Endoscopic cyanoacrylate injection for massive bleeding from a ruptured pseudocyst.

Arterial bleeding is a dreadful late complication of acute pancreatitis that usually mandates emergent endovascular embolization or surgery. We present the case of a massive arterial bleeding resulting from fistulization of a pseudocyst to the stomach, which was successfully managed by endoscopic injection of cyanoacrylate.

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease.

BACKGROUND: Immunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AIMS: This study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. METHODS: We conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. RESULTS: Our study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. CONCLUSIONS: Anti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.

Transforming pharmaceutical education: A needs-based global analysis for policy development.

Background: A needs-based approach is desirable for the transformation of pharmaceutical education, and to link pharmaceutical education with the health needs of populations and national priorities. There are varying levels of data in the literature on the status of pharmaceutical education in all six World Health Organization (WHO) regions, especially in the context of needs identification and evidence-based policy interventions. The framework for this study was the FIP Development Goals. Objectives: The aim of the study was to develop evidence-based policies through a needs-based approach for pharmaceutical education transformation nationally, regionally and globally by addressing the following objectives: 1. Identify global and regional needs in pharmaceutical education, through a regional SWOT analysis and prioritization of FIP development goals; 2. Develop valid and credible regional roadmaps for pharmaceutical education advancement according to the identified prioritized goals and 3. Develop a global call to action as a policy intervention for advancing pharmaceutical education. Methods: This study was conducted between 2020 and 2021 using a mixed methods approach. Surveys of higher education institutions and a series of qualitative interviews were conducted with national professional leadership organizations, with further regional workshops having 284 participants recruited from the International Pharmaceutical Federation (FIP) membership base, spanning all six WHO regions. Results: Eleven out of 21 FIP DGs were identified as priorities for regional roadmaps and FIP DG 1 (Academic capacity) was identified as a priority in four regions. All regions had distinctive results with an area of commonality between them. There were common weaknesses in the adoption of competency-based education and inter-professional education. Conclusions: It is critical for every country and region to develop needs- and evidence-based policies for the transformation of pharmaceutical education, for which FIP DGs provide a systematic framework.

COVID-19-associated secondary sclerosing cholangitis - A case series of 4 patients.

We report a case series of four patients diagnosed with COVID-19-associated secondary sclerosing cholangitis (SSC), a recently described rare late complication of severe COVID-19. Following prolonged stays in the intensive care unit, these patients developed marked sustained cholestasis and jaundice despite clinical improvement. Cholangiography showed beaded appearance of intra-hepatic bile ducts and bile casts were removed in one patient. None of the patients reached normalization of liver enzymes and at least one progressed to liver cirrhosis (follow-up time of 11 to 16 months). COVID-19-associated SSC has a dismal prognosis with rapid progression to advanced chronic liver disease.

Atmospheric microplastic fallout in outdoor and indoor environments in São Paulo megacity.

Plastics are widely used by society, and their degradation into millimetre fragments, called microplastics (MPs), has become a global environmental threat to ecosystems and human health. However, airborne MPs' presence and fallout fluxes from the atmosphere are poorly understood and can vary significantly by different conditions, especially in megacities of low- and middle-income countries, where high levels of vehicular air pollution, a high-density population, high plastic use, and inadequate disposal are environmental threats related to airborne MPs. In this study, we investigate the amount, chemical composition, and morphological characteristics of outdoor and indoor airborne MPs fallout in the megacity of São Paulo and assess the influence of weather and seasons on airborne MPs fallout. The results were as follows: MPs were found in all samples with an average fallout rate of 309.40 ± 214.71 MPs/m2/day in the indoor environment, and 123.20 ± 47.09 MPs/m2/day in the outdoor environment; MPs concentrations were higher in the indoor environment than the outdoor environment, with more fibres than particles; polyester fibres (100%), polyethylene (59%) and polypropylene (26%) particles were the dominant polymers indoors, while in outdoors, polyester fibres (76%) and polyethylene (67%) and polyethylene terephthalate (25%) particles were dominant. Fragment was the dominant morphology of particles found in indoor and outdoor samples (64% and 74%, respectively). Outdoor MPs fallout correlated positively with rainfall, wind velocity, and relative humidity. This evidence is the first on airborne MPs in a Latin America megacity and highlights the relevant role that this source plays in different environments.

