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ObjectiveTo update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).MethodsWe conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel.ResultsRecommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended.ConclusionThese recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.

Shi, Min, Allison R. Jones, Mark S. Niedringhaus, Rebecca J. Pearson, Ann M. Biehl, Manuel Ferreira Jr., Niaz Sahibzada, Joseph G. Verbalis, and Richard A. Gillis. Glucose acts in the CNS to regulate gastric motility during hypoglycemia. Am J Physiol Regul Integr Comp Physiol 285: Rl192-R1202, 2003. First published July 17, 2003; 10.1152/ajpregu.00179.2003.--Our purposes were to 1) develop an animal model where intravenously (iv) administered [ETH]-glucose consistently inhibited antral motility, and 2) use this model to assess whether iv glucose acts to inhibit motility from a peripheral or a central nervous system site and to elucidate the factor(s) that determine(s) whether stomach motor function is sensitive to changes in blood glucose. Rats were anesthetized with [alpha]-chloralose-urethane, and antral motility was measured by a strain-gauge force transducer sutured to the antrum. In some cases, antral motility and gastric tone were measured by monitoring intragastric balloon pressure. Increases in blood glucose were produced by continuous iv infusion of 25% [ETH]-glucose at 2 ml/h. Inhibition of antral motility and gastric tone was observed when gastric contractions were induced by hypoglycemia (subcutaneously administered insulin, 2.5 IU/animal). In contrast, no inhibition of gastric motor function was observed when glucose infusion was tested on gastric contractions that were 1) spontaneously occurring, 2) evoked by iv administered bethanechol in vagotomized animals, and 3) evoked by the TRH analog RX77368, microinjected into the dorsal motor nucleus of the vagus. Using the model of insulin-induced hypoglycemia to increase gastric motor activity, we found that neither sectioning the hepatic branch of the vagus (n = 5), nor treating animals with capsaicin to destroy sensory vagal afferent nerves (n = 5) affected the ability of iv [ETH]-glucose to inhibit gastric motor function. Our results indicate that an important factor determining whether stomach' motor function will be sensitive to changes in blood glucose is the method used to stimulate gastric contractions, and that the primary site of the inhibitory action of iv glucose on gastric motility is the central nervous system rather than the periphery. insulin; gastric tone; antral motility; central nervous system

Background and Aims: Reports of moderate to severe liver injury associated with tocilizumab, an interleukin‐6 (IL‐6) receptor antagonist, have been reported in the post‐marketing setting. This case series aims to characterize cases of tocilizumab‐associated clinically significant hepatic injury. Methods: We analysed cases of severe acute liver injury associated with tocilizumab reported in the FDA Adverse Event Reporting System and the medical literature. Results: We identified 12 cases in which tocilizumab was a suspected primary cause of liver injury and eight cases in which serious sequelae of underlying or coincident viral hepatitis were temporally associated with its use. Using the Drug‐Induced Liver Injury Network (DILIN) severity scale, five of 12 cases were Grade 5 (two liver transplants, three deaths), one was Grade 4 (liver failure) and six were Grade 3 (serious events with elevated bilirubin). Two cases reported liver atrophy with low hepatocellular expression of Ki‐67, a marker of cellular proliferation. Among the eight cases of tocilizumab‐associated viral hepatitis exacerbation, three were scored as DILIN severity Grade 5 (one liver transplant, two deaths), one was Grade 4 (liver failure), and four were Grade 3. The reported viral hepatitis events were hepatitis B virus (HBV) reactivation (n = 3), hepatitis C virus (HCV) flare (n = 1), cytomegalovirus (CMV)‐induced liver failure (n = 1), Epstein‐Barr virus hepatitis (n = 1), acute hepatitis E (HEV, n = 1) and HEV‐induced macrophage activation syndrome (n = 1). Conclusion: Tocilizumab may be a primary cause of severe liver injury, as well as exacerbate underlying viral hepatitis. The disruption by tocilizumab of IL‐6‐mediated immune protection and hepatocyte regeneration may aggravate clinical outcomes in some cases. [ABSTRACT FROM AUTHOR]

Our purposes were to 1) develop an animal model where intravenously (iv) administered D-glucose consistently inhibited antral motility, and 2) use this model to assess whether iv glucose acts to inhibit motility from a peripheral or a central nervous system site and to elucidate the factor(s) that determine(s) whether stomach motor function is sensitive to changes in blood glucose. Rats were anesthetized with α-chloralose-urethane, and antral motility was measured by a strain-gauge force transducer sutured to the antrum. In some cases, antral motility and gastric tone were measured by monitoring intragastric balloon pressure. Increases in blood glucose were produced by continuous iv infusion of 25% D-glucose at 2 ml/h. Inhibition of antral motility and gastric tone was observed when gastric contractions were induced by hypoglycemia (subcutaneously administered insulin, 2.5 IU/animal). In contrast, no inhibition of gastric motor function was observed when glucose infusion was tested on gastric contractions that were 1) spontaneously occurring, 2) evoked by iv administered bethanechol in vagotomized animals, and 3) evoked by the TRH analog RX77368, microinjected into the dorsal motor nucleus of the vagus. Using the model of insulin-induced hypoglycemia to increase gastric motor activity, we found that neither sectioning the hepatic branch of the vagus (n = 5), nor treating animals with capsaicin to destroy sensory vagal afferent nerves (n = 5) affected the ability of iv D-glucose to inhibit gastric motor function. Our results indicate that an important factor determining whether stomach motor function will be sensitive to changes in blood glucose is the method used to stimulate gastric contractions, and that the primary site of the inhibitory action of iv glucose on gastric motility is the central nervous system rather than the periphery. [ABSTRACT FROM AUTHOR]

Background: Infection is common cause of morbidity and mortality in systemic lupus erythematosus (SLE). Our objective was to determine incidence and types of infections, particularly opportunistic infections, in SLE patients receiving cyclophosphamide, and to identify contribution of variables like demographics, steroid, other immunosuppressives, white blood cell and absolute neutrophil count to infection risk., Patients and Methods: We did retrospective chart review of SLE patients in our institute over last 10 years, who received minimum six cyclophosphamide infusions. Types of infection, cumulative steroid dose, and maintenance medications were recorded. Statistical analyses were done using SAS software., Results: 87.1% of the 31 patients were female. Mean age was 37.9 years, 48.4% Hispanic, 25.8% African American, 6.4% Asian and 19.4% were Caucasian. No one was on pneumocystis jirovecii pneumonia (PJP) prophylaxis. There were 42 episodes of infection in 31 patients. Different infections were urinary tract infections (UTI), upper respiratory infections (URI), line sepsis, bacterial pneumonia, PJP, mucocutaneous infections and viral gastroenteritis. Infection frequency was significantly higher among Asians compared to Caucasians (p =0.0152). Infection rate was significantly higher during cyclophosphosphamide induction phase (65.9%) compared to maintenance phase (34.1%) (p value=0.0041). Infection rate was higher with higher cumulative steroid dose and in patients on quarterly cyclophosphamide infusion compared to those on oral azathioprine or mycophenolate mofetil. No association found among baseline white blood cell (WBC) or absolute neutrophil count (ANC) and infection rate., Conclusion: We found higher infection rates among Asians and in patients with higher cumulative steroid dose. Single incidence of PJP noted despite absence of prophylaxis. Quarterly cyclophosphamide was associated with higher infection rates. Larger prospective studies are needed to confirm our results., Competing Interests: Conflict of Interest None of the authors have any financial interests or conflict of interest with regard to this work.