Bilateral lung transplantation improves forced expiratory volume in 1 second and 6-minute walk tests significantly over single lung transplantation (p < 0.0001). Both perioperative mortality and Kaplan-Meier survival (to 3 years) are significantly improved when bilateral rather than single lung transplantation is used for chronic obstructive pulmonary disease in our series (p < 0.05). This is probably the result of significantly reduced primary graft failure.

Immune checkpoint inhibitors have become the mainstay of treatment for metastatic melanoma. This article presents a new case of acquired generalised lipodystrophy (AGL) during anti-programmed cell death-1 (anti-PD-1) therapy and a systematic review of the literature with an aim to further understand the pathogenesis. A comprehensive search was conducted using PubMed, Embase, MEDLINE and Cochrane Central databases. We identified four cases of lipodystrophy associated with anti-PD-1 immunotherapy, including our own. Of these, three were associated with nivolumab, and one with pembrolizumab. Body composition changes occurred at a median of 7 months after anti-PD-1 initiation. All cases reported AGL, with subcutaneous fat loss affecting majority of the body. There were three reported cases of insulin resistance associated with AGL. AGL should be a recognised adverse event associated with anti-PD-1 therapy.

BackgroundEndothelial dysfunction is associated with vascular risk factors such as dyslipidemia, hypertension, and diabetes, leading to coronary atherosclerosis. Sympathetic stress using cold-pressor testing (CPT) has been used to measure coronary endothelial function in humans with positron emission tomography (PET) myocardial blood flow (MBF) imaging, but is not practical in small animal models. This study characterized coronary vasomotor function in mice with [11C]acetate micro-PET measurements of nitric-oxide-mediated endothelial flow reserve (EFRNOM) (adrenergic-stress/rest MBF) and myocardial oxygen consumption (MVO2) using salbutamol β2-adrenergic-activation.Methods[11C]acetate PET MBF was performed at rest + salbutamol (SB 0.2, 1.0 μg/kg/min) and norepinephrine (NE 3.2 μg/kg/min) stress to measure an index of MBF response. β-adrenergic specificity of NE was evaluated by pretreatment with α-adrenergic-antagonist phentolamine (PHE), and β2-selectivity was assessed using SB.ResultsAdjusting for changes in heart rate × systolic blood pressure product (RPP), the same stress/rest MBF ratio of 1.4 was measured using low-dose SB and NE in normal mice (equivalent to human CPT response). The MBF response was correlated with changes in MVO2 (p = 0.02). Nitric oxide synthase (NOS)-inhibited mice (Ng-nitro-L-arginine methyl ester (L-NAME) pretreatment and endothelial nitric oxide synthase (eNOS) knockout) were used to assess the EFRNOM, in which the low-dose SB- and NE-stress MBF responses were completely blocked (p = 0.02). With high-dose SB-stress, the MBF ratio was reduced by 0.4 following NOS inhibition (p = 0.03).ConclusionsLow-dose salbutamol β2-adrenergic-stress [11C]acetate micro-PET imaging can be used to measure coronary-specific EFRNOM in mice and may be suitable for assessment of endothelial dysfunction in small animal models of disease and evaluation of new therapies.

BACKGROUNDDual checkpoint inhibition improves response rates in treatment naïve patients with metastatic melanoma compared to monotherapy. However, it confers a higher rate of toxicity, including immune-related colitis. Steroids may not resolve symptoms in all cases. The use of vedolizumab, a humanized monoclonal antibody against α4β7 integrin has proven effective in cases refractory to standard treatment.CASE SUMMARYWe report the case of a 27-year-old female with Stage IVd metastatic melanoma treated with ipilimumab and nivolumab. She developed severe colitis refractory to methylprednisolone, infliximab and mycophenolate mofetil but responded to vedolizumab.CONCLUSIONThis case report supports vedolizumab use in severe immune related colitis refractory to standard immunosuppression.

Précis: There are published cases of use of cyclosporine in dermatological toxicity with monotherapy but not with combination ipilimumab/nivolumab. AbstractCheckpoint inhibition is the mainstay of treatment in metastatic melanoma. More recently combined cytotoxic T-lymphocyte antigen-4 and programmed-death-1 blockade has resulted in improved response rates and overall survival in treatment naïve patients compared to monotherapy albeit with increased rates of adverse events. Dermatologic toxicities are an emerging consequence of the use of checkpoint inhibitors and have reportedly been more prevalent with the use of combined therapy. However, grade 3 and 4 adverse event rates are still less than 5%. Here, we report a case of a 63-year-old Caucasian male with metastatic melanoma treated with first line combined ipilimumab and nivolumab who then developed a steroid refractory, biopsy confirmed pityriasis lichenoides-like, drug related rash that resolved with cyclosporine. Time of onset was 24 days and presenting symptoms demonstrated a maculopapular rash presenting over the back and chest with pruritus. Unfortunately, the patient subsequently had multi-organ failure with acute kidney injury requiring dialysis, hypotension requiring vasopressor support, hepatic dysfunction, and bilateral lung infiltrates resulting in a fatal outcome. This case report highlights the effective use of cyclosporine as an immunomodulatory agent in the management of severe dermatological toxicity due to combination immunotherapy. K E Y W O R D Scutaneous toxicity, cyclosporine, immune therapy, ipilimumab, metastatic melanoma, nivolumab, steroid-refractory rash