Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology with a significant genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, autoantigens, and several other external factors. The major act of the IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation, leading to the development of psoriatic lesions. Genome-wide association studies (GWASs) offer a better view of psoriasis pathogenic pathways, with approximately one-third of psoriasis's genetic impact on psoriasis development associated with the MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Among the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, induces a burst of pro-inflammatory consequences; both the cutaneous and gut microbiome get involved in the psoriasis pathogenic process. Cutting-edge research studies and comprehensive insights into psoriasis pathogenesis, fostering novel genetic, epigenetic, and immunological factors, have generated a spectacular improvement over the past decades, securing the path toward a specific and targeted immunotherapeutic approach and delayed progression to inflammatory arthritis. This review aimed to offer insight into various domains that underline the pathogenesis of psoriasis and how they influence disease development and evolution. The pathogenesis mechanism of psoriasis is multifaceted and involves an interplay of cellular and humoral immunity, which affects susceptible microbiota and the genetic background. An in-depth understanding of the role of pathogenic factors forms the basis for developing novel and individualized therapeutic targets that can improve disease management.

Dickkopf-Related Protein 1 (DKK-1) as a Possible Link between Bone Erosions and Increased Carotid Intima-Media Thickness in Psoriatic Arthritis: An Ultrasound Study.

Psoriatic arthritis (PsA) is a heterogenous systemic inflammatory disorder that affects peripheral joints and skin, but also causes inflammation at entheseal sites, digits (dactylitis) and the axial skeleton. Despite considerable advances, our understanding of the pathogenesis and management of PsA is hampered by its complex clinical expression. We enrolled patients who met the ClASsification for Psoriatic Arthritis (CASPAR) criteria for PsA (n = 17), and healthy controls (n = 13). The lipid profile, C-reactive protein (CRP) and Dickkopf-related protein 1 (DKK-1) circulating levels were measured for all subjects. For the patients with PsA, (1) the erosive character of the articular disease was assessed by a musculoskeletal ultrasound and (2) the cardiovascular risk was evaluated using the Systematic Coronary Risk Evaluation (SCORE) chart and the ultrasound measurement of the carotid intima-media thickness. A higher titer of serum DKK-1 was associated with the presence of erosions (p < 0.005) and the cIMT correlated with DKK-1 levels in patients with PsA (r = 0.6356, p = 0.0061). Additionally, we observed a positive correlation between increased cIMT and CRP (r = 0.5186, p = 0.0329). Our results suggest that DKK-1 could be used as an early biomarker for the erosive character of the articular disease and for the assessment of the cardiovascular risk in PsA patients.

Methods for Inclusive Underwriting of Breast Cancer Risk with Machine Learning and Innovative Algorithms.

INTRODUCTION: -Due to early detection and improved therapies, the prevalence of long-term breast cancer survivors is increasing. This has increased the need for more inclusive underwriting in individuals with a history of breast cancer. Herein, we developed a method using algorithm aiming facilitating the underwriting of multiple parameters in breast cancer survivors. METHODS: -Variables and data were extracted from the SEER database and analyzed using 4 different machine learning based algorithms (Logistic Regression, GA2M, Random Forest, and XGBoost) that were compared with Kaplan Meier survival estimates. The performances of these algorithms have been compared with multiple metrics (Log Loss, AUC, and SMR). In situ (non-invasive) and metastatic breast cancer were excluded from this analysis. RESULTS: -Parameters included the pathological subtype, pTNM staging (T: tumor size, N; number of nodes; M presence or absence of metastases), Scarff-Bloom-Richardson grading, the expression of estrogen and progesterone hormone receptors were selected to predict the individual outcome at any time point from diagnosis. While all models had identical performance in terms of statistical metrics (AUC, Log Loss, and SMR), the logistic regression was the one and only model that respects all business constraints and was intelligible for medical and underwriting users. CONCLUSION: -This study provides insight to develop algorithms to set underwriter-friendly calculators for more accurate risk estimations that can be used to rationalize insurance pricing for breast cancer survivors. This study supports the development of a more inclusive underwriting based on models that can encompass the heterogeneity of several malignancies such as breast cancer.

Criteria and Non-Criteria Antiphospholipid Antibodies in Antiphospholipid Syndrome: How Strong Are They Correlated?

The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-ß2 glycoprotein I-aß2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aß2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool.

MMP-13, VEGF, and Disease Activity in a Cohort of Rheumatoid Arthritis Patients.

