Risk stratification models incorporating oxidative stress factors to predict survival and recurrence in patients with gastric cancer after radical gastrectomy: A real-world multicenter study.

BACKGROUND: Oxidative stress significantly influences the development and progression of gastric cancer (GC). It remains unreported whether incorporating oxidative stress factors into nomograms can improve the predictive accuracy for survival and recurrence risk in GC patients. METHODS: 3498 GC patients who underwent radical gastrectomy between 2009 and 2017 were enrolled and randomly divided into training cohort (TC) and internal validation cohort (IVC). Cox regression analysis model was used to evaluate six preoperative oxidative stress indicators to formulate the Systemic oxidative stress Score (SOSS). Two nomograms based on SOSS was constructed by multivariate Cox regression and validated using 322 patients from another two hospitals. RESULTS: A total of 3820 patients were included. The SOSS, composed of three preoperative indicators-fibrinogen, albumin, and cholesterol-was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS). The two nomograms based on SOSS showed a significantly higher AUC than the pTNM stage (OS: 0.830 vs. 0.778, DFS: 0.824 vs. 0.775, all P < 0.001) and were validated in the IVC and EVC (all P < 0.001). The local recurrence rate, peritoneal recurrence rate, distant recurrence rate and multiple recurrence rate in high-risk group were significantly higher than those in low-risk group (P < 0.05). CONCLUSIONS: The two novel nomograms based on SOSS which was a combination score of three preoperative blood indicators, demonstrated outstanding predictive abilities for both survival and recurrence in GC patients with different risk groups, which may potentially improve survival through perioperatively active intervention strategies and individualized postoperatively close surveillance.

Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

CDK4/6 Inhibitor Efficacy in ESR1-Mutant Metastatic Breast Cancer.

BACKGROUND: In estrogen receptor-positive metastatic breast cancer, ESR1 mutations (ESR1m) are a common mechanism of acquired resistance to aromatase inhibitors (ArIh). However, the impact ESR1 alterations have on CDK4/6 inhibitor (CDK4/6i) sensitivity has not been established. Analyses of CDK4/6i trials suggest that the endocrine therapy partner and specific ESR1 allele may affect susceptibility. We analyzed a real-world data set to investigate CDK4/6i efficacy in ESR1m metastatic breast cancer and associated clinical factors. METHODS: ESR1m were identified by analysis of circulating-tumor deoxyribonucleic acid. The GuardantINFORM database contains genomic information from tumors linked with claims data. Patients who started a CDK4/6i within 30 days of sequencing were categorized as having ESR1m or non-ESR1-mutant (non-ESR1m) breast cancer. Data were analyzed to determine the real-world time-to-next-treatment, defined as the start of a breast cancer treatment to initiation of the subsequent treatment. RESULTS: One hundred forty-five patients with ESR1m and 612 with non-ESR1m metastatic breast cancer were analyzed. ESR1m and non-ESR1m tumors had similar real-world time-to-next-treatment on CDK4/6i regimens (hazard ratio, 1.02; 95% confidence interval, 0.82 to 1.23). Duration on therapy in the first-line and second-line plus treatment settings were comparable regardless of ESR1 status. We stratified treatment duration by concurrent endocrine therapy, and patients with ESR1m had worse outcomes on ArIh but comparable real-world time-to-next-treatment on fulvestrant. CONCLUSIONS: These data suggest ESR1 variants are not associated with pan-CDK4/6i resistance and are consistent with the hypothesis that CDK4/6 blockade combined with a selective estrogen receptor degrader is potentially an effective option for ESR1m metastatic breast cancer.

Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study.

BACKGROUND: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018. METHODS: This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated. RESULTS: This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5-10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non-HER2-directed therapies (11.0 months [95% CI, 6.3-12.3] vs 7.2 months [95% CI, 5.8-9.6]). CONCLUSIONS: This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.

Multiple epithelioid angiosarcoma of stomach and small intestine with multiple lymph node metastases: A case report.

RATIONALE: Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases. PATIENT CONCERNS: A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for >1 month. DIAGNOSIS, INTERVENTIONS AND OUTCOMES: Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 month after the surgery. LESSONS: Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis.

Taurine-Upregulated Gene 1 Attenuates Cerebral Angiogenesis following Ischemic Stroke in Rats.

Objective: Angiogenesis is one of the therapeutic targets of cerebral infarction. Long noncoding RNAs (lncRNAs) can regulate the pathological process of angiogenesis following ischemic stroke. Taurine-upregulated gene 1 (TUG1), an lncRNA, is correlated to ischemic stroke. We intended to determine the effect of TUG1 on angiogenesis following an ischemic stroke. Materials and Methods: Middle cerebral artery occlusion (MCAO) was adopted to build a focal ischemic model of the rat brain, and pcDNA-TUG1 and miR-26a mimics were injected into rats. Neurological function was estimated through modified neurological severity scores. The volume of focal brain infarction was calculated through 2,3,5-triphenyltetrazolium chloride staining. The level of TUG1 and miR-26a was measured by PCR. The expression of vascular endothelial growth factor (VEGF) and CD31 was checked using immunohistochemistry and western blot. The correlation between miR-26a and TUG1 was verified through a luciferase reporter assay. Results: TUG1 increased noticeably while miR-26a was markedly reduced in MCAO rats. Overexpression of miR-26a improved neurological function recovery and enhanced cerebral angiogenesis in MCAO rats. TUG1 overexpression aggravated neurological deficits and suppressed cerebral angiogenesis in MCAO rats. Bioinformatics analysis revealed that miR-26a was one of the predicted targets of TUG1. Furthermore, TUG1 combined with miR-26a to regulate angiogenesis. TUG1 overexpression antagonized the role of miR-26a in neurological recovery and angiogenesis in MCAO rats. Conclusions: TUG1/miR-26a, which may act as a regulatory axis in angiogenesis following ischemic stroke, can be considered a potential target for cerebral infarction therapy.

Identification of a tripartite motif family gene signature for predicting the prognosis of patients with glioma.

Objectiove: The tripartite motif (TRIM) family genes, which encode a protein subfamily of the RING type E3 ubiquitin ligases, function as important regulators of oncogenesis and development. It is thus of great importance to investigate the potential value of the TRIM family genes for prognostic prediction in glioma. METHODS: The gene expression RNA-Seq data and corresponding clinical information of glioma patients were obtained from The Cancer Genome Atlas (TCGA) dataset and the Chinese Glioma Genome Atlas (CGGA) dataset. LASSO regression and multivariate Cox regression analyses were performed to construct a risk signature of the TRIM family genes. The accuracy of the risk signature in predicting the prognosis of glioma patients was evaluated. The effects of TRIM17 on glioma cell proliferation were further explored. RESULTS: We constructed a prognostic signature based on eight TRIMs for the prediction of overall survival of glioma patients. Internal and external cohorts confirmed the satisfactory accuracy and generalizability of the signature in predicting the prognosis of glioma patients. Of the eight TRIMs, TRIM17 was significantly downregulated in glioma, and decreased with an increase in the tumor grade. Moreover, low expression of TRIM17 predicted poor prognosis in glioma. CCK-8 and colony formation assays indicated that TRIM17 overexpression significantly inhibited cell proliferation. Conversely, silencing of TRIM17 had the opposite effects. CONCLUSION: Our eight-gene signature based on the TRIM gene family is a novel and clinically useful biomarker, which may be helpful for clinical decision-making. Additionally, TRIM17 might be a therapeutic target for glioma.

Shikonin attenuates kidney tubular epithelial cells apoptosis, oxidative stress, and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model.

Natural compounds were used in the treatment of acute kidney injury (AKI) caused by sepsis. This study investigated the function of shikonin from the roots of Arnebia purpurea in sepsis-induced AKI model. The target genes of shikonin were predicted by traditional Chinese medicine integrative database (TCMID). The markers of kidney injury, oxidative stress, and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The pathological changes of kidney tubules were assessed by Hematoxylin and Eosin staining. Apoptosis of kidney tubular epithelial cells (KTECs) was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Protein expression was measured by western blot. Shikonin significantly improved kidney injury induced by cecal ligation and perforation (CLP). Besides, shikonin reduced KTECs apoptosis, malondialdehyde (MDA), reactive oxygen species (ROS), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels, while augmented SOD and IL-10 levels. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 (NOX4) was predicted a target gene of shikonin. The expression of NOX4 was significantly inhibited in shikonin-treated group and the levels of phosphatidylinositol 3,4,5-trisphosphate 3-phosphate and dual specificity protein phosphate (PTEN) and p-p65 were decreased, while level of p-Akt was elevated. In vitro experiments, shikonin inhibited cell apoptosis, inflammatory, and ROS in human HK-2 cells and rat TECs. Shikonin downregulated expression of NOX4, PTEN and p-p65, and upregulated p-AKT and Bcl-2 expression in HK2 cells treated with lipopolysaccharide (LPS). Moreover, overexpression of NOX4 enhanced the effect of LPS on the expression level of PTEN, p-p65, p-AKT, and Bcl-2, which was reversed by the addition of shikonin. Taken together, shikonin could improve sepsis-induced AKI in rats, and attenuate the LPS induced KTECs apoptosis, oxidative stress, and inflammatory reaction via modulating NOX4/PTEN/AKT pathway.

