JAK-STAT Signaling and Beyond in the Pathogenesis of Spondyloarthritis and Their Clinical Significance.

PURPOSE OF REVIEW: Janus kinase-signal transducers and activators of transcription cell signaling proteins (JAK-STATs) play a key regulatory role in functioning of several inflammatory cytokines. JAK-STAT signaling proteins are the key regulators of the cytokine/cytokine receptor system involved in the pathogenesis of various autoimmune disease including spondyloarthritis (SpA). This article mainly highlights the JAK-STAT signaling system, its association with the relevant cytokine/cytokine-receptor system, and its regulatory role in pathogenesis of SpA. Also, we have briefly addressed the principle for the use JAKi in SpA and the current status of use of JAK inhibitors (JAKi) in SpA. RECENT FINDINGS: Recent developments with newer JAK molecules as well as other molecules beyond JAK inhibitors are now an exciting field for the development of novel therapies for autoimmune diseases and various malignant conditions. In this article, we have provided a special emphasis on how various cell signaling systems beyond JAK/STAT pathway are relevant to SpA and have provided a comprehensive review on this upcoming field in respect to the novel TYK2 inhibitors, RORγT inhibitors, mTOR inhibitors, NGF inhibitors, and various STAT kinase inhibitors. SpA are a group of autoimmune diseases with multifactorial etiologies. SpA is linked with genetic predisposition, environmental risk factors, and the immune system-mediated systemic inflammation. Here, we have provided the regulatory role of JAK/STAT pathway and other intracellular signaling system in the pathogenesis of SpA and its therapeutic relevance.

Resource Utilization in Hospitalized Patients With Cancer From Hospice Decision to Discharge and Provider-Type Differences.

Aggressive resource utilization for patients with cancer at the end of life has been associated with poor outcomes for patients and their families. To our knowledge, no previous studies have characterized resource utilization as a proxy for quality end-of-life care in hospitalized patients awaiting discharge to hospice by physician and advanced practice providers (APPs). We conducted a retrospective cohort study to examine resource utilization and the quality metrics for end-of-life care in patients at Memorial Sloan Kettering Cancer Center from the date of hospice decision to discharge. Patients under the care of APP teams were less likely to receive laboratory testing (50% vs 59%, P = .046) and received fewer tests than those with house staff teams, though performance on end-of-life quality metrics was similar. Our findings suggest APPs may improve quality of end-of-life care by avoiding unnecessary or aggressive measures compared to house staff.

Pre- and post-sexual exposure prophylaxis of HIV: An update.

Pitfalls in current HIV prevention strategies include late HIV testing, vulnerability among youth and females; lack of emphasis on treatment, low acceptance of circumcision, and nonavailability of protective vaccines. Continuing high-risk sexual behavior, forceful sex, coercive and nonconsensual sex, rape, and unprotected sexual activities make women the most vulnerable to acquisition of sexually transmitted infection/HIV and necessitates a more radical approach of prevention in high-risk individuals who do not have HIV. Preexposure prophylaxis is defined as the administration of antiretroviral drugs to an uninfected person before potential HIV exposure to reduce the risk of infection and continued during risk. The rationale of this approach is to administer preventive dose of drug(s) before exposure to HIV so the moment virus enters the body, HIV replication is inhibited and HIV is not able to establish permanent infection. Postexposure prophylaxis (PEP) following potential sexual exposure is an important form of nonoccupational PEP which is an emergency intervention to abort HIV acquisition arising from exposure to HIV-infected blood or potentially infectious bodily fluids following sexual exposure.