A comprehensive analysis of Glasgow Prognostic Score (GPS)/the modified Glasgow Prognostic Score (mGPS) on immune checkpoint inhibitor efficacy among patients with advanced cancer.

BACKGROUND: The association between Glasgow Prognostic Score (GPS) and the modified Glasgow Prognostic Score (mGPS) and clinical outcomes in patients receiving immune checkpoint inhibitors (ICIs) remains controversial. Thus, this meta-analysis aimed to examine the prognostic performance of GPS and mGPS in patients treated with ICIs. METHODS: Eligible studies were retrieved from searches of EMBASE, PubMed, Web of Science, and Cochrane Library until July 2021. The hazard ratio (HR) and 95% confidence intervals (CIs) were pooled by using fixed-effect or random-effects model to evaluate the influence of GPS/mGPS on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 1164 patients were included. Overall, mGPS score of 2 and 1 were related to inferior OS (p < 0.001) and PFS (p < 0.001). Subgroup analyses showed no significant association between mGPS score of 1 and OS in patients with non-small cell lung cancer (NSCLC), while this score was significantly associated with poor PFS in patients with NSCLC and head and neck squamous cell carcinoma. Higher GPS (score of 1 or 2) were associated with poor clinical outcomes (OS: p < 0.001; PFS: p = 0.036). Subgroup analysis showed high GPS levels were linked to worse OS in patients with NSCLC and gastric cancer, but not for PFS in these patients. Regarding test time point, GPS was related to worse OS and PFS in pre-treatment GPS group, but not in post-treatment GPS group. CONCLUSION: GPS and mGPS showed great potential to predict survival in patients treated with ICIs. Large and perspective trial are warranted to further validate these findings.

Comparison of the Efficacy and Safety of Transarterial Chemoembolization Plus Microwave Ablation versus Surgical Resection in Patients with Solitary Large Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

Background: The liver resection for solitary large hepatocellular carcinoma (SLHCC) remains controversial due to the high risk of complications and recurrence after resection. This study aimed to compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus microwave ablation (MWA) with resection for SLHCC. Methods: We retrospectively analyzed a total of 148 patients who were treated with either TACE-MWA (n = 94) or resection (n = 54) for SLHCC (≥5 cm). A matched cohort composed of 86 patients was included after propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and safety. Results: The TACE-MWA group was older with higher ALT and AST (all P < 0.05). After PSM, the 1-, 3-, and 5-year OS were 100%, 80.3%, and 51.0% in the TACE-MWA group, and 88.3%, 66.7%, and 39.4% in the liver resection group, respectively. The 1-, 3-, and 5-year PFS were 76.7%, 48.8%, and 19.6% in the TACE-MWA group, and 72%, 40.2%, and 22.6% in the liver resection group, respectively. There was no significant difference in OS and PFS between the two groups (all P > 0.05). For SLHCC patients with tumor size ≥7cm, TACE-MWA showed favorable OS than liver resection. The TACE-MWA group exhibited a lower rate of major complications and shorter hospital stay than the resection group. Conclusion: TACE-MWA showed comparable efficacy to liver resection in patients with SLHCC, but better safety and shorter hospital stay. TACE-MWA might provide a longer OS than liver resection for SLHCC patients with tumor size ≥7cm.

