Acute pancreatitis secondary to severe hypertriglyceridemia induced by antiretroviral therapy (ART).

Hypertriglyceridemia is the third cause of acute pancreatitis after lithiasis and alcohol. When triglycerides are >2000 mg/dL the risk increases to 20%. Acute pancreatitis is an important cause of morbidity in patients infected with human immunodeficiency virus (HIV), especially in those treated with lamivudine, due to hypertriglyceridemia.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Use of 2D minilungs from human embryonic stem cells to study the interaction of Cryptococcus neoformans with the respiratory tract.

Organoids can meet the needs between the use of cell culture and in vivo work, bringing together aspects of multicellular tissues, providing a more similar in vitro system for the study of various components, including host-interactions with pathogens and drug response. Organoids are structures that resemble organs in vivo, originating from pluripotent stem cells (PSCs) or adult stem cells (ASCs). There is great interest in deepening the understanding of the use of this technology to produce information about fungal infections and their treatments. This work aims the use 2D human lung organoid derived from human embryonic stem cells (hESCs), to investigate Cryptococcus neoformans-host interactions. C. neoformans is an opportunistic fungus acquired by inhalation that causes systemic mycosis mainly in immunocompromised individuals. Our work highlights the suitability of human minilungs for the study of C. neoformans infection (adhesion, invasion and replication), the interaction with the surfactant and induction of the host's alveolar pro-inflammatory response.

Antimigration versus conventional fully covered metal stents in the endoscopic treatment of anastomotic biliary strictures after deceased-donor liver transplantation.

INTRODUCTION: Migration of fully covered metal stents (FCMS) remains a limitation of the endoscopic treatment of anastomotic biliary strictures (ABS) following orthotopic liver transplantation (OLT). The use of antimigration FCMS (A-FCMS) might enhance endoscopic treatment outcomes for ABS. METHODS: Single center retrospective study. Consecutive patients with ABS following OLT who underwent ERCP with FCMS placement between January 2005 and December 2020 were eligible. Subjects were grouped into conventional-FCMS (C-FCMS) and A-FCMS. The primary outcome was stent migration rates. Secondary outcomes were stricture resolution, adverse event, and recurrence rates. RESULTS: A total of 102 (40 C-FCMS; 62 A-FCMS) patients were included. Stent migration was identified at the first revision in 24 C-FCMS patients (63.2%) and in 21 A-FCMS patients (36.2%) (p = 0.01). The overall migration rate, including the first and subsequent endoscopic revisions, was 65.8% in C-FCMS and 37.3% in A-FCMS (p = 0.006). The stricture resolution rate at the first endoscopic revision was similar in both groups (60.0 vs 61.3%, p = 0.87). Final stricture resolution was achieved in 95 patients (93.1%), with no difference across groups (92.5 vs 93.5%; p = 0.84). Adverse events were identified in 13 patients (12.1%) with no difference across groups. At a median follow-up of 52 (IQR: 19-85.5) months after stricture resolution, 25 patients (24.5%) developed recurrences, with no difference across groups (C-FCMS 30% vs A-FCMS 21%; p = 0.28). CONCLUSIONS: The use of A-FCMS during ERCP for ABS following OLT results in significantly lower stent migration rates compared to C-FCMS. However, the clinical benefit of reduced stent migration is unclear. Larger studies focusing on stricture resolution and recurrence rates are needed.

Modeling of Respiratory Diseases Evolving with Fibrosis from Organoids Derived from Human Pluripotent Stem Cells.

Respiratory disease is one of the leading causes of morbidity and mortality worldwide. There is no cure for most diseases, which are treated symptomatically. Hence, new strategies are required to deepen the understanding of the disease and development of therapeutic strategies. The advent of stem cell and organoid technology has enabled the development of human pluripotent stem cell lines and adequate differentiation protocols for developing both airways and lung organoids in different formats. These novel human-pluripotent-stem-cell-derived organoids have enabled relatively accurate disease modeling. Idiopathic pulmonary fibrosis is a fatal and debilitating disease that exhibits prototypical fibrotic features that may be, to some extent, extrapolated to other conditions. Thus, respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or the one caused by SARS-CoV-2 may reflect some fibrotic aspects reminiscent of those present in idiopathic pulmonary fibrosis. Modeling of fibrosis of the airways and the lung is a real challenge due to the large number of epithelial cells involved and interaction with other cell types of mesenchymal origin. This review will focus on the status of respiratory disease modeling from human-pluripotent-stem-cell-derived organoids, which are being used to model several representative respiratory diseases, such as idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease, and COVID-19.

