Delineation of the substrate recognition domain of MARCHF6 E3 ubiquitin ligase in the Ac/N-degron pathway and its regulatory role in ferroptosis.

Nα-terminal acetylation in eukaryotic proteins creates specific degradation signals (Ac/N-degrons) targeted for ubiquitin-mediated proteolysis via the Ac/N-degron pathway. Despite the identification of key components of the Ac/N-degron pathway over the past 15 years, the precise recognition domain (Ac/N domain) remains unclear. Here, we defined the Ac/N domain of the endoplasmic reticulum MARCHF6 E3 ubiquitin ligase through a systematic analysis of its cytosol-facing regions using alanine-stretch mutagenesis, chemical crosslinking-based co-immunoprecipitation-immunoblotting, and split-ubiquitin assays in human and yeast cells. The Ac/N domain of MARCHF6 exhibits preferential binding specificity to Nα-terminally acetylated proteins and peptides over their unacetylated counterparts, mediating the degradation of Ac/N-degron-bearing proteins, such as the G-protein regulator RGS2 and the lipid droplet protein PLIN2. Furthermore, abolishing the recognition of Ac/N-degrons by MARCHF6 stabilized RGS2 and PLIN2, thereby increasing the resistance to ferroptosis, an iron-dependent lipid peroxidation-mediated cell death. These findings provide mechanistic and functional insights into how MARCHF6 serves as a rheostatic modulator of ferroptosis by recognizing Ac/N-degron substrates via its Ac/N domain and non-Ac/N-degron substrates via distinct recognition sites.

Detection of Nα-terminally formylated native proteins by a pan-N-formyl methionine-specific antibody.

N-formyl methionine (fMet)-containing proteins are produced in bacteria, eukaryotic organelles mitochondria and plastids, and even in cytosol. However, Nα-terminally formylated proteins have been poorly characterized because of the lack of appropriate tools to detect fMet independently of downstream proximal sequences. Using a fMet-Gly-Ser-Gly-Cys peptide as an antigen, we generated a pan-fMet-specific rabbit polyclonal antibody called anti-fMet. The raised anti-fMet recognized universally and sequence context-independently Nt-formylated proteins in bacterial, yeast, and human cells as determined by a peptide spot array, dot blotting, and immunoblotting. We anticipate that the anti-fMet antibody will be broadly used to enable an understanding of the poorly explored functions and mechanisms of Nt-formylated proteins in various organisms.

Social network analysis for medical narcotics in South Korea: focusing on patients and healthcare organizations.

BACKGROUND: Medical narcotics must be administered under medical supervision because of their potential for misuse and abuse, leading to more dangerous and addictive substances. The control of medical narcotics requires close monitoring to ensure that they remain safe and effective. This study proposes a methodology that can effectively identify the overprescription of medical narcotics in hospitals and patients. METHODS: Social network analysis (SNA) was applied to prescription networks for medical narcotics. Prescription data were obtained from the Narcotics Information Management System in South Korea, which contains all data on narcotic usage nationwide. Two-mode networks comprising hospitals and patients were constructed based on prescription data from 2019 to 2021 for the three most significant narcotics: appetite suppressants, zolpidem, and propofol. Two-mode networks were then converted into one-mode networks for hospitals. Network structures and characteristics were analyzed to identify hospitals suspected of overprescribing. RESULTS: The SNA identified hospitals that overprescribed medical narcotics. Patients suspected of experiencing narcotic addiction seek treatment in such hospitals. The structure of the network was different for the three narcotics. While appetite suppressants and propofol networks had a more centralized structure, zolpidem networks showed a less centralized but more fragmented structure. During the analysis, two types of hospitals caught our attention: one with a high degree, meaning that potential abusers have frequently visited the hospital, and the other with a high weighted degree, meaning that the hospital may overprescribe. For appetite suppressants, these two types of hospitals matched 84.6%, compared with 30.0% for propofol. In all three narcotics, clinics accounted for the largest share of the network. Patients using appetite suppressants were most likely to visit multiple locations, whereas those using zolpidem and propofol tended to form communities around their neighborhoods. CONCLUSIONS: The significance of this study lies in its analysis of nationwide narcotic use reports and the differences observed across different types of narcotics. The social network structure between hospitals and patients varies depending on the composition of the medical narcotics. Therefore, these characteristics should be considered when controlling medication with narcotics. The results of this study provide guidelines for controlling narcotic use in other countries.

A study on the 10-year trend of surgeries performed for lumbar disc herniation and comparative analysis of prescribed opioid analgesics and hospitalization duration: 2010-2019 HIRA NPS Data.

BACKGROUND: This study, utilizing the claims data from the Health Insurance Review and Assessment Service of Korea, aimed to examine the 10-year (2010-2019) trends in various types of lumbar spine surgeries performed on patients diagnosed with lumbar herniated intervertebral disc (HIVD), and the current status of opioid prescriptions, as well as the duration of postoperative hospital stays based on the type of surgery performed. METHOD: This retrospective cross-sectional study examined patients with one or more national health insurance claims carrying a primary or secondary diagnosis of HIVD (ICD-10 codes: M511, M518, M519) over a 10-year period (2010-2019). From the patients undergoing lumbar spine surgery, we selected those who did not require reoperation within 30 days following the initial lumbar surgery. Our final study sample comprised patients who underwent only one type of surgery. RESULTS: Among the patients diagnosed with HIVD and subsequently undergoing lumbar surgery between 2010 and 2019, a slight downward trend was observed in those undergoing open discectomy (OD); however, OD persistently accounted for the highest proportion over the 10 years. Percutaneous endoscopic lumbar discectomy (PELD) demonstrated a consistent upward trend from 2016 to 2018. When inspecting trends, we noted a consistent escalation over the decade in the postoperative opioid prescription rates of strong opioids (50.7% in 2010 to 77.8% in 2019) and tramadol (50.9% in 2010 to 76.8% in 2019). Analyzing these trends by surgery type, spinal fusion exhibited a slightly higher rate of opioid prescriptions than other lumbar surgeries. Regarding the length of postoperative hospital stays, patients undergoing PELD recorded the shortest stay (7.04 ± 6.78 days), while spinal fusion necessitated the longest (20.14 ± 12.18 days). CONCLUSION: This study analyzed the trends in types of lumbar spine surgeries, opioid analgesic prescriptions, and length of hospital stays over 10 years (2010-2019) among patients with HIVD in Korea. Our data and findings provide valuable evidence that may prove beneficial for clinicians and researchers involved in HIVD-related practices.

Clinical features of retinopathy after cardiopulmonary resuscitation.

PURPOSE: To evaluate the clinical patterns of retinopathy in patients who received cardiopulmonary resuscitation (CPR) using wide-field fundus photography and slit-lamp fundus examination. METHODS: The medical records of patients aged ≥ 18 years who survived after receiving CPR and underwent wide-field fundus photography and slit-lamp fundus examination within 3 months were retrospectively analyzed. Fundus findings, including retinal hemorrhage and cotton wool spots, were investigated. The subjects were categorized into the retinopathy and non-retinopathy groups based on the presence of fundus findings. Systemic and CPR-related factors were analyzed to compare the two groups. RESULTS: Twenty eyes (10 patients) and 28 eyes (14 patients) were included in the retinopathy and non-retinopathy groups, respectively. The retinopathy group had longer CPR time than the non-retinopathy group (15 ± 11 min vs. 6 ± 5 min, p = 0.027). In the retinopathy group, retinal nerve fiber layer hemorrhage was observed in all eyes, and intraretinal hemorrhage was observed in 55% of the eyes. 80% of hemorrhages were located in the peripapillary or posterior pole. There were no interval changes in visual acuity, intraocular pressure, and central retinal thickness for 6 months. The average remission periods of retinal hemorrhage and cotton wool spots were 6.8 ± 2.6 month and 5.6 ± 2.1 months, respectively. No retinopathy progression was observed. CONCLUSION: The signs of retinopathy, such as retinal hemorrhages and cotton wool spots, which are found after CPR, mainly occur in patients who receive longer time of CPR and improve over time.

