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Background: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide‐binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. Methods: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high‐throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro‐computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin‐12 (IL‐6) were detected by western blot. Results: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL‐6. Conclusions: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas. [ABSTRACT FROM AUTHOR]

Aim: To compare and evaluate the efficacy of the levonorgestrel‐releasing intrauterine system (LNG‐IUD) and resectoscopy remodeling procedure for intermenstrual bleeding associated with previous cesarean delivery scar defect (PCDS). Methods: A retrospective comparative study was conducted on patients with PCDS receiving LNG‐IUD (levonorgestrel 20 μg/24 h, N = 33) or resectoscopy remodeling (N = 27). Treatment outcomes were compared over 1, 6, and 12 months. Outcomes in patients with a retroverted or large uterus size, defect size, and local vascularization also were evaluated. Results: At 12 months post‐treatment, there were no significant differences between groups in efficacy rate; however, the reduction of intermenstrual bleeding days was higher in the LNG‐IUD group than in the resectoscopy group (13.6 vs. 8.5 days, p = 0.015). Within the first year, both groups experienced a reduction in bleeding days, but the decrease was greater in the LNG‐IUD group. Individuals exhibiting increased local vascularization at the defect site experienced more favorable outcomes in the LNG‐IUD group than the resectoscopy group (p = 0.016), and who responded poorly tended to have a significantly larger uterus in the LNG‐IUD group (p = 0.019). No significant differences were observed in treatment outcomes for patients with a retroverted uterus or large defect in either group. Conclusions: Our findings support that the LNG‐IUD is as effective as resectoscopy in reducing intermenstrual bleeding days associated with PCDS and can be safely applied to patients without recent fertility aspirations. Patients with increased local vascularization observed during hysteroscopy may benefit more from LNG‐IUD intervention than resectoscopy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-related fatigue (CRF) is a common somatic discomfort in gynecological cancer patients; however, it is usually overlooked by physicians. We aimed to explore the prevalence of CRF's and the clinical characteristics of gynecological cancer patients. The results showed that 77.9% of patients had received related CRF management. A five-item predictive model was developed from the identified risk factors contributing to CRF. The risk factors included (1) diagnosis of endometrial/cervical cancer, (2) International Federation of Gynecology and Obstetrics (FIGO) stage >1, (3) Eastern Cooperative Oncology Group (ECOG) status score ≥1, (4) inadequate treatment response, and (5) having received cancer treatment in the past 1 week. The predictive model may help physicians more promptly identify high-risk patients in clinical practice. Cancer-related fatigue (CRF) is the most common somatic discomfort in patients with gynecological cancers. CRF is often overlooked; however, it can impair the patients' quality of life considerably. This cross-sectional study aimed to identify the clinical characteristics of CRF in gynecological cancer patients. Questionnaires and the International Classification of Diseases 10th Revision (ICD-10) criteria were used to identify CRF. The enrolled patients were further categorized according to the amount of fatigue-related management received. Of the enrolled 190 patients, 40.0% had endometrial cancer, 28.9% had cervical cancer, and 31.1% had ovarian cancer. On the basis of the ICD-10 diagnostic criteria, 42.6% had non-cancer-related fatigue, 10% had CRF, and 51% had BFI-T questionnaire-based fatigue. Moreover, 77.9% of the study cohort had ever received fatigue-related management. Further analysis showed that patients with endometrial/cervical cancer, International Federation of Gynecology and Obstetrics stage >1, Eastern Cooperative Oncology Group performance status score ≥1, inadequate cancer treatment response, and receiving cancer treatment in the past week had a higher probability of receiving more fatigue-related management. The five-item predictive model developed from these factors may help physicians recognize patients seeking more fatigue-related management more efficiently. This is important as they may suffer from a more profound CRF. [ABSTRACT FROM AUTHOR]

