Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

[Comparison of allogeneic or autologous hematopoietic stem cell transplant for high-risk peripheral T cell lymphomas].

Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (12-58) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 angioimmunoblastic T-cell lymphoma (AITL). Twenty-one patients (21/60) received allo-HSCT, and thirty-nine (39/60) auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients partial remission (PR) and 18/60 patients not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients auto-HSCT, respectively. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients auto-HSCT, respectively. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS by auto-HSCT and allo-HSCT were 61% and 60% (P=0.724) , respectively. The 5-year OS by auto-HSCT and allo-HSCT were 62% and 61% (P=0.724) , respectively. There were no statistically significant differences between auto-HSCT and allo-HSCT. And the cumulative TRM of auto-HSCT and allo-HSCT were 22.7% and 41.8% (P=0.250) , respectively within 5-years after transplantation. At the end of the last follow-up, 7 and 2 patients relapsed in auto-HSCT and allo-HSCT groups respectively, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively. Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. Outcome by allo-HSCT may be better for NR patients.

[The roles of serum free light chain ratio in the diagnosis and prognosis of newly diagnosed multiple myeloma].

OBJECTIVE: The roles of serum free light chain ratio (sFLCR) in the diagnosis and prognosis of newly diagnosed multiple myeloma (NDMM) patients were analyzed. METHODS: The clinical data was retrospectively analyzed for 82 newly diagnosed multiple myeloma (NDMM) patients in the first affiliated hospital of Soochow University from September 28, 2012 to July 18, 2105. The serum free light chain levels were measured and κ/λ ratios were calculated, so we could analyze the roles of sFLCR in the diagnosis and prognosis of newly diagnosed multiple myeloma (NDMM) patients. RESULTS: It was 85.5% (70/82) positive of M protein by serum protein electrophoresis (SFE) and 93.9%(77/82) by serum immunofixation electrophoresis (IFE). Both sFLC and sFLCR abnormalities were 96.3% (79/82). The estimated 40-months overall survival was 87% for the high free light chain ratio group (sFLCR ≥100 or≤0.01) and 61% for the low free light chain ratio group (0.01

Expression of Raf kinase inhibitor protein in human hepatoma tissues by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight methods.

PURPOSE: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. To reduce the mortality and improve the effectiveness of therapy, it is important to search for changes in tumor-specific biomarkers whose function may involve in disease progression and which may be useful as potential therapeutic targets. Materials and Mehtods: In this study, we use two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to observe proteome alterations of 12 tissue pairs isolated from HCC patients: Normal and tumorous tissue. Comparing the tissue types with each other, 40 protein spots corresponding to fifteen differentially expressed between normal and cancer part of HCC patients. RESULTS: Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein kinase/extracellular signal-regulated kinase, may play an important role in cancer metastasis and cell proliferation and migration of human hepatoma cells. RKIP may be considered as a marker for HCC, because its expression level changes considerably in HCC compared with normal tissue. In addition, we used the methods of Western blotting and real time-polymerase chain reaction to analysis the protein expression and gene expression of RKIP. The result showed RKIP protein and gene expression in tumor part liver tissues of HCC patient is lower than peritumorous non-neoplastic liver tissue of the corresponding HCC samples. CONCLUSION: These results strongly suggest that RKIP may be considered to be a marker for HCC and RKIP are down-regulated in liver cancer cell.

PATHOME: an algorithm for accurately detecting differentially expressed subpathways.

The translation of high-throughput gene expression data into biologically meaningful information remains a bottleneck. We developed a novel computational algorithm, PATHOME, for detecting differentially expressed biological pathways. This algorithm employs straightforward statistical tests to evaluate the significance of differential expression patterns along subpathways. Applying it to gene expression data sets of gastric cancer (GC), we compared its performance with those of other leading programs. Based on a literature-driven reference set, PATHOME showed greater consistency in identifying known cancer-related pathways. For the WNT pathway uniquely identified by PATHOME, we validated its involvement in gastric carcinogenesis through experimental perturbation of both cell lines and animal models. We identified HNF4α-WNT5A regulation in the cross-talk between the AMPK metabolic pathway and the WNT signaling pathway, and further identified WNT5A as a potential therapeutic target for GC. We have demonstrated PATHOME to be a powerful tool, with improved sensitivity for identifying disease-related dysregulated pathways.

Diagnostic performance of serum cystatin C and serum creatinine in the prediction of chronic kidney disease in renal transplant recipients.

BACKGROUND: Chronic kidney disease (CKD) has adverse impacts on mortality and morbidity of renal transplant recipients. Serum cystatin C (sCysC) is a novel marker in predicting the CKD. We therefore compare sCysC and serum creatinine (sCr) with the aim of improving the detection of CKD in renal transplant recipients. METHODS: We enrolled 106 renal transplant recipients and estimated glomerular filtration rates (GFR) using the Cockcroft-Gault (GFR(CG)) and the abbreviated Modification of Diet in Renal Disease (GFR(aMDRD)) formulae. We defined CKD as the presence of structural or functional kidney damage, irrespective of the diagnosis. Comparisons of sCysC and sCr in detecting CKD were analyzed. RESULTS: sCysC correlates with sCr significantly (r = 0.87; P < .001). The receiver operating characteristic curve demonstrates that sCysC has a better specificity and area under the curve, but less sensitivity than sCr in predicting CKD in renal transplant recipients if GFR is estimated by GFR(CG). Additionally, if GFR was estimated by GFR(aMDRD), the role of sCysC or sCr in prediction of CKD was comparable. CONCLUSION: sCysC may be better than sCr to detect CKD in renal transplant recipients using the GFR(CG).

Tumor necrosis factor alpha promoter polymorphism in posttransplantation diabetes mellitus of renal transplant recipients.

Posttransplantation diabetes mellitus (PTDM) is a major complication in renal transplant recipients. Some studies have demonstrated that tumor necrosis factor alpha (TNF-α) expression and its genetic polymorphism are associated with diabetes mellitus. We investigated this association in Asian renal transplant recipients. Polymerase chain reaction-restriction-fragment length polymorphism was used to measure TNF-α G-238A and G-308A gene polymorphisms among 241 nonposttransplantation diabetic subjects and 73 PTDM patients. PTDM patients showed higher values of body weight and body mass index (BMI) than the non-PTDM group. However, no significant association was observed between TNF-α G-238A and TNF-α G-308A polymorphisms with PTDM incidence, gender, age at transplantation, follow-up duration, BMI, or type of immunosuppression.

A Salmonella infection complicated with suppurative thyroiditis and ruptured aortic mycotic aneurysm in a renal transplant recipient.

We report a renal transplant recipient who presented with fever and chills for 2 days. The blood and stool cultures revealed the growth of Salmonella enteriditis. A whole-body gallium scan played an important role in the subsequent diagnosis of suppurative thyroiditis. To our knowledge, this is the first report of acute S. enteriditis thyroiditis in a renal transplant recipient. Despite vigorous antibiotic use and a partial thyroidectomy, he experienced recurrent S. enteriditis infection, resulting in a ruptured thoracic mycotic aneurysm 1 month later. Finally the patient was successfully cured with aneurysm resection, in situ reconstruction of the thoracic aorta, and prolonged antibiotics.

Non-life-threatening leukopenia in a renal transplant recipient with acute overdose of mycophenolate mofetil.

Mycophenolate mofetil (MMF) is increasingly used as an immunosuppressant for organ transplantation and for treatment of autoimmune diseases. As yet, the experience with acute overdose of MMF in humans is limited. Herein we have reported a 40-year-old female kidney recipient with moderate leukopenia and lack of gastrointestinal toxicity following ingestion of 25 g MMF, which was confirmed by serum drug levels. We treated the patient with charcoal decontamination and oral cholestyramine. She recovered completely without sequelae.

Microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers.

BACKGROUND/AIMS: To evaluate microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers after daily use. METHODS: Subjects were provided with preservative-free artificial tears (Groups 1 and 2) and artificial tears containing a preservative (Group 3). After administration three times or more per 10 h, bottles were collected, and any remaining fluid in the bottles was cultured. A risk factor analysis for microbial contamination was performed by the use of univariate and multivariate analysis. RESULTS: A total of 242 eye-drop bottles were evaluated. Five (2.0%) of the 242 bottles had bacterial contamination. In group 1, four (3.9%) of 102 bottles were contaminated, and identified bacteria were all coagulase-negative Staphylococcus. In group 2, one (1.0%) of 105 bottles was contaminated, and it was a Gram-negative Acinetobacter species. No bottles from group 3 showed any contamination. Based on multivariate analysis, advanced age and fingertip touch were statistically significant risk factors for microbial contamination (p<0.05). CONCLUSION: Preservative-free artificial tears in reclosable containers are at risk of contamination in a daily and multiple use setting, especially in patients with a poor administering technique, which is associated with fingertip touch and advanced age.