A novel inflammation-associated prognostic signature for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) are typically situated in a complex inflammatory and immune microenvironment, which has been reported to contribute to the unfavorable prognosis of patients with ccRCC. There would be beneficial clinical implications for elucidating the roles of its molecular characteristics in the inflammatory microenvironment. This is because it would facilitate the development of reliable biomarkers for pre-stratification prior to the designation of individualized treatment strategies. In the present study, RNA-sequencing data from 607 patients were retrospectively analyzed to elucidate the profile of inflammatory molecules. Based on this, an inflammatory prognostic signature (IPS) was developed and further validated using clinical ccRCC samples. Subsequently, the associated mechanisms in terms of the immune microenvironment and molecular pathways were then investigated. This proposed IPS was found to exhibit superior accuracy compared with the criterion of a good prognostic model for the prediction of patient prognosis from ccRCC [area under the receiver operating characteristic curve (AUC)=0.811] in addition to being an independent factor for prognostic risk stratification [hazard ratio: 11.73 (95% CI, 26.98-5.10); log-rank test, P<0.001]. Pathologically, ccRCC cells identified as high-risk according to their IPS presented with a more malignant tumor structure, including voluminous eosinophilic cytoplasm, acinar/lamellar/tubular growth patterns and atypic nuclei. High-risk ccRCC also exhibited higher infiltration levels by four types of immune cells, including T regulatory cells, but lower infiltration levels by mast cells. Pathways associated with immune-inflammation interaction, including the IL-17 pathway, were found to be upregulated in IPS-identified high-risk ccRCC. Furthermore, by combining the IPS with clinical factors, an integrated prognostic index was developed and validated for increasing the accuracy of patient risk-stratification for ccRCC (AUC=0.911). In conclusion, the complex regulatory mechanisms and molecular characteristics involved in ccRCC-inflammation interaction, coupled with their prognostic potential, were systematically elucidated in the present study. This may have important implications in furthering the understanding into the molecular mechanisms underlying this ccRCC-inflammation interaction, which can in turn be exploited for identifying high-risk patients with ccRCC prior to designing their clinical treatment strategy.

Rice bran-modified wheat gluten nanoparticles effectively stabilized pickering emulsion: An interfacial antioxidant inhibiting lipid oxidation.

This study investigated the fabrication of Pickering emulsion stabilized by rice bran-modified wheat gluten nanoparticle (RGNP) and evaluated the effect of rice bran-modification on lipid oxidation of emulsified soybean oil, with native wheat gluten nanoparticle (CGNP) as the control. Compared with CGNP, RGNP exhibited stronger antioxidant activities due to high content of polyphenols. RGNP were roughly spherical (mean size of about 250 nm) with balanced wettability (104.6 ± 2.3°) and had excellent colloidal thermal stability. When used at a concentration of 1.5 wt%, both CGNP and RGNP could stabilize Pickering emulsions at varying oil volume fractions (0.20-0.85). For high internal phase emulsions, nanoparticles adsorbed at an oil-water interface forming an interconnected network structure, depressing the oxidation of soybean oil. RGNP as an interfacial antioxidant further improved the Pickering emulsion' oxidative stability. This work may expand the application of wheat gluten as an antioxidant solid particle in Pickering emulsion.

Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis.

Background: Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0. Results: The eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%-70%). The pooled OS rate was 94% (95% CI: 83%-100%) at 6 months, 87% (95% CI: 74%-96%) at 12 months, and 42% (95% CI: 16%-70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%). Conclusions: Immune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.

The effect of concomitant use of statins, NSAIDs, low-dose aspirin, metformin and beta-blockers on outcomes in patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Immunotherapy shows promising therapeutic efficacy against various types of cancer, but most fail to respond. Preclinical studies have suggested that concomitant medications, such as statins, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, metformin and beta-blockers, might affect clinical outcomes if used with immune checkpoint inhibitors (ICIs), but their clinical roles are conflicting. This meta-analysis investigates the effect of these concomitant medications on outcomes in patients treated with ICIs. A search was conducted for all reports published until 31 March 2021 in PubMed, Web of Science, Cochrane Library, EMBASE and conference proceedings. Studies were included if they investigated the association between the concomitant use of these medications and progression-free survival (PFS) or overall survival (OS) during ICI treatment. A total of 3331 patients from 13 eligible studies were included. Among them, five articles on statins, six studies evaluating NSAIDs, five studies employing low-dose aspirin, eight studies on metformin and four articles on beta-blockers were included. The concomitant use of statins during ICI treatment was correlated with improved OS and PFS. Low-dose aspirin was associated with better PFS instead of OS. No significant association was demonstrated between the concurrent use of NSAIDs, beta-blockers and metformin and OS or PFS. The concomitant use of statins and low-dose aspirin during ICI treatment showed a positive impact on treatment outcomes. The concurrent use of NSAIDs, beta-blockers and metformin is not significantly associated with clinical benefits. The effect of these medications in different cancer patients treated with ICI is needed to be further validated.