Navigation bronchoscopy is an emerging technique used to evaluate pulmonary lesions. Using Veran's SPiN electromagnetic navigation bronchoscopy (ENB) and Archimedes virtual bronchoscopy navigation (VBN), this study aimed to compare the accuracy and safety of these procedures for lung lesions and to identify potentially relevant knowledge for the application of artificial intelligence in interventional pulmonology in a single institute. This single-center, retrospective study compared the ENB and VBN results in patients with pulmonary lesions unsuitable for biopsy via percutaneous transthoracic needle biopsy methods. A total of 35 patients who underwent navigation bronchoscopy for pulmonary lesion diagnosis were enrolled. Nineteen patients were stratified in the ENB group, and sixteen were in the VBN group. The mean age of this cohort was 67.6 ± 9.9 years. The mean distance of the lesion from the pleural surface was 16.1 ± 11.7 mm (range: 1.0–41.0 mm), and most lesions were a solid pattern (n = 33, 94.4%). There were 32 cases (91.4%) of pulmonary lesions with an air-bronchus sign. A statistically significant difference was found between pulmonary size and transparenchymal nodule access (p = 0.049 and 0.037, respectively). The navigation success rate was significantly higher in the VBN group (93.8% vs. 78.9%). Moreover, no procedure-related complications or mortality were noted. The radiographic characteristics, such as size or solid component, can affect the selection of the biopsy procedure, either ENB or VBN. Navigation bronchoscopy-guided biopsy demonstrated acceptable accuracy and a good safety profile in evaluating pulmonary lesions when the percutaneous approach was challenging or life threatening. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to verify the importance and the timing of endobronchial ultrasound with transbronchial biopsy (EBUS TBNA) among lung adenocarcinoma patients after radical resection. Methods: We retrospectively reviewed consecutive patients with non-small cell lung cancer (NSCLC) who had ever received radical resection from January 2002 to December 2021. The patients were divided into two groups, with and without EBUS TBNA, for diagnosis or staging. Results: Of 2018 patients with NSCLC, after surgical resection of lung tumors, there were 232 with recurrences. Under multivariate Cox regression analysis, patients with recurrences who received EBUS TBNA had a statistically higher mean maximum standardized uptake value (SUVmax) (hazard ratio (HR) = 1.115, confidence interval (CI) = 1.004–1.238, p = 0.042) and better survival (HR = 5.966, CI = 1.473–24.167, p = 0.012). Although KM survival analysis showed no statistically significant difference between groups with and without EBUS TBNA (p = 0.072) of lung adenocarcinoma patients with recurrences, patients with mutated epidermal growth factor receptor (EGFR) showed significantly better survival than wild-type EGFR (p = 0.007). Conclusions: The clinical practice of EBUS TBNA is not only for diagnosis, but also for nodal staging. We found that lung adenocarcinoma patients with recurrences who received EBUS TBNA had better overall survival. Therefore, EBUS TBNA is a reliable and feasible tool that could be used in lung adenocarcinoma patients with recurrences for early diagnosis and for adequate tissue specimens for further molecular analysis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) using post-neoadjuvant chemoradiotherapy (nCRT) F-18-fluorodeoxyglucose (18FDG).Methods: This is a retrospective study of patients with locally advanced ESCC receiving nCRT and then esophagectomy between January 2011 and December 2018 in the Tri-Service General Hospital, Taipei, Taiwan. A total of 50 patients were enrolled in the study. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model. Univariate and multivariate analysis were used to determine the independent prognostic factors.Results: Fifty patients were enrolled in the study, and 18 had pathological complete response. Post-nCRT SUVmax ≥ 3 is a poor prognostic factor associated with overall survival (HR: 3.665, P = 0.013) and disease-free survival (HR: 3.417, P = 0.011). Poor prognosis was found in the non-pCR plus post-nCRT SUVmax ≥ 3 group compared with pCR plus post-nCRT SUVmax < 3 group.Conclusions: SUVmax ≥ 3 is a poor prognostic factor in esophageal squamous cell carcinoma after trimodality treatment, even in patients having pathological complete response. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) gene mutation is a known predictor of the response to EGFR tyrosine kinase inhibitors. However, detecting EGFR mutations is a potential challenge because of the ground-glass opacity component, and its prognostic value for stage IA lung adenocarcinoma remains controversial. This study aimed to investigate the associations between EGFR mutation status, clinicopathological characteristics, and prognosis in surgically resected stage IA non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively examined the data of patients who underwent surgical resection for lung cancer between 2004 and 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. Results: A total of 429 patients (female, n = 303; male, n = 126) with surgically resected stage IA NSCLC were analyzed and 343 were nonsmokers. The EGFR mutation rate was 48.3% (n = 207). Of the patients, 192 (44.8%) had stage IA1, 165 (38.5%) had stage IA2, and 72 (16.8%) had stage IA3 NSCLC. In the analysis of the correlations between clinicopathological features and EGFR status, older age (P = 0.032), nonsmoking history (P = 0.039), and pathological stage (P < 0.05) were related to EGFR mutation. Patients with stage IA2 NSCLC had a higher positive expression of EGFR than patients with stages IA1 and IA3. The 5-year overall survival rates and disease-free survival rates were better in the EGFR mutation group; however, the difference was not statistically significant. Conclusion: EGFR mutations are common in older and nonsmoking patients with stage IA NSCLC. Further separate analyses of EGFR gene mutations and pathological stage could improve the diagnostic performance and predict patients with unavailable EGFR gene testing who may benefit from targeted drug treatment. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to verify the predictors of the diagnostic accuracy of rapid on-site evaluation (ROSE) in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) among patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed consecutive patients with NSCLC who underwent EBUS-TBNA for staging or diagnosis at our hospital from June 2016 to June 2018. The patients were divided into two groups—those with a correct diagnosis and an incorrect diagnosis after ROSE. Kaplan–Meier plots and log-rank tests were used to estimate outcomes. Results: A total of 84 patients underwent EBUS-TBNA for staging and diagnosis. Sixty patients with demonstrated malignant mediastinal lymph nodes were enrolled. In the univariate analysis, lymph nodes < 1.5 cm (HR = 3.667, p = 0.031) and a SUVmax > 5 (HR = 41, p = 0.001) were statistically significant for diagnostic accuracy of ROSE. In the multivariate Cox regression analysis, only a SUVmax > 5 (HR = 20.258, p = 0.016) was statistically significant. Conclusions: A SUVmax > 5 is an independent predictor of higher diagnostic accuracy of ROSE in EBUS-TBNA in patients with NSCLC with malignant mediastinal lymph nodes. Therefore, ROSE in patients with a SUVmax < 5 might not be reliable and requires further prudent assessment (more shots or repeated biopsies at mediastinal LNs) in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of levonorgestrel 52 mg intrauterine system for intermenstrual bleeding in patients with previous cesarean delivery scar defects (PCDSs). Methods: The medical records of 28 consecutive patients with previous cesarean delivery scar defect and intermenstrual bleeding who had undergone conservative treatment with levonorgestrel 52 mg intrauterine system were reviewed. The efficacy of treatment and frequency of adverse events were measured retrospectively. Results: After 1 year of treatment, 22 patients (78.6%) reported an improvement in symptoms. The mean duration of menstruation were 18 and 5 days before and after treatment, respectively. No uterine perforations or pelvic inflammatory diseases occurred during or after the insertion procedures. Eighteen (64.3%) patients did not experience any adverse events, and the patients with adverse events reported that they could be managed by adjusting their medications or observation. Conclusion: Levonorgestrel intrauterine system may have a role in the safe and effective management of intermenstrual spotting in patients with PCDSs. [ABSTRACT FROM AUTHOR]

Aim: The predictive accuracy of frozen sections for borderline ovarian tumors (BOTs) is suboptimal. The aim of this study was to determine the diagnostic accuracy of BOTs and factors associated with an upgrade to a permanent pathological diagnosis of invasive carcinoma in patients diagnosed with BOTs by frozen section. Methods: We conducted a retrospective study between 2011 and 2018 at Kaohsiung Chang Gung Memorial Hospital (KCGMH). Two hundred and twenty‐five records of eligible patients with a diagnosis of BOT by frozen section or permanent diagnosis were reviewed. Positive predictive value and the diagnostic accuracy of frozen sections were calculated. Univariate and multivariate analyses were used to determine the clinicopathological factors associated with an upgrade of the diagnosis from a borderline tumor to malignancy. Results: The agreement between frozen section and permanent pathological diagnoses was 