Biomarker-driven targeted therapies for gastric/gastro-esophageal junction malignancies.

Gastroesophageal malignancies often contain high amounts of genetic and molecular alterations that result in an aggressive disease capable of rapidly metastasizing to distant organs and early development of drug resistance. Most patients in the Western hemisphere present with locally advanced or metastatic disease that is treated with systemic chemotherapy used either in the neoadjuvant or palliative setting, respectively. This article will review the various recent advances in the development of targeted therapies for the treatment of advanced gastric and gastroesophageal cancer.

Targeting the anterior superior iliac spine yields significantly longer bone marrow cores.

Pathologists and haematologists generally agree that the length of the biopsy core is a good surrogate for the diagnostic quality of the bone marrow. Previous studies suggested that the angulation of the biopsy needle from the posterior superior iliac spine (PSIS) could influence the length of the biopsy cores, targeting the anterior superior iliac spine (ASIS) from the PSIS would yield longer specimens than the traditional angulation technique (TAT), where the biopsy needle is directed straight in, perpendicular to the plane of the back. Twenty five adult haematology patients were prospectively recruited by haematologists-in-training (HITs), who were trained to target the ASIS using a lateral angulationtechnique (LAT). The mean length of biopsy cores was 16 mm and that was significantly longer (p=0.003) than a comparable group of bone marrow biopsies previously obtained by HITs using the TAT approach. These results support the LAT as a new standard of haematology practice. TRIAL REGISTRATION NUMBER: NCT 02524613.

Investigational therapies for squamous cell lung cancer: from animal studies to phase II trials.

INTRODUCTION: It remains challenging to treat squamous cell lung cancer (SCC) with limited therapeutic options. However, recent breakthroughs in targeted therapies and immunotherapies have shed some light on the management of this deadly disease. Areas covered: The article first reviews the current treatment options for advanced SCC, especially recent FDA approved molecular agents (afatinib, ramucirumab and necitumumab) and immunotherapies (nivolumab, pembrolizumab and atezolimumab). We then provide an overview on investigational therapies with data ranging from preclinical to phase II studies, focusing on new cytotoxic agents, emerging molecularly targeted agents (including a PARP inhibitor for Homologous Recombinant Deficiency positive SCC) and novel immunotherapeutic strategies. Expert opinion summary: Identification of potential therapeutic targets, development of novel clinical trials and the rapid approvals of immune checkpoint inhibitors have shifted the management paradigm for squamous cell lung cancer. On the other hand, continued efforts are needed to identify the predictive biomarkers and to investigate novel mechanistically-driven mono- and combination therapies. We need to learn more about the biology behind immune checkpoint blockade and tumor genomics in SCC for better patient selection and future trial design.

Improving in-hospital cardiac arrest process and outcomes with performance debriefing.

BACKGROUND: Recent investigations have documented poor cardiopulmonary resuscitation (CPR) performance in clinical practice. We hypothesized that a debriefing intervention using CPR quality data from actual in-hospital cardiac arrests (resuscitation with actual performance integrated debriefing [RAPID]) would improve CPR performance and initial patient survival. METHODS: Internal medicine residents at a university hospital attended weekly debriefing sessions of the prior week's resuscitations, between March 2006 and February 2007, reviewing CPR performance transcripts obtained from a CPR-sensing and feedback-enabled defibrillator. Objective metrics of CPR performance and initial return of spontaneous circulation were compared with a historical cohort in which a similar feedback-delivering defibrillator was used but without RAPID. RESULTS: Cardiopulmonary resuscitation quality and outcome data from 123 patients resuscitated during the intervention period were compared with 101 patients in the baseline cohort. Compared with the control period, the mean (SD) ventilation rate decreased (13 [7]/min vs 18 [8]/min; P < .001) and compression depth increased (50 [10] vs 44 [10] mm; P = .001), among other CPR improvements. These changes correlated with an increase in the rate of return of spontaneous circulation in the RAPID group (59.4% vs 44.6%; P = .03) but no change in survival to discharge (7.4% vs 8.9%; P = .69). CONCLUSIONS: The combination of RAPID and real-time audiovisual feedback improved CPR quality compared with the use of feedback alone and was associated with an increased rate of return of spontaneous circulation. Cardiopulmonary resuscitation sensing and recording devices allow for methods of debriefing that were previously available only for simulation-based education; such methods have the potential to fundamentally alter resuscitation training and improve patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00228293.

