The Effect of Laparoscopic Gastric Ischemic Preconditioning Prior to Esophagectomy on Anastomotic Stricture Rate and Comparison with Esophagectomy-Alone Controls.

BACKGROUND: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied. METHODS: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022). Our institution initiated an LGIP protocol on 1 January 2021. The primary outcome was the occurrence of stricture within 1 year of esophagectomy, while secondary outcomes were stricture severity and frequency of interventions within the 6 months following stricture. Bivariable comparisons were performed using Chi-square, Fisher's exact, or Mann-Whitney U tests. Multivariable regression controlling for confounders was performed to generate risk-adjust odds ratios and to identify the independent effect of LGIP. RESULTS: Of 253 esophagectomies, 42 (16.6%) underwent LGIP prior to esophagectomy. There were 45 (17.7%) anastomotic strictures requiring endoscopic intervention, including three patients who underwent LGIP and 42 who did not. Median time to stricture was 144 days. Those who underwent LGIP were significantly less likely to develop anastomotic stricture (7.1% vs. 19.9%; p = 0.048). After controlling for confounders, this difference was no longer significant (odds ratio 0.46, 95% confidence interval 0.14-1.82; p = 0.29). Of those who developed stricture, there was a trend toward less severe strictures and decreased need for endoscopic dilation in the LGIP group (all p < 0.20). CONCLUSION: LGIP may reduce the rate and severity of symptomatic anastomotic stricture following esophagectomy. A multi-institutional trial evaluating the effect of LGIP on stricture and other anastomotic complications is warranted.

Social vulnerability is associated with post-operative morbidity following robotic-assisted lung resection.

Background: The social vulnerability index (SVI) is a neighborhood-based metric used to determine an individual's susceptibility to socioeconomic hardship, with high SVI indicating high susceptibility. SVI has previously been associated with surgical outcomes. We aimed to determine if SVI influences morbidity following robotic-assisted lung resection. Methods: This was a retrospective cohort study at one academic medical center (1/1/2021-11/30/2022). Patients undergoing robotic-assisted lung resection were grouped into low (<75th percentile) and high (≥75th percentile) SVI cohorts. The primary outcome was 30-day overall morbidity; secondary outcomes were individual 30-day post-operative outcomes. Univariate analysis was performed using Chi-squared or Mann-Whitney-U tests, and multivariable logistic regression was performed to generate risk-adjusted odds ratios (ORs) of postoperative complications. Results: We included 320 patients, of which 40 patients (12.5%) in the high-SVI group and 280 (87.5%) in the low-SVI group. High SVI patients were more likely to be non-Caucasian and of Hispanic ethnicity, but there were no other differences in perioperative characteristics (all P>0.05). High SVI patients were more likely to experience a post-operative complication (42.5% vs. 24.6%, P=0.017), surgical site infection (SSI) (12.5% vs. 4.3%, P=0.047), hemothorax (5.0% vs. 0.0%, P=0.015), intensive care need (15.0% vs. 4.6%, P=0.021), sepsis (10.0% vs. 1.1%, P=0.006) and unplanned reoperation (5.0% vs. 0.4%, P=0.042). After risk-adjustment, the association of increased overall morbidity with high SVI persisted (OR =2.53; 95% confidence interval: 1.19-5.35). Conclusions: High SVI was associated with increased risk-adjusted odds of morbidity after robotic-assisted lung resection. Highly vulnerable patients should be allocated perioperative resources to help mitigate the increased risk of these complications.

Prospective Evaluation of a Universally Applied Laparoscopic Gastric Ischemic Preconditioning Protocol Prior to Esophagectomy with Comparison with Historical Controls.

BACKGROUND: Anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Our institution began performing laparoscopic gastric ischemic preconditioning (LGIP) with ligation of the left gastric and short gastric vessels prior to esophagectomy in all patients presenting with resectable esophageal cancer. We hypothesized that LGIP may decrease the incidence and severity of anastomotic leak. METHODS: Patients were prospectively evaluated following the universal application of LGIP prior to esophagectomy protocol in January 2021 until August 2022. Outcomes were compared with patients who underwent esophagectomy without LGIP from a prospectively maintained database from 2010 to 2020. RESULTS: We compared 42 patients who underwent LGIP followed by esophagectomy with 222 who underwent esophagectomy without LGIP. Age, sex, comorbidities, and clinical stage were similar between groups. Outpatient LGIP was generally well tolerated, with one patient experiencing prolonged gastroparesis. Median time from LGIP to esophagectomy was 31 days. Mean operative time and blood loss were not significantly different between groups. Patients who underwent LGIP were significantly less likely to develop an anastomotic leak following esophagectomy (7.1% vs. 20.7%, p = 0.038). This finding persisted on multivariate analysis [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.03-0.42, p = 0.029]. The occurrence of any post-esophagectomy complication was similar between groups (40.5% vs. 46.0%, p = 0.514), but patients who underwent LGIP had shorter length of stay [10 (9-11) vs. 12 (9-15), p = 0.020]. CONCLUSIONS: LGIP prior to esophagectomy is associated with a decreased risk of anastomotic leak and length of hospital stay. Further, multi-institutional studies are warranted to confirm these findings.

