Refractory Fulminant Colitis Requiring Surgical Intervention in a Patient With Ulcerative Colitis on Atezolizumab Therapy for Small Cell Lung Cancer: An Atypical Case.

Atezolizumab is a programmed death-ligand 1 (PD-L1) targeted antibody that prevents the binding of PD-L1 to specific T-cell receptors, thereby increasing anticancer immunity. It has been regarded as a useful first-line treatment in patients with small-cell lung cancer with a more tolerable side effect profile than chemotherapeutic agents. However, few studies focusing on the severity of adverse effects from immune checkpoint inhibitors (ICPI) have been previously reported, particularly acute fulminant colitis requiring surgical invention. We report a case of fulminant colitis refractory to high dose corticosteroid treatment in a patient with known ulcerative colitis (UC) undergoing treatment for small-cell lung cancer (SCLC) with atezolizumab. The upregulation of PD-L1 expression in patients with ulcerative colitis may play a significant role in an imbalanced T-helper cell response creating a pro-inflammatory state. The use of ICPIs to treat SCLC has been reported to increase the risk of developing inflammatory colitis. Atezolizumab use in a patient with known inflammatory bowel disease (IBD) may predispose this population to a higher risk of developing severe inflammatory colitis. We present an unusual complication associated with medical intervention in an immunocompromised patient without an established pathophysiology. The suspicion of using ICPIs in patients with IBD as a potential cause for the development of fulminant colitis is relevant and essential in the diagnostic workup for this patient population complaining of significant gastrointestinal symptoms.

Rapid and robust restoration of breathing long after spinal cord injury.

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess serotonergic (5HT) axon sprouting leading to aberrant tonic activity in the diaphragm that could be mitigated via 5HT2 receptor blockade. Through unmasking of the continuing neuroplasticity that develops after injury, our treatment strategy ensured rapid and robust patterned respiratory recovery after a near lifetime of paralysis.