Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer:A case report

BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Integrated silicon ohotonic MEMS

Silicon photonics has emerged as a mature technology that is expected to play a key role in critical emerging applications,including very high data rate optical communications,distance sensing for autonomous vehicles,photonic-accelerated computing,and quantum information processing.The success of silicon photonics has been enabled by the unique combination of performance,high yield,and high-volume capacity that can only be achieved by standardizing manufacturing technology.Today,standardized silicon photonics technology platforms implemented by foundries provide access to optimized library components,including low-loss optical routing,fast modulation,continuous tuning,high-speed germanium photodiodes,and high-effciency optical and electrical interfaces.However,silicon's relatively weak electro-optic effects result in modulators with a significant footprint and thermo-optic tuning devices that require high power consumption,which are substantial impediments for very large-scale integration in silicon photonics.Microelectromechanical systems(MEMS)technology can enhance silicon photonics with building blocks that are compact,low-loss,broadband,fast and require very low power consumption.Here,we introduce a silicon photonic MEMS platform consisting of high-performance nano-opto-electromechanical devices fully integrated alongside standard silicon photonics foundry components,with wafer-level sealing for long-term reliability,flip-chip bonding to redistribution interposers,and fibre-array attachment for high port count optical and electrical interfacing.Our experimental demonstration of fundamental silicon photonic MEMS circuit elements,including power couplers,phase shifters and wavelength-division multiplexing devices using standardized technology lifts previous impediments to enable scaling to very large photonic integrated circuits for applications in telecommunications,neuromorphic computing,sensing,programmable photonics,and quantum computing.

Wafer-level hermetically sealed silicon photonic MEMS

The emerging fields of silicon(Si) photonic micro–electromechanical systems(MEMS) and optomechanics enable a wide range of novel high-performance photonic devices with ultra-low power consumption, such as integrated optical MEMS phase shifters, tunable couplers, switches, and optomechanical resonators. In contrast to conventional SiO;-clad Si photonics, photonic MEMS and optomechanics have suspended and movable parts that need to be protected from environmental influence and contamination during operation. Wafer-level hermetic sealing can be a cost-efficient solution, but Si photonic MEMS that are hermetically sealed inside cavities with optical and electrical feedthroughs have not been demonstrated to date, to our knowledge. Here, we demonstrate wafer-level vacuum sealing of Si photonic MEMS inside cavities with ultra-thin caps featuring optical and electrical feedthroughs that connect the photonic MEMS on the inside to optical grating couplers and electrical bond pads on the outside. We used Si photonic MEMS devices built on foundry wafers from the iSiPP50G Si photonics platform of IMEC, Belgium. Vacuum confinement inside the sealed cavities was confirmed by an observed increase of the cutoff frequency of the electro-mechanical response of the encapsulated photonic MEMS phase shifters, due to reduction of air damping. The sealing caps are extremely thin, have a small footprint, and are compatible with subsequent flip-chip bonding onto interposers or printed circuit boards. Thus, our approach for sealing of integrated Si photonic MEMS clears a significant hurdle for their application in high-performance Si photonic circuits.