Challenges to Societal Progress - Pull-back in Response to Disparities

There are empirical grounds for supporting unrestrained, globalized cooperative human measures as being beneficial to the international standard of living. A high extent of interconnectedness on multiple levels has already been realized in transportation systems, energy distribution channels, and communication networks. However, in periods of societal transition, as can be the case under rapid technology development, tensions may arise if disparities in wealth, power, or infrastructure access widen extensively. When subgroups of the citizenry that do not sufficiently partake in progress feel left behind or disenfranchised, their triggering of pull-back phenomena is very common. The pattern is repetitive: disparities not remedied on a lower scale impair integration on a larger scale. Equitable infrastructure maintenance and development, regionally, nationally, and globally, is a powerful policy tool for preempting pull-backs – especially if it is applied to communities with weak support or high inequality. The characteristics of the modern world demand far-reaching collaborations. Only universal interdependence, built from the roots up, can enable progress and social justice

Influence of Hospital Volume Effects and Minimum Caseload Requirements on Quality of Care in Pancreatic Surgery in Germany

Introduction: Numerous international studies have identified hospital volume as significant independent variable of death following pancreatic surgery. Most of these studies were limited to regions of countries or portions of a national population and did not include data on volume-outcome effects in Germany. Methods: The Medline database was systematically searched to identify studies that analyzed volume-outcome relationships and effects of minimum caseload requirements on outcomes of pancreatic surgery in Germany. Results: Recent observational studies utilizing German hospital discharge data confirmed that patients undergoing pancreatic surgery in Germany also have better outcomes when treated in facilities with high annual caseloads. Besides a decreased risk of in-hospital mortality, there is also a reduced risk of 1-year mortality in high-volume hospitals. In addition, there is evidence that adherence to already existing minimum caseload requirements reduces morbidity and mortality of pancreatic surgery in Germany. As a result of an insufficient centralization in the recent past, however, a large proportion of hospitals that perform pancreatic surgery still do not meet minimum caseload requirements. Conclusions: Specific measures (i.e. sanctions for failure to achieve minimum volumes) that initiate a sufficient centralization process without threatening patient access to surgical care are needed

The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer

Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and personalized targeted cancer therapy is becoming a promising treatment strategy for PaCa. The central approach of targeted therapy is to find a targetable key and an effective targeting method. In this study, the importance of GPRC5a (the G-protein-coupled receptor family C, member 5, group A) was identified using data mining methods based on published datasets. After analysis of the basic expression of GPRC5a in normal pancreas tissue and various PaCa cell lines, gene editing of GPRC5a in the human PaCa cell line MIA PaCa-2 and the mouse PaCa cell line TB32047 was performed using CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins 9) to investigate the influence of GPRC5a on the proliferation and migration of PaCa cells as well as its effects on chemotherapy drug resistance. The results showed that GPRC5a was upregulated in PaCa tissues and various PaCa cell lines. Knockout of GPRC5a reduced the proliferation and migration ability of PaCa cell lines and suppressed the chemotherapy drug resistance of gemcitabine, oxaliplatin, and fluorouracil in PaCa cells. The phosphorylation of GSK-3β (Glycogen synthase kinase-3β) was found to be upregulated in the MIA PaCa-2 and TB32047 cells after GPRC5a knockout. In conclusion, GPRC5a was upregulated in PaCa leading to an enhanced drug resistance in PaCa cells. These results provide for the first time a theoretical basis for the development of an improved PaCa targeted therapy

Risk Factors for Postoperative Morbidity, Suture Insufficiency, Re-Surgery and Mortality in Patients with Gastroduodenal Perforation

(1) Background: The aim of the present study was to identify risk factors associated with postoperative morbidity, suture/anastomotic insufficiency, re-surgery, and mortality in patients undergoing surgery for gastroduodenal perforation. (2) Methods: A retrospective analysis of 273 adult patients who received surgical treatment for gastroduodenal perforation from January 2006 to June 2021 at the University Hospital Erlangen was performed. The patient demographics and preoperative, intraoperative, and postoperative parameters were collected and compared among the different outcome groups (in-hospital morbidity, suture/anastomotic insufficiency, re-surgery, and 90-day mortality). (3) Results: In-hospital morbidity, suture/anastomotic insufficiency, need for re-surgery, and 90-day mortality occurred in 71%, 10%, 26%, and 25% of patients, respectively. The independent risk factors for morbidity were a significantly reduced general condition, a lower preoperative hemoglobin level, and a higher preoperative creatinine level. The independent risk factors for suture/anastomotic insufficiency could be identified as an intake of preoperative steroids and a perforation localization in the proximal stomach or duodenum. The four parameters were independent risk factors for the need for re-surgery: a significantly reduced general condition, a perforation localization in the proximal stomach, a higher preoperative creatinine level, and a higher preoperative CRP level. An age over 66 years and a higher preoperative CRP level were independent risk factors for 90-day mortality. (4) Conclusions: Our study could identify relevant risk factors for the postoperative outcome of patients undergoing surgical treatment for gastroduodenal perforation. Patients exhibiting the identified risk factors should receive heightened attention in the postoperative period and may potentially benefit from personalized and tailored therapy.</p

Weeds in the treated field - a realistic scenario for pollinator risk assessment?