Clinical Outcomes of Reresection in Patients with High-Risk Nonmuscle-Invasive Bladder Cancer Treated with En Bloc Transurethral Resection: A Retrospective Study with a 1-Year Follow-Up.

Purpose: To evaluate the impact of reresection on the clinical outcome in patients with primary high-risk nonmuscle-invasive bladder cancer (NMIBC) who initially received en bloc transurethral resection. Methods: A retrospective analysis of data on eligible high-risk NMIBC with en bloc resection from June 2015 to June 2019 was performed. Patients were divided into two groups based on the presence or absence of reresection after the initial en bloc resection. In the first group (reresection group), patients underwent en bloc reresection within 6 weeks. In the second group (non-reresection group), patients did not undergo en bloc reresection. Pathologic findings in patients with reresection and cystoscopic findings in all patients 3 months after initial resection were recorded. The primary study endpoint was recurrence-free survival (RFS). The secondary outcomes were the residual rate of the tumor after initial en bloc resection, tumor upstaging rate, and progression-free survival. Results: We identified 115 eligible patients, including 51 (44.3%) who underwent reresection within 6 weeks of the initial en bloc resection and 64 (55.7%) who did not undergo en bloc reresection after the initial en bloc resection. The clinicopathologic features were similar in patients with or without reresection. On finding tumor residues after the first en bloc resection, there were three cases (5.9%) in the reresection group compared with two cases (3.1%) in the non-reresection group (p = 0.473). Two patients (3.9%) in the reresection group had tumor progression to muscle-invasive bladder cancer, whereas one patient (1.6%) in the non-reresection group exhibited tumor progression (p = 0.430). The 1-year RFS rate was 94.1% in the reresection group and 90.6% in the non-reresection group (p = 0.269). In multivariate analysis, multifocality and T1 staging were independent prognostic factors for recurrence in patients with high-risk NMIBC who underwent en bloc resection. Conclusion: In patients with high-risk NMIBC not exceeding 4 cm in diameter with no more than four lesions and not in the anterior bladder wall, reresection after en bloc resection seems to have failed to improve the patient's prognosis. We predict that the future trend in the treatment of patients with high-risk NMIBC is from reresection to en bloc resection. However, a randomized controlled clinical study is required to confirm this hypothesis.

Collision Carcinoma Involving Small Cell Neuroendocrine Carcinoma and Squamous Cell Carcinoma of the Ureter: A Case Report and Review of the Literature.

BACKGROUND: Small cell neuroendocrine carcinoma (SCNEC) of the ureter is a rare tumour, accounting for less than 0.5% of all ureteral tumours. SCNEC tumours are highly aggressive and patients have a poor prognosis. Ureteral SCNEC colliding with other pathological types of tumours is extremely rare. In this paper, we present the case of a patient with ureteral small cell carcinoma colliding with squamous cell carcinoma and review the literature regarding the clinicopathological features, treatment and prognosis of thus tumour. To the best of our knowledge, this is the second identified case of ureteral SCNEC colliding with SCC. CASE PRESENTATION: A 64-year-old male patient presented with a history of 1 month of gross haematuria and 3 months of left flank pain. CT urography revealed a soft tissue mass in the upper ureter, which was slightly enhanced on contrast-enhanced CT. Nephroureterectomy was performed after the patient was diagnosed with a tumour in the left ureter. Microscopy and immunohistochemical examination confirmed the mass to be a SCNEC collision with SCC. Two months after the surgery, the patient received adjuvant chemotherapy (cisplatin/etoposide). After 14 months of follow-up, no local recurrence or distant metastasis was found. CONCLUSION: Ureteral collision carcinoma with SCNEC predominantly occurs in Asian individuals, is difficult to diagnose preoperatively and is highly invasive. The current management of ureteral collision carcinoma is a comprehensive treatment based on surgery.

Prognostic value of liver stiffness measurement in patients with hepatocellular carcinoma (HCC) treated by radiofrequency ablation: a meta-analysis.

