Epidemiological profile, clinico-pathological correlation and treatment response in Adult patients with IgA nephropathy.

INTRODUCTION : First described by Jean Berger as a disease entity with diffuse mesangial deposition of IgA deposits. Once thought to have benign entity of self limiting hematuria, now found to have slowly progressive in nature with the propensity to develope chronic kidney disease in 15-20 percent in 15 -20 years. It presents with constellation of clinical syndrome ranging from asymptomatic urine abnormalities to smoldering rapidly progressive glomerulo nephritis. Diversity of clinical signs and syndrome is a constant feature. With the advance in genetic, more molecular pathways are unraveled, pathogenesis were defined little better than previous, so this commonest glomerulonephritis is revealing its secrets. Better understanding of glycation, galactosylation molecular machineries in depth of enzymes and chaperone, better search of happenings of talks of mesangium, podocytes and proximal tubule through cytokines and receptors, better knowledge of mucosa marrow axis and TLR clearly will open new prospective in treatment. Epidemiological point of view, both increasing awareness such as treatment of for hematuria, prompt referral to the nephrologist, more precise immunoflourescence studies, IgA nephropathy incidence is on increasing trend . Hence proper, long term randomized control trials(RCT) needed in many areas of IgA nephropathy. AIM OF THE STUDY : 1. To study the epidemiological profile of IgA nephropathy in adult patients. 2. To study the clinicopathological correlation of IgA nephropathy. 3. To evaluate the response to treatment, predictors of response and Risk factors in the progression to CKD in these patients. CONCLUSION : 1. Nephrotic syndrome is the most common clinical presentation in IgA nephropathy. 2. Majority of the patients presented with renal failure at entry into study. 3. Severe MEST scoring was significantly associated with renal failure at presentation. 4. Non- responders of proteinuria and those who had severe S and T scores in MEST scoring system progressed to chronic kidney disease. 5. Those who had either complete or partial remission of proteinuria had less chance to progression of CKD during the follow up period

spSeudoMap: cell type mapping of spatial transcriptomics using unmatched single-cell RNA-seq data

Since many single-cell RNA-seq (scRNA-seq) data are obtained after cell sorting, such as when investigating immune cells, tracking cellular landscape by integrating single-cell data with spatial transcriptomic data is limited due to cell type and cell composition mismatch between the two datasets. We developed a method, spSeudoMap, which utilizes sorted scRNA-seq data to create virtual cell mixtures that closely mimic the gene expression of spatial data and trains a domain adaptation model for predicting spatial cell compositions. The method was applied in brain and breast cancer tissues and accurately predicted the topography of cell subpopulations. spSeudoMap may help clarify the roles of a few, but crucial cell types

Prognostic impact of an integrative analysis of [18F]FDG PET parameters and infiltrating immune cell scores in lung adenocarcinoma

Background : High levels of 18F-fluorodeoxyglucose (18F-FDG) tumor uptake are associated with worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, high levels of immune cell infiltration in primary tumor have been linked to better prognosis in NSCLC. We conducted this study for precisely stratified prognosis of the lung adenocarcinoma patients using the integration of 18F-FDG positron emission tomography (PET) parameters and infiltrating immune cell scores as assessed by a genomic analysis. Results : Using an RNA sequencing dataset, the patients were divided into three subtype groups. Additionally, 24 different immune cell scores and cytolytic scores (CYT) were obtained. In 18F-FDG PET scans, PET parameters of the primary tumors were obtained. An ANOVA test, a Chi-square test and a correlation analysis were also conducted. A Kaplan–Meier survival analysis with the log-rank test and multivariable Cox regression test was performed to evaluate prognostic values of the parameters. The terminal respiratory unit (TRU) group demonstrated lower 18F-FDG PET parameters, more females, and lower stages than the other groups. Meanwhile, the proximal inflammatory (PI) group showed a significantly higher CYT score compared to the other groups (P = .001). Also, CYT showed a positive correlation with tumor-to-liver maximum standardized uptake value ratio (TLR) in the PI group (P = .027). A high TLR (P = .01) score of 18F-FDG PET parameters and a high T follicular helper cell (TFH) score (P = .005) of immune cell scores were associated with prognosis with opposite tendencies. Furthermore, TLR and TFH were predictive of overall survival even after adjusting for clinicopathologic features and others (P = .024 and .047). Conclusions : A high TLR score was found to be associated with worse prognosis, while high CD8 T cell and TFH scores predicted better prognosis in lung adenocarcinoma. Furthermore, TLR and TFH can be used to predict prognosis independently in patients with lung adenocarcinoma.This study was supported by the National Research Foundation of Korea (NRF) (NRF-2019M2D2A1A01058210, NRF-2020R1C1C1009000, 2021M2E8A1039564) and Creative-Pioneering Researchers Program through Seoul National University (SNU)

