Citations

AbstractBackgroundThe study aims were to model acute pain intensity and opioid consumption trajectories up to 72 hr after open hepatic resection, identify predictors of trajectory membership and examine the association between trajectory memberships and 6‐month pain and psychological outcomes. This is a long‐term analysis of a published randomized controlled trial on the impact of medial open transversus abdominis plane catheters on post‐operative outcomes.MethodsA total of 152 patients (89 males; mean age 63.0 [range: 54–72]) completed questionnaires on pain and related characteristics pre‐operatively and 6 months post‐operatively. Total opioid use was recorded several times over a 72‐hr period while self‐reported pain intensity scores were collected multiple times until hospital discharge. Analyses were carried out using growth mixture modelling, logistic regression and general linear models.ResultsBoth pain intensity and opioid consumption showed that a four‐trajectory model best fits the data. Patients in the lowest opioid consumption trajectory were more likely to be classified in the constant mild pain intensity trajectory. Age and baseline levels of anxiety significantly predicted opioid trajectory membership while baseline depressive symptoms significantly predicted pain intensity trajectory membership. Patients in the two highest opioid consumption trajectories reported significantly higher levels of pain catastrophizing at 6 months compared to patients in the other 3 trajectories (all p < 0.05).ConclusionHigh consumption of opioids after surgery is associated with higher levels of pain catastrophizing 6 months later. Identification of patients within these trajectories may lead to the development of early interventions targeted to high risk individuals.SignificanceDifferences in initial levels of opioid consumption and rates of change in opioid consumption shortly after surgery can help predict long‐term psychological responses to pain. Identifying key characteristics associated with initial opioid consumption can lead to the development of cost‐effective early interventions targeted to high risk individuals.

Background. The present multicenter study investigated whether equivalent outcomes to primary liver transplant (LT) could be achieved with liver retransplant (reLT) and whether improvements in outcomes have taken place over time, particularly in the direct-acting antiviral era. Methods. All reLT performed at Mayo Clinic Florida, Mayo Clinic Rochester, and Mayo Clinic Arizona were divided into era 1 (2002–2007), era 2 (2008–2012), and era 3 (2013–2017) based on the date of reLT. Results. Improvement in graft survival (GS) after reLT was seen over the 3 eras (P < 0.001). In era 1, GS after reLT was inferior to primary LT (P < 0.001), whereas no difference was seen between reLT and primary LT in era 2 (P = 0.68) or era 3 (P = 0.36). A significantly higher proportion of patients achieved sustained viral response (SVR) within the first year after reLT in each subsequent era (era 1: 10.3%, era 2: 22.5%, and era 3: 100%) (P < 0.001). Graft survival was superior in patients undergoing reLT for recurrent hepatitis C virus who achieved SVR after reLT compared with those who did not (P = 0.03). Conclusions. Results similar to primary LT were achieved in era 3. These improvements coincide with the availability of direct-acting antivirals, which resulted in a 100% SVR rate in era 3 and a decrease in the number of patients undergoing reLT for recurrent hepatitis C virus. The historic dogma that reLT results in inferior outcomes should be revisited.

Abstract Catechol-O-methyltransferase (COMT) regulates extracellular catecholamines. A widely studied COMT single nucleotide polymorphism (rs4680) changes the translated amino acid from valine to methionine (Val158Met); the polymorphism has been shown to influence opioid use. The aims of this study were to investigate the influence of COMT Val158Met on the likelihood and dose of opioid use in adults with chronic pain. Adults with chronic pain consecutively admitted to an outpatient pain rehabilitation program were recruited for study participation (N = 298). Individuals were genotyped for COMT Val158Met (rs4680). The polymorphism was analyzed using an additive and codominant genotype model. The distribution of genotypes was 23% (N = 70) for Val/Val, 49% (N = 146) for Val/Met, and 27% (N = 82) for Met/Met (Hardy–Weinberg, P > 0.90). No significant association was observed between opioid use and genotype under the additive model; however, a significant association was observed under the codominant model (P = 0.027). A post hoc comparison demonstrated that the Met/Met genotype was more likely to use opioids compared with the Val/Met genotype (P = 0.0089). No significant association was observed between morphine equivalent dose and genotype under the additive model; however, a significant association was observed under the codominant model (P = 0.0496). A post hoc comparison demonstrated that the Val/Met (P = 0.019) and Met/Met (P = 0.043) genotypes used greater morphine equivalent dose compared with the Val/Val genotype. This study extends key knowledge about the influence of the Met/Met genotype and Met allele on opioid use in adults with chronic pain.

