Elena Angeloudi

Despite continuously evolving medical advances, CVD risk in Rheumatoid Arthritis (RA) remains paradoxically high to date. Carotid intima-media thickness (cIMT) is a widely used surrogate marker for atherosclerosis. However, issues related to operator-dependent assessment, availability and cost of carotid ultrasound are barriers to its wide implementation as an aid to cardiovascular risk assessment in RA. We aimed to develop a computational artificial intelligence (AI) model for cIMT prediction in RA. The recently proposed DERGA algorithm (Data Ensemble Refinement Greedy Algorithm) was employed in a database of datasets from 101 patients with RA, utilizing information on a wide range of clinical and laboratory variables, classical cardiovascular risk factors, disease-related parameters, and vascular assessments obtained with nailfold videocapillaroscopy (NVC). A total of 13,917,800 models were designed and trained. Among the four evaluated regression metaheuristic algorithms, the best predictive performance was achieved by the DERGA–Extra Trees model. The optimal model utilized only 8 of the 52 available input variables, while maintaining excellent predictive accuracy. Eventually, the 8 most important parameters predicting cIMT, listed from the most influential to the least influential, were white blood count, age, high density lipoprotein cholesterol, capillary density, systolic blood pressure, microhemorrhages, inhibitors of the renin-angiotensin-aldosterone, and methotrexate. A very strong positive linear correlation was observed between predicted and actual (measured) cIMT values ( R = 0.9843), supporting the high predictive capability of the proposed computational intelligence model. Pending external validation in larger cohorts, the findings of the present study should be considered preliminary. Nevertheless, they provide further evidencesupporting the potential utility of AI applications for the assessment of subclinical vascular involvement in RA. While the role of NVC as an indicator of cardiovascular health is beginning to unfold, these findings underscore its promise as an adjunctive modality to facilitate more effective CVD risk stratification in RA.

Arthritis (RA) is characterized by immune-mediated chronic inflammation and endothelial dysfunction, ultimately resulting in clinically overt cardiovascular complications. As a prototypical disease of microvascular dysfunction, RA represents an ideal model to study microvascular alterations. The dermal capillary network offers an easily accessible window to the peripheral microcirculation, whose function can be easily assessed using Nailfold videocapillaroscopy (NVC) or laser techniques. Whereas the clinical significance of structural alterations is not always clear, functional abnormalities may provide more direct insight into the dynamic status of the microvasculature and endothelial integrity. The present narrative review aims to provide an integrative overview of available studies evaluating functional abnormalities of the dermal microcirculation in RA, with particular emphasis on the emerging role of NVC as a dynamic vascular assessment tool. Several studies in RA have assessed the structure and morphology of the peripheral microvasculature using NVC, but far fewer data exist on functional alterations assessed with this method. The study of functional alterations of the dermal microvascular network in RA has largely been based on laser techniques, which consistently point towards altered microvascular reactivity. By contrast, functional NVC-related approaches remain limited, despite their potential ability to simultaneously assess structural and dynamic capillary abnormalities in vivo. Available evidence supports that NVC may be reframed as a promising functional vascular biomarker in RA. However, the available literature is characterized by small sample sizes, predominantly cross-sectional designs, and methodological heterogeneity, highlighting the need for standardized prospective studies.

Rheumatoid arthritis (RA) is characterized by immune-mediated inflammation resulting in excess cardiovascular disease (CVD) risk. Increased sodium, decreased potassium intake and their ratio have been acknowledged as CVD risk modifiers, while pathophysiological studies suggest a role in autoimmunity and inflammation. We aimed to review in a systematic manner the literature regarding the effects of dietary sodium, potassium intake and their ratio, on cardiovascular and disease-related outcomes in patients with RA. We performed a systematic literature search in Medline and Cochrane. Our research concluded to 1,283 patients (8 studies). Although not all studies coincide, most agree that increased dietary sodium and reduced dietary potassium intake are adversely associated with disease related (rheumatic and immunologic) outcomes. The ratio between sodium and potassium emerges a potential indicator of autoimmunity state that needs to be further balanced. Only 4 studies reported associations with cardiovascular outcomes in RA, particularly hypertension, although not consistently and none with hard CVD endpoints. These findings support that interventions promoting a poor in sodium and rich in potassium diet in RA may have beneficial effects in terms of autoimmunity regulation, suppression of inflammation and improvement in cardiovascular health.

BACKGROUND Autoimmune autonomic ganglionopathy (AAG), formerly known as acute pandysautonomia, is a rare, acquired, antibody-mediated, potentially curable autonomic disorder that presents with diffuse autonomic failure. High levels of anti-ganglionic nicotinic acetylcholine receptor (gAChR) serum antibodies are detected in approximately 50% of AAG cases, confirming the diagnosis. CASE SUMMARY We present the case of a 68-year-old man who developed autonomic failure gradually over a 2-year period. Recently, the patient was unable to stand upright for more than a few seconds before fainting. Additionally, he presented with decreased sweating, dry mouth, urinary retention, early satiety, weight loss, bloating, constipation, and erectile dysfunction. Neurological examination revealed dilated pupils that were unresponsive to light. Deep tendon reflexes were absent or diminished. Serologic evaluation revealed the presence of gAChR autoantibodies. An orthostatic hypotension test yielded a positive result. The patient did not respond to symptomatic therapy, including midodrine, fludrocortisone and atomoxetine. Second-line therapy with immunoadsorption produced a noticeable clinical improvement; however, orthostatic hypotension persisted. Sequential rituximab infusion therapy successfully led to a significant improvement in symptoms. CONCLUSION Our case report supports the benefit of combined immunomodulatory therapy for refractory AAG cases that are unresponsive to single-agent treatment.

