Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Lymphoplasmacytic plaque in children: Case report and literature review

We report a case of benign lymphoplasmacytic plaque (LPP) in a child. These asymptomatic erythematous papulonodular lesions are an emerging clinicopathological entity. Herein, we describe a previously unreported site for LPP lesions, namely, the volar wrist and the distal ipsilateral palm.     

Is Involvement a Good Thing? The Undesirable Consequences of Topical and Conversational Involvement in the Context of Alcohol Consumption

Whereas there is evidence that interpersonal communication, or conversation, influences predictors of alcohol consumption, the role of involvement in conversation effects remains unclear. This study explored how three aspects of involvement (topical relevance, or how relevant the topic of alcohol is; conversational relevance, or how relevant a conversation about alcohol is; and conversational effort, or how much effort people put into such a conversation), influence conversation effects. After assessing topical relevance, 46 same-sex dyads were requested to talk about the negative consequences of heavy drinking. Within each dyad, one participant was asked to take on an active talking role and the other participant a passive listening role. Next, conversational relevance, effort, and predictors of heavy drinking were measured. Results showed that participants who drank more alcohol found the topic of heavy drinking more relevant. This topical relevance increased conversational relevance and conversational effort. Conversational effort further increased when a talking role was assigned. Furthermore, participants who put more effort in the conversation and found it more relevant had more positive norms, identified more strongly with alcohol, and had higher intentions to drink. These findings suggest that more involvement in an alcohol-related conversation does not always lead to desirable outcomes.