Curriculum for diagnostic endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in diagnostic endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in diagnostic EUS. This curriculum is set out in terms of the prerequisites prior to training; the recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should have achieved competence in upper gastrointestinal endoscopy before training in diagnostic EUS. 2: The development of diagnostic EUS skills by methods that do not involve patients is advisable, but not mandatory, prior to commencing formal training in diagnostic EUS. 3: A trainee's principal trainer should be performing adequate volumes of diagnostic EUSs to demonstrate maintenance of their own competence. 4: Training centers for diagnostic EUS should offer expertise, as well as a high volume of procedures per year, to ensure an optimal level of quality for training. Under these conditions, training centers should be able to provide trainees with a sufficient wealth of experience in diagnostic EUS for at least 12 months. 5: Trainees should engage in formal training and supplement this with a range of learning resources for diagnostic EUS, including EUS-guided fine-needle aspiration and biopsy (FNA/FNB). 6: EUS training should follow a structured syllabus to guide the learning program. 7: A minimum procedure volume should be offered to trainees during diagnostic EUS training to ensure that they have the opportunity to achieve competence in the technique. To evaluate competence in diagnostic EUS, trainees should have completed a minimum of 250 supervised EUS procedures: 80 for luminal tumors, 20 for subepithelial lesions, and 150 for pancreaticobiliary lesions. At least 75 EUS-FNA/FNBs should be performed, including mostly pancreaticobiliary lesions. 8: Competence assessment in diagnostic EUS should take into consideration not only technical skills, but also cognitive and integrative skills. A reliable valid assessment tool should be used regularly during diagnostic EUS training to track the acquisition of competence and to support trainee feedback. 9: A period of supervised practice should follow the start of independent activity. Supervision can be delivered either on site if other colleagues are already practicing EUS or by maintaining contacts with the training center and/or other EUS experts. 10: Key performance measures including the annual number of procedures, frequency of obtaining a diagnostic sample during EUS-FNA/FNB, and adverse events should be recorded within an electronic documentation system and evaluated.

Assessing the impact of center volume on the cost-effectiveness of centralizing ERCP.

BACKGROUND AND AIMS: ERCP is a complex endoscopic procedure in which the center's procedure volume influences outcomes. With the increasing healthcare expenses and limited resources, promoting cost-effective care becomes essential for healthcare provision. This study performed a cost-effectiveness analysis to evaluate the hypothesis that high-volume (HV) centers perform ERCP with higher quality at lower costs than low-volume (LV) centers. METHODS: A baseline case compared the current distribution of ERCPs among HV and LV centers with a hypothetical scenario in which all ERCPs are performed at HV centers. A cost-effectiveness analysis was constructed, followed by one-way and two-way sensitivity analyses and probabilistic sensitivity analysis (PSA) using Monte Carlo simulations. RESULTS: In the baseline case, the ICER was -141,017€/year, due to the hypothetical scenario's lower costs and slightly higher QALYs. The model was most sensitive to changes in the transportation costs (109.34%), probability of significant adverse events (AEs) after successful ERCP at LV centers (42.12%), utility after ERCP with significant AEs (30.10%), and probability of significant AEs after successful ERCP at HV centers (23.53%) but only transportation cost above 3,407€ changed the study outcome. The current ERCP distribution would only be cost-effective if LV centers achieved higher success (≥ 92.4% vs. 89.3%) with much lower significant AEs (≤ 0.5% vs 6.7%). The study's main findings remained unchanged while combining all model parameters in the PSA. CONCLUSIONS: Our findings show that HV centers have high-performance rates at lower costs, raising the need to consider the principle of centralization of ERCPs into HV centers to improve the quality of care.

Mediastinal Abscess Formation after EUS-Guided Sampling in a Young Patient with Sarcoidosis: Be Aware of the Increased Risk!

International guidelines establish EUS-guided sampling as safe and accurate for the evaluation of mediastinal solid lesions, such as lymphadenopathies of unknown origin, and point out an increased risk of severe infectious complications induced by needle puncture in mediastinal cystic lesions. A retrospective case series and a systematic review documented an increased risk of mediastinal abscess formation after EUS-guided lymph nodes sampling in patients with sarcoidosis. The authors describe a case of a 38-year-old male patient with a final diagnosis of sarcoidosis, who developed a large mediastinal abscess after EUS-guided fine-needle biopsy of mediastinal lymphadenopathies. Endoscopists should be aware of the potential increased risk of severe infectious complications when sampling mediastinal lymph nodes in suspected sarcoidosis, and a strategy to minimize such risk should be pursued.

