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Purpose Evaluation of a novel ultrasound-simulation-app for training fetal echocardiography as a possible useful addition for students, residents and specialist doctors. Furthermore, comparison to a conventional learning-method with special attention on orientation and recognition of physiological structures. Methods Prospective two-arm study with the participation of 226 clinical students. 108 students were given an extract from a textbook on fetal echocardiography (PDF-group, n = 108) for 30 min to study. 118 students were able to use the new ultrasound-simulator-app (Simulator-group, n = 118) to learn for 30 min. The knowledge of the students was examined both before and after the learning-period by having them identify sonographic structures in videos using single-choice selection. Results There were no significant differences between the two groups regarding age (p = 0.87), gender (p = 0.28), and the number of previously performed ultrasound-examinations (p = 0.45). In the Simulator-group, there was a significantly higher learning effect regarding the proportion of students with an increase of correct answers in the video test examination (p = 0.005). At the end of learning, the students in the Simulator-group needed significantly less time to display the structures in the app’s simulation (median initially 10.9 s vs. 6.8 s at the end; p Conclusions The novel ultrasound-simulation-app seems to be a useful addition and improvement to ultrasound training. Previous difficulties such as simultaneously having patients, ultrasound-machines, and professors at disposal can thus be avoided. This means that another important step towards remote learning can be taken, which has been proven increasingly essential lately, due to the COVID-19 pandemic.

Splenosis is a rare disease, which is often discovered incidentally years after surgical procedures on the spleen or traumatic splenic lesions. Through injury of the splenic capsule, splenic cells are able to spread and autoimplant in a fashion similar to the process of metastatic cancer. Here we present the case of a 62-year-old female patient with a palpable tumor of the lower abdomen. Her medical history was unremarkable, except for splenectomy after traumatic splenic lesion in her childhood. Clinical examination and diagnostic imaging raised the suspicion of advanced ovarian cancer, which was further substantiated by the typical presentation of adnexal masses and disseminated peritoneal metastases during the following staging laparotomy. Surprisingly, we also found peritoneal implants macroscopically similar to splenic tissue. Microscopic examination of tissue specimens by intrasurgical frozen section confirmed the diagnosis of intra-abdominal splenosis. The patient then underwent cytoreductive surgery with complete resection of all cancer manifestations, sparing the remaining foci of splenosis to avoid further morbidity. This case demonstrates the rare coincidence of intra-abdominal carcinoma and splenosis, which could lead to intraoperative difficulties by misinterpreting benign splenic tissue. Therefore, splenosis should be considered in patients with medical history of splenic lesions and further diagnostic imaging like Tc-99m-tagged heat-damaged RBC scan could be used for presurgical distinguishing between tumor spread in the abdominal cavity and disseminated splenosis. The presented case report should not only raise awareness for the rare disease splenosis, but also emphasize the need to consider the possibility of simultaneous incidence of benign and malignant intra-abdominal lesions, as to our knowledge this is the first published case of simultaneous peritoneal carcinomatosis and splenosis.

Background: The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described.Patients and methods: In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields.Results: The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months).Conclusion: Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV– tumors.

Introduction: Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist. Material and Methods: Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (n = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors. Results: 595 (64.9%) patients had a Ki67 n = 717), 20% for HR+/HER2+ (n = 76), 30% for HR−/HER2+ (n = 45), and 60% for HR−/HER2− (n = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (Conclusion: This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors.

Effective pharmacotherapy for major depressive disorder remains a major challenge, as more than 30% of patients are resistant to the first line of treatment (selective serotonin reuptake inhibitors)1. Sub-anaesthetic doses of ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist2,3, provide rapid and long-lasting antidepressant effects in these patients4–6, but the molecular mechanism of these effects remains unclear7,8. Ketamine has been proposed to exert its antidepressant effects through its metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK)9. The antidepressant effects of ketamine and (2R,6R)-HNK in rodents require activation of the mTORC1 kinase10,11. mTORC1 controls various neuronal functions12, particularly through cap-dependent initiation of mRNA translation via the phosphorylation and inactivation of eukaryotic initiation factor 4E-binding proteins (4E-BPs)13. Here we show that 4E-BP1 and 4E-BP2 are key effectors of the antidepressant activity of ketamine and (2R,6R)-HNK, and that ketamine-induced hippocampal synaptic plasticity depends on 4E-BP2 and, to a lesser extent, 4E-BP1. It has been hypothesized that ketamine activates mTORC1–4E-BP signalling in pyramidal excitatory cells of the cortex8,14. To test this hypothesis, we studied the behavioural response to ketamine and (2R,6R)-HNK in mice lacking 4E-BPs in either excitatory or inhibitory neurons. The antidepressant activity of the drugs is mediated by 4E-BP2 in excitatory neurons, and 4E-BP1 and 4E-BP2 in inhibitory neurons. Notably, genetic deletion of 4E-BP2 in inhibitory neurons induced a reduction in baseline immobility in the forced swim test, mimicking an antidepressant effect. Deletion of 4E-BP2 specifically in inhibitory neurons also prevented the ketamine-induced increase in hippocampal excitatory neurotransmission, and this effect concurred with the inability of ketamine to induce a long-lasting decrease in inhibitory neurotransmission. Overall, our data show that 4E-BPs are central to the antidepressant activity of ketamine. The antidepressant-like effects of ketamine in mice depend on the expression of specific eIF4E-binding proteins in excitatory and inhibitory neurons.

Purpose The purpose of this article was to compare clinical outcomes between therapeutic penetrating keratoplasty (TPK), therapeutic deep anterior lamellar keratoplasty (TDALK), and optical penetrating keratoplasty (OPK) in Acanthamoeba keratitis. Methods A literature search was conducted in online libraries from 1980 to 2021. The primary end points were best-corrected visual acuity (VA), graft survival, and infection recurrence. In addition, we enrolled 35 consecutive patients with AK from our practice evaluating best-corrected VA and high-order aberrations. Results A total of 359 AK eyes from 33 published studies were retrieved from 175 publications screened. One hundred sixty-five eyes (73%) that underwent TPK and 39 eyes (84%) treated with TDALK had a clear graft at the last follow-up visit. Only the patients treated with OPK had 82 clear grafts (94%) during the follow-up period. Forty-seven (21%) of TPK patients reached VA ≥20/30, compared with 11 (25%) of TDALK patients and 35 (40%) of OPK patients. Acanthamoeba infection recurrence occurred in 38 eyes (16.8%) that underwent TPK, 9 (19%) that underwent TDALK, and 8 (9.5%) that underwent OPK. In our series, best-corrected visual acuity in nonsurgically treated patients was 1 ± 0.50 logMAR compared with 0 logMAR of surgically treated patients. High-order aberrations were significantly lower in surgically treated eyes after AK resolution, particularly in TDALK when compared with TPK patients. Best-corrected visual acuity was better in TDALK patients compared with TPK patients. Conclusions After AK resolution by 6 to 12 months of medical treatment, OPK seems to be the best surgical choice in patients with AK. If AK could not be eradicated by medical therapy, TDALK may be chosen in the early disease stage and TPK in later stages.

