A polysomnographic study of slow-wave sleep loss in elderly patients with epilepsy.

Objective: The primary objective is to explore what causes slow-wave sleep loss in elderly patients with epilepsy. The secondary objective is to identify the PSG characteristics in elderly patients with epilepsy. The clinical demographics, sleep architecture, sleep-related events, and interictal epileptiform discharges are to be evaluated in the objectives. Methods: The video electroencephalography (VEEG) and polysomnogram (PSG) data from 44 elderly patients with epilepsy and 52 elderly patients with sleep disorders but without definite central nervous system diseases were analysed. This was a case-control study. The differences in the PSG sleep architecture parameters (total sleep time (TST), sleep efficiency, wake after sleep onset, etc.) and sleep-related events (apnea hypopnea index, oxygen desaturation index (ODI), periodic limb movement index, etc.) between the epilepsy and control groups. As Additionally, these parameters were assessed within the elderly patients with epilepsy, comparing the slow-wave sleep existence and slow-wave sleep loss groups, using VEEG and PSG. Results: The epileptic group exhibited significantly lower TST (343.477 ± 96.3046min vs 389.115 ± 61.5727min, p < 0.05), rapid eye movement (%) (13.011 ± 7.5384 vs 16.992 ± 6.7025, p < 0.05), non-rapid eye movement stage 3 (%) (1.35[0,7.225] vs 3.65[0.425,13.75], p < 0.05), and sleep efficiency (%) (69.482 ± 14.1771% vs 77.242 ± 10.6171%, p < 0.05). Conversely, the ODI (25.6[9.825,51.775] events/hour vs 16.85[5.3,30.425] events/hour, p < 0.05) and spontaneous arousal index (4.0455[2.1805,6.9609] events/hour vs 2.9709[1.4747,5.0554] events/hour, p < 0.05) were significantly higher in elderly patients with epilepsy. The prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) was significantly higher in the slow-wave sleep loss group than in the slow-wave sleep existence group (100% vs 77.8%, p < 0.05). The incidence of slow-wave sleep loss was lower in patients with epilepsy aged between 75 and 85 years compared to those aged between 65 and 75 years. Conclusion: Elderly patients with epilepsy exhibit higher levels of ODI and spontaneous arousal index. Our findings indicate that OSAHS could be a contributing factor to slow-wave sleep loss in this population. The incidence of slow-wave sleep loss was lower in patients aged above 75 years among elderly patients with epilepsy.

Insulin resistance-related features are associated with cognitive decline: a cross-sectional study in adult patients with type 1 diabetes.

BACKGROUND: To investigate the associations between insulin resistance (IR)-related features and cognitive function in type 1 diabetes (T1D). METHODS: A total of 117 adult patients with T1D were recruited in this cross-sectional study. IR-related features include overweight/obesity/central obesity, hypertension, atherogenic dyslipidemia, and decreased estimated insulin sensitivity (eIS). The Wechsler Memory Scale-Chinese Revision, Wisconsin Card Sorting Test, and Sustained Attention to Response Task was used to assess memory, executive function and sustained attention, respectively. A z-score was generated from each test, and a composite measure of global cognitive performance was calculated by averaging the z-scores of all tests. Cognitive differences were measured between T1D patients with and without IR-related features. The associations between IR-related features and and cognitive performance were analyzed using: logistic regression, partial correlation, and multivariate linear regression analysis. RESULTS: A total of 53 (45.3%) T1D patients were defined as having IR-related features. Individuals with IR-related features displayed worse overall cognitive scores compared to those without and had a 4-fold increase in the risk for having global cognitive z-score < 0. Among the IR-related features, higher triglyceride (TG) and lower eIS showed linear correlation with lower global cognitive performance. And the subsequent regression analysis identified eIS as the factor independently associated with global cognitive performance. CONCLUSIONS: We have provided evidence linking IR-related features to deteriorated cognitive function in adult patients with T1D. And eIS showed an independent positive correlation with global cognitive performance. Although no causal relationship can be drawn, IR emerges as an important factor reflecting cognitive function. TRIAL REGISTRATION: ClinicalTrials.gov NCT03610984.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Radionecrosis mimicking pseudo­progression in a patient with lung cancer and brain metastasis following the combination of anti­PD­1 therapy and stereotactic radiosurgery: A case report.

Brain metastases (BMs) usually develop in patients with non-small cell lung cancer. In addition to systemic therapy, radiation therapy and surgery, anti-programmed cell death-ligand 1 (PD-L1) therapy is another promising clinical anticancer treatment modality. However, the optimal timing and drug-drug interactions of anti-PD-L1 therapy with other combined treatments remain to be elucidated. Treatment with anti-PD-L1 therapy is associated with an increased risk of radionecrosis (RN) regardless of tumor histology. The present study described a case of RN in a patient with lung adenocarcinoma and with BM who received anti-PD-L1 therapy. Before anti-PD-L1 treatment, the patient received whole brain radiotherapy. During durvalumab treatment, the intracranial metastases regressed. The progression of intracranial lesions 9 months later prompted a second-line of therapy with PD-L1 inhibitor durvalumab and stereotactic radiotherapy (SRT). Despite stereotactic irradiation, the lesions progressed further, leading to surgical resection. On examination, RN was detected, but there was no evidence of metastatic lung cancer. The aim of the present study was to present the longitudinal change in magnetic resonance imaging in RN following STR and anti-PD-L1 combined therapy. The atypical image of RN is conditionally important for making an accurate preoperative diagnosis.

Fat-to-muscle ratio is associated with insulin resistance and cardiometabolic disorders in adults with type 1 diabetes mellitus.

AIMS: This study aimed to investigate the correlation of the fat-to-muscle ratio (FMR) with insulin resistance (IR) and cardiometabolic disorders (CMD) in patients with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: We retrospectively recruited 420 adults with T1DM [52.6% men, median age 32.4 (24.5, 43.0) years]. Body composition was assessed by bioelectrical impedance analysis and FMR was calculated. The characteristics of the overall participants were compared between tertiles of FMR. Logistic regression analyses were performed to assess the association of FMR tertiles with IR and cardiometabolic risk factors. RESULTS: Median age and median haemoglobin A1c of all participants were 32.4 (24.5, 43.0) years and 7.4 (6.5, 8.7)%, respectively. The prevalence of IR and CMD was 18% and 38.6%. The FMR significantly differed between men and women [0.39 (0.31, 0.53) vs. 0.74 (0.63, 0.92), respectively, p < .001]. The proportion of IR and CMD gradually increased as the FMR increased. The multivariable-adjusted odd ratios for IR and CMD in FMR tertile 3 compared with tertile 1 were 4.8 [95% confidence interval (CI): (1.9, 12.1)] and 9.7 (95% CI: 4.2, 22.3), respectively, in men. For women, the corresponding odd ratios were 4.0 (95% CI: 1.2, 12.9) for IR and 5.8 (95% CI: 2.4, 13.6) for CMD. CONCLUSIONS: FMR is associated with IR and CMD in adults with T1DM and could be used as a promising parameter for targeting treatment in T1DM.

Biology of breast cancer brain metastases and novel therapies targeting the blood brain barrier: an updated review.

Brain metastasis (BM) is a critical cause of morbidity and mortality in patients with breast cancer (BC). Compared with other cancer cells, BC cells (BCs) exhibit special features in the metastatic process. However, the underlying mechanisms are still unclear, especially the crosstalk between tumour cells and the microenvironment. To date, novel therapies for BM, including targeted therapy and antibody‒drug conjugates, have been developed. Due to an improved understanding of the blood‒brain barrier (BBB) and blood-tumour barrier (BTB), the development and testing of therapeutic agents in clinical phases have substantially increased. However, these therapies face a major challenge due to the low penetration of the BBB or BTB. As a result, researchers have increasingly focused on finding ways to promote drug penetration through these barriers. This review provides an updated overview of breast cancer brain metastases (BCBM) and summarizes the newly developed therapies for BCBM, especially drugs targeting the BBB or BTB.

