Use of endoloop in video-assisted thoracoscopic enucleation of a very rare esophageal tumor

A gastrointestinal stromal tumor is an infrequent tumor of the gastrointestinal tract with very rare involvement of the esophagus. We present a case of a patient with dysphagia and a 4 cm submucosal mass. The patient underwent thoracoscopic enucleation with complete resection of the mass. We present case details and operative video highlighting the important surgical steps of exposure and retraction. We believe that the Endoloop is a very useful tool in providing countertraction needed during minimally invasive resection of such lesions

Periesophageal Pseudoaneurysms: Rare Cause of Refractory Bleeding Treated with Transarterial Embolization

A 43-year-old female with history of systemic lupus erythematosus, prior cytomegalovirus esophagitis treated with ganciclovir, and long segment Barrett’s esophagus (Prague class C8 M9) with high grade dysplasia treated with radiofrequency ablation presented to the hospital with hematemesis. An upper gastrointestinal endoscopy showed multiple esophageal ulcers with active arterial spurting which could not be controlled with endoscopic interventions including placement of hemostatic clips. An emergent angiogram demonstrated actively bleeding saccular dilations (pseudoaneurysms) in the esophageal branches of the lower thoracic aorta as well as left gastric artery for which gelfoam and coil embolization was initially successful. Due to recurrence of massive bleeding, she subsequently underwent emergent esophagectomy and bipolar exclusion. Pathology demonstrated submucosal hemorrhage, esophagitis with dysplastic Barrett’s mucosa, and an ulcer containing cytomegaloviral inclusions. We report the first case of arterial bleeding from periesophageal pseudoaneurysms as well as use of angiographic embolization for arterial bleeding in the esophagus

Emergent Esophagectomy in Patients with Esophageal Malignancy Is Associated with Higher Rates of Perioperative Complications but No Independent Impact on Short-Term Mortality

Background: Data on perioperative outcomes of emergent versus elective resection in esophageal cancer patients requiring esophagectomy are lacking. We investigated whether emergent resection was associated with increased risks of morbidity and mortality. Methods: Data on patients with esophageal malignancy who underwent esophagectomy from 2005 to 2020 were retrospectively analyzed from the American College of Surgeons National Surgical Quality Improvement Program database. Thirty-day complication and mortality rates were compared between emergent esophagectomy (EE) and non-emergent esophagectomy. Logistic regression assessed factors associated with complications and mortality. Results: Of 10,067 patients with malignancy who underwent esophagectomy, 181 (1.8%) had EE, 64% had preoperative systemic inflammatory response syndrome, sepsis, or septic shock, and 44% had bleeding requiring transfusion. The EE group had higher American Society of Anesthesiologists (ASA) class and functional dependency. More transhiatal esophagectomies and diversions were performed in the EE group. After EE, the rates of 30-day mortality (6.1% vs. 2.8%), overall complications (65.2% vs. 44.2%), bleeding, pneumonia, prolonged intubation, and positive margin (17.7% vs. 7.4%) were higher, while that of anastomotic leak was similar. On adjusted logistic regression, older age, lower albumin, higher ASA class, and fragility were associated with increased complications and mortality. McKeown esophagectomy and esophageal diversion were associated with a higher risk of postoperative complications. EE was associated with 30-day postoperative complications (odds ratio, 2.39; 95% confidence interval, 1.66–3.43; p<0.0001). Conclusion: EE was associated with a more than 2-fold increase in complications compared to elective procedures, but no independent increase in short-term mortality. These findings may help guide data-driven critical decision-making for surgery in select cases of complicated esophageal malignancy

A Highly Efficient Catalyst for Oxime Ligation and Hydrazone–Oxime Exchange Suitable for Bioconjugation

Imine-based reactions are useful for a wide range of bioconjugation applications. Although aniline is known to catalyze the oxime ligation reaction under physiological conditions, it suffers from slow reaction kinetics, specifically when a ketone is being used or when hydrazone–oxime exchange is performed. Here, we report on the discovery of a new catalyst that is up to 15 times more efficient than aniline. That catalyst, <i>m</i>-phenylenediamine (mPDA), was initially used to analyze the kinetics of oxime ligation on aldehyde- and ketone-containing small molecules. While mPDA is only modestly more effective than aniline when used in equal concentrations (∼2-fold), its much greater aqueous solubility relative to aniline allows it to be used at higher concentrations, resulting in significantly more efficient catalysis. In the context of protein labeling, it was first used to site-specifically label an aldehyde-functionalized protein through oxime ligation, and its kinetics were compared to reaction with aniline. Next, a protein was labeled with an aldehyde-containing substrate in crude cell lysate, captured with hydrazide-functionalized beads and then the kinetics of immobilized protein release via hydrazone-oxime exchange were analyzed. Our results show that mPDA can release and label 15 times more protein than aniline can in 3 h. Then, using the new catalyst, ciliary neurotrophic factor, a protein with therapeutic potential, was successfully labeled with a fluorophore in only 5 min. Finally, a protein containing the unnatural amino acid, <i>p</i>-acetyl phenylalanine, a ketone-containing residue, was prepared and PEGylated efficiently via oxime ligation using mPDA. This new catalyst should have a significant impact on the field of bioconjugation, where oxime ligation and hydrazone–oxime exchange are commonly employed

Dynamic Long-Range Interactions Influence Substrate Binding and Catalysis by Human Histidine Triad Nucleotide-Binding Proteins (HINTs), Key Regulators of Multiple Cellular Processes and Activators of Antiviral ProTides

Human histidine triad nucleotide-binding (hHINT) proteins catalyze nucleotide phosphoramidase and acyl-phosphatase reactions that are essential for the activation of antiviral proTides, such as Sofosbuvir and Remdesivir. hHINT1 and hHINT2 are highly homologous but exhibit disparate roles as regulators of opioid tolerance (hHINT1) and mitochondrial activity (hHINT2). NMR studies of hHINT1 reveal a pair of dynamic surface residues (Q62, E100), which gate a conserved water channel leading to the active site 13 Å away. hHINT2 crystal structures identify analogous residues (R99, D137) and water channel. hHINT1 Q62 variants significantly alter the steady-state kcat and Km for turnover of the fluorescent substrate (TpAd), while stopped-flow kinetics indicate that KD also changes. hHINT2, like hHINT1, exhibits a burst phase of adenylation, monitored by fluorescent tryptamine release, prior to rate-limiting hydrolysis and nucleotide release. hHINT2 exhibits a much smaller burst-phase amplitude than hHINT1, which is further diminished in hHINT2 R99Q. Kinetic simulations suggest that amplitude variations can be accounted for by a variable fluorescent yield of the E·S complex from changes in the environment of bound TpAd. Isothermal titration calorimetry measurements of inhibitor binding show that these hHINT variants also alter the thermodynamic binding profile. We propose that these altered surface residues engender long-range dynamic changes that affect the orientation of bound ligands, altering the thermodynamic and kinetic characteristics of hHINT active site function. Thus, studies of the cellular roles and proTide activation potential by hHINTs should consider the importance of long-range interactions and possible protein binding surfaces far from the active site

Draft genome sequence of pigeonpea (cajanus cajan), an orphan legume crop of resource-poor farmers

Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries