Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Extracellular vesicles called exosomes are primarily used as mediators of intercellular signal transmission to control tumor metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with exosome generation in chondrosarcoma motility remains undetermined. Our results found that overexpressing visfatin augments the production of exosomes from chondrosarcoma cells. Visfatin-treated chondrosarcoma exosomes educate macrophage polarization towards the M2 but not M1 phenotype. Interestingly, M2 macrophages polarized by exosomes return to chondrosarcoma cells to facilitate cell motility. According to these findings, chondrosarcoma cells emit more exosomes when treated with visfatin. The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.

Transforaminal Unilateral Biportal Endoscopic Spinal Surgery for Extraforaminal Lumbar Disc Herniation: A Retrospective Observational Study.

OBJECTIVE: Biportal endoscopic spinal surgery (BESS) is recommended as a safer and less destructive option for lumbar disc herniations. However, limited data exist on clinical outcomes for extraforaminal lumbar disc herniation (ELDH) surgery. This retrospective study presents our preliminary experience with transforaminal unilateral BESS for ELDH. METHODS: Patients with lumbar radiculopathy refractory to conservative treatment, diagnosed with ELDH by magnetic resonance imaging, and treated with transforaminal unilateral BESS in 2021-2023 in 2 institutions in Taiwan were eligible for inclusion. Those with lumbar spondylolisthesis grade 2 or more with segmental instability, history of drug abuse or psychiatric diseases, or with a follow-up duration <1 year were excluded. Primary outcomes included visual analog scale for pain, assessed at 1 week, 1 month, 6 months, and 1 year using generalized estimating equations analysis; success and satisfaction of BESS graded by the Macnab criteria; and perioperative complications. Secondary outcomes were operative time and hospital length of stay. RESULTS: Seventeen patients were included in the analysis, with a mean age of 65.8 years; 11 (64.7%) were males and 15 (88.2%) had no prior lumbar spine surgery. mean operative time was 107.9 minutes, and length of stay was 3.5 days. Graded by Macnab criteria, 16 (94.1%) of patients had good to excellent outcomes. Only 1 patient experienced complications. No recurrence/reoperation was observed. Generalized estimating equations analysis showed that postoperative visual analog scale scores decreased significantly at 1 week (adjusted Beta [aBeta] = -5.47, standard error: 0.29, P < 0.001), 1 month (aBeta = -5.82), 6 months (aBeta = -5.88), and 1 year (aBeta = -6.29). CONCLUSIONS: Transforaminal unilateral BESS is an alternative and feasible method for treating ELDH, producing good surgical outcomes with few complications and sustaining pain improvement. Future studies with larger patient numbers and comparisons between BESS and other minimally invasive techniques for ELDH are warranted.

Ugonin P inhibits lung cancer motility by suppressing DPP-4 expression via promoting the synthesis of miR-130b-5p.

Lung cancer is the leading cause of cancer-related death worldwide, and the survival rate of metastatic lung cancer is exceedingly low. Helminthostatchys Zeylanica (H. Zeylanica) is a Chinese herbal medicine renowned for its anti-inflammatory, immunomodulatory, and anti-cancer activities in various cellular and animal studies. The current study evaluated the effects of H. Zeylanica derivatives on lung cancer cells. We determined that dipeptidyl peptidase-4 (DPP-4) expression levels were higher in lung cancer tissues than in normal tissues. We also determined that DPP-4 expression levels were higher in the metastatic stage and strongly correlated with lung cancer survival rates. An H. Zeylanica derivative (ugonin P) was shown to inhibit DPP-4 mRNA and protein expression in two lung cancer cell lines in a dose-dependent manner. Ugonin P was shown to decrease migration and invasion activities in lung cancer cells while promoting the synthesis of miR-130b-5p, which was found to negatively regulate DPP-4 protein expression and cell motility in lung cancer. We determined that ugonin P suppresses the DPP-4-dependent migration and invasion of lung cancer cells by downregulating the RAF/MEK/ERK signalling pathway and enhancing the expression of miR-130b-5p. This study provides compelling evidence that ugonin P could be used to develop novel therapeutic agents for the treatment of lung cancer.