As normas de consenso internacionais estabelecem a biopsia guiada por ecoendoscopia como segura e precisa no diagnóstico de lesões sólidas do mediastino, tais como adenopatias de origem indeterminada, e sublinham o risco significativo de complicações infecciosas graves associado à punção de lesões mediastínicas quísticas. Uma série retrospectiva e uma revisão sistemática apontaram para um risco aumentado de abcesso mediastínico após punção guiada por ecoendoscopia de gânglios linfáticos em doentes com sarcoidose. Os autores descrevem o caso cínico de um jovem de 38 anos, com o diagnóstico final de sarcoidose, que desenvolveu um volumoso abcesso mediastínico após biopsia guiada por ecoendoscopia de adenopatias mediastínicas. Os endoscopistas deverão reconhecer o risco aumentado de complicações infeciosas graves aquando da punção de adenopatias mediastínicas na suspeita de sarcoidose e procurar definir uma estratégia preventiva para minimizar o referido risco.

Behavioural and biochemical responses of the sea snail Tritia reticulata to lithium concentration gradient.

Lithium (Li) is present in many modern technologies, most notably in rechargeable batteries. Inefficient recycling strategies for electronic waste containing this element may result in its release into aquatic systems, which may induce harmful effects on wildlife. The present study evaluated the effect of Li contamination on the gastropod Tritia reticulata exposed to different concentrations of Li (100, 200, 500 and 1000 µg L-1) for 21 days. Biochemical analyses showed that this species was not significantly affected by this contaminant at the cellular level, as no significant differences were observed in terms of metabolism, oxidative stress, and neurotoxicity. Results further revealed that snails attempted to avoid Li accumulation by burying in the sediment at a faster rate when exposed to the highest concentrations (500 and 1000 µg L-1). More research is needed to fully assess the response of T. reticulata to Li contamination, such as investigating longer exposure periods or other endpoints.

Face and content validity of a biological papilla designed for the Boskoski-Costamagna ERCP simulator.

BACKGROUND AND AIMS: A biological papilla made of chicken heart tissue, incorporated into the Boskoski-Costamagna ERCP Trainer simulator, was recently designed to allow training in sphincterotomy. This study aimed to evaluate the face and content validity of this tool. METHOD: Participants from 2 groups (nonexperienced and experienced [<600 or >600 lifetime ERCPs, respectively]) were invited to perform standardized assignments on the model: sphincterotomy and precut for both groups and papillectomy for the experienced group. Following these assignments, all participants filled out a questionnaire to rate their appreciation of the realism of the model, and experienced endoscopists were also asked to evaluate its didactic value using a 5-point Likert scale. RESULTS: A total of 19 participants were included (nonexperienced, n = 10; experienced, n = 9). Parameters regarding the realism of the tool in terms of general appearance, sphincterotomy, precut, and papillectomy were overall considered realistic (4 of 5), with good agreement rates in terms of overall realism between groups. Experienced operators reported the highest realism for "positioning the scope and needle-knife in the field of view" and "during precut," "cutting in small increments during precut," and "controlling the scope during papillectomy," and they highly agreed that this papilla should be included for training novice and intermediate trainees in sphincterotomy, precut, and papillectomy. CONCLUSIONS: Our results show good face validity and excellent content validity of this biological papilla combined with the Boskoski-Costamagna ERCP Trainer. This new tool provides a useful, inexpensive, versatile, and easy tool for training regarding sphincterotomy, precut, and papillectomy. Future studies should explore whether including this model in real-life training improves the learning curve of endoscopy trainees.

Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis.

Background: The Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors. Methods: The Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). Results: A total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1-2, and 49 (16%) Grade 3-4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4-21.6 months]) than those without (10.1 months [95% CI, 8.3-12.0 months]) (p<0.001), either if Grade 1-2 (p=0.003) or Grade 3-4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0-11.2 months]) than those without (6.1 months [95% CI, 5.2-7.1 months]) (p<0.001), either if Grade 1-2 (p=0.011) or Grade 3-4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1-2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008). Conclusions: These results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1-2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.

