Rejected

Chronic mesenteric ischemia most frequently presents with abdominal pain, weight loss, and food fear. Ischemic involvement of the liver is infrequent because of the dual blood supply via the portal vein and hepatic artery. Hepatic infarction has been associated with embolization, thrombosis, arterial injury, prothrombotic states, and impairment of portal venous flow. We report a patient with chronic mesenteric ischemia and severe mesenteric arterial disease who presented with large liver masses suspicious for neoplasm. Tissue samples from two hepatic biopsies confirmed ischemic lesions. After open surgical mesenteric revascularization, the patient had complete symptom improvement and nearly complete regression of the liver lesions.

Ramucirumab is a fully human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2). An initial phase I study evaluated ramucirumab administered weekly in advanced cancer patients. This phase I study of ramucirumab [administered every 2 or 3 weeks (Q2W or Q3W)] examined safety, maximum tolerated dose, pharmacokinetics, immunogenicity, antitumor activity, and pharmacodynamics.

Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is a potentially fatal complication, which occurs in 7-27% of children undergoing hematopoietic stem cell transplantation. In this article, we review commonly accepted diagnostic criteria, atypical diagnostic features as well as preventative and treatment measures associated with VOD. Reversal of portal venous flow by Doppler ultrasound is often a late finding; many patients with anicteric VOD may never develop hyperbilirubinemia, and yet perish from severe VOD. Transjugular liver biopsy is usually not available and/or is often avoided. Prophylactic therapies with ursodeoxycholic acid, heparin and defibrotide are discussed. Supportive care with fluid restriction and diuretic therapy, analgesia, blood and platelet transfusions, paracentesis as well as other pulmonary and renal therapies remain imperative to superior outcomes. Specific therapy with thrombolytics such as defibrotide and recombinant tissue plasminogen activator is discussed and a classification of severity of VOD is proposed.

Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL).

Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC.

Sedation and analgesia using opioids and benzodiazepines is frequently required in critically ill children to minimize pain and anxiety. In some patients, difficult sedation occurs when tolerance or unacceptable side effects limit the efficacy of conventional analgo-sedative treatment. We describe seven patients (age range 1 to 17 yr) where difficult sedation was successfully managed with enteral levomepromazine (LMZ). LMZ is a neuroleptic antipsychotic agent that exhibits potent analgo-sedative properties without respiratory depression, through non-opioid and non-benzodiazepine pathways. We describe its use in our pediatric intensive care unit to control agitation in patients with known behavioral disorders who frequently pose a significant sedation challenge. We also illustrate its successful use in cases of withdrawal syndrome and delirium, and discuss the association of fever and its distinction from neuroleptic malignant syndrome in two patients. LMZ should be considered as a useful sedative in critically ill children where difficult sedation occurs and conventional agents are exhausted.

This review presents the pathogenesis and medical treatment of equine osteoarthritis (OA), focusing on firocoxib. Inhibition of prostaglandin E remains a fundamental treatment for decreasing clinical symptoms (ie, pain and lameness) associated with OA in horses. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the production of prostaglandin E from the arachidonic acid pathway, continue to be a mainstay for the clinical treatment of OA. Firocoxib is a cyclooxygenase (COX)-2-preferential NSAID that has been shown to be safe and to have a 70% oral bioavailability in the horse. Three clinical reports identified symptom-modifying effects (reduction in pain and/or lameness) in horses with OA administered the once-daily recommended dose (0.1 mg/kg) of oral firocoxib following 7 days of administration. Other reports have suggested that a one-time loading dose (0.3 mg/kg) of firocoxib provides an earlier (1-3 days) onset of action compared to the recommended dose. It is noteworthy that OA disease-modifying effects have been reported in horses for other COX-2-preferential NSAIDs (meloxicam and carprofen), but have not been attributed to firocoxib due to a lack of investigation to date.

Twenty adult female goats affected with chronic mastitis were subjected to mastectomy or hemimastectomy under subarachnoid regional analgesia using a ketamine-lidocaine combination. Ketamine at 1.5 mg/kg and lidocaine hydrochloride at 1.25 mg/kg were administered intrathecally at the lumbosacral intervertebral space. Goats were then subjected to a 120-minute observation period for systemic or neurotoxic symptoms such as agitation, restlessness, hind limb paralysis, or seizures. In addition, analgesia of the caudal abdominal region and signs of systemic sedation were scored on a scale of 0-3. Heart rate, respiratory rate, and rectal temperature were also recorded prior to (baseline values) and at 5, 15, 30, 60, 90, and 120 minutes after administration. Mastectomy or hemimastectomy operation was carried out after full assurance of the analgesic effect on the udder and caudal abdominal region. Time of onset of surgical analgesia (score 3) was achieved at 15 minutes and lasted for 60 minutes. Maximal sedation score was recorded at 15 minutes and lasted for 60 minutes, then decreased thereafter, with the lowest sedation score recorded at 120 minutes. There was a significant (0.05) rise in heart rate at some point between 5-90 minutes, while the respiratory rate and rectal temperature did not change significantly from baseline values. Postoperatively, animals did not show any signs of pain or discomfort. Follow-up on the operated goats showed that all wounds were fully healed without any significant complications. In goats, intrathecal administration of ketamine-lidocaine combination resulted in a safe and effective analgesia of the caudal abdominal and udder region sufficient to perform mastectomy or hemimastectomy.

Large multivesicular liposomes (LMVV) remotely loaded with bupivacaine (Bupisome) were previously demonstrated to be a stable, long-acting local anesthetic. We demonstrate that this is not the case for small unilamellar vesicles (SUV) of the same lipid composition also remotely loaded with bupivacaine. We show that the trapped volume in LMVV is 21-fold higher and the drug-to-lipid mole ratio is 10-fold higher than in SUV. Cryo-transmission electron micrographs and differential interference contrast microscopy show that there are no bupivacaine crystals inside LMVV and SUV. The thermotropic characterization studied by DSC demonstrates that the drug interacts with the liposome membrane, which, together with the above results on the drug-to-lipid ratio, explains the small in vitro drug release from the SUV and large (but <100%) release from the LMVV after 24 h at 37 °C. The absence of analgesia in mice treated locally with SUV loaded with bupivacaine compared with prolonged analgesia from LMVV correlates well with the in vitro results. The study indicates that in LMVV and SUV, part of the bupivacaine is associated with the liposomal membrane, which is poorly available for analgesia. The membrane fraction is very high in SUV and much smaller in LMVV. The much larger trapped volume of the LMVV explains the higher drug availability and better analgesia of LMVV.

In the United States, chronic pain affects at least 116 million Americans, differentially impacting older adults. One of the leading causes of pain for older adults is osteoarthritis. This disease affects approximately 14% of the United States population and can cause disability and mobility problems, in addition to having a high cost for the healthcare system. The methods individuals use to manage their pain are contingent upon their model of the disease (e.g., their beliefs about osteoarthritis pain management). The purpose of the present investigation was to: 1) understand what variables older adults with osteoarthritis believe impact pain, and 2) understand current approaches for self-management of osteoarthritis pain. We conducted structured interviews with eight older adults who have osteoarthritis. The interviews revealed current approaches in pain management, as well as gaps in knowledge. We propose an expansion of the idea of a general disease model for pain management that is patient-centered, allowing for personal customization of factors for reducing pain and increasing successful pain-management.