Social vulnerability is associated with increased postoperative morbidity following esophagectomy.

OBJECTIVES: The effect of a patient's Social Vulnerability Index (SVI) on complication rates after esophagectomy remains unstudied. The purpose of this study was to determine how social vulnerability influences morbidity following esophagectomy. METHODS: This was a retrospective review of a prospectively collected esophagectomy database at one academic institution, 2016 to 2022. Patients were grouped into low-SVI (<75%ile) and high-SVI (>75%ile) cohorts. The primary outcome was overall postoperative complication rate; secondary outcomes were rates of individual complications. Perioperative patient variables and postoperative complication rates were compared between the 2 groups. Multivariable logistic regression was used to control for covariates. RESULTS: Of 149 patients identified who underwent esophagectomy, 27 (18.1%) were in the high-SVI group. Patients with high SVI were more likely to be of Hispanic ethnicity (18.5% vs 4.9%, P = .029), but there were no other differences in perioperative characteristics between groups. Patients with high SVI were significantly more likely to develop a postoperative complication (66.7% vs 36.9%, P = .005) and had greater rates of postoperative pneumonia (25.9% vs 6.6%, P = .007), jejunal feeding-tube complications (14.8% vs 3.3%, P = .036), and unplanned intensive care unit readmission (29.6% vs 12.3%, P = .037). In addition, patients with high SVI had a longer postoperative hospital length of stay (13 vs 10 days, P = .017). There were no differences in mortality rates. These findings persisted on multivariable analysis. CONCLUSIONS: Patients with high SVI have greater rates of postoperative morbidity following esophagectomy. The effect of SVI on esophagectomy outcomes warrants further investigation and may prove useful in identifying populations that benefit from interventions to mitigate these complications.

Assessing detergent-mediated virus inactivation, protein stability, and impurity clearance in biologics downstream processes.

Detergent-mediated virus inactivation (VI) provides a valuable orthogonal strategy for viral clearance in mammalian processes, in particular for next-generation continuous manufacturing. Furthermore, there exists an industry-wide need to replace the conventionally employed detergent Triton X-100 with eco-friendly alternatives. However, given Triton X-100 has been the gold standard for VI due its minimal impact on protein stability and high inactivation efficacy, inactivation by other eco-friendly detergents and its impact on protein stability is not well understood. In this study, the sugar-based detergent commonly used in membrane protein purification, n-dodecyl-ß- d-maltoside was found to be a promising alternative for VI. We investigated a panel of detergents to compare the relative VI efficacy, impact on therapeutic quality attributes, and clearance of the VI agent and other impurities through subsequent chromatographic steps. Detergent-mediated inactivation and protein stability showed comparable trends to low pH inactivation. Using experimental and modeling data, we found detergent-mediated product aggregation and its kinetics to be driven by extrinsic factors such as detergent and protein concentration. Detergent-mediated aggregation was also impacted by an initial aggregation level as well as intrinsic factors such as the protein sequence and detergent hydrophobicity, and critical micelle concentration. Knowledge gained here on factors driving product stability and VI provides valuable insight to design, standardize, and optimize conditions (concentration and duration of inactivation) for screening of detergent-mediated VI.

Postoperative Swallowing Assessment After Lung Transplantation.

BACKGROUND: Dysphagia, aspiration, and potential pneumonia represent a major source of morbidity in patients undergoing lung transplantation. Conditions that potentiate dysphagia and aspiration include frailty and prolonged intubation. Our group of speech-language pathologists has been actively involved in performance of a bedside evaluation of swallowing, and instrumental evaluation of swallowing with modified barium swallow, and postoperative management in patients undergoing lung transplantation. METHODS: All lung transplant patients from April 2009 to September 2012 were evaluated retrospectively. A clinical bedside examination was performed by the speech-language pathology team, followed by a modified barium swallow or fiberoptic endoscopic evaluation of swallowing. RESULTS: A total of 321 patients were referred for evaluation. Twenty-four patients were unable to complete the evaluation. Clinical signs of aspiration were apparent in 160 patients (54%). Deep laryngeal penetration or aspiration were identified in 198 (67%) patients during instrumental testing. A group of 81 patients (27%) had an entirely normal clinical examination, but were found to have either deep penetration or aspiration. CONCLUSIONS: The majority of patients aspirate after lung transplantation. Clinical bedside examination is not sensitive enough and will fail to identify patients with silent aspiration. A standard of practice following lung transplantation has been established that helps avoid postoperative aspiration associated with complications.

