Single Induction Dose Research Articles

Comparison of airway collapsibility following single induction dose ketamine with propofol versus propofol sedation in children undergoing magnetic resonance imaging: A randomised controlled study.

Adequate sedation is essential for children undergoing magnetic resonance imaging (MRI) console. Propofol is commonly used for sedation, but it has the drawback of upper airway collapse at higher doses, which may be overcome by ketamine. This study was designed to evaluate the beneficial effect of ketamine on propofol in preventing airway collapse. Fifty-eight children undergoing MRI were randomised to Group P (propofol bolus dose followed by infusion or Group KP (bolus dose of ketamine and propofol followed by propofol infusion). The primary aim is to compare the upper airway cross-sectional area (CSA) and diameters (transverse diameter [TD] and anteroposterior diameter [APD]) obtained from MRI during inspiration and expiration. Upper airway collapse as measured by delta CSA in mean (SD) [95% confidence interval] was statistically more significant between the two groups [at the soft palate level, 16.9 mm2 (19.8) [9.3-24.4] versus 9.0 mm2 (5.50) [6.9-11.1] (P = 0.043); at the base of the tongue level, 15.4 mm2 (11.03) [11.2-19.6] versus 7.48 mm2 (4.83) [5.64-9.32] (P < 0.001); at the epiglottis level, 23.9 (26.05) [14.0-33.8] versus 10.9 mm2 (9.47) [7.35-14.5] (P = 0.014)]. A significant difference was obtained for TD at all levels and for APD at the soft palate and base of tongue level. Adding a single dose of ketamine to propofol reduced the upper airway collapse significantly, as evidenced by the MRI-based measurements of upper airway dimensions, compared to propofol alone.

DOP18 Efficacy of risankizumab versus ustekinumab by baseline Crohn’s Disease location: post-hoc analysis of the SEQUENCE head-to-head trial

Abstract Background In Crohn’s disease (CD), disease location may impact treatment effect. This post-hoc analysis of the SEQUENCE head-to-head trial (NCT04524611) compared the efficacy of risankizumab (RZB), an interleukin (IL)-23 p19 inhibitor, versus ustekinumab (UST), an IL-12/23 p40 inhibitor, by CD location. Methods SEQUENCE was an open-label, efficacy assessment-blinded, randomized controlled trial, which enrolled patients (pts) with moderate to severe CD who previously failed ≥1 anti-tumor necrosis factor (TNF) therapy. Pts included in the primary efficacy analysis were randomised 1:1 to receive RZB (selected dosing: intravenous 600 mg induction dose administered at weeks (wks) 0, 4, and 8, followed by subcutaneous 360 mg maintenance dose every 8 wks starting at wk 12) or UST (a single weight-based induction dose administered at wk 0, followed by subcutaneous 90 mg maintenance dose every 8 wks starting at wk 8. A mandatory steroid taper began at wk 2. The primary endpoints were clinical remission (CD Activity Index &amp;lt;150) at wk 24 and endoscopic remission (Simple Endoscopic Score for CD ≤4 and at least a 2-point reduction versus baseline and no subscore &amp;gt;1 in any individual variable, as scored by a central reviewer blinded to treatment allocation) at wk 48. In this post-hoc analysis, both endpoints were evaluated in 100% of pts included in the primary efficacy analysis, stratified by baseline CD location subgroups (ileal only, colonic only, ileal-colonic). Nominal P-values were reported for treatment differences within subgroups. Results At baseline, majority of pts had either ileal-colonic (225 [43.3%]) or colonic (208 [40%]) CD; 87 (16.7%) pts had isolated ileal disease. At wk 24, numerically greater proportions of pts achieved clinical remission with RZB versus UST, regardless of disease location (treatment difference [95% confidence interval], P-value: ileal only, Δ0.8 [-20.1, 21.7], P=0.941; colonic only, Δ22.4 [9.2, 35.5], P=0.001; ileal-colonic, Δ18.2 [5.3, 31.0], P=0.007) (Figure). Pts randomized to RZB with colonic only disease had numerically higher rates of clinical remission relative to pts with ileal only or ileo-colonic disease. At wk 48, RZB-treated pts demonstrated numerically higher rates of endoscopic remission than UST-treated pts (ileal only, Δ22.5 [4.4, 40.6], P=0.017; colonic only, Δ18.3 [6.6, 30.0], P=0.003; ileal-colonic, Δ10.3 [-0.2, 20.9], P=0.057) (Figure). Endoscopic remission rates in the RZB-treated pts were generally similar between ileal only and colonic only CD. Conclusion In pts who have failed ≥1 anti-TNF therapy, RZB demonstrated greater rates of endoscopic remission compared to UST regardless of CD location, and greater rates of clinical remission in ileo-colonic and colonic CD.