Key PointsDUSP22-rearranged ALCLs belong to a distinct subset of ALCLs lacking activated STAT3. DUSP22-rearranged ALCLs have a unique molecular signature characterized by DNA hypomethylation and an immunogenic phenotype.

Autoimmune epilepsy (AE) is becoming increasingly recognized as a potentially reversible cause of frequent or medically intractable seizures and cognitive deterioration. We describe various presentations of autoimmune encephalopathy which have specifically presented with seizure and describe reported imaging findings. This is organized as a review of the more common autoantibodies which can specifically precipitate seizure according to the intracellular or extracellular location of the targeted antigen. For each antibody, we illustrate their pathophysiology, characteristic clinical presentations with typical effective treatments and prognoses and imaging findings on MRI and PET/CT exams. Parenchymal involvement is variable with the limbic structures typically affected; however, non-limbic cortex, cerebellum, brainstem and basal ganglia can also be involved. In the acute setting, affected regions typically demonstrate T 2 hyperintensity with mild mass effect from edema and increased 18F-fludeoxyglucose uptake. Chronically involved parenchyma will often undergo atrophy and demonstrate decreased metabolism; mesial temporal sclerosis is often the end result when the limbic system is involved. Without treatment, long-term effects from AE range from ongoing cognitive dysfunction and refractory seizures to death. Familiarity with AE may prompt appropriate antibody screening, particularly in cases of refractory seizure disorders. Early investigation and proper management of AE cases may help to prevent parenchymal and neurologic deterioration in these patients.

Abstract BACKGROUND Perioperative steroid protocols for patients undergoing transsphenoidal surgery (TSS) for pituitary pathology vary by institution. OBJECTIVE To assess the safety of withholding glucocorticoids in patients undergoing TSS. METHODS Patients with an intact hypothalamic-pituitary-adrenal (HPA) axis undergoing TSS for a pituitary tumor at the same academic institution between 2012 and 2015 were randomized to either receive 100 mg of intravenous hydrocortisone followed by 0.5 mg of intravenous dexamethasone every 6 h for 4 doses (STER, n = 23) or to undergo surgery without steroids (NOSTER, n = 20). Postoperative cortisol levels were then used to determine the need for glucocorticoids after surgery. Data regarding postoperative cortisol levels, hospital stay length, and complications were collected. RESULTS Mean postoperative 8 am cortisol levels were higher in the NOSTER group compared to the STER group (745 ± 359 nmol/L and 386 ± 193 nmol/L, respectively, P = .001) and more patients were discharged on glucocorticoids in the STER group (42% vs 12%, P = .07). There was no difference in the incidence of postoperative complications, including hyperglycemia, diabetes insipidus, or permanent adrenal insufficiency. Permanent adrenal insufficiency occurred in 8% of patients. CONCLUSION Perioperative steroids can be safely withheld in patients with an intact HPA axis undergoing TSS. Although administration of perioperative glucocorticoids does not appear to increase the risk of complications, it may interfere with assessment of the HPA axis after surgery.

Metabolic alterations are increasingly recognized as important novel anti‐cancer targets. Among several regulators of metabolic alterations, fructose 2,6 bisphosphate (F2,6BP) is a critical glycolytic regulator. Inhibition of the active form of PFKFB3ser461 using a novel inhibitor, PFK158 resulted in reduced glucose uptake, ATP production, lactate release as well as induction of apoptosis in gynecologic cancer cells. Moreover, we found that PFK158 synergizes with carboplatin (CBPt) and paclitaxel (PTX) in the chemoresistant cell lines, C13 and HeyA8MDR but not in their chemosensitive counterparts, OV2008 and HeyA8, respectively. We determined that PFK158‐induced autophagic flux leads to lipophagy resulting in the downregulation of cPLA2, a lipid droplet (LD) associated protein. Immunofluorescence and co‐immunoprecipitation revealed colocalization of p62/SQSTM1 with cPLA2 in HeyA8MDR cells uncovering a novel pathway for the breakdown of LDs promoted by PFK158. Interestingly, treating the cells with the autophagic inhibitor bafilomycin A reversed the PFK158‐mediated synergy and lipophagy in chemoresistant cells. Finally, in a highly metastatic PTX‐resistant in vivo ovarian mouse model, a combination of PFK158 with CBPt significantly reduced tumor weight and ascites and reduced LDs in tumor tissue as seen by immunofluorescence and transmission electron microscopy compared to untreated mice. Since the majority of cancer patients will eventually recur and develop chemoresistance, our results suggest that PFK158 in combination with standard chemotherapy may have a direct clinical role in the treatment of recurrent cancer.