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.

Objective: The mandible is the most common fractured craniofacial bone of all craniofacial fractures in the Philippines, with the mandibular body as the most involved segment of all mandibular fractures. To the best of our knowledge, there are no existing guidelines for the diagnosis and management of mandibular body fractures in particular. General guidelines include the American Academy of Otolaryngology – Head and Neck Surgery Foundation (AAOHNSF) Resident Manual of Trauma to the Face, Head, and Neck chapter on Mandibular Trauma, the American Association of Oral and Maxillofacial Surgeons (AAOMS) Clinical Practice Guidelines for Oral and Maxillofacial Surgery section on the Mandibular Angle, Body, and Ramus, and a 2013 Cochrane Systematic Review on interventions for the management of mandibular fractures. On the other hand, a very specific Clinical Practice Guideline on the Management of Unilateral Condylar Fracture of the Mandible was published by the Ministry of Health Malaysia in 2005. Addressing the prevalence of mandibular body fractures, and dearth of specific guidelines for its diagnosis and management, this clinical practice guideline focuses on the management of isolated mandibular body fractures in adults. Purpose: This guideline is meant for all clinicians (otolaryngologists – head and neck surgeons, as well as primary care and specialist physicians, nurses and nurse practitioners, midwives and community health workers, dentists, and emergency first-responders) who may provide care to adults aged 18 years and above that may present with an acute history and physical and/or laboratory examination findings that may lead to a diagnosis of isolated mandibular body fracture and its subsequent medical and surgical management, including health promotion and disease prevention. It is applicable in any setting (including urban and rural primary-care, community centers, treatment units, hospital emergency rooms, operating rooms) in which adults with isolated mandibular body fractures would be identified, diagnosed, or managed. Outcomes are functional resolution of isolated mandibular body fractures; achieving premorbid form; avoiding use of context-inappropriate diagnostics and therapeutics; minimizing use of ineffective interventions; avoiding co-morbid infections, conditions, complications and adverse events; minimizing cost; maximizing health-related quality of life of individuals with isolated mandibular body fracture; increasing patient satisfaction; and preventing recurrence in patients and occurrence in others. Action Statements The guideline development group made strong recommendationsfor the following key action statements: (6) pain management- clinicians should routinely evaluate pain in patients with isolated mandibular body fractures using a numerical rating scale (NRS) or visual analog scale (VAS); analgesics should be routinely offered to patients with a numerical rating pain scale score or VAS of at least 4/10 (paracetamol and a mild opioid with or without an adjuvant analgesic) until the numerical rating pain scale score or VAS is 3/10 at most; (7) antibiotics- prophylactic antibiotics should be given to adult patients with isolated mandibular body fractures with concomitant mucosal or skin opening with or without direct visualization of bone fragments; penicillin is the drug of choice while clindamycin may be used as an alternative; and (14) prevention- clinicians should advocate for compliance with road traffic safety laws (speed limit, anti-drunk driving, seatbelt and helmet use) for the prevention of motor vehicle, cycling and pedestrian accidents and maxillofacial injuries.The guideline development group made recommendations for the following key action statements: (1) history, clinical presentation, and diagnosis - clinicians should consider a presumptive diagnosis of mandibular fracture in adults presenting with a history of traumatic injury to the jaw plus a positive tongue blade test, and any of the following: malocclusion, trismus, tenderness on jaw closure and broken tooth; (2) panoramic x-ray - clinicians may request for panoramic x-ray as the initial imaging tool in evaluating patients with a presumptive clinical diagnosis; (3) radiographs - where panoramic radiography is not available, clinicians may recommend plain mandibular radiography; (4) computed tomography - if available, non-contrast facial CT Scan may be obtained; (5) immobilization - fractures should be temporarily immobilized/splinted with a figure-of-eight bandage until definitive surgical management can be performed or while initiating transport during emergency situations; (8) anesthesia - nasotracheal intubation is the preferred route of anesthesia; in the presence of contraindications, submental intubation or tracheostomy may be performed; (9) observation - with a soft diet may serve as management for favorable isolated nondisplaced and nonmobile mandibular body fractures with unchanged pre - traumatic occlusion; (10) closed reduction - with immobilization by maxillomandibular fixation for 4-6 weeks may be considered for minimally displaced favorable isolated mandibular body fractures with stable dentition, good nutrition and willingness to comply with post-procedure care that may affect oral hygiene, diet modifications, appearance, oral health and functional concerns (eating, swallowing and speech); (11) open reduction with transosseous wiring - with MMF is an option for isolated displaced unfavorable and unstable mandibular body fracture patients who cannot afford or avail of titanium plates; (12) open reduction with titanium plates - ORIF using titanium plates and screws should be performed in isolated displaced unfavorable and unstable mandibular body fracture; (13) maxillomandibular fixation - intraoperative MMF may not be routinely needed prior to reduction and internal fixation; and (15) promotion - clinicians should play a positive role in the prevention of interpersonal and collective violence as well as the settings in which violence occurs in order to avoid injuries in general and mandibular fractures in particular.
Mandibular Fractures ; Jaw Fractures ; Classification ; History ; Diagnosis ; Diagnostic Imaging ; Therapeutics ; Diet Therapy ; Drug Therapy ; Rehabilitation ; General Surgery

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide