Real-world assessment of isocitrate dehydrogenase inhibitor-associated differentiation syndrome.

Ivosidenib and enasidenib are targeted agents that inhibit mutant isocitrate dehydrogenase (IDH) enzymes, restoring normal cellular differentiation in affected acute myeloid leukemia patients. Both agents carry a risk of differentiation syndrome (DS), a potentially life-threatening complication. In this multicenter, retrospective study we sought to determine the real-world incidence and characterize DS in patients with a myeloid malignancy treated with an IDH inhibitor. Of 49 total patients, 15 patients (31%) had a documented diagnosis of DS and 8 patients (16%) met the criteria of DS by Montesinos, et al. The most common signs and symptoms of DS were dyspnea/hypoxia (56%), unexplained fever (56%), bone pain/arthralgia (44%), edema/weight gain (39%), and pleural/pericardial effusions (33%). Our study reports a higher real-world incidence of DS in patients treated with IDH inhibitors for myeloid malignancies than previously reported.

Paramedian incisional complications after prophylactic laparoscopy-assisted gastropexy in 411 dogs.

OBJECTIVE: To determine the frequency and types of paramedian incisional complications after prophylactic laparoscopy-assisted gastropexy (LAG) in dogs and to evaluate potential risk factors for complications. STUDY DESIGN: Multi-institutional retrospective study. ANIMALS: Client-owned dogs (N = 411). METHODS: Records for dogs that underwent single-incision-port laparoscopy-assisted gastropexy (SIPLAG) or multiple-port laparoscopy-assisted gastropexy (MPLAG) at five veterinary referral hospitals were reviewed. Information regarding signalment, surgical procedures, perioperative care, and incisional complications was collected. Follow-up information was obtained by review of medical records and/or communication with owners. Potential risk factors for complications were examined statistically. RESULTS: Paramedian incisional complications were observed in 78 of 411 (19%) dogs. The most common complication was seroma formation, which occurred in 51 (12.4%) dogs. Surgical site infections were observed in 16 (3.9%) dogs, and dehiscence or development of excessive scar tissue at the incision site were each observed in nine (2.2%) dogs. Complications resolved with conservative treatment in 75 of 78 (96.2%) dogs and with surgical treatment in three of 78 (3.8%) dogs. The odds of complications were approximately twice as high in dogs undergoing SIPLAG than in dogs undergoing MPLAG (odds ratio, 2.03; P = .006). CONCLUSION: Minor paramedian incisional complications, particularly seroma formation, were frequently observed after LAG. Most complications were successfully managed conservatively. Single-incision-port laparoscopy-assisted gastropexy was associated with a higher complication rate compared with MPLAG. CLINICAL SIGNIFICANCE: Owners should be informed that there is a relatively high rate of minor paramedian incisional complications after LAG. The risk of complications appears to be higher for SIPLAG than for MPLAG.

Minimally invasive small intestinal exploration and targeted abdominal organ biopsy with a wound retraction device in 42 cats (2005-2015).

OBJECTIVE: To describe the surgical technique and evaluate short-term outcome after minimally invasive small intestinal exploration and targeted organ biopsy with a wound retractor device (WRD) in cats. STUDY DESIGN: Multi-institutional retrospective study. ANIMALS: Forty-two cats. METHODS: A wound retractor was inserted into the abdomen on the ventral midline through a 2-4 cm incision at the level of the umbilicus. Short segments (6-10 cm long) of intestinal tract were sequentially exteriorized and explored through the WRD. Full thickness, small intestinal biopsies were obtained extracorporeally via the WRD. A commercially available single-port device was inserted through the WRD for laparoscopic exploration of the abdomen. RESULTS: The majority of the small intestine could be exteriorized and explored through the WRD. In all cases, full thickness biopsies of the small intestine of diagnostic quality were obtained. The most common histological findings were inflammatory bowel disease (n = 16), intestinal lymphoma (n = 14), and eosinophilic enteritis (n = 7). Two cases required conversion to a traditional open laparotomy due to abdominal pathology diagnosed after placement of the WRD (abdominal adhesions and need for a splenectomy). Postoperative complications occurred in 4 of 39 cats (10.3%), leading to 2 deaths after discharge from the hospital. CONCLUSIONS AND CLINICAL RELEVANCE: MISIETB with a WRD alone or combined with laparoscopy is a safe technique for small intestinal exploration and targeted abdominal organ biopsy in cats. Single-port laparoscopy can effectively be performed through the WRD for complete abdominal exploration and biopsy of abdominal organs.

BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia.

The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs.

Ado-trastuzumab emtansine (T-DM1): a novel antibody-drug conjugate for the treatment of HER2-positive metastatic breast cancer.

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is an aggressive form of breast cancer associated with poorer prognosis and shortened survival. Primary and acquired resistance to existing HER2-targeted therapies presents a challenge for the management of patients with HER2-positive metastatic breast cancer. Ado-trastuzumab emtansine, a drug-antibody conjugate, has shown promising results for patients failing prior treatment with trastuzumab. Ado-trastuzumab emtansine consists of the monoclonal antibody trastuzumab linked to a potent microtubule inhibitor (emtansine), allowing a targeted delivery of chemotherapy to cells that overexpress HER2. Ado-trastuzumab emtansine has been approved for use in patients with metastatic breast cancer who have failed prior therapy with trastuzumab and a taxane. Although well-tolerated in clinical trials, thrombocytopenia has been reported and platelet values should be monitored closely. Increased liver enzymes and bilirubin, as well as cardiotoxicity, have also been documented, and recommendations for dose reduction or discontinuation due to these toxicities are available. Clinical trials are currently ongoing to further define the role of ado-trastuzumab emtansine in both the metastatic and early breast cancer settings.