Secondary peristalsis and esophagogastric junction distensibility in symptomatic post-fundoplication patients.

BACKGROUND: The impact of esophageal dysmotility among patients with post-fundoplication esophageal symptoms is not fully understood. This study aimed to investigate secondary peristalsis and esophagogastric junction (EGJ) opening biomechanics using functional lumen imaging probe (FLIP) panometry in symptomatic post-fundoplication patients. METHODS: Eighty-seven adult patients post-fundoplication who completed FLIP for symptomatic esophageal evaluation were included. Secondary peristaltic contractile response (CR) patterns and EGJ opening metrics (EGJ distensibility index (EGJ-DI) and maximum EGJ diameter) were evaluated on FLIP panometry and analyzed against high-resolution manometry (HRM), patient-reported outcomes, and fundoplication condition seen on esophagram and/or endoscopy. KEY RESULTS: FLIP CR patterns included 14 (16%) normal CR, 30 (34%) borderline CR, 28 (32%) impaired/disordered CR, 13 (15%) absent CR, and 2 (2%) spastic reactive CR. Compared with normal and borderline CRs (i.e., CR patterns with distinct, antegrade peristalsis), patients with impaired/disordered and absent CRs demonstrated significantly greater time since fundoplication (2.4 (0.6-6.8) vs. 8.9 (2.6-14.5) years; p = 0.002), greater esophageal body width on esophagram (n = 50; 2.3 (2.0-2.8) vs. 2.9 (2.4-3.6) cm; p = 0.013), and lower EGJ-DI (4.3 (2.7-5.4) vs. 2.6 (1.7-3.7) mm2/mmHg; p = 0.001). Intact fundoplications had significantly higher rates of normal CRs compared to anatomically abnormal (i.e., tight, disrupted, slipped, herniated) fundoplications (9 (28%) vs. 5 (9%); p = 0.032), but there were no differences in EGJ-DI or EGJ maximum diameter. CONCLUSIONS & INFERENCES: Symptomatic post-fundoplication patients were characterized by frequent abnormal secondary peristalsis after fundoplication, potentially worsening with time after fundoplication or related to EGJ outflow resistance.

Targeting PEA3 transcription factors to mitigate small cell lung cancer progression.

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro. We utilized time-course resolved RNA-sequencing to globally profile transcriptome changes as SCLC cells responded to a combination of cisplatin and etoposide-the standard-of-care in SCLC. Comparisons across time points demonstrated a distinct transient transcriptional state resembling embryonic diapause. Differential gene expression analysis revealed that expression of the PEA3 transcription factors ETV4 and ETV5 were transiently upregulated in the surviving fraction of cells which we determined to be necessary for efficient clonogenic expansion following chemotherapy. The FGFR-PEA3 signaling axis guided the identification of a pan-FGFR inhibitor demonstrating in vitro and in vivo efficacy in delaying progression following combination chemotherapy, observed inhibition of phosphorylation of the FGFR adaptor FRS2 and corresponding downstream MAPK and PI3K-Akt signaling pathways. Taken together, these data nominate PEA3 transcription factors as key mediators of relapse progression in SCLC and identify a clinically actionable small molecule candidate for delaying relapse of SCLC.

Acute Respiratory Distress Syndrome: An Unexpected Outcome of Suspected Viral Gastroenteritis.

Acute respiratory distress syndrome (ARDS) is a life-threatening manifestation of diffuse inflammation damaging the lung pleura. Risk factors for development are numerous with most cases arising in those already hospitalized for critical illness. We describe a unique case of a healthy 20-year-old female developing myocarditis and severe ARDS while hospitalized for septic shock after initially presenting with gastroenteritis from a suspected Coxsackie B infection in the setting of an overseas military deployment. After two transfers via land and air, she reached a facility that delivered definitive care and survived. This case highlights how a common disease can develop into something far more deadly and how early recognition of ARDS risk factors can improve clinical decision-making at the time of admission.

Comparison of a Novel Trainer to a Traditional Swine Model for Training Providers in Lateral Canthotomy and Cantholysis.

RESEARCH OBJECTIVE: Military personnel are at greater risks of head and facial traumas and permanent blindness from orbital compartment syndrome in modern warfare. Rapid treatment must be implemented with a low-risk surgical remedy: lateral canthotomy and cantholysis (LCC). Traditional training of LCC is primarily performed using an animal tissue trainer (ATT); however, limitations to these types of trainers exist. Therefore, our research objectives were focused on highlighting the effectiveness, benefits, and vision-saving potential of learning LCC on a synthetic trainer. METHODS: Participants included 22 second-year medical students and 6 healthcare professionals. A pre-quiz assessed baseline knowledge. Next, an experienced ophthalmologist provided an overview and instruction. Subjects were randomized to either the synthetic trainer or the ATT and then switched to the other model for comparison. After performing LCC procedures on both models, a post-quiz and survey were administered. RESULTS: Participants found the synthetic trainer easier to use than the ATT model (p < 0.01). There was no statistically significant preference (p = 0.23), or preference of practical eye anatomy (p = 0.26) between the trainers. Post-quiz results demonstrated an overall improvement from pre-quiz scores for participants (p < 0.001). CONCLUSIONS: The synthetic trainer is comparable to the traditional swine model for training LCC procedures, and should be considered as a future training platform.