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Key Clinical Message: Medication-induced mood disorders following epidural steroid injections are possible therefore should be disclosed to the patient. Abstract: Medication-induced mood disorders have been rarely reported following epidural steroid injections (ESI). This case series presents three patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for substance/medication-induced mood disorder after an ESI. In considering a candidacy for ESI, the rare but significant, side effects of psychiatric side effects should be disclosed to patients.
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BACKGROUND: Exogenous systemic steroid exposure is a well-established risk factor for spinal epidural lipomatosis (SEL), however the association between lumbosacral epidural steroid injections (LESIs) and lumbosacral epidural lipomatosis (LEL) is generally regarded as poorly understood. Our objective was to investigate the rationale and the evidence implicating LESI(s) as a potential cause of LEL as well as the evidence related to use of LESI(s) as a potential pain relieving treatment option for radicular pain in the setting of LEL. METHODS: PubMed, Embase, Google Scholar, OVID were searched from inception until April 2021. Three investigators identified literature that provided original descriptive patient clinical data attributing the development/progression of LEL to LESI(s) or described the use of LESI(s) as a pain relieving modality for radicular pain in the setting of LEL. RESULTS: Fourteen publications were included for review. Overall, the current level of evidence is of low-quality. There are significant methodological gaps on this subject matter and many studies do not account for confounding variables independently associated with LEL. CONCLUSIONS: This review has identified substantial limitations in the literature regarding that which is truly known regarding LESI(s) and LEL, as well as conservative management overall. To provide a well-rounded perspective, we synthesized literature as it pertains to: 1) current knowledge regarding SEL, notable associations and potential implications for corticosteroid exposure; 2) corticosteroid exposure and lipoatrophy; 3) current management recommendations for SEL and 4) areas for future focus. Although LESI(s) have been associated with LEL in the literature, presently due to a lack of rigorous, high-quality studies, the presence or absence of an independent causal relationship between LESI(s) and LEL cannot be stated with confidence.
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We have previously shown clinical activity of a mammalian target of rapamycin (mTOR) complex 1 inhibitor in Waldenstrom macroglobulinemia (WM). However, 50% of patients did not respond to therapy. We therefore examined mechanisms of activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR in WM, and mechanisms of overcoming resistance to therapy. We first demonstrated that primary WM cells show constitutive activation of the PI3K/Akt pathway, supported by decreased expression of phosphate and tensin homolog tumor suppressor gene (PTEN) at the gene and protein levels, together with constitutive activation of Akt and mTOR. We illustrated that dual targeting of the PI3K/mTOR pathway by the novel inhibitor NVP-BEZ235 showed higher cytotoxicity on WM cells compared with inhibition of the PI3K or mTOR pathways alone. In addition, NVP-BEZ235 inhibited both rictor and raptor, thus abrogating the rictor-induced Akt phosphorylation. NVP-BEZ235 also induced significant cytotoxicity in WM cells in a caspase-dependent and -independent manner, through targeting the Forkhead box transcription factors. In addition, NVP-BEZ235 targeted WM cells in the context of bone marrow microenvironment, leading to significant inhibition of migration, adhesion in vitro, and homing in vivo. These studies therefore show that dual targeting of the PI3K/mTOR pathway is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR signaling cascade, such as WM.
