Cutaneous Papilloma and Squamous Cell Carcinoma Therapy Utilizing Nanosecond Pulsed Electric Fields (nsPEF)

Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses), two nominal electric fields (40 KV/cm and 31 KV/cm), and two pulse durations (7 ns and 14 ns). Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%), and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%). 13.5% of carcinogen-induced tumors (5 of 37) were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay) after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma

A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers

Measurable Residual Disease Conversion Rate with Consolidation Chemotherapy in Acute Myeloid Leukemia

Patients with acute myeloid leukemia (AML) who achieve complete remission (CR) following induction therapy but continue to have measurable residual disease (MRD) have inferior outcomes following allogeneic hematopoietic cell transplant (alloHCT). Determining the historical rate of MRD clearance in response to standard consolidation therapy is needed as an initial step in developing a new therapeutic strategy to clear MRD prior to alloHCT. A multi-institution retrospective analysis was performed on 83 consecutively treated AML patients in morphologic complete remission (CR) with detectable MRD post-induction therapy who received standard chemotherapy consolidation from January 2016 to December 2021. In response to consolidation therapy, 27 of the 83 patients had MRD eliminated (33%) after all given cycles of consolidation cytarabine. Multivariable logistic regression showed that, when controlling for age, higher ELN risk category, higher dose of cytarabine, or more cycles of consolidation did not affect the likelihood of MRD conversion

Secondary clonal hematologic neoplasia following successful therapy for acute promyelocytic leukemia (APL): A report of two cases and review of the literature

Although rare, secondary clonal hematologic neoplasia may occur after successful therapy for acute promyelocytic leukemia (APL). These secondary clonal events may be considered therapy-related, but may also be due to an underlying background of clonal hematopoiesis from which both malignancies may develop. In this manuscript, we describe two patients with secondary clones after APL therapy characterized in one patient by deletion of chromosome 11q23 and, in the other, by monosomy of chromosome 7, and also provide a review of all secondary clonal disorders described after APL therapy. We suggest that since most reports identify karyotypic abnormalities not typically associated with chemotherapy, there may be another mechanism underlying secondary clonal development after complete response to initial APL therapy. Keywords: Acute myelocytic leukemia (AML), Secondary clone, Myelodysplastic syndrome (MDS), Therapy-related acute myelocytic leukemia (t-AML), Therapy-related myelodysplastic syndrome (t-MDS

Hepatic Abscess in a Returning Traveler with Crohn’s Disease: Differentiating Amebic from Pyogenic Liver Abscess

Liver abscess is a rare but serious complication of Crohn’s disease. Patients with Crohn’s disease are at risk for pyogenic liver abscesses due to immunosuppressive therapy, fistulous disease, and intraabdominal abscesses. Inflammatory bowel disease patients are also known to have a greater prevalence of amebiasis compared to the rest of the population; however, a higher incidence of amebic liver abscess has not been reported. We describe a case of a liver abscess in a patient with Crohn’s disease that was initially presumed pyogenic but later determined to be amebic in origin. Epidemiology, clinical presentation, diagnosis, and treatment of amebic and pyogenic liver abscesses are discussed

B-Cell Acute Lymphoblastic Leukemia as a Secondary Malignancy Following Diffuse Large B-Cell Lymphoma

Secondary acute lymphoblastic leukemia (ALL) is a rare disease that has not been well characterized compared with secondary myelodysplastic syndrome or secondary acute myeloid leukemia. We present a report of two patients who developed ALL following complete remission of diffuse large B-cell lymphoma (DLBCL). The first case is more consistent with a therapy-related ALL as a PCR analysis of bone marrow aspirate revealed a distinct clone and the mixed-lineage leukemia gene rearrangement, commonly associated with exposure to topoisomerase II inhibitors. The second case is more consistent with clonal evolution given positive MYC and BCL2 fusion signals in the original diagnosis of DLBCL and the secondary ALL

Anti-CD19 CAR T-cell therapy remission despite prior anti-CD19 antibody Tafasitamab in relapsed/refractory DLBCL

Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal antibody that targets CD19. The L-MIND (NCT02399085) trial, an open-label, single-arm, phase II study of Tafasitamab (TAFA) plus lenalidomide (LEN), reported progression-free survival of 16 months in R/R DLBCL patients ineligible for autologous stem cell transplantation. Despite recent advances in anti-CD19 therapy, no clinical evidence exists to direct the sequencing of CAR T cell therapy following relapse after prior anti-CD19 therapy. We present the first published case of TAFA/LEN treatment followed by CAR T therapy with sustained remission. Disease progression following treatment with Tafasitamab may not preclude patients from CAR T cell therapy