Randomized Controlled Trial Evaluating the Benefit of a Novel Clinical Decision Support System for the Management of COVID-19 Patients in Home Quarantine: A Study Protocol.

(1) Background: We present the protocol of a randomized controlled trial designed to evaluate the benefit of a novel clinical decision support system for the management of patients with COVID-19. (2) Methods: The study will recruit up to 500 participants (250 cases and 250 controls). Both groups will receive the conventional telephone follow-up protocol by primary care and will also be provided with access to a mobile application, in which they will be able to report their symptoms three times a day. In addition, patients in the active group will receive a wearable smartwatch and a pulse oximeter at home for real-time monitoring. The measured data will be visualized by primary care and emergency health service professionals, allowing them to detect in real time the progression and complications of the disease in order to promote early therapeutic interventions based on their clinical judgement. (3) Results: Ethical approval for this study was obtained from the Drug Research Ethics Committee of the Valladolid East Health Area (CASVE-NM-21-516). The results obtained from this study will form part of the thesis of two PhD students and will be disseminated through publication in a peer-reviewed journal. (4) Conclusions: The implementation of this telemonitoring system can be extrapolated to patients with other similar diseases, such as chronic diseases, with a high prevalence and need for close monitoring.

Visual perception alterations in COVID-19: a preliminary study.

AIM: To compare the visual perception (color and chromatic-achromatic contrast vision) of a small cohort of COVID-19 patients at the time of infection and after 6mo with that of a healthy population matched for sex and age. METHODS: A total of 25 patients (9 females, 16 males, mean age: 54±10y) with COVID-19 hospitalized in the COVID-19 Unit of the University Clinical Hospital of Valladolid were recruited for this preliminary study. Visual perception, as determined by monocular measurement of contrast sensitivity function (CSF) and color vision was assessed in each patient using the Optopad test. The results obtained were then compared with those of a sample of 16 age- and sex-matched healthy controls (5 females, 11 males, mean age: 50±6y) in which the same measurement procedure was repeated. Statistically significant differences between groups were assessed using the Mann-Whitney U test. Measurements were repeated after a minimum follow-up period of 6mo and statistically significant differences between the two time points in each group were assessed using the Wilcoxon signed rank test. RESULTS: Discrimination thresholds (color and chromatic-achromatic contrast vision) and their corresponding sensitivity, calculated as the inverse of the discrimination threshold, were evaluated. Analysis of the data revealed higher contrast threshold results (i.e., worse contrast sensitivity) in the COVID-19 group than in the control group for all spatial frequencies studied in the Optopad-CSF achromatic test and most of the spatial frequencies studied in the Optopad-CSF chromatic test for the red-green and blue-yellow mechanisms. In addition, color threshold results in the COVID-19 group were also significantly higher (i.e., worse color sensitivity) for almost all color mechanisms studied in the Optopad-Color test. At 6mo, most of the differences found between the groups were maintained despite COVID-19 recovery. CONCLUSION: The present results provide preliminary evidence that visual perception may be impaired in COVID-19, even when the infection has passed. Although further research is needed to determine the precise causes of this finding, analysis of CSF and color vision could provide valuable information on the visual impact of COVID-19.

Postreperfusion Biopsy as a Predictor of Biliary Complication After Deceased Donor Liver Transplantation. A Retrospective Cohort Study.