Impact of center and endoscopist ERCP volume on ERCP outcomes: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopist experience and center volume might be associated with ERCP outcomes, as in other fields of endoscopy and in surgery. An effort to assess this relationship is important to improve practice. This systematic review and meta-analysis aimed to evaluate these comparative data and to assess the impact of endoscopist and center volume on ERCP procedure outcomes. METHODS: We performed a literature search in PubMed, Web of Science, and Scopus through March 2022. Volume classification included high- and low-volume (HV and LV) endoscopists and centers. The primary outcome was the impact of endoscopist and center volume on ERCP success. Secondary outcomes were the overall adverse event (AE) rate and the specific AE rate. The quality of the studies was assessed using the Newcastle-Ottawa scale. Data synthesis was obtained by direct meta-analyses using a random-effects model; results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Of 6833 relevant publications, 31 studies met the inclusion criteria. Procedure success was higher among HV endoscopists (OR, 1.81; 95% CI, 1.59-2.06; I2 = 57%) and in HV centers (OR, 1.77; 95% CI, 1.22-2.57; I2 = 67%). The overall AE rate was lower for procedures performed by HV endoscopists (OR, .71; 95% CI, .61-.82; I2 = 38%) and in HV centers (OR, .70; 95% CI, .51-.97; I2 = 92%). Bleeding was less frequent in procedures performed by HV endoscopists (OR, .67; 95% CI, .48-.95; I2 = 37%) but did not differ based on center volume (OR, .68; 95% CI, .24-1.90; I2 = 89%). No statistical differences were detected concerning pancreatitis, cholangitis, and perforation rates. CONCLUSIONS: HV endoscopists and centers provide higher ERCP success rates with fewer overall AEs, especially bleeding, compared with respective LV comparators.

A portrait of Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound training programs in Europe: Current practices and opportunities for improvement.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and EUS are challenging procedures requiring a high level of expertise to provide effective and safe patient care. Thus, high-quality training is needed to achieve competence. We aimed to evaluate the status of European ERCP/EUS training programs, to evaluate adherence to international recommendations, and to propose possible solutions for future improvements. METHODS: A web-based survey was developed and ERCP/EUS experts and trainees across Europe were invited to participate. RESULTS: Forty-one experts (out of 50; 82%) and 30 trainees (out of 70; 42.9%) from 18 countries answered the questionnaire. The training program application process is mainly driven by individual requests (87.8%). All surveyed departments offer combined ERCP/EUS training and the majority have adequate facilities and trainers. Although centers are high-volume and provide long-term fellowships, trainee hands-on exposure is not very high (43% expect to do (or did) 100-150 ERCPs and 69% up to 150 EUSs). A formal curriculum is in place in 53.7% centers, including simulation-training in 27.3%. Competence is assessed in 65.7% of centers, but validated tools are applied in only 33.3%. CONCLUSIONS: This survey first provides an overview of ERCP/EUS training programs across Europe. It shows that there is adherence to international guidelines to a certain degree, but several gaps in the application process, use of simulators for training, training curriculum and assessment of performance have been recognized. Overcoming these shortcomings could serve as a basis for further improvement in ERCP/EUS training.

Interactions of circadian clock genes with the hallmarks of cancer.

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer. In addition, researchers have proposed that circadian genes may have a tissue-dependent and/or context-dependent role in tumorigenesis and may function both as tumor suppressors and oncogenes. Finally, circadian clock core genes may trigger or at least be involved in different hallmarks of cancer. Hence, expanding the knowledge of the molecular basis of the circadian clock would be helpful to identify new prognostic markers of tumorigenesis and potential therapeutic targets.

Who will excel in advanced endoscopy? A study assessing the criteria and perceptions of experts with regard to selection of ERCP and EUS trainees.

Background and study aims Training program directors (TPDs) and experts play a crucial role in selecting ERCP/EUS trainees and determining the workforce in endoscopy. Additionally, prospective trainees should know what TPDs/experts expect from them. Nonetheless, the criteria and perceptions used in this selection have not been clarified. The aim of this study was to identify TPD/expert values/beliefs regarding personal attributes needed for selecting trainees that can excel and those which may lead to disqualification; compare perspectives between TPDs/experts and trainees regarding the selection process and critical trainee characteristics; and investigate the general approach and satisfaction regarding current application process for ERCP/EUS training. Methods We conducted a web-based survey to collect general opinion and data regarding the application process and trainee selection and disqualification from training. European TPDs/experts and trainees were invited to participate. Results Thirty-six TPDs/experts and 25 trainees from 18 countries responded. The application process is mainly driven by individual request (86.1 %). Almost half of TPDs/experts felt only moderately (38.9 %) to slightly (8.3 %) satisfied with the current application process. TPDs/experts value a diversity of trainee characteristics, but mainly traits such as "honesty," "being a team player," and "self-awareness" (72.2 % each). Technical skills ranked seventh as considered "extremely important." "Disregard for patient welfare" and "lack of work ethic" were the most common reasons for disqualification. TPDs/experts and trainees agreed in most questions. Conclusions This survey outlines trainee selection criteria for ERCP/EUS training. Non-technical skills are the most valued by TPDs/experts. While knowledge and technical expertise are clearly important, understanding that professional attitudes are highly regarded may help direct the application process more effectively.

