Incidence of hemorrhagic cystitis after cyclophosphamide therapy with or without mesna: A cohort study and comprehensive literature review.

BACKGROUND: Cyclophosphamide is an alkylating agent associated with significant toxicities, most importantly hemorrhagic cystitis. Many approaches including mesna use were established to reduce this toxicity. However, data on mesna efficacy are conflicting. OBJECTIVE: To investigate the incidence of hemorrhagic cystitis in patients receiving cyclophosphamide therapy with or without mesna. METHODS: A retrospective chart review was done on all adult patients receiving cyclophosphamide therapy with or without mesna at the King Saud University Medical City. The incidence of hemorrhagic cystitis was recorded. Patients receiving mesna were compared with those not receiving mesna. Data were reported as numbers and percentages, and appropriate statistical tests of association were used. This step was followed by a comprehensive literature review using appropriate keywords in PubMed from the inception of the database until August 2019. All studies of interest were reported. RESULTS: A total of 718 patients' medical records were reviewed. The majority of the patients received mesna (n = 433, 60%). The mesna group had a greater incidence of hemorrhagic cystitis (3.5% vs. 0.4%, p < 0.004) and received a significantly larger cumulative dose (3103 ± 1696 vs. 2465 ± 1528, p < 0.001) mg of cyclophosphamide therapy. Our literature review revealed large differences in the conclusions of published trials with highly diverse study designs and populations, emphasizing on the need of large prospective trials to address this topic.Conclusion and relevance: Our study results do not support the use of mesna in preventing hemorrhagic cystitis. We found that the only influential factor in the development of hemorrhagic cystitis was the dose of cyclophosphamide therapy.

Quantitative analysis of soluble costimulatory molecules as potential diagnostic biomarkers for rheumatoid arthritis using LC-MS/MS in MRM mode.

BACKGROUND AND AIMS: Rheumatoid arthritis (RA) is a chronic autoimmune disease. RA-induced immunological responses are coordinated by T-cell stimulation. The costimulatory signal CD28-B7 is essential for T-cell activation by interacting CD28 with CD80 and CD86 costimulatory proteins. CTLA4 is another costimulatory protein that binds to CD80 and CD86 to inhibit T-cell activity. The soluble costimulatory proteins: sCD80, sCD86, sCD28, and sCTLA-4 were detected and quantified in human plasma and correlated with RA development. As potential diagnostic biomarkers for RA, developing a sensitive, specific, and reproducible method for quantifying these costimulatory molecules in human plasma and establishing quantitative ranges for each protein in healthy and RA patients' plasma is essential for advancing the clinical diagnostic and health outcomes. MATERIALS AND METHODS: A novel quantitative liquid chromatography-tandem spectrometry (LC-MS/MS) technique using multiple reaction monitoring (MRM) modes was developed and validated to measure soluble costimulatory molecules sCTLA4, sCD28, sCD80, and sCD86 in human plasma samples. Furthermore, the method was applied to determine sCTLA4, sCD28, sCD80, and sCD86 levels in plasma samples from RA patients (n = 23) and healthy controls (n = 21). RESULTS: The method was successfully developed and validated according to international inter- and intra-assay precision and accuracy guidelines. The linearity of the method was achieved between 0.5 nM and 100 nM for each protein with a correlation coefficient of > 0.998. The plasma level of sCTLA4, sCD80, and sCD86 in RA patients was significantly elevated compared to controls. RA patients had 63.32 ± 17.63 nM sCTLA4 and controls 36.05 ± 18.83 nM; p < 0.0001. The performance of the four proteins was determined using ROC curves, where sCTLA4 showed the highest diagnostic and clinical performance compared to the others. CONCLUSIONS: This study reports the first use of LC-MS/MS in MRM mode to accurately quantify soluble costimulatory molecules in plasma samples as potential RA diagnostic biomarkers. Determination of the reference range for each protein with high selectivity and sensitivity increases the potential for utilizing this method as a clinical diagnostic.

Impact of COVID-19 outbreak on rheumatic patients' perceptions and behaviors: A cross-sectional study.

AIM: The dynamics of coronavirus disease 2019 (COVID-19) pandemic has become of special concern to the rheumatology community. Rheumatic patients are required to engage in effective health management but their behavior is often influenced by intrinsic and extrinsic factors. This cross-sectional study aims to examine patients' experiences during the current pandemic and its implication on their health perception and behavior. METHOD: A patient-centered electronic survey was used, randomly sampling rheumatic patients in Saudi Arabia during March and April 2020. Questions included patients' socio-demographics, diseases, medications, COVID-19 knowledge, source of information, fear level, disease activity perception, health care utilization, medication accessibility, and therapeutic compliance (measured using a modified version of Medication Adherence Reporting Scale). Correlation and regression coefficients were used to evaluate associations among the aforementioned variables. RESULTS: A total of 637 respondents were included. The majority were rheumatoid arthritis patients (42.7%). Patients' knowledge about COVID-19 was correlated with social media use (P = .012). Fear of COVID-19 infection correlated with healthcare facility for follow-up visits (P = .024) and fear of disease deterioration if contracting the infection correlated with patients' levels of knowledge (P = .035). Both types of fear did not correlate with patients' perceptions of disease activity. However, patients' perceptions of worsened disease activity were correlated with unplanned healthcare visits (P < .001), medication non-adherence, and difficulty accessing medication (P = .010 and .006, respectively). CONCLUSION: The COVID-19 pandemic and surrounding public health measures could affect rheumatic patients' health management which might contribute to disease flare-up and subsequently taxing healthcare systems even further.