Combination of chemotherapy and immunotherapy for colon cancer in China: A meta-analysis

AIM:To investigate whether autologous dendritic cell(DC)-cytokine-induced killer(CIK)cell therapy is able to improve the therapeutic efficacy of chemotherapy in colon cancer.METHODS:We conducted a systematic review of published papers from the sources of MEDLINE,the Cochrane Central Register of Controlled Trials,EMBASE,the Wanfang Database,the China Science and Technology Periodical Database and China Journal Net.Published data were extracted independently by two authors using predefined database templates.The quality of the data from individual papers was also assessed.The effects of chemotherapy were compared with those of chemotherapy in combination with DC-CIK immunotherapy.The pooled analysis was performed using the data from random or fixed-effect models.RESULTS:Seven trials matched our inclusion criteria(n=533).The overall analysis showed significant survival benefit[one-year overall survival(OS),P<0.0001;twoyear OS,P=0.009;three-year OS,P=0.002]in favor of DC-CIK immunotherapy combined with chemotherapy.Disease-free survival(DFS)rate was improved after the combination of DC-CIK immunotherapy and chemotherapy(one-year DFS,P<0.0001;two-year DFS,P=0.002;three-year DFS,P=0.02).An improved overall response rate(P=0.009)was also observed in patients who received DC-CIK therapy.Furthermore,the analysis of T-lymphocyte subsets in peripheral blood indicated that the number of CD4+T cells significantly increased in the DC-CIK plus chemotherapy group(P<0.05).CONCLUSION:The combination of DC-CIK immunotherapy and chemotherapy was superior in prolonging the survival time and enhancing immunological responses.     

A retrospective study of enteral nutrition on immune and inflammatory factors after liver cancer surgery

This retrospective study aimed to explore the effect of enteral nutrition (EN) on immune and inflammatory factors after liver cancer surgery (LCS).It was retrospectively conducted on enrolled LCS patients between January 2017 and May 2020. The medical records of 528 patient case records were collected and reviewed. After selection, a total of 80 eligible patient case records were finally included. All those patients received routine diet, and they were allocated to a treatment group (n = 40) and a control group (n = 40). In addition, patients in the treatment group also received EN. The primary outcomes were immune factors (CD4⁺, CD8⁺, CD4⁺/CD8⁺) and inflammatory factors (interleukin-1, interleukin-6, and tumor necrosis factor-α). The secondary outcomes were postoperative hospital stay (day), time to first bowel sounds (hour), time to first flatus (day), time to first defecation (day), and complications.There were not significant differences in CD4⁺/CD8⁺ (P = .34), postoperative hospital stay (P = .39), and time to first bowel sounds (P = .17) between 2 groups. However, there were significant differences in CD4⁺ (P < .01), CD8⁺ (P < .01), interleukin-1 (P < .01), interleukin-6 (P < .01), tumor necrosis factor-α (P < .01), time to first flatus (P < .01), and time to first defecation (P < .01) between 2 groups. As for complications, there were not significant differences between 2 groups (P > .05).The results of this study found that EN may benefit for patients after LCS during the recovery period. Future high quality prospective studies are needed to warrant the present conclusion.     

Peripheral blood CD45RO+T cells is a predictor of the effectiveness of neoadjuvant chemoradiotherapy in locally advanced rectal cancer

To investigate the relationship between the changes in circulating CD45RO⁺T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO⁺T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO⁺ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO⁺ratio.Circulating CD45RO⁺ratio of 1.07 was determined as the optimal cut-off point and CD45RO⁺ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO⁺ratio-high group was significantly higher than that in the CD45RO⁺ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO⁺ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153–0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082–0.726; P = .011).Circulating CD45RO⁺ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.     