Insulin resistance is more frequent in type 1 diabetes patients with long disease duration.

AIMS: To investigate the clinical status of insulin resistance (IR) and its correlation with disease duration in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional data from a T1D cohort were obtained (n = 923). IR-related metabolic disorders including hypertension, obesity, and dyslipidemia were used as outcome variables to explore the cut-off point for estimated glucose disposal rate (eGDR) by restricted cubic spline (RCS) curve. Regression models were used for multivariate analysis of the clinical factors associated with IR. The correlation between the status of IR and diabetes duration was depicted with the RCS curve. RESULTS: IR-related metabolic disorders were observed in 39.4% of patients, with 9.1% meeting the criteria for metabolic syndrome. Specifically, patients with ≥10 years of T1D were more likely to have IR-related metabolic disorders (54.7% vs. 36.9%, p < 0.05). The presence of IR, defined as an eGDR ≤9.0 mg/kg/min, was observed in 42.2% of patients. Patients with IR had a longer diabetes duration (3.5 vs. 2.7, years, p = 0.003) and higher insulin dose (0.5 vs. 0.4, units per kg per day, p < 0.001). Moreover, the presence of IR showed a gradual increase during 10 years' disease duration and further analysis showed that diabetes duration ≥10 years was a key element behind the development of IR and IR-related metabolic disorders. CONCLUSIONS: The status of IR is common in T1D patients, especially in those with ≥10 years of disease duration. Therapies targeting balancing glycaemic control and IR are needed to decrease the future risk of cardiovascular diseases in T1D. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03610984 (cohort study of patients with type 1 diabetes).

Circ_0000285 regulates nasopharyngeal carcinoma progression through miR-1278/FNDC3B axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is cancer with high mortality and poor prognosis. Circular RNAs (circRNAs) have been identified in a wide variety of cancers. But the functional mechanism of circ_000285 in NPC remains unclear. PURPOSE: To decipher the biological function and molecular mechanism of circ_000285 in NPC. METHODS: Quantitative PCR (RT-qPCR) was applied for detecting the expression of circ_0000285, miR-1278, and FNDC3B. Western blot was used to measure the protein levels of Fibronectin type III domain containing 3B (FNDC3B), Bcl2 associated X (Bax), and B cell leukemia/lymphoma 2 (Bcl2). Cell proliferation, migration, and invasion were analyzed by colony formation, 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays. Cell apoptosis was detected by flow cytometry assays. ELISA assay was used to analyze Caspase-3 activity. Bioinformatics was used to predict, and the target relationship between miR-1278 and circ_0000285 or FNDC3B was verified by luciferase reporter assay. Tumor xenograft models were established to examine how circ_0000285 functions during the mediation of NPC tumor growth in vivo. RESULTS: Increased circ_0000285 and FNDC3B expressions, and a decreased miR-1278 expression were observed in NPC tissues and cell lines. Knockdown of circ_0000285 inhibited NPC cell proliferation, migration, invasion, and while promoting NPC cell apoptosis in vitro. Circ_0000285 knockdown-mediated anti-tumor effects in NPC cells could be largely reversed by silencing of miR-1278 or overexpression of FNDC3B. Circ_0000285 could up-regulate FNDC3B expression by sponging miR-1278 in NPC cells. Knockdown of circ_0000285 could inhibit tumor growth in vivo. CONCLUSION: Circ_0000285 upregulates FNDC3B expression by adsorbing miR-1278 to promote NPC development.

Poorly differentiated cluster grade-a vital predictor for lymph node metastasis and oncological outcomes in patients with T1 colorectal cancer: a retrospective study.

BACKGROUND: T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers. METHODS: We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated. RESULTS: Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 = < 0.001, 0.139) in T1 colorectal cancer patients; moreover, it had the best predictive value (AIC = 61.626) among all indicators. It was also screened for inclusion in the predictive model. Accordingly, a high poorly differentiated cluster grade independently indicated shorter overall survival (hazard ratio [HR]G 2 = 4.315; 95% CIG 2 = 1.506, 12.568; HRG 3 = 5.049; 95% CIG 3 = 1.326, 19.222) and disease-free survival (HRG 3 = 6.621; 95% CIG 3 = 1.472, 29.786). CONCLUSIONS: Poorly differentiated cluster grade is a vital reference to manage T1 colorectal cancer. It could serve as an indicator to screen endoscopically curable T1 colorectal cancers.