A comparison between magnesium sulphate and fentanyl as adjuvants to propofol infusion for sedation in endoscopic retrograde cholangiopancreatography: A randomized controlled trial

ABSTRACT Background Propofol-based sedations are used widely during endoscopic retrograde cholangiopancreatography (ERCP) procedures. However, respiratory depression and cardiovascular adverse events commonly occur. Therefore, we designed this study to evaluate the effects of adding a single boules induction dose of fentanyl or magnesium sulphate to propofol infusion for sedation of patients subjected to ERCP. Methods This randomized parallel double-blind controlled trial included 60 adult patients scheduled for ERCP procedures. Before starting the propofol infusion, patients immediately received either magnesium sulphate 50 mg.kg−1 intravenously (IV) over 10 min (Group M) (n = 30) or fentanyl 2 µg.kg−1 IV over 10 min (Group F) (n- = 30). Continuous propofol infusion was given with a syringe pump for maintenance, with the initial rate set at 25–75 mic/kg/min IV during the first 10–15 min. Results The magnesium group had significantly reduced the total propofol consumption and increased the onset time of sedation than the fentanyl group (P < 0.05). Heart rate and mean arterial pressure were statistically lower after adjuvant bolus injection and 15 min in the magnesium group than in the fentanyl group (P < 0.001). Procedure time, involuntary movement, physician satisfaction, and complications exhibited no significant differences between both groups. Conclusions During ERCP, adding a single bolus of magnesium sulphate to propofol was associated with a lower total propofol consumption and better hemodynamics than fentanyl but with a delayed onset time of sedation and comparable respiratory depression.

The impact of universal induction therapy on early hospital readmission of kidney transplant recipients.

Early hospital readmission (EHR) is associated with worse outcomes. The use of anti-thymocyte globulin (rATG) induction therapy is associated with increased efficacy in preventing acute rejection, although safety concerns still exist. This retrospective single-center study compared the incidence, causes of EHR, and one-year clinical outcomes of patients receiving a kidney transplant between August 18, 2011 and December 31, 2012 (old era), in which only high-risk patients received 5 mg/kg rATG, with those transplanted between August 18, 2014 and December 31, 2015 (new era), in which all patients received a single 3 mg/kg dose of rATG. There were 788 patients from the Old Era and 800 from the New Era. The EHR incidence in the old era patients was 26.4% and in the new era patients, 22.5% (p = 0.071). The main cause of EHR in both eras was infection (67% vs. 68%). The incidence of acute rejection episodes was lower (22.7% vs 3.5%, p < 0.001) and the one-year patient survival was higher (95.6% vs. 98.1%, vs. p = 0.004) in new era patients. The universal use of 3 mg/kg rATG single-dose induction therapy in the new era was associated with a trend towards reduced EHR and a reduction in the incidence of acute rejection and mortality.

Clinical outcomes after a single induction dose of etomidate versus ketamine for emergency department sepsis intubation: a randomized controlled trial

Patients with sepsis often require emergency intubation. In emergency departments (EDs), rapid-sequence intubation with a single-dose induction agent is standard practice, but the best choice of induction agent in sepsis remains controversial. We conducted a randomized, controlled, single-blind trial in the ED. We included septic patients who were aged at least 18 years and required sedation for emergency intubation. Patients were randomly assigned by a blocked randomization to receive 0.2–0.3 mg/kg of etomidate or 1–2 mg/kg of ketamine for intubation. The objectives were to compare the survival outcomes and adverse events after intubation between etomidate and ketamine. Two hundred and sixty septic patients were enrolled; 130 patients/drug arm whose baseline characteristics were well balanced at baseline. In the etomidate group, 105 patients (80.8%) were alive at 28 days, compared with 95 patients (73.1%) in the ketamine group (risk difference [RD], 7.7%; 95% confidence interval [CI], − 2.5 to 17.9%; P = 0.092). There was no significant difference in the proportion of patients who survived at 24 h (91.5% vs. 96.2%; P = 0.097) and survived at 7 days (87.7% vs. 87.7%; P = 0.574). A significantly higher proportion of the etomidate group needed a vasopressor within 24 h after intubation: 43.9% vs. 17.7%, RD, 26.2% (95% CI, 15.4 to 36.9%; P < 0.001). In conclusion, there were no differences in early and late survival rates between etomidate and ketamine. However, etomidate was associated with higher risks of early vasopressor use after intubation. Trial registration: The trial protocol was registered in the Thai Clinical Trials Registry (identification number: TCTR20210213001). Registered 13 February 2021—Retrospectively registered, https://www.thaiclinicaltrials.org/export/pdf/TCTR20210213001.