Identifying certain serum biomarkers associated with the degree of rheumatoid arthritis (RA) activity can provide us with a more accurate view of the evolution, prognosis, and future quality of life for these patients. Our aim was to analyze the presence and clinical use of matrix metalloproteinase-13 (MMP-13), along with vascular endothelial growth factor (VEGF) and well-known cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) for patients with RA. We also wanted to identify the possible correlations between MMP-13 and these serological markers, as well as their relationship with disease activity indices, quality of life, and ultrasonographic evaluation. For this purpose, we analyzed serum samples of 34 RA patients and 12 controls. In order to assess serum concentrations for MMP-13, VEGF, TNF-α, and IL-6, we used the enzyme-linked immunosorbent assay (ELISA) technique. Our results concluded that higher levels of MMP-13, VEGF, TNF-α, and IL-6 were present in the serum of RA patients compared to controls, with statistical significance. We furthermore identified moderately positive correlations between VEGF, MMP-13, and disease activity indices, as well as with the ultrasound findings. We also observed that VEGF had the best accuracy (97.80%), for differentiating patients with moderate disease activity. According to the data obtained in our study, that although MMP-13, TNF-α and C-reactive protein (CRP) have the same sensitivity (55.56%), MMP-13 has a better specificity (86.67%) in the diagnosis of patients with DAS28(4v) CRP values corresponding to moderate disease activity. Thus, MMP-13 can be used as a biomarker that can differentiate patients with moderate or low disease activity. VEGF and MMP-13 can be used as additional parameters, along with TNF-α and IL-6, that can provide the clinician a better picture of the inflammatory process, disease activity, and structural damage in patients with RA. Our data can certainly constitute a start point for future research and extended studies with multicenter involvement, to support the selection of individualized and accurate therapeutic management strategies for our patients.

Chronic Complete Distal Aortic Occlusion and Pulmonary Embolism-Atypical Antiphospholipid Syndrome?

Complete aortic occlusion is a rare pathology with various possible etiologies. According to current data, it is most frequently caused by atherosclerosis. However, thrombosis or vasculitis could also be involved. We present the case of a 42-year-old female with chronic complete distal aortic occlusion, associated pulmonary embolism and positive antiphospholipid antibodies. The patient had an obstetric history suggestive of antiphospholipid syndrome (APS). She presented with typical intermittent claudication symptoms persisting for approximately five years at the time of admission. Arteriography revealed complete infrarenal aortic occlusion and the presence of collateral arteries. Aortoiliac bypass surgery was performed. This case emphasizes an unusual, yet possible, etiology of chronic aortic occlusion-most probably, combining atherosclerosis and chronic thrombosis-in a relatively young patient, in which the diagnosis was significantly delayed due to the peculiar association of traits.

Time to redefine hyperuricemia? The serum uric acid cut-off level for precipitation might be lower: a pilot study.

BACKGROUND: Hyperuricemia is classically defined as serum uric acid (SUA) value higher than 6.8 mg∕dL; between hyperuricemic patients, only 15-20% will develop gout. Our first goal was to find if there is a specificity of the "snowstorm" feature on ultrasound (US) for hyperuricemia. Moreover, we aimed to determine if there is a level of SUA from which the urates tend to appear in the synovial fluid, without generating a typical clinical gouty flare. PATIENTS, MATERIALS AND METHODS: We conducted a cross-sectional, transverse study, including 108 consecutive patients that displayed a set of clinical and imaging features, such as swollen knee and US proof for knee joint effusion. RESULTS: Performing binary logistic regression, the relation between the explanatory variable (hyperechogenic spots) and the response variable (SUA) was demonstrated to be a significant one (p=0.005). The value of 0.397 for the statistical phi coefficient suggests a medium intensity association between the diagnosis of gout or asymptomatic hyperuricemia and whether the patients have hyperechogenic spots or not. We found the cut-off value for SUA equal to 4.815 mg∕dL, regardless of gender, from which, the urate starts to precipitate. Values for men tend to be higher in comparison to the ones found for women (4.95 mg∕dL vs. 3.9 mg∕dL). CONCLUSIONS: The "snowstorm" aspect of the fluid might be the result of an increased level of SUA and more than this, the cut-off level for SUA to precipitate might be lower than the fore used values.