Narcotics information management system in South Korea: system development and innovation.

BACKGROUND: As the misuse and abuse of medical narcotics are increasing in South Korea, an information system for the integrated information management of medical narcotic drugs across the nation is needed. This paper presents the development process of the Narcotics Information Management System (NIMS) for the monitoring of medical narcotics usage and the results of its implementation. METHODS: As the NIMS enforces that all narcotics handlers digitally report all information on handling medical narcotic drugs, the functional requirements of the NIMS have been identified in accordance with the Narcotics Control Act. In addition to the functional requirements, the non-functional requirements of the NIMS have been elicited by major narcotics handlers and their associations. The non-functional requirements include privacy, availability, connectivity, interoperability, and data integrity. The system design with entity-relationship diagrams and its implementation processes have been presented. RESULTS: The NIMS encompasses all narcotic handlers, which comprise exporting, importing, and pharmaceutical companies; wholesalers; hospitals and clinics; and pharmacies, collecting over 120 million cases annually. It enables transparent monitoring throughout the life cycle, from manufacturing, sales, purchase, and disposal of narcotics. As a result, the number of prescriptions for medical narcotics has been reduced by 9.2%. CONCLUSIONS: To the best of our knowledge, the NIMS is the world's first system to manage all information on the total life cycle of medical narcotics, including imports, production, distribution, use, and disposal of drugs. This system has enabled the safety management and monitoring of medical narcotic drugs. Additionally, it provides consistent and transparent information to physicians and patients, leading to the autonomous safety management of narcotics. The successful development of the NIMS can provide guidelines for implementing a narcotics management system in other countries.

Risk Factors for Feeding Tube Dependency in Patients Undergoing Function Preservation Surgery for Advanced-Stage Laryngohypopharyngeal Cancer.

Dysphagia and feeding tube dependency commonly occur in patients with laryngeal or hypopharyngeal cancer (LHC) during and after treatment, often leading to poor functional outcomes. Therefore, we examined the factors related to feeding tube dependency among advanced-stage LHC patients undergoing curative surgery. This study included 69 consecutive patients who underwent conservative surgery for previously untreated, advanced-stage LHC (squamous cell carcinoma) between 2006 and 2016. Persistent feeding tube dependency was defined as 1 year or more after treatment completion. Binary logistic regression analysis was used to determine the factors associated with reactive prolonged and persistent feeding tube dependency. Cox proportional hazard regression analysis was used to determine the association between feeding tube dependency and survival. None of the study patients had a prophylactic feeding tube, but 15 (21.7%) patients had reactive feeding tube placement for 3 months or more. A total of 9 (13.0%) patients had persistent feeding tube dependency. Univariate analysis showed that age, tracheostomy, and common terminology criteria for adverse events (CTCAE) ≥ 3 were significantly associated with reactive prolonged and persistent feeding tube dependency (all P < 0.05). In the multivariate analysis, advanced age and CTCAE ≥ 3 remained the independent factors of reactive prolonged and persistent feeding tube dependency (all P < 0.05). Feeding tube dependency was not associated with overall survival or disease-free survival (P > 0.1). Feeding tube dependency might be related to clinical factors, such as age and severe adverse events, in the patients undergoing function-preserving surgery for advanced-stage LHC.

Asymmetric transepicondylar axis between varus and valgus osteoarthritic knees in windswept deformity can be predicted by hip-knee-ankle angle difference.