CPR quality improvement during in-hospital cardiac arrest using a real-time audiovisual feedback system.

BACKGROUND: Cardiopulmonary resuscitation (CPR) quality during actual cardiac arrest has been found to be deficient in several recent investigations. We hypothesized that real-time feedback during CPR would improve the performance of chest compressions and ventilations during in-hospital cardiac arrest. METHODS: An investigational monitor/defibrillator with CPR-sensing and feedback capabilities was used during in-hospital cardiac arrests from December 2004 to December 2005. Chest compression and ventilation characteristics were recorded and quantified for the first 5 min of resuscitation and compared to a baseline cohort of arrest episodes without feedback, from December 2002 to April 2004. RESULTS: Data from 55 resuscitation episodes in the baseline pre-intervention group were compared to 101 resuscitations in the feedback intervention group. There was a trend toward improvement in the mean values of CPR variables in the feedback group with a statistically significant narrowing of CPR variable distributions including chest compression rate (104+/-18 to 100+/-13 min(-1); test of means, p=0.16; test of variance, p=0.003) and ventilation rate (20+/-10 to 18+/-8 min(-1); test of means, p=0.12; test of variance, p=0.04). There were no statistically significant differences between the groups in either return of spontaneous circulation or survival to hospital discharge. CONCLUSIONS: Real-time CPR-sensing and feedback technology modestly improved the quality of CPR during in-hospital cardiac arrest, and may serve as a useful adjunct for rescuers during resuscitation efforts. However, feedback specifics should be optimized for maximal benefit and additional studies will be required to assess whether gains in CPR quality translate to improvements in survival.

Difficulty of cardiac arrest rhythm identification does not correlate with length of chest compression pause before defibrillation.

OBJECTIVE: Performing high-quality cardiopulmonary resuscitation immediately before electrical defibrillation serves as an important predictor of shock success. Long preshock pauses in cardiopulmonary resuscitation frequently occur, as noted by recent clinical investigations. We sought to determine whether these long pauses were due to difficulties in identifying shockable rhythms or rather due to local factors during resuscitation attempts. DESIGN: Prospective in-hospital study of cardiac arrest resuscitation attempts coupled with a retrospective review of preshock pause rhythms by 12 trained providers. Reviewers scored rhythms by ease of identification using a discrete Likert scale from 1 (most difficult to identify) to 5 (easiest to identify). The resuscitation cohort was organized into preshock pause-duration quartiles for statistical analysis. Resident physicians were then surveyed regarding human factors affecting preshock pauses. RESULTS: A total of 118 preshock pauses from 45 resuscitation episodes were collected. When evaluated by quartiles of preshock pause duration, difficulty of rhythm identification did not correlate with increasing pause time. In fact, the opposite was found (longest preshock pause quartile of 23.8-60.2 secs vs. shortest pause quartile of 1.1-7.9 secs; rhythm difficulty scores, 3.2 vs. 3.0; p = .20). When 29 resident physicians who recently served on resuscitation teams were surveyed, 18 of 29 (62.1%) attributed long pauses to lack of time sense during resuscitation, and 16 of 29 (55.2%) thought that room crowding prevented rapid defibrillation. CONCLUSIONS: Long cardiopulmonary resuscitation pauses before defibrillation are likely due to human factors during the resuscitation and not due to inherent difficulties with rhythm identification. This preliminary work highlights the need for more research and training in the area of team performance and human factors during resuscitation.