A retrospective study of ulinastatin for the treatment of severe sepsis

This retrospective study aimed to investigate the efficacy and safety of existing approach of ulinastatin for the treatment of severe sepsis (SS).A total of 130 eligible patients with SS were included in this study. We divided them into an intervention group (n = 65) and a control group (n = 65). Patients in both groups received conventional therapy. In addition, patients in the intervention group received ulinastatin for 7 days. Outcomes were measured by Acute Physiology and Chronic Health Evaluation II (APACHE II), Multiple Organ Failure (MOF), Glasgow Coma Scale (GCS), CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺, and adverse events. We assessed all outcomes before and after treatment.After treatment, patients in the intervention group showed better improvement in APACHE II (P < .01), MOF (P < .01), GCS (P < .01), CD3⁺ (P = .03), CD4⁺ (P = .03), and CD4⁺/CD8⁺ (P < .01), than those of patients in the control group. There are similar safety profiles between both groups.This study suggests that ulinastatin may be beneficial for SS. Future studies are still needed to warrant the results of this study.     

Biomarkers involved in evaluation of platelets function in South-Eastern Romanian patients with hematological malignancies subtypes

At present, various researches presented how subtypes of hematological malignancies are related to stages of the immune response, because the activated immune system represents a promising form in cancer treatment. This study explores the relationship between the adaptive immune system (T cells), and the coagulation system (platelets, platelet membrane glycoproteins, platelets derivate microparticles) which seems to play an important role in host immune defense of patients with acute myeloblastic leukemia (AML) or B cell lymphoma (BCL), 2 of the most common hematological malignancies subtypes.Blood samples (n = 114) obtained from patients with AML or BCL were analyzed for platelet membrane glycoproteins (CD42b, CD61), glycoprotein found on the surface of the T helper cells (CD4⁺), protein complex-specific antigen for T cells (CD3⁺), platelet-derived microparticles (CD61 PMP) biomarkers by flow cytometry, and hematological parameters were quantified by usual methods.In patients with AML, the means of the percentage of the expressions of the molecules on platelet surfaces (CD61 and CD42b, P < .01; paired T test) were lower as compared to both control subgroups. The expression of cytoplasmic granules content (CD61 PMP) had a significantly higher value in patients with AML reported to controlling subgroups (P < .01; paired T test), which is suggesting an intravascular activation of platelets.The platelet activation status was presented in patients with low stage BCL because CD61 and CD42b expressions were significantly higher than control subgroups, but the expression of CD 61 PMP had a significantly decreased value reported to control subgroups (all P < .01; paired T test). T helper/inducer lineage CD4⁺ and T lymphoid lineage CD3⁺ expressions presented significant differences between patients with AML or low stage BCL reported to control subgroups (all P < .01; paired T test).Platelet–lymphocyte interactions are involved in malignant disorders, and CD61, CD42b present on platelet membranes, as functionally active surface receptors mediate the adhesion of active platelets to lymphocytes, endothelial cells, and cancer cells.     

Intramuscular administration of autologous total immunoglobulin G induces immunomodulatory effects on T cells in healthy human subjects: An open-labeled prospective single-arm trial

Background:We hypothesized that intramuscular administration of autologous total immunoglobulin G (IgG) could induce an immunomodulatory effect in human subjects. In our previous studies, we showed that intramuscular administration of autologous total IgG could induce significant clinical improvements and increases of the serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-γ) in patients with atopic dermatitis.Objective:To investigate the mechanism of immunomodulation induced by intramuscular administration of autologous total IgG, we evaluated changes in T cells before and after intramuscular administrations of autologous total IgG in this study.Methods:Thirteen healthy adults received 8 intramuscular injections of 50 mg autologous total IgG for 4 weeks (from week 0 to week 4). The percentages of IL-10- or IFN-γ-producing peripheral blood T cells, as well as serum levels of IL-10, IFN-γ, and immunoglobulins, were measured at baseline (week 0) and at weeks 4, 8, and 12.Results:The percentage of IL-10-producing CD4⁺ T cells was significantly increased at weeks 8 and 12 compared to baseline (P < .05), while the percentage of IFN-γ-producing CD3⁺ T cells was significantly increased at week 12 compared to baseline (P < .05). There were no significant differences in the serum levels of IL-10, IFN-γ, and immunoglobulins before and after intramuscular administration of autologous total IgG (P > .05). No serious adverse events were observed.Conclusion:Intramuscular administration of autologous total IgG induced immunomodulatory effects on T cells in healthy human subjects. This simple intervention could be a safe, effective, and economical T cell immunomodulation method for human subjects ({"type":"clinical-trial","attrs":{"text":"NCT03695757","term_id":"NCT03695757"}}NCT03695757).     