Association of metabolic and genetic heterogeneity in head and neck squamous cell carcinoma with prognostic implications: integration of FDG PET and genomic analysis

Purpose The linkage between the genetic and phenotypic heterogeneity of the tumor has not been thoroughly evaluated. Herein, we investigated how the genetic and metabolic heterogeneity features of the tumor are associated with each other in head and neck squamous cell carcinoma (HNSC). We further assessed the prognostic significance of those features. Methods The mutant-allele tumor heterogeneity (MATH) score (n = 508), a genetic heterogeneity feature, and tumor glycolysis feature (GlycoS) (n = 503) were obtained from the HNSC dataset in the cancer genome atlas (TCGA). We identified matching patients (n = 33) who underwent 18F-fluorodeoxyglucose positron emission tomography (FDG PET) from the cancer imaging archive (TCIA) and obtained the following information from the primary tumor: metabolic, metabolic-volumetric, and metabolic heterogeneity features. The association between the genetic and metabolic features and their prognostic values were assessed. Results Tumor metabolic heterogeneity and metabolic-volumetric features showed a mild degree of association with MATH (n = 25, ρ = 0.4~0.5, P < 0.05 for all features). The patients with higher FDG PET features and MATH died sooner. Combination of MATH and tumor metabolic heterogeneity features showed a better stratification of prognosis than MATH. Also, higher MATH and GlycoS were associated with significantly worse overall survival (n = 499, P = 0.002 and 0.0001 for MATH and GlycoS, respectively). Furthermore, both MATH and GlycoS independently predicted overall survival after adjusting for clinicopathologic features and the other (P = 0.015 and 0.006, respectively). Conclusion Both tumor metabolic heterogeneity and metabolic-volumetric features assessed by FDG PET showed a mild degree of association with genetic heterogeneity in HNSC. Both metabolic and genetic heterogeneity features were predictive of survival and there was an additive prognostic value when the metabolic and genetic heterogeneity features were combined. Also, MATH and GlycoS were independent prognostic factors in HNSC; they can be used for precise prognostication once validated.This study was supported by the National Research Foundation of Korea (NRF) (NRF-2017R1D1A1B03035556, and NRF-2019M2D2A1A01058210), and the Ministry of Health and Welfare Korea (HI18C0886, and HI19C0339)

Image-level trajectory inference of tau pathology using variational autoencoder for Flortaucipir PET.