Needle knife fistulotomy in flat and diverticular papillae: Is it time for redemption?

BACKGROUND: European Society of Gastrointestinal Endoscopy (ESGE) recommends needle-knife fistulotomy (NKF) as the preferred precut technique in cases when standard cannulation techniques fail. Despite scarce scientific evidence, flat and diverticular papillae are thought not to be ideal for NKF, as they are associated with poor outcomes. The present study aimed to determine the outcomes of the use of NKF in relation to flat and intradiverticular papillae. METHODS: This prospective multicenter study enrolled consecutive patients, evidencing naïve flat (group A, n = 49) or diverticular papilla (group B, n = 28), who underwent NKF after failure of standard cannulation techniques. Diverticular morphology was subdivided into intradiverticular (group B1, n = 14) and diverticular border papillae (group B2, n = 14), using a previously validated endoscopic classification of the major papilla. The success of biliary cannulation at initial endoscopic retrograde cholangiopancreatography (ERCP), overall biliary cannulation, overall cannulation time, and the rate of adverse events were assessed in the study. RESULTS: The initial cannulation rates were 93.9%, 64.3% and 71.4% for group A, B1, and B2, respectively (P = 0.005); overall cannulation rates after a second ERCP were 98.0%, 92.9% and 85.7%, respectively (P = 0.134). Adverse events occurred in 11.7% of patients, with post-ERCP pancreatitis (PEP) being the most common adverse event (10.4%). Although there was a trend towards a higher incidence of PEP in flat papillae, univariate and multivariate analyses did not show any significant relationship between pancreatitis and trainee involvement, papillary morphology, nor overall cannulation time. CONCLUSIONS: Although flat papillae are associated with high success rates of biliary cannulation using NKF, the rate of PEP is not negligible. NKF is feasible in diverticular papillae, but it is associated with a modest success rate in the initial ERCP.

Factors Influencing Performance of Cholangioscopy-Guided Lithotripsy Including Available Different Technologies: A Prospective Multicenter Study with 94 Patients.

BACKGROUND: Peroral cholangioscopy (POC)-guided lithotripsy is an effective treatment for difficult biliary stones. A clear definition of factors associated with the efficacy of POC-guided lithotripsy in one session and the performance of electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL) have not clearly emerged. METHODS: This was a non-randomized prospective multicenter study of all consecutive patients who underwent POC lithotripsy (using EHL and/or LL) for difficult biliary stones. The primary endpoint of the study was the number of sessions needed to achieve complete ductal clearance and the factors associated with this outcome. Secondary endpoints included the evaluated efficacies of LL and EHL. RESULTS: Ninety-four patients underwent 113 procedures of EHL or LL. Complete ductal clearance was obtained in 93/94 patients (98.94%). In total, 80/94 patients (85.11%) achieved stone clearance in a single session. In the multivariate analysis, stone size was independently associated with the need for multiple sessions to achieve complete ductal clearance (odds ratio = 1.146, 95% confidence interval: 1.055-1.244; p = 0.001). Using ROC curves and the Youden index, 22 mm was found to be the optimal cutoff for stone size (95% confidence interval: 15.71-28.28; p < 0.001). The majority of the patients (62.8%) underwent LL in the first session. Six patients failed the first session with EHL after using two probes and therefore were crossed over to LL, obtaining ductal clearance in a single additional session with a single LL fiber. EHL was significantly associated with a larger number of probes (2.0 vs. 1.02) to achieve ductal clearance (p < 0.01). The mean procedural time was significantly longer for EHL than for LL [72.1 (SD 16.3 min) versus 51.1 (SD 10.5 min)] (p < 0.01). CONCLUSIONS: POC is highly effective for difficult biliary stones. Most patients achieved complete ductal clearance in one session, which was significantly more likely for stones < 22 mm. EHL was significantly associated with the need for more probes and a longer procedural time to achieve ductal clearance.

Airborne microplastics and SARS-CoV-2 in total suspended particles in the area surrounding the largest medical centre in Latin America.

