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Topic Review
Ultrastructure in Transthyretin Amyloidosis
Transthyretin (TTR) amyloidosis is caused by systemic deposition of wild-type or variant amyloidogenic TTR (ATTRwt and ATTRv, respectively). ATTRwt amyloidosis has traditionally been termed senile systemic amyloidosis, while ATTRv amyloidosis has been called familial amyloid polyneuropathy. Although ATTRwt amyloidosis has classically been regarded as one of the causes of cardiomyopathy occurring in the elderly population, recent developments in diagnostic techniques have significantly expanded the concept of this disease. For example, this disease is now considered an important cause of carpal tunnel syndrome in the elderly population. The phenotypes of ATTRv amyloidosis also vary depending on the mutation and age of onset. Peripheral neuropathy usually predominates in patients from the conventional endemic foci, while cardiomyopathy or oculoleptomeningeal involvement may also become major problems in other patients. Electron microscopic studies indicate that the direct impact of amyloid fibrils on surrounding tissues leads to organ damage, whereas accumulating evidence suggests that nonfibrillar TTR, such as oligomeric TTR, is toxic, inducing neurodegeneration. Microangiopathy has been suggested to act as an initial lesion, increasing the leakage of circulating TTR. Regarding treatments, the efficacy of liver transplantation has been established for ATTRv amyloidosis patients, particularly patients with early-onset amyloidosis. Recent phase III clinical trials have shown the efficacy of TTR stabilizers, such as tafamidis and diflunisal, for both ATTRwt and ATTRv amyloidosis patients. 
  • 486
  • 19 Jul 2021
Topic Review
Reporting Thyroid Cytology
The Italian SIAPEC-AIT 2014 classification, the 2017 Bethesda System for Reporting Thyroid Cytology (TBSRTC), the 2016 UK Royal College of Pathologists (RCPath) thyroid reporting system, and the 2019 Japanese reporting system for thyroid aspiration cytology (JRSTAC2019) represent the most widely used reporting systems among clinicians and pathologists for the purpose of cytologically diagnosing, estimating the potential risk of malignancy (ROM), and defining the most appropriate treatment for a patient with a thyroid nodule. Although all the systems use overlapping diagnostic categories and morphologic criteria, they differ on the basis of the criteria for inclusion in the cytologic categories, which may, in turn, affect the ROM of a given category and the clinical management of the patient, particularly with regard to the “indeterminate” categories. 
  • 483
  • 17 Sep 2021
Topic Review
Targeted Therapeutic Approach for AML
Acute myeloid leukemia (AML) is a heterogenous hematopoietic neoplasm with various genetic abnormalities in myeloid stem cells leading to differentiation arrest and accumulation of leukemic cells in bone marrow (BM). The multiple genetic alterations identified in leukemic cells at diagnosis are the mainstay of World Health Organization classification for AML and have important prognostic implications. Recently, understanding of heterogeneous and complicated molecular abnormalities of the disease could lead to the development of novel targeted therapeutic agents. In the past years, gemtuzumab ozogamicin, BCL-2 inhibitors (venetovlax), IDH 1/2 inhibitors (ivosidenib and enasidenib) FLT3 inhibitors (midostaurin, gilteritinib, and enasidenib), and hedgehog signaling pathway inhibitors (gladegib) have received US Food and Drug Administration (FDA) approval for the treatment of AML. Especially, AML patients with elderly age and/or significant comorbidities are not currently suitable for intensive chemotherapy. Thus, novel therapeutic planning including the abovementioned target therapies could lead to improve clinical outcomes in the patients.
  • 481
  • 01 Jun 2021
Topic Review
Coronary Atherosclerosis Imaging
Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. 
  • 481
  • 14 Jul 2021
Topic Review
Cartilage Conduction Hearing
Cartilage conduction (CC) is a form of conduction that allows a relatively loud sound to be audible when a transducer is placed on the aural cartilage. The CC transmission mechanism has gradually been elucidated, allowing for the development of CC hearing aids (CC-HAs), which are clinically available in Japan. However, CC is still not fully understood.
  • 480
  • 09 Jun 2021
Topic Review
Viral Vector-Based Melanoma Gene Therapy
Gene therapy applications of oncolytic viruses represent an attractive alternative for cancer treatment. A broad range of oncolytic viruses, including adenoviruses, adeno-associated viruses, alphaviruses, herpes simplex viruses, retroviruses, lentiviruses, rhabdoviruses, reoviruses, measles virus, Newcastle disease virus, picornaviruses and poxviruses, have been used in diverse preclinical and clinical studies for the treatment of various diseases, including colon, head-and-neck, prostate and breast cancer as well as squamous cell carcinoma and glioma. The majority of studies have focused on immunotherapy and several drugs based on viral vectors have been approved. However, gene therapy for malignant melanoma based on viral vectors has not been utilized to its full potential yet.
  • 479
  • 30 Jun 2021
Topic Review
The Role of Annexin A1 in the Kidney
Renal disorders are very prevalent and associated with significant morbidity and mortality. Among diverse pathogenic mechanisms, the dysregulation of immune and inflammatory responses plays an essential role in such disorders. Consequently, the discovery of Annexin A1, as a glucocorticoid-inducible anti-inflammatory protein, has fueled investigation of its role in kidney pathologies. Thus, its role has been examined in diverse renal pathologies, including acute kidney injury, diabetic nephropathy, immune-mediated nephropathy, drug-induced kidney injury, kidney stone formation, and renal cancer.
  • 479
  • 03 Mar 2022
Topic Review
Familial Hypercholesterolaemia
Familial hypercholesterolaemia (FH) is a common inherited cause of premature cardiovascular disease, but the majority of patients remain undiagnosed. 
  • 478
  • 15 May 2021
Topic Review
Metabolic Obesity in People with Normal Body Weight
The term Metabolic Obesity in People with Normal Body Weight (MONW) is used to describe people who, despite having a healthy body weight - usually defined by the body index (BMI), and more and more often also the percentage of adipose tissue - show metabolic disorders characteristic of obese people. 
  • 477
  • 29 Mar 2022
Topic Review
Endocrine-Disrupting Chemicals and Infectious Diseases
Endocrine-disrupting chemicals (EDCs) are hormonally active compounds in the environment that interfere with the body’s endocrine system and consequently produce adverse health effects. Despite persistent public health concerns, EDCs remain important components of common consumer products, thus representing ubiquitous contaminants to humans. While scientific evidence confirmed their contribution to the severity of Influenza A virus (H1N1) in the animal model, their roles in susceptibility and clinical outcome of the coronavirus disease (COVID-19) cannot be underestimated.
  • 476
  • 28 Apr 2021
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