Subtyping of Salmonella enterica Subspecies I Using Single-Nucleotide Polymorphisms in Adenylate Cyclase.

Methods to rapidly identify serotypes of Salmonella enterica subspecies I are of vital importance for protecting the safety of food. To supplement the serotyping method dkgB-linked intergenic sequence ribotyping (ISR), single-nucleotide polymorphisms were characterized within adenylate cyclase (cyaA). The National Center for Biotechnology Information (NCBI) database had 378 cyaA sequences from S. enterica subspecies I, which included 42 unique DNA sequences and 19 different amino acid sequences. Five representative isolates, namely serotypes Typhimurium, Kentucky, Enteritidis phage type PT4, and two variants of Enteritidis phage type PT13a, were differentiated within a microsphere-based fluidics system in cyaA by allele-specific primer extension. Validation against 25 poultry-related environmental Salmonella isolates representing 11 serotypes yielded a ∼89% success rate at identifying the serotype of the isolate, and a different region could be targeted to achieve 100%. When coupled with ISR, all serotypes were differentiated. Phage lineages of serotype Enteritidis 13a and 4 were identified, and a biofilm-forming strain of PT13a was differentiated from a smooth phenotype within phage type. Comparative ranking of mutation indices to genes such as the tRNA transferases, the diguanylate cyclases, and genes used for multilocus sequence typing indicated that cyaA is an appropriate gene for assessing epidemiological trends of Salmonella because of its relative stability in nucleotide composition.

Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones, display activity as cytotoxic phytoalexins and transcriptional mediators.

Plant damage promotes the interaction of lipoxygenases (LOXs) with fatty acids yielding 9-hydroperoxides, 13-hydroperoxides, and complex arrays of oxylipins. The action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downstream products, termed "jasmonates." As signals, jasmonates have related yet distinct roles in the regulation of plant resistance against insect and pathogen attack. A similar pathway involving 9-LOX activity on linolenic and linoleic acid leads to the 12-OPDA positional isomer, 10-oxo-11-phytodienoic acid (10-OPDA) and 10-oxo-11-phytoenoic acid (10-OPEA), respectively; however, physiological roles for 9-LOX cyclopentenones have remained unclear. In developing maize (Zea mays) leaves, southern leaf blight (Cochliobolus heterostrophus) infection results in dying necrotic tissue and the localized accumulation of 10-OPEA, 10-OPDA, and a series of related 14- and 12-carbon metabolites, collectively termed "death acids." 10-OPEA accumulation becomes wound inducible within fungal-infected tissues and at physiologically relevant concentrations acts as a phytoalexin by suppressing the growth of fungi and herbivores including Aspergillus flavus, Fusarium verticillioides, and Helicoverpa zea. Unlike previously established maize phytoalexins, 10-OPEA and 10-OPDA display significant phytotoxicity. Both 12-OPDA and 10-OPEA promote the transcription of defense genes encoding glutathione S transferases, cytochrome P450s, and pathogenesis-related proteins. In contrast, 10-OPEA only weakly promotes the accumulation of multiple protease inhibitor transcripts. Consistent with a role in dying tissue, 10-OPEA application promotes cysteine protease activation and cell death, which is inhibited by overexpression of the cysteine protease inhibitor maize cystatin-9. Unlike jasmonates, functions for 10-OPEA and associated death acids are consistent with specialized roles in local defense reactions.

Handgrip strength and dysphagia assessment following cardiac surgery.

OBJECTIVES/HYPOTHESIS: Prolonged intubation has been recognized as a risk factor for dysphagia following cardiac surgery. We conducted a study to determine whether those patients intubated longer than 12 hours following cardiac surgery exhibit low handgrip strength and if dysphagia is prevalent in those with low handgrip strength. STUDY DESIGN: Feasibility study. METHODS: Patients intubated more than 12 hours after cardiac surgery were enrolled. Handgrip strength was measured. If subjects were found to have low grip strength they underwent clinical swallowing exam by a speech-language pathologist followed by modified barium swallow (MBS) to assess for dysphagia. Severity of dysphagia was assessed with the Penetration-Aspiration Scale (PAS) and need for diet modification. RESULTS: Eighty-six percent (12/14) of patients tested had low handgrip strength. Eight patients with low grip strength completed the bedside swallowing exam and MBS. Four of the eight patients (50%) had deep laryngeal penetration (PAS scores 4-5) on MBS and three (38%) patients were found to have silent aspiration (PAS 8). The findings on MBS resulted in the recommendation of a swallowing strategy and/or modified diet for six of the eight (80%) patients. Nonoral feedings were recommended for two patients (25%) based on MBS results. CONCLUSIONS: A majority of patients intubated >12 hours after cardiac surgery exhibit low handgrip strength. Dysphagia is prevalent among those with low handgrip strength. The role of frailty measures in screening for dysphagia deserves further investigation. LEVEL OF EVIDENCE: 4.