Cardiac resynchronization therapy in inotrope-dependent heart failure: a meta-analysis.

Aims: The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate.

Methods And Results: We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of 'inotrope dependence' or 'inability to wean'.

Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer.

The therapeutic effectiveness of oncolytic viruses (OVs) delivered intravenously is limited by the development of neutralizing antibody responses against the virus. To circumvent this limitation and to enable repeated systemic administration of OVs, here we develop Synthetic RNA viruses consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21, we demonstrate vRNA delivery and replication, virus assembly, spread and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream.

P2X7-dependent constitutive Interleukin-1β release from pyramidal neurons of the normal mouse hippocampus: Evidence for a role in maintenance of the innate seizure threshold.

Disruption of Interleukin-1β (IL-1β) signaling sensitized mice to convulsant stimuli, suggesting that this quintessential cytokine of the innate immune system contributes to maintenance of the innate seizure threshold (ST). However, much remains unknown about where and how IL-1β secretion occurs in the normal brain. This study examined the possibility that neurons of the hippocampus are key sources of constitutive IL-1β secretion and that the release from these cells is dependent on the purinoceptor, P2X7.

ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity.

ONCR-177 is an engineered recombinant oncolytic herpes simplex virus (HSV) with complementary safety mechanisms, including tissue-specific miRNA attenuation and mutant UL37 to inhibit replication, neuropathic activity, and latency in normal cells. ONCR-177 is armed with five transgenes for IL12, FLT3LG (extracellular domain), CCL4, and antagonists to immune checkpoints PD-1 and CTLA-4. assays demonstrated that targeted miRNAs could efficiently suppress ONCR-177 replication and transgene expression, as could the HSV-1 standard-of-care therapy acyclovir.

Design of an Interferon-Resistant Oncolytic HSV-1 Incorporating Redundant Safety Modalities for Improved Tolerability.

Development of next-generation oncolytic viruses requires the design of vectors that are potently oncolytic, immunogenic in human tumors, and well tolerated in patients. Starting with a joint-region deleted herpes simplex virus 1 (HSV-1) to create large transgene capability, we retained a single copy of the ICP34.5 gene, introduced mutations in UL37 to inhibit retrograde axonal transport, and inserted cell-type-specific microRNA (miRNA) target cassettes in HSV-1 genes essential for replication or neurovirulence.