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro

AIM: To investigate the effects of activated rat hepatic stellate cells(HSCs) on rat Th1/Th2 profile in vitro.METHODS: Growth and survival of activated HSCs and CD4+ T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4+ T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon(IFN)-γ+] and Th2 [interleukin(IL)-4+] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4+ T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs.RESULTS: Co-culture of CD4+ T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions(-1.73% ± 0.71%; P 0.05), whereas the proportion of Th2 cells was not altered; the Th1/Th2 ratio was significantly decreased(-0.44 ± 0.13; P 0.05). In addition, the level of IFN-γ in Th1 cells wasdecreased(-65.71 ± 9.67; P 0.01), whereas the level of IL-4 in Th2 cells was increased(82.79 ± 25.12; P 0.05) by co-culturing, as measured by mean fluorescence intensity by flow cytometry. Apoptosis rates in Th1(12.27% ± 0.99%; P 0.01) and Th2(1.71% ± 0.185%; P 0.01) cells were increased 24 h after co-culturing with activated HSCs; the Th1 cell apoptosis rate was significantly higher than in Th2 cells(P 0.01). Galectin-9 protein expression was significantly decreased in HSCs only 24 h after coculturing(P 0.05) but not after 48 h. Co-culture for 48 h significantly increased the differentiation of Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells(1.85% ± 0.48%; P 0.05).CONCLUSION: Activated rat HSCs lower the Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.     

Differential Effects of Viremia and Microbial Translocation on Immune Activation in HIV-Infected Patients Throughout Ritonavir-Boosted Darunavir Monotherapy

The purpose of this article is to evaluate the evolution of microbial translocation (MT) and its role in CD4⁺ and CD8⁺ T cells immune activation (IA) in HIV-1-infected patients on ritonavir-boosted darunavir monotherapy (mtDRV/rtv).Prospective study of consecutive HIV-1-infected patients switched to mtDRV/rtv as a simplification regimen. Subjects were classified according to the virological behavior during a 24-month follow-up as continuous undetectable viral load, blips, intermittent viremia, and virological failure (VF). MT was evaluated by plasma LPS and 16S genomic rDNA (16S rDNA) levels, whereas IA was assessed by the coexpression of HLA-DR and CD38 in CD4⁺ and CD8⁺ T cells, and plasma sCD14 levels.Seventy-one patients were included in this substudy of the MonDar cohort (ClinicalTrials.gov: NCT01505722). At baseline, CD4⁺ (ρ = −0.352, P = 0.01) and CD8⁺ T-cell activation (ρ = −0.468, P < 0.001) were correlated with time with viral suppression, but not with MT markers. A significant decrease in plasma LPS levels was found only in patients without VF (baseline, 77.8 vs month 24, 60.4 pg/mL; P < 0.001]. Both plasma 16S rDNA and sCD14 levels were unchanged irrespective of the viral behavior. The only variable independently associated with a decrease in CD4⁺ and CD8⁺ T cells activation was an undetectable HIV-1 viremia (β = 4.78, P < 0.001 and β = 2.93, P = 0.005, respectively).MT does not have a pivotal role in T-cell activation, at least in patients with long-term viral suppression. The viremic episodes and VF are the main factors related to CD4⁺ and CD8⁺ T-cells IA, even during mtDRV/rtv.     