BACKGROUND: In patients with stage 0-A (as per Milan criteria) hepatocellular carcinoma (HCC) image-guided ablation is less invasive and requires shorter hospitalization than resection, but long-term prognosis is poorer. This meta-analysis was conducted to investigate whether liver stiffness measurement (LSM) could be used to predict prognosis in HCC patients after tumor ablation. METHODS: A literature search was conducted for all studies published till July 2020 in PubMed, Web of Science, Cochrane Library and EMBASE. Studies were included if they investigated the association between pretreatment LSM and prognosis in HCC patients treated with ablation. Subgroup analysis, meta-regression, publication bias assessment and sensitivity were conducted. RESULTS: Eight studies (with a total of 1276 HCC patients) were included in this meta-analysis. All patients were treated with radiofrequency ablation. Pooled results showed that high pretreatment LSM were associated with poor overall survival (OS) (hazard ratio [HR] = 4.31, 95% confidence interval [CI]: 2.27-8.20, p < .001) and recurrence-free survival (RFS), regardless of whether LSM was considered as a categorical variable (HR = 2.63, 95% CI = 1.63-4.22, p < .001) or as a continuous variable (HR = 1.02, 95% CI = 1.01-1.04, p = .003). Among studies treating LSM value as a categorical variable, liver stiffness measured using acoustic radio force impulse (ARFI) or transient elastography (TE) was significantly associated with RFS, but not liver stiffness measured using two-dimensional shear wave elastography (SWE). CONCLUSIONS: High baseline LSM value appears to be associated with poor prognosis in HCC patients treated with radiofrequency ablation.

Robust W/O/W Emulsion Stabilized by Genipin-Cross-Linked Sugar Beet Pectin-Bovine Serum Albumin Nanoparticles: Co-encapsulation of Betanin and Curcumin.

Betanin and curcumin hold promise as natural colorants and antioxidants for food purposes due to their anti-hypertensive, anti-inflammation, and anti-tumor effects. However, the thermal stability and bioavailability of betanin and curcumin still need improvement. Here, we fabricated sugar beet pectin-bovine serum albumin nanoparticles (SBNPs) with a mean particle size of 180 ± 5.2 nm through a genipin cross-linking strategy to stabilize a type of Pickering water-in-oil-in-water (W/O/W) emulsion and co-encapsulated betanin and curcumin. First, the W1/O emulsion was homogenized with gelatin (the gelling agent) in the water phase and polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase. Later, W1/O was homogenized with another water phase containing SBNPs. The microstructure of the emulsion was regulated by the particle concentration (c) and W1/O volume fraction (Φ), especially the gel-like high internal phase emulsions were formed at the Φ up to 70%. In this case, betanin was encapsulated in the internal water phase (encapsulation efficiency = 65.3%), whereas curcumin was in the medium-chain triglyceride (encapsulation efficiency = 84.1%). Meanwhile, the shelf stability of betanin and curcumin was improved. Furthermore, the stability of bioactive compounds was potentiated by an emulsion gel in simulated gastrointestinal digestion, resulting in higher bioaccessibility. The aforementioned results suggest that SBNP-stabilized Pickering W/O/W emulsions could be a potential alternative to co-encapsulate betanin and curcumin with enhancement of shelf stability and bioaccessibility.

Prognostic Value and Risk Factors of Treatment-Related Lymphopenia in Malignant Glioma Patients Treated With Chemoradiotherapy: A Systematic Review and Meta-Analysis.

Background: Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses to immune checkpoint inhibitors. Treatment-related lymphopenia has been associated with poor survival in patients with various tumors. This meta-analysis evaluated the risk and impact of lymphopenia in patients with glioma. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched. Eligible studies were included if they reported the incidence and risk factors of lymphopenia and the impact of lymphopenia on survival. Stata 16.0 was used for this meta-analysis. Results: A total of 21 studies were included in the final systematic review and 20 were included in the quantitative analysis. The overall incidence of grade III/IV lymphopenia was 31.6% [95% confidence interval (CI), 22.3-40.8%]. Pooled results based on pathology of glioma revealed that the incidence in astrocytoma and astrocytoma oligodendroglioma patients was 20.2% (95% CI:5.9-34.4%), and the incidence in glioblastoma patients was 27.6% (95% CI:16.2-38.9%). Lymphopenia was associated with poor overall survival (hazard ratio, 1.99; 95% CI, 1.74-2.27; P< 0.001) compared to no lymphopenia. Brain receiving radiation dose of 20 or 25 Gy, female sex, older age, lower baseline lymphocyte count, and dexamethasone dose > 2 mg instead of baseline use were risk factors for lymphopenia. Conclusions: Treatment-related lymphopenia was associated with decreased survival in patients with glioma. Optimization of chemoradiation regimens, particularly in patients with concurrent risk factors, can reduce lymphopenia and potentially improve survival in the era of immunotherapy.

