Exposure of cinnamyl alcohol in co-culture of BEAS-2B and dendritic cells: Interaction between CYP450 and cytokines.

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h. CYP1A1, CYP1A2, CYP1B1, CYP2A6, and CYP2A13 were analyzed by RT-PCR and IL-10, IL-12p70, IL-18, IL-33, and thymic stromal lymphopoietin (TSLP) by Cytometric Bead Array (CBA). Through RT-PCR analysis, we observed that CA increased CYP1A2 and CYP1B1 expression in BEAS-2B, with a further increased in BEAS-2B-mDC co-culture. Additionally, exposure to CA increased IL-12p70 levels in mDC rather than in BEAS-2B-mDC co-culture. In regards to IL-18, level was higher in BEAS-2B than in BEAS-2B-mDC co-culture. A positive correlation between the levels of IL-10 and CYP1B1 was found in mDC-CA-exposed and between IL-12p70 and CYP1A1 was found in BEAS-2B after CA exposure. However, IL-12p70 and CYP1A2 as well as IL-18, IL-33, and CYP1A1 levels were negative, correlated mainly in co-culture control. These correlations highlight potential immunomodulatory interactions and complex regulatory relationships. Overall, exposure to CA enhances CYP450 expression, suggesting that CA can influence immune responses by degrading ligands on xenosensitive transcription factors.

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.

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.

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.

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.

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.

Design, synthesis and cytotoxicity of the antitumor agent 1-azabicycles for chemoresistant glioblastoma cells.

Twelve multi-functional pyrrolizidinones, indolizidinones and pyrroliazepinones were prepared from formal aza-[3 + 2] and aza-[3 + 3] cycloadditions of five- to seven-membered heterocyclic enaminones as diverse ambident electrophiles. The antitumor activity of these alkaloid-like compounds was investigated through an initial screening performed on human glioblastoma multiform (GBM) cell lines (GL-15, U251), on murine glioma cells line (C6) and on normal glial cells. Of the compounds tested, the new pyrrolo[1,2a]azepinone, [ethyl (3-oxo-1,2-diphenyl-6,7,8,9-tetrahydro-3H-pyrrolo[1,2a]azepin-9a(5H)-yl)acetate] or (Compound-13) exhibited selective cytotoxic effects on GBM-temozolomide resistant cells. Compound-13 exerted dose-dependent cytotoxic activity by promoting arrest of cells in the G0/G1 phase of the cell cycle in the first 24 h. The apoptotic effect observed was in a time-dependent manner. Anti-migratory effect promoted by the treatment with compound-13 was also observed. Moreover, healthy mixed glial cell cultures from rat brain exhibited no cytotoxicity effect upon exposure to compound-13. Thus, the present study paves the way for the use of compound-13 as novel antitumor scaffold candidate for glioma cell therapy.

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.

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

We report the case of a 61-year-old male patient with a history of acute necrotizing biliary pancreatitis and a disconnected duct syndrome. He underwent transgastric drainage using a luminal apposing metal stent and transgastric necrosectomy with complete resolution of the necrosis. A pancreatic fistula was identified during pancreatography and a pancreatic plastic stent was placed in order to manage the disconnected duct syndrome. The tip of the pancreatic stent could be seen inside the pancreatic collection, which is an unusual finding. There was a resolution of the collection and the pancreatic stent was removed.

Clinical relevance of pulmonary vasculature involvement in sickle cell disease.

Pulmonary complications are frequent in patients with sickle cell disease (SCD), but few studies have described lung pathology in SCD. We studied the lung tissue of 30 deceased SCD patients (1994-2012). Demographics, genotype, clinical characteristics, cause of death and associated conditions are presented. We quantified the presence of pulmonary arterial changes, thrombosis and venous thickening. Alveolar capillary abnormalities were demonstrated using CD34 expression and confocal microscopy. Autopsy and echocardiography reports were reviewed to classify heart abnormalities. Tissue expression of markers of endothelial activation (vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and vascular endothelial growth factor) was quantified in pulmonary vessels. Median age was 33 years; genotype was SS in 19, SC in 7 and Sß in 4, and there were 18 males. Hypertensive arterial changes were present in 76% of the patients, recent thrombosis in 80% and old thrombosis in 43%. Venous thickening was present in 23% and pulmonary capillary haemangiomatosis foci in 87%. Ten percent of the patients presented right ventricular hypertrophy. There was no increased expression of endothelial activation markers when compared to controls. SCD affects the whole pulmonary vascular tree and reflects the multiple burden on lung vasculature imposed by the disease upon time.

