BackgroundInhalative nanocarriers for local or systemic therapy are promising. Gold nanoparticles (AuNP) have been widely considered as candidate material. Knowledge about their interaction with the lungs is required, foremost their uptake by surface macrophages and epithelial cells.Diseased lungs are of specific interest, since these are the main recipients of inhalation therapy. We, therefore, used Scnn1b-transgenic (Tg) mice as a model of chronic obstructive pulmonary disease (COPD) and compared uptake and localization of inhaled AuNP in surface macrophages and lung tissue to wild-type (Wt) mice.MethodsScnn1b-Tg and Wt mice inhaled a 21-nm AuNP aerosol for 2 h. Immediately (0 h) or 24 h thereafter, bronchoalveolar lavage (BAL) macrophages and whole lungs were prepared for stereological analysis of AuNP by electron microscopy.ResultsAuNP were mainly found as singlets or small agglomerates of ≤ 100 nm diameter, at the epithelial surface and within lung-surface structures. Macrophages contained also large AuNP agglomerates (> 100 nm). At 0 h after aerosol inhalation, 69.2±4.9% AuNP were luminal, i.e. attached to the epithelial surface and 24.0±5.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 35.3±32.2% AuNP were on the epithelium and 58.3±41.4% in macrophages. The percentage of luminal AuNP decreased from 0 h to 24 h in both groups. At 24 h, 15.5±4.8% AuNP were luminal, 21.4±14.2% within epithelial cells and 63.0±18.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 9.5±5.0% AuNP were luminal, 2.2±1.6% within epithelial cells and 82.8±0.2% in macrophages. BAL-macrophage analysis revealed enhanced AuNP uptake in Wt animals at 0 h and in Scnn1b-Tg mice at 24 h, confirming less efficient macrophage uptake and delayed clearance of AuNP in Scnn1b-Tg mice.ConclusionsInhaled AuNP rapidly bound to the alveolar epithelium in both Wt and Scnn1b-Tg mice. Scnn1b-Tg mice showed less efficient AuNP uptake by surface macrophages and concomitant higher particle internalization by alveolar type I epithelial cells compared to Wt mice. This likely promotes AuNP depth translocation in Scnn1b-Tg mice, including enhanced epithelial targeting. These results suggest AuNP nanocarrier delivery as successful strategy for therapeutic targeting of alveolar epithelial cells and macrophages in COPD.

BACKGROUNDAfter the successful implementation in trauma, damage-control surgery (DCS) is being increasingly used in patients with nontraumatic emergencies. However, the role of DCS in the nontrauma setting is not well defined. The aim of this study was to investigate the effect of DCS on mortality in patients with nontraumatic abdominal emergencies.METHODSSystematic literature search was done using PubMed. Original articles addressing nontrauma DCS were included. Two meta-analyses were performed, comparing (1) mortality in patients undergoing nontrauma DCS versus conventional surgery (CS) and (2) the observed versus expected mortality rate in the DCS group. Expected mortality was derived from Acute Physiology And Chronic Health Evaluation, Simplified Acute Physiology Score, and Portsmouth Physiological and Operative Severity Score for enUmeration of Mortality and Morbidity scores.RESULTSA total of five nonrandomized prospective and 16 retrospective studies were included. Nontrauma DCS was performed in 1,238 and nontrauma CS in 936 patients. Frequent indications for surgery in the DCS group were (weighted proportions) hollow viscus perforation (28.5%), mesenteric ischemia (26.5%), anastomotic leak and postoperative peritonitis (19.6%), nontraumatic hemorrhage (18.4%), abdominal compartment syndrome (17.8%), bowel obstruction (15.5%), and pancreatitis (12.9%). In meta-analysis 1, including eight studies, mortality was not significantly different between the nontrauma DCS and CS group (risk difference, 0.09; 95% confidence interval, −0.06 to 0.24). Meta-analysis 2, including 14 studies, revealed a significantly lower observed than expected mortality rate in patients undergoing nontrauma DCS (risk difference, −0.18; 95% confidence interval, −0.29 to −0.06).CONCLUSIONThis meta-analysis revealed no significantly different mortality in patients undergoing nontrauma DCS versus CS. However, observed mortality was significantly lower than the expected mortality rate in the DCS group, suggesting a benefit of the DCS approach. Based on these two findings, the effect of DCS on mortality in patients with nontraumatic abdominal emergencies remains unclear. Further prospective investigation into this topic is warranted.LEVEL OF EVIDENCESystematic review and meta-analysis, level III.