Relationship Between Serum Ustekinumab Trough Concentration and Clinical and Biochemical Disease Activity: A Real-World Study in Adult Patients with Crohn's Disease.

The role of therapeutic drug monitoring for ustekinumab in the treatment of Crohn's disease has not been defined. This study aimed to explore the relationship of serum ustekinumab trough concentration (UTC) with clinical and biochemical disease outcomes in a real-world setting. We performed a retrospective analysis of Crohn's disease patients treated at a single tertiary centre. Ustekinumab was given as a single intravenous induction dose, followed by maintenance subcutaneous injections every 4 to 8 weeks. Rates of clinical remission (Harvey-Bradshaw Index ≤ 4), biochemical remission (C-reactive protein < 5 mg/l and faecal calprotectin < 150 μg/g) and complete remission were assessed at baseline and at the time of UTC testing during maintenance therapy. The association between baseline variables and UTC was tested using linear regression. We also performed an external validation analysis of UTC cut-offs established in four previously published studies. This study included 43 patients. Compared to 8-weekly dosing, a 2.49- and 2.65-fold increase in UTC was associated with 6-weekly and 4-weekly dosing respectively. However, there was no significant difference in clinical, biochemical or complete remission among the dosing groups. An external validation of previously published optimal UTC cut-offs found low predictive value for our patient population. In this study, dosing interval was the only determinant significantly associated with a higher UTC for patients on maintenance ustekinumab therapy. While a higher UTC may be achieved with dose escalation, it was not associated with improved rates of clinical or biochemical response in our cohort.

Delayed emergence after general anesthesia using remimazolam for induction agent in laparoscopic cholecystectomy: a case report

Remimazolam’s ultrashort-acting properties, including reduced injection discomfort, minimal impact on respiratory and cardiovascular functions and rapid metabolism, have garnered significant attention in the field of anesthesia. However, despite its widespread acclaim, we encountered an unusual case in which a patient without hepatic or renal impairment experienced unexpected delays in regaining consciousness following a single intravenous induction dose of remimazolam. The patient, a 63-year-old undergoing laparoscopic cholecystectomy for gallbladder stones, had preoperative tests revealing atrial fibrillation and a reduced ejection fraction observed in an echocardiogram. Anesthesia induction included the administration of remimazolam (0.3 mg/kg), sufentanil and rocuronium. The surgery proceeded uneventfully and was maintained with desflurane and sufentanil. However, after the surgery, the patient experienced delayed emergence from anesthesia. Opioid overdose was ruled out, and we suspected a metabolic delay associated with remimazolam. In response to this suspicion, we administered flumazenil, which promptly restored consciousness and normal breathing. Subsequent post-anesthetic observation revealed no complications, and the patient was discharged two days after surgery. This case highlights the significant delayed emergence phenomenon linked to remimazolam, even when administered as a bolus. Instances of delayed emergence following remimazolam administration underscore the complexities in anesthesia responses, emphasizing the importance of vigilant clinical monitoring and the need for ongoing research in this area.

Effectiveness and Safety of Ustekinumab for Moderate to Severely Active Crohn's Disease: Results from an Early Access Program in Brazil.

This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn's disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.

Rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog.

To report a case of rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog. A 5-year-old intact male Shih-Tzu dog was presented for pigmenturia occurring a few hours following anesthesia for comprehensive oral health assessment and treatment. After premedication with IV diazepam (0.5mg/kg), anesthesia was induced with IV propofol (4mg/kg) and maintained with isoflurane vaporized in oxygen. A few hours following recovery from anesthesia, the dog developed rhabdomyolysis and myoglobinuria associated with increased serum alanine aminotransferase and C-reactive protein concentrations, as well as mild hypokalemia and euglycemic glycosuria. Approximately 48hours after IV fluid therapy, the dog was clinically normal, and myoglobinuria progressively resolved. This is the first case description of rhabdomyolysis and myoglobinuria following a single dose of injectable propofol.