Diesel exhaust exposure intensifies inflammatory and structural changes associated with lung aging in mice.

Life expectancy is increasing worldwide. Lung aging is a process marked by changes in multiple morphological, physiological and age-related biomarkers (e.g., sirtuins) and is influenced by external factors, such as air pollution. Hence, the elderly are considered more vulnerable to the air pollution hazards. We hypothesized that diesel exhaust (DE) exposure intensifies changes in lung inflammatory and structural parameters in aging subjects. Two- and fifteen-month-old mice were exposed to DE for 30 days. Lung function was measured using the forced oscillation method. The inflammatory profile was evaluated in the bronchoalveolar lavage fluid (BALF) and blood, and lung volumes were estimated by stereology. Antioxidant enzyme activity was evaluated by spectrophotometry, sirtuin 1 (SIRT1), sirtuin 2 (SIRT2) and sirtuin 6 (SIRT6) expression was assessed by reverse transcription polymerase chain reaction (RT-PCR), and levels of the sirtuin proteins were evaluated by immunohistochemical staining in lung tissues. Older mice presented decreased pulmonary resistance and elastance, increased macrophage infiltration and decreased tumor necrosis factor (TNF) and interleukin 10 (IL-10) levels in the BALF, reduced activities of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), and increased activity glutathione S-transferase (GST); increased lung volumes with decreased elastic fiber and increased airway collagen content. SIRT1 gene expression was decreased in older animals, but protein levels were increased. DE exposure increased macrophage infiltration and oxidative stress in the lungs of animals of both ages. SIRT6 gene expression was decreased by DE exposure, with increased protein levels. In older animals, DE affected lung structure and collagen content. Lung aging features, such as decreased antioxidant reserves, lower IL-10 expression, and decreased SIRT1 levels may predispose subjects to exacerbated responses after DE exposure. Our data support the hypothesis that strategies designed to reduce ambient air pollution are an important step towards healthy aging.

Hepatocellular carcinoma presenting with Budd-Chiari syndrome, right atrial thrombus and pulmonary emboli.

A 47-year-old patient presented with a two-week history of right upper quadrant pain, abdominal distention and new onset of shortness of breath. He had a history of intravenous drug abuse, no alcohol consumption and denied any known liver disease. On physical examination, he was tachypneic and had dullness in the flanks. His blood analysis at admission was as follows: hemoglobin, 12.9 g/dL; leukocyte count, 6,800/uL; platelet count, 63,000/uL; INR, 2.1; serum creatinine, 1.27 mg/dL; liver biochemistry tests were notable for marginal derangement, HBsAg was negative, anti-HCV was positive, HCV RNA was 367,498 IU/ml and alpha-fetoprotein was 992 mg/dL. Abdominal ultrasound showed a right liver lobe mass (13 cm in diameter) with inferior vena cava (IVC) thrombosis and mild peri-hepatic ascites. A 2D echocardiogram showed a presumed right atrial tumor thrombus. A multiphasic contrast-enhanced abdominal tomography (CT) confirmed a hepatocellular carcinoma (HCC) with IVC obstruction and extensive tumoral thrombus to the right atrium (14 cm long).

Primary Gastric Tuberculosis in an Immunocompetent Patient: The Truth Lying beneath the Surface.

Gastrointestinal tuberculosis is an uncommon entity, in which clinical presentation can be widely variable, from mild and nonspecific symptoms to an acute abdomen and gastrointestinal bleeding. Gastric involvement by Mycobacterium tuberculosis is rare, especially when it occurs without other recognized infectious foci - primary gastric tuberculosis - with only a few reported cases. Endoscopic findings can be very heterogeneous, from areas of hyperemia to pseudotumor lesions. We present a case of primary gastric tuberculosis in an immunocompetent patient, in which the absence of an epidemiological context and nonspecific endoscopic findings led to a delay in the diagnosis. Bite-on-bite biopsies proved to be essential, allowing to obtain samples from deeper layers of the submucosa where M. tuberculosis was identified. This case aimed to increase awareness for this entity, especially in endemic countries or regions with a high prevalence of tuberculosis since the diagnosis is based mainly on a high index of suspicion.

