Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab. RESULTS: After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT. CONCLUSION: Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.     

Nutritional status of alcoholics of different socioeconomic class.

Most studies concerning the nutritional status of alcoholics have focused on the indigent alcoholic but programs now increasingly consider the working patient. The role of socioeconomic status in determining nutritional status of the alcoholic is further clarified in this study. One hundred patients from an alcoholic population were studied, 50 with low socioeconomic status and 50 with middle or higher socioeconomic status. The nutritional status of these two different socioeconomic groups was examined and compared. The middle-income alcoholic had significantly higher values in weight to height index (P less than .02), the triceps skinfold (P less than .01), the midarm muscle circumference (P less than .05), hematocrit (P less than .01), and epilation force (P less than .001) than the lower-income alcoholic group. Hair-pulling tension was compared in both groups as an index of protein malnutrition. There was a highly significant difference in the two groups.     

Difficulties in Differentiating Coronaviruses from Subcellular Structures in Human Tissues by Electron Microscopy

Efforts to combat the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have placed a renewed focus on the use of transmission electron microscopy for identifying coronavirus in tissues. In attempts to attribute pathology of COVID-19 patients directly to tissue damage caused by SARS-CoV-2, investigators have inaccurately reported subcellular structures, including coated vesicles, multivesicular bodies, and vesiculating rough endoplasmic reticulum, as coronavirus particles. We describe morphologic features of coronavirus that distinguish it from subcellular structures, including particle size range (60–140 nm), intracellular particle location within membrane-bound vacuoles, and a nucleocapsid appearing in cross section as dense dots (6–12 nm) within the particles. In addition, although the characteristic spikes of coronaviruses may be visible on the virus surface, especially on extracellular particles, they are less evident in thin sections than in negative stain preparations.     

Vasopressin Receptor Antagonists: From Pivotal Trials to Current Practice

Heart failure is a growing health and economic problem in America, and outcomes continue to remain dismal, particularly for those presenting with acute heart failure syndrome (AHFS). In theory, arginine vasopressin antagonists (VRAs) could be useful in both acute and chronic heart failure, depending on which vasopressin receptor is targeted. Most studies of VRAs in heart failure have focused on V2 receptor antagonism, and to a lesser extent on combined V1a/V2 antagonism, due to the availability of appropriate agents and the unmet need of improving outcomes in AHFS. These agents are particularly attractive as adjunctive or alterative agents in AHFS because of their ability to produce a substantial diuresis without some of the drawbacks intrinsic to loop diuretics. While VRAs have been shown to ameliorate signs and symptoms of congestion when added to standard care, the largest trial of these agents showed no improvement in long-term morbidity, mortality, or hospitalization rates when added to standard care. This article reviews the mechanism of action of VRAs, the relevant clinical trials data, and current recommendations for clinical use, and suggests future directions for study of these agents in patients with heart failure.     

Sindbis Viral Vectors Transiently Deliver Tumor-associated Antigens to Lymph Nodes and Elicit Diversified Antitumor CD8+ T-cell Immunity

Tumors are theoretically capable of eliciting an antitumor immune response, but are often poorly immunogenic. Oncolytic viruses (OVs) have recently emerged as a promising strategy for the immunogenic delivery of tumor-associated antigens (TAAs) to cancer patients. However, safe and effective OV/TAA therapies have not yet been established. We have previously demonstrated that vectors based on Sindbis virus (SV) can inhibit tumor growth and activate the innate immune system in mice. Here, we demonstrate that SV vectors carrying a TAA generate a dramatically enhanced therapeutic effect in mice bearing subcutaneous, intraperitoneal, and lung cancers. Notably, SV/TAA efficacy was not dependent on tumor cell targeting, but was characterized by the transient expression of TAAs in lymph nodes draining the injection site. Early T-cell activation at this site was followed by a robust influx of NKG2D expressing antigen-specific cytotoxic CD8⁺ T cells into the tumor site, subsequently leading to the generation of long-lasting memory T cells which conferred protection against rechallenge with TAA-positive as well as TAA-negative tumor cells. By combining in vivo imaging, flow cytometry, cytotoxicity/cytokine assays, and tetramer analysis, we investigated the relationship between these events and propose a model for CD8⁺ T-cell activation during SV/TAA therapy.