Association between underweight status and chylothorax after esophagectomy for esophageal cancer: A propensity score-matched analysis.

Objective: To use a nationwide database of hospitalizations to investigate underweight status as a risk factor for postesophagectomy complications. Methods: We identified all patients who underwent esophagectomy with a diagnosis of esophageal cancer and known body mass index in the 2018-2020 Nationwide Readmissions Database. All hospital visits for esophagectomy and within 30 days of initial discharge were analyzed for postoperative complications, including chylothorax. Patients who were underweight were propensity score matched with patients who were not. Multivariable logistic regression was performed to identify complications that were significantly associated with underweight status. Results: There were 1877 patients with esophageal cancer meeting inclusion criteria. Following propensity score matching, 433 patients who were underweight were matched to 433 patients who were not. In the multivariable model of the matched sample, which adjusted for age, sex, Charlson Comorbidity Index, history of chemotherapy or radiation therapy, and preoperative surgical feeding access, patients who were underweight were estimated to have 2.06 times the odds for chylothorax (95% confidence interval [CI], 1.07-4.25, P = .035). Underweight status was also significantly associated with acute bleed (odds ratio [OR], 1.52; 95% CI, 1.12-2.05, P = .007), pneumothorax (OR, 2.33; 95% CI, 1.19-4.85; P = .017), pneumonia (OR, 2.30; 95% CI, 1.53-3.50, P < .001), and in-hospital mortality (OR, 2.42; 95% CI, 1.31-4.69, P = .006). Conclusions: Underweight status was found to be a risk factor for chylothorax after esophagectomy, which may have implications for perioperative care of esophageal cancer patients. Future studies should assess whether using feeding tubes or total parenteral nutrition preoperatively or thoracic duct ligation intraoperatively decreases risk of chylothorax among patients who were underweight.

Longer hospitalizations, more complications, and greater readmissions for patients with comorbid psychiatric disorders undergoing pulmonary lobectomy.

OBJECTIVE: To examine the influence of comorbid psychiatric disorders (PSYD) on postoperative outcomes in patients undergoing pulmonary lobectomy. METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2016 to 2018 was performed. Patients with lung cancer with and without psychiatric comorbidities who underwent pulmonary lobectomy were collated and analyzed (International Classification of Diseases, 10th Revision, Clinical Modification Mental, Behavioral and Neurodevelopmental disorders [F01-99]). The association of PSYD with complications, length of stay, and readmissions was assessed using a multivariable regression analysis. Additional subgroup analyses were performed. RESULTS: A total of 41,691 patients met inclusion criteria. Of these, 27.84% (11,605) of the patients had at least 1 PSYD. PSYD was associated with a significantly increased risk of postoperative complications (relative risk, 1.041; 95% CI, 1.015-1.068; P = .0018), pulmonary complications (relative risk, 1.125; 95% CI, 1.08-1.171; P < .0001), longer length of stay (PSYD mean, 6.79 days and non-PSYD mean, 5.68 days; P < .0001), higher 30-day readmission rate (9.2% vs 7.9%; P < .0001), and 90-day readmission rate (15.4% vs 12.9%; P < .007). Among patients with PSYD, those with cognitive disorders and psychotic disorders (eg, schizophrenia) appear to have the highest rates and risks of postoperative morbidity and in-hospital mortality. CONCLUSIONS: Patients with lung cancer with comorbid psychiatric disorders undergoing lobectomy experience worse postoperative outcomes with longer hospitalization, increased rates of overall and pulmonary complications, and greater readmissions suggesting potential opportunities for improved psychiatric care during the perioperative period.

Adjuvant chemotherapy, not radiotherapy, prolongs survival for node-negative non-small cell lung cancer with positive surgical margins.