Ugonin L inhibits osteoclast formation and promotes osteoclast apoptosis by inhibiting the MAPK and NF-κB pathways.

Bone loss is a major issue for patients with osteoporosis, arthritis, periodontitis, and bone metastasis; however, anti-resorption drugs used to treat bone loss have been linked to a variety of adverse effects. Helminthostachys zeylanica (L.) Hook, belonging to the family Ophioglossaceae, is commonly used in traditional Chinese medicine to treat inflammation and liver problems. In the current study, ugonin L extracted from H. zeylanica was shown to reduce the receptor activator of nuclear factor kappa beta ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells in a concentration-dependent manner. Ugonin L treatment also inhibited the mRNA expression of osteoclast markers. Ugonin L was also shown to promote cell apoptosis in mature osteoclasts and suppress RANKL-induced ERK, p38, JNK, and NF-κB activation. Taken together, ugonin L appears to be a promising candidate for the development of novel anti-resorption therapies.

Visfatin upregulates VEGF-C expression and lymphangiogenesis in esophageal cancer by activating MEK1/2-ERK and NF-κB signaling.

Lymph node metastasis is a recognized prognostic factor in esophageal cancer. Adipokines, including visfatin, and the molecule vascular endothelial growth factor (VEGF)-C, are implicated in lymphangiogenesis, but whether any association exists between esophageal cancer, adipokines and VEGF-C is unknown. We examined the relevance of adipokines and VEGF-C in esophageal squamous cell carcinoma (ESCC) in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We found significantly higher levels of visfatin and VEGF-C expression in esophageal cancer tissue than in normal tissue. Immunohistochemistry (IHC) staining identified that higher levels of visfatin and VEGF-C expression were correlated with advanced stage ESCC. Visfatin treatment of ESCC cell lines upregulated VEGF-C expression and VEGF-C-dependent lymphangiogenesis in lymphatic endothelial cells. Visfatin induced increases in VEGF-C expression by activating the mitogen-activated protein kinase kinases1/2-extracellular signal-regulated kinase (MEK1/2-ERK) and Nuclear Factor Kappa B (NF-κB) signaling cascades. Transfecting ESCC cells with MEK1/2-ERK and NF-κB inhibitors (PD98059, FR180204, PDTC, and TPCK) and siRNAs inhibited visfatin-induced increases in VEGF-C expression. It appears that visfatin and VEGF-C are promising therapeutic targets in the inhibition of lymphangiogenesis in esophageal cancer.

Diarylheptanoid 35d overcomes EGFR TKI resistance by inducing hsp70-mediated lysosomal degradation of EGFR in EGFR-mutant lung adenocarcinoma.

Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) patients often respond to EGFR tyrosine kinase inhibitors (TKIs) initially but eventually develop resistance to TKIs. The switch of EGFR downstream signaling from TKI-sensitive to TKI-insensitive is a critical mechanism-driving resistance to TKIs. Identification of potential therapies to target EGFR effectively is a potential strategy to treat TKI-resistant LUADs. In this study, we developed a small molecule diarylheptanoid 35d, a curcumin derivative, that effectively suppressed EGFR protein expression, killed multiple TKI-resistant LUAD cells in vitro, and suppressed tumor growth of EGFR-mutant LUAD xenografts with variant TKI-resistant mechanisms including EGFR C797S mutations in vivo. Mechanically, 35d triggers heat shock protein 70-mediated lysosomal pathway through transcriptional activation of several components in the pathway, such as HSPA1B, to induce EGFR protein degradation. Interestingly, higher HSPA1B expression in LUAD tumors associated with longer survival of EGFR-mutant, TKI-treated patients, suggesting the role of HSPA1B on retarding TKI resistance and providing a rationale for combining 35d with EGFR TKIs. Our data showed that combination of 35d significantly inhibits tumor reprogression on osimertinib and prolongs mice survival. Overall, our results suggest 35d as a promising lead compound to suppress EGFR expression and provide important insights into the development of combination therapies for TKI-resistant LUADs, which could have translational potential for the treatment of this deadly disease.

