Medical hypotheses
-
Despite aggressive intervention, patients who survive an out-of-hospital cardiac arrest (OHCA) generally have very poor prognoses, with nationwide survival rates of approximately 10-20%. Approximately 90% of survivors will have moderate to severe neurological injury ranging from moderate cognitive impairment to brain death. Currently, few early prognostic indicators are considered reliable enough to support patients' families and clinicians' in their decisions regarding medical futility. ⋯ Specifically, during and after immediate resuscitation and return of ROSC, clinicians and families face a series of important questions regarding patient prognosis, futility of care and allocation of scarce resources such as the early initiation of extracorporeal cardiopulmonary resuscitation (ECPR). The ability to provide early prognostic information in this setting is highly valuable. Currently available, as well as potential biomarkers that could be good candidates in prognostication of neurological outcomes after OHCA or in the setting of refractory cardiac arrest will be reviewed and discussed.
-
Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure. ⋯ TSCM cells, compared to TCM cells, exhibit stem cell properties that more closely match those of ESCs and ASCs, including self-renewal and differentiation into all memory T cell subsets. It is our hypothesis that activation of AMPK, a master regulator of cellular metabolism that plays a critical role in T cell activation and differentiation of ESCs and ASCs, will lead to both T cell activation-induced latent HIV-1 reactivation, facilitating virus destruction, as well as "activation", differentiation, and/or apoptosis of CSCs, thus inhibiting tumorigenesis. We also propose the novel observation that compounds that have been shown to both facilitate latent HIV-1 reactivation and promote CSC differentiation/apoptosis (e.g. bryostatin-1, JQ1, metformin, butyrate, etc.) likely do so through a common mechanism of AMPK activation.
-
Chronic pain after spinal cord injury (SCI) is a form of central neuropathic pain that is debilitating and often refractory to current pharmacological treatments. Neurostimulation pain therapies, such as epidural spinal cord stimulation, have only moderate success in reducing SCI pain. The pathogenesis of SCI pain may involve a state of central neuronal hyperexcitability, especially in the spinal cord dorsal horn, that develops after injury. ⋯ Our hypothesis can be readily tested in preclinical models of SCI pain by using a combination of in vivo electrophysiological (neuronal activity) and animal behavioral (pain response) approaches. Since ISMS electrodes stimulate the spinal structures directly, we expect that the effective stimulus intensity and energy consumption can be lower than that for epidural spinal cord stimulation. The proposed hypothesis may provide insights and rationales for developing a novel neurostimulation pain therapy by directly inhibiting the pain generators in the spinal cord, and ISMS may be an alternative strategy to treat SCI pain.
-
Cannabinoid hyperemesis syndrome (CHS), a variant of cyclic vomiting syndrome, is an enigmatic and challenging clinical disorder. As cannabis legalization, use, and potency has increased worldwide over the past decade, so has the prevalence of CHS. These patients often require acute care and inpatient treatment for refractory emesis, electrolyte derangement, dehydration, acute renal failure, and injury to the upper gastrointestinal tract. ⋯ Hydrotherapy with hot water provides short-term symptomatic relief from acute episodes of CHS. The reasons for this may be from chronic and/or excessive cannabis use leading to abnormal stimulation of the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic nervous system (SNS) in CHS patients. Overuse of cannabis may also lead to dysfunction of the endocannabinoid system, which is essential for allostasis of the autonomic nervous system after stress.