Prioritization, Incentives, and Resource Use for Sustainable Dentistry: The EU PRUDENT Project.

KNOWLEDGE TRANSFER STATEMENT: The EU PRUDENT project aims to enhance the financing of oral health systems through novel evidence and implementation of better financing solutions together with citizens, patients, providers, and policy makers. The multicountry nature of the project offers unique windows of opportunity for rapid learning and improving within and across various contexts. PRUDENT is anticipated to strengthen capacities for better oral care financing in the EU and worldwide.

Income inequality and depressive symptoms among Chinese adults: a quasi-experimental study.

OBJECTIVE: There is a lack of causal evidence on the impact of income inequality on depressive symptoms. The impact of China's Targeted Poverty Alleviation (TPA) policy on depressive symptoms is also unclear. Using a quasi-experimental design, this study aims to investigate the causal effects of TPA and income inequality on depressive symptoms among Chinese adults. STUDY DESIGN: This is a population-based study. METHODS: Three waves (2012, 2016, and 2018) of the China Family Panel Studies (CFPS), a nationally representative sample of China, were included in this study. We performed difference-in-difference (DID) models to assess the effect of TPA and income inequality on depressive symptoms. We further conducted the mixed effect models to examine the impact of income inequality on depressive symptoms. The study considered a range of spatial factors and spatial splines to address spatial autocorrelations. RESULTS: This study included valid measures of depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D-8] score) from 14,442 adults of CFPS. The DID results indicated that at the provincial level, the CES-D-8 score of the TPA treatment group was on average 0.570 (95% confidence interval [CI]: 0.358-0.783) less than the control group. Furthermore, a 0.1 increase in Gini index would lead to a 0.256 (95% CI: 0.064-0.448) increase in CES-D-8 score. The mixed effect model showed that income inequality was a risk factor for depressive symptoms at the provincial level (excess risk = 5.602% [95% CI: 3.047%-8.219%]). CONCLUSIONS: Our findings suggest that income inequality adversely affects mental health, but China's Targeted Poverty Alleviation improves the mental health of the Chinese population.

[Surgery for primary splenic tumors and metastases of the spleen]. / Chirurgie bei primären Milztumoren und Metastasen der Milz.

The correct indications for surgical treatment of primary splenic tumors as well as metastases of the spleen are challenging due to the rarity of the various entities. Primary solid splenic tumors include benign lesions, such as hemangiomas, hamartomas and sclerosing angiomatous nodular transformation (SANT) of the spleen. In these cases, surgical treatment is indicated only in the case of inconclusive imaging and after careful consideration of the risk-benefit ratio, even in the case of pronounced symptoms. In contrast, primary angiosarcoma or undifferentiated pleomorphic sarcoma as highly malignant tumors represent an urgent indication for surgery. Although more frequent than primary splenic malignancies, secondary splenic tumors are also not that frequent. Solitary splenic metastases are rare; however, from an oncological point of view they can be treated by resection. In the case of oligometastasis with splenic involvement, splenectomy is used only as part of a palliative concept in cases of pronounced symptoms or in the context of cytoreductive surgery. In general, the laparoscopic approach is to be preferred when the operation is technically feasible as it is associated with fewer pulmonary and infectious complications and a shorter hospital stay. In addition, to reduce the risk of severe infections after splenectomy, the option of partial splenectomy should be considered, especially for benign lesions. A thorough informing of the patient regarding both intraoperative and perioperative risks as well as potential long-term sequelae, especially severe infectious diseases, is an essential component of informed consent before surgery.

Effect of thoracic cage width on surgery time and postoperative outcome in minimally invasive esophagectomy.

