Low field vortex dynamics over seven time decades in a Bi_2Sr_2CaCu_2O_{8+\delta} single crystal for temperatures 13 K < T < 83 K

Using a custom made dc-SQUID magnetometer, we have measured the time relaxation of the remanent magnetization M_rem of a Bi_2Sr_2CaCu_2O_{8+\delta} single crystal from the fully critical state for temperatures 13 K < T < 83 K. The measurements cover a time window of seven decades 10^{-2} s < t < 10^5 s, so that the current density j can be studied from values very close to j_c down to values considerably smaller than j_c. From the data we have obtained: (i) the flux creep activation barriers U as a function of current density j, (ii) the current-voltage characteristics E(j) in a typical range of 10^{-7} V/cm to 10^{-15} V/cm, and (iii) the critical current density j_c(0) at T = 0. Three different regimes of vortex dynamics are observed: For temperatures T < 20 K the activation barrier U(j) is logarithmic, no unique functional dependence U(j) could be found for the intermediate temperature interval 20 K < T < 40 K, and finally for T > 40 K the activation barrier U(j) follows a power-law behavior with an exponent mu = 0.6. From the analysis of the data within the weak collective pinning theory for strongly layered superconductors, it is argued that for temperatures T < 20 K pancake-vortices are pinned individually, while for temperatures T > 40 K pinning involves large collectively pinned vortex bundles. A description of the vortex dynamics in the intermediate temperature interval 20 K < T < 40 K is given on the basis of a qualitative low field phase diagram of the vortex state in Bi_2Sr_2CaCu_2O_{8+\delta}. Within this description a second peak in the magnetization loop should occur for temperatures between 20 K and 40 K, as it has been observed in several magnetization measurements in the literature.Comment: 12 pages, 10 figure

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2): study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day FitbitTM measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023

Implementation and outcome of minimally invasive pancreatoduodenectomy in Europe:a registry-based retrospective study A critical appraisal of the first 3 years of the E-MIPS registry

BACKGROUND: International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe. MATERIALS AND METHODS: A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019-2021). The main outcomes of interest were major morbidity (Clavien-Dindo grade ≥3) and 30-day/in-hospital mortality. RESULTS: Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8-21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 ( P =0.424). Rates of conversion (7.4 vs. 14.8% P &lt;0.001) and reoperation (8.9 vs. 15.1% P &lt;0.001) were lower in centers, which fulfilled the Miami volume cut-off. CONCLUSION: During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period.</p

Implementation and outcome of minimally invasive pancreatoduodenectomy in Europe:a registry-based retrospective study A critical appraisal of the first 3 years of the E-MIPS registry

BACKGROUND: International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe. MATERIALS AND METHODS: A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019-2021). The main outcomes of interest were major morbidity (Clavien-Dindo grade ≥3) and 30-day/in-hospital mortality. RESULTS: Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8-21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 ( P =0.424). Rates of conversion (7.4 vs. 14.8% P &lt;0.001) and reoperation (8.9 vs. 15.1% P &lt;0.001) were lower in centers, which fulfilled the Miami volume cut-off. CONCLUSION: During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period.</p

An updated evaluation of the implementation of the sigmoid take-off landmark 1 year after the official introduction in the Netherlands

PURPOSE: The definition of rectal cancer based on the sigmoid take-off (STO) was incorporated into the Dutch guideline in 2019, and became mandatory in the national audit from December 2020. This study aimed to evaluate the use of the STO in clinical practice and the added value of online training, stratified for the period before (group A, historical cohort) and after (group B, current cohort) incorporation into the national audit.METHODS: Participants, including radiologists, surgeons, surgical and radiological residents, interns, PhD students, and physician assistants, were asked to complete an online training program, consisting of questionnaires, 20 MRI cases, and a training document. Outcomes were agreement with the expert reference, inter-rater variability, and accuracy before and after the training.RESULTS: Group A consisted of 86 participants and group B consisted of 114 participants. Familiarity with the STO was higher in group B (76% vs 88%, p = 0.027). Its use in multidisciplinary meetings was not significantly higher (50% vs 67%, p = 0.237). Agreement with the expert reference was similar for both groups before (79% vs 80%, p = 0.423) and after the training (87% vs 87%, p = 0.848). Training resulted in significant improvement for both groups in classifying tumors located around the STO (group A, 69-79%; group B, 67-79%, p &lt; 0.001).CONCLUSIONS: The results of this study show that after the inclusion of the STO in the mandatory Dutch national audit, the STO was consequently used in only 67% of the represented hospitals. Online training has the potential to improve implementation and unambiguous assessment.</p

Robot-assisted versus laparoscopic pancreatoduodenectomy: a pan-European multicenter propensity-matched study

