A Retrospective Cohort Study of Cerebrovascular Fibromuscular Dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare vasculopathy for which limited data are available particularly from Europe. Our aim was to study the clinical characteristics of a regional cohort of carotid fibromuscular dysplasia patients to assess their clinical outcomes and the rate of vascular complications. METHODS: A retrospective cohort study of all cases of carotid/cerebrovascular FMD presenting to our regional vascular service (catchment population approximately 2 million), between 1998 and 2020. Imaging reports and patient case notes were screened using the keywords "FMD", "Fibromuscular Dysplasia", and "carotid". From case-note and imaging review, all relevant clinical data were extracted and the anatomical extent of vascular disease recorded. RESULTS: Eighty six patients with a diagnosis of cerebrovascular fibromuscular dysplasia were identified on imaging (31 computed tomography angiography, 46 magnetic resonance angiography, and 9 digital subtraction angiography) by a neurovascular radiologist. The mean age was 64 years, 78 (90%) patients were female, and 45/59 (75%) were Caucasian. Presenting clinical syndromes were Stroke/transient ischemic attack in 54 (63%) patients, symptomatic intracranial aneurysm in 6 (10%), and other neurological symptoms (headache/migraine, tinnitus) in 14 (16%), with 11 (13%) presenting incidentally. Six patients (7%) had a positive family history of FMD (2 patients) or other cerebrovascular event (4 patients: carotid dissection, intracerebral bleed, or stroke). Eight patients (9%) had a known or suspected hereditary connective tissue disorder (2 Ehlers-Danlos syndrome). Involved vessels were as follows: Carotid (mainly extracranial) in 79 (92%), vertebral 19 (22%), and a combination of these in 15 (17%) patients. Fifty eight (67%) patients had bilateral disease. Cerebrovascular complications were observed in 35 (41%) patients as follows: carotid dissection 11 (23%), carotid stenosis or occlusion 8 (9%), carotid aneurysm 8 (9%), cerebral aneurysm 9 (11%), vertebral aneurysm/dissection 2 (2%), and carotid-cavernous fistula 2 (2%). Of the 22 patients who had extracranial imaging, 14 (60%) had FMD affecting other beds-renal artery in 8 (36%) patients, other visceral arteries in 4 (18%), and aorta in 2 (9%). In addition, 4 (18%) patients had aneurysm or dissection affecting renal, splenic, and lower limb arteries. Overall, 67 (80%) patients had FMD affecting more than 1 vessel and 50 (58%) had multisite FMD (>/ = 2 vascular beds involved). Fifty nine (68%) patients were managed conservatively on close surveillance. Nineteen (21%) patients required carotid/cerebrovascular intervention and 9 (10%) required vascular intervention at other sites. Recurrent cerebrovascular events (stroke/transient ischemic attack, symptomatic Berry aneurysm) were seen in 20 (23%) patients. Overall mortality was 7% over a median follow-up period of 47 months. CONCLUSIONS: Carotid FMD patients have a high rate of multisite involvement, extracerebral vascular complications, and evidence of hereditary vasculopathy, requiring careful screening and surveillance.

PD-L1.

Programmed death ligand 1 (PD-L1) is the principal ligand of programmed death 1 (PD-1), a coinhibitory receptor that can be constitutively expressed or induced in myeloid, lymphoid, normal epithelial cells and in cancer. Under physiological conditions, the PD-1/PD-L1 interaction is essential in the development of immune tolerance preventing excessive immune cell activity that can lead to tissue destruction and autoimmunity. PD-L1 expression is an immune evasion mechanism exploited by various malignancies and is generally associated with poorer prognosis. PD-L1 expression is also suggested as a predictive biomarker of response to anti-PD-1/PD-L1 therapies; however, contradictory evidence exists as to its role across histotypes. Over the years, anti-PD-1/PD-L1 agents have gained momentum as novel anticancer therapeutics, by inducing durable tumour regression in numerous malignancies including metastatic lung cancer, melanoma and many others. In this review, we discuss the immunobiology of PD-L1, with a particular focus on its clinical significance in malignancy.

Is transoral robotic surgery a safe and effective multilevel treatment for obstructive sleep apnoea in obese patients following failure of conventional treatment(s)?

A best evidence topic was written according to a structured protocol. The question addressed was whether TransOral Robotic Surgery (TORS) is a safe and effective multilevel treatment for Obstructive Sleep Apnoea (OSA) in obese patients following failure of conventional treatment(s). A total of 39 papers were identified using the reported searches of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Existing treatments for OSA - primarily CPAP - though highly effective are poorly tolerated resulting in an adherence often lower than 50%. As such, surgery is regaining momentum, especially in those patients failing non-surgical treatment (CPAP or oral appliances). TORS represents the latest addition to the armamentarium of Otorhinolaryngologists - Head and Neck Surgeons for the management of OSA. The superior visualisation and ergonomics render TORS ideal for the multilevel treatment of OSA. However, not all patients are suitable candidates for TORS and its suitability is questionable in obese patients. In view of the global obesity pandemic, this is an important question that requires addressing promptly. Despite the drop in success rates with increasing BMI, the success rate of TORS in non-morbidly obese patients (BMI = 30-35kgm-2) exceeds 50%. A 50% success rate may at first seem low, but it is important to realize that this is a patient cohort suffering from a life-threatening disease and no option left other than a tracheostomy. As such, TORS represents an important treatment in non-morbidly obese OSA patients following failure of conventional treatment(s).