INTRODUCTION: Minimally invasive esophagectomy (MIE) for esophageal cancer is a complex procedure that reduces postoperative morbidity in comparison to open approach. In this study, thoracic cage width as a factor to predict surgical difficulty in MIE was evaluated. METHODS: All patients of our institution receiving either total MIE or robotic-assisted MIE (RAMIE) with intrathoracic anastomosis between February 2016 and April 2021 for esophageal cancer were included in this study. Right unilateral thoracic cage width on the level of vena azygos crossing the esophagus was measured by the horizontal distance between the esophagus and parietal pleura on preoperative computer tomography. Patients' data as well as operative and postoperative details were collected in a prospective database. Correlation between thoracic cage width with duration of the thoracic procedure and postoperative complication rates was analyzed. RESULTS: Overall, 313 patients were eligible for this study. Thoracic width on vena azygos level ranged from 85 to 149 mm with a mean of 116.5 mm. In univariate analysis, a small thoracic width significantly correlated with longer duration of the thoracic procedure (p = 0.014). In multivariate analysis, small thoracic width and neoadjuvant therapy were identified as independent factors for long duration of the thoracic procedure (p = 0.006). Regarding postoperative complications, thoracic cage width was a significant risk factor for occurrence of postoperative pneumonia in the multivariate analysis (p = 0.045). Dividing the cohort into two groups of patients with narrow (≤ 107 mm, 19.5%) and wide thoraces (≥ 108 mm, 80.5%), the thoracic procedure was significantly prolonged by 17 min (204 min vs. 221 min, p = 0.014). CONCLUSION: A small thoracic cage width is significantly correlated with longer operation time during thoracic phase of a MIE in Europe, which suggests increased surgical difficulty. Patients with small thoracic cage width may preferably be operated by MIE-experienced surgeons.

Education Team Time Out in Oncologic Visceral Surgery Optimizes Surgical Resident Training and Team Communication-Results of a Prospective Trial.

BACKGROUND: Surgical education is highly dependent on intraoperative communication. Trainers must know the trainee's training level to ensure high-quality surgical training. A systematic preoperative dialogue (Educational Team Time Out, ETO) was established to discuss the steps of each surgical procedure. METHODS: Over 6 months, ETO was performed within a time limit of 3 minutes. Digital surveys on the utility of ETO and its impact on performance were conducted immediately after surgery and at the end of the study period among the staff of the participating disciplines (trainer, trainee, surgical nursing staff, anaesthesiologists, and medical students). The number of surgical substeps performed was recorded and compared with the equivalent period one year earlier. RESULTS: ETO was performed in 64 of the 103 eligible operations (62%). Liver resection (n = 37) was the most frequent procedure, followed by left-sided colorectal surgery (n = 12), partial pancreaticoduodenectomy (n = 6), right-sided hemicolectomies (n = 5), and thyroidectomies (n = 4). Anaesthesiologists most frequently reported that ETO had a direct impact on their work during surgery (90.9%). The influence scores were 46.8% for trainees, 8.8% for trainers, 53.3% for surgical nursing staff and 66.6% for medical students. During the implementation of ETO, a trend towards more assisted substeps in oncologic visceral surgery was seen compared to the corresponding period one year earlier (51% vs.40%; p = 0.11). CONCLUSION: ETO leads to improved intraoperative communication and more performed substeps during complex procedures, which increases motivation and practical training. This concept can easily be implemented in all surgical specialties to improve surgical education.

ISSLS PRIZE in Clinical Science 2023: comparison of degenerative MRI features of the intervertebral disc between those with and without chronic low back pain. An exploratory study of two large female populations using automated annotation.

OBJECTIVES: The relationship of degeneration to symptoms has been questioned. MRI detects apparently similar disc degeneration and degenerative changes in subjects both with and without back pain. We aimed to overcome these problems by re-annotating MRIs from asymptomatic and symptomatics groups onto the same grading system. METHODS: We analysed disc degeneration in pre-existing large MRI datasets. Their MRIs were all originally annotated on different scales. We re-annotated all MRIs independent of their initial grading system, using a verified, rapid automated MRI annotation system (SpineNet) which reported degeneration on the Pfirrmann (1-5) scale, and other degenerative features (herniation, endplate defects, marrow signs, spinal stenosis) as binary present/absent. We compared prevalence of degenerative features between symptomatics and asymptomatics. RESULTS: Pfirrmann degeneration grades in relation to age and spinal level were very similar for the two independent groups of symptomatics over all ages and spinal levels. Severe degenerative changes were significantly more prevalent in discs of symptomatics than asymptomatics in the caudal but not the rostral lumbar discs in subjects < 60 years. We found high co-existence of degenerative features in both populations. Degeneration was minimal in around 30% of symptomatics < 50 years. CONCLUSIONS: We confirmed age and disc level are significant in determining imaging differences between asymptomatic and symptomatic populations and should not be ignored. Automated analysis, by rapidly combining and comparing data from existing groups with MRIs and information on LBP, provides a way in which epidemiological and 'big data' analysis could be advanced without the expense of collecting new groups. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Efficacy of a Mouthwash Containing CHX and CPC in SARS-CoV-2-Positive Patients: A Randomized Controlled Clinical Trial.