In July 2013 the European Food Safety Authority (EFSA) released its final guidance on the risk assessment of plant protection products (PPPs) to bees1. One objective of the guidance was to produce a simple and cost effective first tier risk assessment scheme to ensure that the appropriate level of protection is achieved. However, recent impact analyses have indicated that the first tier of this risk assessment does not act effectively as a screen for compounds of low risk to bees. For example substances showing no toxicity to bees often fail the tier 1 risk assessment based on a worst-case exposure to flowering weeds inside the treated field. If realistic farming practices (e.g. tillage and herbicide applications) are considered, weeds are not usually prevalent in arable fields. It is therefore suggested that the scenarios in the guidance could be considered overly conservative and in some instances unrealistic. The EFSA guidance states that if &lt;10% of the area of use is flowering weeds then the exposure route is not relevant in the 90th %ile case, and thus does not need to be considered. However, despite this, the option to generate data or refine assessments based on available data is questioned as no guidance for the assessment of the abundance of weeds is available. As part of an industry-led initiative we present and discuss the use of empirical evidence (i.e. occurrence and growth stage of weeds in control plots from herbicide efficacy field trials conducted for regulatory submission) to illustrate that the scenarios in the guidance document could be modified using currently available data to create a more effective tier 1 risk assessment and still ensure that the appropriate level of protection is achieved. We have demonstrated here that less than 2% of all weeds recorded in arable crop trials (represented here by wheat, oilseed rape, sugar beet, sunflower, potatoes, maize, peas and beans) are at a flowering growth stage; therefore in arable crops the flowering weeds scenario is not applicable for the 90th %ile exposure. For permanent crop trials (represented here by orchards and vines) 37% of weeds were recorded at a flowering growth stage. When the attractiveness and density data are considered, the percentage of attractive, flowering weeds which cover &gt;10% of the ground area is only 12.3%, indicating that for permanent crops further investigation may be required as to whether this scenario is relevant

Continuous or interrupted suture technique for hepaticojejunostomy during pancreatoduodenectomy (HEKTIK trial): study protocol of a randomized controlled multicenter trial

Background Hepaticojejunostomy is commonly performed in hepato-bilio-pancreatic surgery, particularly during pancreaticoduodenectomy. The purpose of this study is to evaluate the safety and efficiency of two commonly applied suture techniques (the interrupted versus the continuous suture technique) in patients undergoing a hepaticojejunostomy during pancreatoduodenectomy. Methods The HEKTIK trial is a multicenter, randomized controlled, patient-blinded surgical explorative trial with two parallel study groups. An adaptive sample size design was chosen: First, 100 patients scheduled for surgery including a hepaticojejunostomy will be randomized 1:1 either to the interrupted suture technique or the continuous suture technique after informed consent. Based on this data, needed sample size will be adjusted. The primary endpoint will be the occurrence of anastomotic leakage of hepaticojejunostomy, defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis (according to the definition of ISGLS). Further perioperative parameters like other morbidities as well as duration and costs of the hepaticojejunostomy will be analyzed as secondary outcomes. Discussion Until now there are no randomized controlled comparative data of these two suture techniques for hepaticojejunostomy. The HEKTIK trial will investigate the yet unanswered question of whether the interrupted suture or the continuous suture technique has advantages performing a hepaticojejunostomy during pancreatoduodenectomy. Trial registration German Clinical Trials Register DRKS00024395. Registered on 01 February 2021

The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection

Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.info:eu-repo/semantics/publishedVersio

Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions

Pancreatic cancer is one of the most lethal malignancies and is associated with a poor prognosis. Surgery is considered the only potential curative treatment for pancreatic cancer, followed by adjuvant chemotherapy, but surgery is reserved for the minority of patients with non-metastatic resectable tumors. In the future, neoadjuvant treatment strategies based on molecular testing of tumor biopsies may increase the amount of patients becoming eligible for surgery. In the context of non-metastatic disease, patients with resectable or borderline resectable pancreatic carcinoma might benefit from neoadjuvant chemo- or chemoradiotherapy followed by surgeryPatients with locally advanced or (oligo-/poly-)metastatic tumors presenting significant response to (neoadjuvant) chemotherapy should undergo surgery if R0 resection seems to be achievable. New immunotherapeutic strategies to induce potent immune response to the tumors and investigation in molecular mechanisms driving tumorigenesis of pancreatic cancer may provide novel therapeutic opportunities in patients with pancreatic carcinoma and help patient selection for optimal treatment