Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. We performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab monotherapy or concurrent with other immunologic agents, such as ipilimumab. Sixty-one publications on 85 patients (mean age 66.9 years [range 34–86]; male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3.6 (range 1–28). Symptoms included oculomotor (47%), respiratory (43%), bulbar (35%), and proximal weakness (35%), as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%), or a combination of these (16%). After a critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 25% of patients had signs of additional NMDs. Cardiac complications occurred in more than 30% of patients diagnosed with myasthenia gravis or myositis. Mortality was high in these patients, despite adequate treatment strategies including corticosteroid, IV immunoglobulins, and plasma exchange. The clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with considerable overlap between myasthenia gravis and myopathy, and cardiac/respiratory complications are common.

The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia.

PurposeTo compare mean global cerebral blood flow (CBF) measured by phase‐contrast mapping magnetic resonance imaging (PCM MRI) and by 15O‐H2O positron emission tomography (PET) in healthy subjects. PCM MRI is increasingly being used to measure mean global CBF, but has not been validated in vivo against an accepted reference technique.Materials and MethodsSame‐day measurements of CBF by 15O‐H2O PET and subsequently by PCM MRI were performed on 22 healthy young male volunteers. Global CBF by PET was determined by applying a one‐tissue compartment model with measurement of the arterial input function. Flow was measured in the internal carotid and vertebral arteries by a noncardiac triggered PCM MRI sequence at 3T. The measured flow was normalized to total brain weight determined from a volume‐segmented 3D T 1‐weighted anatomical MR‐scan.ResultsMean CBF was 34.9 ± 3.4 mL/100 g/min measured by 15O‐H2O PET and 57.0 ± 6.8 mL/100 g/min measured by PCM MRI. The measurements were highly correlated (P = 0.0008, R2 = 0.44), although values obtained by PCM MRI were higher compared to 15O‐H2O PET (absolute and relative differences were 22.0 ± 5.2 mL/100 g/min and 63.4 ± 14.8%, respectively).ConclusionThis study confirms the use of PCM MRI for quantification of global CBF, but also that PCM MRI systematically yields higher values relative to 15O‐H2O PET, probably related to methodological bias. Level of Evidence: 3J. Magn. Reson. Imaging 2017;45:692–699.

Objective To assess the cost effectiveness of screening men aged 65 for abdominal aortic aneurysm. Design Cost effectiveness analysis based on a probabilistic, enhanced economic decision analytical model from screening to death. Population and setting Hypothetical population of men aged 65 invited (or not invited) for ultrasound screening in the Danish healthcare system. Data sources Published results from randomised trials and observational epidemiological studies retrieved from electronic bibliographic databases, and supplementary data obtained from the Danish Vascular Registry. Data synthesis A hybrid decision tree and Markov model was developed to simulate the short term and long term effects of screening for abdominal aortic aneurysm compared with no systematic screening on clinical and cost effectiveness outcomes. Probabilistic sensitivity analyses using Monte Carlo simulation were carried out. Results were presented in a cost effectiveness acceptability curve, an expected value of perfect information curve, and a curve showing the expected (net) number of avoided deaths from abdominal aortic aneurysm over time after the introduction of screening. The model was validated by calibrating base case health outcomes and expected activity levels against evidence from the recent Cochrane review of screening for abdominal aortic aneurysm. Results The estimated costs per quality adjusted life year (QALY) gained discounted at 3% per year over a lifetime for costs and QALYs was £43 485 (€54 852; $71 160). At a willingness to pay threshold of £30 000 the probability of screening for abdominal aortic aneurysm being cost effective was less than 30%. One way sensitivity analyses showed the incremental cost effectiveness ratio varying from £32 640 to £66 001 per QALY. Conclusion Screening for abdominal aortic aneurysm does not seem to be cost effective. Further research is needed on long term quality of life outcomes and costs.