Rejected

To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV).

Several guidelines recommend the risk-adapted monitoring of patients with chronic pancreatitis (CP). However, dedicated risk stratification is widely missing in CP. Elderly-CP (disease onset with 60 or more years of age) may represent a subgroup of CP subjects with a distinct course of disease.

: Chronic non-cancer pain is a common cause of primary care physicians' office visits. : To determine the impact of adopting screening and monitoring measures in primary care settings on the illicit substance use behavior of patients receiving opioid analgesic prescriptions. : This was a retrospective analysis of data on patients who were prescribed opioid analgesics for chronic non-cancer pain between 2014 and 2017 Q1 (i.e., first quarter of 2017). Study participants were patients who sought medical care at our academic primary care clinic practice that is part of an internal medicine residency program. Participants were adults (>18 years) who were considered eligible for opioid analgesics for chronic non-cancer pain. : (1) Rolling out of the chronic non-cancer pain management policy to clinic staff; (2) pain medication contracts with patients; (3) random urine drug screen (UDS) testing performed on patients during their clinic visits; 4) a didactics curriculum for internal medicine residents to highlight the key elements in utilizing and interpreting UDS results; (5) adding alerts to the electronic medical record that notifies clinic staff of discrepancy between patients' prescribed medications and UDS findings, as well as for quick identification of patients who had violated a stipulation of the contract; (6) mandatory regular utilization of Michigan State's online prescription monitoring records; and (7) employment of an on-site behavioral specialist for patients with mental illness or at risk of drug abuse. : The main endpoint was the percentage of illicit drug use detected per year. : A total of 8096 UDS samples were collected over the study period. Mean (SD) participant age was 52 (SD 12) and 51% were male. Urine samples which had at least one illicit substance constituted 41% of the samples in 2014 prior to intervention. We found a significant decrease in the percentage of illicit substances after initiation of the intervention to 37% in 2015, 19% in 2016, and 12% in 2017Q1 ( < 0.001). : Adopting a system-wide screening and monitoring measures in a primary care setting can significantly reduce the amount of illicit drug use among patients receiving an opioid prescription for non-cancer pain. This has important implications for patient safety and the current opioid epidemic in the USA. Further studies are needed to evaluate similar interventions in other settings such as a pain clinic.

Beside diverse therapeutic properties of palmitoylethanolamide (PEA) including: neuroprotection, inflammation and pain alleviation, prophylactic effects have also been reported in animal models of infections, inflammation, and neurological diseases. The availability of PEA as (ultra)micronized nutraceutical formulations with reportedly no side effects, renders it accordingly an appealing candidate in human preventive care, such as in population at high risk of disease development or for healthy aging. PEA's mode of action is multi-facetted. Consensus exists that PEA's effects are primarily modulated by the peroxisome proliferator-activated receptor alpha (PPARα) and that PEA-activated PPARα has a pleiotropic effect on lipid metabolism, inflammation gene networks, and host defense mechanisms. Yet, an exhaustive view of how the prophylactic PEA administration changes the lipid signaling in brain and periphery, thereby eliciting a beneficial response to various negative stimuli remains still elusive. We therefore, undertook a broad lipidomic and transcriptomic study in brain and spleen of adult mice to unravel the positive molecular phenotype rendered by prophylactic PEA. We applied a tissue lipidomic and transcriptomic approach based on simultaneous extraction and subsequent targeted liquid chromatography-multiple reaction monitoring (LC-MRM) and mRNA analysis by qPCR, respectively. We targeted lipids of COX-, LOX- and CYP450 pathways, respectively, membrane phospholipids, lipid products of cPLA, and free fatty acids, along with various genes involved in their biosynthesis and function. Additionally, plasma lipidomics was applied to reveal circulatory consequences and/or reflection of PEA's action. We found broad, distinct, and several previously unknown tissue transcriptional regulations of inflammatory pathways. In hippocampus also a PEA-induced transcriptional regulation of neuronal activity and excitability was evidenced. A massive downregulation of membrane lipid levels in the splenic tissue of the immune system with a consequent shift towards pro-resolving lipid environment was also detected. Plasma lipid pattern reflected to a large extent the hippocampal and splenic lipidome changes, highlighting the value of plasma lipidomics to monitor effects of nutraceutical PEA administration. Altogether, these findings contribute new insights into PEA's molecular mechanism and helps answering the questions, how PEA prepares the body for insults and what are the "good lipids" that underlie this action.

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes.

In the context of a causal relationship between stress and migraine, coping strategies are aimed at managing stressful life events and reducing the distressing emotions connected to them.

