This study investigated the development of a novel approach to surface characterization of drug poly-morphism and the extension of the capabilities of this method to perform ‘real time’ in situ measure-ments. This was achieved using diffuse reflectance visible (DRV) spectroscopy and dye deposition, using the pH sensitive dye, thymol blue (TB). Two polymorphs, SFN-β and SFN-γ, of the drug substance sul-fanilamide (SFN) were examined. The interaction of adsorbed dye with polymorphs showed different behavior, and thus reported different DRV spectra. Consideration of the acid/base properties of the morphological forms of the drug molecule provided a rationalization of the mechanism of differential coloration by indicator dyes. The kinetics of the polymorphic transformation of SFN polymorphs was monitored using treatment with TB dye and DRV spectroscopy. The thermally-induced transformation fitted a first-order solid-state kinetic model (R2 ? 0.992), giving a rate constant of 2.43 ? 10 ? 2 s ? 1.

Little is known of the lung cellular immunophenotypes in patients with non-tuberculous mycobacterial lung disease (NTM-LD). Flow-cytometric analyses for the major myeloid and lymphoid cell subsets were performed in less- and more-diseased areas of surgically resected lungs from six patients with NTM-LD and two with Pseudomonas aeruginosa lung disease (PsA-LD). Lymphocytes, comprised mainly of NK cells, CD4 + and CD8 + T cells, and B cells, accounted for ~60% of all leukocytes, with greater prevalence of T and B cells in morediseased areas. In contrast, fewer neutrophils were found with decreased number in morediseased areas. Compared to NTM-LD, lung tissues from patients with PsA-LD demonstrated relatively lower numbers of T and B lymphocytes but similar numbers of NK cells. While this study demonstrated a large influx of lymphocytes into the lungs of patients with chronic NTM-LD, further analyses of their phenotypes are necessary to determine the significance of these findings.

Background/Aims: The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratify PNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NFPNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. Methods: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NFPNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. Results: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordance was the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028) were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumor size >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. Conclusions NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs with intermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUSFNA can be monitored without surgical intervention, up to tumor size 20 mm.

BACKGROUND AND PURPOSE: Bariatric surgery is associated with improved cognitive function, but the mechanisms underlying these gains remain poorly understood. Disturbed leptin and ghrelin systems are common in obese individuals and are associated with impaired cognitive function in other samples. Bariatric surgery has been shown to improve serum leptin and ghrelin levels, and these changes may underlie postoperative cognitive improvements. METHODS: Eighty-four patients completed a computerized cognitive test battery prior to bariatric surgery and at 12 months postoperatively. Participants also submitted to an 8-hour fasting blood draw to quantify serum leptin and ghrelin concentrations at these same time points. RESULTS: Baseline cognitive impairments and disturbed leptin and ghrelin levels improved at the 12-month follow-up compared to presurgery. Higher leptin levels were associated with worse attention/executive function at baseline; no such findings emerged for ghrelin. Regression analyses controlling for baseline factors and demographic characteristics showed that both decreased leptin and increased ghrelin following surgery was associated with better attention/executive function at the 12-month follow-up. These effects diminished after controlling for the postoperative change in body mass index (BMI); however, BMI change did not predict 12-month cognitive function. CONCLUSIONS: Improvements in leptin and ghrelin levels following bariatric surgery appear to contribute to postoperative cognitive benefits. These gains may involve multiple mechanisms, such as reduced inflammation and improved glycemic control. Future studies that employ neuroimaging are needed to clarify the underlying mechanisms and determine whether the effects of bariatric surgery on leptin and ghrelin levels can attenuate adverse brain changes and/or risk of dementia in severely obese individuals.
Bariatric Surgery* ; Body Mass Index ; Brain ; Dementia ; Fasting ; Follow-Up Studies ; Ghrelin* ; Humans ; Inflammation ; Leptin* ; Neuroimaging ; Obesity

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.