The effects of cytokine-induced killer cells for the treatment of patients with solid tumors: a clinical retrospective study

Background

Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches for malignant tumors. This study aimed to evaluate the effect of adjuvant immunotherapy with CIK cells on the prognosis of solid tumor.

Methods

Peripheral blood mononuclear cells were collected by a blood cell separator from 40 patients, then expanded by priming them with interferon-gamma followed by monoclonal antibody against CD3 and interleukin-2 the next day. The phenotypic patterns of CIK cells were characterized by flow cytometry on days 0, 7, 10, 14 and 21 of incubation, respectively. Then, 5?ml of venous blood was obtained from 40 patients before and after CIK cells were transfused into patients to assess the influence of CIK cells on the percentages of effector cells.

Results

After 14?days of incubation in vitro, the percentages of CD3⁺, CD8⁺, CD3⁺ and CD56⁺ increased significantly (P?Conclusions Our results indicated that CIKs immunotherapy can be an effective adjuvant instrument of the routine therapy of malignancy.     

Circulating tumor cells counts are associated with CD8+ T cell levels in programmed death-ligand 1-negative non-small cell lung cancer patients after radiotherapy: A retrospective study

This study aimed to explore the dynamics of circulating tumor cells (CTCs) and CD8+ T cells in stage II–III non-small cell lung cancer patients with CTCs in different programmed death-ligand 1 (PD-L1) status treated with radiotherapy and evaluate the correlation between CTCs and CD8+ T cells.This study was a retrospective study which reviewed 69 stage II–III non-small cell lung cancer patients underwent postoperative radiotherapy and peripheral blood tests of CTCs and T lymphocyte were available before radiation, 1 week after radiation and 1 month after radiation.In this study, 25 patients had PD-L1 positive CTCs and 44 patients had PD-L1 negative CTCs. The CTCs count was significantly decreased compared with baseline in patients with different PD-L1 status CTCs at 1 week and 1 month after radiotherapy. The proportion of CD8+ T cells was significantly increased at 1 month after radiotherapy compared with baseline in the total population (mean change, 7.24 ± 2.12; P < .05) and patients with PD-L1 negative CTCs (mean change, 7.17 ± 2.65; P < .05). One month after radiotherapy, the proportion of CD8+ T cells was negatively correlated with the CTCs count in the total population (r = −0.255, P = .034) and PD-L1 negative patients (r = –0.330, P = .029). In patients with PD-L1 negative CTCs, the CTCs count 1 week after radiotherapy (hazard ratio, 0.150 [95% confidence intervals., 0.027–0.840], P = .031) and the proportion of CD8+ T cells 1 month after radiotherapy (hazard ratio, 7.961 [95% confidence intervals, 1.028–61.68], P = .047) were independent prognostic factors for disease recurrence.After radiotherapy, only PD-L1-negative patients had a significant increase in the CD8+ T cell levels, while it was negatively correlated with CTCs count and was an independent prognostic factors of disease recurrence.     

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer: A PRISMA-compliant systematic review and meta-analysis

Background:Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC.Methods:From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THM + PBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed.Results:Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THM + PBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratio = 1.24, 95% confidence intervals [CI] [1.11, 1.39], P < .001), progression-free survival/time to progression (median survival ratio = 1.22, 95% CI [1.09, 1.37], P < .001), and the 1-year survival rate (risk ratio [RR] = 1.56, 95% CI [1.31, 1.86], P < .001). THM + PBCT also led to a higher tumor response rate (RR = 1.39, 95% CI [1.22, 1.59], P < .001) and lower incidence of thrombocytopenia (RR = 0.72, 95% CI [0.56, 0.92], P = .009) and nausea/vomiting (RR = 0.35, 95% CI [0.21, 0.57], P < .001), while there was no significant effect observed on leukopenia (RR = 0.68, 95% CI [0.34, 1.36], P = .27).Conclusion:THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.     