Soon after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, preprocedural mouthwashes were recommended for temporarily reducing intraoral viral load and infectivity of individuals potentially infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to protect medical personnel. Particularly, the antiseptic cetylpyridinium chloride (CPC) has shown virucidal effects against SARS-CoV-2 in vitro. Therefore, the aim of this randomized controlled clinical trial was to investigate the efficacy of a commercially available mouthwash containing CPC and chlorhexidine digluconate (CHX) at 0.05% each in SARS-CoV-2-positive patients as compared to a placebo mouthwash. Sixty-one patients who tested positive for SARS-CoV-2 with onset of symptoms within the last 72 h were included in this study. Oropharyngeal specimens were taken at baseline, whereupon patients had to gargle mouth and throat with 20 mL test or placebo (0.9% NaCl) mouthwash for 60 s. After 30 min, further oropharyngeal specimens were collected. Viral load was analyzed by quantitative reverse transcriptase polymerase chain reaction, and infectivity of oropharyngeal specimens was analyzed by virus rescue in cell culture and quantified via determination of tissue culture infectious doses 50% (TCID50). Data were analyzed nonparametrically (α = 0.05). Viral load slightly but significantly decreased upon gargling in the test group (P = 0.0435) but not in the placebo group. Viral infectivity as measured by TCID50 also significantly decreased in the test group (P = 0.0313), whereas there was no significant effect but a trend in the placebo group. Furthermore, it was found that the specimens from patients with a vaccine booster exhibited significantly lower infectivity at baseline as compared to those without vaccine booster (P = 0.0231). This study indicates that a preprocedural mouthwash containing CPC and CHX could slightly but significantly reduce the viral load and infectivity in SARS-CoV-2-positive patients. Further studies are needed to corroborate these results and investigate whether the observed reductions in viral load and infectivity could translate into clinically useful effects in reducing COVID-19 transmission (German Clinical Trials Register DRKS00027812).

Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis.

PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

Comparison of open and robotic-assisted partial nephrectomy approaches using multicentric data (UroCCR-47 study).

We compared the outcomes of robotic-assisted partial nephrectomy (RPN) and open partial nephrectomy (OPN) using contemporary data to respond to unmet clinical needs. Data from patients included in the registry who underwent partial nephrectomy between January 01, 2014 and June 30, 2017 within 20 centres of the French Network for Research on Kidney Cancer UroCCR were collected (NCT03293563). Statistical methods included adjusted multivariable analyses. Rates of peri- and post-operative transfusion, and of surgical revision, were lower in the RPN (n = 1434) than the OPN (n = 571) group (2.9% vs. 6.0%, p = 0.0012; 3.8% vs. 11.5%, p < 0.0001; 2.4% vs. 6.7%, p < 0.0001, respectively). In multivariable analyses, RPN was independently associated with fewer early post-operative complications than OPN (overall: odds-ratio [95% confidence interval, CI] = 0.48 [0.35-0.66]; severe: 0.29 [0.16-0.54], p < 0.0001 for both) and shorter hospital stays (34% [30%; 37%], p < 0.0001). RPN was also a significantly associated with a decresedrisk of post-operative acute renal failure, and new-onset chronic kidney disease at 3 and 12 months post-surgery. There were no between-group differences in oncological outcomes. In comparison with OPN, RPN was associated with improved peri- and post-operative morbidity, better functional outcomes, and shorter hospital stays. Our results support the use of RPN, even for large and complex tumours.

A mixed-methods study on evaluating an updated, francophone version of ETAT+ training in Madagascar.