PURPOSE: Studies regarding the best strategy to determine appropriate femoral component rotation during bilateral total knee arthroplasty (TKA) in wind swept deformities (WSD) are very limited. The purpose of this study was (1) to evaluate whether femoral rotational profiles differ between varus and valgus osteoarthritic knees in WSD and (2) to analyze the correlation between femoral rotational profiles and coronal radiologic parameters. METHODS: A total of 40 patients who were diagnosed with bilateral knee osteoarthritis with WSD between January 2010 and December 2020 at a single institution were retrospectively reviewed. On axial computed tomography scans, femoral rotational profile parameters such as the clinical transepicondylar axis (cTEA) and anterior-posterior (AP) axis were compared between valgus and varus osteoarthritic knees. In standing full-limb AP radiographs, coronal radiographic parameters including hip-knee-ankle angle (HKA), valgus correction angle (VCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured in both knees. The correlation between the varus-valgus cTEA difference, and differences in coronal radiologic parameters was analyzed. RESULTS: In valgus osteoarthritic knees, cTEA was significantly increased compared to varus osteoarthritic knees by 1.5° (valgus: 7.65° ± 1.82°, varus: 6.15° ± 1.58°, p < 0.001). All coronal radiologic parameters, including HKA, LDFA, MPTA, JLCA, and VCA, were significantly different between valgus and varus knees. In correlation analysis, the varus-valgus cTEA difference was significantly correlated with LDFA (r = 0.365, p = 0.021), MPTA (r = 0.442, p = 0.004), and HKA differences (r = 0.693, p < 0.001), with the HKA difference showing the strongest correlation with the cTEA difference. CONCLUSION: In bilateral knee osteoarthritis with WSD, valgus knees showed significantly increased cTEA compared to varus knees, and the cTEA difference positively correlated with the HKA difference between valgus and varus knees. To determine the optimal femoral component rotation during TKA in WSD, assessment of cTEA with pre-operative CT scans or careful intra-operative measurement is recommended, especially in patients with large HKA difference. LEVEL OF EVIDENCE: III, Retrospective cohort study.

Implementation effect of institutional policy of EGD observation time on neoplasm detection.

BACKGROUND AND AIMS: The observation time in EGD is associated with detection rate of premalignant or neoplastic lesions in the upper GI (UGI) tract. The aim of this study was to evaluate an institutional policy of EGD observation time on the detection rate of UGI neoplasms. METHODS: From July 2017 to March 2019, all endoscopists were requested to comply with our institutional policy of spending more than 3 minutes of observation time in every screening EGD. Observation time was defined as the time from when the endoscope reached the duodenum to when it was withdrawn. We obtained a neoplasm detection rate (NDR) during this period and compared it with that of a baseline period from 2009 to 2015. RESULTS: During the study period, 30,506 EGDs were performed. Mean subject age was 49.9 ± 10.5 years, and 56.5% were men. All endoscopists achieved an average EGD observation time of more than 3 minutes during this period. Mean observation time was 3:35 ± 0:50, which was significantly longer than the baseline (2:38 ± 0:21, P < .001). NDR was .33%, which was higher than the baseline (.23%, P < .001). Even after adjusting for subjects' age and gender, smoking history, and endoscopists' biopsy sampling rate, prolonged EGD observation time of more than 3 minutes increased the NDR of UGI neoplasms (odds ratio, 1.51; 95% confidence interval, 1.21-1.75). CONCLUSIONS: This study provides evidence that implementing a protocol of a prolonged observation time could increase NDR. Observation time should be an important quality indicator of the EGD examination.

Early Surgical Treatment of Both Tumor and Fracture in Patients With Enchondroma of the Hand Combined With Pathologic Fracture.