BACKGROUND: Ischemia reperfusion injury (IRI) on postreperfusion biopsies is associated with worse outcomes after liver transplantation, although the influence on biliary complications (BC) remains poorly studied. Therefore, the primary aim of our study was to assess the influence of IRI on the incidence of BC. A secondary aim was to assess the influence of steatosis on biliary complications and determine factors that predictor BC. METHODS: We report a retrospective cohort study including patients with liver transplantation and postreperfusion injury. Biopsies were classified as relevant and nonrelevant ischemia reperfusion injury for assessment of BC. BC included anastomotic stricture, ischemic cholangiopathy, leaks, and bilomas. Independent predictive factors of biliary complications were assessed using univariate and multivariate analyses. RESULTS: 302 patients were included, and 125 patients fulfilled the criteria for relevant IRI (41.4%). Worse IRI was not associated with biliary complications (42.5% vs 40.1%; P = .68), nor was liver graft steatosis associated with BC (40.5% vs 41.5%, P = .95). The median time until biliary complications did not differ between the 2 groups (2 months; interquartile range = 1-15 vs 3 months; interquartile range = 1-12.5; P = .18). Hepatic artery thrombosis (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.4-8.2; P = .004), older donor age (OR = 2.1; 95% CI, 1.1-4.1; P = .024), and prolonged cold ischemia time (OR = 1.9; 95% CI, 1.1-3.2) were independent factors of biliary complications. CONCLUSION: Severe IRI on the postreperfusion injury does not predict development of biliary complications.

Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract.

The new generation of organoids derived from human pluripotent stem cells holds a promising strategy for modeling host-bacteria interaction studies. Organoids recapitulate the composition, diversity of cell types, and, to some extent, the functional features of the native organ. We generated lung bud organoids derived from human embryonic stem cells to study the interaction of Streptococcus pneumoniae (pneumococcus) with the alveolar epithelium. Invasive pneumococcal disease is an important health problem that may occur as a result of the spread of pneumococcus from the lower respiratory tract to sterile sites. We show here an efficient experimental approach to model the main events of the pneumococcal infection that occur in the human lung, exploring bacterial adherence to the epithelium and internalization and triggering an innate response that includes the interaction with surfactant and the expression of representative cytokines and chemokines. Thus, this model, based on human minilungs, can be used to study pneumococcal virulence factors and the pathogenesis of different serotypes, and it will allow therapeutic interventions in a reliable human context. IMPORTANCE Streptococcus pneumoniae is responsible for high morbidity and mortalities rates worldwide, affecting mainly children and adults older than 65 years. Pneumococcus is also the most common etiologic agent of bacterial pneumonia and nonepidemic meningitis, and it is a frequent cause of bacterial sepsis. Although the introduction of pneumococcal vaccines has decreased the burden of pneumococcal disease, the rise of antibiotic-resistant strains and nonvaccine types by serotype replacement is worrisome. To study the biology of pneumococcus and to establish a reliable human model for pneumococcal pathogenesis, we generated human minilungs from embryonic stem cells. The results show that these organoids can be used to model some events occurring during the interaction of pneumococcus with the lung, such as adherence, internalization, and the initial alveolar innate response. This model also represents a great alternative for studying virulence factors involved in pneumonia, drug screening, and other therapeutic interventions.

Effects of Hypocalcemic Vitamin D Analogs in the Expression of DNA Damage Induced in Minilungs from hESCs: Implications for Lung Fibrosis.

In our previous work, we evaluated the therapeutic effects of 1α,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, in the context of bleomycin-induced lung fibrosis. Contrary to the expected, vitamin D supplementation increased the DNA damage expression and cellular senescence in alveolar epithelial type II cells and aggravated the overall lung pathology induced in mice by bleomycin. These effects were probably due to an alteration in the cellular DNA double-strand breaks' repair capability. In the present work, we have evaluated the effects of two hypocalcemic vitamin D analogs (calcipotriol and paricalcitol) in the expression of DNA damage in the context of minilungs derived from human embryonic stem cells and in the cell line A549.

Acute liver failure due to anti-tuberculous treatment: when you travel without medical follow-up.

We present an uncommon cause of liver transplant in a patient with a particular personal situation, who suffered loss of follow-up during his antitubercular treatment. He presented a dress syndrome with fulminant liver failure that required a liver transplant. This case demonstrates the importance of close monitoring of liver function during this treatment.