Background: Madagascar needs major efforts to achieve the UN Sustainable Development Goals, despite the considerable reduction of child mortality during past years. In this context, implementation of emergency triage assessment and treatment (ETAT) plays an important role. In recent years, ETAT training activities rarely took place in Madagascar. To strengthen ETAT in Madagascar, a pilot training course was conducted in December 2019 at the University Hospital Mahajanga. Objectives: This study aims to evaluate if the ETAT+ pilot training content matches clinical needs in Madagascar and whether participants achieved their learning objectives. Methods: In this cross-sectional mixed-methods study, a 41-item questionnaire was used at the end of the ETAT+ training to evaluate their learning experience from the 12 participants (paediatricians, physicians, nurses and midwives). Six weeks after the training, guided interviews were conducted among five participants to describe how training content could be transferred into clinical practice in five health facilities. Results: Results suggest that this pilot project designed to contribute to the re-establishment of ETAT in Madagascar meets participants' needs and is adapted to clinical realities in terms of transmitted knowledge, skills and competencies. However, results also show that considerable multi-disciplinary efforts are needed to advance ETAT+ implementation in Madagascar. Conclusion: Implementation processes of ETAT training programmes need re-evaluation to assure their validity to contribute to quality of care improvements efficiently. Further operational research is required to evaluate sustainable, innovative implementation strategies adapted to contexts in Madagascar. Contributions of the study: This study aims to evaluate an updated Malagasy version of the Emergency Triage Assessment and Treatment Plus (ETAT+). The training met the participants' needs and was adapted to the clinical realities in Madagascar relating to transmitted knowledge, skills and competencies.

Multi-modality imaging of aggressive submural neoplasia of the hoof in two horses.

This case series presents a 20-year-old Quarter horse gelding and a 10-year-old Thoroughbred gelding with a histologic diagnosis of aggressive submural neoplasia, including an anaplastic sarcoma and a squamous cell carcinoma respectively. The current case series describes these neoplasias with radiography, computed tomography, magnetic resonance imaging and histopathology with immunohistochemistry. The purpose of this case series is to identify the clinical pattern of chronic reoccurring lameness in these cases and highlight the appearance of expansile osteolytic pathology of the distal phalanx with adjacent hoof wall abnormalities. Advanced imaging has the potential to assist with a differential diagnosis list and surgical planning in patients such as these however obtaining a cellular sample for histopathological examination remains necessary for definitive diagnosis.

Extended lower paratracheal lymph node resection during esophagectomy for cancer - safety and necessity.

BACKGROUND: The ideal extent of lymphadenectomy (LAD) in esophageal oncological surgery is debated. There is no evidence for improved survival after standardized paratracheal lymph node resection performing oncological esophagectomy. Lymph nodes from the lower paratracheal station are not standardly resected during 2-field Ivor-Lewis esophagectomy for esophageal cancer. The objective of this study was to evaluate the impact of lower paratracheal lymph node (LPL) resection on perioperative outcome during esophagectomy for cancer and analyze its relevance. METHODS: Retrospectively, we identified 200 consecutive patients operated in our center for esophageal cancer from January 2017 - December 2019. Patients with and without lower paratracheal LAD were compared regarding demographic data, tumor characteristics, operative details, postoperative complications, tumor recurrence and overall survival. RESULTS: 103 out of 200 patients received lower paratracheal lymph node resection. On average, five lymph nodes were resected in the paratracheal region and cancer infiltration was found in two patients. Those two patients suffered from neuroendocrine carcinoma and melanoma respectively. Cases with lower paratracheal lymph node yield had significantly less overall complicated procedures (p = 0.026). Regarding overall survival and recurrence rate no significant difference could be detected between both groups (p = 0.168 and 0.371 respectively). CONCLUSION: The resection of lower paratracheal lymph nodes during esophagectomy remains debatable for distal squamous cell carcinoma or adenocarcinoma of the esophagus. Tumor infiltration was only found in rare cancer entities. Since resection can be performed safely, we recommend LPL resection on demand.

Second Heart Field-Derived Cells Contribute to Angiotensin II-Mediated Ascending Aortopathies.