Single-stage intraoperative ERCP combined with laparoscopic cholecystectomy versus preoperative ERCP Followed by laparoscopic cholecystectomy in the management of cholecystocholedocholithiasis: A meta-analysis of randomized trials

ObjectivesThe optimal treatment strategy for cholecystocholedocholithiasis is still controversial. We conducted an up-to-date meta-analysis to compare the efficacy and safety of the intra- endoscopic retrograde cholangiopancreatography (ERCP) + LC procedure with the traditional pre-ERCP +  laparoscopic cholecystectomy (LC) procedure in the management of cholecystocholedocholithiasis.MethodsWe searched the PubMed, Embase, Cochrane Library, and Web of Science databases up to September 2020. Published randomized controlled trials comparing intra-ERCP + LC and pre-ERCP + LC were considered. This meta-analysis was performed by Review Manager Version 5.3, and outcomes were documented by pooled risk ratio (RR) and mean difference (MD) with 95% confidence intervals.ResultsEight studies with a total of 977 patients were included in this meta-analysis. There was no significant difference between the two groups regarding CBD stone clearance (RR = 1.03, P = .27), postoperative papilla bleeding (RR = 0.41, P = .13), postoperative cholangitis (RR = 0.87, P = .79), and operation conversion rate (RR = 0.71, P = .26). The length of hospital stay was shorter in the intra-ERCP + LC group (MD = −2.75, P < .05), and intra-ERCP + LC was associated with lower overall morbidity (RR = 0.54, P < .05), postoperative pancreatitis (RR = 0.29, P < .05) and cannulation failure rate (RR = 0.22, P < .05).ConclusionsIntra-ERCP + LC was a safer approach for patients with cholecystocholedocholithiasis. It could facilitate intubation, shorten hospital stay, and lower postoperative complications, especially postoperative pancreatitis, and reduce stone residue and reduce the possibility of reoperation for stone removal.     

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer: A meta-analysis

Background:The use of standard cytotoxic chemotherapy seems to have reached a “treatment plateau”. The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.Methods:According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.Results:The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).Conclusion:Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.     

Number of cells in parathyroid tissue in primary hyperparathyroidism cases and its relationship with serum calcium value

Background:The relationship between serum calcium (Ca) level to serum parathyroid hormone (PTH), phosphorus (P) levels and tissue properties of the parathyroid gland is unknown in primary hyperparathyroidism cases. Revealing this relationship may be useful for understanding the etiopathogenesis of primary hyperparathyroidism and determining the time of treatment.Methods:Ninety patients (71 females, 19 males, age range; 27–73 years, average age; 46) who underwent single gland excision with the diagnosis of primary hyperparathyroidism were studied. The patients were divided into 2 groups as serum Ca level <12 and serum Ca level ≥12. Age and sex of the patients, mean cell number of the gland, mean volume of the gland, serum levels of PTH, P, and histopathologic type of hyperplasia were evaluated.Results:The mean cell number per cubic centimeter is 22.9 (10–220 range) million in all glands. Serum Ca level was <12 in 82 (91.1%) of the patients, and ≥12 in 8 (8.9%) cases. Mean cell number of the gland, mean volume of the gland, existence of cystic hyperplasia of the gland, serum levels of PTH and P were statistically significant between the 2 groups (P < .001, P < .001, P < .05, P < .001, P < .05 respectively).Conclusion:In primary hyperparathyroidism cases serum Ca level is not related to age and sex but directly related to proportionals to the cell number and volume of the gland and serum levels of PTH, inversely related to cystic hyperplasia and serum levels of P. Early surgical intervention should be planned since the serum Ca level will be high in large adenomas with a noncystic radiological appearance.     

Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis

Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4)⁺ cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3)⁺, cluster of differentiation 4 (CD4)⁺, and cluster of differentiation 45 (CD45)⁺ cells, and lower percentages of CD8⁺ cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis.     

Efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitor versus chemotherapy for advanced lung cancer: A meta-analysis

Background:This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer.Methods:Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I² and P-value.Results:Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71–0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71–0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66–2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53–4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21–3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97–1.77, P = .02) were observed between the 2 groups.Conclusion:Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.     

The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors

Background:The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet.Methods:We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS).Results:Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74–2.61, P < .001, I² = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44–2.17, P < .001, I² = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17–1.91, P < .001, I² = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38–1.89, P < .001, I² = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34–0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47–0.77, P < 0.001, I² = 0.0%, P < .001).Conclusion:High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.     

Assessment of Activity of Crohn Disease by Diffusion-Weighted Magnetic Resonance Imaging

To assess the diagnostic efficacy of diffusion-weighted MR imaging (DWI) for evaluating inflammatory activity in patients with Crohn''s disease (CD). A total of 47 CD patients underwent MR enterography (MRE) and DWI using 3 b values of 50, 400, and 800 s/mm.² Apparent diffusion coefficients (ADCs) of inflamed and normal bowel wall were calculated. The conventional MRE findings and DWI signal intensities were qualitatively scored from 0 to 3. The correlation between Crohn disease activity index (CDAI) and both ADCs and magnetic resonance imaging scores was analyzed. Receiver-operating characteristic curve analysis was used to determine the diagnostic accuracy of CD activity. Of the 47 patients, 25 were active CD (CDAI≥150) and 22 were inactive (CDAI<150). Diffusion-weighted MR imaging and MRE + DWI scores of active CD were significantly higher than that of inactive CD (both P < 0.001). Apparent diffusion coefficients in inflamed segments of active CD were lower than that of inactive CD (P < 0.001). The DWI scores (r = 0.74, P < 0.001), ADCs (r = −0.71, P < 0.001), MRE scores (r = 0.54, P < 0.001), and MRE + DWI scores (r = 0.66, P < 0.001) were all correlated with CDAI. The areas under the receiver-operating characteristics curves for ADCs, DWI scores, MRE scores, and MRE + DWI scores ranged from 0.83 to 0.98. The threshold ADC value of 1.17 × 10⁻³ mm²/s allowed differentiation of active from inactive CD with 100% sensitivity and 88% specificity. Diffusion-weighted MR imaging and ADC correlated with CD activity, and had excellent diagnostic accuracy for differentiating active from inactive CD.     

The effect of pretreatment BMI on the prognosis and serum immune cells in advanced LSCC patients who received ICI therapy

This study aims to evaluate the prognosis and serum immune cells of patients with different pretreatment body mass index (BMI) values. The data of 61 newly diagnosed patients with advanced lung squamous cell carcinoma (LSCC) who received immune checkpoint inhibitors (ICIs) combined with chemotherapy were obtained from the database of Rizhao People''s Hospital (Rizhao, Shandong). According to the cutoff value of BMI (23.2 kg/m²), 32 patients had a high BMI and the remaining 29 patients had a low BMI. The effects of different BMIs on the prognosis and serum immune cells of patients were analyzed. The median progression-free survival (PFS) times were 7.72 months in the high BMI group and 4.83 months in the low BMI group [adjusted hazard ratio (HR), 0.23; 95% confidence interval (CI), 0.11–0.48; P < .001]. In terms of the overall survival (OS), the median times of the high BMI group and low BMI group were 18.10 and 13.90 months, respectively (adjusted HR, 0.15; 95% CI, 0.07–0.32; P < .001). After 4 cycles of ICI therapy combined with chemotherapy, the objective response rate was 59.4% for the high BMI group and 20.7% for the low BMI group (P = .002). In addition, the number of serum immune cells in patients with high BMI was significantly higher than that in patients with low BMI (all P < .001). There was a linear relationship between BMI value and the number of serum immune cells (all R² > 0.7). The current results showed that high BMI is associated with better prognosis in LSCC patients who received ICIs, which may be related to higher levels of serum immune cells.