Single-Dose Induction of Osteogenic Differentiation of Mesenchymal Stem Cells Using a Cyclic AMP Activator, Forskolin

Single-Dose Induction of Osteogenic Differentiation of Mesenchymal Stem Cells Using a Cyclic AMP Activator, Forskolin

The Effect of Intraoperative Diphenhydramine/Morphine on Acute Pain and Opioid Consumption after Spine Surgery

Background: One of the most common problems after spine surgery is very severe pain that usually affects outcome of patients after surgery and duration of hospital stay. Acute postoperative pain has several mechanisms, and multimodal analgesia by different mechanism of action will help control to it. In this study, we intended to investigate the effect of intravenous diphenhydramine injection during induction of anesthesia and morphine before incision on the control of acute pain in postoperative laminectomy. Methods: 130 patients scheduled for spine surgeries were assigned to receive a single pre induction dose of diphenhydramine 0.4mg/kg IV (D group) and morphine 0.15mg/kg before incision in addition acetaminophen 1gr IV at the end of surgery and just morphine 0.15mg/kg and acetaminophen 1gr IV (C group) in a randomized, double-blind trial. Postoperative pain, analgesic requirements in recovery and 24 hr after surgery were assessed. Results: The mean pain intensity in recovery was lower in the diphenhydramine group than in the control group (MD, 2.13; 95% confidence interval (CI), 1.72–2.53; P &lt; .0001) and the need for analgesia was much lower in the diphenhydramine group than in the control group. P &lt; 0.001. The severity of pain and the need for analgesics in the diphenhydramine group had a significant decrease in the ward compared to the control group. Conclusion: Prophylactic diphenhydramine 0.4 mg/kg at induction of general anesthesia in combination with morphine 0.15mg/kg before incision and acetaminophen 1gr at the end of surgery reduced the postoperative severity of acute pain and opioids requirement in the early postoperative period after spine surgeries.

Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate.

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

Pain on Injection: Propofol MCT Vs Propofol LCT

Background: Propofol is one of the safest drugs in the induction of general anesthesia. The routinely available preparation in market being Propofol LCT (long chain triglycerides) which do have a disadvantage of pain on injection. This pain is very discomforting for the patient and also anesthesiologist. So, they are coming up with new preparation Propofol MCT (medium chain triglycerides) which do have a property of reduction of pain on injection. In view of which we compare the occurrence of pain on injection of Propofol MCT with Propofol LCT and rise in serum triglyceride levels after single induction dose. Materials and methods: After obtaining institutional ethical committee approval, 150 patients of ASA I & II were enrolled in the study undergoing various elective surgeries under general anesthesia, where propofol is used as an induction agent. The study patients were divided into two groups who received Propofol MCT (Group M) and Propofol LCT (Group L) as an induction drug. The intensity of pain is evaluated by using visual analogue score (VAS). Similarly, side effects of Propofol MCT were observed. Results: Group M showed reduced pain score (4.15 ± 1.90) after Propofol MCT injection along with less incidence of pain compared to Group L (6.37± 2.49). Serum triglyceride levels had no significant difference in preoperative and postoperative values. Conclusion: In conclusion, pain on injection with Propofol MCT (4.15 ± 1.90) is less compared to Propofol LCT (6.37± 2.49); there is no evidence of elevation of triglyceride levels after single induction dose in the study. Keywords: Propofol, Pain on Injection, Propofol MCT, Propofol LCT, Serum Triglycerides

Use of Accelerated Induction Strategy of Infliximab for Ulcerative Colitis in Hospitalized Patients at a Tertiary Care Center.

Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy. To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC. We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics. From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction. In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.

