Objective: Early identification of atherosclerosis using a non-invasive tool like ankle–brachial index (ABI) could help reduce the risk for cardiovascular disease among long-term hemodialysis patients. The study objective was to assess the frequency and impact of abnormal ABI as a marker of subclinical peripheral artery disease (PAD) in chronic hemodialysis patients.
Methods: This was a historic cohort study of kidney failure patients on long-term hemodialysis for at least 6 months. The ABI, measured with two oscillometric blood pressure devices simultaneously, was used to assess subclinical atherosclerosis of low limb extremities. Abnormal ABI was defined as ABI <0.9 or >1.3 (PAD present). Survival was defined as time to death. Independent factors associated with abnormal ABI were assessed using multiple logistic regression analysis. Kaplan–Meier method (log-rank test) was used to compare cumulative survival between the two groups; a P value <0.05 was statistically significant.
Results: Abnormal ABI was noted in 50.6% (n=43) of the 85 kidney failure patients included in the study; 42.4% (n=36) had a low ABI, and 8.2% (n=7) had a high ABI. Factors associated with PAD present were cholesterol (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 1.01–1.04; P=0.019), inflammation (AOR, 9.44; 95% CI, 2.30–18.77; P=0.002), phosphocalcic product (AOR, 6.25; 95% CI, 1.19–12.87; P=0.031), and cardiac arrhythmias (AOR, 3.78; 95% CI, 1.55–7.81, P=0.009). Cumulative survival was worse among patients with PAD present (log-rank; P=0.032).
Conclusion: The presence of PAD was a common finding in the present study, and associated with both traditional and emerging cardiovascular risk factors as well as a worse survival rate than patients without PAD.
Query (Q) fever is a zoonotic bacterial infection caused by Coxiella burnetii. In a minority of patients, chronic disease can occur after acute infection. Endocarditis and infections of aneurysms or vascular prostheses are the most common forms of chronic Q fever in adults. We report a case of an elderly female patient with chronic Q fever vertebral osteomyelitis at the site of her previous cement vertebroplasty, complicated by paravertebral abscess. Patient treatment required prolonged drainage in addition to the long duration of antibiotic treatment by doxycycline and hydroxychloroquine. Osteomyelitis is a rare clinical presentation in adults with chronic Q fever. However, it is important to consider Q fever in the differential diagnosis of culture-negative osteomyelitis, especially in countries where C. burnetii is endemic, such as Israel.
During the past few years, thousands of articles have been published concerning medical cannabis useage. Unfortunately, most publications are case studies or small and poorly designed research projects. In attempting to understand the reasons behind this situation, the obstacles impeding the use of medical cannabis and related research merit more in-depth examination. This editorial looks at some of the issues.
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.
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.
Throughout history, Jewish people have long been recognized for their achievements in the world of medical science. For example, prior to the Holocaust, many outstanding physicians in Germany were Jewish. However, even in the 1930s, refugee European Jewish doctors faced significant barriers when they tried to escape and practice elsewhere because of long-standing prejudices and anti-Jewish quotas in medical schools and hospitals around the world. Eventually quotas fell, and the period after World War II once again saw a tremendous growth in numbers of Jews excelling in medicine internationally. Since the Hamas attack on Israel on October 7, 2023, there has been a resurgence of antisemitism worldwide. It is especially noticeable in the world of healthcare. This article evaluates and highlights examples of antisemitism in four countries by authors from each of these jurisdictions.
Viral hepatitis, primarily caused by hepatitis B virus and hepatitis C virus, is widely recognized for its impact on liver function, but emerging evidence suggests it also affects cognitive function. This review explores the causes, manifestations, and impact of cognitive impairments in patients with viral hepatitis, to better understand this often-overlooked aspect of the disease. A literature review was conducted, focusing on studies published in PubMed up to August 2024. Key areas covered include the pathophysiological mechanisms behind cognitive impairment in viral hepatitis, clinical manifestations observed in affected patients, the implications for their daily functioning and overall well-being, and the tools used in cognitive assessments. Common manifestations included deficits in attention, memory, executive function, and psychomotor speed. These cognitive challenges can significantly impact daily activities, occupational performance, and social interactions, contributing to reduced quality of life. Cognitive impairments in viral hepatitis patients represent a significant concern that extends beyond liver health. Recognizing and addressing these cognitive issues are crucial for improving patient outcomes. Enhanced diagnostic strategies and targeted interventions are needed to better manage cognitive symptoms and support affected individuals in maintaining their quality of life. This narrative review aims to enhance clinical practice and inform future research directions.
Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.
Context and Objective: Cardiovascular diseases are the leading cause of mortality in patients. In this context, proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to be the new biomarker identified as interfering in lipid homeostasis. This study aimed to investigate the association between PCSK9, dyslipidemia, and future risk of cardiovascular events in a population of black Africans.
Methods: A cross-sectional study was conducted between August 2016 and July 2020 in six hemodialysis centers in the city of Kinshasa, Democratic Republic of the Congo. Serum PCSK9 was measured by ELISA; lipid levels of 251 chronic kidney disease grade 5 (CKD G5) hemodialysis patients and the Framingham predictive instrument were used for predicting cardiac events.
Results: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were significantly increased in the tertile with the highest PCSK9. By contrast, high-density lipoprotein cholesterol (HDL-c) was significantly decreased in the same tertile. A strong positive and significant correlation was found between PCSK9 and TC, TG, and LDL-c. Negative and significant correlation was observed between PCSK9 and HDL-c. The levels of PCSK9, smoking, overweight, and atherogenic dyslipidemia were associated with future risks for cardiovascular events in univariate analysis. After adjustment, all these variables persisted as independent determinants of future risk for cardiovascular events. The probability of having a cardiovascular event in this population was independently associated with PCSK9 levels. Compared to the patients having lowest PCSK9 tertile, patients with PCSK9 levels in the middle (aOR 5.9, 95% CI 2.06-17.3, P<0.001) and highest tertiles (aOR 8.9, 95% CI 3.02-25.08, P<0.001) presented a greater risk of cardiac event.
Conclusion: Increased PCSK9 serum levels are associated with higher levels of TC, LDL-c, and TG and lower levels of HDL-c in black African hemodialysis patients. Serum PCSK9 levels in these patients predict increased risk of cardiovascular events, independent of traditional potential confounders.
