The association between proton pump inhibitor (PPI) use and gastric cancer related to
eradication has not been fully investigated in geographical regions with high risk of gastric cancer. We aimed to ...evaluate the association between PPIs and gastric cancer in Korea.
This study analysed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. We compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. We also analysed the incidence of gastric cancer among PPI users after
eradication.
The analysis included 11 741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI≥30 days vs non-PPI; 118/51 813 person-years vs 40/49 729 person-years; HR 2.37, 95% CI 1.56 to 3.68, p=0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In
-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI≥180 days vs non-PPI; 30/12 470 person-years vs 9/7814 person-years; HR 2.22, 95% CI 1.05 to 4.67, p=0.036).
PPI use was associated with gastric cancer, regardless of
eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.
The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP ...has recently been associated with the progression of disease in many cancer types. The principal objective of this study was to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and to correlate them with disease status and prognosis.
A total of 115 patients who underwent gastrectomy were enrolled in this study. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumor size, depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (6th AJCC Stage Groupings: The staging systems; Primary tumor, regional LN, metastasis).
Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels were correlated with invasion depth (P < 0.001, P = 0.001), LN metastasis (P < 0.001, P = 0.024) and TNM stage (P < 0.001, P < 0.001). The presence of peritoneal seeding metastasis is associated with IL-6 levels (P = 0.012). When we established the cutoff value for IL-6 level (6.77 pg/dL) by ROC curve, we noted significant differences in time to progression (TTP; P < 0.001) and overall survival (OS; P = 0.010). However, CRP evidenced no significance with regard to patients' TTP and OS levels. Serum IL-6 levels were correlated positively with CRP levels (r2 = 0.049, P = 0.018).
Preoperative serum IL-6 and CRP levels might be markers of tumor invasion, LN metastasis, and TNM stage. Preoperative high IL-6 levels were proposed as a poor prognostic factor for disease recurrence and overall survival in patients with gastric cancers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
The comparative efficacy of various bariatric procedures has not been completely elucidated. We aimed to evaluate efficacy and safety of various bariatric procedures comprehensively.
...Methods
We searched for randomized controlled trials investigating the efficacy of bariatric surgery. Network meta-analyses were performed to determine the percentage of excess weight loss (%EWL) and remission of diabetes mellitus (DM).
Results
Of 45 studies, 33 and 24 provided the data for %EWL and DM remission rates, respectively. Six months after surgery, biliopancreatic diversion with duodenal switch (BPD-DS), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) showed superior efficacy for %EWL compared to the standard-of-care (mean difference MD, 95% confidence interval CI: BPD-DS, 38.2% 7.3%, 69.1%; RYGB, 32.1% 3.1%, 61.1%; SG, 32.5% 5.5%, 59.5%). However, adjustable gastric banding was not superior to standard-of-care (MD 95% CI = − 0.2% − 19.6%, 19.2%). At 1 year, all bariatric procedures were superior to standard-of-care. At 3 years, RYGB and SG showed superior efficacy when compared to standard-of-care (MD 95% CI: RYGB, 45.0% 21.8%, 68.2%; SG, 39.2% 15.2%, 63.3%). With respect to DM remission 3–5 years after surgery, BPD-DS, RYGB, and SG were superior to standard-of-care. Hernias, obstruction/stricture, bleeding, and ulcers were less common in patients who underwent SG than in those who underwent RYGB.
Conclusions
RYGB and SG had excellent long-term outcomes for both the %EWL and DM remission rates. Additionally, SG had a relatively lower risk of adverse events than RYGB.
The association between vasomotor tone of the peripheral arteries and cerebral hemisphere function has not been established. This study analyzed the peripheral vasoreactivity of patients with acute ...ischemic stroke and hemiplegia using a modified Raynaud scan, which is a new technology for blood flow measurement. In this retrospective case-control study, we examined patients with unilateral weakness consistent with ischemic lesions who underwent brain magnetic resonance imaging and modified Raynaud scanning within five days from the onset of symptoms. The modified Raynaud scan was used to quantify the radioactivity of the bilateral fingertips during rest and cooling-heating thermal stress conditions and estimate vasoreactivity based on the change in the blood amount per time under rest-thermal stress. The subjects were classified into the preserved and impaired groups based on their degrees of vasomotor reaction. Based on the modified Raynaud scanning, 37 (mean age = 69.1 ± 10.6) and 32 (mean age = 62.6 ± 11.8) subjects were allocated to the preserved and impaired groups, respectively. Binary logistic regression showed that the affected limb edema (odds ratio (OR) 6.15; confidence interval (CI) 1.40-26.97; p = 0.016) and anterior circulation (OR 3.68; CI 1.01-13.48; p = 0.049) were associated with impaired vasoreactivity. The modified Raynaud scans confirmed that central lesions in the anterior circulation with hemiparesis may influence the vasoreactivity of edematous peripheral arteries. These results may inform treatment and rehabilitation for stroke patients with hemiparesis.