Antibiotic Prescription and In-Hospital Mortality in COVID-19: A Prospective Multicentre Cohort Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, empiric antibiotics (ATBs) have been prescribed on a large scale in both in- and outpatients. We aimed to assess the impact of antibiotic treatment on the outcomes of hospitalised patients with moderate and severe coronavirus disease 2019 (COVID-19). METHODS: We conducted a prospective multicentre cohort study in six clinical hospitals, between January 2021 and May 2021. RESULTS: We included 553 hospitalised COVID-19 patients, of whom 58% (311/553) were prescribed antibiotics, while bacteriological tests were performed in 57% (178/311) of them. Death was the outcome in 48 patients-39 from the ATBs group and 9 from the non-ATBs group. The patients who received antibiotics during hospitalisation had a higher mortality (RR = 3.37, CI 95%: 1.7-6.8), and this association was stronger in the subgroup of patients without reasons for antimicrobial treatment (RR = 6.1, CI 95%: 1.9-19.1), while in the subgroup with reasons for antimicrobial therapy the association was not statistically significant (OR = 2.33, CI 95%: 0.76-7.17). After adjusting for the confounders, receiving antibiotics remained associated with a higher mortality only in the subgroup of patients without criteria for antibiotic prescription (OR = 10.3, CI 95%: 2-52). CONCLUSIONS: In our study, antibiotic treatment did not decrease the risk of death in the patients with mild and severe COVID-19, but was associated with a higher risk of death in the subgroup of patients without reasons for it.

Psoriasis beyond the skin: Ophthalmological changes (Review).

Psoriasis is a chronic, immune-mediated inflammatory disease of unknown etiology that may be associated with abnormal T-lymphocyte function. Ocular manifestations associated with psoriasis, particularly artropathic or pustular psoriasis, usually affect men, often during exacerbations of the disease. It has been reported that eye damage tends to occur later compared with cutaneous or joint manifestations, blindness being the most disabling complication. Previous studies have focused on ophthalmic manifestations and identified several etiopathogenic mechanisms. Psoriasis may be associated with eye complications such as lesions of the eyelids, conjunctiva and others, with systemic inflammation being the main contributor. In addition, the treatment used for psoriasis may cause ocular changes. The main ophthalmic manifestations associated with psoriasis are keratoconjunctivitis sicca, blepharitis, conjunctivitis and uveitis. The treatment of uveitis, perceived as one of the most serious eye conditions, is controversial and has yet to be clearly determined. Thus, the aim of the present review was to emphasize the importance of regular eye examination for patients with psoriasis, either those receiving biological treatment or those not receiving treatment, in order to diagnose and manage the disease appropriately.

Entheseal involvement in a group of psoriatic arthritis patients: An ultrasonographic study.

Psoriatic arthritis (PsA) is an inflammatory potentially destructive disease that requires early diagnosis and therapeutic approach. Its main pathogenic event and the condition's hallmark is considered to be enthesitis. Clinical examination of the enthesis can be a challenge in the clinical practice; thus, ultrasonography (US) has emerged as an indispensable imaging tool for evaluating both structural and inflammatory changes of this structure. In the present study, we aimed to analyze the type and frequency of entheseal involvement in PsA patients by US examination, performing a retrospective study on 41 patients diagnosed with PsA. Ultrasonographically confirmed enthesitis, identified according to Outcome Measures in Rheumatology group (OMERACT, initially Outcome Measures in Rheumatoid Arthritis Clinical Trials) definitions, was present in 26 of the included patients, Achilles enthesis being the most common site involved. The prevalence of tendon structure abnormalities and the presence of entesophytes underlines the importance of chronic inflammation on entheseal sites. US examination has proven to be a reliable imaging method, with significant and continuous improvement, which is clearly a requisite part for current understanding and diagnosis of enthesitis and more than this, for the patient follow-up algorithm.

The Impact of Smoking on Psoriasis Patients with Biological Therapies in a Bucharest Hospital.

Psoriasis is an immune-mediated chronic inflammatory skin disease with extracutaneous manifestations, that affects about 1-3% of the world's population. The disease is not life-threatening, but the disability which comes with it is comparable to the disability caused by other serious chronic diseases, such as oncologic or cardiovascular disease. Several risk factors, such as infections, stress, smoking, excessive alcohol consumption and genetic predisposition have been involved in inducing psoriasis. Smoking status is a risk factor for many chronic diseases, including psoriasis. Moreover, recent studies have tried to answer the question of whether smoking also influences the response to biologic therapy in patients with psoriasis. Through the current study, our intention is to find out how smoking affects the response to biologic treatment. A hospital-based cross-sectional, observational, non-interventional, retrospective study of moderate and severe psoriasis patients receiving biologic treatment was developed. Two groups were defined based on smoking status: group 1 included smokers (more than 10 cigarettes/day) and former smokers, and group 2 included non-smokers. The data that resulted from the analysis of the cohort of patients demonstrate that smoking status does not affect the response of biologic therapy in patients with moderate and severe psoriasis.

