Transcriptomic analysis of the temporal host response to skin infestation with the ectoparasitic mite Psoroptes ovis

<p>Abstract</p> <p>Background</p> <p>Infestation of ovine skin with the ectoparasitic mite <it>Psoroptes ovis </it>results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Little is known regarding the mechanisms by which such a profound inflammatory response is instigated and to identify novel vaccine and drug targets a better understanding of the host-parasite relationship is essential. The main objective of this study was to perform a combined network and pathway analysis of the <it>in vivo </it>skin response to infestation with <it>P. ovis </it>to gain a clearer understanding of the mechanisms and signalling pathways involved.</p> <p>Results</p> <p>Infestation with <it>P. </it>ovis resulted in differential expression of 1,552 genes over a 24 hour time course. Clustering by peak gene expression enabled classification of genes into temporally related groupings. Network and pathway analysis of clusters identified key signalling pathways involved in the host response to infestation. The analysis implicated a number of genes with roles in allergy and inflammation, including pro-inflammatory cytokines (<it>IL1A, IL1B, IL6, IL8 </it>and <it>TNF</it>) and factors involved in immune cell activation and recruitment (<it>SELE, SELL, SELP, ICAM1, CSF2, CSF3, CCL2 </it>and <it>CXCL2</it>). The analysis also highlighted the influence of the transcription factors NF-kB and AP-1 in the early pro-inflammatory response, and demonstrated a bias towards a Th2 type immune response.</p> <p>Conclusions</p> <p>This study has provided novel insights into the signalling mechanisms leading to the development of a pro-inflammatory response in sheep scab, whilst providing crucial information regarding the nature of mite factors that may trigger this response. It has enabled the elucidation of the temporal patterns by which the immune system is regulated following exposure to <it>P. ovis</it>, providing novel insights into the mechanisms underlying lesion development. This study has improved our existing knowledge of the host response to <it>P. ovis</it>, including the identification of key parallels between sheep scab and other inflammatory skin disorders and the identification of potential targets for disease control.</p

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Utility of the Iwate difficulty scoring system for laparoscopic right posterior sectionectomy: do surgical outcomes differ for tumors in segments VI and VII?

Introduction: The Iwate Score (IS) have not been well-validated for specific procedures, especially for right posterior sectionectomy (RPS). In this study, the utility of the IS was determined for laparoscopic (L)RPS and the effect of tumor location on surgical outcomes was investigated. Methods: Post-hoc analysis of 647 L-RPS performed in 40 international centers of which 596L-RPS cases met the inclusion criteria. Baseline characteristics and perioperative outcomes of patients stratified based on the Iwate score were compared to determine whether a correlation with surgical difficulty existed. A 1:1 Mahalanobis distance matching was utilized to investigate the effect of tumor location on L-RPS outcomes. Results: The patients were stratified into 3 levels of difficulty (31 intermediate, 143 advanced, and 422 expert) based on the IS. When using a stepwise increase of the IS excluding the tumor location score, only Pringle’s maneuver was more frequently used in the higher surgical difficulty level (35.5%, 54.6%, and 65.2%, intermediate, advanced, and expert levels, respectively, Z = 3.34, p = 0.001). Other perioperative results were not associated with a statistical gradation toward higher difficulty level. 80 of 85 patients with a segment VI lesion and 511 patients with a segment VII lesion were matched 1:1. There were no significant differences in the perioperative outcomes of the two groups including open conversion, operating time, blood loss, intraoperative blood transfusion, postoperative stay, major morbidity, and mortality. Conclusion: Among patients undergoing L-RPS, the IS did not significantly correlate with most outcome measures associated with intraoperative difficulty and postoperative outcomes. Similarly, tumor location had no effect on L-RPS outcomes

Impact of body mass index on perioperative outcomes of laparoscopic major hepatectomies

Background: Data on the effect of body mass index on laparoscopic liver resections are conflicting. We performed this study to investigate the association between body mass index and postoperative outcomes after laparoscopic major hepatectomies. Methods: This is a retrospective review of 4,348 laparoscopic major hepatectomies at 58 centers between 2005 and 2021, of which 3,383 met the study inclusion criteria. Concomitant major operations, vascular resections, and previous liver resections were excluded. Associations between body mass index and perioperative outcomes were analyzed using restricted cubic splines. Modeled effect sizes were visually rendered and summarized. Results: A total of 1,810 patients (53.5%) had normal weight, whereas 1,057 (31.2%) were overweight and 392 (11.6%) were obese. One hundred and twenty-four patients (3.6%) were underweight. Most perioperative outcomes showed a linear worsening trend with increasing body mass index. There was a statistically significant increase in open conversion rate (16.3%, 10.8%, 9.2%, and 5.6%, P <.001), longer operation time (320 vs 305 vs 300 and 266 minutes, P <.001), increasing blood loss (300 vs 300 vs 295 vs 250 mL, P =.022), and higher postoperative morbidity (33.4% vs 26.3% vs 25.0% vs 25.0%, P =.009) in obese, overweight, normal weight, and underweight patients, respectively (P <.001). However, postoperative major morbidity demonstrated a “U”-shaped association with body mass index, whereby the highest major morbidity rates were observed in underweight and obese patients. Conclusion: Laparoscopic major hepatectomy was associated with poorer outcomes with increasing body mass index for most perioperative outcome measures