The alarming onset of some cases of myocarditis and pericarditis following the administration of Pfizer–BioNTech and Moderna COVID-19 mRNA-based vaccines in adolescent males has recently been highlighted. All occurred after the second dose of the vaccine. Fortunately, none of patients were critically ill and each was discharged home. Owing to the possible link between these cases and vaccine administration, the US and European health regulators decided to continue to investigate the potential causal relationship between COVID-19 mRNA vaccines and myocarditis. In any case, none of the patients fulfilled the criteria for multi-system inflammatory syndrome or Kawasaki-like disease and there was no evidence of acute SARS-CoV-2 infection.

Background Despite the use of optimal medical therapy, HFrEF remains a leading cause of morbidity, mortality and health care costs. The introduction of angiotensin receptor/neprilysin inhibitors (ARNIs) had a revolutionary impact on the treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF). Methods The aim of the study was to monitor over time the perceived quality of life, the physical performance, the trend of BNP and NT-ProBNP and the NYHA functional class in patients with HFrEF during treatment with sacubitril/valsartan. We enrolled 37 patients (63 ± 10 years old, 76% men) who underwent a total of one year follow-up. All patients underwent clinical evaluation, 6MWT, blood analysis (in particular NT-pro-BNP and BNP, renal function test); Kansas City Cardiomyopathy Questionnaire (KCCQ) and the NYHA functional class assessment were also performed, at the beginning of the study and after 3, 6 and 12 months of therapy. Results We observed at each follow-up a significant improvement of KCCQ score, 6MWT, NTProBNP, BNP and of NYHA class. However, analyzing the Δ % of variation of each single parameter, the improvement was not uniform in time. We also observed that only 37% of patients tolerated the full recommended dose of sacubitril/valsartan (97/103 mg b.i.d.); of the remaining, 40% tolerated the intermediate dose (49/51 mg b.i.d.) and 23% the minimum (24/26 md b.i.d.). Conclusions Sacubitril/valsartan therapy improves significantly quality of life, physical effort resistance, BNP and NT-ProBNP and NYHA functional class in patients with HFrEF. Although not all the patients tolerated the maximum recommended dose, the beneficial effects were significant even at lower doses.

Background The prognostic value of lymph node removal in ovarian cancer varies depending on the tumor stage. While in the advanced stage the removal of clinically normal lymph nodes does not improve the prognosis, this is still unclear in the early stages. Evaluation of the lymph nodes based on preoperative imaging influences the surgical procedure. Methods This retrospective analysis was performed by analyzing data from 114 patients with ovarian cancer, treated in our university hospital in the years 2000 – 2012. Diagnostic performance of imaging by computer tomography with respect to the correct prediction of lymph node status was analyzed in terms of sensitivity, specificity, positive predictive value and negative predictive value. Results Imaging by computer tomography showed a rather limited diagnostic performance with regard to the detection of lymph node metastases in ovarian cancer, with a sensitivity of 40.7%, a specificity of 89.1%, a positive predictive value of 80.0%, and a negative predictive value of 58.3%. A separate analysis for pelvic and paraaortic lymph node involvement showed a better diagnostic performance of computer tomography for the detection of positive paraaortic lymph nodes (41.2, 93.1, 84.0, and 64.3% for sensitivity, specificity, positive predictive value and negative predictive value, respectively) as compared to the detection of positive pelvic lymph nodes (25.6, 91.8, 62.5, and 69.8%). Conclusion The preoperative prediction of lymph node status by computer tomography is limited. A decision for or against lymphadenectomy should not be made solely on the basis of this approach.

Background: Nodal status is the most important prognostic factor in cervical cancer. However, further risk stratification in node positive cervical cancer patients is warranted for optimal therapeutic decisions. Material and Methods: Nodal positive patients (n = 86) were retrospectively stratified into two groups according to either number of positive nodes (>3 vs. 1–3) or lymph node ratio (LNR) (≥10 vs. 6.6 vs. ≤6.6%). Univariable log-rank tests and both univariable and adjusted multivariable Cox regression models were used to evaluate the association between number of positive nodes or LNR and disease-free survival (DFS) and overall survival (OS). Results: LNR was significantly associated with worse DFS in adjusted multivariable analysis, both when categorized as ≥10 versus p = 0.034) and when categorized as >6.6 versus ≤6.6% (HR 2.79, 95% CI 1.23–6.37, p = 0.015). However, we found no significant association between number of positive nodes or LNR and OS. Discussion:In operable node-positive cervical cancer, both number of positive lymph nodes and LNR can be used for further risk stratification with regard to DFS but not OS.

Background and Objectives: Tributaries of inferior vena cava (IVC) are not com pletely described. As IVC has a complex developmental origin, variations in the feeding vessels are common. The main objective of this study was to report the occurrence of any ventral tributary in the level 1 region of IVC. During the study, origin of such ventral tributary and course was also noted. Methodology: In a retrospective/prospective observational study from 2015 to 2018, comprising 168 para-aortic lymphadenectomy (PLA) procedures conducted at Department of Gynaecological Oncology, University Hospital of Ulm, Germany, the presence of ventral tributaries of IVC was evaluated. Results: Out of 148 retrospective cases of PLA, the presence of a prominent ventral tributary within 2 cm distance from the bifurcation of aorta was assumed in more than 60% cases. Within 20 prospectively assessed cases, the vein could be identified in 17 patients and was located within the right mesoureter. Only on one patient, this feeding vessel was draining into IVC at the level below the aortic bifurcation. Conclusion: In 85% of the prospectively assessed patients considered in the study, lymphadenectomy there was a constant ventral tributary feeding the IVC within 2 cm from the bifurcation of the aorta.

Purpose Discordance in human epidermal growth factor receptor 2 (HER2) status between primary tumor and metastases might have important implications for treatment response and therapy decisions. Here, we evaluate both the frequency of circulating tumor cells (CTCs) and the factors predicting HER2 discordance between primary tumor and CTCs as a potential surrogate for tumor biology and tumor heterogeneity in patients with metastatic breast cancer. Patients and Methods The number of CTCs in 7.5 mL of peripheral blood and HER2 status were evaluated in 1,123 women with HER2-negative metastatic breast cancer. HER2 discordance was defined as the presence of at least one CTC with a strong immunocytochemical HER2 staining intensity. Factors predicting discordance in HER2 phenotype were assessed using multivariable logistic regression. Results Overall, 711 (63.3%) of 1,123 screened patients were positive for CTCs (≥ one CTC). Discordance in HER2 phenotype between primary tumor and CTCs was observed in 134 patients (18.8%) and was significantly associated with histologic type (lobular v ductal; odds ratio [OR], 2.67; 95% CI, 1.63 to 4.39; P < .001), hormone receptor status (positive v negative; OR, 2.84; 95% CI, 1.15 to 7.02; P = .024), and CTC number (≥ five v one to four; OR, 7.64; 95% CI, 3.97 to 14.72; P < .001). Conclusion HER2 discordance between primary tumor and CTCs was observed in 18.8% of patients and was associated with histologic type, hormone receptor status of the primary tumor, and CTC number. The clinical utility of CTCs as liquid biopsy to assess tumor heterogeneity of metastatic disease and guide treatment decisions must be evaluated in prospective randomized trials.