Objective: The study objective was to determine differences in survival depending on adjuvant therapy type, timing, and sequence in node-negative disease with positive margins after non-small cell lung cancer resection. Methods: The National Cancer Database was queried for patients with positive margins after surgical resection of treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer who underwent adjuvant radiotherapy or chemotherapy from 2010 to 2016. Adjuvant treatment groups were defined as surgery alone, chemotherapy alone, radiotherapy alone, concurrent chemoradiotherapy, sequential chemotherapy then radiotherapy, and sequential radiotherapy then chemotherapy. The impact of adjuvant radiotherapy initiation timing on survival was evaluated using multivariable Cox regression. Kaplan-Meier curves were generated to compare 5-year survival. Results: A total of 1713 patients met inclusion criteria. Five-year survival estimates differed significantly between cohorts: surgery alone, 40.7%; chemotherapy alone, 47.0%; radiotherapy alone, 35.1%; concurrent chemoradiotherapy, 45.7%; sequential chemotherapy then radiotherapy, 36.6%; and sequential radiotherapy then chemotherapy, 32.2% (P = .033). Compared with surgery alone, adjuvant radiotherapy alone had a lower estimated survival at 5 years, although overall survival did not differ significantly (P = .8). Chemotherapy alone improved 5-year survival compared with surgery alone (P = .0016) and provided a statistically significant survival advantage over adjuvant radiotherapy (P = .002). Compared with radiotherapy-inclusive multimodal therapies, chemotherapy alone yielded similar 5-year survival (P = .066). Multivariable Cox regression showed an inverse linear association between time to adjuvant radiotherapy initiation and survival, but with an insignificant trend (10-day hazard ratio, 1.004; P = .90). Conclusions: In treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer with positive surgical margins, only adjuvant chemotherapy was associated with a survival improvement compared with surgery alone, with no radiotherapy-inclusive treatment providing additional survival benefit. Delayed timing of radiotherapy initiation was not associated with a survival reduction.

Olfactory receptor neurons generate multiple response motifs, increasing coding space dimensionality.

Odorants binding to olfactory receptor neurons (ORNs) trigger bursts of action potentials, providing the brain with its only experience of the olfactory environment. Our recordings made in vivo from locust ORNs showed that odor-elicited firing patterns comprise four distinct response motifs, each defined by a reliable temporal profile. Different odorants could elicit different response motifs from a given ORN, a property we term motif switching. Further, each motif undergoes its own form of sensory adaptation when activated by repeated plume-like odor pulses. A computational model constrained by our recordings revealed that organizing responses into multiple motifs provides substantial benefits for classifying odors and processing complex odor plumes: each motif contributes uniquely to encode the plume's composition and structure. Multiple motifs and motif switching further improve odor classification by expanding coding dimensionality. Our model demonstrated that these response features could provide benefits for olfactory navigation, including determining the distance to an odor source.

Translation of Microbiota Short-Chain Fatty Acid Mechanisms Affords Anti-infective Acyl-Salicylic Acid Derivatives.

The discovery of specific microbiota metabolite mechanisms has begun to motivate new therapeutic approaches. Inspired by our mechanistic studies of microbiota-derived short chain fatty acid (SCFA) acylation of bacterial virulence factors, here we explored covalent protein acylation therapeutics as potential anti-infectives. For these studies, we focused on acetyl-salicylic acid, aspirin, and discovered that SCFA analogues such as butyryl-salicylic acid showed significantly improved anti-infective activity against Salmonella Typhimurium. Structure-activity studies showed that the ester functionality of butyryl-salicylic acid was crucial and associated with the acylation of key bacterial virulence factors and metabolic enzymes, which are important for Salmonella infection of host cells and bacterial growth. Beyond the Gram-negative bacterial pathogens, butyryl-salicylic acid also showed better antibacterial activity compared to aspirin against Clostridioides difficile, a clinically challenging Gram-positive bacterial pathogen. Notably, coadministration of butyryl-salicylic acid, but not aspirin, effectively attenuated Salmonella pathogenesis in vivo. This study highlights how the analysis of microbiota metabolite mechanisms may inspire the repurposing and development of new anti-infective agents.