Diarrhea secondary to intestinal infiltration secondary to renal epidermoid carcinoma.

Renal squamous cell carcinoma is a rare neoplasm in adults, but with an aggressive behavior. It is diagnosed in most cases in advanced stages. The invasion of the digestive tract by this type of tumor is rare, due to the anatomical arrangement of the colon, however, when it occurs, it carries a poor prognosis for the patient. Digestive endoscopy allows us to reach a definitive diagnosis since these patients usually present digestive manifestations, such as diarrhoea, digestive bleeding or abdominal pain.

The role of endoscopic ultrasound guidance for biliary and pancreatic duct access and drainage to overcome the limitations of ERCP: a retrospective evaluation.

BACKGROUND: Endoscopic ultrasound (EUS)-guided ductal access and drainage (EUS-DAD) of biliary/pancreatic ducts after failed endoscopic retrograde cholangiopancreatography (ERCP) is less invasive than percutaneous transhepatic biliary drainage (PTBD). The actual need for EUS-DAD remains unknown. We aimed to determine how often EUS-DAD is needed to overcome ERCP failure. METHODS: Consecutive duct access procedures (n = 2205; 95 % biliary) performed between June 2013 and November 2015 at a tertiary-care center were reviewed. ERCP was used first line, EUS-DAD as salvage after ERCP, and PTBD when both had failed. Procedures were defined as "index" in patients without prior endoscopic duct access and "combined" when EUS-DAD followed successful ERCP. The main outcomes were the EUS-DAD and PTBD rates. RESULTS: EUS-DAD was performed in 7.7 % (170/2205) of overall procedures: 9.1 % (116/1274) index and 5.8 % (54/931) follow-up. Most index EUS-DADs were performed following (46 %) or anticipating (39 %) ERCP failure, whereas 15 % followed successful ERCP (combined procedures). Among index procedures, the EUS-DAD rate was higher in surgically altered anatomy (58.2 % [39 /67)] vs. 6.4 % [77/1207]); PTBD was required in 0.2 % (3/1274). Among follow-up procedures, ERCP represented 85.7 %, cholangiopancreatography through mature transmural fistulas 8.5 %, and EUS-DAD 5.8 %; no patient required PTBD. The secondary PTBD rate was 0.1 % (3/2205). Six primary PTBDs were performed (overall PTBD rate 0.4 % [9/2205]). CONCLUSIONS: EUS-DAD was required in 7.7 % of ERCPs for benign and malignant biliary/pancreatic duct indications. Salvage PTBD was required in 0.1 %. This high EUS-DAD rate reflects disease complexity, a wide definition of ERCP failure, and restrictive PTBD use, not poor ERCP skills. EUS-DAD effectively overcomes the limitations of ERCP eliminating the need for primary and salvage PTBD in most cases.

Safety and efficacy of endoscopic ultrasound-guided gallbladder drainage combined with endoscopic retrograde cholangiopancreatography in the same session.

BACKGROUND AND AIM: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an emerging option for acute cholecystitis in non-surgical candidates. Combining endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones with EUS-GBD in a single session might become a non-surgical management strategy to comprehensively treat gallstone disease in selected patients. METHODS: Single-center retrospective cohort study comparing outcomes between EUS-GBD alone (group A) and single-session ERCP combined with EUS-GBD (group B). Consecutive patients who underwent EUS-GBD with a lumen-apposing metal stent (LAMS) between June 2011 and August 2018 were analyzed. Exclusion criteria were subjects included in randomized clinical trials, patients who had had ERCP within 5 days of EUS-GBD, patients in whom ERCP or EUS-GBD was carried out for salvage of one or the other procedure, and patients who underwent concurrent EUS-guided biliary drainage. RESULTS: One hundred and nine consecutive patients underwent EUS-GBD with LAMS during the study period. Seventy-one patients satisfied the inclusion criteria and 34 patients were in group A and 37 in group B. Baseline characteristics were similar in both groups. There were no significant differences in technical (97.1% vs 97.3%; P = 0.19) and clinical success rates (88.2% vs 94.6%; P = 0.42) of EUS-GBD in group A versus group B. Rate of adverse events was similar in both groups, five (14.7%) in group A versus five (13.5%) in group B. CONCLUSIONS: Single-session EUS-GBD combined with ERCP has comparable rates of technical and clinical success to EUS-GBD alone. A combined EUS-GBD and ERCP procedure does not appear to increase adverse events and makes possible comprehensive treatment of gallstone disease by purely endoscopic means.