Im Gegensatz zum Eierstockkrebs, wo bisherige Ergebnisse eher ernuchternd sind, scheinen sich sowohl das Zervix- als auch das Endometriumkarzinom gut fur eine Immuntherapie zu eignen. Ursachlich ist einerseits die HPV(humane Papillomviren)-Infektion beim Zervixkarzinom, wahrend beim Endometriumkarzinom eine haufig vorliegende Mikrosatelliteninstabilitat (MSI) jeweils zu einer erhohten Immunogenitat dieser Tumoren fuhrt. In den USA ist mit Pembolizumab jeweils schon ein Wirkstoff fur MSI bzw. PDL1(„programmed cell death protein 1 ligand“)-positive Tumoren zugelassen. Auf dem ESMO(European Society for Medical Oncology)-Kongress 2019 wurden fur beide Entitaten vielversprechende Studien zu Kombinationstherapien gezeigt.

BACKGROUND/AIM The high rate of root resorption resulting from tooth replantation represents a serious clinical problem. In order to prevent ankylosis and replacement resorption, the contemporary literature highlights the importance of using a flexible stabilization for traumatized teeth. For this purpose, orthodontic devices may be promising for obtaining a better prognosis and periodontal repair. The aim of this study was to evaluate the effect of an active splinting protocol with controlled force in dog's teeth following replantation. MATERIAL AND METHODS Sixty premolar roots from three dogs were used. They were submitted to endodontic treatment, hemisected, atraumatically extracted and subsequently replanted. They were divided into four groups: Passive Stabilization (n = 20)-after 20 min in a dry medium; Active Stabilization (n = 20)-after 20 min in a dry medium; Negative control (n = 10)-immediate replantation and passive Stabilization; and Positive control (n = 10)-90 min of extra-alveolar time and passive Stabilization. The samples were collected and submitted to histologic processing. They were then evaluated for the count of inflammatory cells, expression of neurotrophin 4, osteoclasts, apoptotic cells and collagen fibres. The results were submitted to ANOVA or Kruskal-Wallis statistical tests followed by Tukey or Dunn post-tests (α = 5%). RESULTS Passive Stabilization with orthodontic brackets without traction used after replantation had the highest number of inflammatory cells (p = .0122), osteoclasts (p = .0013) and percentage of collagen fibres in the periodontal ligament (p

BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).

In der Gruppe der Mammakarzinome hat das triple-negative Mammakarzinom (TNBC, „triple-negative breast cancer“) das heterogenste Outcome und die schlechteste Prognose. Durch das Fehlen von Hormonrezeptoren und des HER2/neu(„human epidermal growth factor receptor 2“)-Rezeptor bestehen in der aktuellen klinischen Routine keine Zielstrukturen fur eine spezifische Therapie. Es erfolgte eine Literaturrecherche zur aktuellen Studienlage und vielversprechenden Therapieansatzen. In der kurativen Situation finden sich neue Ansatze in der Hinzunahme von Checkpointinhibitoren zusatzlich zur Standardchemotherapie. Ebenfalls gibt es mit Capecitabin analog der CREATE-X-Studie bei non-PCR eine postneoadjuvante Therapie. In der palliativen Situation findet man neben verschiedenen Chemotherapien einen Ansatz in der Testung von Tumorgewebe und der Keimbahn. Bei PD-L1(„programmed cell death 1 ligand 1“)-Positivitat kann auf den bereits zugelassenen Checkpointinhibitor Atezolizumab zuruckgegriffen werden. Bevacizumab ist auch bei manchen Patientinnen eine Option. Weitere mogliche Antikorpertherapien umfassen in Zukunft Pembrolizumab sowie die Antikorper-drug-Konjugate Sacituzumab-Govitecan und Trastuzumab-Deruxtecan. Bei einer Aktivierung des AKT/PI3K(Phosphoinositid-3-Kinase)-Signalwegs scheinen AKT-Inhibitoren wie Capivasertib oder Ipatasertib eine Option darzustellen. Bei BRCA-Positivitat stehen PARP(Poly[ADP-ribose]-Polymerasen)-Inhibitoren zur Verfugung. Trotz Fehlens der Hormonrezeptoren und des HER2/neu-Rezeptors bestehen mittlerweile mit der PD-L1-Testung, der Keimbahnanalyse und auch der Testung auf eine Aktivierung des AKT/PI3K-Signalwegs weitere zielgerichtete Therapieoptionen fur das TNBC sowohl in der kurativen als auch in der palliativen Situation.

Esta pesquisa objetivou investigar nas publicações referentes às edições XIII, XIV, XV, XVI e XVII do Encontro Paranaense de Educação Ambiental (EPEA), as tendências teórico-metodológicas que têm balizado a formação de professores para a Educação Ambiental (EA). A coleta e análise dos dados subsidiaram-se na Análise de Conteúdo. Entre as considerações conclusivas, identificamos que a supressão dos temas ambientais nos documentos orientadores das licenciaturas e o predomínio de compreensões ingênuas de EA, tanto para licenciandos quanto para professores formadores, apresentam-se como as principais lacunas da formação inicial. No âmbito continuado, destaca-se a dificuldade dos professores em desenvolver a interdisciplinaridade. Os desdobramentos futuros ao campo apontam para: a ambientalização curricular; a superação da fragmentação do conhecimento; a constituição de processos de formação continuada que propiciem subsídios a um entendimento multifacetado das problemáticas ambientais.

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.

Italy is a country with high seismic hazard, however since the delay in the seismic classification of the national territory, most of the existing building heritage does not comply with the current technical standards for buildings. The seismic events that have hit different Italian regions in recent years have highlighted the complexity of the challenge for the public bodies both in the emergency management and post-event reconstruction and in the planning of effective risk prevention and mitigation measures to be implemented in ‘peacetime’. These difficulties concern, in particular, the capacity to properly manage the financial and technical resources available and to identify the intervention priorities throughout the entire emergency cycle. For correct management, the priority is to quantify and localize, through simulations, the quantification of probable damages and to evaluate in terms of cost-benefits the possible alternative strategies for mitigation, also taking into account the potential, in terms of cost-effectiveness, of integrated measures for seismic and energy retrofitting. In this framework, the project CAESAR II (Complementary Analyses for Emergency planning based on Seismic Risks impact evaluations) has been developed as a Decision Support System for Public Authorities in charge of developing Disaster Risk Reduction plans, with the possibility of programming mid to long-term investments for public and private properties, as well as defining custom financial support mechanisms and tax incentives.

Emilio Pedrotti,1 Erika Bonacci,1 Arianna De Rossi,1 Jacopo Bonetto,1 Chiara Chierego,1 Adriano Fasolo,1,2 Alessandra De Gregorio,3 Giorgio Marchini1 1Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Policlinico G.B. Rossi, Verona, 37134, Italy; 2Research Unit, The Veneto Eye Bank Foundation, Venezia, 30174, Italy; 3Ophthalmic Unit, San Bassiano Hospital, Bassano Del Grappa, 36061, Vicenza, ItalyCorrespondence: Adriano FasoloThe Veneto Eye Bank Foundation, c/o Pad. G. Rama, via Paccagnella 11, Venice, 30174, ItalyTel +390419656400Fax +390419656401Email adriano.fasolo@yahoo.itPurpose: To determine whether type 1 big-bubble (BB) formation is influenced by the sequence of incisions created with the Victus femtosecond laser (FSL) enabled with software version 3.4 (SV 3.4) during deep anterior lamellar keratoplasty (DALK).Materials and Methods: Consecutive FSL-assisted DALK BB procedures were performed on 20 human donor corneas: 10 shaped by tunnel incision followed by lamellar incision (tunnel-lamellar group, TL) and 10 in the reverse order (lamellar-tunnel group, LT). The BB type was assessed by evaluating dynamic air movement during air inflation; bubble diameter and floor thickness were measured by anterior segment optical coherence tomography.Results: Overall, a type 1 BB formed in 85% of eyes: 100% in the TL group and 70% in the LT group. In the LT group, a type 2 BB formed in 2 corneas and one cornea was perforated during cannula insertion. Type 1 BB was achieved after one attempt in 90% of eyes in the TL group and in 57% in the LT group.Conclusion: Shaping the tunnel before rather than after lamellar incision may be more effective for obtaining a type 1 BB by air injection.Keywords: deep anterior lamellar keratoplasty, femtosecond laser, big bubble, intrastromal incision, lamellar incision

Objective A mobile handheld snapshot hyperspectral imaging device was developed and tested for in vivo skin evaluation using a new spectral imaging technology. Methods The device is equipped with four different LED light sources (VIS, 810 nm, 850 nm, and 940 nm) for illumination. Based on a diffractive optical element (DOE) combined with a CMOS sensor chip, a snapshot hyperspectral imager is achieved for the application on human skin. The diffractive optical element (DOE) consists of a two‐dimensional array of identically repeated diffractive microstructures. One hyperspectral image for all wavelength regions is taken within a few seconds. Complex recalculation of the VIS spectral distribution and image information from the received DOE image requires several minutes, depending on computing performance. A risk assessment on the irradiation sources shows no risk of harm due to the LED radiation. Results Skin tone color patches experiments reproducibly deliver images and spectra of different skin tones. First in vivo use of the device identified pigmentation changes within the field of view. Conclusion We present a working mobile snapshot hyperspectral imaging tool based on diffractive optical elements. This device or future developments thereof can be used for broad skin evaluation in vivo.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by several eliciting drugs in patients with a genetic predisposition. Incidence of DRESS in children is very variable, frome 1:1000 to 1:10.000, and the mortality rate seems to be lower than 10%. Anti-convulsants are the main drugs involved both in adults and in children. The treatment of choice is the prompt withdrawn of the offending drug and using intravenous immunoglobulins and corticosteroids used in synergy. In recent years, emerging studies have outlined the disease more clearly. We present a pediatric case in which the patient developed DRESS syndrome as a result of exposure to lamotrigine before and carbamazepine after and a relapse after exposure to omeprazole. Starting from this case report we provide an overview on DRESS Syndrome.

Background Low back pain (LBP) and knee osteoarthritis (OA) are major contributors to disability worldwide. These conditions result in a significant burden at both individual and societal levels. Engagement in regular physical activity and exercise programs are known to improve physical function in both chronic LBP and knee OA populations. For people residing in rural areas, musculoskeletal conditions are often more frequent and disabling compared to urban populations, which could be the result of reduced access to appropriate health services and resources in rural settings. EHealth is an innovative solution to help provide equitable access to treatment for people with musculoskeletal pain living in rural settings. Methods/design We will conduct a randomised clinical trial investigating the effects of an eHealth intervention compared to usual care, for people with chronic non-specific LBP or knee OA in rural Australia. We will recruit 156 participants with non-specific chronic LBP or knee OA. Following the completion of baseline questionnaires, participants will be randomly allocated to either the eHealth intervention group, involving a tailored physical activity and progressive resistance exercise program remotely delivered by a physiotherapist (n = 78), or usual care (n = 78) involving referral to a range of care practices in the community. Outcomes will be measured at baseline, 3 and 6 months post-randomisation. The primary outcome will be physical function assessed by the Patient-Specific Functional Scale (PSFS). Secondary outcomes include pain intensity, physical activity levels, activity limitations, quality of life, pain coping. We will also collect process evaluation data such as recruitment rate, attendance and adherence, follow-up rate, participants’ opinions and any barriers encountered throughout the trial. Discussion The findings from this trial will establish the effectiveness of eHealth-delivered interventions that are known to be beneficial for people with LBP and knee OA when delivered in person. As a result, this trial will help to inform health care policy and clinical practice in Australia and beyond for those living in non-urban areas. Trial registration This study was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12618001494224) registered 09.05.2018.

Variant-specific loss of heterozygosity (LOH) analyses may be useful to classify BRCA1/2 germline variants of unknown significance (VUS). The sensitivity and specificity of this approach, however, remains unknown. We performed comparative next-generation sequencing analyses of the BRCA1/2 genes using blood-derived and tumour-derived DNA of 488 patients with ovarian cancer enrolled in the observational AGO-TR1 trial (NCT02222883). Overall, 94 pathogenic, 90 benign and 24 VUS were identified in the germline. A significantly increased variant fraction (VF) of a germline variant in the tumour indicates loss of the wild-type allele; a decreased VF indicates loss of the variant allele. We demonstrate that significantly increased VFs predict pathogenicity with high sensitivity (0.84, 95% CI 0.77 to 0.91), poor specificity (0.63, 95% CI 0.53 to 0.73) and poor positive predictive value (PPV; 0.71, 95% CI 0.62 to 0.79). Significantly decreased VFs predict benignity with low sensitivity (0.26, 95% CI 0.17 to 0.35), high specificity (1.0, 95% CI 0.96 to 1.00) and PPV (1.0, 95% CI 0.85 to 1.00). Variant classification based on significantly increased VFs results in an unacceptable proportion of false-positive results. A significantly decreased VF in the tumour may be exploited as a reliable predictor for benignity, with no false-negative result observed. When applying the latter approach, VUS identified in four patients can now be considered benign. Trial registration number NCT02222883., publishedVersion

Since the publication of the updated German guideline in 2015, the recommendations for performing pelvic lymphadenectomy (LAE) in patients with vulvar cancer (VSCC) have changed considerably. The guideline recommends surgical lymph node staging in all patients with a higher risk of pelvic lymph node involvement. However, the current data do not allow the population at risk to be clearly defined, therefore, the indication for pelvic lymphadenectomy is still not clear. There are currently two published German patient populations who had pelvic LAE which can be used to investigate both the prognostic effect of histologically verified pelvic lymph node metastasis and the relation between inguinal and pelvic lymph node involvement. A total of 1618 patients with primary FIGO stage ≥ IB VSCC were included in the multicenter AGO CaRE-1 study (1998 – 2008), 70 of whom underwent pelvic LAE. During a retrospective single-center evaluation carried out at the University Medical Center Hamburg-Eppendorf (UKE), a total of 514 patients with primary VSCC treated between 1996 – 2018 were evaluated, 21 of whom underwent pelvic LAE. In both cohorts, around 80% of the patients who underwent pelvic LAE were inguinally node-positive, with a median number of three affected groin lymph nodes. There were no cases of pelvic lymph node metastasis without inguinal lymph node metastasis in either of the two cohorts. Between 33 – 35% of the inguinal node-positive patients also had pelvic lymph node metastasis; the median number of affected groin lymph nodes in these patients was high (> 4), and the maximum median diameter of the largest inguinal metastasis was > 40 mm in both cohorts. Pelvic lymph node staging and pelvic radiotherapy is therefore probably not necessary for the majority of node-positive patients with VSCC, as the relevant risk of pelvic lymph node involvement was primarily found in node-positive patients with high-grade disease. More, ideally prospective data collections are necessary to validate the relation between inguinal and pelvic lymph node involvement.