Impact of liver cirrhosis and portal hypertension on minimally invasive limited liver resection for primary liver malignancies in the posterosuperior segments: An international multicenter study

Introduction: To assess the impact of cirrhosis and portal hypertension (PHT) on technical difficulty and outcomes of minimally invasive liver resection (MILR) in the posterosuperior segments. Methods: This is a post-hoc analysis of patients with primary malignancy who underwent laparoscopic and robotic wedge resection and segmentectomy in the posterosuperior segments between 2004 and 2019 in 60 centers. Surrogates of difficulty (i.e, open conversion rate, operation time, blood loss, blood transfusion, and use of the Pringle maneuver) and outcomes were compared before and after propensity-score matching (PSM) and coarsened exact matching (CEM). Results: Of the 1954 patients studied, 1290 (66%) had cirrhosis. Among the cirrhotic patients, 310 (24%) had PHT. After PSM, patients with cirrhosis had higher intraoperative blood transfusion (14% vs. 9.3%; p = 0.027) and overall morbidity rates (20% vs. 14.5%; p = 0.023) than those without cirrhosis. After coarsened exact matching (CEM), patients with cirrhosis tended to have higher intraoperative blood transfusion rate (12.1% vs. 6.7%; p = 0.059) and have higher overall morbidity rate (22.8% vs. 12.5%; p = 0.007) than those without cirrhosis. After PSM, Pringle maneuver was more frequently applied in cirrhotic patients with PHT (62.2% vs. 52.4%; p = 0.045) than those without PHT. Conclusion: MILR in the posterosuperior segments in cirrhotic patients is associated with higher intraoperative blood transfusion and postoperative morbidity. This parameter should be utilized in the difficulty assessment of MILR

Impact of neoadjuvant chemotherapy on the difficulty and outcomes of laparoscopic and robotic major liver resections for colorectal liver metastases: A propensity-score and coarsened exact-matched controlled study

Background: Minimal invasive liver resections are a safe alternative to open surgery. Different scoring systems considering different risks factors have been developed to predict the risks associated with these procedures, especially challenging major liver resections (MLR). However, the impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive MLRs remains poorly investigated. Methods: Patients who underwent laparoscopic and robotic MLRs for colorectal liver metastases (CRLM) performed across 57 centers between January 2005 to December 2021 were included in this analysis. Patients who did or did not receive NAT were matched based on 1:1 coarsened exact and 1:2 propensity-score matching. Pre- and post-matching comparisons were performed. Results: In total, the data of 5189 patients were reviewed. Of these, 1411 procedures were performed for CRLM, and 1061 cases met the inclusion criteria. After excluding 27 cases with missing data on NAT, 1034 patients (NAT: n = 641; non-NAT: n = 393) were included. Before matching, baseline characteristics were vastly different. Before matching, the morbidity rate was significantly higher in the NAT-group (33.2% vs. 27.2%, p-value = 0.043). No significant differences were seen in perioperative outcomes after the coarsened exact matching. After the propensity-score matching, statistically significant higher blood loss (mean, 300 (SD 128–596) vs. 250 (SD 100–400) ml, p-value = 0.047) but shorter hospital stay (mean, 6 [4-8] vs. 6 [5-9] days, p-value = 0.043) were found in the NAT-group. Conclusion: The current study demonstrated that NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for CRLM

Comparison between the difficulty of laparoscopic limited liver resections of tumors located in segment 7 versus segment 8: An international multicenter propensity-score matched study

Background: Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma-sparing resection of the liver segments 7 and 8. Methods: A post hoc analysis of patients undergoing LLR of segments 7 and 8 in 46 centers between 2004 and 2020 was performed. 1:1 Propensity score matching (PSM) was used to compare isolated LLR of segments 7 and 8. Subset analyses were also performed to compare atypical resections and segmentectomies of 7 and 8. Results: A total of 2411 patients were identified, and 1691 patients met the inclusion criteria. Comparison after PSM between the entire cohort of segment 7 and segment 8 resections revealed inferior results for segment 7 resection in terms of increased blood loss, blood transfusions, and conversions to open surgery. Subset analyses of only atypical resections similarly demonstrated poorer outcomes for segment 7 in terms of increased blood loss, operation time, blood transfusions, and conversions to open surgery. Conversely, a subgroup analysis of segmentectomies after PSM found better outcomes for segment 7 in terms of a shorter operation time and hospital stay. Conclusion: Differences in the outcomes of segments 7 and 8 resections suggest a greater difficulty of laparoscopic atypical resection of segment 7 compared to segment 8, and greater difficulty of segmentectomy 8 compared to segmentectomy 7