Microplastics (MPs) have been reported in the outdoor/indoor air of urban centres, raising health concerns due to the potential for human exposure. Since aerosols are considered one of the routes of Coronavirus disease 2019 (COVID-19) transmission and may bind to the surface of airborne MPs, we hypothesize that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be associated with the levels of MPs in the air. Our goal was to quantify the SARS-CoV-2 RNA and MPs present in the total suspended particles (TSP) collected in the area surrounding the largest medical centre in Latin America and to elucidate a possible association among weather variables, MPs, and SARS-CoV-2 in the air. TSP were sampled from three outdoor locations in the areas surrounding a medical centre. MPs were quantified and measured under a fluorescence microscope, and their polymeric composition was characterized by Fourier transform infrared (FT-IR) microspectroscopy coupled with attenuated total reflectance (ATR). The viral load of SARS-CoV-2 was quantified by an in-house real-time PCR assay. A generalized linear model (GzLM) was employed to evaluate the effect of the SARS-CoV-2 quantification on MPs and weather variables. TSP samples tested positive for SARS-CoV-2 in 22 out of 38 samples at the three sites. Polyester was the most frequent polymer (80%) found in the samples. The total amount of MPs was positively associated with the quantification of SARS-CoV-2 envelope genes and negatively associated with weather variables (temperature and relative humidity). Our findings show that SARS-CoV-2 aerosols may bind to TSP, such as MPs, and facilitate virus entry into the human body.

Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative.

Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, 1H and 13C NMR spectra. The antioxidant potential was evaluated against the radical ABTS•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (p < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

Quantification of airborne SARS-CoV-2 genomic particles in different hospital settings.

We quantified the presence of SARS-CoV-2 RNA in the air of different hospital settings and the autopsy room of the largest medical centre in Sao Paulo, Brazil. Real-time reverse-transcription PCR was used to determine the presence of the envelope protein of SARS-CoV-2 and the nucleocapsid protein genes. The E-gene was detected in 5 out of 6 samples at the ICU-COVID-19 ward and in 5 out of 7 samples at the ward-COVID-19. Similarly, in the non-dedicated facilities, the E-gene was detected in 5 out of 6 samples collected in the ICU and 4 out of 7 samples in the ward. In the necropsy room, 6 out of 7 samples were positive for the E-gene. When both wards were compared, the non-COVID ward presented a significantly higher concentration of the E-gene than in the COVID-19 ward (p = 0.003). There was no significant difference in E-gene concentration between the ICU-COVID-19 and the ICU (p = 0.548). Likewise, there was no significant difference among E-gene concentrations found in the autopsy room versus the ICUs and wards (dedicated or not) (p = 0.245). Our results show the widespread presence of aerosol contamination in different hospital units.

Artificial intelligence application in diagnostic gastrointestinal endoscopy - Deus ex machina?

The close relationship of medicine with technology and the particular interest in this symbiosis in recent years has led to the development of several computed artificial intelligence (AI) systems aimed at various areas of medicine. A number of studies have demonstrated that those systems allow accurate diagnoses with histological precision, thus facilitating decision-making by clinicians in real time. In the field of gastroenterology, AI has been applied in the diagnosis of pathologies of the entire digestive tract and their attached glands, and are increasingly accepted for the detection of colorectal polyps and confirming their histological classification. Studies have shown high accuracy, sensitivity, and specificity in relation to expert endoscopists, and mainly in relation to those with less experience. Other applications that are increasingly studied and with very promising results are the investigation of dysplasia in patients with Barrett's esophagus and the endoscopic and histological assessment of colon inflammation in patients with ulcerative colitis. In some cases AI is thus better than or at least equal to human abilities. However, additional studies are needed to reinforce the existing data, and mainly to determine the applicability of this technology in other indications. This review summarizes the state of the art of AI in gastroenterological pathology.

Presence of airborne microplastics in human lung tissue.

