Correlation between baseline immature platelets fraction levels and peak troponin in patients with acute myocardial infarction.

INTRODUCTION: Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. METHODS: Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. RESULTS: Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPF ≥ 4.2% had significantly higher peak troponin levels ( P  = 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients ( P  = 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. CONCLUSION: This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.

Transcatheter edge-to-edge repair in acute mitral regurgitation following acute myocardial infarction: Recent advances.

Acute mitral regurgitation (MR) is not a rare finding following acute myocardial infarction (AMI). It may develop due to papillary muscle rupture (primary MR) or due to rapid remodeling of the infarcted areas leading to geometric changes and leaflets tethering (secondary or functional MR). The clinical presentation can be catastrophic, with pulmonary edema and refractory cardiogenic shock. Acute MR is a potentially life-threatening complication and is linked to worse clinical outcomes. Until recently, medical treatment or mitral valve surgery were the only established treatment options for these patients. However, there is growing evidence for the benefits of safe and effective trans-catheter interventions in this condition, specifically transcatheter edge-to-edge repair (TEER). We aimed to review the current role of TEER in post-MI acute MR patients, focusing on different etiologies.

Can laboratory evaluation differentiate between coronavirus disease-2019, influenza, and respiratory syncytial virus infections? A retrospective cohort study.

AIM: To identify clinical and laboratory parameters that can assist in the differential diagnosis of coronavirus disease 2019 (COVID-19), influenza, and respiratory syncytial virus (RSV) infections. METHODS: In this retrospective cohort study, we obtained basic demographics and laboratory data from all 685 hospitalized patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, or RSV from 2018 to 2020. A multiple logistic regression was employed to investigate the relationship between COVID-19 and laboratory parameters. RESULTS: SARS-CoV-2 patients were significantly younger than RSV (P=0.001) and influenza virus (P=0.022) patients. SARS-CoV-2 patients also displayed a significant male predominance over influenza virus patients (P=0.047). They also had significantly lower white blood cell count (median 6.3×106 cells/µ) compared with influenza virus (P<0.001) and RSV (P=0.001) patients. Differences were also observed in other laboratory values but were insignificant in a multivariate analysis. CONCLUSIONS: Male sex, younger age, and low white blood cell count can assist in the diagnosis of COVID-19 over other viral infections. However, the differences between the groups were not substantial enough and would probably not suffice to distinguish between the viral illnesses in the emergency department.

Ferritin as a Marker of Severity in COVID-19 Patients: A Fatal Correlation.

BACKGROUND: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic. OBJECTIVES: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19). METHODS: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel. RESULTS: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02. CONCLUSIONS: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.

Acute onset of psoriatic spondyloarthritis as a new manifestation of post-streptococcal reactive arthritis: a case series.

Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7-10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection. KEY POINTS: • Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7--10 days of a confirmed streptococcal infection and progressed to full blown chronic disease. • Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

Characteristics of Pericardial Biopsy: 100 Cases in a Single Center.

BACKGROUND: Pericardial biopsies are rarely performed during the diagnosis and management of pericardial diseases. The circumstances and clinical profile of patients undergoing pericardial biopsies are largely uncharacterized. OBJECTIVES: To examine the circumstances in which pericardial biopsies are obtained and to evaluate their diagnostic yield. METHODS: We studied a total of 100 cases (71% males, mean age 60.8 years, range 8.1-84.5 years) of surgically resected pericardium specimens obtained from 2000 to 2015 at Sheba Medical Center, the largest medical center in Israel. Patients were classified into groups according to four major histological etiologies: idiopathic pericarditis, constrictive pericarditis, malignant pericarditis, and post-cardiac injury syndrome (PCIS). The clinical history and course, laboratory, echocardiography, and histological results were reviewed retrospectively. RESULTS: Causes of pericarditis according to histological definitions included idiopathic pericarditis (29%), constrictive pericarditis (29%), PCIS (9%), and malignant pericarditis (26%). Overall sensitivity of the pericardial biopsy in patients with malignancy was 57.7%. During the study period, we found a trend toward an increased number of biopsies due to constrictive pericarditis and PCIS, along with a decrease in the number of biopsies performed in patients with malignant or idiopathic pericarditis. The diagnosis following biopsy did not change for any of the patients. CONCLUSIONS: Our findings suggest a low diagnostic yield from pericardial biopsies, especially in malignant pericarditis. This conclusion, along with novel therapies, resulted in the infrequent use of pericardial biopsy in recent years.

Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin-Phosphorylcholine.

Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin-phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1ß, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.

Calcium/Calmodulin Kinase IV Controls the Function of Both T Cells and Kidney Resident Cells.