Purpose Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11–13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p

Complementary feeding (CF) is a pivotal phase of the individual’s growth, during which children develops their future dietary habits. To date, only few studies investigated and compared weaning modalities between different geographical areas. The aim of this article is to describe the current Italian practice for CF in healthy term infants among different areas (North, Center, South) of Italy. Two different multiple-choice questionnaires were produced and sent to 665 Italian primary care pediatricians (PCP) and 2023 families with children under 1 year of age. As emerged from our investigation, in Italy CF is usually started between the 5th and 6th month of life. The preferred approach (chosen by 77% of families) involves the use of home-cooked liquid or semi-liquid ailments, or industrial baby foods. A new CF modality is emerging, consisting of traditional complementary foods with adult food tastings (10% of families). Approximately 91% of pediatricians give written dietary suggestions, and 83% of families follow their advice. We found significantly divergent weaning habits among different areas of Italy. PCP have a key role in guiding parents during the introduction of new foods in their infant’s diet and should take this as an opportunity to educate the whole family to healthy dietary habits.

This chapter reports an overview of the experience and the results achieved during the development of the robotized system for switchgear wiring carried out in the WIRES experiment. This specific application is particularly challenging for a robotic system due to the complexity of the manipulation task. As a matter of fact, in this task deformable linear objects, such as electric wires, are involved. Moreover, the precision requested during the assembly task and the typical crowded space inside the switchgear imply, on one side, the development of specific hardware and software tools and, on the other side, high adaptability and flexibility of the robotic system. In the WIRES experiment, a software package to extract the wiring information and to generate the robot task sequence directly from the switchgear CAD files has been developed. Additionally, a computer vision system able to recognize the location of the wires and of the electromechanical components inside the switchgear has been developed. To deal with the wire deformability and occlusion problems during the wire insertion, machine learning and sensor fusion techniques have been adopted to enable the wire manipulation by means of tactile sensors and 2D cameras feedback. From the hardware point of view, a specific end effector has been developed to manipulate and connect the wire to the components. This end effector is equipped with an electric screwdriver and a customized tactile sensor used to evaluate the wire shape, the wire end pose and its interaction with the environment during the manipulation. The entire task pipeline, going from the switchgear information extraction, to the wire grasp and manipulation, its connection and the routing along the desired wire path is presented in this chapter. The preliminary experimental results show that the developed system can achieve a success rate of about 95% in the wire insertion and connection task.

For a space mission the re-entry into earth atmosphere is a crucial phase, because of the severe aerothermodynamic conditions. This has always represented a problem of great interest, as it is fundamental to study the behavior of the structures of the spacecraft invested by the atmosphere where very high temperatures are generated. The necessity of testing the models in similar conditions to re-entry phase pushed towards the realization of specific on-ground facilities. In these laboratories one of the main purposes is to reproduce very high heat fluxes onto the models, representative of what happens during the re-entry mission phase. In this scenario, the Plasma Wind Tunnel "SCIROCCO"" of the Italian Aerospace Research Center (C.I.R.A. S.C.p.A) in Capua represents the largest and most powerful hypersonic facility in the world. Here it is possible to test models with heat fluxes up to 3000 kW/m. The measure of the heat fluxes in the test facility are performed with Gardon Gauge transducers. Despite the fundamental importance of these sensors, there is currently no possibility to calibrate them for the aforementioned heat flux values. In this work an innovative calibration methodology is proposed, using a pulsed LASER beam which allows to obtain high and repeatable heat flux with low power consumption. The results show the feasibility of the proposed methodology.

Neuropathic pain is a pathological condition induced by a lesion or disease affecting the somatosensory system, with symptoms like allodynia and hyperalgesia. It has a multifaceted pathogenesis as it implicates several molecular signaling pathways involving peripheral and central nervous systems. Affective and cognitive dysfunctions have been reported as comorbidities of neuropathic pain states, supporting the notion that pain and mood disorders share some common pathogenetic mechanisms. The understanding of these pathophysiological mechanisms requires the development of animal models mimicking, as far as possible, clinical neuropathic pain symptoms. Among them, the Spared Nerve Injury (SNI) model has been largely characterized in terms of behavioral and functional alterations. This model is associated with changes in neuronal firing activity at spinal and supraspinal levels, and induces late neuropsychiatric disorders (such as anxious-like and depressive-like behaviors, and cognitive impairments) comparable to an advanced phase of neuropathy. The goal of this review is to summarize current findings in preclinical research, employing the SNI model as a tool for identifying pathophysiological mechanisms of neuropathic pain and testing pharmacological agent.

Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected. The target population includes the German “Alb-Allgau-Bodensee Region” which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets. Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients. The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.

Aims: To assess toxicity and clinical outcomes of moderately hypofractionated helical tomotherapy (HT) for the curative treatment of localized prostate cancer (PC). Methods: From December 2012 to May 2018, 170 patients were treated with definitive intent for PC. Thirty-four percent were low risk, 30% intermediate risk (IR) and 36% high risk (HR). All patients received 70Gy in 28 fractions to the prostate; 61.6Gy were delivered to the seminal vesicles for IR; pelvic lymph nodes irradiation for a total dose of 50.4Gy was added in the HR subgroup. Toxicity was assessed using CTCAE V4.0, and biochemical failure was defined following Phoenix criteria. Time-to-event data were analyzed using the Kaplan–Meier method and log-rank test. Results: The median follow-up was 36months (range 12–78); acute toxicity was as follows: G1 and G2 in 27.6% and 19.4% for GI; 53% and 24% for GU. No G ≥ 3 event was observed. For late toxicity, G ≥ 3 GI and GU rates were, respectively, 3% and 2.4% at 3years and 3% and 4.8% at 4years; no G4 occurred. A statistical correlation between acute or late G3 incidence and clinical or dosimetric parameters was not found. At the time of analysis, 2- and 3-year biochemical relapse-free survival rates were 90% and 87.5% and 2- and 3-year overall survival rates were 96.4% and 90%, respectively. The log-rank test revealed no difference between the risk groups in terms of biochemical control (p = 0.16). Conclusions: Moderately hypofractionated RT with HT for localized prostate cancer reported excellent outcomes with mild acute and late toxicity incidence, with promising biochemical control rates.

Objective: At the end of the year 2018, a new FIGO classification for cervical cancer was published, mainly revising stage IB and introducing a new stage IIIC, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. Methods: We retrospectively analyzed all cases of cervical cancer stage I to IIB who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome according to the new stages. Results: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage IB and from any stage to stage IIIC1. Kaplan-Meier curves for new stages showed a significant difference in disease-free survival (DFS) and overall survival (OS) between stages I versus II versus III (log-rank test, both p < 0.001). Overall, patients that were upstaged had a significant worse DFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive IB or IIB tumors were upstaged to IIIC tumors. Conclusion: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.