Diffuse symptomatic pneumocephalus after biportal endoscopic spinal surgery: illustrative case.

BACKGROUND: Percutaneous endoscopic lumbar decompression is gaining attention as a minimally invasive surgery. Here, the authors report a rare complication of pneumocephalus caused by vacuum drain after biportal endoscopic spinal surgery (BESS) for lumbar stenosis. OBSERVATIONS: A 79-year-old woman with spinal stenosis over the L4-5 level received BESS. No visible dural tear was encountered during surgery, and a vacuum drain was placed after surgery. Approximately 150 mL of cerebrospinal fluid was drained on postoperative day 1. Simultaneously, symptoms of intracranial hypotension were noted. Brain computed tomography (CT) revealed pneumocephalus. The patient was advised to have bed rest and hydration, and her symptoms improved subsequently. Follow-up brain CT indicated the resolution of pneumocephalus. LESSONS: Pneumocephalus after endoscopic lumbar surgery is rare. Dural tear, high rate of normal saline irrigation, and vacuum drain placement are the associated risk factors.

Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression.

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.

Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma ≤2 cm in size: A retrospective cohort study.

BACKGROUND/PURPOSE: Lung cancer patients can have advanced-stages at diagnosis, even the tumor size is ≤2 cm. We aimed to study the relationship between image characteristics, clinical, and patholoigcal results. METHODS: We retrospectively enrolled patients with lung adenocarcinoma at Taichung Veterans General Hospital and Chang Gung Memorial Hospital from 2007 to 2015, who were diagnosed with treatment naïve primary tumor lesions at sizes less than 2 cm, as measured by computed tomography (CT) scans. The patient was analyzed for lymph node (LN) and distant metastasis evaluation, with clinicopathological characteristics, including tumor-disappearance ratio (TDR) (tumor diameter at the mediastinal/lung window) over chest CT scans, pathological diagnosis, disease-free survival (DFS), and overall survival (OS). RESULTS: Totally 280 patients were surveyed initially and showed significantly increase of clinical LN involvement and distant metastasis when TDR ≤75% compared with >75% (21.6% vs 0% for LN involvement; 27.1% vs 0% for distant metastasis; both p < 0.001). We included 199 patients having surgical treatment and follow-up for the survival analysis. With a TDR ≤75%, significantly worse DFS (HR, 19.23; 95% CI, 2.60-142.01; p = 0.004) and a trend of worse OS (HR, 4.97; 95% CI, 0.61-40.61; p = 0.134) were noted by Kaplan-Meier method. TDR ≤75% revealed more advanced pathological stage, and more tumors containing micropapillary or solid subtypes when diagnosed adenocarcinoma. CONCLUSION: For lung cancer patients with primary tumor ≤2 cm, TDR ≤75% was related to more advanced stages, the presence of micropapillary or solid components of adenocarcinoma subtypes, worse DFS, and a trend of worse OS.

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue.

AIMS: Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. METHODS AND RESULTS: Nephrectomy specimens of PRCC and PA from our 10-year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow-up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild-type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non-type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non-type D PAs. CONCLUSIONS: Type D PA was different from other types of PA and represented an analogue or a small-sized PRNRP for their identical morphology, immunophenotype and molecular signature.

How does benevolent leadership lead to work-family enrichment? The mediating role of positive group affective tone.

