A comparison between conventional and the Paris systems of reporting urinary cytopathology with a literature update.

INTRODUCTION: Owing to certain inherent limitations of earlier reporting systems, "The Paris System for Reporting Urinary Cytology (TPS)" was implemented in 2015 to standardize reporting urine cytology with more stringent cytomorphologic criteria. We share our post-TPS experience, comparing it with the conventional system (CS). AIM: To assess and compare the cyto-histopathologic/cystoscopic agreement between the conventional and the Paris systems (CS and TPS) for reporting urine cytology. MATERIALS AND METHODS: It is a cross-sectional study involving urine samples from 170 patients divided into two groups (CS and TPS). Of the 170 cases, 85 were reported according to the CS, and 85 were reported according to TPS with all the relevant clinical, radiologic, and cystoscopic findings. Using the kappa statistics, both groups were statistically analyzed for sensitivity, specificity, predictive values, and agreement. RESULTS: The sensitivity and specificity for high-grade urothelial carcinoma (HGUC) as per TPS were 83.33% and 94.59%, respectively, while they were 73.47% and 80.56% for the conventional system. The agreement for HGUC with TPS was 87.06% with a kappa value of 0.7416, while it was 76.5% with a kappa value of 0.53 for the CS. Implementing the TPS minimized usage of the atypical urothelial cells (AUC) category, increasing the clarity in detecting HGUC. CONCLUSION: TPS provides better agreement with histopathology than the CS for diagnosing HGUC, which is attributable to stringent TPS criteria that prompt cytopathologists to look more diligently for morphologic and numeric criteria.

Budget impact and cost-utility analysis of prophylactic emicizumab versus on-demand bypassing agents for adolescent severe haemophilia A patients with inhibitors in India.

Introduction: Severe Haemophilia A patients with inhibitors are currently being treated with bypassing agents like activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa. Emicizumab is a recombinant humanized monoclonal antibody, introduced to reduce the bleeding events, improve treatment adherence, and quality of life. However, cost-effectiveness and long-term sustainability of the intervention is not studied in a low middle income setting like India. Aim: The primary objective of this study was to evaluate the cost-utility of Emicizumab compared to traditional bypassing agents in the treatment of severe haemophilia A patients with inhibitors in India. Secondary objective was to analyze the budgetary impact of introducing Emicizumab for this patient population from the perspective of public health system in India. Methods: Markov model was created to compare the prophylactic emicizumab therapy against bypassing agents for a hypothetical cohort of 10-year-old adolescents in India. The time horizon was 10 years and model built based on health system perspective. Cost utility was expressed as costs per quality-adjusted life-years (QALYs) gained. All costs were expressed as 2021 US dollars. Probabilistic sensitivity analysis was performed to check the robustness of the estimates. Results: Prophylactic emicizumab was a cost saving intervention with negative Incremental Cost Utility Ratio (ICUR) against recombinant factor VIIa of -853,573 USD (INR -63,109,773), and negative ICUR of -211,675 USD (INR -15,650,403) against APCC. The estimated total budget for treating all the severe Haemophilia A patients with inhibitors in India was USD 59,042,000 (INR 4,365,329,312) for 10 years' time horizon (per patient cost of USD 295,210 [INR 21,826,646.56]). Conclusion: Prophylactic emicizumab therapy is a cost saving intervention when compared to both the bypassing agents as it is less costly and more effective for severe Haemophilia A patients with inhibitors in India.

The Utility of CD43 and CD200 in Differentiating Chronic Lymphocytic Leukemia from Other Mature B-Cell Neoplasms: A Cross Sectional Study.

To evaluate the utility of CD43 and CD200 in differentiating chronic lymphocytic leukemia (CLL) from other mature B-cell neoplasms. This was a cross-sectional study on patients diagnosed with B-cell neoplasms on flowcytometry. The median fluorescence intensity (MFI) of CD43, CD200 expressing neoplastic B-cells were compared between the CLL and non-CLL B-cell neoplasms followed by receiver operating characreristic curve (ROC) analysis. In addition, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CD43 and CD200 in diagnosing CLL were analysed. A total of 137 patients were included. The CLL group consisted 87 patients and non-CLL group consisted 50 patients. The Mann-Whitney U test showed significant CD43 expression (U = 997.5, Z= - 5.265, p < 0.001) and CD200 expression (U = 932.0, Z = - 5.5, p < 0.01) in CLL patients compared to non-CLL patients. The area under the curve were 0.771 and 0.786 for MFI of CD43 and CD200 in differentiating CLL from non-CLL group respectively. The optimal cut-off of MFI for CD43 and CD200 were 1323 and 1775 respectively. The sensitivity, specificity, PPV and NPV of CD43 in diagnosing CLL cases were 97.7%, 66%, 83.3% and 94.2% respectively. The sensitivity, specificity, PPV and NPV of CD200 in diagnosing CLL cases were 100%, 32%, 71.9% and 100% respectively. CD43 and CD200 are useful markers in differentiating CLL from other mature B-cell neoplasms with higher MFI expression of both markers found in CLL.

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition.

To clarify the significance of bone marrow fibrosis and amyloid deposition in plasma cell neoplasm, a retrospective cross-sectional study for a period of 3 years was conducted. Patients who underwent bone marrow aspiration and biopsy with suspicion of plasma cell neoplasms were included in the study. The bone marrow findings were correlated with clinical profile of the patient along with biochemical parameters, cytogenetics, Fluorescent in situ hybridization (FISH) wherever available. A total of 273 bone marrow aspirates and biopsies of patients with suspected plasma cell neoplasms were analyzed. There were 181 male patients and 92 female patients (Male: Female = 1.96: 1). There were 245 cases of multiple myeloma (89.7%), 8 cases of primary amyloidosis (2.9%) and 6 monoclonal gammopathy of undetermined significance (MGUS) (2.1%), 5 cases of plasmacytoma (1.8%) and 4 cases of smouldering myeloma (1.4%), 5 cases of POEMS syndrome (1.8%). Bone marrow fibrosis was noted in 12 patients at diagnosis (4.3%). Among the parameters studied, only the mean Hemoglobin was significantly low in patients with marrow fibrosis. Amyloid deposition in various organs including bone marrow, kidney, liver etc., were noted in 17 patients overall (6.2%). In conclusion, the incidence of fibrosis (4.3%) and amyloidosis (6.2%) associated with plasma cell neoplasms were much lower in our study as compared to published studies.