PURPOSE: The aims of this study were to evaluate the degree of cortical thinning and the tumor area in simple radiographs in patients with enchondroma of the hand combined with pathologic fracture and to determine the surgical outcome of simultaneous tumor curettage and internal fixation of fracture. METHODS: We enrolled 23 bone lesions of 21 patients diagnosed with enchondroma of the hand. Of them, 9 bone lesions of 8 patients had pathologic fracture. We evaluated the degree of cortical thinning and tumor area in simple radiographs and compared them between patients with and without pathologic fracture. For patients with pathologic fracture, we performed curettage of the tumor through the fracture site and fixed the fracture using K-wires. We then evaluated the clinical outcome of these patients using the visual analog scale to measure pain intensity and Takigawa's criteria 1 year after surgery. RESULTS: There was a significant difference in the degree of cortical thinning between the 2 groups (P < 0.001); however, there was no significant difference in the percentage of tumor area (P = 0.259). The average time from surgery to bony union was 8.5 weeks in patients with pathologic fracture. The patients reported that they could return to their previous activities of daily living within 12 weeks of surgery. The average visual analog scale score was 0.6 at 1 year after surgery, and 6 patients were graded as excellent and 2 as good according to Takigawa's criteria. CONCLUSIONS: Cortical thinning seems to be related to pathologic fracture. Our scoring system for cortical thinning may be helpful in evaluating the risk for pathologic fracture. Early 1-stage surgical treatment for pathologic hand fracture with enchondroma is a very useful method with satisfactory outcomes that could shorten the treatment period.

Analysis of factors affecting visual field recovery following surgery for pituitary adenoma.

PURPOSE: To analyze the factors influencing visual field recovery in patients with pituitary adenoma following surgical treatment. METHODS: We retrospectively reviewed 144 eyes of 72 patients with pituitary adenoma who had been followed up for more than 6 months following surgery between January 2016 and December 2019. Pre and postoperative visual acuity, visual field test and retinal nerve fiber layer (RNFL) thickness were investigated. We defined recovery of visual field defects as being an improvement in mean deviation (MD) of 2 dB or more. RESULT: The average age of the 72 patients (144 eyes) was 51.94 ± 14.69 years, making for 37 patients in the recovery group and 35 patients in the non-recovery group. Preoperative MD, pattern standard deviation (PSD), and visual field indexes (VFI) were negatively correlated to postoperative MD, PSD and VFI changes and positively correlated to postoperative MD, PSD, and VFI values. Using multiple regression analysis, a shorter duration of symptoms (Odds ratio [OR], 0.990; p = 0.033), higher preoperative MD values (OR, 0.871; p = 0.025), and thicker temporal RNFL (OR, 1.068; p = 0.048) were associated with a visual field recovery following surgery. CONCLUSIONS: The prognosis for visual field recovery is favorable for patients who have a short period from symptom onset to surgery, a higher MD value of preoperative VF, and a thicker peripapillary temporal RNFL thickness. Therefore, the preoperative MD, temporal RNFL thickness, and the symptom period can be predictive variables affecting postoperative visual field recovery.

Clinically Node-Negative Parotid Gland Cancers: Prognostic Factors of Survival and Surgical Extent.

OBJECTIVE: Conservative parotidectomy is known to reduce morbidity, but has been rarely examined in patients with clinically node-negative (cN0) parotid cancers. We evaluated the clinicopathological variables influencing the outcomes of these patients and the efficacy of conservative parotidectomy. METHODS: We reviewed the clinical and pathological data of 256 patients with cN0 parotid carcinomas who underwent curative surgery at our institution. Of these, 110 and 146 underwent conservative and total parotidectomy, respectively, with 83 undergoing elective neck dissection and 135 receiving postoperative radiotherapy. Univariate and multivariate analyses of variables predicting recurrence-free survival (RFS) and overall survival (OS) were performed. Morbidity, survival, and recurrence rates were compared between the conservative and total parotidectomy groups. RESULTS: The 5-year RFS and OS rates in all patients were 85.7 and 91.4%, respectively. Multivariate analysis showed that advanced T classification, positive resection margin, and high-histologic grade were independent prognostic factors for both RFS and OS. Among the 201 patients with low- or intermediate-grade parotid cancers, those who underwent total parotidectomy had a greater chance of facial nerve paralysis than those who underwent conservative parotidectomy (p < 0.001). The 5-year RFS and OS after conservative parotidectomy (93.7 and 100%, respectively) were not worse than those after total parotidectomy (85.5 and 90.9%, respectively). CONCLUSION: Patients with cN0 parotid cancers may be stratified by histological grade and T classification. Conservative parotidectomy may be suitable for early T1-2 low- or intermediate-grade tumors if a resection margin is secured.

