.7%, respectively). Abutment assessment had a moderate interobserver agreement (K = 0.705), and abutment degree and protrusion assessment had a fair and slight interobserver agreement (K = 0.553 and 0.287)., Conclusions: Sonographic features of posterior capsular abutment are sensitive and reliable for diagnosis of posterior minor ETE and are associated with lymphovascular invasion and lateral neck lymph node metastasis in PTMC patients. The assessment of posterior minor ETE is important for considering candidates for active surveillance among PTMC patients., Key Points: • PTMC patients with posterior minor ETE were more likely to have lymphovascular invasion and lateral neck lymph node metastasis. • Sonographic features of posterior capsular abutment are sensitive and reliable for the diagnosis of posterior minor ETE. • The assessment of posterior minor ETE is important for considering candidates for active surveillance among PTMC patients., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Hyperparathyroidism is common in patients with chronic kidney disease with reduced renal function and has been observed after kidney transplantation. The optimal treatment for cases in which hyperparathyroidism persists after kidney transplantation has not been determined., Methods: This retrospective study included 83 patients with tertiary hyperparathyroidism who underwent kidney transplantation between 2000 and 2018 at a single tertiary center in Korea. Sixty-four patients underwent parathyroidectomy and 19 patients were treated with cinacalcet following renal transplantation. Biochemical parameters and clinical outcomes were compared between the two groups., Results: Serum calcium and parathyroid hormone (PTH) levels improved in both the parathyroidectomy and cinacalcet groups. One year after treatment, parathyroidectomy resulted in a lower mean serum calcium level than cinacalcet (9.7 ± 0.7 mg/dL vs. 10.5 ± 0.7 mg/dL, p = 0.001). Regarding serum PTH, the parathyroidectomy group showed a significantly lower PTH level than the cinacalcet group at 6 months (129.1 ± 80.3 pg/mL vs. 219.2 ± 92.5 pg/mL, p = 0.002) and 1 year (118.8 ± 75.5 pg/mL vs. 250.6 ± 94.5 pg/ mL, p &lt; 0.001). There was no statistically significant difference in the incidence of kidney transplant rejection, graft failure, cardiovascular events, fracture risk, or bone mineral density changes between the two groups., Conclusion: Parathyroidectomy appears to reduce PTH and calcium levels effectively in tertiary hyperparathyroidism. However, creatinine level and allograft rejection should be monitored closely.