ZusammenfassungDie plastisch-kosmetische Brustrekonstruktion wird aus unterschiedlichsten Indikationen durchgeführt. Patientinnen mit einem entsprechenden Eingriff sind körper-bewusst und nehmen an verschiedensten körperlichen Aktivitäten bzw. Sport teil. Da die postoperativen Empfehlungen nur auf niedrigem Evidenzniveau bei Brustrekonstruktion existieren, wurde mittels einer online Befragung ein erster Überblick über die Empfehlungen erhoben. Demzufolge kann die Wiederaufnahme von Sport unterstützt werden, es sollte jedoch auf mögliche Risiken hingewiesen werden. Grundsätzlich ist nach derzeitigem Kenntnisstand nicht von Sport und körperlicher Aktivität nach einem Brustwiederaufbau abzuraten.

Background: Further progress in the treatment of breast cancer will likely come from contributions of molecular biology and immunologic approaches. The search for druggable molecular aberrations may enable treatment based on the molecular profile. A better identification of patients with a high risk of relapse facilitates the selection of these pts for clinical trials investigating early therapeutic molecular-based interventions. Trial Design: The BRandO BiO Registry is a multi-center regional registry to record clinical, epidemiological, and biological data from patients with newly diagnosed breast and ovarian cancer at the University of Ulm, Dept. of Gynecology and 19 affiliated network hospitals and practices in the Alb-Allgäu Bodensee region (outreach area of the Comprehensive Cancer Center Ulm). Longitudinal biobanking is included with collection of paraffin-embedded samples of the primary tumor as well as blood samples at first diagnosis, after 6 and 12 months and at first relapse to isolate and investigate cell-free and germline DNA. Epidemiological, life style and quality of life (QOL) questionnaires are collected at first diagnosis, after 12, 36 and 60 months. The follow up is planned for 10 years. Eligibility criteria: Patients with primary newly diagnosed untreated breast or ovarian cancer of ≥ 18 years are eligible; primary metastatic untreated disease is allowed. Exclusion criteria comprise severe neurological or psychiatric disorders interfering with the ability to give an informed consent, no consent for registration, storage and processing of the individual disease characteristics and bio samples, and any malignant tumor in the last 3 years (except in situ disease). Specific aims: To register the majority of patients with newly diagnosed breast or ovarian cancer in all BRandO-BiO participating centers of a well-defined geographical area. To assess clinical characteristics and outcome data (event-free survival, overall survival) of these patients. To evaluate the primary tumor of all patients for mutational (druggable) aberrations. Further to assess cell-free DNA in the serial blood samples at baseline, 6 and 12 months and correlate these results with clinical outcome data as well as tumor and patient characteristics to look for early markers predicting relapse. To perform a longitudinal assessment of the patients' sociodemographic factors, comorbidities, lifestyle and QOL factors by analyzing serial questionnaires collected at recruitment and at 12, 36 and 60 months. Present accrual and target accrual: The BRandO BiO Registry started January 2016 in the Dept. of Gynecology, University of Ulm and February 2017 at the network hospitals and practices. Until June 2018, 1180 patients with primary breast or ovarian cancer have been enrolled. The current adherence to serial blood testing and serial questionnaires is good with a return rate of 90%. A sample size of 3000 patients is planned. Contact information: Jens Huober, University of Ulm, Dept of Gynecology, Breast Center, jens.huober@uniklinik-ulm.de Amelie de Gregorio, University of Ulm, Dept of Gynecology, Breast Center, Amelie.de Gregorio@uniklinik-ulm.de Citation Format: Huober J, Nagel G, Rempen A, Schlicht E, Flock F, Fritz S, Thiel F, Wiesmüller L, Felderbaum R, Heilmann V, Bekes I, Fink V, Albrecht S, De Gregorio N, Tzschaschel M, Ernst K, Wolf C, Kuhn P, Friedl T, Janni W, De Gregorio A. The BRandO BiO registry – A multicenter regional registry for patients with primary breast and ovarian cancer with longitudinal biobanking and evaluation of epidemiological, life style and quality of life factors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-11-01.

In the framework of the emergency management in the case of seismic events, the evaluation of the expected damage represents a basic requirement for risk informed planning. Seismic risk is defined by the probability to reach a level of damage on given exposed elements caused by seismic events occurring in a fixed period and in a fixed area. To this purpose, the expected seismic input, the exposed elements and their vulnerability have to be correctly evaluated. The aim of the research is to define a correct model of vulnerability curves, in PGA, for masonry structures in Italy, by heuristic approach starting from damage probability matrices (DPMs). To this purpose, the PLINIVS database, containing data on major Italian seismic events, has been used and supported by “critical” assumption on missing data. To support the reliability of this assumption, two vulnerability models, considering or not the hypothesis on the missing data, have been estimated and used to calculate the seismic scenario of the L’Aquila 2009 earthquake through the IRMA (Italian Risk MAp) platform. Finally, a comparison between the outcomes elaborated by IRMA platform and the observed damage collected in the AEDES forms, has been done.

Introduction The objective of this study was to evaluate tracheal reactivity induced by a biodegradable polydioxanone tracheal stent. Materials and methods Twenty-two rabbits were divided into 3 groups assigned to different survival times (30, 60 and 90 days post-implantation). A biodegradable stent was implanted in each animal, except for 1 from each group (negative control). Implantation was performed through a small tracheotomy under fluoroscopic control. CT and histopathological studies were scheduled at the end of survival times. Results No animal died during the procedure or follow-up. The stent had disappeared in 100% of the cases at 90 days, in 50% at 60 days, and in none at 30 days. CT studies revealed a greater tracheal wall thickness at 30 days than at 60 and 90 days (1.60 ± 0.41 mm in the central part of the stent versus 1.11 ± 0.18 and 0.94 ± 0.11; P = .007, respectively). No granulomas were observed on histopathology. Some degree of histological changes were noted at 30 days, which had reduced at 60 and 90 days. Differences were also found in both CT and histology between animals in which the stent was present and animals in which it had degraded. Conclusions Polydioxanone stents produce a mild reaction that reverts with tracheal degradation. The use of these biodegradable stents in benign tracheal disease is promising.

Resumen Introduccion El objetivo de este estudio es evaluar la reactividad traqueal inducida por un stent traqueal biodegradable de polidioxanona. Material y metodos Veintidos conejos se dividieron en 3 grupos con diferentes tiempos de supervivencia (30, 60 y 90 dias postimplantacion). Se implanto un stent biodegradable en cada animal, excepto en uno de cada grupo (control negativo). La implantacion se realizo a traves de una pequena traqueotomia y bajo control fluoroscopico. Al finalizar los tiempos de supervivencia programados se realizaron estudios de TC y anatomopatologicos. Resultados Ningun animal murio durante el procedimiento ni en el seguimiento. El stent habia desaparecido en el 100% de los casos a los 90 dias, en el 50% a los 60 dias y en ninguno a los 30 dias. En los estudios de TC se observo un grosor de la pared traqueal mayor a los 30 que a los 60 y 90 dias (1,60 ± 0,41 mm en la parte central del stent frente a 1,11 ± 0,18 y 0,94 ± 0,11; p = 0,007). En el estudio anatomopatologico no se encontraron granulomas. A los 30 dias se observaba cierto grado de alteracion histologica, la cual se reduce a los 60 y 90 dias. Tambien se encuentran las diferencias, tanto en las TC como en la histologia, entre animales con el stent presente y animales con el stent degradado. Conclusiones Los stents de polidioxanona producen una leve reaccion traqueal que revierte con la degradacion. El uso de estos stents biodegradables en la patologia traqueal benigna es prometedor.

