Concise nanotherapeutic modality for cancer involving graphene oxide dots in conjunction with ascorbic acid.

Cancer cells tend to have higher intracellular reactive oxygen species (ROS) levels and are more vulnerable to ROS-generating therapies such as ascorbic acid (H2Asc) therapy, whose potency has been explored by several clinical trials. However, its efficiency is restricted by the requirement of pharmacologically high local H2Asc concentrations. Here, we show that nitrogen-doped graphene oxide dots (NGODs), which are highly crystalline and biocompatible, can serve as a catalytic medium for improving H2Asc cancer therapy at orally achievable physiological H2Asc concentrations. NGODs catalyze H2Asc oxidation for H2O2 and dehydroascorbic acid generation to disrupt cancer cells by consuming intracellular glutathione (GSH) and inducing ROS damage. This is the first study to demonstrate the direct consumption of GSH using a carbon-based nano-catalyst (NGODs), which further expedites tumor killing. In addition, as in our previous study, NGODs can also serve as a highly efficient photosensitizer for photodynamic therapy. Under illumination, NGODs produce a considerable amount of H2O2 in the presence of physiological levels of H2Asc as a hole scavenger and further enhance the therapeutic efficiency. Thus, a concise nanotherapeutic modality could be achieved through the conjunction of multifunctional NGODs and H2Asc to selectively eliminate deep-seated and superficial tumors simultaneously (under 65% of normal cell viability, it kills almost all cancer cells). Note that this level of therapeutic versatility generally requires multiple components and complex manufacturing processes that run into difficulties with FDA regulations and clinical applications. In this study, the concise NGOD-H2Asc nanotherapeutic modality has demonstrated its great potential in cancer therapy.

Pneumocystis Jirovecii Pneumonia in Systemic Lupus Erythematosus: A Nationwide Cohort Study in Taiwan.

OBJECTIVE: To evaluate Pneumocystis jirovecii pneumonia (PJP) infection risk in patients with systemic lupus erythematosus (SLE) in Taiwan. METHODS: We identified 24,367 patients with SLE from the National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age- and sex-matched non-SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model. RESULTS: The SLE patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person-years and IR ratio of 27.65 (95% confidence interval 17.2-45.3; P < 0.001). Male sex (hazard ratio [HR] 2.42, P < 0.01), end-stage renal disease (ESRD; HR 1.74, P = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, P < 0.001), and average oral dosage of >7.5 mg/day prednisolone or equivalent treatment (HR 4.83, P < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, P = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model. CONCLUSION: Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, and oral prednisolone or equivalent treatment (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.

Epidemiology and risk of invasive fungal infections in systemic lupus erythematosus: a nationwide population-based cohort study.

INTRODUCTION: Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited. METHODS: Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan's National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs. RESULTS: A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 [95% confidence interval (CI): 9.8-12.6] relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9-86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30-36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes. CONCLUSION: Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE. PLAIN LANGUAGE SUMMARIES: Patients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections.Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens.Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.

Risk of severe herpes simplex virus infection in systemic lupus erythematosus: analysis of epidemiology and risk factors analysis in Taiwan.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are susceptible to herpes simplex virus (HSV) infection, which occasionally leads to severe complications including meningoencephalitis and keratitis. However, few attempts to analyse the associated incidence and risk factors have been made. METHODS: We enrolled patients with SLE recorded between 1997 and 2012 and compared the incidence rate (IR) of severe HSV infection, including meningoencephalitis, septicaemia, ocular and visceral involvement, and other specific complications demanding hospitalisation, with that of a non-SLE cohort. A Cox multivariate proportional hazards model was applied to analyse the risk factors of severe HSV infection in patients with SLE. RESULTS: A total of 122 520 subjects (24 504 patients with SLE and 98 016 age-matched and sex-matched non-SLE controls) were included, and a higher IR of severe HSV infection was revealed in the SLE group (IR ratio=3.93, p<0.001). In patients with SLE, previous oral and genital infection (HR=2.29, p=0.049), intravenous steroid pulse therapy (HR=5.32, p<0.001) and daily oral dose of over 7.5 mg of prednisolone (HR=1.59, p=0.024) were independent risk factors for severe HSV infection, whereas age of ≤18 (HR=0.45, p=0.029) was a protective factor. CONCLUSIONS: Patients with SLE are at higher risk of severe HSV infection, and related risk factors include being older than 18 years, having a history of HSV mucocutaneous infection, recent receipt of steroid pulse therapy and a daily oral dose of steroid over 7.5 mg prednisolone.