Hepatic Osteodystrophy: A Global (Re)View of the Problem.

Hepatic osteodystrophy is a common and frequently untreated complication, manifested as osteoporosis or osteopenia, encountered in the evolution of chronic liver diseases. This article provides a narrative review of hepatic osteodystrophy. The aim is to revise the prevalence, pathophysiology, diagnosis and management of hepatic osteodystrophy. We searched medical literature via PubMed, Google Scholar, Wiley, Science Direct, and Springer Link using respective keywords to obtain data on low bone mineral density connected to chronic liver diseases. Many studies have reported an increased prevalence of osteoporosis/osteopenia in patients with chronic liver diseases. The pathogenesis is multifactorial, involving genetic factors, vitamin deficiencies, proinflammatory cytokines, hypogonadism, hyperbilirubinemia, antiviral therapy, corticosteroid drugs, and lifestyle factors. The management of patients should include individualized assessment for fracture risk factors and bone mineral density. Vitamin D and calcium supplementation should be recommended in all patients with chronic liver diseases and osteoporosis. Bisphosphonates are the most efficient drugs used in the treatment of hepatic osteodystrophy. In the future, it is necessary to define better the management and specific treatment of hepatic osteodystrophy for prevention of fragility fractures and to improve the patient quality of life.

Influence of the JAK2 V617F Mutation and Inherited Thrombophilia on the Thrombotic Risk among Patients with Myeloproliferative Disorders.

BACKGROUND: A number of studies showed that the JAK2 V617F mutation increases the thrombotic risk in patients with myeloproliferative disorders (MPN) while others did not reveal this correlation, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. Our aim was to clarify the contribution of JAK2 V617F to a hypercoagulable state, as well as its interaction with other thrombophilic factors in patients with thrombosis and myeloproliferative disorders. METHOD: We studied 192 patients with myeloproliferative disorders, 90 with Essential thrombocytemia (ET), 42 with Polycythemia vera (PV) and 60 with Primary or idiopathic myelofibrosis (PMI). From these patients a subgroup of only 62 patients underwent laboratory screening for thrombophilia. RESULTS: The JAK2 V617F mutation was present in 62.8% patients with myeloproliferative disorders, 97.6% with PV, 54.5 % with ET and 53.44% patients with PMI. The mutated patients had a relative risk (RR) for thrombosis at any time of 2.94 in comparison with "wild-type" patients which was 0.93; in those patients having both the mutation and thrombophilia the RR was 3.56 (95% CI 2.41-7.34) compared to patients with neither the mutation nor thrombophilia, suggesting an additive interaction between the two risk factors. CONCLUSION: In patients with myeloproliferatives neoplasias, the thrombotic risk is higher in the JAK2 V617F-mutated subgroup and it is further increased by the presence of inherited thrombophilia (especially by the presence of mutated F V Leiden and lupus anticoagulant).

Does this patient have cancer? The assessment of age, anemia, and erythrocyte sedimentation rate in cancer as a cause of weight loss. A retrospective study based on a secondary care university hospital in Romania.

BACKGROUND: "Does this patient have cancer?" is a question frequently asked when confronted by patients with involuntary weight loss. The aim of this study was to assess the value of age, erythrocyte sedimentation rate (ESR), and anemia in the diagnosis of cancer as a cause of involuntary weight loss. METHODS: A retrospective study of 7850 patients admitted to the Department of Internal Medicine from January to September 2003 was performed. Especially selected were 431 patients with weight loss. Age, ESR, hemoglobin, and the discharge diagnosis were recorded. RESULTS: Twenty-four percent of the patients with involuntary weight loss had cancer. Age, ESR, and anemia were found not to be of value in the diagnosis of cancer (areas under the curve were 0.684, 0.690, and 0.766, respectively). When diagnostic tests for age, a high ESR, and anemia were used serially, the positive predictive value for a malignancy was 64% (CI: 27-90%); when the tests were utilized in parallel, the negative predictive value was 91% (CI: 85-100%). CONCLUSIONS: Any patient admitted to our Department of Internal Medicine for involuntary weight loss had a 24% probability of having a malignancy. Neither age, nor ESR, nor anemia, used separately as a multilevel, diagnostic test or combined serially or in parallel, could exclude or rule in the diagnosis of cancer. However, they could increase (from 24% to 64%) or decrease (from 24% to 9%) the probability of cancer.