Percutaneous trans-foramen ovale (FO) radiofrequency ablation (RFA) of Gasserian ganglion (GG) is commonly used to treat V3 trigeminal neuralgia (TN). However, this intracranial approach is less selective and safe. To report a novel percutaneous within-FO RFA of the V3 under CT-guidance and outcomes with both bipolar and monopolar techniques. Twenty-six patients with isolated V3 primary TN and FO >6 mm in diameter underwent either monopolar (n=12) or bipolar RFAs (n=14) based on their preference. Successful analgesia over V3, residual pain, recurrent pain, and complications were compared between the two groups. The ex vivo egg albumen model was used to demonstrate the size difference in the thermocoagulation lesion created by monopolar vs bipolar electrodes. In the bipolar group, there were more cases of masticatory atonia as compared to the monopolar (=0.104), but no residual pain was observed. In the monopolar group, there were two cases of residual pain found, which led to immediate repeat RFAs. Therefore, during the immediate post-operative period, both groups obtained 100% complete V3 analgesia with a similar risk of facial hematoma (=0.641). During up to 27-months of post-operative follow-up, in the bipolar group, complete pain relief persisted in all patients; in the monopolar group, 1 case of recurrent pain was found at 14 months. Ex vivo study demonstrated that, at 90 °C/90 seconds of RFA, the width of lesions is significantly larger by the 6-mm spacing parallel-tip bipolar electrodes compared to the monopolar electrode (9.5±0.567 vs 5.5±0.07 mm). In treating patients with isolated V3 TN and FO >6mm in diameter, this percutaneously within-FO RFA of the V3 under CT guidance is both clinically practical and effective, while bipolar RFA is associated with a lower incidence of residual and recurrent pain likely due to larger lesion sizes.

Maropitant is a neurokinin-1 (NK1) receptor antagonist that can be used for pain management. The objective of this study was to evaluate the effect of continuous infusion of two doses of maropitant on cardiorespiratory parameters and its postoperative analgesic effect in cats undergoing ovariohysterectomy. Thirty cats were randomly assigned to one of three groups (10 cats each group): the control group (CG) received a continuous infusion of 10 ml/kg/h Ringer's lactate; GM30 and GM100 first received an intravenous (IV) bolus of 1 mg/kg maropitant; GM30 then received continuous infusion of 30 g/kg/h maropitant; and GM100 then received continuous infusion of 100 g/kg/h maropitant. The maropitant was diluted into Ringer's lactate and the GM30 and GM100 also received fluids intraoperatively. In all groups, premedication included intramuscular injections of morphine and acepromazine, followed by induction with propofol and maintenance with isoflurane. Temperature, heart rate (HR), Doppler blood pressure (DBP), respiratory rate, oxygen saturation, and measuring the end-tidal carbon dioxide and isoflurane were monitored. Postoperative pain was evaluated using a visual analog scale and the UNESP-Botucatu multidimensional composite pain scale in cats; morphine was used for analgesic rescue. During the surgical procedure, cats in GM100 demonstrated lower HR and DBP than those in CG. With regard to the evaluation of postoperative pain, GM100 required the least frequent morphine rescue and less rescue analgesia compared with CG. In conclusion, cats in GM100 maintained lower DBP and HR and required lower analgesic rescue during the postoperative period. The results suggested that animals receiving maropitant bolus (1 mg/kg) plus (100 g/kg/h) experienced greater postoperative comfort, reflected by the lesser need for analgesic rescue. The use of maropitant in surgical procedures in cats contributes to postoperative comfort.

The diterpenoid compound, Oridonin, extracted from the Chinese herb, , possesses multiple biological activities and properties. Oridonin exhibited efficient anti-inflammatory activity by inducing a switch in macrophage polarization to the anti-inflammatory phenotype through inhibition of the Notch pathway in our study; therefore, its potential therapeutic effects were further investigated in the animal model of human Guillain-Barré syndrome (GBS) and other polyneuropathies – experimental autoimmune neuritis (EAN). Either preventive or therapeutic treatments with Oridonin greatly attenuated disease peak severity, suppressed paraparesis, shortened disease duration, and even delayed EAN onset. Progression of neuropathic pain, demyelination, inflammatory cellular accumulations, and inflammatory cytokines in peripheral nerves were significantly attenuated. Meanwhile, accumulation of immune cells in the spinal roots and microglial activation in the lumbar spinal cord were also reduced. Interestingly, Oridonin treatment significantly increased the proportion of anti-inflammatory macrophages and made them locally dominant among all infiltrated macrophages in the peripheral nerves. The down-regulation of local Notch pathway proteins, together with our results indicated their possible involvement. Taken together, our results demonstrated that Oridonin effectively suppressed EAN by attenuating local inflammatory reaction and increasing the proportion of immune regulating macrophages in the peripheral nerves, possibly through blockage of the Notch pathway, which suggests Oridonin as a potential therapeutic candidate for human GBS and neuropathies.

This case series illustrates an integrated model of care for migraine that combines standard neurological care with chiropractic treatment. For each patient, we describe the rationale for referral, diagnosis by both the neurologist and chiropractor, the coordinated care plan, communication between the neurologist and chiropractor based on direct face-to-face "hallway" interaction, medical notes, team meetings, and clinical outcomes. Findings are evaluated within the broader context of the multicause nature of migraine and the impact of integrative chiropractic. Suggestions for future areas of research evaluating integrative approaches are discussed.