BACKGROUND: The ascending aorta is a common location for aneurysm and dissection. This aortic region is populated by a mosaic of medial and adventitial cells that are embryonically derived from either the second heart field (SHF) or the cardiac neural crest. SHF-derived cells populate areas that coincide with the spatial specificity of thoracic aortopathies. The purpose of this study was to determine whether and how SHF-derived cells contribute to ascending aortopathies. METHODS: Ascending aortic pathologies were examined in patients with sporadic thoracic aortopathies and angiotensin II (AngII)-infused mice. Ascending aortas without overt pathology from AngII-infused mice were subjected to mass spectrometry-assisted proteomics and molecular features of SHF-derived cells were determined by single-cell transcriptomic analyses. Genetic deletion of either Lrp1 (low-density lipoprotein receptor-related protein 1) or Tgfbr2 (transforming growth factor-ß receptor type 2) in SHF-derived cells was conducted to examine the effect of SHF-derived cells on vascular integrity. RESULTS: Pathologies in human ascending aortic aneurysmal tissues were predominant in outer medial layers and adventitia. This gradient was mimicked in mouse aortas after AngII infusion that was coincident with the distribution of SHF-derived cells. Proteomics indicated that brief AngII infusion before overt pathology occurred evoked downregulation of smooth muscle cell proteins and differential expression of extracellular matrix proteins, including several LRP1 ligands. LRP1 deletion in SHF-derived cells augmented AngII-induced ascending aortic aneurysm and rupture. Single-cell transcriptomic analysis revealed that brief AngII infusion decreased Lrp1 and Tgfbr2 mRNA abundance in SHF-derived cells and induced a unique fibroblast population with low abundance of Tgfbr2 mRNA. SHF-specific Tgfbr2 deletion led to embryonic lethality at E12.5 with dilatation of the outflow tract and retroperitoneal hemorrhage. Integration of proteomic and single-cell transcriptomics results identified PAI1 (plasminogen activator inhibitor 1) as the most increased protein in SHF-derived smooth muscle cells and fibroblasts during AngII infusion. Immunostaining revealed a transmural gradient of PAI1 in both ascending aortas of AngII-infused mice and human ascending aneurysmal aortas that mimicked the gradient of medial and adventitial pathologies. CONCLUSIONS: SHF-derived cells exert a critical role in maintaining vascular integrity through LRP1 and transforming growth factor-ß signaling associated with increases of aortic PAI1.

[Sepsis with hemolysis due to a liver abscess in a 60-year-old male patient]. / Sepsis mit Hämolyse im Rahmen eines Leberabszesses bei einem 60-jährigen Patienten.

Many cases of Clostridium perfringens sepsis prove to be fatal. We present a case of C. perfringens sepsis with a liver abscess as the focus of infection, which was successfully treated by an interdisciplinary intensive medical care management. The sepsis with this rare pathogen was favored by the presence of a bilioenteric anastomosis and immunosuppressive treatment of a pre-existing Crohn's disease. Antibiotic treatment with clindamycin and penicillin G was initiated and the abscess was drained. Hemodialysis with high cut-off filters was started because of acute kidney failure in the Acute Kidney Injury Network (AKIN) stage III, hemolysis and rhabdomyolysis. Therapeutic plasma exchange was performed due to sepsis and acute liver failure.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus minimally invasive esophagectomy for resectable esophageal adenocarcinoma, a randomized controlled trial (ROBOT-2 trial).

BACKGROUND: For patients with esophageal adenocarcinoma or cancer of the gastroesophageal junction, radical esophagectomy with 2-field lymphadenectomy is the cornerstone of the multimodality treatment with curative intent. Both conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE) were shown to be superior compared to open transthoracic esophagectomy considering postoperative complications. However, no randomized comparison exists between MIE and RAMIE in the Western World for patients with esophageal adenocarcinoma. METHODS: This is an investigator-initiated and investigator-driven multicenter randomized controlled parallel-group superiority trial. All adult patients (age ≥ 18 and ≤ 90 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 218) with resectable esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction are randomized to either RAMIE (n = 109) or MIE (n = 109). The primary outcome of this study is the total number of resected abdominal and mediastinal lymph nodes specified per lymph node station. CONCLUSION: This is the first randomized controlled trial designed to compare RAMIE to MIE as surgical treatment for resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. The hypothesis of the proposed study is that RAMIE will result in a higher abdominal and mediastinal lymph node yield specified per station compared to conventional MIE. Short-term results and the primary endpoint (total number of resected abdominal and mediastinal lymph nodes per lymph node station) will be analyzed and published after discharge of the last randomized patient within this trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04306458 . Registered 13th March 2020, https://clinicaltrials.gov/ct2/show/NCT04306458; Date of first enrolment 18.01.2021; Target sample size 218; Recruitment status: Recruiting; Protocol version 2; Issue date 10.03.2020; Rev. 02.02.2021; Authors ET, PCvdS, PPG.