Plastics are ubiquitously used by societies, but most of the plastic waste is deposited in landfills and in the natural environment. Their degradation into submillimetre fragments, called microplastics, is a growing concern due to potential adverse effects on the environment and human health. Microplastics are present in the air and may be inhaled by humans, but whether they have deleterious effects on the respiratory system remain unknown. In this study, we determined the presence of microplastics in human lung tissues obtained at autopsies. Polymeric particles (n = 33) and fibres (n = 4) were observed in 13 of 20 tissue samples. All polymeric particles were smaller than 5.5 µm in size, and fibres ranged from 8.12 to 16.8 µm. The most frequently determined polymers were polyethylene and polypropylene. Deleterious health outcomes may be related to the heterogeneous characteristics of these contaminants in the respiratory system following inhalation.

Outcomes of single-endoscopist-performed needle-knife fistulotomy for selective biliary access in 842 consecutive patients: learning curve and changes over a 14-year period in a retrospective study.

BACKGROUND AND AIMS: Needle-knife fistulotomy (NKF) has emerged as the preferred precut technique. From a late strategy, NKF has shifted to an early rescue technique and has been used recently as a primary method for biliary access. It is unknown how these changes have affected NKF outcomes. We analyzed the outcomes of NKF over time in a large cohort of patients. METHODS: Multicenter retrospective cohort study of 842 patients who underwent NKF for biliary access between 2006 and 2019. Patients were divided into four study periods according to a late or early cannulation strategy and to the use of post-ERCP pancreatitis prophylaxis (Period 1-Period 4). We assessed outcomes of NKF, learning curves and shifts over time. RESULTS: Bile duct access was obtained in 88.0% of the patients. The initial cannulation rate increased significantly from 77.5% in P1 to 92.0% in P4 (p < .001). An endoscopist can obtain 80% success rate after performing 100 NKF procedures (95% CI: 0.79-0.86) and a 95% success rate after 830 procedures (95% CI: 0.92-0.98). Adverse events and pancreatitis were observed in 6.5% and 4.9% of patients respectively. The rate of pancreatitis was not significantly different during the 4 periods (p = .190). A decline in the pancreatitis rate was observed from 2006 until 2016 (no trainees) and then an increase until 2019 (trainees involved). The presence of trainees increased the rate of pancreatitis in the last period by 9.9%. CONCLUSIONS: The success of NKF has increased significantly over the years, initially in a rapid manner and then more slowly. It is associated with a low rate of complications, which tend to decrease with experience. The involvement of trainees is associated with an increased rate of pancreatitis.

Efficacy and safety of primary, early and late needle-knife fistulotomy for biliary access.

European Society of Gastrointestinal Endoscopy recommends needle-knife fistulotomy (NKF) as the preferred precut technique. However, there is little information on whether NKF performed at different times is associated with different success and adverse event rates. We compared the outcomes of 3 different timings of NKF. This was an observational study conducted at 4 institutions and this was a retrospective analysis of prospectively collected data. We included 330 consecutive patients submitted to NKF attempt for biliary access. Patients were divided into three groups: NKF as an initial procedure for biliary access (group A, n = 121); early NKF defined as after 5 min, 5 attempts, or 2 pancreatic passages (group B, n = 99); and late NKF: after at least 10 min of unsuccessful standard biliary cannulation (group C, n = 110). We assessed the success rate of biliary cannulation at initial ERCP, time to perform NKF until biliary cannulation, overall biliary cannulation rate (second ERCP when initial failure), adverse event rate, and predictors of post-ERCP pancreatitis (PEP). The initial cannulation rate was 98%, 91% and 94% for groups A, B and C respectively, p = 0.08, whereas overall biliary cannulation rate was 100%, 95% and 98%, p = 0.115. The adverse event rate/PEP was 4.1%/2.5%, 7.1%/4% and 10.9%/8.2%, for groups A, B and C respectively, (p = 0.197 and p = 0.190). Median time for creating the fistula was A = 4.0 min, B = 3.2 min, and C = 5.6 min, p < 000.1. Each additional minute spent attempting cannulation increased the odds ratio (OR) for PEP by 1.072, and patients with 3 or more risk factors for pancreatitis had a higher chance of PEP. In conclusion, the timing of NFK does not appear to influence success rates but late NFK is associated with a higher time to create a fistula and an increased risk of pancreatitis. Primary NFK is associated with a high rate of success and a low rate of PEP and deserves additional investigation.

Pharmacy Electronic Records and Patient Clustering: Exploring New Ways to Increase the Provision of Tailored Pharmaceutical Services.

