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Background Biological medicines account for a significant cost to healthcare systems. With the advent of anti-tumour necrosis factor biosimilars, switching from originator to biosimilar has enabled cost saving in inflammatory bowel disease (IBD) without compromising disease control. However, with more biosimilars entering the market, the effect on IBD activity and pharmacokinetics (PK) of a second switch to another biosimilar is uncertain. This study aims to assess the effect on disease activity and drug levels associated with switching from infliximab (IFX) biosimilar Remsima® (Celltrion, Hungary) to another biosimilar, Flixabi® (Samsung Bioepis, The Netherlands), and to compare those switching for the first and second time. Methods All IBD patients on IFX biosimilar Remsima® were prospectively followed during their switch to Flixabi® in a single centre. Baseline data including C-reactive protein (CRP), trough IFX level, and clinical disease activity indices were collected; Harvey Bradshaw Index for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index for ulcerative colitis (UC). These indices were repeated after at least two infusions of Flixabi®. Results 221 patients (179 CD, 42 UC) on stable IFX treatment were included in the study. 174 (79%) were on a concomitant immunomodulator. 5 (2%) patients ceased IFX prior to follow-up due to sustained remission, and 3 (1%) patients discontinued due to factors not directly related to drug or disease. 112 patients had PK analysis performed pre and post switch. An increase in IFX trough level was observed after switching IFX biosimilars; baseline median (IQR) trough level of 4.5µg/ml (2.9–6.3) compared with post switch of 5.1µg/ml (3.4–7.0) (p = 0.02). There was no difference in clinical scores or CRP post switch, and no new anti-IFX antibodies were detected. 107 patients (48%) were switching IFX agent for the second time, of which 51 had PK analysis performed. A similar increase in median IFX trough level was observed post switch in those switching for the first (4.7 vs. 6.1 µg/ml, p = 0.03) and second (4.0 vs. 4.5µg/ml, p = 0.05) times (Figure 1). No change in clinical disease activity or CRP occurred in either group. Concomitant immunomodulator and disease classification had no impact on change in IFX level (p = 0.72 and 0.37, respectively, on univariate analysis). Conclusion In a cohort of IBD patients switching to a new IFX biosimilar either for the first or second time, an increase in IFX level was observed with no impact on clinical and biochemical disease activity indices. Switching IFX biosimilars in IBD appears safe in the short term with respect to maintaining drug pharmacokinetic profile and disease control whether switching for the first or second time.

Background:General anesthesia as a technique for laparoscopic cholecystectomies has disadvantage in terms of the stress response, lack of postoperative analgesia and emesis. Regional anesthesia offers advantages over general anesthesia in terms of cost, postoperative analgesia, intact respiratory control mechanism and early ambulation. Shoulder tip pain remains the main concerns that can be alleviated by adding various adjuvants to local anesthetics.Aims and Objectives:To study the effect of adding intrathecal dexmedetomidine to bupivacaine to decrease shoulder tip pain, onset and duration of sensory and motor block, hemodynamic changes and side effects if any.Materials and Methods:Totally, 60 patients were divided into two groups of 30 each. Group A received 3 ml of bupivacaine heavy and group B received 5 µg of dexmedetomidine along with 3 ml of bupivacaine diluted to total volume of 3.5 ml in each group.Statistical Analysis:It was done using Chi-square and Student's t-test.Results and Conclusions:Intrathecal dexmedetomidine provides stable hemodynamics, excellent sedation and analgesia and abolishes shoulder tip pain.

Canine heartworm, Dirofilaria immitis, is a nematode parasite that infects dogs by way of mosquito bite. Rarely, humans play accidental hosts to this parasite and are not a suitable environment for the nematode to live. As the parasite dies in the pulmonary vessels it embolizes the vessels causing infarction and eventual nodule formation in the lungs. In the right clinical context, a nodule can be considered malignant prompting invasive tissue sampling. We describe a case of a 48-year-old man who was found to have multiple asymptomatic scattered pulmonary nodules during imaging workup for an insulinoma. Fine needle biopsy of the largest nodule revealed a necrotic granuloma, lab testing and culture ruled out fungal and bacterial causes. Clinically, this picture was consistent with D. immitis infection.

Summary Background Biologics account for a significant cost in inflammatory bowel disease (IBD) management; however, switching from infliximab originator to its biosimilars has enabled cost saving without compromising disease control. The effects on IBD activity and infliximab trough levels of a second switch to another biosimilar are, however, uncertain. Aims To assess the effects on disease activity and infliximab trough levels associated with switching from infliximab biosimilar CT‐P13 to another biosimilar SB2 and compare outcomes in those switching for the first and second time. Methods IBD patients on CT‐P13, including some previously switched from originator, were prospectively followed during a switch to SB2. C‐reactive protein (CRP), trough infliximab level and clinical disease activity indices were collected at baseline, Infusion 3 or 4 (‘early’ after switch), and 1 year. Results One hundred eighty‐six patients (n = 99 second switch) on stable infliximab dosing underwent switching. Compared with baseline, there was no significant change in CRP, clinical disease activity scores or median trough infliximab level at the early time point among first‐switch (baseline vs early: 5.7 vs 6.6 µg/mL, P = 0.05) and second‐switch (4.3 vs 4.9 µg/mL, P = 0.07) patients nor at 1 year (median infliximab trough levels, baseline vs 1 year, in first‐switch [5.7 vs 5.7 µg/mL, P = 0.37] and second‐switch [4.3 vs 4.7 µg/mL, P = 0.06] patients). The proportion of patients in clinical remission did not significantly change at the early (92% vs 91% at baseline, P = 0.75) or 1 year (95% vs 91% at baseline, P = 0.16) time points. There was no significant difference in time to loss of response between patients switching for the first or second time (P = 0.69). Conclusions Switching from one infliximab biosimilar to another had no adverse impact on infliximab trough levels, and clinical and biochemical disease activity, regardless of whether switching for the first or second time.