Cerebral blood flow (CBF) reductions in Alzheimer’s disease (AD) patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences on AD pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to wildtype animals, largely due to neutrophils that adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to an immediate increase in CBF and to rapidly improved performance in spatial and working memory tasks. This study identified a novel cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of AD and demonstrated that improving CBF rapidly improved short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a novel strategy for improving cognition in AD patients.

Abstract:The existence of cerebral blood flow (CBF) reductions in Alzheimer's disease (AD) patients and related mouse models has been known for decades, but the underlying mechanisms and the resulting impacts on cognitive function and AD pathogenesis remain poorly understood. In the APP/PS1 mouse model of AD we found that an increased number of cortical capillaries had stalled blood flow as compared to wildtype animals, largely due to leukocytes that adhered in capillary segments and blocked blood flow. These capillary stalls were an early feature of disease development, appearing before amyloid deposits.Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to an immediate increase in CBF and to rapidly improved performance in spatial and working memory tasks. Our work has thus identified a cellular mechanism that explains the majority of the CBF reduction seen in a mouse model of AD and has also demonstrated that improving CBF rapidly improved short-term memory function. Restoring cerebral perfusion by preventing the leukocyte adhesion that plugs capillaries may provide a novel strategy for improving cognition in AD patients.

and 7 Functioning as the lay volunteer/patient representative.

Recent technological advances in the management of patients with cardiovascular implantable electronic devices (CIEDs) have expanded clinicians’ ability to remotely monitor patients with CIEDs. Remote monitoring, in addition to periodic in-person device evaluation, provides many advantages to patients and clinicians. Aside from the therapeutic and diagnostic benefits of pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization therapy devices, and implantable loop recorders, improvement in clinical outcomes, clinical efficiencies, and patient experience can be realized with the adoption of remote CIED monitoring. These advantages create significant value to both patients and CIED follow-up centers.

Globally, 38 million persons live with human immunodeficiency virus (HIV) (PLWH), and a significant portion live with chronic pain. While not yet fully characterized, preliminary data suggest 40%‐83% of PLWH experience chronic pain, and many report undertreatment. A growing body of literature suggests undertreatment of chronic pain in PLWH leads to adverse clinical outcomes, such as poor retention in HIV care, suboptimal adherence to antiretroviral therapy, and increased use of intravenous drug use (eg, heroin). Chronic pain experienced by PLWH ranges from neuropathic to musculoskeletal with different etiologies and treatment modalities for each. Although opioids have been used to achieve analgesia in PLWH, there is growing interest in alternative pain therapies. Recently, medical cannabis (delta‐9‐tetrahydrocannabinol [THC] and cannabidiol [CBD]) products have been of high interest. Anecdotal evidence exists for medical cannabis and pain relief; however, robust clinical trial data are limited due to scheduling restrictions within the United States. The purposes of this narrative review are to summarize key literature for pain in PLWH and medical cannabis, discuss pertinent dosage forms and dosing schedules, and summarize safety and efficacy considerations for PLWH. Finally, the authors provide recommendations on cannabis rescheduling and pharmacists' and healthcare providers' roles in its prescribing and indication. Medical cannabis and pharmaceutical preparations containing both THC and CBD are a viable alternatives to opioid analgesics in the treatment of neuropathic pain in PLWH. The risks of misuse and cannabis use disorder warrant careful consideration, yet the benefits of effective analgesia associated with cannabis may outweigh these risks. Cannabis rescheduling and subsequent expansions in pain management research are warranted, particularly for CBD‐predominant and CBD‐isolate medical cannabis products.