Alzheimer’s disease, one of the most common causes of dementia, places a significant socioeconomic burden on aging societies. Encouragingly, extensive research on this neurocognitive disorder has finally uncovered the underpinnings of its pathophysiology, igniting a new era of treatment possibilities. Furthermore, the advent of amyloid PET imaging has allowed diagnosis of the amyloid pathology, the underlying cause of Alzheimer’s disease. Notwithstanding the initial setback with aducanumab, the subsequent full FDA approval of two antiamyloid antibody drugs (Lecanemab and Donanemab) has revolutionized the treatment landscape. These disease-modifying drugs are designed to target and remove beta-amyloid.This review covers the updated diagnostic criteria for Alzheimer’s disease and discusses recent developments in treatment strategies, including these new disease-modifying drugs.

Alzheimer’s disease, one of the most common causes of dementia, places a significant socioeconomic burden on aging societies. Encouragingly, extensive research on this neurocognitive disorder has finally uncovered the underpinnings of its pathophysiology, igniting a new era of treatment possibilities. Furthermore, the advent of amyloid PET imaging has allowed diagnosis of the amyloid pathology, the underlying cause of Alzheimer’s disease. Notwithstanding the initial setback with aducanumab, the subsequent full FDA approval of two antiamyloid antibody drugs (Lecanemab and Donanemab) has revolutionized the treatment landscape. These disease-modifying drugs are designed to target and remove beta-amyloid.This review covers the updated diagnostic criteria for Alzheimer’s disease and discusses recent developments in treatment strategies, including these new disease-modifying drugs.

Alzheimer’s disease, one of the most common causes of dementia, places a significant socioeconomic burden on aging societies. Encouragingly, extensive research on this neurocognitive disorder has finally uncovered the underpinnings of its pathophysiology, igniting a new era of treatment possibilities. Furthermore, the advent of amyloid PET imaging has allowed diagnosis of the amyloid pathology, the underlying cause of Alzheimer’s disease. Notwithstanding the initial setback with aducanumab, the subsequent full FDA approval of two antiamyloid antibody drugs (Lecanemab and Donanemab) has revolutionized the treatment landscape. These disease-modifying drugs are designed to target and remove beta-amyloid.This review covers the updated diagnostic criteria for Alzheimer’s disease and discusses recent developments in treatment strategies, including these new disease-modifying drugs.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

OBJECTIVES: Inhalation exposure to humidifier disinfectants has resulted to various types of health damages in Korea. To determine the epidemiological correlation necessary for presuming the legal causation, we aimed to develop a method to synthesize the entire evidence. METHODS: Epidemiological and toxicological studies are systematically reviewed. Target health problems are selected by criteria such as frequent complaints of claimants. Relevant epidemiologic studies are reviewed and the risk of bias and confidence level of the total evidence are evaluated. Toxicological literature reviews are conducted on three lines of evidence including hazard information, animal studies, and mechanistic studies, considering the source-to-exposure-to-outcome continuum. The confidence level of the body of evidence is then translated into the toxicological evidence levels for the causality between humidifier disinfectant exposure and health effects. Finally, the levels of epidemiological and toxicological evidence are synthesized. RESULTS: Under the Special Act revised in 2020, if the history of exposure and the disease occurred/worsened after exposure were approved, and the epidemiological correlation between the exposure and disease was verified, the legal causation is presumed unless the company proves the evidence against it. The epidemiological correlation can be verified through epidemiological investigations, health monitoring, cohort investigations and/or toxicological studies. It is not simply as statistical association as understood in judicial precedents, but a general causation established by the evidence as a whole, i.e., through weight-of-the-evidence approach. CONCLUSIONS The weight-of-the-evidence approach differs from the conclusive single study approach and this systematic evidence integration can be used in presumption of causation.

Background: The Continuous Quality Improvement program for cytopathology in 2020 was completed during the coronavirus pandemic. In this study, we report the result of the quality improvement program. Methods: Data related to cytopathology practice from each institute were collected and processed at the web-based portal. The proficiency test was conducted using glass slides and whole-slide images (WSIs). Evaluation of the adequacy of gynecology (GYN) slides from each institution and submission of case glass slides and WSIs for the next quality improvement program were performed. Results: A total of 214 institutions participated in the annual cytopathology survey in 2020. The number of entire cytopathology specimens was 8,220,650, a reduction of 19.0% from the 10,111,755 specimens evaluated in 2019. Notably, the number of respiratory cytopathology specimens, including sputum and bronchial washing/ brushing significantly decreased by 86.9% from 2019, which could be attributed to the global pandemic of coronavirus disease. The ratio of cases with atypical squamous cells to squamous intraepithelial lesions was 4.10. All participating institutions passed the proficiency test and the evaluation of adequacy of GYN slides. Conclusions Through the Continuous Quality Improvement program, the effect of coronavirus disease 2019 pandemic, manifesting with a reduction in the number of cytologic examinations, especially in respiratory-related specimen has been identified. The Continuous Quality Improvement Program of the Korean Society for Cytopathology can serve as the gold standard to evaluate the current status of cytopathology practice in Korea.

The perivascular space (PVS) of the brain, also known as Virchow-Robin space, consists of cerebrospinal fluid and connective tissues bordered by astrocyte endfeet. The PVS, in a word, is the route over the arterioles, capillaries, and venules where the substances can move. Although the PVS was identified and described first in the literature approximately over 150 years ago, its importance has been highlighted recently after the function of the waste clearing system of the interstitial fluid and wastes was revealed. The PVS is known to be a microscopic structure detected using T2-weighted brain MRI as dot-like hyperintensity lesions when enlarged. Although until recently regarded as normal with no clinical consequence and ignored in many circumstances, several studies have argued the association of an enlarged PVS with neurodegenerative or other diseases. Many questions and unknown facts about this structure still exist; we can only assume that the normal PVS functions are crucial in keeping the brain healthy. In this review, we covered the history, anatomy, pathophysiology, and MRI findings of the PVS; finally, we briefly touched upon the recent trials to better visualize the PVS by providing a glimpse of the brain fluid dynamics and clinical importance of the PVS.