Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus.
SUMMARY The gut microbiota influences development 1 – 3 and homeostasis 4 – 7 of the mammalian immune system, and is associated with human inflammatory- 8 and immune diseases 9 , 10 as well as patients’ responses to immunotherapy 11 – 14 . Still, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans where a lack of deliberate manipulations makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—cancer patients receiving hematopoietic cell transplantation as they recover from chemotherapy and stem cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and >10,000 longitudinal microbiota samples from patients revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera relative to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota—in concert and over time—on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.
PURPOSE Coronavirus-2019 (COVID-19) mortality is higher in patients with cancer than in the general population, yet the cancer-associated risk factors for COVID-19 adverse outcomes are not fully characterized. PATIENTS AND METHODS We reviewed clinical characteristics and outcomes from patients with cancer and concurrent COVID-19 at Memorial Sloan Kettering Cancer Center until March 31, 2020 (n = 309), and observed clinical end points until April 13, 2020. We hypothesized that cytotoxic chemotherapy administered within 35 days of a COVID-19 diagnosis is associated with an increased hazard ratio (HR) of severe or critical COVID-19. In secondary analyses, we estimated associations between specific clinical and laboratory variables and the incidence of a severe or critical COVID-19 event. RESULTS Cytotoxic chemotherapy administration was not significantly associated with a severe or critical COVID-19 event (HR, 1.10; 95% CI, 0.73 to 1.60). Hematologic malignancy was associated with increased COVID-19 severity (HR, 1.90; 95% CI, 1.30 to 2.80). Patients with lung cancer also demonstrated higher rates of severe or critical COVID-19 events (HR, 2.0; 95% CI, 1.20 to 3.30). Lymphopenia at COVID-19 diagnosis was associated with higher rates of severe or critical illness (HR, 2.10; 95% CI, 1.50 to 3.10). Patients with baseline neutropenia 14-90 days before COVID-19 diagnosis had worse outcomes (HR, 4.20; 95% CI, 1.70 to 11.00). Findings from these analyses remained consistent in a multivariable model and in multiple sensitivity analyses. The rate of adverse events was lower in a time-matched population of patients with cancer without COVID-19. CONCLUSION Recent cytotoxic chemotherapy treatment was not associated with adverse COVID-19 outcomes. Patients with active hematologic or lung malignancies, peri–COVID-19 lymphopenia, or baseline neutropenia had worse COVID-19 outcomes. Interactions among antineoplastic therapy, cancer type, and COVID-19 are complex and warrant further investigation.
Routine monitoring of carcinoembryonic antigen (CEA) levels is standard in patients with resected colorectal cancer (CRC). The incidence of false-positives and the upper limits of false-positive elevations have not been previously well characterized. A search of medical records at Memorial Sloan-Kettering Cancer Center identified 728 patients who underwent an R0 resection of locoregional CRC between January 2003 and December 2012 and who had an increase in CEA level above the normal range after a normal perioperative CEA level. Of these, 358 had a false-positive elevation of CEA level, 335 had a true-positive elevation indicative of recurrent CRC, and 35 had a true-positive elevation indicative of the development of a new, non-CRC malignancy. Of those with false elevations, 111 had a single isolated CEA level elevation (median highest CEA level of 5.5 ng/mL) with no further abnormal measurements, whereas 247 had elevations on 2 or more readings, with a median highest level of 6.7 ng/mL. Of these 247 patients with confirmed false-positive CEA level elevations, only 5 (2%) had measurements greater than 15 ng/mL, and no confirmed elevation greater than 35 ng/mL was a false-positive. False-positive CEA test results in the range of 5 to 15 ng/mL are common. Confirmation of CEA elevation in this range before initiating imaging studies may be appropriate. False-positive results greater than 15 ng/mL are rare, and all confirmed CEA levels greater than 35 ng/mL were associated with cancer recurrence.
BACKGROUND Adoptive immunotherapy using engineered lymphocytes has shown promising results in treating cancers even in patients who have failed other treatments. As the first essential step, the number of peripheral mononuclear cell (MNC) collection procedures is rapidly increasing. In this retrospective study, we reviewed the collection results to determine factors that affect MNC collection. STUDY DESIGN AND METHODS We reviewed 184 collections that were performed on 169 adult allogenic donors and patients with acute lymphoid leukemia, chronic lymphoid leukemia, lymphoma, multiple myeloma, or solid‐organ tumors. All the leukapheresis procedures were performed after a complete cell count with differential was obtained. Total blood volume (TBV) was defined as processed blood volume divided by patient blood volume. RESULTS There was a significant association between the precollection MNC count (pre‐MNC) and the MNC yields normalized by TBV (r = 0.926; p < 0.001) and a regression formula was created to predict MNC yields. Multiple regression analyses showed that pre‐MNC, TBV, and precollection hemoglobin were strongly associated with MNC yield (R 2 = 0.866; F (3180) = 388.472; p < 0.001), and pre‐MNC had the greatest influence on MNC yield (β = 0.960; p < 0.001) followed by TBV (β = 0.302; p < 0.001), and Hgb (β = 0.136; p < 0.001). CONCLUSION Our results suggest that the optimal time for MNC collection can be determined based on pre‐MNC and that processing volume should be determined based on collection goal and pre‐MNC to optimize and personalize the harvesting procedure.
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