Although researchers have confirmed the relationship between positive leadership styles and work-family enrichment, benevolent leadership has received little attention. Drawing from the concept of mood contagion, this study explores the underlying mechanism between benevolent leadership and work-family enrichment. Using a survey of 459 employees, across 36 supervisors and their work groups, and multilevel structural equation modelling, this study revealed that benevolent leadership is positively associated with work-family enrichment via cross-level paths. The results indicated that benevolent leadership is associated with positive group affective tone, which further predicts subordinates' work-family enrichment. Moreover, work engagement mediates the relationship between positive group affective tone and work-family enrichment. Theoretical and practical implications are discussed.

Granuloma With an Underlying Lymphoma: A Diagnostic Challenge and a Wider Histologic Spectrum Including Adult T-Cell Leukemia/Lymphoma.

Granulomatous reaction is not uncommon in histopathology, with various etiologies in different organs and geographic regions. Lymphoma is one of the underlying causes of granuloma; and sometimes the neoplastic cells may be masked by the granulomatous reaction. In this report, we present our experience with 7 lymphoma cases of various histologic types with coexisting granuloma to show the diagnostic challenges. In all cases, a granulomatous reaction was simultaneously present with the neoplastic cells. The 7 cases included 3 cases of adult T-cell leukemia/lymphoma in the lymph node or skin including one coexisting with mycobacterial infection, 2 cases of classical Hodgkin lymphoma involving the liver, and 1 case each of systemic Epstein-Barr virus-positive peripheral T-cell lymphoma and a hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma. Three cases were initially misdiagnosed as reactive change or mycobacterial infection instead of lymphoma, and a wrong histologic lymphoma type was diagnosed in 1 case. In this report, we showed that granulomatous reaction might mask lymphomas of various histologic types; and a diagnosis of mycobacterial infection or sarcoidosis could not exclude the possibility of an underlying lymphoma. We emphasized the importance of detailed histologic examination with the aid of ancillary studies to reach a correct diagnosis and to avoid inappropriate management of the patients. Our study also broadened the spectrum of lymphoma types coexisting with granuloma.

Health care utilization pattern prior to maltreatment among children under five years of age in Taiwan.

BACKGROUND: Several studies have hypothesized that the pattern of health care utilization among maltreated children differ from others without the experience. However, the conclusions have not been consistent. OBJECTIVE: The study aims to examine whether the pattern of health care utilization among children 0-5 years old with maltreatment different from their counterparts without maltreatment in Taiwan. SUBJECTS AND SETTING: All children born in 2007 in Taiwan. METHOD: This is a population-based and case-controlled study. Cases are children under five years of ago with maltreatment-related diagnosis in the claims data of the National Health Insurance in Taiwan during the 2007-2013 period. For each case, there were 10 birth date-matched controls. Exposure variables include the number of injury or non-injury-related outpatients, emergency department (ED) visits, and hospitalization. Multivariate models were employed, with adjustment for sex, urbanization level, and comorbidities of children. RESULTS: Of children born in 2007, 382 had maltreatment-related diagnosis during the age of 0-5. The adjusted odds ratio (aOR) for having two or more ED visits with or without injury-related diagnosis is 3.52 (95% CI 1.75-7.07) and 2.0-0 (95% CI 1.47-2.72), respectively. Children with maltreatment also had significantly higher number of hospitalization without injury-related diagnosis and aOR for those having two more hospitalizations stands at 2.47 (95% CI 1.59-3.83). CONCLUSIONS: Children with maltreatment when 0-5 years old had higher number of ED visits with injury-related diagnosis, as well as hospitalization without injury-related diagnosis. Recognition of the health care utilization is conducive to early identification of children with risk for maltreatment.

Application of the Milan System for Reporting Salivary Gland Cytopathology: A retrospective study in a tertiary institute.