An Invited Commentary "Day care surgery versus inpatient percutaneous nephrolithotomy: A systemic review and meta-analysis".

Day-care percutaneous nephrolithotomy (day-PCNL) is being performed more routinely and rapidly, irrespective of that, medical literature comparative analysis of day-PCNL with inpatient percutaneous nephrolithotomy is scares, despite the advancement in clinical surgical systems, safety and efficiency of these two procedures are still a mainstay concern to surgical professionals globally. The purpose of this systemic review and/or meta-analysis study was to assess the safety and efficacy of PCNL as a day care surgical procedure compared to conventional inpatient PCNL.

An Invited Commentary "Prognostic effect of the new 5-factor modified frailty index in patients undergoing carotid endarterectomy with regional anesthesia - A prospective cohort study".

Frailty has been studied as a valuable predictor of adverse health events and poor postoperative outcomes in patients undergoing surgery. Thus, the use of simple and adapted indexes to define frailty, like the modified frailty index (Mfi)-11, proved useful in assessing patients undergoing vascular surgery. The role of carotid endarterectomy (CEA) continues to be debated in the age of optimal medical therapy, particularly for patients with limited life expectancy (Rothenberg et al., 2020) [3]. The Risk Analysis Index (RAI) measures frailty, a syndrome of decreased physiologic reserve, which increases vulnerability to adverse outcomes. However, the literature about the applicability of an even more pragmatic index, the modified frailty (mFi) index mFI-5 in vascular patients is scarce, particularly in those submitted to carotid endarterectomy (CEA). This study aimed to validate and estimate the prognostic value of the mFI-5 on the postoperative period and long-term survival of this population (Araújo-Andrade et al., 2020) [1].

An Invited Commentary on 'Evidence Based Management Guideline for the COVID-19 pandemic- Review article'.

COVID 19 been declared recently as a pandemic, to date has affected over 1,8881,365 with over 119,403 deaths in accordance to the global pandemic Real-Time Report. In this paper, the prime motive is to enlighten the key variables to the public on the pandemic and essential key points to note and practice in accordance to standard regulation to curb the aggressive COVID-19 pandemic.

Molecular hybridization of grape seed extract: Synthesis, structural characterization and anti-proliferative activity in vitro.

The grape seed extract (GSE) hybridized with medium-chain saturated fatty acids (decanoic acid) exhibited higher lipophilicity, antioxidant activity, and anti-proliferative activity than its parents. The chemical structures of individual hybridized GSE derivatives were identified as 3'-O-decanoyl catechin, 3'-O-decanoyl epicatechin, 3', 5'-2-O-decanoyl epigallocatechin, and 3', 4', 3″, 5″-4-O-decanoyl epicatechin gallate by HPLC-MS2 and 1H and 13C NMR. For growth inhibitory effect on HepG2 cells, hybridized GSE derivatives (EC50 = 44.38 µg/mL) were significantly (p < 0.01) stronger than natural GSE (EC50 = 60.83 µg/mL) due to increased lipophilicity. The effects of GSE derivatives on apoptosis and cell cycle in HepG2 cells were further evaluated by flow cytometry. The results showed that the percentage of apoptotic cells increased markedly in the presence of hybridized GSE derivatives. Moreover, hybridized GSE derivatives were capable of inducing cell cycle arrest in G1 phase. This research suggests that hybridized GSE derivatives are effective lipophilic antioxidants and show the potential as adjuvant therapy for cancer.