This inhibition blocks the PD-L1 and PL-L2 ligands located on the surface of normal tissue cells from binding to PD-1 receptors on activated T-cells and thereby blocks the T-cells from organizing an inflammatory response that kills the normal cells. Tumor cells may use this inflammation-evading tactic: they may express PD-L1/PD-L2 and thereby block the T-cell-mediated immune responses to them (see Immune checkpoint). From ~47% to ~73% of UPS cases contain tumor cells that express PD-L1. In a retrospective review of 10 patients with UPS, 1 patient had a complete response, 3 had partial responses, and 6 had no response to pembrolizumab. (Further studies of the 4 pembrolizumab-responsive patients indicated that their tumor cells expressed PD-L1 in two cases but not in the other two cases.) In a retrospective study of 25 patients (21 patients treated with pembrolizumab, 4 treated with other immunotherapy agents), 7 attained stable disease, 7 attained partial responses, and 1 attained a complete response. In a study of 16 patients with UPS, 5 achieved short-term (lasting 1.2 to 1.4 months) stable disease in response to a regimen of pembrolizumab combined with the chemotherapy drug, cyclophosphamide. It is clear that new treatment strategies as well as further studies on the efficacy of pembrolizumab and similarly acting immunotherapy drugs used with or without radiotherapy and/or chemotherapy over longer time periods are needed to evaluate their usefulness in treating UPS. References


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Spasmodic croup is caused by the same group of viruses as acute laryngotracheitis, but lacks the usual signs of infection (such as fever, sore throat, and increased white blood cell count). Treatment, and response to treatment, are also similar. Bacteria and cocci
Croup caused by a bacterial infection is rare. Bacterial croup may be divided into laryngeal diphtheria, bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis. Laryngeal diphtheria is due to Corynebacterium diphtheriae while bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis are usually due to a primary viral infection with secondary bacterial growth. The most common cocci implicated are Staphylococcus aureus and Streptococcus pneumoniae, while the most common bacteria are Haemophilus influenzae, and Moraxella catarrhalis. Pathophysiology
The viral infection that causes croup leads to swelling of the larynx, trachea, and large bronchi due to infiltration of white blood cells (especially histiocytes, lymphocytes, plasma cells, and neutrophils). Swelling produces airway obstruction which, when significant, leads to dramatically increased work of breathing and the characteristic turbulent, noisy airflow known as stridor. Diagnosis
Croup is typically diagnosed based on signs and symptoms. The first step is to exclude other obstructive conditions of the upper airway, especially epiglottitis, an airway foreign body, subglottic stenosis, angioedema, retropharyngeal abscess, and bacterial tracheitis.A frontal X-ray of the neck is not routinely performed, but if it is done, it may show a characteristic narrowing of the trachea, called the steeple sign, because of the subglottic stenosis, which resembles a steeple in shape.