Calcium calmodulin kinase IV (CaMK4) regulates multiple processes that significantly contribute to the lupus-related pathology by controlling the production of IL-2 and IL-17 by T cells, the proliferation of mesangial cells, and the function and structure of podocytes. CaMK4 is also upregulated in podocytes from patients with focal segmental glomerulosclerosis (FSGS). In both immune and non-immune podocytopathies, CaMK4 disrupts the structure and function of podocytes. In lupus-prone mice, targeted delivery of a CaMK4 inhibitor to CD4+ T cells suppresses both autoimmunity and the development of nephritis. Targeted delivery though to podocytes averts the deposition of immune complexes without affecting autoimmunity in lupus-prone mice and averts pathology induced by adriamycin in normal mice. Therefore, targeted delivery of a CaMK4 inhibitor to podocytes holds high therapeutic promise for both immune (lupus nephritis) and non-immune (FSGS) podocytopathies.

The relationship between serum cytokine levels and degree of psychosis in patients with schizophrenia.

Several observations indicate that cytokine concentrations might also relate to the severity of the psychosis. In this study we assessed whether inflammatory and anti-inflammatory cytokine concentrations are associated with the degree of the psychotic manifestations. A group of 41 patients with schizophrenia suffering from an acute psychosis leading to hospitalization in a psychiatric ward were assessed for the intensity of their psychotic manifestations by the PANSS score. Serum IL-2R, IL-6, IL-8, IL-10 were analyzed by commercial ELISA kits. These patients were compared to controls without schizophrenia. At the univariate analysis, statistically significant elevated levels of the cytokines IL-6, IL-2R and IL-8 were detected in the sera of the patients with schizophrenia compared to controls. At the multivariate analysis, statistically significance held only for IL-2R concentration. Furthermore, positive correlation was found between symptom severity as measured by the PANSS and IL-6 levels as well as IL-2R levels. In Conclusion, our data indicate that elevated serum concentrations of IL-6, IL-8 and IL-2R are associated with severe clinical symptoms measured by the total, general, negative and positive scores of the PANSS scale.

The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.

A Picture is Worth a Thousand Words: Art and Medicine.

BACKGROUND: Medical practice is a form of art, with each complex detail essential to the welfare of the individuals in the care of the physician. Art and medicine have shared a close relationship in a variety of ways for centuries, as demonstrated by anatomical drawings and textbooks from the 16th century. Leonardo da Vinci, driven by his fascination with the details of the human body and how it functioned, succeeded in creating an anatomical model of the cerebral ventricles and the aorta using molten wax and a glass structure, respectively (Heart and Its Blood Vessels). By using water that contained grass seeds, this experiment enabled him to study blood flow. da Vinci's engrossment with the complexity of the human body is reflected in many of his drawings, including the famous depiction of the human physique in his drawing of the Vitruvian Man. This drawing, which defines the ideal proportions of the human body and their correlation with geometry, is an example of how artistic and scientific objectives integrate with each other.

Adherence and Persistence with Drug Therapy among Fibromyalgia Patients: Data from a Large Health Maintenance Organization.

OBJECTIVE: To assess 1-year persistence and adherence rates with drug therapy among patients with fibromyalgia (FM) and to identify factors associated with therapy discontinuation. METHODS: This retrospective, cohort study included members ≥ 21 years old from the Maccabi Healthcare Services, a large health maintenance organization in Israel, who were diagnosed with FM from 2008 through 2011. Medications of interest included the anticonvulsant pregabalin, antidepressants [selective serotonin reuptake inhibitor (SSRI), serotonin/norepinephrine reuptake inhibitor (SNRI)], and tricyclic antidepressants (TCA). Time to treatment discontinuation and proportion of days covered (PDC) with FM-specific therapies during the year from first dispensed were analyzed. PDC < 20% was considered low adherence and PDC ≥ 80% was considered high adherence. Logistic regression models were constructed for multivariable analyses. RESULTS: Overall, 3932 patients with FM were included; 88.7% were female. Pre-diagnosis use of medication of interest was documented in 41% of the study population. Of the remaining 2312 patients, 56.1% were issued a prescription, 45.0% were dispensed at least 1 medication in the year following diagnosis, and only 28.8% had prescriptions filled twice within the first year from diagnosis. Among newly prescribed patients, 1-year discontinuation was highest for TCA (91.0%) and lowest for SSRI/SNRI antidepressants (73.7%). Over half of the patients (60.5%) had fewer than 20% of the days covered by any medication during the year and only 9.3% were very adherent (PDC ≥ 80%). CONCLUSION: This study clearly shows that in an Israeli "real-life" population of patients with FM, persistence and adherence with FM therapy in the year following diagnosis is remarkably low.

Dietary factors in rheumatic autoimmune diseases: a recipe for therapy?

Today, we are facing a new era of digitization in the health care system, and with increased access to health care information has come a growing demand for safe, cost-effective and easy to administer therapies. Dietary habits have a crucial influence on human health, affecting an individual's risk for hypertension, heart disease and stroke, as well as influencing the risk of developing of cancer. Moreover, an individual's lifestyle choices can greatly influence the progression and manifestation of chronic autoimmune rheumatic diseases. In light of these effects, it makes sense that the search for additional therapies to attenuate such diseases would include investigations into lifestyle modifications. When considering the complex web of factors that influence autoimmunity, it is not surprising to find that several dietary elements are involved in disease progression or prevention. In this Review, several common nutritional components of the human diet are presented, and the evidence for their effects on rheumatic diseases is discussed.