Patients' electronic records in community pharmacy are an untapped resource to uncover new ways of providing healthcare services. In this paper, we present a preliminary work, where we explore this resource, aiming to identify patients' clusters that will help to define a future algorithm. This algorithm will then enable community pharmacists to provide tailored pharmaceutical interventions according to patient's risk assessment and needs. In this way, this work will provide a way to overcome known barriers for community pharmacists' provision of services and integration in the health system, while also contributing to support a better care for chronic patients.

Effects of long-standing exposure to heavy-duty diesel vehicle traffic on respiratory symptoms and airway inflammation in older adults.

In the present study, we evaluated the effects of chronic exposure to traffic from a heavy-duty diesel-fueled vehicle area on respiratory symptoms and airway inflammation in a nonsmoking adult and elderly population. Respiratory symptoms were evaluated by the ISAAC questionnaire (International Study of Asthma and Allergies questionnaire), and airway inflammation was assessed by fractional exhaled nitric oxide (FeNO). Forty volunteers were selected from the 112 volunteers who completed the ISAAC questionnaire for the measurement of FeNO. The FeNO population comprised seven men (six aged ≥ 64 years old, four aged ≥ 75 years old) and 32 women (27 aged ≥ 64 years old, nine aged ≥ 75 years old). FeNO levels were tracked for six months, from November 2014 to June 2015. Results: Twenty-four percent of the volunteers reported having had wheezing in the chest in the last 12 months. However, only 2.7% of the volunteers reported doctor-diagnosed asthma. There was a positive association between FeNO and pollutants in most of the study months. An increase of 1 µg m-3 in NO2 was associated with a mean increase of 1.08 ppb in FeNO, and an increase of 1 µg m-3 in O3 was associated with a mean increase of 1.06 ppb in FeNO. The relative risk for NO2 ranged from 1.009 to 1.32 and that for O3 ranged from 1.014 to 1.020. Conclusion: The frequency of respiratory symptoms was much higher than the previously described levels of 6% in the Brazilian adult population. In summary, a high frequency of respiratory symptoms and high levels of FeNO were described in an underdiagnosed adult population living very close to a heavy-duty diesel-traffic area. Older elderly adults presented greater susceptibility to airway inflammation than younger adults.

An emerging class of air pollutants: Potential effects of microplastics to respiratory human health?

It is increasingly recognized that the ubiquity of convenient single-use plastic has resulted in a global plastic pollution challenge, with substantial environmental and health consequences. Physical, chemical, and biological processes result in plastic weathering, with eventual formation of debris in the micro to nano size range. There is an increasing awareness that plastic fragments are dispersed in the air and can be inhaled by humans, which may cause adverse effects on the respiratory system and on other systems. Urban environments are often characterized by high concentrations of fine airborne dust from various sources. To date, however, there is limited information on the distribution, shape, and size of microplastics in the air in urban and other environments. In this article, we review and discuss our current understanding of the exposure characteristics of airborne plastic debris in urbanized areas, focusing on concentration, size, morphology, presence of additives and distributions of different polymers. The natural and extend data are compiled and compared to laboratory-based analyses to further our understanding of the potential adverse effects of inhaled plastic particles on human health.

Endoscopic therapy in disconnected duct syndrome: re-connecting the duct

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A complex case of low-phospholipid-associated cholelithiasis syndrome

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A complex case of low-phospholipid-associated cholelithiasis syndrome.

The low-phospholipid-associated cholelithiasis (LPAC) syndrome is a form of symptomatic and recurring cholelithiasis occurring in young adults, associated with mutations in the ABCB4 gene. It is a clinical syndrome characterized by at least two of the following criteria: age at onset of biliary symptoms below 40 years, intrahepatic echogenic foci or microlithiasis and recurrence of biliary symptoms after cholecystectomy. In the rare cases progressing to end-stage liver disease, a liver transplant may be indicated. We report a case of a 40-year-old female patient with clinical criteria for LPAC syndrome and with ABCB4 gene mutation. She had a complex history of choledocholithiasis recurrence despite treatment with ursodeoxycholic acid and multiple therapeutic endoscopic retrograde cholangiopancreatography, and she developed portal vein thrombosis.