Rare case of life-threatening thrombocytopenia occurring after radiotherapy in a patient treated with immune checkpoint inhibitor.

Immune checkpoint inhibitors (ICIs) improve significantly outcome of patients with advanced renal cancer. Although immune-related adverse events involve frequently skin, digestive tract, lung, liver and endocrine organs, haematological toxicities are rare. We describe the case of a patient with metastatic renal cancer who was treated with nivolumab. Eight courses of nivolumab were administered without any toxicity; brain metastases were then diagnosed and treated with stereotactic radiotherapy. As the extra-cranial disease was stable, the ninth course of nivolumab was administered 5 days after the end of radiotherapy. One week later, he presented with rectal and nasal bleeding in a context of severe thrombocytopenia (1000/mm3). High dose of steroids and intravenous immunoglobulin reversed slowly the thrombocytopenia. This case highlights the possibility of life-threatening thrombocytopenia with ICIs. Interestingly, the close time relation with radiotherapy highlights a potential interaction, warranting a close follow-up of patients in this situation.

Isolated adrenocorticotropic hormone (ACTH) deficiency and Guillain-Barré syndrome occurring in a patient treated with nivolumab.

The increased use of immune checkpoint inhibitors (ICIs) has led to the observation of a variety of immune-related adverse events (irAEs). These irAEs occur usually within the first months after ICIs onset and can involve theorically all organs. We describe two rare irAEs occurring in a 70-year-old caucasian man who was treated with nivolumab for an advanced urothelial cancer of the left kidney. He developed an isolated adrenocorticotropic hormone deficiency that was diagnosed at week 19 and a neurological complication that appeared at week 79 and initially confounded with a lumbar spinal stenosis. Diagnosis of Guillain-Barré syndrome was finally confirmed with the complete resolution of symptoms after 5 days of intravenous immunoglobulin and corticosteroids. We highlight the importance of quickly recognising these potential life-threatening irAEs such as cortisol insufficiency and neurologic adverse events whose initially presentation could be non-specific.

Cascade of immunologic adverse events related to pembrolizumab treatment.

Immune checkpoint inhibitors, such as pembrolizumab, have significantly improved cancer patient outcome. Toxicities are usually moderate and manageable. However, some adverse events, if not early recognised, could be life-threatening. We report a patient with non-small cell lung cancer who received treatment with pembrolizumab and developed multiple immune-related adverse events both during and after completing treatment, including rash, pericarditis, colitis and myasthenia gravis.

Immune checkpoint inhibitors as a real hope in advanced urothelial carcinoma.

Metastatic urothelial cancer is an aggressive disease associated with a poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. After failure of platinum-based therapy and in cisplatin-ineligible patients, therapeutic options are limited. Malignant cells evolve mechanisms to evade immune recognition, including the expression of cell-surface molecules, named immune checkpoints, on tumor and tumor-specific lymphocytes. Immunotherapy, by targeting these checkpoints, represents a new tool to improve the patient outcome in advanced urothelial carcinoma (UC). Recently, the US FDA approved, in a short time, several immune checkpoint inhibitors in metastatic UC, both after failure of platinum-based therapy and in first-line setting in cisplatin-ineligible patients. This article aims to review the place of immunotherapy in advanced UC.

Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108.

Identification, management and outcome of postoperative hemoperitoneum in 23 horses after emergency exploratory celiotomy for gastrointestinal disease.

OBJECTIVE: To investigate postoperative hemoperitoneum in a population of horses that had surgery for colic. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 23). METHODS: Preoperative, intraoperative, and postoperative information was obtained from medical records (1985-2012) of horses with postoperative hemoperitoneum after emergency exploratory celiotomy. Pre-existing hemoperitoneum during surgery and nonsurgical hemoperitoneum were excluded. RESULTS: Of 4520 horses that had emergency exploratory celiotomy for gastrointestinal disease, 23 horses met inclusion criteria; an incidence of 0.5%. Horse signalment approximated the colic population, although Thoroughbreds were significantly overrepresented. Hemoperitoneum was significantly associated with intestinal resection. Postoperative hemoperitoneum was recognized a mean (± SD) of 1.0 ± 0.7 days after surgery and associated with tachycardia, decreasing hematocrit, incisional drainage, or ultrasonographic identification of swirling, echogenic abdominal fluid. Primary treatments included intravenous fluid therapy (n = 23), colloid support (20), blood transfusion (13), and antifibrinolytic agents (11). Fifteen horses (65%) survived to discharge, which was associated with admission lactate and days of hospitalization. CONCLUSIONS: Postoperative hemoperitoneum is a rare complication of exploratory celiotomy in horses that should be considered when there are signs of abdominal discomfort and declining hematocrit in the early postoperative period. Prognosis is guarded because of potential sequelae of septic peritonitis and adhesion formation.

Peritoneal and plasma D-lactate concentrations in horses with colic.

OBJECTIVE: To evaluate the association between peritoneal fluid and plasma d-lactate concentration with variables used in the diagnosis and prognosis of horses with colic. ANIMALS: Clinically healthy horses (n=6) and 90 horses with colic. STUDY DESIGN: Prospective cross-sectional study. METHODS: D-lactate concentration was determined in peritoneal fluid and plasma of all horses. Information on other blood and peritoneal fluid variables, signalment, results from the physical examination, outcome, need for surgery, lesion location, and type was retrieved from medical records. RESULTS: Peritoneal D-lactate concentration was strongly correlated with plasma D-lactate concentration (r=0.71; P<.001). Peritoneal and plasma D-lactate concentrations were positively correlated with peritoneal (r=0.8; P<.001) and plasma L-lactate (r=0.33; P=.001) concentrations, respectively. Peritoneal D-lactate concentration was negatively correlated with survival to discharge (U=430.5; P<.001). Median peritoneal D-lactate concentration of horses with septic peritonitis (455.2 µmol/L) and horses with gastrointestinal rupture (599.5 µmol/L) were higher compared with horses with nonstrangulating obstructions (77.7 µmol/L). A cut-off concentration of peritoneal D-lactate of 116.6 µmol/L had a sensitivity of 0.813 and a specificity of 0.651 to differentiate between nonstrangulating and strangulating obstructions. CONCLUSIONS: Peritoneal D-lactate concentration may be more useful for identifying horses with strangulating obstructions (high sensitivity, low probability of a false negative) than to ruling out strangulating obstruction (moderate specificity, high probability of a false positive).

Pull-through technique for palmar digital neurectomy: forty-one horses (1998-2004).

OBJECTIVES: To report outcome of horses treated for navicular syndrome using a pull-through (PT) technique for palmar digital neurectomy (PDN). DESIGN: Retrospective study. ANIMALS: Horses (n=41) with navicular syndrome (NS). METHODS: Medical records (1998-2002) for horses that had NS and failed to respond to conservative management that had unilateral or bilateral forelimb, biaxial PDN were reviewed. Outcome for up to 6 years was obtained by telephone questionnaire or lameness examination. Survival analysis was used to assess time to recurrence of lameness. RESULTS: One year after PDN, 36 horses (88%) were free of lameness. Mean survival with no lameness after surgery was estimated at 4.14+/-0.33 years (median, 5 years). CONCLUSIONS: PT-PDN technique resulted in soundness for 88% of horses for at least 1 year. PT-PDN was easily and quickly performed without specialized equipment, and had a low incidence of complications. CLINICAL RELEVANCE: The PT technique is an effective and viable alternative surgical method for PDN.