The Multitasker Protein: A Look at the Multiple Capabilities of NUMB.

NUMB, a plasma membrane-associated protein originally described in Drosophila, is involved in determining cell function and fate during early stages of development. It is secreted asymmetrically in dividing cells, with one daughter cell inheriting NUMB and the other inheriting its antagonist, NOTCH. NUMB has been proposed as a polarizing agent and has multiple functions, including endocytosis and serving as an adaptor in various cellular pathways such as NOTCH, Hedgehog, and the P53-MDM2 axis. Due to its role in maintaining cellular homeostasis, it has been suggested that NUMB may be involved in various human pathologies such as cancer and Alzheimer's disease. Further research on NUMB could aid in understanding disease mechanisms and advancing the field of personalized medicine and the development of new therapies.

Endoscopic Reconstruction of an Oral Feeding Route Using a Rendezvous Approach.

Background: The approach to esophageal obstruction or discontinuity remains challenging and often involves complex reconstructive surgeries. The rendezvous endoscopic technique might be interesting in cases of complete esophageal obstruction. Case Presentation: Herein we describe a successful case of endoscopic recanalization of the esophageal lumen in a patient with a long-standing esophageal discontinuity resulting from several surgeries and chemoradiation for a squamous cell carcinoma of the hypopharynx, ending in a major cervical amputation, construction of a neopharynx, and definitive surgical closure of the superior esophagus with a PEG placement. With a rendezvous technique (peroral and through the gastrostomy) and under radiographic guidance, puncture from the neopharynx into the distal esophagus was performed, followed by balloon dilation and covered metal stent placement in order to reconstruct a neoesophagus. Five weeks later, the stent was removed (using a stent-in-stent technique). No complications occurred. The patient has been able to eat soft food and is being kept under regular endoscopic surveillance to control/treat a luminal stenosis of the neoesophagus. Conclusions: This case report illustrates a successful endoscopic treatment of post-surgical complete esophageal obstruction. This approach should be considered in the therapeutic armamentarium of these difficult clinical settings.

Introdução: A abordagem da descontinuidade esofágica permanece desafiante e frequentemente envolve cirurgias reconstrutivas complexas. A técnica endoscópica de rendez-vous pode ser interessante em casos de obstrução esofágica completa. Apresentação do caso: Descrevemos um caso de sucesso de recanalização endoscópica do lúmen esofágico de um doente com descontinuidade esofágica de longa duração, em resultado de múltiplas cirurgias e quimioradiação por um carcinoma pavimento-celular da hipofaringe, que resultou numa amputação cervical major, construção de uma neofaringe e encerramento cirúrgico definitivo do esófago com colocação de PEG. Por técnica de rendez-vous (peroral e por gastrostomia) e sob apoio radiológico, foi realizada punção da neofaringe, seguido de dilatação com balão e colocação de prótese metálica coberta para criar um neo-esófago. Cinco semanas depois, a prótese foi removida (por técnica stent-in-stent). Não ocorreram complicações. O doente tem mantido capacidade de ingerir comida pastosa e é submetido a vigilância regular endoscópica para controlar/tratar uma estenose do lúmen do neo-esófago. Conclusão: Este caso ilustra o tratamento endoscópico bem-sucedido de um doente com obstrução pós-cirúrgica completa do esófago. Esta abordagem deverá ser considerada no arsenal terapêutico destes quadros clínicos complexos.

Computational Study of the pH-Dependent Ionic Environment around ß-Lactoglobulin.

Ions are involved in multiple biological processes and may exist bound to biomolecules or may be associated with their surface. Although the presence of ions in nucleic acids has traditionally gained more interest, ion-protein interactions, often with a marked dependency on pH, are beginning to gather attention. Here we present a detailed analysis on the binding and distribution of ions around ß-lactoglobulin using a constant-pH MD (CpHMD) method, at a pH range 3-8, and compare it with the more traditional Poisson-Boltzmann (PB) model and the existing experimental data. Most analyses used ion concentration maps built around the protein, obtained from either the CpHMD simulations or PB calculations. The requirements of approximate charge neutrality and ionic strength equal to bulk, imposed on the MD box, imply that the absolute value of the ion excess should be half the protein charge, which is in agreement with experimental observation on other proteins ( Proc. Natl. Acad. Sci. U.S.A. 2021, 118, e2015879118) and lends support to this protocol. In addition, the protein total charge (including territorially bound ions) estimated with MD is in excellent agreement with electrophoretic measurements. Overall, the CpHMD simulations show good agreement with the nonlinear form of the PB (NLPB) model but not with its linear form, which involves a theoretical inconsistency in the calculation of the concentration maps. In several analyses, the observed pH-dependent trends for the counterions and co-ions are those generally expected, and the ion concentration maps correctly converge to the bulk ionic strength as one moves away from the protein. Despite the overall similarity, the CpHMD and NLPB approaches show some discrepancies when analyzed in more detail, which may be related to an apparent overestimation of counterion excess and underestimation of co-ion exclusion by the NLPB model, particularly at short distances from the protein.

Handling, Reproducing and Cryopreserving Five European Sea Urchins (Echinodermata, Klein, 1778) for Biodiversity Conservation Purposes.

In this work, five local sea urchin species found in European waters were studied. Four were regular species: Sphaerechinus granularis, Psammechinus miliaris, Echinus esculentus (Linnaeus, 1758) and the edible sea urchin Paracentrotus lividus; and one was an irregular species, Echinocardium cordatum. These five species of sea urchins have been studied regarding their fertility, toxicity of cryoprotecting agents, cryopreservation of different cell types and chilling injury. The baseline fertility is similar in P. lividus, P. miliaris and S. granularis. Nonetheless, the sperm:egg ratio, contact time and development of the fertilization envelope would need to be studied further on a case-by-case basis. Sperm can be maintained inactively in the gonad (4 °C), and oocytes also maintain quality in sea water (4 °C), even after 72 h. Sperm was cryopreserved for four species with some post-thaw intra specific variability, and embryo cryopreservation was only possible for S. granularis. Overall, this study provided a wider vision of the biology and reproduction of these species that will help us develop tools for their biodiversity conservation through cryopreservation.

Starting gastrointestinal endoscopy in a lower middle-income country in Africa: Training, creating an endoscopy facility and developing telemedicine.

Background and study aims The prevalence of digestive diseases seems to be high in African countries. Nonetheless, the human and material resources are scarce. The aim of the Portuguese volunteering project described in this report was to develop the specialty of digestive endoscopy in Sao Tome and Principe, a lower-middle-income country in Africa. Methods Beginning by assessing the local needs and available resources and managing immediate issues related to this field, we aimed to provide the tools necessary to improve gastroenterological and endoscopic care in the country. The first step included training of the local teams, through the development and accomplishment of an adapted curriculum for a 3-year medical gastroenterological fellowship and a short-term nursing fellowship, both in Portugal, and the organization of regular gastroenterological and endoscopic theoretical and practical sessions in Sao Tome and Principe. Second, the endoscopy facilities of the unit were significantly optimized. Third, a web platform was designed to provide telemedicine incorporating real-time endoscopic imaging available remotely. Results Through these sequential steps achieved in collaboration with Portuguese and local teams, this 5-year project provided the basis for gastroenterology care in this country. Conclusions At the present time, Sao Tome and Principe has an autonomous, efficient and skilled team and unit to provide care for patients with gastrointestinal diseases who need endoscopic procedures.

Endoscopic Management of Symptomatic Duodenal Duplication Cysts: Two Case Reports.

Background: Duodenal duplication cysts (DDCs) are rare congenital anomalies typically manifesting during childhood. Clinical manifestations are uncommon in adulthood. DDCs were classically treated surgically, but endoscopic treatment has been increasingly reported. Endoscopic cyst marsupialization establishes a communication between the cyst cavity and the duodenal lumen so that the cystic content can be drained continuously into the duodenum. We herein describe two cases of symptomatic DDCs diagnosed in adulthood and submitted to endoscopic marsupialization using different techniques and devices. Case Summary: Case 1: A 23-year-old female patient was admitted with the diagnosis of acute pancreatitis. Endoscopic ultrasound revealed a 35-mm duodenal subepithelial lesion whose proximal limit was immediately distal to the ampulla of Vater and filled with fluid and calcifications. Using a duodenoscope, deroofing of the lesion was made with a diathermic snare. Pathology confirmed the diagnosis of DDC. Case 2: A 41-year-old female, submitted to laparoscopic cholecystectomy 1 month earlier due to suspected lithiasic acute pancreatitis, was admitted due to suspicion of iatrogenic biliary fistula. An endoscopic retrograde cholangiopancreatography was performed and the bile leak was treated. Immediately distal to the papillary orifice, a 20-mm subepithelial lesion was also detected. A biopsy forceps was used to fenestrate its wall, allowing the exit of mucous fluid and stones, and a sphincterotome was used to expand the incision. No recurrence was documented in both cases. Conclusion: These cases highlight DDC as a potential cause for acute pancreatitis in adults and endoscopy as an easy treatment option.