Impacts of age and sedation on cardiocerebrovascular adverse events after diagnostic GI endoscopy: a nationwide population-based study.

BACKGROUND AND AIMS: Data are limited regarding the impact of age and sedation on cardiocerebrovascular disease (CCD) adverse events after GI endoscopy. We investigated the incidence of and risk factors for CCD adverse events after diagnostic GI endoscopy and the impact of age and sedation on these unfavorable outcomes. METHODS: In this nationwide population-based study, the incidence of and risk factors for newly diagnosed CCD within 14 days after diagnostic endoscopy were analyzed using Health Insurance Review and Assessment Service data from January to December 2015. RESULTS: Among 1,943,150 subjects, CCD adverse events occurred in approximately 2.23% within 14 days after endoscopy. According to the performance of sedation during endoscopy (60.1% nonsedation vs 39.9% sedation, midazolam alone [96.4%]), the incidence rates of CCD adverse events (per 10,000 persons) were 275.8 versus 302.8 for EGD, 116.9 versus 143.8 for colonoscopy, and 230.4 versus 243.2 for EGD + colonoscopy, respectively. On multivariate analysis, older age (70-99 years) and sedation were independent risk factors for CCD adverse events. Regarding CCD risk stratified by age and sedation, older age had a significant impact on CCD adverse events in individuals who underwent EGD only or EGD + colonoscopy, but sedation did not. However, both older age and sedation had considerable influence on CCD adverse events in individuals who underwent colonoscopy only. Sedation during endoscopy was significantly associated with minor but not major CCD adverse events. CCD adverse events were significantly higher for inpatients. CONCLUSION: CCD adverse events after diagnostic endoscopy were significantly frequent in individuals with older age (70-99 years) and/or sedation during endoscopy. Stratification by age and sedation shows that the impact of these 2 factors on CCD adverse events differs according to endoscopy type.

Predictors of recurrence after total thyroidectomy plus neck dissection and radioactive iodine ablation for high-risk papillary thyroid carcinoma.

BACKGROUND: American Thyroid Association (ATA) proposed management guidelines for differentiated thyroid cancer, including a three-tiered risk stratification system for structural recurrence. This study aimed to compare the various 2015 ATA criteria for the strength of association with the recurrence of high-risk papillary thyroid carcinoma (PTC). STUDY DESIGN: This study included 545 consecutive patients who underwent total thyroidectomy plus neck dissection and radioactive iodine ablation (RAI) for previously untreated high-risk PTC. The association of recurrence-free survival (RFS) with clinicopathological factors was evaluated by univariate and multivariate Cox proportional hazard regression analyses. RESULTS: During a follow-up median period of 89 months, 90 (16.5%) patients had any-site recurrence. Of the high-risk factors, high stimulated thyroglobulin (sTg) level and >3-cm sized lymph nodes (LNs) were significantly associated with recurrence (all P < .005). Sex, tumor size, lymphovascular invasion, multifocality, number of positive LNs, extranodal extension, T and N classifications, and overall tumor-node-metastasis stage were also significantly associated with recurrence (all P < .05). In multivariate analyses, high sTg level [adjusted hazard ratio (HR) = 7.18] and N1b (adjusted HR = 3.27) were independent factors predictive of recurrence (all P ≤ .001). CONCLUSIONS: Postoperative high serum sTg level might be the most important predictor of PTC recurrence after total thyroidectomy plus neck dissection and RAI.

Utilization of liquid pig manure for resource cycling agriculture in rice-green manure crop rotation in South Korea.

A 2-year field experiment was carried out on rice (Oryza sativa, Japonica type) cultivation in South Korea. The objective of this study was to investigate the effect of application of liquid pig manure on biomass production and nutrient supply of green barley (Hordeum vulgare L.) and hairy vetch (Vicia villosa Roth) green manure crops and to evaluate the effect of nutrients supplied from these sources on rice yield and soil quality in a rice-green manure crop rotation system. Over the 2-year study period, application of liquid pig manure increased biomass production of green manure crops of barley and hairy vetch by more than 216% and 135%, respectively, compared with without liquid pig manure. Moreover, the results showed that the application of liquid pig manure significantly increased the nutrient supply levels in green barley- and hairy vetch-treated areas. Positive effects related to nutrient supply in green barley and hairy vetch treated with liquid pig manure were observed on rice yield, soil chemical characteristics, and microbial biomass C and N contents. In conclusion, the addition of liquid pig manure systems using green manure crops of green barley and hairy vetch improved rice productivity and soil quality. It is suggested that these combinations can be effective in developing resource cycling agriculture in a rice-green manure crop rotation system as it reduces the need for inorganic fertilizer.

Risk Factors for Recurrence After Treatment of N1b Papillary Thyroid Carcinoma.

OBJECTIVES: To examine risk factors for posttreatment recurrence in papillary thyroid carcinoma (PTC) patients with initial presentation of lateral neck metastasis (N1b). SUMMARY OF BACKGROUND DATA: N1b PTC recurs after definitive treatment. METHODS: Study subjects were 437 consecutive PTC patients who underwent total thyroidectomy and therapeutic neck dissection of central and lateral compartments and postoperative radioactive iodine ablation therapy. The patients' demographics and pathological factors, including factors related to tumors and lymph nodes (LNs), and postoperative thyroglobulin levels were reviewed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify factors associated with recurrence-free survival (RFS). RESULTS: During a median follow-up of 83 months (range, 32-135 months), recurrence occurred in 81 (18.1%) patients. Univariate analyses showed that male sex, tumor size, macroscopic extrathyroidal extension, perineural invasion, extranodal extension, LN involvement, LN ratio, MACIS score, and postoperative serum levels of thyroglobulin were significantly associated with RFS (P < 0.05). Multivariate analyses revealed that LN ratio (> 0.25) in the lateral compartment (adjusted hazard ratio = 2.099, 95% confidence interval = 1.278-3.448; P = 0.003), and postoperative serum levels of stimulated (>5.0 ng/mL; 3.172, 1.661-6.056, P < 0.001) and unstimulated (>0.1 ng/mL; 3.200, 1.569-6.526, P = 0.001) thyroglobulin were independent predictors of any-site RFS. Clinical and tumor factors were not independent predictors of RFS outcomes (P > 0.1). CONCLUSIONS: Posttreatment recurrence is predicted by the LN ratio in the lateral compartment and postoperative serum levels of thyroglobulin in patients with metastatic PTC in the lateral neck.

Number of positive lymph nodes better predicts survival for oral cavity cancer.

BACKGROUND: We compared the predictive ability of our proposed N classification with that of the American Joint Committee on Cancer (AJCC) nodal (N) classification for oral cavity squamous cell carcinoma (OCC). METHODS: We assessed 345 OCC patients who underwent primary tumor extirpation and neck lymph node (LN) dissection. N classification was analyzed by recursive partitioning analysis and compared with the AJCC N classification by c-index. Cox proportional hazards regression analyses were used to determine associations between tumor or nodal factors and disease-free survival (DFS) or overall survival (OS). RESULTS: Positive LNs were found in 149 patients (43.2%). In multivariate models, the number of positive LNs and LN ratio strongly associated with DFS and OS (P < 0.001). Our new N classification was proposed with four categories of N0, N1 (1 positive LN), N2 (2-4 positive LNs or extranodal extension > 2 mm), and N3 (≥5 positive LNs). The c-index for the proposed N classification showed improvement in survival predictions (0.735; 95% CI, 0.703-0.767) compared with the AJCC N classification (0.701; 0.667-0.735). CONCLUSIONS: The number of positive LNs and LN ratios strongly associated with posttreatment recurrence and survival for OCC. Using positive LN numbers with the N classification improves OCC survival predictions.

Tumor-related leukocytosis predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma.