Using Glycated Albumin and Stimulated C-Peptide to Define Partial Remission in Type 1 Diabetes.

Objective: To propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the optimal cut-off values for stimulated C-peptide to diagnose PR in different age-groups. Research Design and Methods: Patients with newly diagnosed T1D (n=301) were included. GA/insulin dose was used to diagnose PR, and insulin dose-adjusted glycated albumin (IDAGA) was proposed to facilitate clinical application. The optimal diagnostic levels of IDAGA and stimulated C-peptide were determined in different age-groups (≤ 12y, 12-18y and ≥ 18y). Furthermore, the diagnostic consistency between different PR definitions was studied. Results: GA≤ 23%/insulin dose ≤ 0.5u/kg/day was used to define PR, and IDAGA (GA (%) + 40 * insulin dose(u/kg/day)) ≤ 40 was feasible in all age-groups. Whereas, the optimal diagnostic level showed difference for stimulated C-peptide (265.5, 449.3 and 241.1 pmol/L for the ≤ 12y, 12-18y and ≥ 18y age-group, respectively). About 40% of patients met the PR definition by stimulated C-peptide but not GA/insulin dose or IDAGA, who showed dyslipidemia and higher insulin resistance. Conclusions: A new definition of the PR phase is proposed using GA/insulin dose, and the calculated IDAGA≤ 40 applies to all age-groups. The stimulated C-peptide to diagnose PR is the highest in the 12-18y age-group, which reflects the effect of puberty on metabolism. For patients with insulin resistance, it is not recommended to use stimulated C-peptide alone to diagnose PR.

Asiaticoside Suppresses Gastric Cancer Progression and Induces Endoplasmic Reticulum Stress through the miR-635/HMGA1 Axis.

Objective: Gastric cancer is a prevalent malignant tumor with high morbidity and poor prognosis. Asiaticoside (AC) has antitumor effects, while its role in gastric cancer is elusive. Thus, this study investigated the effect of AC on gastric cancer progression. Methods: Cell viability and migration were determined using the CCK-8 and Transwell migration assay. Endoplasmic reticulum stress was detected through measuring the expressions of GRP78, Chop, and hnRNPA1 by Western blot. The luciferase assay confirmed the relationship between miR-635 and High Mobility Group AT-Hook 1 (HMGA1). The effect of AC on tumor growth was evaluated by establishing a xenograft tumor. The survival rate of mice was analyzed by Kaplan-Meier analysis. Results: AC suppressed gastric cancer cell viability and restrained cell migration. AC inhibited the expressions of the cell proliferation marker PCNA and EMT-related marker N-cadherin and increased E-cadherin expression. AC elevated the levels of GRP78 and Chop and suppressed the level of hnRNPA1. In addition, AC restrained gastric cancer proliferation and migration ability and induced endoplasmic reticulum stress by upregulating miR-635 expression. Furthermore, HMGA1 was proven to be a target of miR-635. AC constrained gastric cancer cell proliferation and migration and promoted endoplasmic reticulum stress by regulating HMGA1. Moreover, AC suppressed in vivo tumor growth and improved the survival time of mice. Additionally, AC elevated the expressions of miR-635, E-cadherin, GRP78, and Chop and inhibited Ki-67, HMGA1, N-cadherin, and hnRNPA1 expressions in tumor tissues of mice. Conclusion: AC suppressed gastric cancer progression and induced endoplasmic reticulum stress via the miR-635/HMGA1 axis, providing a valuable drug against gastric cancer.

Identifying Patients at High Risk of Chronic Pain After Video-Assisted Thoracoscopic Surgery Using Thermal Quantitative Sensory Testing.