BACKGROUND: Fine needle aspiration (FNA) cytology has been widely used in the preoperative evaluation of salivary gland lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a tiered risk-stratification scheme designed to standardize reporting and facilitate decision making. We aimed to clarify the validity and diagnostic utility of the MSRSGC-based classification of salivary gland lesions. METHODS: A total of 1020 salivary gland FNA specimens were retrieved between 2008 and 2017, with histologic follow-up data available for 349 specimens. Within the present retrospective study, each specimen with follow-up data was reclassified according to the MSRSGC diagnostic categories: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), and malignant. The risk of malignancy (ROM) was calculated based on the histologic follow-up data. RESULTS: The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the MSRSGC-based classification of the malignant potential of salivary gland lesions were 80.1%, 70.4%, 99.2%, 90.5%, and 96.7%, respectively. The ROM calculated for specimens assigned to the nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, SM, and malignant categories were 8.6%, 15.4%, 36.8%, 2.6%, 32.3%, 71.4%, and 100%, respectively. CONCLUSION: The present results confirm the validity and diagnostic utility of MSRSGC, supporting its use in clinical practice to help devise adequate management strategies for salivary gland lesions.

Long-Term Follow-up in Patients with Spontaneous Intracerebral Hemorrhage Treated With or Without Surgical Intervention: a Large-Scale Retrospective Study.

Debates regarding the most beneficial medical or surgical procedures for patients with spontaneous intracerebral hemorrhage (sICH) are still ongoing. We aimed to evaluate the risk of subsequent vascular disease and mortality in patients with sICH treated with and without surgical intervention, in a large-scale Asian population. Patients hospitalized within 2000 to 2013 who were newly diagnosed with sICH were identified using the National Health Insurance Research Database of Taiwan. Neuroendoscopy and craniotomy groups comprised patients who underwent surgical treatment within 1 week, while those in the control group did not undergo early surgical treatment. Outcomes included subsequent hemorrhagic and ischemic stroke, following acute myocardial infarction, congestive heart failure, and mortality. After propensity score matching, there were 663 patients in each group. Compared to that in the control group, the neuroendoscopy and craniotomy groups had a significantly higher risk of secondary vascular events at 1 to 3 months of follow-up (adjusted HR, 2.08 and 1.95; 95% CI, 1.21-3.58 and 1.13-3.35; p < 0.01 and p < 0.05, respectively), but a significantly lower risk after 3 years of follow-up (adjusted HR, 0.52 and 0.52; 95% CI, 0.35-0.78 and 0.35-0.77; p < 0.01 and p < 0.01, respectively). The mortality rate was higher in the craniotomy group at 6 to 12 months of follow-up (adjusted HR, 2.18; 95% CI, 1.06-4.49; p < 0.05) compared to that in the control group. Thus, a timely surgical intervention for hematoma evacuation is advantageous in preventing secondary vascular events and improving outcomes in the long term. However, greater attention to secondary ischemic stroke following the initial sICH episode is needed.

Comparison of radiological outcomes and complications between single-level and multilevel anterior cervical discectomy and fusion (ACDF) by using a polyetheretherketone (PEEK) cage-plate fusion system.

This study aimed to compare the differences in radiological outcomes and complications between single- and multilevel anterior cervical discectomy and fusion (ACDF) by using a polyetheretherketone (PEEK) cage-plate fusion system.Fifty-seven patients who underwent ACDF via the PEEK cage-plate fusion system were enrolled and subjected to ≥6 months of follow-up. The patients were divided into 4 groups according to different cage-plate implantation levels: 1-level group (n = 17), 2-level group (n = 24), 3-level group (n = 12), and 4-level group (n = 4). Fusion time, changes in segment and global lordotic angle, subsidence rate, and changes in disc and adjacent segmental disc height were subjected to radiological evaluation.The fusion period of multilevel ACDF was longer than that of single-level ACDF. The fusion period of the 3-level (4.09 ±â€Š0.94, P = .004) and 4-level (5.25 ±â€Š0.89, P = .004) group was also significantly longer than that of the 1-level group. The mean lordotic angle in all of the groups was changed in the immediate postoperative period and in the final follow-up. The cage subsidence rates were 11.76% (2/17) in the 1-level group, 20.83% (5/24) in the 2-level group, and 2/12 (16.67%) in the 3-level group. No subsidence occurred in the 4-level groups. Changes in the lower adjacent segmental disc height were significantly increased in multilevel ACDF compared with those in single-level ACDF.Despite the longer fusion time, the outcomes of the proposed system were even better with the greater number of treatment levels by using PEEK cage-plate fusion system. Changes in the lower adjacent segmental disc height should also prolong follow-up duration to investigate the symptomatic adjacent segment degeneration in multilevel ACDF.