842 Impact of Response and Inflammatory Burden at Start of Maintenance Therapy on Clinical Efficacy of Ustekinumab Dosing Regimen in UC: Week 44 Results From UNIFI

INTRODUCTION: The UNIFI maintenance study was a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study in pts with moderate to severely active ulcerative colitis (UC) who failed conventional or biologic therapy and were in clinical response 8 wks after receiving a single ustekinumab (UST) IV induction dose. In this study, pts were randomized to placebo, UST 90 mg SC q8w or q12w. METHODS: To examine the relative efficacy of the UST 90 mg SC q8w or q12w maintenance regimens, subgroup analyses were performed for outcomes of clinical remission, symptomatic remission, and endoscopic improvement at Wk44 for pts who did and did not achieve these endpoints at the start of maintenance. Analyses of clinical remission and endoscopic improvement at Wk44 based on pre-specified cut-points of the concentrations of inflammatory biomarkers (CRP [≤3 mg/L, &gt;3 mg/L] and fecal calprotectin [≤250 mg/kg, &gt;250 mg/kg]) at maintenance baseline were also conducted. RESULTS: For pts who had achieved clinical remission, symptomatic remission, or endoscopic improvement at maintenance baseline, efficacy of UST q8w and q12w regimens for the respective endpoint at Wk44 was similar (Table 1). By contrast, for pts who did not achieve clinical or symptomatic remission or endoscopic improvement at maintenance baseline, UST q8w demonstrated greater efficacy than UST q12w for that endpoint at Wk44. Pts with low inflammatory burden marked by CRP ≤3 mg/L at maintenance baseline achieved similar efficacy at Week 44 with UST q8w and q12w dosing regimens as measured by clinical remission and endoscopic improvement (Table 1). By contrast, pts with high inflammatory burden, marked by CRP &gt;3 mg/L at maintenance baseline, achieved greater efficacy at Wk44 with UST q8w versus q12w dosing over the endpoints. Generally similar trends were seen in pts with fecal calprotectin measurements for low (≤ 250 mg/kg) and high (&gt;250 mg/kg) inflammatory burden at maintenance baseline. CONCLUSION: Among pts with a clinically meaningful response to a single IV induction dose of UST, maintenance treatment with UST q8w or q12w demonstrated similar efficacy at Wk44. By contrast, the efficacy of UST q8w at Week 44 was greater than the q12w regimen for pts with higher inflammatory burden or who did not achieve clinical or symptomatic remission or endoscopic improvement at Wk8. These data suggest that multiple clinical measures can help inform the decision on the most appropriate maintenance dosing regimen for UST in the treatment of pts with UC.

Pretransplant assessment of cyclosporine level as a predictor of cyclosporine dose requirements after kidney transplantation

Introduction and aimsPretransplant administration of cyclosporine (CsA) may reduce post-transplant maintenance dose and consequently CsA inhibitor nephrotoxicity and helps in achieving the desired target C2 levels earlier. The optimum dose or timing of administration of CsA induction dose is still debatable.Patients and methodsWe compared three different protocols for pretransplant administration of CsA aiming to reach a target C2 therapeutic level of greater than 800 ng/ml on the third day post-transplant. Sixty kidney transplant recipients from Cairo University hospitals were divided into: group 1 (n=20) who received a single CsA induction dose of 2 mg/kg 12 h pretransplant; group 2 (n=20) who received four CsA consecutive doses of 4 mg/kg 48 h pre-transplant; and group 3 (n=20) who received four CsA consecutive doses of 2 mg/kg 48 h pretransplant.ResultsThe desired therapeutic level in the earlier post-transplantation period was achieved in 65% in group 1, 100% in groups 2 and 3). In group 2 a lower dose was needed to maintain C2 within the therapeutic range during the first year post-transplantation (P<0.01). Furthermore, a lower number of cases were complicated by CsA nephrotoxicity in group 2 in comparison to groups 1 and 3 (25, 0, 5% in group 1, 2, 3, respectively, P<0.039). A higher longer dose of CsA pretransplant associated with early withdrawal of CsA had a better effect on graft function than lower or shorter induction doses with late withdrawal as evidenced by lower serum creatinine levels all through the follow-up period in group 2 compared with group 3.ConclusionForty-eight-hour pretransplant induction with CsA at a dose of 4 mg/kg with early dose reduction post-transplant was associated with lower CsA maintenance and a better 1-year graft function.

Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis.

Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis. Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported. Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels. In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

Late breaking abstracts

Late breaking abstracts

Response and Remission After 16 Weeks of Ustekinumab: An All Patients Analysis From the UNITI Crohnʼs Studies

Introduction: UST has been shown to induce&maintain clinical response & remission in moderate-severe Crohn's disease(CD) in 2 induction[(UNITI-1(anti-TNF failures)&UNITI-2(anti-TNF non-failures) &1 maintenance(IM-UNITI)] randomized, PBO-controlled Ph3 trials. We evaluated efficacy (response & remission) for all pts who received an IV induction dose of approximately 6mg/kg, including responders(CDAI decrease ≥100)&non-responders, 8wks after first UST maintenance dose of 90mg SC, ie, 6wks from the IV induction dose. Methods: Pts achieving clinical response 8wks after a single IV induction dose were randomized to SC PBO, UST 90mg q12wks or q8wks. UST pts not in clinical response 8wks after IV induction dose were given UST90mg SC & if in clinical response 8wks later were continued on 90mg SC q8w. A total of 458pts were exposed to an IV induction dose of 6mg/kg(UNITI-1,N=249 & in UNITI-2 N=209) with a response rate at wk8 of 37.8%&57.9% vs PBO response rate of 20.2%&32.1% respectively. The remission rate at wk8 in UNITI-1 & UNITI-2 was 20.9%&40.7 vs PBO of 7.3%&19.6% respectively. For this evaluation, response & remission status of the entire population exposed to an IV induction dose of 6mg/kg of UST was evaluated 8wks after the first SC maintenance dose of UST. All pts who received 6mg/kg IV UST induction were included, including responders randomized to SC PBO(who did not receive SC UST at wk8). Results: Of the 219 pts not in clinical response in UNITI 1&2, 37.6%&60.5% respectively were in clinical response 8wks after first maintenance UST dose (90 mg SC). Evaluating all pts exposed to 6mg/kg IV UST induction, response rates 8wks after first SC injection(16wks after IV induction dose) for UNITI1&2 are 47.4%&73.7% respectively (Table). Similar assessments were calculated in the sub-population who were anti-TNF naïve upon enrolment into UNITI-2.Table: Table. Response rates and remission rates for all pts 16wks after induction of 6mg/kg IV USTConclusion: These numbers at wk16 are expected to reflect real world experience in pts who receive the induction dose & one additional maintenance dose 8wks later. The resulting rates of response & remission are higher than previously reported in induction studies across all populations(anti-TNF non-failures & anti-TNF failures). About 73% of anti-TNF non-failures attain clinical response & over half are in remission.The data support clinical rationale for providing at least one SC maintenance dose of UST irrespective of clinical response 8wks after IV induction.

English

INTRODUCTION: The post operative nausea and vomiting is one of the common complications following anaesthesia. The incidence of post operative nausea and vomiting is more following general anaesthesia than regional anaesthesia. The patients undergoing laparoscopic surgeries are more prone for developing post operative nausea and vomiting. Hence we evaluated the efficacy of the effectiveness of intravenous Palonosetron 75mcg with intravenous Ondansetron 4mg as single pre induction dose in laparoscopic cholecystectomy in preventing PONV following general anaesthesia. METHODOLOGY: After obtaining Institutional Human Ethics Committee clearance the study was carried out in PSGIMS&R during July 2014 – May 2015. A total of 100 patients who were posted for laparoscopic cholecystectomy belonging to ASA Class I & II were included in the study. These patients were randomized into 2 groups of 50 each by computer generated randomized numbers. The patients belonging to Group – A received Inj. Ondansetron 4mg just before induction of anaesthesia and patients belonging to Group – B received Inj. Palonosetron 75mcg just before induction of anaesthesia. All patients were followed for 24 hours post operatively. The incidences of nausea, retching and vomiting were observed postoperatively during 2 hrs, 6 hrs and 24 hrs post procedure interval period. RESULTS: In our study, the incidence of nausea, retching, vomiting at 24 hrs post procedure in Ondansetron group are 38%, 16% and 28% respectively. The incidence of nausea and vomiting at 24 hrs post procedure in Palonosetron group are 12% and 4%. The incidence of nausea and vomiting are more at period between 6hrs and 24 hrs post procedure. The incidence of nausea was 38 percent in Ondansetron group and 12 percent in Palonosetron group [p value 0.003]. The incidence of vomiting was 28 percent in Ondansetron group and 4 percent in Palonosetron group [p value 0.001]. Need for rescue medication was also high in Ondansetron group when compared to Palonosetron group [p value 0.001]. The complete responders in Ondansetron group are 62% and in Palonosetron group are 88% [p value 0.003]. There were no adverse events reported throughout the study in both the groups. CONCLUSION: Based on our study, it is observed that Palonosetron a second generation 5HT3 receptor antagonist has prolonged duration of action and has decreased the incidence of post operative nausea and vomiting significantly when compared to Ondansetron, providing patients with lesser episodes of PONV in patients undergoing laparoscopic cholecystectomy under general anesthesia.