Clinicopathologic profiling and oncologic outcomes of secretory carcinoma of the breast.

Secretory carcinoma of the breast (SCB) is a rather rare entity of invasive breast cancer, the clinicopathologic characteristics and survival outcomes remain to be elaborated. A retrospective review was conducted in SEER database. A total of 190 SCB patients identified in SEER were eligible for inclusion in the analysis. Median age at diagnosis was 56 years (range 2-96 years). Both sexes and bilateral breast could be affected. Intriguingly, the incidence of SCB tended towards to decreasing in recent decades. Small tumor burden was observed with a mean tumor size of 2.13 cm. In a subgroup with sufficient details, positive staining of estrogen receptor (ER) and progesterone receptor (PR) was 58% and 40%, respectively. The vast majority of patients were of well to moderate differentiation (86.86%) and negative regional lymph nodes involvement (70.71%). Nearly half of the patients took radiotherapy and chemotherapy. Seniors were inclined to have an inferior breast cancer specific survival (BCSS) than their younger counterparts (P = 0.018). Patients underwent breast conserving surgery (BCS) and radiotherapy had much better BCSS than its mastectomy counterparts (P = 0.014). Collectively, SCB is a clinical indolent invasive breast cancer with excellent prognosis. BCS in conjunction with radiotherapy would be a rational alternative for this distinct entity.

Prognostic and clinicopathological significance of C-reactive protein/albumin ratio (CAR) in patients with gastric cancer: A meta-analysis.

BACKGROUND: In recent years, many studies have explored the potential prognostic utility of C-reactive protein/albumin ratio (CAR) in patients with gastric cancer (GC), however, the results remain conflicting. We thus performed a meta-analysis to determine the association of CAR and prognosis of GC. METHODS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed, Web of science, Embase, and Cochrane Library were searched. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and cancer-specific survival (CSS) of included studies were pooled to estimate the prognostic value of CAR. RESULTS: Eight studies with a total of 3,216 patients were included in this meta-analysis. High CAR was significantly associated with poor OS (HR = 1.59, 95%CI = 1.36-1.85, p<0.001) and worse CSS (HR = 1.65, 95%CI = 1.21-2.25, p = 0.002). In addition, high CAR was significantly associated with male sex (OR = 1.80, 95%CI = 1.31-2.47, p<0.001), advanced tumor stage (OR = 2.14, 95%CI = 1.48-3.09, p<0.001), and tumor size ≥3cm (OR = 2.69, 95%CI = 1.84-3.93, p<0.001). CONCLUSION: Elevated pretreatment CAR is a prognostic marker of poor OS and CSS in patients with GC. Furthermore, high CAR levels are associated with clinicopathological features reflecting tumor progression.

Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size.

BACKGROUND: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, tocilizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. METHODS: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14-day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). RESULTS: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08-6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62-16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39-4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. CONCLUSION: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflammation of COVID-19 patients and inhibit the deterioration of the disease.

Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4.

Previous investigations have proved that microRNA (miR)-765 is significantly overexpressed in multiple tumor types. Nevertheless, the underlying molecular mechanism of miR-765 in mediating breast carcinoma cell growth and metastasis remains unclear. Quantitative real-time polymerase chain reaction was used to determine the levels of miR-765 and inhibitor of growth 4 (ING4) in breast carcinoma tissues and breast carcinoma cells. Cell proliferation, colony formation, wound healing, and Transwell invasion assays were used to analysis the role of miR-765 on breast carcinoma cell growth and aggressiveness. The expressions of ING4 were determined using Western blot analysis and immunohistochemical staining. The direct target of ING4 and miR-765 was confirmed using the luciferase reporter assay. Nude mice were subcutaneously implanted with miR-765 inhibitor transfected MDA-MB-231 cells to determine the potential role of miR-765 in tumor growth in vivo. We observed that miR-765 is overexpressed in breast carcinoma tissue and breast cancer cells. By using luciferase reporter gene bioassay, we find that ING4 is the direct target of miR-765 in breast carcinoma. The level of ING4 is inversely associated with the level of miR-765. The gain-of-function and loss-of-function experiments in vitro indicate that the downregulation of miR-765 suppresses the growth, mobility, and invasion abilities of breast cancer cells by inhibiting ING4. In addition, overexpression of ING4 suppresses the aggressiveness of the MDA-BA-231 cell that is induced by miR-761 in vitro. In this study, we prove that miR-765 regulates the growth and metastasis of breast cancer via modulating miR-765-ING4-negative feedback loop.

Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies.

Many molecular epidemiological studies have been performed to explore the association between MTHFR C677T polymorphism and cancer risk in diverse populations. However, the results were inconsistent. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR C677T (150,086 cases and 200,699 controls from 446 studies) polymorphism. Overall, significantly increased cancer risk was found when all eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significantly increased breast cancer risk was found in Asians and Indians, significantly decreased colon cancer risk was found, significantly decreased colorectal cancer risk was found in male population, significantly increased gastric cancer risk was found in Caucasians and Asians, significantly increased hepatocellular cancer risk was found in Asians, significantly decreased adult acute lymphoblastic leukemia (AALL) risk was found in Caucasians, significantly decreased childhood acute lymphoblastic leukemia (CALL) risk was found in Asians, and significantly increased multiple myeloma and NHL risk was found in Caucasians. In summary, this meta-analysis suggests that MTHFR C677T polymorphism is associated with increased breast cancer, gastric cancer, and hepatocellular cancer risk in Asians, is associated with increased gastric cancer, multiple myeloma, and NHL risk in Caucasians, is associated with decreased AALL risk in Caucasians, is associated with decreased CALL risk in Asians, is associated with increased breast cancer risk in Asians, is associated with decreased colon cancer risk, and is associated with decreased colorectal cancer risk in male population. Moreover, this meta-analysis also points out the importance of new studies, such as Asians of HNC, Asians of lung cancer, and Indians of breast cancer, because they had high heterogeneity in this meta-analysis (I(2) > 75%).

A Markov model of the cost-effectiveness of pharmacist care for diabetes in prevention of cardiovascular diseases: evidence from Kaiser Permanente Northern California.

BACKGROUND: It has been demonstrated in previous studies that pharmacist management of patients with type 2 diabetes mellitus (T2DM) in the outpatient setting not only improves diabetes-related clinical outcomes such as hemoglobin A1c but also blood pressure (BP), total cholesterol (TC), and quality of life. Improved control of BP and TC has been shown to reduce the risks of cardiovascular disease (CVD), which has placed a heavy economic burden on the health care system. However, no study has evaluated the cost-effectiveness of pharmacist intervention programs with respect to the long-term preventive effects on CVD outcomes among T2DM patients. OBJECTIVES: To (a) quantify the long-term preventive effects of pharmacist intervention on CVD outcomes among T2DM patients using evidence from a matched cohort study in the outpatient primary care setting and (b) assess the relative cost-effectiveness of adding a clinical pharmacist to the primary care team for the management of patients with T2DM based on improvement in CVD risks with the aid of an economic model. METHODS: Clinical data between the periods of June 2007 to February 2010 were collected from electronic medical records at 2 separate clinics at Kaiser Permanente (KP) Northern California, 1 with primary care physicians only (control group) and the other with the addition of a pharmacist (enhanced care group). Patients in the enhanced care group were matched 1:1 with patients in the control group according to baseline characteristics that included age, gender, A1c, and Charlson comorbidity score. The estimated 10-year CVD risk for both groups was calculated by the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine (version 2) based on age, sex, race, smoking status, atrial fibrillation, duration of diabetes, levels of A1c, systolic BP (SBP) and TC, and high-density lipoprotein cholesterol (HDL-C) observed at 12 months. There was no statistical difference in the baseline clinical inputs to the Risk Engine (A1c [P=0.115], SBP [P=0.184], TC [P=0.055], and HDL-C [P=0.475]) between the 2 groups. A Markov model was developed to simulate the estimated CVD outcomes over 10 years and to estimate cost-effectiveness. The final outcomes examined included incremental cost and effectiveness measured by life years and per quality-adjusted life year gained. Both deterministic sensitivity analysis (SA) and probabilistic SA were conducted to examine the robustness of the results. RESULTS: The estimated risks for coronary heart disease (CHD) and stroke (both nonfatal and fatal) at the end of the follow-up were consistently lower in the enhanced care group compared with the control group, even though baseline risks in both groups were similar. The absolute risk reduction (ARR) between the enhanced care and control groups increased over time. For example, the ARR for nonfatal CHD risk in year 1 was 0.5% (1.2% vs. 0.7%), whereas the ARR increased to 5.5% in year 10 (14.8% vs. 9.3%). Similarly, the ARR between the enhanced care and the control groups was calculated as 0.3% for fatal CHD in year 1 and increased to 4.6% in year 10. Results from the Markov model suggest that the enhanced care group was shown to be a dominant strategy (less expensive and more effective) compared with the control group in the 10-year evaluation period in the base-case (average or mean results) scenario. Sensitivity analysis that took into account the uncertainty in all important variables, such as wage of pharmacists, utility weight (the degree of preference individuals have for a particular health state or condition), response rate to pharmacists' care, and uncertainty associated with the estimated 10 years of CVD risk, revealed that the relative value of enhanced care was robust to most of the variations in these parameters. Notably, the level of cost-effectiveness measured by net monetary value depends on the time horizon adopted by the payers and the magnitude of CVD risk reduction. The enhanced care group has a higher chance of being considered as a cost-effective strategy when a longer time horizon such as a minimum of 4 to 5 years is adopted. CONCLUSIONS: Adding pharmacists to the health care management team for diabetic patients improves the long-term CVD risks. The longer-term CVD risk reductions were shown to be more dramatic than the short-term reduction. A longer time horizon adopted by health plans in managing T2DM patients has a higher probability of making the intervention cost-effective.

Autofluorescence generation and elimination: a lesson from glutaraldehyde.

Glutaraldehyde causes especially high autofluorescence. It reacted with proteins and peptides to generate visible to near-IR emitters. A model indicated that ethylenediamine and a secondary amine in the molecule were key components for the formation of emissive species. The mechanism enables us to control the generation and elimination of autofluorescence.

The cost-effectiveness of immediate treatment, percutaneous biopsy and active surveillance for the diagnosis of the small solid renal mass: evidence from a Markov model.

PURPOSE: The most effective diagnostic strategy for the very small, incidentally detected solid renal mass is uncertain. We assessed the cost-effectiveness of adding percutaneous biopsy or active surveillance to the diagnosis of a 2 cm or less solid renal mass. MATERIALS AND METHODS: A Markov state transition model was developed to observe a hypothetical cohort of healthy 60-year-old men with an incidentally detected, 2 or less cm solid renal mass, comparing percutaneous biopsy, immediate treatment and active surveillance. The primary outcomes assessed were the incremental cost-effectiveness ratio measured by cost per life-year gained at a willingness to pay threshold of $50,000. Model results were assessed by sensitivity analysis. RESULTS: Immediate treatment was the highest cost, most effective diagnostic strategy, providing the longest overall survival of 18.53 life-years. Active surveillance was the lowest cost, least effective diagnostic strategy. On cost-effectiveness analysis using a societal willingness to pay threshold of $50,000 active surveillance was the preferred choice at a $75,000 willingness to pay threshold while biopsy and treatment were acceptable ($56,644 and $70,149 per life-year, respectively). When analysis was adjusted for quality of life, biopsy dominated immediate treatment as the most cost-effective diagnostic strategy at $33,840 per quality adjusted life-year gained. CONCLUSIONS: Percutaneous biopsy may have a greater role in optimizing the diagnosis of an incidentally detected, 2 cm or less solid renal mass.

Developing luminescent silver nanodots for biological applications.

Though creation and characterization of water soluble luminescent silver nanodots were achieved only in the past decade, a large variety of emitters in diverse scaffolds have been reported. Photophysical properties approach those of semiconductor quantum dots, but relatively small sizes are retained. Because of these properties, silver nanodots are finding ever-expanding roles as probes and biolabels. In this critical review we revisit the studies on silver nanodots in inert environments and in aqueous solutions. The recent advances detailing their chemical and physical properties of silver nanodots are highlighted with an effort to decipher the relations between their chemical/photophysical properties and their structures. The primary results about their biological applications are discussed here as well, especially relating to their chemical and photophysical behaviours in biological environments (216 references).