Peritoneal disease: key imaging findings that help in the differential diagnosis

The peritoneum is a unique serosal membrane, which can be the site of primary tumors and, more commonly, secondary pathologic processes. Peritoneal carcinomatosis is the most common malignant process to affect the peritoneal cavity, and the radiologist plays an important role in making the diagnosis and assessing the extent of disease, especially in sites that may hinder surgery. In this review we address the role of the radiologist in the setting of peritoneal pathology, focusing on peritoneal carcinomatosis as this is the predominant malignant process, followed by revising typical imaging findings that can guide the differential diagnosis. We review the most frequent primary and secondary peritoneal tumor and tumor-like lesions, proposing a systemic approach based on clinical history and morphological appearance, namely distinguishing predominantly cystic from solid lesions, both solitary and multiple.

Could melatonin be an adjunct therapy for post-TB lung disease?

Post-tuberculosis (post-TB) lung disease is a complex interplay between organism, host, and environmental factors, and it affects long-term respiratory health. It associates with underlying processes such as inflammation, fibrosis, and oxidative stress. Decades of research has demonstrated melatonin as a potent anti-inflammatory, anti-fibrotic, antioxidant, and vasodilatory agent. These effects have been observed in numerous experimental and clinical models of lung diseases. Moreover, melatonin has significant anti-microbial activity, which has also been observed in the context of TB bacterial growth. It is worth pointing out that these effects of melatonin are a reminder of the pathologic processes that underpin post-TB lung disease. Based on the intriguing evidence presented and discussed in this paper, melatonin could be considered a safe, affordable, and adjunct therapy against post-TB lung disease. Melatonin may provide health benefits in this context, mediated via its anti-inflammatory, anti-fibrotic, vasodilatory, antimicrobial and antioxidant properties.

FAP and FAPI-PET/CT Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases.

NLRP3 Inflammasome in Cardiovascular Disease: David`s Stone against Goliath?

Inflammation is involved in initiation, development and complications of the vast majority of non-communicable diseases. Recent research demonstrated that infl ammation is involved in pathogenesis of all major cardiovascular diseases. Different endogenous factors (LDL, nucleic acid strands, uric acid – collectively called „Damage Associated Molecular Patterns – DAMPs”) activate dedicated receptors („Pattern Recognition Receptors – PRR”) on monocytes, macrophages or dendritic cells responsible for the innate immunologic response. They have a major role in natural defense mechanisms against different pathogens and in normal conditions have a protective role. Among PRRs „NOD-like, leucin rich, pyrin containing (NLRP)” receptors are a 14-member family located in the cytoplasm. One of these is the NLRP3 resulting from nuclear transcription under the infl uence of NF-kB, a second messenger from membrane PRRs to the nucleus. Mostly the same factors responsible for NLRP3 intracellular expression stimulate its oligomerization resulting in a large protein complex, the NLRP3 infl ammasome. This activates caspase-1 responsible for IL-1b and IL-18 production and initiates an inflammatory reaction leading to various pathologic processes, such as atherosclerosis, hypertension, diabetes and heart failure. This is the current story as we know it of the NLRP3 infl ammasome, a small intracellular component that when inappropriately activated may does more harm than good.

Correlations of Radiographic and Endoscopic Observations in Subglottic Stenosis

Objective(s): Subglottic stenosis (SGS) represents a constellation of diverse pathologic processes that ultimately lead to narrowing of the subglottic region and can produce significant morbidity. Existing endoscopic and radiographic assessments may not be consistent in practice. Methods: Severity of stenosis was evaluated and reported using the Cotton-Myer classification system from 33 endoscopic procedures from 32 unique subjects. Radiographic imaging within the preceding 3 month period was subsequently reviewed and narrowing was measured by a blinded radiologist. Degree of stenosis was reported as a percentage in 30 out of 33 endoscopic evaluations and subsequently compared to radiographically determined percentage of stenosis. Statistical analyzes were conducted to evaluate concordance between endoscopic and radiographic assessments. Results: About 45.5% (15/33) of the evaluations were in agreement using Cotton-Myer scoring, while 27.3% (9/33) were discrepant by 1 grade and 27.3% (9/33) by 2 grades. Correlation of degree of stenosis as a percentage using Spearman (coefficient: 0.233, P-value: .214) and Pearson (coefficient: 0.138, P-value: .466) methods demonstrated very weak relationships. Radiographic scoring did not predict endoscopic classification to a significant degree using mixed effects regression. Conclusions: Radiographic and endoscopic grading of subglottic stenosis may not be reliably concordant in practice.