OBJECTIVE: To evaluate the prognostic values of tumor-related leukocytosis (TRL) as a reliable biomarker predictive of recurrence and survival after definitive surgery for oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This retrospective study involved 322 patients who underwent tumor extirpation combined with neck dissection for treatment-naïve OSCC between 2006 and 2014. Multivariate binary logistic regression analyses were used to analyze the relationship between TRL and pathological variables. Cox proportional hazard regression analyses were used to find associations between factors and disease-free survival (DFS) or overall survival (OS). RESULTS: TRL was significantly related to advanced disease status, tumor size, invasion depth, poor differentiation, and T and N classifications, resulting in increased post-treatment recurrence rate, particularly in the distant site. Multivariate logistic regression analyses showed that only the T classification was significantly associated with baseline TRL (p = 0.018). Multivariate analyses also showed that the tumor depth of invasion, pathological N classification, extranodal extension, and TRL remained the independent variables predictive of DFS and OS (all p < 0.05). TRL was related to a more than twofold increased risk of post-treatment recurrence and mortality. CONCLUSIONS: TRL is associated with advanced tumor disease and increased recurrence and mortality in OSCC patients.

Gender Specific Differences in Prevalence and Risk Factors for Gastro-Esophageal Reflux Disease.

BACKGROUND: Gender-related factors might play an important role in the development of reflux esophagitis (RE) and symptomatic gastro-esophageal reflux disease (GERD). We aimed to evaluate the prevalence and risk factors for RE and symptomatic GERD and determine whether gender specific differences exist. METHODS: This study was conducted on a health cohort consisting of 10,158 participants who underwent comprehensive health screening. Lifestyles and gastrointestinal symptoms were investigated using a self-reported structured questionnaire. Questionnaires about menstrual status were added for the women. RESULTS: The prevalence of RE in men was significantly higher than that in women (10.6% vs. 2.0%, P < 0.001); however, symptomatic GERD showed predominance in women (6.2% vs. 2.5%, P < 0.001). Although the prevalence of RE gradually increased with the duration of menopause stratified by decade (P = 0.007), that of symptomatic GERD rapidly increased across the menopausal transit in women. Apart from common risk factors of obesity and current smoking for RE, over 70 years of age in women and hiatal hernia and hypertriglyceridemia in men were significant risk factors. In symptomatic GERD, high somatization was a common risk factor. Excessive alcohol drinking was a significant risk factor in men, but not in women. CONCLUSION: This study showed a predominance of RE in men, but a predominance of symptomatic GERD in women. In women, dynamic increase in the prevalence of GERD is closely related to the menopause conditions and its duration. There are specific risk factors for RE and symptomatic GERD according to gender differences.

Identification of beta-arrestin-1 as a diagnostic biomarker in lung cancer.

BACKGROUND: Distinguishing lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has a tremendous therapeutic implication. Sometimes, the commonly used immunohistochemistry (IHC) markers fail to discriminate between them, urging for the identification of new diagnostic biomarkers. METHODS: We performed IHC on tissue microarrays from two cohorts of lung cancer patients to analyse the expression of beta-arrestin-1, beta-arrestin-2 and clinically used diagnostic markers in ADC and SCC samples. Logistic regression models were applied for tumour subtype prediction. Parallel reaction monitoring (PRM)-based mass spectrometry was used to quantify beta-arrestin-1 in plasma from cancer patients and healthy donors. RESULTS: Beta-arrestin-1 expression was significantly higher in ADC versus SCC samples. Beta-arrestin-1 displayed high sensitivity, specificity and negative predictive value. Its usefulness in an IHC panel was also shown. Plasma beta-arrestin-1 levels were considerably higher in lung cancer patients than in healthy donors and were higher in patients who later experienced a progressive disease than in patients showing complete/partial response following EGFR inhibitor therapy. CONCLUSIONS: Our data identify beta-arrestin-1 as a diagnostic marker to differentiate ADC from SCC and indicate its potential as a plasma biomarker for non-invasive diagnosis of lung cancer. Its utility to predict response to EGFR inhibitors is yet to be confirmed.