63.1%, and the positive predictive value was 72.1%. The multivariate analysis revealed that CA‐125 level > 136 U/mL (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 1.3–6.9; p = 0.012), and tumor histologic type (clear cell/endometrioid vs. mucinous; OR:32.8, 95% CI = 6.9–154.8, p < 0.001; clear cell/endometrioid vs. serous: OR 48.1, 95% CI = 8.8–261.8, p < 0.001) were independent risk factors for an upgrade of the permanent diagnosis from a BOT to ovarian carcinoma. Conclusion: An elevated CA‐125 level (over 136 U/mL) and tumor histologic type (clear cell and endometrioid subtypes) were associated with an upgrade in the diagnosis of ovarian tumor from a BOT on frozen section to a permanent diagnosis of malignancy. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC). Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O'Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival. Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (< 23 days), intermediate (23– 43 days) and late (> 43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10– 0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group. Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3– 6 weeks post-operatively. Initiating chemotherapy early (< 23 days) did not appear to benefit PFS. [ABSTRACT FROM AUTHOR]

Abstract Background This study was to explore the effects of Gan-Lu-Yin (GLY) on the migration of vascular smooth muscle cells (VSMCs) induced by fetal bovine serum and on neointima formation in a rat model of carotid artery balloon injury. Methods VSMCs were treated with different concentrations of GLY, and then analyzed with Flow cytometric analysis, zymography, transwell, and western blotting. SD rats received balloon-injury were analyzed with H&E staining. Results Our results showed that GLY significantly decreased the thickness of neointima. The inhibition by non-cytoxic doses of GLY of VSMCs migration was through its negative regulatory effects on phosphorylated ERK1/2, PI3K/AKT, and FAK. The data showed that GLY can inhibit the migration of VSMCs cells, and might block injury-induced neointima hyperplasia via the inhibition of VSMCs migration, without inducing apoptosis. Conclusions These observations provide a mechanism of GLY in attenuating cell migration, thus as a potential intervention for restenosis.

Bone healing in tooth extraction sockets occurs in a complex environment containing saliva and many microorganisms and is affected by many factors. Endoplasmic reticulum (ER) stress affects bone metabolism, but the role of ER stress in bone healing after tooth extraction remains unclear. We utilized a rat tooth extraction model, in which we promoted wound healing by using salubrinal to regulate the ER stress response. Western blot analysis showed increased expression of p‐eIF2α/eIF2α, Runx2 and alkaline phosphatase (ALP) in bone tissue, and histological assays showed irregularly arranged and new bone with more collagen fibres 14 days after tooth extraction and after modulating the degree of ER stress. Micro‐CT showed that modulating ER stress to an appropriate degree increases bone filling in regards to the density in the bottom and the surrounding bone wall of the tooth extraction wounds. Transmission electron microscopy showed rough ER expansion and newly formed collagen fibrils in osteoblasts after modulating ER stress to an appropriate degree. We also used different concentrations of salubrinal to evaluate the resistance to tunicamycin‐induced ER stress in an osteogenic induction environment. Salubrinal restored the tunicamycin‐induced decrease in the viability of primary calvarial osteoblasts and increased the expression of Runx2 and ALP, and decreased p‐eIF2α/eIF2α in a dose‐dependent manner. Taken together, the results demonstrate that ER stress occurred after tooth extraction, and regulating the degree of ER stress can promote bone healing in tooth extraction sockets, providing clinical evidence for bone healing. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of levonorgestrel intrauterine system (LNG‐IUS) treatment in patients with previous cesarean delivery scar defect (PCDS)‐related intermenstrual bleeding. Methods: A total of six premenopausal patients who experienced PCDS‐related intermenstrual bleeding were enrolled for conservative therapy with LNG‐IUS (levonorgestrel 20 μg/24 h) insertion. The durations of menstruation before and after LNG‐IUS insertion at 1, 6 and 12 months were recorded. A total of three missed menstrual cycles was defined as amenorrhea. Any side effects and the device expulsion rate were also recorded. Patient follow‐up was at an outpatient clinic. Any missing data were obtained by telephone. Results: At the start of the study the median duration of intermenstrual bleeding was 6.5 days (range 3–22 days). After 6 months treatment, two of the six patients had developed amenorrhea and two patients experienced cessation of vaginal spotting. One patient reported expulsion of the device. All patients except the one with device expulsion responded to the conservative treatment after 1 year. Conclusion: The findings of the current study support LNG‐IUS being effective for the treatment of PCDS‐related intermenstrual bleeding. The authors recommend LNG‐IUS as a treatment option for PCDS‐related intermenstrual bleeding. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the impact of epidermal growth factor receptor (EGFR) mutation status and tyrosine kinase inhibitors (TKIs) on the survival of brain metastases (BM) in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: We selected the patients who had developed metastatic NSCLC; analyzed the differences between brain metastases and other sites of metastases, including patient characteristics, EGFR status, and survival; and selected the patients who had BM for further investigation. We also compared the treatment effects of first-generation TKIs with those of second-/third-generation TKIs. Results: A total of 785 cases of stage I-IIIa NSCLC were reviewed. Thirty-six (4.6%) patients were identified as having BM. Among them, 14 patients had a mutated EGFR status. No association between EGFR mutation and the incidence of BM was observed (p = 0.199). Patients with mutated EGFRs had significantly longer overall survival and post-recurrence survival than patients with wild-type EGFR mutation (p = 0.001 for both). However, there was no survival difference between patients with exon 19 and exon 21 mutations (p = 0.426). Furthermore, patients who received the second- and/or third-generation EGFR-TKIs had better survival than patients who only received first-generation EGFR-TKIs (p = 0.031). A multivariate analysis indicated that the next-generation TKIs (HR, 0.007; 95% CI, 0.000 to 0.556; p = 0.026) and a longer interval before BM development (HR, 0.848; 95% CI, 0.733 to 0.980; p = 0.025) were significant factors in longer survival. Conclusions: EGFR-TKIs were effective in treating NSCLC patients with BM after curative pulmonary surgery, especially in those patients harboring EGFR mutations. Furthermore, the second-/third-generation EGFR-TKIs showed more promising results than the first-generation EGFR-TKIs in treating those particular patients, though larger studies needed to further prove the results. [ABSTRACT FROM AUTHOR]

Background The Nuss procedure is a minimally invasive technique for correcting pectus excavatum. We hypothesized that three-dimensional (3D) simulation may shorten operation time and provide better morphologic outcome. This study aimed to demonstrate the feasibility of the 3D model-assisted Nuss procedure and to compare its potential benefits with those of the traditional Nuss procedure. Methods We simulated the targeted curvature, length, and planned intercostal space of a metallic bar, based on the preoperative chest computed tomographic images. After the use of a 3D printing technique, a plastic template bar was produced and sterilized. The metallic bar was bent and placed at the planned intercostal space accordingly. The patients' characteristics, total number of pectus bar placement, total operation time, and improvement percentage of Haller indices were compared with patients who underwent the traditional Nuss procedure. Results A total of 419 patients underwent the Nuss procedure from January 2010 to July 2017 in our hospital, and 357 patients were eligible and enrolled for the following analysis. Fifteen patients underwent 3D simulation. After performing propensity-score matching analysis, the 3D printing group had a shorter operative time (60.36 versus 74.34 minutes, p < 0.001), fewer metallic bar placements (1.00 versus 1.36 bars, p < 0.001), and better improvement percentages in the Haller indices (20.34% versus 10.06%, p < 0.001) compared with the traditional Nuss procedure. Conclusions In this preliminary study, 3D-printed model-assisted Nuss procedure may provide benefits of shorter operative time, fewer metallic bar insertions, and comparable morphologic outcome by preoperative simulation. [ABSTRACT FROM AUTHOR]

Many different benign and malignant tumors develop in the chest wall and pose a diagnostic and therapeutic challenge to clinicians. Chest wall schwannomas of the intercostal nerve are rare. This report describes the clinical and imaging findings of a patient who presented with persistent and progressive chest pain. The intercostal tumor was treated using wide excision with chest wall reconstruction and titanium plate fixation. Schwannoma was diagnosed on the basis of histopathologic examination. [ABSTRACT FROM AUTHOR]