Clinical and Paraclinical Biomarkers and the Hitches to Assess Conversion to Secondary Progressive Multiple Sclerosis: A Systematic Review

Conversion to secondary progressive (SP) course is the decisive factor for long-term prognosis in relapsing multiple sclerosis (MS), generally considered the clinical equivalent of progressive MS-associated neuroaxonal degeneration. Evidence is accumulating that both inflammation and neurodegeneration are present along a continuum of pathologic processes in all phases of MS. While inflammation is the prominent feature in early stages, its quality changes and relative importance to disease course decreases while neurodegenerative processes prevail with ongoing disease. Consequently, anti-inflammatory disease-modifying therapies successfully used in relapsing MS are ineffective in SPMS, whereas specific treatment for the latter is increasingly a focus of MS research. Therefore, the prevention, but also the (anticipatory) diagnosis of SPMS, is of crucial importance. The problem is that currently SPMS diagnosis is exclusively based on retrospectively assessing the increase of overt physical disability usually over the past 6–12 months. This inevitably results in a delay of diagnosis of up to 3 years resulting in periods of uncertainty and, thus, making early therapy adaptation to prevent SPMS conversion impossible. Hence, there is an urgent need for reliable and objective biomarkers to prospectively predict and define SPMS conversion. Here, we review current evidence on clinical parameters, magnetic resonance imaging and optical coherence tomography measures, and serum and cerebrospinal fluid biomarkers in the context of MS-associated neurodegeneration and SPMS conversion. Ultimately, we discuss the necessity of multimodal approaches in order to approach objective definition and prediction of conversion to SPMS.

Ferroptosis: the potential value target in atherosclerosis

In advanced atherosclerosis (AS), defective function-induced cell death leads to the formation of the characteristic necrotic core and vulnerable plaque. The forms and mechanisms of cell death in AS have recently been elucidated. Among them, ferroptosis, an iron-dependent form of necrosis that is characterized by oxidative damage to phospholipids, promotes AS by accelerating endothelial dysfunction in lipid peroxidation. Moreover, disordered intracellular iron causes damage to macrophages, vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs), and affects many risk factors or pathologic processes of AS such as disturbances in lipid peroxidation, oxidative stress, inflammation, and dyslipidemia. However, the mechanisms through which ferroptosis initiates the development and progression of AS have not been established. This review explains the possible correlations between AS and ferroptosis, and provides a reliable theoretical basis for future studies on its mechanism.

The Macroscopic and Radiographic Skull and Dental Pathology of the Tasmanian Devil (Sarcophilus harrisii)

While the gross skull and dental morphology, masticatory biomechanics, dental eruption patterns, and radiographic dental anatomy has been described in the Tasmanian devil (Sarcophilus harrisii), to date no studies have comprehensively examined the prevalence and appearance of pathologic processes affecting their skulls and dentition. As such, the aim of this study was to describe macroscopic and radiographic anatomy and identify the prevalence of anatomic variations and pathological processes in Tasmanian devil dentition and skulls. To do so, anatomical and pathological findings were documented in Tasmanian devil skulls using photography and dental radiography. Assessment of skull trauma, anatomical and developmental abnormalities, periodontitis, endodontic disease, and tooth resorption was performed. A total of 28 Tasmanian devil skulls containing 1,028 teeth were examined. Evidence of postmortem trauma was common. The most common positional abnormality was palatal or buccal rotation of the premolar teeth. While the alveolar bone margin was commonly positioned apically to the cementoenamel junction (98.2%), only 14.2% demonstrated evidence of periodontitis. Tooth fractures were common, affecting 27 skulls, however radiographic signs of endodontic disease were only noted in 4.5% of affected teeth, as was non-inflammatory root resorption (2.0%). A wider root canal width, which was used as a criterion for age determination, was associated with smaller skull dimensions, incompletely erupted teeth, and subjectively less fusion of the mandibular symphysis. Through an improved understanding of what constitutes normal anatomy and the appearance and frequency of pathologic processes that affect the skulls and teeth, this knowledge can help develop a foundation for understanding the oral health and management of live animals for this endangered species.