[Review of anesthetic technique and 30-day mortality for cholecystectomies based on the Swedish Perioperative Registry]. / Anestesival och 30-dagars- mortalitet vid kolecystektomi.

The Swedish Perioperative Registry (SPOR) offers a unique opportunity for monitoring the peri- and early postoperative processes. It can be utilized for quality monitoring within individual clinics or for epidemiological studies. Combining SPOR's data with organ-specific registries provides a more comprehensive understanding of the overall peri- and early postoperative care and outcomes of surgical procedures. In our example, we present the expected patient profile for gall bladder surgery in Sweden. Inhalation anesthesia is the dominant technique, but Total Intravenous Anesthesia (TIVA) is showing an increasing trend in usage. There are minimal differences between the techniques in terms of early complications, with a mere 8-minute variation in recovery time. The mortality rate for cholecystectomy in Sweden is reassuringly low, with 0.02% of patients passing away within 24 hours and a 30-day mortality rate of 0.13%. As expected, advancing age and higher ASA class increase the risk of mortality within 30 days. Additionally, there is a clear area for improvement identified in increasing the utilization of LÖF's Safe Surgery Checklist.

Anaesthesia practice, quality indices including all-cause 30-day mortality associate to wrist fracture repositioning and surgery in Sweden: A perioperative register-based study 2018-2021.

BACKGROUND: Wrist fracture is one of most common fractures frequently requiring surgical anaesthesia. There is limited information related to the anaesthetic practice and quality including 30-day mortality associated with wrist fracture in Sweden in recent years. AIM: The aim of the present register-based study was to investigate the anaesthesia techniques used and quality indices including 30-day mortality associated with wrist fracture surgery in Sweden during the period 2018-2021. MATERIALS AND METHODS: All fracture repositions, and surgical interventions related to wrist fracture requiring anaesthesia in patients aged >18 years registered in the Swedish Perioperative Register (SPOR) between 2018 and 2021 were included in the analysis. Information on age, ASA class, anaesthesia technique, severe operative events, most reported side-effects during recovery room stay and all-cause 30-day mortality was collected. RESULTS: The data set included 25,147 procedures split into 14,796 females and 10,252 males (missing information n = 99) with a mean age of 52.9 ± 18.7 years and a significant age difference between females and males, 60.3 ± 15.4 and 42.2 ± 17.7 years, respectively. Mean age and ASA class increased during the study period (2018-2021), from 52.8 ± 18.6 to 54.0 ± 18.4 and ASA class 3-5 from 8.1% to 9.4% (p < .001 and p < .041, respectively). General anaesthesia (GA), GA combined with regional anaesthesia (RA), RA with or without sedation and sedation only was used in 41%, 13%, 40% and 6% of procedures, respectively, with minor changes over the study period. Pain at arrival in the recovery room (RR), (3.4%), severe pain during RR stay (2.1%), hypothermia (1.4%), postoperative nausea and vomiting (PONV) (1.2%) and urinary retention (0.5%) were the most reported side-effects during the RR stay. (RA) was associated with significantly lower occurrence of pain and PONV, and shorter RR stay, compared with GA (p < .001). The all-cause 30-day mortality was low (19 of 25,147 (0.08%)) with no differences over the period studied or anaesthetic technique. CONCLUSION: General anaesthesia or general anaesthesia combined with regional anaesthesia are the most used anaesthetic techniques for wrist fracture procedures in Sweden. Recovery room pain, PONV, hypothermia and urinary retention is reported in overall low frequencies, with no change over the period studied, but in lower frequencies for regional anaesthesia. All-cause 30-day mortality was low; 0.08% with no change over time or between anaesthetic techniques. Thus, the present quality review based on SPOR data supports high quality of perioperative anaesthesia care.

Proteomics uncover EPHA2 as a potential novel therapeutic target in colorectal cancer cell lines with acquired cetuximab resistance.

BACKGROUND: In metastatic colorectal cancer (mCRC), acquired resistance against anti-EGFR targeted monoclonal antibodies, such as cetuximab (CET), was shown to be frequently caused by activating alterations in the RAS genes KRAS or NRAS. To this day, no efficient follow-up treatment option has emerged to treat mCRC in such a setting of resistance. METHODS: To uncover potential targets for second-line targeted therapies, we used mass-spectrometric proteomics to shed light on kinome reprogramming in an established cellular model of acquired, KRAS-associated CET resistance. RESULTS: This CET resistance was reflected by significant changes in the kinome, most of them individual to each cell line. Interestingly, all investigated resistant cell lines displayed upregulation of the Ephrin type-A receptor 2 (EPHA2), a well-known driver of traits of progression. Expectedly resistant cell lines displayed increased migration (p < 0.01) that was significantly reduced by targeting the EPHA2 signalling axis using RNA interference (RNAi) (p < 0.001), ephrin-A1 stimulation (p < 0.001), dasatinib (p < 0.01), or anti-EPHA2 antibody treatment (p < 0.001), identifying it as an actionable target in mCRC with acquired CET resistance. CONCLUSION: These results highlight EPHA2 and its role in mCRC with KRAS-gene mutated acquired CET resistance and support its use as a potential actionable target for the development of future precision medicine therapies.

Pulmonary Vasodilation by Intravenous Infusion of Organic Mononitrites Of 1,2-Propanediol in Acute Pulmonary Hypertension Induced by Aortic Cross Clamping and Reperfusion: A Comparison With Nitroglycerin in Anesthetized Pigs.

INTRODUCTION: Suprarenal aortic cross clamping (SRACC) and reperfusion may cause acute pulmonary hypertension and multiple organ failure. HYPOTHESIS: The organic mononitrites of 1,2-propanediol (PDNO), an nitric oxide donor with a very short half-life, are a more efficient pulmonary vasodilator and attenuator of end-organ damage and inflammation without significant side effects compared with nitroglycerin and inorganic nitrite in a porcine SRACC model. METHODS: Anesthetized and instrumented domestic pigs were randomized to either of four IV infusions until the end of the experiment (n = 10 per group): saline (control), PDNO (45 nmol kg min), nitroglycerin (44 nmol kg min), or inorganic nitrite (a dose corresponding to PDNO). Thereafter, all animals were subjected to 90 min of SRACC and 10 h of reperfusion and protocolized resuscitation. Hemodynamic and respiratory variables as well as blood samples were collected and analysed. RESULTS: During reperfusion, mean pulmonary arterial pressure and pulmonary vascular resistance were significantly lower, and stroke volume was significantly higher in the PDNO group compared with the control, nitroglycerin, and inorganic nitrite groups. In parallel, mean arterial pressure, arterial oxygenation, and fraction of methaemoglobin were similar in all groups. The serum concentration of creatinine and tumor necrosis factor alpha were lower in the PDNO group compared with the control group during reperfusion. CONCLUSIONS: PDNO was an effective pulmonary vasodilator and appeared superior to nitroglycerin and inorganic nitrite, without causing significant systemic hypotension, impaired arterial oxygenation, or methaemoglobin formation in an animal model of SRACC and reperfusion. Also, PDNO may have kidney-protective effects and anti-inflammatory properties.

Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia-reperfusion model involving aortic clamping.

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia-reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)-sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.