MATERIALS AND METHODS: A search of relevant literature from 2014 to 2016 concerning targeted therapies in RA was conducted. The RA Update Working Group evaluated the evidence and proposed updated recommendations using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, to describe the quality of evidence and strength of recommendations. Recommendations were finalized through consensus using the Delphi technique.

RESULTS: This update provides 16 RA treatment recommendations based on current best evidence and expert clinical opinion. Recommendations 1-3 deal with the use of conventional synthetic disease-modifying antirheumatic drugs. The next three recommendations (4-6) cover the need for screening and management of infections and comorbid conditions prior to starting targeted therapy, while the following seven recommendations focus on use of these agents. We address choice of targeted therapy, switch, tapering and discontinuation. The last three recommendations elaborate on targeted therapy for RA in special situations such as pregnancy, cancer, and major surgery.

Methods: Septic patient with hyperlactatemia and metabolic acidosis were randomized to receive either high SID fl uid or Hartmann's solution during initial fl uid resuscitation. The primary outcome measures the pH and bicarbonate levels difference pre- and post- resuscitation.

Results: One hundred and sixty-two patients underwent randomization, 81 were assigned each to receive high SID fluid or Hartmann's solution. Both groups had similar baseline characteristics. High SID group received 23.5 mL/kg and the Hartmann's group received 22.7 mL/kg (p = 0.360). High SID fluid increased the mean (± SD) pH by 0.107 (± 0.09) vs. Hartmann's solution by 0.014 (± 0.12), p ≤ 0.001. Mean bicarbonate level increased signifi cantly in high SID group compared to Hartmann's (4.30 ± 3.76 vs. 1.25 ± 3.33, p ≤ 0.001). High SID group had higher post resuscitation lactate clearance than Hartmann's group (25.4 ± 28.3% vs. 12.0 ± 34.1%, p = 0.009). Shorter hospital stay was observed in highSID group 8.04 ± 5.96 days vs. Hartmann's group 12.18 ± 12.41 days (p = 0.048). Both groups showed no difference in incidence of pulmonary oedema, acute kidney injury and mortality.

Methods: The 5-FU-loaded NPs were prepared utilizing a simple double emulsion method using polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) with or without PEG 6000. The surface charge, particle size, and shape of NPs were evaluated by standard procedures. Both Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra of the 5-FU loaded NPs were compared against the pure 5-FU. The in vitro release profile of 5-FU from the NPs was monitored by the dialysis tubing method. Cell death and apoptosis induction in response to 5-FU NP exposure were measured by MTT and Annexin-V/7-amino-actinomycin D (7-AAD) assays, respectively, in Daoy, HepG2, and HT-29 cancer cell lines.

Results: The 5-FU loaded NPs were found to be spherical in shape with size ranging between 176±6.7 and 253.9±8.6 nm. The zeta potential varied between -7.13± 0.13 and -27.06±3.18 mV, and the entrapment efficiency was between 31.96% and 74.09%. The in vitro release of the drug followed a two-phase mode characterized by rapid release in the first 8 hrs followed by a period of slow release up to 72 hrs with composition-based variable extents. Cells exposed to NPs demonstrated a significant cell death which correlated with the ratio of PEG in the formulations in Daoy and HepG2 cells but not in HT-29 cells. Formulations (F1-F3) significantly induced early apoptosis in HT-29 cell lines.