A case of kidney transplantation for complete C4 deficiency with recurrent IgM-monoclonal gammopathy of renal significance (MGRS) associated nephropathy

We present a rare case of a patient with complete C4 deficiency who underwent kidney transplantation and experienced immunoglobulin M-monoclonalgammopathyofrenalsignificance (IgM-MGRS) recurrence after the procedure. A 45-year-old male patient presented with end-stage renal failure due to membranoproliferative glomerulonephritis (MPGN). The initial immunosuppressive regimen consisted of tacrolimus, steroids, mycophenolate mofetil, basiliximab, and rituximab. He underwent ABO-incompatible kidney transplantation from his mother in August 2021. The clinical course after kidney transplantation was uneventful for a month. A biopsy of the transplanted kidney was performed due to decreased renal function. The allograft biopsy result led to the suspicion of primary macroglobulinemia-associated nephropathy. Bone marrow biopsy revealed an increase in plasma cells; however, no diagnosis of primary macroglobulinemia was made. At this point, IgM-MGRS was diagnosed instead of primary macroglobulinemia. A follow-up allograft biopsy was performed, and IgM-MGRS-associated nephropathy was diagnosed. Eventually, his retrieved autologous kidney biopsy from the initial examination showed that the primary disease was not MPGN but recurrent IgM-MGRS-associated nephropathy. Dexamethasone, rituximab, and cyclophosphamide (DRC) were started to treat IgM-MGRS due to worsening renal function (serum creatinine levels were in the 4–5 mg/dL range). Additional doses of DRC with 20 cycles of plasma exchange were introduced. Severe side effects occurred but did not result in death

Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma CellsSummary

Background & Aims: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. Results: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine. Keywords: 3D Organoids, Autophagy, CD44, 5-Fluorouraci