This review describes cyclooxygenase (COX), which synthesizes prostanoids that play an important role in living things. The authors conducted a national and international literature review on the subject. The COX enzyme uses arachidonic acid to form prostanoids, which play a role in several physiological and pathological conditions. This enzyme has different isoforms, mainly COX-1 and COX-2. The constitutive isoform is COX-1, while COX-2 is the inducible isoform. Both are expressed in different tissues and at different levels, but they may also coexist within the same tissue. Both isoforms show essentially the same mode of action, but their substrates and inhibitors may differ. The COX-1 isoform, which plays a role in the continuation of physiological events, has an increased expression level in various carcinomas, and the COX-2 isoform, which is increased in inflammatory conditions, is typically expressed at low physiological levels in some tissues such as the brain, kidney, and uterus. In addition to investigating the efficacies of the COX-1 and COX-2 isoforms, the discovery of potential new COX enzymes and their effect continues. This review also looks at the roles of the COX enzyme in certain physiological and pathological conditions.
The world, as a global village, is currently taking part in a real-time public health, medical, socio-cultural, and economic experiment on how best to combat the COVID-19 pandemic. Extraordinary times demand extraordinary measures. Depending on the time from the outbreak, strategies have ranged from minimal intervention to mitigation by quarantine for high-risk groups (elderly with chronic illnesses) to containment and lockdown. Adherence to such restrictions have depended on the individual and national psyche and culture. One can understand and forgive governments for being over-cautious, but not for being ill-prepared. It seems that Singapore after SARS (2003) and South Korea after MERS (2015) learnt from their experiences and have fared relatively well with minimal disruption to daily routines. Coping with the challenge of COVID-19 is an urgent global task. We use the Sociotype ecological framework to analyze different coping responses at three levels: Context (government and leadership, social context, health services, and media); Relationships; and the Individual. We describe the many negative outcomes (e.g. mortality [obviously], unemployment, economic damage, food insecurity, threat to democracy, claustrophobia) and the positive ones (e.g. new, remote teaching, working, and medical routines; social bonding and solidarity; redefining existential values and priorities) of this surreal situation, which is still evolving. We highlight the importance of humor in stress reduction. Regular and reliable communication to the public has to be improved, acknowledging incomplete data, and learning to deal with fake news, misinformation, and conspiracy theories. Excess mortality is the preferred statistic to follow and compare outcomes. When the health risks are over, the economic recovery responses will vary according to the financial state of countries. If world order is to be reshaped, then a massive economic aid plan should be launched by the rich countries—akin to the Marshall plan after the Second World War. It should be led preferably by the USA and China. The results of the tradeoffs between health and economic lockdowns will only become apparent in the months to come. The experiences and lessons learned from this emergency should be used as a rehearsal for the next epi-/pandemic, which will surely take place in the foreseeable future.
Transverse myelitis is an inflammatory lesion of the spinal cord, occurring in different autoimmune, infectious, and traumatic diseases but is the hallmark of neuromyelitis optica (NMO), a rare neurologic autoimmune disease. Patients with systemic lupus erythematosus (SLE) may develop transverse myelitis as a neuropsychiatric complication of active disease; however, at times, NMO co-exists as an additional primary autoimmune condition in a SLE patient. Correct diagnosis of a SLE–NMO overlap is important not only for the different disease course and prognosis compared with SLE-related LETM, but especially for the emerging and highly specific NMO treatment options, not established for SLE-related LETM—such as anti-aquaporin 4 antibodies, anti-VEGF antibodies, complement modulation, or IVIg.
Objective: The aim of this study was to compare and correlate mast cell density (MCD) and microvessel density (MVD) between normal oral mucosa, oral lichen planus, various grades of dysplasia, and oral squamous cell carcinoma (OSCC).
Materials and Methods: The study comprised a total of 75 samples, of which 65 were archival tissue blocks of histopathologically confirmed cases, which included 10 cases of oral lichen planus, 25 cases of dysplasia (mild [n=10], moderate [n=10], and severe [n=5]), and 30 cases of OSCC (well differentiated [n=10], moderately differentiated [n=10], and poorly differentiated [n=10]), and 10 samples of normal oral mucosa. All the sections were immunohistochemically stained with anti-CD34 and counterstained with toluidine blue stain. Mean MCD and MVD were determined and analyzed using ANOVA test and compared between the lesions using Tukey HSD test. Pearson’s correlation coefficient test was used to correlate these two factors between various lesions.
Results: Mean MCD and mean MVD were found to be increased in all the lesions compared to normal oral mucosa, and the values were statically significant. Overall, MCD and MVD showed a significant positive correlation (r=0.640).
Conclusion: Increase of MCD and MVD and their positive correlation in all the lesions have emphasized their role in the pathogenesis and disease progression.
Background: Adequate lymphadenectomy is an important factor affecting survival in gastric cancer patients. Retrieval and examination of at least 15 lymph nodes is recommended in order to properly stage gastric malignancies. The objectives of this study were to evaluate the proportion of patients undergoing inadequate lymphadenectomies and possible risk factors for inadequate surgery.
Methods: This was a retrospective study that included patients, 18 years and older, who underwent gastrectomies with oncologic intent in the Hillel Yaffe Medical Center. We analyzed the association of demographic, clinical, and pathological variables with adequate number of lymph nodes.
Results: The retrieval of less than 15 lymph nodes was reported in 51% (53/104) patients undergoing gastrectomies with oncologic intent. The extent of surgery was the only variable associated with inadequate lymphadenectomy on univariate analysis: subtotal/proximal versus total gastrectomy (P=0.047). Differ¬ences observed for previous surgery (P=0.193), T stage (P=0.053), N stage (P=0.051), and lymphovascular invasion (P=0.14) did not reach significance. Subtotal/proximal gastrectomy resulted in inadequate resec¬tion of lymph nodes in 56% of the patients, while this occurred in only 30% of the patients undergoing total gastrectomy (relative risk 1.865; 95% CI 0.93, 3.741). Logistic regression confirmed that only subtotal/prox¬imal versus total gastrectomy was associated with inadequate number of lymph nodes resected (P=0.043).
Discussion and Conclusion: In this study we analyzed the association of patient, tumor, and surgery-related factors on adequate lymphadenectomy in patients undergoing gastrectomies for possible gastric cancer. Larger extent of the surgery (total, rather than subtotal/proximal gastrectomy) was revealed to be the only indicator positively associated with adequate lymphadenectomy.
Background: Avoiding rectal thermometry is recommended in patients with neutropenic fever. Permeability of the anal mucosa may result in a higher risk of bacteremia in these patients. Still, this recommendation is based on only a few studies.
Methods: This retrospective study included all individuals admitted to our emergency department during 2014–2017 with afebrile (body temperature <38.3°C) neutropenia (neutrophil count <500 cells/microL) who were over the age of 18. Patients were stratified by the presence or absence of a rectal temperature measurement. The primary outcome was bacteremia during the first five days of index hospitalization; the secondary outcome was in-hospital mortality.
Results: The study included 40 patients with rectal temperature measurements and 407 patients whose temperatures were only measured orally. Among patients with oral temperature measurements, 10.6% had bacteremia, compared to 5.1% among patients who had rectal temperature measurements. Rectal temperature measurement was not associated with bacteremia, neither in non-matched (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.07–1.77) nor in matched cohort analyses (OR 0.37, 95% CI 0.04–3.29). In-hospital mortality was also similar between the groups.
Conclusions: Patients with neutropenia who had their temperature taken using a rectal thermometer did not experience a higher frequency of events of documented bacteremia or increased in-hospital mortality.
Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.
Idiopathic inflammatory myopathies (IIM) are a rare group of disorders that feature progressive immune-mediated skeletal muscle destruction along with skin, lung, and joint involvement. Management of IIMs necessitates glucocorticoid therapy followed by conventional steroid-sparing agents to control disease activity. In the settings of refractory myositis or life-threatening manifestations, e.g. lung involvement or oropharyngeal dysphagia, second-line therapies are needed to minimize disease burden, avoid end-organ damage and steroid toxicity, and decrease mortality. These therapies may include biological disease-modifying antirheumatic drugs (bDMARDs), and to a lesser extent, targeted synthetic disease-modifying antirheumatic drugs (TSD). This article reviews the current use of bDMARDs, e.g. intravenous immunoglobulin and rituximab, and a TSD—Janus kinase inhibitors (JAKI)—along with their indications, efficacy, and safety in managing IIM.
Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells through CCR3 receptor binding. Higher levels of CCL24 and CCR3 were found in the skin and sera of patients with SSc compared with healthy controls; elevated levels of CCL24 and CCR3 were associated with fibrosis and predictive of greater lung function deterioration. Growing evidence supports the potency of a CCL24-blocking antibody as an anti-inflammatory and anti-fibrotic modulating agent in multiple preclinical models that involve liver, skin, and lung inflammation and fibrosis. This review highlights the role of CCL24 in orchestrating immune, vascular, and fibrotic pathways, and the potential of CCL24 inhibition as a novel treatment for SSc.
Objectives: This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
Materials and Methods: A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
Results: A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
Conclusions: Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