Lange Zeit war eine Chemotherapie die einzige Therapieoption beim metastasierten triple-negativen Mammakarzinom. Mittlerweile hat sich das Therapiespektrum um die Substanzklasse der Immuntherapeutika erweitert, wobei basierend auf der IMpassion130-Studie der Checkpointinhibitor Atezolizumab bei positivem PD-L1-Status in der ersten Linie mit nab-Paclitaxel die Zulassung hat. Bei Vorliegen einer BRCA-Mutation erweitern die Poly(ADP-Ribose)-Polymerase-Inhibitoren (PARP-Inhibitoren) Olaparib und Talazoparib das therapeutische Spektrum nicht nur beim triple-negativen, sondern auch beim hormonrezeptorpositiven Her2-negativen metastasierten Mammakarzinom. Weitere vielversprechende Substanzen wie AKT-Inhibitoren und das Antikorper-Chemokonjugat Sacituzumab-Govitecan werden aktuell noch im Rahmen klinischer Studien untersucht.

La calidad educativa es tema de permanente debate en el mundo, debido a la importancia que tiene para el fortalecimiento de las naciones de cara a los retos y desafíos que encierra el siglo XXI. Por eso, el presente estudio, tuvo como propósito el análisis de la pertinencia de la investigación en el ámbito de la enseñanza del derecho en Ecuador, desde una perspectiva teórica. Se constituyó en un estudio no experimental, de tipo documental y descriptivo. Se revisaron diferentes fuentes legales, bibliográficas y antecedentes investigativos. Producto de ello, se reporta un análisis de los fundamentos legales que rigen los fines de la educación superior en Ecuador como base para la disertación sobre consideraciones que inciden en la enseñanza del derecho, dando lugar a una serie de reflexiones sobre el rol del docente-investigador de significación en este ámbito.

OBJECTIVE Normothermic machine perfusion (NMP) enables optimized ex-vivo preservation of a donor liver in a normal physiologic state. The impact of this emerging technology on donor liver utilization has yet to be assessed. SUMMARY BACKGROUND DATA NMP of the donor liver and ex-vivo enhancement of its function has been envisioned for decades, however only with recent technological advances have devices been suitable for transition to clinical practice. The present study examines the effect NMP on liver utilization in the United States. METHODS The United Network for Organ Sharing database was queried to identify deceased donor livers procured from 2016 to 2019 (n = 30596). Donor livers were divided by preservation method: standard cold-static preservation (COLD, n = 30,368) versus NMP (n = 228). Donor and recipient risk factors, liver disposition, and discard reasons were analyzed. The primary outcome was liver discard rate between 2 groups. RESULTS A total of 4037 livers were discarded. The NMP group had a 3.5% discard rate versus 13.3% in the COLD group (P < 0.001), and this was despite NMP donors being older (47.7 vs 39.5 years, P < 0.0001), more frequently donation after cardiac death (DCD) (18% vs 7%, P < 0.001), and having a greater donor risk index (1.6 vs 1.5, P < 0.05). The most common reasons for liver discard in the COLD group were biopsy findings (38%), DCD warm ischemic time (11%), and prolonged preservation time (10%). Survival analysis, following propensity score matching, found no significant difference in 1-year overall survival between recipients of NMP versus COLD livers. CONCLUSIONS NMP reduces the discard rate of procured livers despite its use in donors traditionally considered of more marginal quality. NMP maintains excellent graft and patient survival. Broader application of NMP technology holds the potential to generate a significant number of additional liver grafts for transplantation every year, thus greatly reducing the nationwide disparity between supply and demand.

In a 37-year-old cardiac arrest survivor with autosomal dominant Carvajal syndrome and arrhythmogenic cardiomyopathy, a desmoplakin mutation was identified. Cascade screening identified 2 affected family members and 2 healthy children carrying the mutation. Strategies for primary and secondary risk prevention emphasize the role of genetic testing in rare cardiomyopathies. (Level of Difficulty: Advanced.), Graphical abstract, In a 37-year-old cardiac arrest survivor with autosomal dominant Carvajal syndrome and arrhythmogenic cardiomyopathy, a desmoplakin mutation was…

ObjectiveObesity is associated with worse survival and an increased risk of relapse in several malignancies. The influence of obesity on vulvar cancer recurrence has not been previously described. The primary objective of this study was to evaluate the association between obesity and tumor recurrence in patients with vulvar cancer.MethodsThis is an analysis of the AGO-CaRE-1 study. Patients diagnosed with squamous cell vulvar cancer (stage IB and higher), treated in 29 cancer centers between January 1998 and December 2008, were registered in a centralized database. The cohort was divided into two gropus depending on the body mass index (BMI) (ResultsIn 849 (52.4%) of 1618 patients in the database, the BMI was documented. Patients were grouped according to their BMI (ConclusionsIn this study a BMI ≥30 kg/m² was associated with a shorter time to recurrence in patients with vulvar cancer and this was mainly attributed to a higher risk of local recurrence.

COVID-19 (SARS-CoV-2 virus) pandemic was recently declared by the WHO as a global health emergency. A group of interventional radiology senior experts developed a consensus document for infection control and management of patients with COVID-19 in interventional radiology (IR) departments. This consensus statement has been brought together at short notice with the help of different protocols developed by governmental entities and scientific societies to be adapted to the current reality and needs of IR Departments. Recommendations are the specific strategies to follow in IR departments, preventive measures and regulations, step by step for donning and doffing personal protective equipment, specific IR procedures which can not be delayed, and aerosol-generating procedures in IR with COVID-19 patients. It is advisable with this document to be adapted to local workplace policies.

Objective Ospemifene is a nonsteroidal selective estrogen receptor modulator (SERM) for the treatment of moderate symptomatic vulvar and vaginal atrophy (VVA) due to menopause. A postauthorization safety study is currently examining the incidence of venous thromboembolism (VTE) among postmenopausal women receiving ospemifene or other SERM (raloxifene, bazedoxifene, or tamoxifen, for noncancer indications), or with untreated VVA. Methods This interim analysis used the US MarketScan Commercial and Medicare Supplemental claims database from 2013 to 2017 to identify incident VTE. The incidence rate and 95% confidence interval of VTE during the first continuous course of treatment (or continuous untreated time for the untreated cohort) were calculated for each cohort overall and by age group, with sensitivity analyses examining incidence in the short term (up to 90 days) and long term (all available follow-up, regardless of treatment changes). Results Analyses included 8,188 ospemifene users, 11,777 other SERM users, and 220,242 women with untreated VVA. The incidence per 1,000 person-years and 95% confidence interval of VTE were 3.7 (1.7-7.1) for ospemifene, 11.5 (8.9-14.6) for other SERM, and 11.3 (10.8-11.7) for untreated VVA. Stratification by age and altering the time frame for analysis produced results with similar patterns to the primary analysis. Conclusions This interim analysis of an ongoing study suggests a favorable safety profile for ospemifene with respect to VTE. Comparative analyses with covariate adjustment will be performed when data accrual is complete.