A tuberculose gastrointestinal é uma entidade pouco comum, com uma apresentação clínica amplamente variável, desde sintomas ligeiros e inespecíficos até quadros de abdómen agudo e hemorragia digestiva. O envolvimento gástrico pelo Mycobacterium tuberculosis é raro, especialmente quando ocorre sem outros focos infeciosos reconhecidos ­ tuberculose gástrica primária ­, havendo apenas alguns casos descritos na literatura. Os achados endoscópicos podem ser muito heterogéneos, variando desde áreas de mucosa hiperemiada até lesões pseudo-tumorais. Apresentamos o caso de uma doente imunocompetente com diagnóstico de tuberculose gástrica primária, em que a ausência de um contexto epidemiológico e achados endoscópicos inespecíficos conduziram a um atraso no diagnóstico. As biópsias sobre biópsias mostraram ser essenciais para o diagnóstico, pois permitiram obter amostras de camadas mais profundas da submucosa do antro gástrico onde foi identificado o agente infecioso. Este caso pretende sensibilizar para existência desta entidade, especialmente em países endémicos ou regiões com alta prevalência de tuberculose, uma vez que o seu diagnóstico implica um elevado grau de suspeição.

Validation of a novel BCM model for recurrence risk prediction after mucosectomy of colorectal lateral spreading tumors in a European cohort.

BACKGROUND AND AIM: Piecemeal endoscopic mucosal resection (pEMR) is the best approach to resect large lateral spreading tumors (LST, > 20 mm width). However, it is associated with early recurrence (ER) and late recurrence (LR). This study aims to assess the risk factors associated with ER and LR and to validate different predictive scores (SMSA, SERT, and BCM) in identifying the risk of ER and LR after LST resected by pEMR in a European cohort. METHODS: Retrospective observational cohort study, based on a prospectively collected database, of large LST submitted to pEMR. RESULTS: A total of 108 patients were included in the study and the incidence rates of ER and LR were 22 % and 8 %, respectively. The lesion's size, SERT, and BCM scores were independent predictor factors of ER (p-value < 0.05), while the lesion's site and BCM score were independent predictor factors of LR (p-value < 0.05). For the prediction of ER, the SERT score (cut-off > 1) presented the highest AUROC (0.758 vs 0.697 from BCM and 0.647 from SMSA). Regarding LR, the BCM model (cut-off > 2) presented the highest AUROC (0.817 vs 0.708 from SERT and 0.691 from SMSA). CONCLUSIONS: We present the first external validation of the three scores mentioned in an European cohort. SERT and BCM scores had an acceptable performance in predicting ER and LR. However, the BCM model was the only score that proved to be an independent predictor of both ER and LR, proving to be valuable for both applications.

Microplastics in the Olfactory Bulb of the Human Brain.

Importance: Microplastic (MP) pollution is an emerging environmental and health concern. While MPs have been detected in various human tissues, their presence in the human brain has not been documented, raising important questions about potential neurotoxic effects and the mechanisms by which MPs might reach brain tissues. Objective: To determine the presence of MPs in the human olfactory bulb and to analyze their characteristics such as size, morphology, color, and polymeric composition. Design, Setting, and Participants: This case series study used a cross-sectional design involving the analysis of olfactory bulb tissues obtained from deceased individuals during routine coroner autopsies. The sampling procedures were conducted at São Paulo City Death Verification Service, with laboratory analysis carried out at the Brazilian Synchrotron Light Laboratory (LNLS). Participants included 15 adult individuals who had been residents of São Paulo for more than 5 years and underwent coroner autopsies. Exclusion criteria included previous neurosurgical interventions. Data analysis was performed in April 2024. Exposure: The primary exposure assessed was the presence of MPs in the olfactory bulb, analyzed through direct tissue examination and digested tissue filtration followed by micro-Fourier transform infrared spectroscopy. Main Outcomes and Measures: The main outcomes were the identification and characterization of MPs within the olfactory bulb, including their size, morphology, color, and polymeric composition. Results: The median age of the 15 deceased individuals was 69.5 years, ranging from 33 to 100 years, with 12 males and 3 females. MPs were detected in the olfactory bulbs of 8 out of 15 individuals. A total of 16 synthetic polymer particles and fibers were identified, with 75% being particles and 25% being fibers. The most common polymer detected was polypropylene (43.8%). Sizes of MPs ranged from 5.5 µm to 26.4 µm for particles, and the mean fiber length was 21.4 µm. Polymeric materials were absent in procedural blank and negative control filters, indicating minimal contamination risk. Conclusions and Relevance: This case series provides evidence of MPs found in the human olfactory bulb, suggesting a potential pathway for the translocation of MPs to the brain. The findings underscore the need for further research on the health implications of MP exposure, particularly concerning neurotoxicity and the potential for MPs to bypass the blood-brain barrier.

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.