Introdução: Os quistos de duplicação duodenais (QDD) são anomalias congénitas raras que tipicamente se manifestam durante a infância. As manifestações clínicas são pouco frequentes em adultos. Os QDD eram classicamente tratados cirurgicamente, mas o tratamento endoscópico tem sido crescentemente reportado. A marsupialização endoscópica do quisto estabelece uma comunicação entre a cavidade do quisto e o lúmen duodenal, permitindo que o conteúdo do quisto drene continuamente para o duodeno. Reportamos 2 casos de QDD diagnosticados em adultos e submetidos a marsupialização endoscópica, utilizando diferentes técnicas e dispositivos. Casos clínicos: Caso 1: Doente do sexo feminino, 23 anos, internada por pancreatite aguda. Por ecoendoscopia documentou-se lesão subepitelial duodenal com 35 mm com limite proximal imediatamente distal à ampola de Vater, preenchida por líquido e calcificações. Usando um duodenoscópio, foi feita marsupialização da lesão com ansa diatérmica. Histologia confirmou o diagnóstico de QDD. Caso 2: Doente do sexo feminino, 41 anos, submetida a colecistectomia laparoscópica 1 mês antes por suspeita de pancreatite aguda litiásica, foi internada por suspeita de fístula biliar iatrogénica. Por CPRE confirmouse fuga biliar que foi tratada. Imediatamente distal ao orifício papilar, foi também detetada uma lesão subepitelial com 20 mm. Uma pinça de biopsia foi usada para fenestrar a sua parede, permitindo a saída de fluido mucoso e cálculos e um esfincterótomo foi usado para expandir a incisão. Não se registou recorrência em nenhum dos casos. Conclusão: Estes casos destacam os QDD como causa potencial de pancreatite aguda em adultos e a endoscopia como possível opção terapêutica.

FixBox: A General Algorithm to Fix Molecular Systems in Periodic Boxes.

Periodic boundary conditions (PBCs) are a standard feature of molecular simulations, and their mathematical and computational aspects are well-understood and relatively straightforward. However, they can in practice be a nuisance when simulating heterogeneous systems, especially when different types of molecules change their relative positions during the simulation. Although the translation required to fix a broken molecular complex of interest can in most cases be easily inferred by visual inspection, it typically depends on the type of system, its configuration, and the box geometry, making automated procedures problematic. We present here a general algorithm, named FixBox, that can fix a molecular complex of interest from a minimal set of definitions of its assembling parts and intended arrangement in the simulation box. It uses a unified triclinic framework for the box geometric periodicity, does not require a full molecular topology, and is applicable to various types of systems and configurations, making it possible to fully and easily automate the fixing of a broken molecular complex. The performance of the algorithm is illustrated with problematic configurations of various types of simulated systems. The presented formal framework can generally be useful for algorithms that need to perform geometrical transformations on systems with PBCs.

Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper.

Sepsis is a common illness. Immune responses are considered major drivers of sepsis illness and outcomes. However, there are no proven immunomodulator therapies in sepsis. We hypothesised that in-depth characterisation of sepsis-specific immune trajectory may inform immunomodulation in sepsis-related critical illness. We describe the protocol of the IMMERSE study to address this hypothesis. We include critically ill sepsis patients without documented immune comorbidity and age-sex matched cardiac surgical patients as controls. We plan to perform an in-depth biological characterisation of innate and adaptive immune systems, platelet function, humoral components and transcriptional determinants of the immune system responses in sepsis. This will be done at pre-specified time points during their critical illness to generate an illness trajectory. The sample size for each biological assessment is different and is described in detail. In summary, the overall aim of the IMMERSE study is to increase the granularity of longitudinal immunology model of sepsis to inform future immunomodulation trials.