PURPOSE Alzheimer's disease (AD) studies revealed that abnormal deposition of tau spreads in a specific spatial pattern, namely Braak stage. However, Braak staging is based on post mortem brains, each of which represents the cross section of the tau trajectory in disease progression, and numerous studies were reported that do not conform to that model. This study thus aimed to identify the tau trajectory and quantify the tau progression in a data-driven approach with the continuous latent space learned by variational autoencoder (VAE). METHODS A total of 1080 [18F]Flortaucipir brain positron emission tomography (PET) images were collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. VAE was built to compress the hidden features from tau images in latent space. Hierarchical agglomerative clustering and minimum spanning tree (MST) were applied to organize the features and calibrate them to the tau progression, thus deriving pseudo-time. The image-level tau trajectory was inferred by continuously sampling across the calibrated latent features. We assessed the pseudo-time with regard to tau standardized uptake value ratio (SUVr) in AD-vulnerable regions, amyloid deposit, glucose metabolism, cognitive scores, and clinical diagnosis. RESULTS We identified four clusters that plausibly capture certain stages of AD and organized the clusters in the latent space. The inferred tau trajectory agreed with the Braak staging. According to the derived pseudo-time, tau first deposits in the parahippocampal and amygdala, and then spreads to the fusiform, inferior temporal lobe, and posterior cingulate. Prior to the regional tau deposition, amyloid accumulates first. CONCLUSION The spatiotemporal trajectory of tau progression inferred in this study was consistent with Braak staging. The profile of other biomarkers in disease progression agreed well with previous findings. We addressed that this approach additionally has the potential to quantify tau progression as a continuous variable by taking a whole-brain tau image into account

99mTc-MAA accumulation within tumor in preoperative lung perfusion SPECT/CT associated with occult lymph node metastasis in patients with clinically N0 non-small cell lung cancer

Background 99mTc-MAA accumulation within the tumor representing pulmonary arterial perfusion, which is variable and may have a clinical significance. We evaluated the prognostic significance of 99mTc-MAA distribution within the tumor in non-small cell lung cancer (NSCLC) patients in terms of detecting occult nodal metastasis and lymphovascular invasion, as well as predicting the recurrence-free survival (RFS). Methods Two hundred thirty-nine NSCLC patients with clinical N0 status who underwent preoperative lung perfusion SPECT/CT were retrospectively evaluated and classified according to the visual grading of 99mTc-MAA accumulation in the tumor. Visual grade was compared with the quantitative parameter, standardized tumor to lung ratio (TLR). The predictive value of 99mTc-MAA accumulation with occult nodal metastasis, lymphovascular invasion, and RFS was assessed. Results Eighty-nine (37.2%) patients showed 99mTc-MAA accumulation and 150 (62.8%) patients showed the defect on 99mTc-MAA SPECT/CT. Among the accumulation group, 45 (50.5%) were classified as grade 1, 40 (44.9%) were grade 2, and 4 (4.5%) were grade 3. TLR gradually and significantly increased from grade 0 (0.009 ± 0.005) to grade 1 (0.021 ± 0.005, P < 0.05) and to grade 2–3 (0.033 ± 0.013, P < 0.05). The following factors were significant predictors for occult nodal metastasis in univariate analysis: central location, histology different from adenocarcinoma, tumor size greater than 3cm representing clinical T2 or higher, and the absence of 99mTc-MAA accumulation within the tumor. Defect in the lung perfusion SPECT/CT remained significant at the multivariate analysis (Odd ratio 3.25, 95%CI [1.24 to 8.48], p = 0.016). With a median follow-up of 31.5 months, the RFS was significantly shorter in the defect group (p = 0.008). Univariate analysis revealed that cell type of non-adenocarcinoma, clinical stage II-III, pathologic stage II-III, age greater than 65 years, and the 99mTc-MAA defect within tumor as significant predictors for shorter RFS. However, only the pathologic stage remained statistically significant, in multivariate analysis. Conclusion The absence of 99mTc-MAA accumulation within the tumor in preoperative lung perfusion SPECT/CT represents an independent risk factor for occult nodal metastasis and is relevant as a poor prognostic factor in clinically N0 NSCLC patients. 99mTc-MAA tumor distribution may serve as a new imaging biomarker reflecting tumor vasculatures and perfusion which can be associated with tumor biology and prognosis.This research was supported by the National Research Foundation of Korea (NRF) and funded by the Korean government (MSIT) (No.2020M3A9B6038086