OBJECTIVE: To examine whether perioperative thermal quantitative sensory testing could be used to identify patients at high risk of chronic pain after video-assisted thoracoscopic surgery (VATS). DESIGN: A single-center, prospective, observational study. SETTING: At the Peking University People's Hospital. PARTICIPANTS: A total of 111 patients scheduled to undergo VATS were enrolled. INTERVENTIONS: Quantitative sensory testing was conducted at the anterior intercostal incision prior to surgery and after chest tube removal. MEASUREMENTS AND MAIN RESULTS: The patient's chronic pain was assessed at 3 months after surgery using a questionnaire. The incidence of chronic pain was 35 out of 107 evaluable patients (32.7%). Among the 35 patients with chronic pain, 26 had features characteristic of neuropathic pain (74.3%). Compared to the patients without chronic pain, subjects with chronic pain had a significantly greater perioperative change in cold pain threshold (CPT; p = 0.032), but not cold detection threshold, warm detection threshold, and hot pain threshold . In the multivariate regression, perioperative CPT change was associated with chronic pain after VATS (odds ratio = 1.043, p = 0.026). CONCLUSIONS: Chronic pain after VATS is typically neuropathic. The change in perioperative CPT at the incision site may help to identify patients at higher risk of chronic pain after VATS.

Chitosan oligosaccharide regulates AMPK and STAT1 pathways synergistically to mediate PD-L1 expression for cancer chemoimmunotherapy.

After regular chemotherapy, the expression of programmed cell death ligand 1 (PD-L1) in almost all kinds of cancers is significantly increased, leading to reduced efficacy of T cell mediated immune killing in tumors. To solve this, a lot of PD-L1 antibodies were produced and used, but their high cost and serious toxic side effects still limit its usage. Recently, small molecule compounds that could effectively regulate PD-L1 expression possess the edges to solve the problems of PD-L1 antibodies. Chitosan oligosaccharide (COS), a biomaterial derived from the N-deacetylation product of chitin, has a broad spectrum of biological activities in treating tumors. However, the mechanism of its anti-cancer effect is still not well understood. Here, for the first time, we clearly identified that COS could inhibit the upregulated PD-L1 expression induced by interferon γ (IFN-γ) in various tumors via the AMPK activation and STAT1 inhibition. Besides, COS itself significantly restricted the growth of CT26 tumors by enhancing the T cell infiltration in tumors. Furthermore, we observed that combining COS with Gemcitabine (GEM), one of the typical chemotherapeutic drugs, leaded to a more remarkable tumor remission. Therefore, it was demonstrated that COS could be used as a useful way to improve the efficacy of existing chemotherapies by effective PD-L1 downregulation.

Suprascapular nerve block and axillary nerve block versus interscalene nerve block for arthroscopic shoulder surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: The interscalene brachial plexus block (ISB) is a commonly used nerve block technique for postoperative analgesia in patients undergoing shoulder arthroscopy surgery; however, it is associated with potentially serious complications. The use of suprascapular nerve block (SSNB) and axillary Nerve Block (ANB) has been reported as an alternative nerve block with fewer reported side effects for shoulder arthroscopy. This review aimed to compare the impact of SSNB and ANB with ISB during shoulder arthroscopy surgery. METHODS: A meta-analysis was conducted to identify relevant randomized or quasirandomized controlled trials involving SSNB and ISB during shoulder arthroscopy surgery. We searched Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database from 2010 through August 2021. RESULTS: We identified 641 patients assessed in 10 randomized or quasirandomized controlled trials. Compared with the ISB group, the SSNB+ANB group had higher visual analog scale or numerical rating scale in PACU (P = .03), 4 hour (P = .001),6 hour after the operation (P = .002), and lower incidence of complications such as Numb/Tingling (P = .001), Weakness (P <.00001), Horner syndrome (P = .001) and Subjective dyspnea (P = .002). No significant difference was found for visual analog scale or numerical rating scale 8 hour (P = .71),12 hour (P = .17), 16 hour (P = .38),1day after operation (P = .11), patient satisfaction (P = .38) and incidence of complications such as hoarseness (P = .07) and nausea/vomiting (P = .41) between 2 groups. CONCLUSION: Our high-level evidence has established SSNB+ ANB as an effective and safe analgesic technique and a clinically attractive alternative to interscalene block during arthroscopic shoulder surgery, especially for severe chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity. Given our meta-analysis's relevant possible biases, we required more adequately powered and better-designed randomized controlled trial studies with long-term follow-up to reach a firmer conclusion.