Prognostic Significance of 14-3-3ε, Aldo-keto Reductase Family 1 B10 and Metallothionein-1 in Hepatocellular Carcinoma.

BACKGROUND/AIM: Expression of 14-3-3ε is associated with prognostic outcomes of hepatocellular carcinoma (HCC) patients. Metallothionein-1 (MT-1) proteins and aldo-keto-reductase family 1 B10 (AKR1B10) are considered potential tumor regulators of HCC. The aim of this study, was to examine the prognostic value of 14-3-3ε, MT-1 and AKR1B10 expression in HCC. MATERIALS AND METHODS: The expression levels of 14-3-3ε, MT-1 and AKR1B10 in HCC cell lines and paraffin-embedded tissues were examined by western blotting and immunohistochemical analysis. RESULTS: 14-3-3ε positivity was significantly associated with decreased MT-1 expression in HCC. Patients with decreased MT-1 expression had worse survival rates and a higher risk of metastasis than 14-3-3ε-positive HCC patients with unchanged MT-1 expression. Distinct expression patterns of 14-3-3ε/MT-1/AKR1B10 were significantly associated with the metastatic incidence and survival rates of HCC patients. Patients with negative 14-3-3ε staining in primary tumors had better prognostic outcomes. In contrast, patients with positive 14-3-3ε staining, decreased MT-1 expression and no increase in AKR1B10 expression in primary tumors had the worst overall and disease-free survival rates and the highest metastatic risk. CONCLUSION: 14-3-3ε, AKR1B10, and MT-1 act as potential prognostic biomarkers of HCC.

Characteristics and Predictive Value of PD-L1 Status in Real-World Non-Small Cell Lung Cancer Patients.

Immunotherapy targeting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway has emerged as an effective treatment for lung cancer patients. It is important to evaluate the practicality of PD-L1 testing in real-world practice. A total of 211 non-small cell lung cancer patients were enrolled to detect 5 driver mutations and PD-L1 status (22C3 and SP263 assays) and to evaluate the characteristics of PD-L1 expression and its predictive value of immunotherapy. The PD-L1 positive (≥1%) and strong positive (≥50%) rate by SP263 assay was 27.0% and 12.8%. The concordance rates between 2 PD-L1 assays while using 1%, 10%, 25%, and 50% positive tumor cells as the cutoffs were 76.8%, 81.5%, 90.5%, and 94.3%, respectively. Smokers and patients without known actionable driver mutation were more likely to present strong positive PD-L1 [adjusted hazard ratio, 5.00 (95% confidence interval-CI, 1.60-15.64); P=0.006 and 3.59 (95% CI, 1.25-10.33); P=0.018, respectively]. Higher levels of smoking were associated with higher PD-L1 expressions. None of the EGFR, ALK, HER2, or BRAF-mutant nonsmokers displayed strong positive PD-L1 expression by SP263 assay. Among patients undergoing PD-1 checkpoint inhibitors therapy, high PD-L1 expression by SP263 was associated with a longer progression-free survival [adjusted hazard ratio, 0.15 (95% CI, 0.03-0.71); P=0.017]. In conclusion, our results suggest that PD-L1 status remains an important predictor of immunotherapy efficacy. The concordance between 22C3 and SP263 assays was greater at a higher cutoff level of positivity. Patients without known actionable driver mutation, along with smokers, particularly those having high smoking pack-years, were more likely to have strong PD-L1 expression.