Persons chronically infected with hepatitis C (HCV) may be at higher risk for developing and dying from non-liver as well as liver cancers than the general population. We therefore assessed cancer incidence and mortality among HCV-infected patients in four large health systems in the United States serving over 1.6 million adults, and compared with rates for the general population during the five-year period from 2006 to 2010. 12,126 chronic HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS) contributed 39,984 person-years of follow-up from 2006 to 2010, and were compared to 133,795,010 records from 13 Surveillance, Epidemiology and End Results Program (SEER) cancer registries, and approximately 12 million US death certificates from Multiple Cause of Death (MCOD) data. Standardized rate ratios (SRR) and relative risk (RR) were calculated for incidence and mortality, respectively. The incidence of the following cancers was significantly higher among patients with chronic HCV infection: liver (SRR, 48.6 [95% CI, 44.4–52.7]), pancreas (2.5 [1.7–3.2]), rectum (2.1 [1.3–2.8]), kidney (1.7 [1.1–2.2]), non-Hodgkin lymphoma (1.6 [1.2–2.1]), and lung (1.6 [1.3–1.9]). Age-adjusted mortality was significantly higher among patients with: liver (RR, 29.6 [95% CI, 29.1–30.1]), oral (5.2 [5.1–5.4]), rectum (2.6 [2.5–2.7]), non-Hodgkin lymphoma (2.3 [2.2–2.31]), and pancreatic (1.63 [1.6–1.7]) cancers. The mean age of cancer diagnosis and cancer-related death was significantly younger in CHeCS HCV cohort patients compared to the general population for many cancers. Conclusions Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population.

Data on pulmonary gas exchange were collected in breathhold dives to 90 feet in a tank and in open-sea breathhold dives to depths of 217.5 and 225 feet. Thoracic blood volume displacements were measured at depths of 25, 50, 90, and 130 feet, by use of the impedance plethysmograph. The open-sea dives were carried out with an average speed of descent of 3.95 feet per second and an average rate of ascent of 3.50 feet per second. End-dive alveolar oxygen tensions did not fall below 36 millimeters of mercury, while alveolar carbon dioxide tension did not rise above 40 millimeters of mercury except in one case. These findings indicate that for diver Croft, who has unusual lung capacity, neither hypoxia nor hypercapnia determined the depth limits under those conditions. At depths of 90 and 130 feet blood was forced into the thorax, amounting to 1047 and 850 milliliters respectively.

Adoptive T cell therapy has shown clinical potential for patients with cancer, though effective treatment is dependent on longevity and potency of the exploited tumor-reactive T cells. Previously, we showed that ex vivo inhibition of AKT using the research compound Akt-inhibitor VIII retained differentiation and improved functionality of minor histocompatibility antigen (MiHA)-specific CD8+ T cells. Here, we compared a panel of clinically applicable AKT-inhibitors with an allosteric or adenosine triphosphate-competitive mode of action. We analyzed phenotype, functionality, metabolism and transcriptome of AKT-inhibited CD8+ T cells using different T cell activation models. Most inhibitors facilitated T cell expansion while preserving an early memory phenotype, reflected by maintenance of CD62L, CCR7 and CXCR4 expression. Moreover, transcriptome profiling revealed that AKT-inhibited CD8+ T cells clustered closely to naturally occurring stem cell-memory CD8+ T cells, while control T cells resembled effector-memory T cells. Interestingly, AKT-inhibited CD8+ T cells showed enrichment of hypoxia-associated genes, which was consistent with enhanced glycolytic function. Notably, AKT-inhibition during MiHA-specific CD8+ T cell priming uncoupled preservation of early memory differentiation from ex vivo expansion. Furthermore, AKT-inhibited MiHA-specific CD8+ T cells showed increased polyfunctionality with co-secretion of IFN-γ and IL-2 upon antigen recall. Together, these data demonstrate that AKT-inhibitors with different modality of action promote the ex vivo generation of stem cell memory-like CD8+ T cells with a unique metabolic profile and retained polyfunctionality. Akt-inhibitor VIII and GDC-0068 outperformed other inhibitors, and are therefore promising candidates for ex vivo generation of superior tumor-reactive T cells for adoptive immunotherapy in cancer patients.

Injection drug use and blood transfusion before 1990 are dominant risk factors for HCV acquisition; intranasal cocaine use may be a surreptitious route of parenteral spread. After a mean of 25 years of HCV infection, histologic outcomes were relatively mild: 85% had no or mild fibrosis, and only 2% had cirrhosis. Nearly one-fifth spontaneously recovered.