Anabolic androgenic steroids (AAS) are prohibited as performance-enhancing drugs in sports. Among them, testosterone and its precursors are often referred to as “pseudoendogenous” AAS, that is, endogenous steroids that are prohibited when administered exogenously. To detect their misuse, among other methods, the World Anti-Doping Agency-accredited laboratories monitor the steroid profile (concentrations and concentration ratios of endogenous steroids, precursors and metabolites) in urine samples collected from athletes in and out of competition. Alterations in steroid profile markers are used as indicators for misuse of anabolic steroids in sports. Therefore, especially their metabolic pathways with possible interactions are crucial to elucidate. As steroid metabolism is very complex, and many enzymes are involved, certain non-prohibited drugs may influence steroid metabolite excretion. One important group of steroid-metabolizing enzymes is aldo–keto reductases (AKRs). An inhibition of them by non-steroidal anti-inflammatory drugs (NSAIDs), which are neither prohibited nor monitored, but frequently used drugs in sports, was demonstrated in vitro. Thus, this work aims to investigate the influence of NSAID intake on the urinary steroid profile. Kinetic and inhibitory studies were performed using 5α-dihydrotestosterone as substrate. The results obtained from in vitro experiments show that ibuprofen inhibits AKR1C2 and thus influences steroid biotransformation. For in vivo investigations, urine samples prior, during and postadministration of ibuprofen were analyzed using routine methods to monitor the steroid profile. Changes in markers of the steroid profile of volunteers were observed. The combination of in vitro and in vivo results suggests that monitoring of ibuprofen may be useful in doping control analysis. The presented work illustrates the importance to consider co-administration of (non-prohibited) drugs during antidoping analysis. Intake of multiple substances is likely leading to interfering effects. Divergent results in antidoping analysis may therefore be observed and misinterpretation of analytical data may occur. Similar considerations may be appropriate for other fields of forensic applications.

Although thrombocytosis in patients with primary ovarian cancer has been widely investigated, there are only very few data about the role of thrombocytosis in recurrent ovarian cancer. The aim of our study was to investigate the impact of pretreatment thrombocytosis prior to chemotherapy on clinical outcome in patients with recurrent platinum eligible ovarian cancer. In our retrospective analysis we included 300 patients who were treated by AGO Study Group Centers within three prospective, randomized phase-III-trials. All patients included had been treatment-free for at least 6 months after platinum-based chemotherapy. We excluded patients who underwent secondary cytoreductive surgery before randomization to the trial. Thrombocytosis was defined as a platelet count of ≥ 400⋅109/L. Pretreatment thrombocytosis was present in 37 out of 300 (12.3%) patients. Patients with thrombocytosis responded statistically significantly less to chemotherapy (overall response rate 35.3% and 41.6%, P = 0.046). The median progression-free survival (PFS) for patients with thrombocytosis was 6.36 months compared to 9.00 months for patients without thrombocytosis (hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 0.84–1.69, P = 0.336). Median overall survival (OS) of patients with thrombocytosis was 16.33 months compared to 23.92 months of patients with a normal platelet count (HR = 1.46, 95% CI = 1.00–2.14, P = 0.047). The present analysis suggests that pretreatment thrombocytosis is associated with unfavorable outcome with regard to response to chemotherapy and overall survival in recurrent ovarian cancer.

Benign strictures of the bile duct may be difficult to treat endoscopically due to altered bowel anatomy. Furthermore, recurrence of stenosis and symptoms remains high. The aim of the Spanish Prospective Registry BiELLA study was to investigate the safety and efficacy of absorbable stents in the treatment of benign biliary strictures and their outcomes on the medium and long-term follow-up. A prospective, multicenter, observational, non-randomized study (the BiELLA study) was conducted from January 2014 to September 2018. One hundred fifty-nine patients with benign biliary strictures, mostly postsurgical, were enrolled for implantation of absorbable biliary stents in the 11 participating Spanish tertiary hospitals. The average patient follow-up was 45.4 ± 15.9 months (range, 12–60 months). The follow-up data included symptoms, biochemical parameters, and ultrasound images at 1, 6, and 12 months and then yearly for up to 60 months. The immediate technical and clinical success rates were 100%. In all patients, stent placement resulted in improvement of clinical symptoms and biochemical parameters. The primary mean patency for stent was 86.7, 79.6, and 78.9% at 12, 36, and 60 months, respectively (95% CI). Biliary restenosis and occlusion occurred in 40 (26.6%) patients. Of the 40 patients, 18 (12%) patients were treated with a second stent and 22 (14.6%) patients had operative repair of the recurrent strictures. There were no major complications associated with stent implantation. Implantation of an absorbable polydioxanone biliary stent is safe and effective for treatment of benign biliary strictures refractory to balloon dilatation or other biliary intervention. • Percutaneous implantation of biodegradable prostheses for the treatment of benign postsurgical biliary strictures is a safe and effective procedure. • More than 75% of the patients presented patency of the stented biliary tree at 5 years follow-up. • Absorbable stents improved clinical symptoms and signs (jaundice, itching, fever), and laboratory parameters in a few days after stent placement.

Vaginal lactobacilli (LAB) in probiotic formulas constitute a promising alternative for microbiome reconstitution and for the prevention and treatment of urogenital infections. A double-blind, randomised clinical trial was conducted to assess the safety of LAB-gelatine capsules vaginally administered to healthy sexually active women. Participants were randomised into three groups: intervention A: Lactobacillus reuteri CRL1324, L. gasseri CRL1263 and CRL1307; intervention B: L. rhamnosus CRL1332, L. gasseri CRL1256 and CRL1320; and intervention C: placebo. In a survey and clinical evaluation, participants received a blister with 7 capsules to be administered 1 per day. A second sampling and a new survey were conducted 3-10 days after completing application. Colposcopy was performed to assess adverse effects on vaginal-cervical mucosa. Vaginal swabs were taken for Gram staining to determine the Nugent score, and obtainment of viable-cell cultures to quantify cultivable lactic acid bacteria and pathogens. The main outcomes evaluated were overall satisfaction and secondary effects, including discomfort, urogenital infection, inflammatory response or other symptoms. No significant differences were found in Nugent score or in leukocyte numbers in vaginal samples either before or after the three interventions. However, a tendency to decrease in both the Nugent score and in leukocyte numbers was observed after interventions A and B, though not after C. A significant increase in cultivable lactobacilli was determined after LAB interventions. No severe adverse events were detected. LAB-containing capsules were well tolerated by subjects, so they could be proposed as an adequate alternative to restore vaginal lactobacilli in sexually active women. Fil: de Gregorio, Priscilla Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Maldonado, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Vera Pingitore, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leccese Terraf, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Juárez Tomás, María Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Ruiz, C. Silva. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Santos, V.. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Wiese, B.. Medizinische Hochschule Hannover; Alemania Fil: Bru Chauve, Elena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Paiz, M.C.. Hospital de Clínicas Nicolás Avellaneda; Argentina Fil: Reina, M.F.. Hospital de Clínicas Nicolás Avellaneda; Argentina Fil: Schujman, D.E.. Hospital de Clínicas Nicolás Avellaneda; Argentina Fil: Nader, Maria Elena Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina