Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.
BackgroundDelays to timely admission from emergency departments (EDs) are known to harm patients.ObjectiveTo assess and quantify the increased risk of death resulting from delays to inpatient admission from EDs, using Hospital Episode Statistics and Office of National Statistics data in England.MethodsA cross-sectional, retrospective observational study was carried out of patients admitted from every type 1 (major) ED in England between April 2016 and March 2018. The primary outcome was death from all causes within 30 days of admission. Observed mortality was compared with expected mortality, as calculated using a logistic regression model to adjust for sex, age, deprivation, comorbidities, hour of day, month, previous ED attendances/emergency admissions and crowding in the department at the time of the attendance.ResultsBetween April 2016 and March 2018, 26 738 514 people attended an ED, with 7 472 480 patients admitted relating to 5 249 891 individual patients, who constituted the study’s dataset. A total of 433 962 deaths occurred within 30 days. The overall crude 30-day mortality rate was 8.71% (95% CI 8.69% to 8.74%). A statistically significant linear increase in mortality was found from 5 hours after time of arrival at the ED up to 12 hours (when accurate data collection ceased) (p<0.001). The greatest change in the 30-day standardised mortality ratio was an 8% increase, occurring in the patient cohort that waited in the ED for more than 6 to 8 hours from the time of arrival.ConclusionsDelays to hospital inpatient admission for patients in excess of 5 hours from time of arrival at the ED are associated with an increase in all-cause 30-day mortality. Between 5 and 12 hours, delays cause a predictable dose–response effect. For every 82 admitted patients whose time to inpatient bed transfer is delayed beyond 6 to 8 hours from time of arrival at the ED, there is one extra death.
Wide local excision with clear resection margins is essential to achieve local control and long-term survival. There is a need for cross-specialty collaboration in order to accrue the evidence which will be necessary to improve long-term outcomes.
SLNB is a safe and accurate diagnostic technique for staging the neck with a negative predictive value in our series of 97.5%. Furthermore, in our series three patients (5%) had positive contralateral neck drainage that would have been missed by conventional ipsilateral neck dissection.
INTRODUCTIONA total of 17 cases of penetrating neck injury were managed by the otolaryngology team at King’s College Hospital over a 3-year period in the 1980s. In April 2010 King’s College Hospital became the major trauma centre for South East London. This prospective cohort study compares the incidence, changing demographic features and treatment outcomes of penetrating neck trauma in South East London over the previous 23 years.METHODSData were collected over a 12-month period (April 2010 to March 2011) and a selective management protocol was introduced to standardise initial investigations and further treatment.RESULTSThe past 23 years have seen a 550% increase in the incidence of penetrating neck injuries in South East London, with a marked increase in gun crime. Only 38% of cases underwent negative neck exploration in 2011 compared with 65% in 1987. Selective conservative management based on the absence of haemodynamic instability or radiological findings reduces length of hospital stay, lightens surgical workload and cuts costs without affecting morbidity or mortality.CONCLUSIONSThe increased incidence of penetrating neck injury is a reflection of more interpersonal violence rather than a consequence of the larger South East London trauma centre catchment area. Tackling this problem requires focus on wider issues of community prevention. Sharing of data between the four London trauma centres and the police is needed to help prevent interpersonal violence and develop a universal treatment algorithm for other institutions to follow.
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