Temporal trends in incidence and mortality rates of laryngeal cancer at the global, regional and national levels, 1990-2017.

OBJECTIVES: Laryngeal cancer is the most prevalent entity of head and neck cancer. Knowing the trends of incidence and mortality of laryngeal cancer is important for the reduction in related disease burden. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The incidence and mortality data of laryngeal cancer were retrieved from the Global Burden of Disease study 2017 online database. The estimated average percentage change was used to quantify the trends of laryngeal cancer incidence and mortality at the global, regional and national levels. RESULTS: Globally, the numbers of incident cases and deaths due to laryngeal cancer increased 58.7% and 33.9%, respectively, from 1990 to 2017. However, the overall age-standardised incidence rate (ASIR) and age-standardised mortality rate decreased by 0.99% (95% CI 0.83% to 1.14%) and 1.62% (95% CI 1.50% to 1.74%) per year, respectively. These decreases were ubiquitous worldwide. However, unfavourable trends in the ASIR of laryngeal cancer were also observed in a total of 51 developing countries. CONCLUSIONS: The incidence and mortality rates of laryngeal cancer have significantly decreased at the global level and in most countries over the past three decades. The regions that showed an increasing incidence trend deserve more attention.

SPP1 overexpression is associated with poor outcomes in ALK fusion lung cancer patients without receiving targeted therapy.

The screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer.

Suprascapular nerve block is a clinically attractive alternative to interscalene nerve block during arthroscopic shoulder surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: The interscalene brachial plexus block (ISB) is a commonly used nerve block technique for postoperative analgesia in patients undergoing shoulder arthroscopy surgery; however, it is associated with potentially serious complications. The use of suprascapular nerve block (SSNB) has been described as an alternative strategy with fewer reported side effects for shoulder arthroscopy. This review aimed to compare the impact of SSNB and ISB during shoulder arthroscopy surgery. METHODS: A meta-analysis was conducted to identify relevant randomized controlled trials involving SSNB and ISB during shoulder arthroscopy surgery. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through March 2021. RESULTS: We identified 1255 patients assessed in 17 randomized controlled trials. Compared with the ISB group, the SSNB group had higher VAS at rest in PACU (P = 0.003), 1 h after operation (P = 0.005), similar pain score 2 h (P = 0.39), 3-4 h (P = 0.32), 6-8 h after operation (P = 0.05), then lower VAS 12 h after operation (P = 0.00006), and again similar VAS 1 day (P = 0.62) and 2 days after operation (P = 0.70). As for the VAS with movement, the SSNB group had higher pain score in PACU (P = 0.03), similar VAS 4-6 h after operation (P = 0.25), then lower pain score 8-12 h after operation (P = 0.01) and again similar VAS 1 day after operation (P = 0.3) compared with the ISB group. No significant difference was found for oral morphine equivalents use at 24 h (P = 0.35), duration of PACU stay (P = 0.65), the rate of patient satisfaction (P = 0.14) as well as the rate of vomiting (P = 0.56), and local tenderness (P = 0.87). However, the SSNB group had lower rate of block-related complications such as Horner syndrome (P < 0.0001), numb (P = 0.002), dyspnea (P = 0.04), and hoarseness (P = 0.04). CONCLUSION: Our high-level evidence established SSNB as an effective and safe analgesic technique and a clinically attractive alternative to interscalene block with the SSNB'S advantage of similar pain control, morphine use, and less nerve block-related complications during arthroscopic shoulder surgery, especially for severe chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity. Given our meta-analysis's relevant possible biases, we required more adequately powered and better-designed RCT studies with long-term follow-up to reach a firmer conclusion.

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.