Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials.

Background: A factory-calibrated flash glucose monitoring system (FGMS; FreeStyle Libre) recently was evaluated in dogs with uncomplicated diabetes mellitus. It is not known if this system is reliable during diabetic ketoacidosis (DKA). Objectives: To assess the performance of the FGMS in dogs with DKA and to determine the effect of severity of ketosis and acidosis, lactate concentration, body condition score (BCS), and time wearing the sensor on the accuracy of the device. Animals: Fourteen client-owned dogs with DKA. Methods: The interstitial glucose (IG) measurements were compared with blood glucose (BG) measurements obtained using a validated portable glucometer. The influence of changes in metabolic variables (β-hydroxybutyrate, pH, bicarbonate, and lactate) and the effect of BCS and time wearing on sensor performance were evaluated. Accuracy was determined by fulfillment of ISO15197:2013 criteria. Results: Metabolic variables, BCS, and time wearing were not associated with the accuracy of the sensor. Good agreement between IG measurements and BG was obtained both before and after DKA resolution (r = .88 and r = .93, respectively). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% and 99.6% of results in zones A + B of the Parkes consensus error grid analysis before and after DKA resolution, respectively. Conclusions and Clinical Importance: Changes in metabolic variables, BCS, and time wearing do not seem to affect agreement between IG and BG. Despite not fulfilling the ISO requirements, the FGMS provides clinically accurate estimates of BG in dogs with DKA.

Two mechanisms are involved in the immune escape of cancer cells: the immunoediting of tumor cells and the suppression of the immune system. Both processes have been revealed in multiple myeloma (MM). Complex interactions between tumor plasma cells and the bone marrow (BM) microenvironment contribute to generate an immunosuppressive milieu characterized by high concentration of immunosuppressive factors, loss of effective antigen presentation, effector cell dysfunction, and expansion of immunosuppressive cell populations, such as myeloid-derived suppressor cells, regulatory T cells and T cells expressing checkpoint molecules such as programmed cell death 1. Considering the great immunosuppressive impact of BM myeloma microenvironment, many strategies to overcome it and restore myeloma immunosurveillance have been elaborated. The most successful ones are combined approaches such as checkpoint inhibitors in combination with immunomodulatory drugs, anti-monoclonal antibodies, and proteasome inhibitors as well as chimeric antigen receptor (CAR) T cell therapy. How best to combine anti-MM therapies and what is the optimal timing to treat the patient are important questions to be addressed in future trials. Moreover, intratumor MM heterogeneity suggests the crucial importance of tailored therapies to identify patients who might benefit the most from immunotherapy, reaching deeper and more durable responses.

Background: The FreeStyle Libre (Abbott Laboratories) is a flash glucose monitoring system (FGMS) that measures interstitial glucose concentration (IG). The system is factory-calibrated, easy to use, inexpensive, and could be useful for monitoring diabetic cats.Objectives: To evaluate the analytical and clinical accuracy of the FGMS in cats and establish the lag-time between IG and blood glucose concentration (BG).Animals: Twenty client-owned diabetic cats and 7 purpose-bred healthy cats.Methods: Prospective study. Blood glucose concentration was measured using a portable glucose meter validated for use in cats that served as a reference method for IG, as measured by FGMS. In diabetic cats, data were collected for sensor wearing time with different methods of application and accuracy across glycemic ranges. Accuracy was determined by fulfillment of ISO15197:2013 criteria. In healthy cats, lag-time between IG and BG was established after IV administration of exogenous glucose.Results: Good agreement between IG and BG was obtained (r = .93). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% of the results in zones A + B of the Parkes consensus error grid analysis. In the immediate 30 minutes after an IV bolus of glucose, when BG was increasing rapidly (approximately 2%/min), IG increased slowly, resulting in a difference of as much as 579 mg/ dL, and no positive correlation between BG and IG was found.Conclusions and Clinical Importance: The FGMS did not fulfill ISO requirements but is sufficiently accurate for glucose monitoring in cats, while considering the lag between IG and BG during periods of rapid changes in BG.