Background
Several studies have shown that the neutrophil to lymphocyte ratio (NLR) in peripheral blood is a prognostic factor of various cancers. However, there is limited information on the ...clinical and prognostic significance of NLR in patients with metastatic advanced gastric cancer (AGC). Therefore, we examined whether the NLR can be used as a prognostic marker for predicting chemotherapeutic response and survival outcomes in metastatic AGC patients who are receiving palliative chemotherapy.
Method
A total of 268 patients diagnosed with metastatic AGC were enrolled. NLR was calculated from complete blood cell count taken before the first chemotherapy treatment. Patients were divided into two groups according to the median value of NLR: a high NLR group and a low NLR group.
Result
The median follow-up period was 340 days (range 72–1796 days) and median NLR was 3.06 (range 0.18–18.16). The high NLR group (NLR >3.0) contained 138 patients and the low NLR group (NLR ≤3.0) contained 130 patients. Low NLR group patients had a significantly higher chemotherapeutic disease control rate (90.0 % vs. 80.4;
P
= 0.028), and longer progression-free survival (PFS) and overall survival (OS) than the high NLR group patients (186 vs. 146 days;
P
= 0.001; 414 vs. 280 days;
P
< 0.001, respectively). In multivariate analysis, NLR showed a significant association with PFS (HR 1.478; 95 % CI 1.154–1.892;
P
= 0.002) and OS (HR 1.569; 95 % CI 1.227–2.006;
P
< 0.001).
Conclusion
Pretreatment NLR is a useful prognostic marker in patients with metastatic AGC who are undergoing palliative chemotherapy.
Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative ...studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.
We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics.
Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%).
PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Engineering T cells with a chimeric antigen receptor (CAR) that reprograms their antigen selectivity and signaling has recently emerged as one of the most promising therapeutic approaches for ...treating cancers. For example, two CD19-specific CAR T cell (CAR-T) therapies have shown remarkable responses in patients with relapsed/refractory B-cell cancers, and were approved by the US Food and Drug Administration in 2017. This initial clinical success has spurred an explosion of interests in this novel therapy from both academia and industry, and results from basic and clinical research have enabled the rapid evolution of the CAR-T field. In this review, we describe the basic structure of the CAR and discuss how each of its domains affect the efficacy and safety of CAR-T therapies. In addition, we discuss some of the novel concepts and other considerations that are essential for ensuring the future success of CAR-T therapy.
Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells ...once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the selective formation of immunological synapses, in which the sCAR-T cell, switch, and target cell interact in a structurally defined and temporally controlled manner. Optimized switches specific for CD19 controlled the activity, tissue-homing, cytokine release, and phenotype of sCAR-T cells in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The sCAR–T-cell dosing regimen could be tuned to provide efficacy comparable to the corresponding conventional CART-19, but with lower cytokine levels, thereby offering a method of mitigating cytokine release syndrome in clinical translation. Furthermore, we demonstrate that this methodology is readily adaptable to targeting CD20 on cancer cells using the same sCAR-T cell, suggesting that this approach may be broadly applicable to heterogeneous and resistant tumor populations, as well as other liquid and solid tumor antigens.
The adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a promising cancer therapy. Despite impressive clinical efficacy, the general ...application of current CAR–T-cell therapy is limited by serious treatment-related toxicities. One approach to improve the safety of CAR-T cells involves making their activation and proliferation dependent upon adaptor molecules that mediate formation of the immunological synapse between the target cancer cell and T-cell. Here, we describe the design and synthesis of structurally defined semisynthetic adaptors we refer to as “switch” molecules, in which anti-CD19 and anti-CD22 antibody fragments are site-specifically modified with FITC using genetically encoded noncanonical amino acids. This approach allows the precise control over the geometry and stoichiometry of complex formation between CD19- or CD22-expressing cancer cells and a “universal” anti-FITC–directed CAR-T cell. Optimization of this CAR–switch combination results in potent, dose-dependent in vivo antitumor activity in xenograft models. The advantage of being able to titrate CAR–T-cell in vivo activity was further evidenced by reduced in vivo toxicity and the elimination of persistent B-cell aplasia in immune-competent mice. The ability to control CAR-T cell and cancer cell interactions using intermediate switch molecules may expand the scope of engineered T-cell therapy to solid tumors, as well as indications beyond cancer therapy.
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