HPV and systemic lupus erythematosus: a mosaic of potential crossreactions.

Etiology, pathogenesis, and immunology of systemic lupus erythematosus (SLE) form a complex, still undeciphered picture that recently has been further made complicated by a new factor of morbidity: human papillomaviruses (HPVs). Indeed, a prevalence of HPV infections has been reported among SLE patients. Searching for molecular mechanisms that might underlie and explain the relationship between HPV infection and SLE, we explored the hypothesis that immune responses following HPV infection may crossreact with proteins that, when altered, associate with SLE. Analyzing HPV L1 proteins and using Epstein-Barr virus (EBV) and human retrovirus (HERV) as controls, we found a vast peptide overlap with human proteins comprehending lupus Ku autoantigen proteins p86 and p70, lupus brain antigen 1 homolog, lupus antigen expressed in neurons and muscles, natural killer cell IgG-like receptors, complement proteins C4-A and C4-B, complement receptor CD19, and others. The multitude and heterogeneity of peptide overlaps not only further support the hypothesis that crossreactivity can represent a primum movens in SLE onset, but also provide a molecular framework to the concept of SLE as "an autoimmune mosaic syndrome." Finally, once more, it emerges the need of using the principle of peptide uniqueness as a new paradigm for safe and efficacious vaccinology.

Pancreatitis after human papillomavirus vaccination: a matter of molecular mimicry.

A 20-year-old man developed severe abdominal pain 1 week after being vaccinated with the first dose of quadrivalent human papillomavirus (HPV) vaccine (Gardasil®). Despite ongoing symptoms of nausea and pain, he received the second dose of the vaccine. Only 10 days later, laboratory results revealed significantly elevated pancreatic enzymes, and with concomitant abdominal pain and vomiting, he was diagnosed with acute pancreatitis. This case of acute pancreatitis after HPV vaccination is not a novel entity. Although confirming the relationship between pancreatitis and vaccine is challenging, some factors suggest a possible link, including the positive re-challenge upon repeated exposure to the vaccine, HPV vaccine as probable causal relationship to other autoimmune diseases and a probable mechanism of molecular mimicry. In conjunction with aluminum adjuvant, the induction of immunity through molecular mimicry may potentially culminate in production of cytotoxic autoantibodies with a particular affinity for pancreatic acinar cells.

Does inflammatory bowel disease coexist with systemic lupus erythematosus?

BACKGROUND: The data regarding the association between inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) is mostly composed of case reports and case series indicating an infrequent association. OBJECTIVES: To investigate the association between IBD and SLE. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The prevalence of UC was significantly higher in patients with SLE than in controls in a univariate analysis (0.4% and 0.2%, respectively; p<0.017). However, in a multivariate logistic regression model SLE was not associated with UC (OR 1.67, 95% CI 0.99-2.815, p<0.052). The prevalence of CD was higher in patients with SLE than in controls in a univariate analysis (0.7% and 0.3%, respectively; p<0.001). A multivariate logistic regression model confirmed this finding and corroborated that SLE was associated with comorbid CD (OR 2.23, 95% CI 1.46-3.4, p<0.001). CONCLUSIONS: Patients with SLE have a greater prevalence of CD than matched controls. The distinction of IBD from SLE gastrointestinal involvement can be challenging as clinical manifestations, laboratory tests, and radiographic findings may appear similar between the two diseases. Therefore, physicians treating patients with rather IBD or SLE should consider this potential association.

All disease begins in the gut: Celiac disease co-existence with SLE.

BACKGROUND: Case reports and case series have indicated a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE), but additional population-based studies are required. The true prevalence of CD in SLE patients is still unknown, but is indeed an important factor when considering the clinical implications, notably the necessity of screening strategies in SLE patients. Our objective was to investigate the association between CD and SLE using a community-based approach in a real-life population database. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of CD in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The prevalence of CD was significantly higher in patients with SLE than in controls in univariate analysis (0.8% and 0.2%, respectively, p<0.001). Also, SLE was associated with CD (OR 3.92, 95% CI 2.55-6.03, p<0.001) in a multivariate logistic regression model. CONCLUSIONS: Patients with SLE had a greater prevalence of CD than matched controls in a large case-control study. A complex combination of genetic, immunological and novel environmental factors may explain this positive association. Physicians should keep in mind that CD can be a tricky diagnosis in SLE patients, yet a treatable condition, probably more common in this population than we used to think.

Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

Autoimmune diseases refer to a spectrum of diseases characterized by an active immune response against the host, which frequently involves increased autoantibody production. The pathogenesis of autoimmune diseases is multifactorial and the exploitation of novel effective treatment is urgent. Capsaicin is a nutritional factor, the active component of chili peppers, which is responsible for the pungent component of chili pepper. As a stimuli, capsaicin selectively activate transient receptor potential vanilloid subfamily 1(TRPV1) and exert various biological effects. This review discusses the effect of capsaicin through its receptor on the development and modulation of autoimmune diseases, which may shed light upon potential therapies in capsaicin-targeted approaches.