Safety and clinical outcomes of endoscopic ultrasound-guided gallbladder drainage with lumen-apposing metal stents in patients with dwell time over one year.

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has proved effective in patients with cholecystitis at high surgical risk. The long-term risks of gallstone-related disease and stent-related adverse events are unknown. METHODS: We performed a retrospective evaluation of a case series including subjects who underwent EUS-GBD using lumen-apposing metal stents (LAMS). Patients were identified from a prospective LAMS registry at a single tertiary center. Patients with a stent indwell time <1 year were excluded. Data regarding stent deployment and adverse events were retrieved from the prospective LAMS registry, while emergency room visits, admissions and causes of death were retrieved from electronic medical records. RESULTS: We included 22 patients with a median age of 88.3 years (interquartile range [IQR]: 82.6-92.7), 14 (63.6%) were male. Median follow up was 24.4 months (IQR: 18.2-42.4) and median time to the last available imaging procedure was 607 days (IQR: 463-938). No LAMS-related adverse events were identified beyond the first year of follow up. During follow up, 12 patients (54.5%) visited the emergency room 34 times (1 visit/patient, IQR: 0-3) and a total of 36 hospital admissions were required, with a median of 1 admission/patient (IQR: 0-3). Fourteen (63.6%) patients died during follow up. Only 1 patient (4.5%) required new hospital admissions for gallstone-related disease. CONCLUSIONS: There were no adverse events beyond the first year after stent deployment, with only 4.5% of subjects requiring gallstone-related admissions. Permanent EUS-GBD with LAMS may be a definitive treatment for acute cholecystitis in patients ineligible for cholecystectomy.

Cumulative risks of stent migration and gastrointestinal bleeding in patients with lumen-apposing metal stents.

BACKGROUND: Delayed gastrointestinal (GI) bleeding and stent migration are known adverse events which may occur following placement of lumen-apposing metal stents (LAMSs). METHODS: All consecutive patients who underwent LAMS placement between May 2011 and June 2017 at a single tertiary medical center were included. Demographics and procedural details were prospectively collected. Post-procedure follow-up and outcome measures were retrospectively collected. The cumulative risks of migration and LAMS-related GI bleeding were estimated using the life-table method. Risk predictors were assessed using Cox proportional hazards models. RESULTS: We analyzed 250 patients (64.8 % men; median age 71.6 [interquartile range (IQR) 57.9 - 83.6]). Median follow-up was 78.5 days (IQR 31 - 246.5 days). Thirty-four stent migrations (13.6 %) occurred (5 symptomatic). On multivariable analysis, associations with migration included nasocystic drains (hazard ratio [HR] 6.5, 95 % confidence interval [CI] 2.2 - 19.3), pancreatic fluid collections (PFCs; HR 4.2, 95 %CI 1.8 - 10.1), and double-pigtail stents (HR 2.4, 95 %CI 1.2 - 4.9). Migration risk at 12 months was 25.5 % (95 %CI 17.9 % - 35.7 %) and was higher for PFCs 48.9 % (33.4 % - 66.9 %) than other indications 8.4 % (4.9 % - 17.5 %; P < 0.001). LAMSs placed for longer durations (i. e. enteral anastomoses, biliary and gallbladder drainage) presented an 8.4 % cumulative risk at 2 years. There were 13 LAMS-related GI hemorrhages (5.2 %), two of them fatal, presenting a median of 3 days (IQR 1 - 9 days) after deployment. The cumulative risk of bleeding at 12 months was 6.9 % (3.6 % - 12.7 %). CONCLUSIONS: LAMS migration occurs in 1 out of 7 cases and is most common when treating PFCs. Bleeding related to LAMS placement occurs much less commonly but can be life-threatening.