Objective After the successful implementation in trauma patients, damage control surgery (DCS) is being increasingly used in non-traumatic abdominal emergencies, too. However, non-trauma DCS (NT-DCS) is currently a matter of debate and has not yet been comprehensively assessed. The aim of this meta-analysis was to investigate the effect of NT-DCS on mortality in patients with abdominal emergencies. Methods Systematic literature search using PubMed. Original articles addressing mortality in patients undergoing NT-DCS or non-trauma conventional surgery (NT-CS) for abdominal emergencies were included. Descriptive statistics and two meta-analyses were performed. Meta-analysis 1 compared mortality in patients undergoing NT-DCS vs. NT-CS. Meta-analysis 2 assessed the observed vs. expected mortality rate, based on APACHE, POSSUM and SAPS scores, in the NT-DCS group. Continuous and categorical variables were reported as weighted means and proportions. Effect sizes were described as risk differences (RD) with 95% confidence intervals (CI). Results Literature search revealed 1314 articles. Of these, 21 studies published 2004-2019 were included. NT-DCS was performed in 1238 and NT-CS in 936 patients. In the NT-DCS vs. NT-CS group mean age was 61.0 vs. 64.9 years and the proportion of male patients 58.6% vs. 52.9%, respectively. Most frequent indications for NT-DCS were hollow viscus perforation (28.4%), mesenteric ischemia (26.5%), anastomotic leak (19.6%), haemorrhage (18.4%), abdominal compartment syndrome (17.4%), bowel obstruction (15.5%), and pancreatitis (13.1%). In meta-analysis 1, mortality was not significantly different in the NT-DCS vs. NT-CS group (RD 0.09, 95% CI -0.06/0.24). Meta-analysis 2 revealed a significantly lower observed than the expected mortality rate in patients undergoing NT-DCS (RD -0.18, 95 % CI -0.29/-0.06). Heterogeneity of included studies was high in both meta-analyses (I2=89.0% and 79.9%, respectively). Conclusion This meta-analysis revealed no significantly different mortality in patients with abdominal emergencies undergoing NT-DCS vs. NT-CS. However, observed mortality was significantly lower than the expected mortality rate in the NT-DCS group, suggesting a benefit of the DCS approach. Based on these results, the effect of DCS in patients with non-traumatic abdominal emergencies remains unclear. Further prospective investigation into this topic is warranted.

Objective Running emergency general surgery (EGS) services is challenging and requires significant personnel and institutional resources. In addition, increasing specialization of surgeons has made the provision of EGS services more problematic. The aim of this study was to elaborate a nationwide overview of the individual hospital organization systems of EGS services in Switzerland and to find related challenges and difficulties. Methods Telephone based standardized survey of all Swiss hospitals with a state medical treatment contract of the Swiss Federal Office of Public Health (FOPH) including a surgical and emergency unit (ER). The telephone interviews were conducted between December 2021 and January 2022. A corresponding junior, senior consultant or attending surgeon was interviewed per hospital by one of four interviewers. Descriptive and univariate analysis was performed using SPSS Version 28. Results A total of 72 of 79 (91.1%) surgical clinics participated in the telephone survey. There were 19 (26.4%) hospitals with <100 beds, 37 (54.2%) hospitals with 100–300 beds, 7 (9.7%) with 300–600 beds, and 7 (9–7%) with >600 beds. 57 (79.2%) hospitals have both, an ER and an intensive care unit (ICU). Eight (11.1%) hospitals have solely an intermediate care unit (IMC), 7 (9.7%) solely an ER. The average number of surgeons per hospital was proportional to the size of the hospital: 11.1±4.1 surgeons in hospitals <100 beds, 23.1±8.8 surgeons in hospitals with 100–300 beds, 29.1±10 surgeons in hospitals with 300–600 beds, and 37.7±9.4 surgeons in hospitals >600 beds. The percentage of surgical staff on EGS service per hospital was significantly higher in smaller hospitals (<100 beds), however, with a smaller number of surgeons on service per day. Regarding personal resources to run the EGS services, for hospitals with >300 beds similar person-days per month were found (159.7±24.7). Conclusion This study elaborates and characterises for the first time EGS services in Switzerland. Different EGS systems are in place and are related to the size of the hospitals. The individual EGS systems have been discussed regarding (1) surgical expertise, (2) continuity of treating surgical teams, (3) teaching and (4) optimization of personnel hospital resources. Moreover, based on these results, recommendations have been made to optimize EGS services.