‘Gain’ of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers1–13 and is associated with poor prognosis7,10,14. The well-characterized myelocytomatosis (MYC) oncogene resides in the 8q24.21 region and is consistently co-gained with an adjacent ‘gene desert’ of approximately 2 megabases that contains the long non-coding RNA gene PVT1, the CCDC26 gene candidate and the GSDMC gene. Whether low copy-number gain of one or more of these genes drives neoplasia is not known. Here we use chromosome engineering in mice to show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsdmc fails to advance cancer measurably, whereas a single supernumerary segment encompassing all four genes successfully promotes cancer. Gain of PVT1 long non-coding RNA expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumours, and copy number of PVT1 was co-increased in more than 98% of MYC-copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency. As MYC protein has been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 long non-coding RNA provides a much needed therapeutic target.

Purpose The overall goal is to develop MR Elastography (MRE) derived shear stiffness as a biomarker for the early identification of chemotherapy response, allowing dose, agent type and treatment regimen to be tailored on a per patient basis, improving therapeutic outcome and minimizing normal tissue toxicity. The specific purpose of this study is to test the feasibility of this novel biomarker to measure the treatment response in a well-known chemotherapy model. Methods Tumors were grown in the right flank of genetically modified mice by subcutaneous injection of DoHH2 (non-Hodgkin’s lymphoma) cells. MRE was used to quantify tumor stiffness before and after injection of a chemotherapeutic agent or saline. Histological tests were also performed on the tumors. Results A significant decrease (P < 0.0001) in MRE-derived tumor shear stiffness was observed within 4 days of chemotherapy treatment, while no appreciable change was observed in saline-treated tumors. No significant change in volume occurred at this early stage, but there were decreased levels of cellular proliferation in chemotherapy-treated tumors. Conclusion These results demonstrate that MRE-derived estimates of shear stiffness reflect an initial response to cytotoxic therapy and suggest that this metric could be an early and sensitive biomarker of tumor response to chemotherapy.

Background Problem lists represent an integral component of high-quality care. However, they are often inaccurate and incomplete. We studied the effects of alerts integrated into the inpatient and outpatient computerized provider order entry systems to assist in adding problems to the problem list when ordering medications that lacked a corresponding indication. Methods We analyzed medication orders from 2 healthcare systems that used an innovative indication alert. We collected data at site 1 between December 2018 and January 2020, and at site 2 between May and June 2021. We reviewed random samples of 100 charts from each site that had problems added in response to the alert. Outcomes were: (1) alert yield, the proportion of triggered alerts that led to a problem added and (2) problem accuracy, the proportion of problems placed that were accurate by chart review. Results Alerts were triggered 131 134, and 6178 times at sites 1 and 2, respectively, resulting in a yield of 109 055 (83.2%) and 2874 (46.5%), P&lt; .001. Orders were abandoned, for example, not completed, in 11.1% and 9.6% of orders, respectively, P&lt;.001. Of the 100 sample problems, reviewers deemed 88% ± 3% and 91% ± 3% to be accurate, respectively, P = .65, with a mean of 90% ± 2%. Conclusions Indication alerts triggered by medication orders initiated in the absence of a justifying diagnosis were useful for populating problem lists, with yields of 83.2% and 46.5% at 2 healthcare systems. Problems were placed with a reasonable level of accuracy, with 90% ± 2% of problems deemed accurate based on chart review.

Objectives: Wrong-patient errors are common and have the potential to cause serious harm. The Office of the National Coordinator for Health Information Technology Patient Identification SAFER Guide recommends displaying patient photographs in electronic health record (EHR) systems to facilitate patient identification and reduce wrong-patient errors. A potential barrier to implementation is patient refusal; however, patients' perceptions about having their photograph captured during registration and integrated into the EHR are unknown. Methods:The study was conducted in an emergency department (ED) and primary care outpatient clinic within a large integrated health system in New York City. The study consisted of 2 components: (1) direct observation of the registration process to quantify the frequency of patient refusals and (2) semistructured interviews to elicit patients' feedback on perceived benefits and barriers to integrating their photograph into the EHR.Results: Of 172 registrations where patients were asked to take a photograph for patient identification, 0 refusals were observed (ED, 0 of 87; primary care outpatient clinic, 0 of 85). A convenience sample of 30 patients were interviewed (female, 70%; age ≥55 years, 43%; Hispanic/Latino, 67%; Black, 23%). Perceived benefits of integrating patient photographs into the EHR included improved security (40%), improved patient identification (23%), and ease of registration (17%). A small proportion of patients raised privacy concerns.Conclusions: Patient refusal was not found to be a barrier to implementation of patient photographs in the EHR. Efforts to identify and address other potential barriers would help ensure that the highest proportion of patients has photographs in their medical record.

INTRODUCTION: Endotracheal (ET) tube biting is a common problem with oropharyngeal intubation, though is usually treatable with patient redirection or sedation. Here we present a rare case of cardiac arrest from ET tube biting.CASE PRESENTATION: A 27-year-old man with hyper IgE syndrome and cervical syringomyelia was admitted to the intensive care unit for planned intubation in the setting of chronic progressive hypercarbic respiratory failure. He had undergone bilateral lower lobectomies as a child for recurrent pneumonias, and the combination of neuromuscular weakness and severe kyphoscoliosis caused him to have restrictive lung physiology. The plan of care was for intubation, subsequent tracheostomy, and neurosurgical intervention on his syrinx. On the day of admission to the ICU, intubation went smoothly, and post-intubation the patient required low dose fentanyl infusion to maintain a Richmond Agitation Sedation Scale (RASS) of zero. He was alert and oriented. Overnight the same day, the patient was observed to be strongly biting his ET tube which obstructed airflow from the ventilator. Attempts to redirect patient were not successful, and he was given boluses of fentanyl and midazolam without resolution of biting. He then sustained hypoxic PEA cardiac arrest with return of spontaneous circulation achieved after 8 minutes of CPR. Post arrest, his mental status was poor and there was concern for status epilepticus, so propofol infusion was started and levetiracetam was given. Subsequent workup immediately post arrest including 5 days of continuous video EEG in the ICU did not demonstrate any seizure activity. Computed tomography angiogram of his head and neck vessels did not demonstrate any vascular occlusion or hemorrhage. After targeted temperature management and weaning of sedation, his mental status returned to normal. A bite guard was placed to prevent further ET tube obstruction. Tracheostomy was then performed. Within the next month the patient developed bilateral jerking movements of his lower extremities as well as tongue biting during his sleep. He underwent multiple video EEG studies which demonstrated these events without EEG correlate for seizure. Neurology diagnosed the patient with spinal segmental myoclonus, and he was initiated on clonazepam for treatment.DISCUSSION: ET tube biting is a known complication of oropharyngeal intubation. However, previous reports of major complications related to ET tube biting have come from damage to the tube itself (1-3). To our knowledge, this is the first case reported of a patient biting on the ET tube for long enough to arrest from hypoxemia. His diagnosis of spinal myoclonus is the most likely explanation for this event.CONCLUSIONS: In patients with a history of myoclonus, it may be prudent to prophylactically apply bite guard devices to prevent this rare complication of mechanical ventilation.