Introduction Rheumatoid arthritis (RA) is associated with elevated cardiovascular risk. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor and marker of endothelial dysfunction, has been implicated in inflammation-driven vascular injury. However, the association between ADMA and micro- and macrovascular function in RA remains unclear. Methods Patients with RA underwent nailfold videocapillaroscopy (NVC) to assess microvascular alterations in the dermal capillary network. Macrovascular function was evaluated with well-known markers of arterial stiffness [carotid–femoral pulse wave velocity (PWV), augmentation index], and subclinical atherosclerosis [carotid intima–media thickness]. Serum ADMA was measured using enzyme-linked immunosorbent assay (ELISA). Results A total of 103 consecutive RA patients (61.1 ± 11.6 years, 76.7% female) were studied with median disease duration 6 (12) years. Patients were under methotrexate (54.4%), corticosteroids (35.9%) and biologics (38.8%). A considerable portion had been previously diagnosed with hypertension (38.8%) and dyslipidemia (31.1%), and 41.7% were smokers. ADMA was not significantly associated with cardiovascular risk factors or markers of vascular injury in the total cohort. However, in the subgroup of patients not receiving cardiovascular medication (n = 48), ADMA significantly correlated with PWV, venous limb diameter and capillary tortuosity, even after adjustment for other variables in multivariate analysis. Conclusions Circulating ADMA was not associated with markers of vascular impairment in a real-life RA cohort presenting with various treatments and comorbidities. However, ADMA independently correlated with arterial stiffness and NVC abnormalities in the subgroup of RA patients not on cardiovascular medications. These findings are consistent with a role of impaired NO homeostasis in vascular injury in RA. Key Points • This study is the first to investigate the association between circulating ADMA levels and both micro- and macrovascular injury in rheumatoid arthritis using nailfold videocapillaroscopy and markers of arterial stiffness and subclinical atherosclerosis. • Significant correlations between ADMA, pulse wave velocity, and nailfold videocapillaroscopic abnormalities were observed in patients not receiving cardiovascular medications. • These findings suggest that impaired nitric oxide metabolism may contribute to peripheral microangiopathy and vascular dysfunction in rheumatoid arthritis.

Infections with multidrug-resistant (MDR) organisms remain a significant cause of morbidity and mortality among liver transplant recipients, despite advances in surgical techniques and immunosuppressive therapy. This prospective observational study aimed to evaluate the impact of targeted perioperative antibiotic prophylaxis against MDR Gram-negative bacteria on postoperative infections and mortality in liver transplant recipients. Seventy-nine adult patients who underwent liver transplantation and were admitted to the ICU for more than 24 h postoperatively were included. Demographics, disease severity scores, comorbidities, and lengths of ICU and hospital stay were recorded. Colonization with carbapenem-resistant Gram-negative bacteria was assessed via preoperative and postoperative cultures from the blood, urine, rectum, and tracheal secretions. Patients were divided into two groups: those with MDR colonization or infection who received targeted prophylaxis and controls who received standard prophylaxis. Infectious complications (30.4%) occurred significantly less frequently than non-infectious ones (62.0%, p = 0.005). The most common infections were bacteremia (22.7%), pneumonia (17.7%), and surgical site infections (2.5%), with most events occurring within 15 days post-transplant. MDR pathogens isolated included Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Although overall complication and mortality rates at 30 days and 3 months did not differ significantly between groups, the targeted prophylaxis group had fewer infectious complications (22.8% vs. 68.5%, p = 0.008), particularly bacteremia (p = 0.007). Infection-related mortality was also significantly reduced in this group (p = 0.039). These findings suggest that identification of MDR colonization and administration of targeted perioperative antibiotics may reduce septic complications in liver transplant patients. Further prospective studies are warranted to confirm benefits on outcomes and resource utilization.

According to data from the World Health Organization (WHO), lung cancer is becoming a global epidemic. It is particularly high in the list of the leading causes of death not only in developed countries, but also worldwide; furthermore, it holds the leading place in terms of cancer-related mortality. Nevertheless, many breakthroughs have been made the last two decades regarding its management, with one of the most prominent being the implementation of artificial intelligence (AI) in various aspects of disease management. We included 473 papers in this thorough review, most of which have been published during the last 5–10 years, in order to describe these breakthroughs. In screening programs, AI is capable of not only detecting suspicious lung nodules in different imaging modalities—such as chest X-rays, computed tomography (CT), and positron emission tomography (PET) scans—but also discriminating between benign and malignant nodules as well, with success rates comparable to or even better than those of experienced radiologists. Furthermore, AI seems to be able to recognize biomarkers that appear in patients who may develop lung cancer, even years before this event. Moreover, it can also assist pathologists and cytologists in recognizing the type of lung tumor, as well as specific histologic or genetic markers that play a key role in treating the disease. Finally, in the treatment field, AI can guide in the development of personalized options for lung cancer patients, possibly improving their prognosis.

The management of resistant tuberculosis (tb) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensively drug-resistant (XDR) tb who received a treatment regimen including pretomanid, bedaquiline, linezolid, cycloserine, and amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG), and laboratory examinations, were typical for acute myocarditis; however, the patient was considered unstable, and further investigations, including magnetic resonance imaging (MRI), pericardiocentesis, and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which raised a high suspicion of drug induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant tb should be aware of this newly reported, potentially lethal, adverse event.

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.