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Introduction Pain which persists after thoracotomy is well recognized, and activation of the N‐methyl‐d‐aspartate (NMDA) receptor could be a contributing factor. This study sought to establish whether ketamine given peri‐operatively could reduce persistent post‐surgical pain. Trial design Double‐blind, randomized, placebo‐controlled trial comparing low‐dose intravenous ketamine and saline placebo. Methods Seventy patients undergoing thoracotomy were randomized to receive either intravenous ketamine (0.1 mg kg−1 hr−1) or saline placebo for 96 hr, starting 10 min prior to surgery. A bolus dose of 0.1 mg/kg of ketamine/placebo was given prior to starting the infusion. Post‐operative analgesia consisted of either an epidural infusion or patient‐controlled analgesia (PCA), +/− a paravertebral infusion of local anaesthetic. Pain scores and opioid consumption were collected at 24 and 48 hr after surgery. Patients completed numeric pain scores (NPS), modified Brief Pain Inventory (BPI), the short form Leeds Assessment of Neuropathic Symptoms and Signs (S‐Lanss) at baseline, 6 weeks, 3, 6 and 12 months after surgery. Results There were no significant differences in post‐operative pain, except the ketamine group reported less pain at rest 48 hr after surgery (p = 0.03). The ketamine group requested significantly less morphine via PCA in the first 24 hr (p = 0.03). There were no differences in pain measures or opioid consumption at 6 weeks, 3, 6 or 12 months. Patients in the ketamine group were more lightheaded (p = 0.02) and experienced more vivid dreams (p = 0.001). Conclusions Ketamine reduced opioid consumption compared to placebo after surgery, but we were unable to detect any differences in persistent post‐surgical pain between the groups. Significance This study adds to the growing body of evidence advocating the use of ketamine to reduce opioid consumption. No previous studies of peri‐operative ketamine have followed patients for a year after thoracotomy. This study found no reduction in persistent post‐surgical pain.

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants.

Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and adolescents. OS has a 60% survival rate with current treatments; hence, there is a need to identify novel adjuncts to chemotherapeutic regimens. In this pilot study, we investigated the dose-response to 1a,25-dihdroxyvitamin D 3 (1,a 25(OH) 2 Keywords: osteosarcoma; vitamin D; proliferation; differentiation; apoptosis Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and adolescents.1 Current chemotherapy regimens and surgical interventions have not led to significant improvement in the present 60-70% survival rate. In addition, therapies in OS have remained relatively unchanged over the past 20 years. 2,3 There is a need to identify novel therapeutic regimens to improve survival rates for individuals over those achieved with the current treatment approaches.The active form of vitamin D, 1a,25-dihdroxyvitamin D 3 (1a,25(OH) 2 D 3 ) is increasingly recognized for its anti-cancer properties. 4,5 The main biologic function of 1a,25(OH) 2 D 3 is to maintain serum calcium levels within normal range by increasing the efficiency of intestinal absorption of dietary calcium 6,7 and mobilizing calcium stores from the bone into circulation.8-10 Extra-skeletal cells and tissues produce 1a,25(OH) 2 D 3 .7 By binding to the nuclear vitamin D receptor (VDR), 1a,25(OH) 2 D 3 regulates expression of genes responsible for cellular proliferation, differentiation, apoptosis, and angiogenesis in local tissues. 11,12Previous studies demonstrate that 1a,25(OH) 2 D 3 inhibits proliferation and enhances differentiation of OS cells. [13][14][15][16] The mechanisms by which 1a, 25(OH) 2 D 3 regulates proliferation and differentiation in OS are not completely understood. Evidence that 1a,25(OH) 2 D 3 induces apoptosis in canine OS cells comes from TUNEL studies detecting DNA fragmentation, a hallmark of apoptotic cells.17 Studies in rodent and human OS cell lines are contradictory. Those studies show that 1a,25(OH) 2 D 3 either inhibits 15,18,19 or has no effect on apoptosis.20 There are significant unknowns and contradictions in the current literature on the effects of 1a,25(OH) 2 D 3 on OS cells. The doseresponse to 1a,25(OH) 2 D 3 by different OS cells is not well-defined or characterized. The mechanisms involving inhibition of proliferation and promotion of differentiation remain unclear.The objectives of this pilot study were to determine the dose-response to 25(OH)D 3 or 1a,25(OH) 2 D 3 by OS cell lines, and thus, to identify the effects of vitamin D (25D or 1a,25(OH) 2 D 3 ) on cellular processes in human OS cell lines: SaOS-2 and 143B. The rationale for choosing the above mentioned cell lines versus other Additional supporting information may be found in the online version of this article.

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