Background: The use of robot -assisted and laparoscopic pancreatoduodenectomy is increasing, yet large adjusted analyses that can be generalized internationally are lacking. This study aimed to compare outcomes after robot -assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy in a pan-European cohort. Methods: An international multicenter retrospective study including patients after robot -assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy from 50 centers in 12 European countries (2009-2020). Propensity score matching was performed in a 1:1 ratio. The primary outcome was major morbidity (Clavien-Dindo >= III). Results: Among 2,082 patients undergoing minimally invasive pancreatoduodenectomy, 1,006 underwent robot -assisted pancreatoduodenectomy and 1,076 laparoscopic pancreatoduodenectomy. After matching 812 versus 812 patients, the rates of major morbidity (31.9% vs 29.6%; P = .347) and 30-day/inhospital mortality (4.3% vs 4.6%; P = .904) did not differ significantly between robot -assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy, respectively. Robot -assisted pancreatoduodenectomy was associated with a lower conversion rate (6.7% vs 18.0%; P < .001) and higher lymph node retrieval (16 vs 14; P = .003). Laparoscopic pancreatoduodenectomy was associated with shorter operation time (446 minutes versus 400 minutes; P < .001), and lower rates of postoperative pancreatic fistula grade B/C (19.0% vs 11.7%; P < .001), delayed gastric emptying grade B/C (21.4% vs 7.4%; P < .001), and a higher R0 -resection rate (73.2% vs 84.4%; P < .001). Conclusion: This European multicenter study found no differences in overall major morbidity and 30day/in-hospital mortality after robot -assisted pancreatoduodenectomy compared with laparoscopic pancreatoduodenectomy. Further, laparoscopic pancreatoduodenectomy was associated with a lower rate of postoperative pancreatic fistula, delayed gastric emptying, wound infection, shorter length of stay, and a higher R0 resection rate than robot -assisted pancreatoduodenectomy. In contrast, robot -assisted pancreatoduodenectomy was associated with a lower conversion rate and a higher number of retrieved lymph nodes as compared with laparoscopic pancreatoduodenectomy. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2):study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023.</p

Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics

Aldosterone is synthesised by aldosterone synthase (CYP11B2). CYP11B2 has a highly homologous isoform, steroid 11β-hydroxylase (CYP11B1), which is responsible for the biosynthesis of aldosterone precursors and glucocorticoids. To investigate aldosterone biosynthesis and facilitate the search for selective CYP11B2 inhibitors, we constructed three-dimensional models for CYP11B1 and CYP11B2 for both human and rat. The models were constructed based on the crystal structure of Pseudomonas Putida CYP101 and Oryctolagus Cuniculus CYP2C5. Small steric active site differences between the isoforms were found to be the most important determinants for the regioselective steroid synthesis. A possible explanation for these steric differences for the selective synthesis of aldosterone by CYP11B2 is presented. The activities of the known CYP11B inhibitors metyrapone, R-etomidate, R-fadrazole and S-fadrazole were determined using assays of V79MZ cells that express human CYP11B1 and CYP11B2, respectively. By investigating the inhibitors in the human CYP11B models using molecular docking and molecular dynamics simulations we were able to predict a similar trend in potency for the inhibitors as found in the in vitro assays. Importantly, based on the docking and dynamics simulations it is possible to understand the enantioselectivity of the human enzymes for the inhibitor fadrazole, the R-enantiomer being selective for CYP11B2 and the S-enantiomer being selective for CYP11B1

Will emergency and surgical patients participate in and complete alcohol interventions? A systematic review

<p>Abstract</p> <p>Background</p> <p>In the everyday surgical life, staff may experience that patients with Alcohol Use Disorders (AUDs) seem reluctant to participate in alcohol intervention programs. The objective was therefore to assess acceptance of screening and intervention as well as adherence to the intervention program among emergency department (ED) and surgical patients with AUDs.</p> <p>Methods</p> <p>A systematic literature search was followed by extraction of acceptance and adherence rates in ED and surgical patients. Numbers needed to screen (NNS) were calculated. Subgroup analyses were carried out based on different study characteristics.</p> <p>Results</p> <p>The literature search revealed 33 relevant studies. Of these, 31 were randomized trials, 28 were conducted in EDs and 31 evaluated the effect of brief alcohol intervention. Follow-up was mainly conducted after six and/or twelve months.</p> <p>Four in five ED patients accepted alcohol screening and two in three accepted participation in intervention. In surgical patients, two in three accepted screening and the intervention acceptance rate was almost 100%. The adherence rate was above 60% for up to twelve months in both ED and surgical patients. The NNS to identify one eligible AUD patient and to get one eligible patient to accept participation in alcohol intervention varied from a few up to 70 patients.</p> <p>The rates did not differ between randomized and non-randomized trials, brief and intensive interventions or validated and self-reported alcohol consumption. Adherence rates were not affected by patients' group allocation and type of follow-up.</p> <p>Conclusions</p> <p>Most emergency and surgical patients with AUD accept participation in alcohol screening and interventions and complete the intervention program.</p