Exploring the Pathogenesis of Spondylarthritis beyond HLA-B27: A Descriptive Review.

Spondylarthritis (SpA) is a chronic inflammatory condition that encompasses damage to the axial or peripheral skeleton, accompanied by specific extra-articular symptoms. Within this group, Ankylosing Spondylitis stands out as the hallmark member. Although the heritability of Ankylosing Spondylitis is estimated to be over 95%, only a portion of the heritability has been explained, with HLA-B27 accounting for 20.1% of it; therefore, ongoing research endeavors are currently concentrated on investigating the potential participation of different entities in the development of the disease. Genome-wide association studies have led to significant advances in our understanding of the genetics of SpA. In this descriptive review, we delve into the pathogenesis of Spondylarthritis beyond HLA-B27. We summarize the latest research on the potential participation of various entities in the development of the disease, including other genetic loci, immune dysregulation, microbiota, and environmental factors. The multifactorial nature of SpA and the complex interplay of genetic, immunological, and environmental factors are being increasingly recognized; therefore, it is of paramount importance to consider a holistic approach to comprehend the pathogenesis of SpA in order to identify novel therapeutic targets.

Autoimmune and Non-Autoimmune Comorbidities in Myasthenic Patients of East-European Descent: A Case-Control Study.

Background: As the life expectancy of patients with myasthenia gravis (MG) is improving, so the number of comorbidities continues to rise, with a potentially significant impact on the overall morbidity and mortality. The main aim of the study was to assess comorbidities of MG in a group of patients of East-European descent. Methods: We retrospectively compared 185 adult myasthenic patients with 895 sex- and age-matched controls, admitted from January 2013 to December 2021. Results: Of these patients, 60% had late-onset MG (LOMG), with a clear predominance of women in both the LOMG and early-onset (EOMG) types; and 23.8% of the patients had a radiological description consistent with thymoma. All myasthenic patients had at least one comorbidity; 20 (10.8%) of the patients associated at least one autoimmune comorbidity. Obesity (p < 0.01), type 2 diabetes (p < 0.0001), cerebrovascular diseases (p < 0.0001), essential hypertension (p < 0.01), and cardiac arrythmias (p < 0.0001) were more frequent in patients than in the control group. The granulocyte-to-lymphocyte ratio was higher in the myasthenic patients compared to the controls (p < 0.01 for LOMG). Discussion: We, thus, suggest a common chronic low-grade inflammatory background as a possible connection between MG subtypes and some of these apparently unconnected comorbidities. Conclusions: The East-European origin of the patients offered a different social and cultural angle of a disease studied mainly on populations of West-European and Asian descent.

Cyclophilin A: An Independent Prognostic Factor for Survival in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab and Chemotherapy.

Colorectal cancer (CRC) ranks as second most common cause of cancer-related deaths. The CRC management considerably improved in recent years, especially due to biological therapies such as bevacizumab. The lack of predictive or prognostic biomarkers remains one of the major disadvantages of using bevacizumab in the CRC management. We performed a prospective study to analyze the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) investigated by ELISA in 56 patients with metastatic CRC undergoing bevacizumab and chemotherapy between May 2019 and September 2021 at baseline and after one and six months of therapy. We showed that low levels of CypA at baseline and after one month of treatment were associated with better overall survival (OS) (42 versus 24 months, p = 0.029 at baseline; 42 versus 25 months, p = 0.039 after one month). For copeptin and Tie2, Kaplan-Meier curves showed no correlation between these biomarkers and OS or progression-free survival. When adjusting for baseline and post-treatment factors, a multivariate Cox analysis showed that low values of CypA at baseline and after one month of treatment were independent prognostic factors for OS and correlated with a better prognosis in metastatic CRC patients.

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Autoimmune myasthenia gravis and COVID-19. A case report-based review.

A potential relationship between COVID-19 infection and new onset myasthenia gravis (MG) has been suggested by the coexistence of these two diseases in a number of reports. This study aimed to assess their relationship by reviewing case studies of COVID-19 followed by new onset MG published between 01 December 2019 and 30 June 2023 identified by a search of PubMed/Medline database. In addition, we reviewed evidence in favour and against a potential cause and effect association, and described possible mechanisms that would underpin such a relationship. We identified 14 publications that reported 18 cases. Analysis showed the following features: age 19-83 years; 10 men/8 women; median time interval between COVID-19 and MG (17, 5-56 days); autoimmune comorbidities (4); generalised MG (14); ocular MG (4); thymoma (3); antiacetylcholine receptor antibody (16); antimuscle-specific kinase antibodies (2). All patients improved following treatment. Proof of direct causality between the two conditions can only be established in time by confirming epidemiological increase in the incidence of MG or elucidating pathogenic mechanisms to substantiate a possible cause-effect association, or both.

Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants.

C-reactive protein (CRP) has been one of the most investigated inflammatory-biomarkers during the ongoing COVID-19 pandemics caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The severe outcome among patients with SARS-CoV-2 infection is closely related to the cytokine storm and the hyperinflammation responsible for the acute respiratory distress syndrome and multiple organ failure. It still remains a challenge to determine which of the hyperinflammatory biomarkers and cytokines are the best predictors for disease severity and mortality in COVID-19 patients. Therefore, we evaluated and compared the outcome prediction efficiencies between CRP, the recently reported inflammatory modulators (suPAR, sTREM-1, HGF), and the classical biomarkers (MCP-1, IL-1ß, IL-6, NLR, PLR, ESR, ferritin, fibrinogen, and LDH) in patients confirmed with SARS-CoV-2 infection at hospital admission. Notably, patients with severe disease had higher serum levels of CRP, suPAR, sTREM-1, HGF and classical biomarkers compared to the mild and moderate cases. Our data also identified CRP, among all investigated analytes, to best discriminate between severe and non-severe forms of disease, while LDH, sTREM-1 and HGF proved to be excellent mortality predictors in COVID-19 patients. Importantly, suPAR emerged as a key molecule in characterizing the Delta variant infections.

The Influence of Maternal KIR Haplotype on the Reproductive Outcomes after Single Embryo Transfer in IVF Cycles in Patients with Recurrent Pregnancy Loss and Implantation Failure-A Single Center Experience.

(1) Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) have in common a deficient maternal adaptation to the semi-allogeneic fetus, in which killer immunoglobulin-like receptor (KIR) family expressed by natural killer (NK) cells play an important role. The aim of this study was to evaluate the influence of maternal KIR haplotype on the reproductive outcomes after single embryo transfer in IVF cycles in patients with RPL and RIF. (2) Methods: Patients with RIF and RPL who presented at Origyn Fertility Center from Iasi, Romania, were prospectively enrolled between January 2020 and December 2022. Clinical and paraclinical data was examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. (3) Results: Patients with a KIR AA haplotype had significantly more chances of miscarriage if they underwent an IVF procedure (aOR: 4.15, 95% CI: 1.39-6.50, p = 0.032) compared with those who spontaneously achieved a pregnancy. Moreover, it appeared that the same haplotype increased the chances of obtaining a pregnancy for patients who underwent an IVF procedure (aOR: 2.57, 95% CI: 0.85-6.75, p = 0.023). (4) Conclusions: Determination of KIR haplotype could be beneficial for patients with RPL or RIF in order to offer an individualized management.

Combined flow cytometry natural killer immunophenotyping and KIR/HLA-C genotyping reveal remarkable differences in acute myeloid leukemia patients, but suggest an overall impairment of the natural killer response.

Introduction: Natural killer (NK) cells are key anti-tumor effectors of the innate immunity. Phenotypic differences allow us to discriminate in between three functional stages of maturation, named immature, mature and hypermature that are distinctive in terms of receptor expression, cytokine secretion, cytotoxic properties and organ trafficking. NKs display an impressive repertoire of highly polymorphic germline encoded receptors that can be either activating, triggering the effector's function, or inhibitory, limiting the immune response. In our study, we have investigated peripheral blood NK cells of acute myeloid leukemia (AML) patients. Methods: The Killer Immunoglobulin-like receptors (KIRs) and the HLA-C genotypes were assessed, as HLA-C molecules are cognate antigens for inhibitory KIRs. Results: The AA mainly inhibitory KIR haplotype was found in a higher proportion in AML, while a striking low frequency of the 2DS3 characterized the mainly activating Bx haplotype. Flow cytometry immunophenotyping evidenced a lower overall count of NK cells in AML versus healthy controls, with lower percentages of the immature and mature subpopulations, but with a markedly increase of the hypermature NKs. The analysis of the KIR2DL1, KIR2DL2, KIR2DL3, KIR3DL1, and NKG2A inhibitory receptors surface expression revealed a remarkable heterogeneity. However, an overall trend for a higher expression in AML patients could be noticed in all maturation subpopulations. Some of the AML patients with complex karyotypes or displaying a FLT3 gene mutation proved to be extreme outliers in terms of NK cells percentages or inhibitory receptors expression. Discussion: We conclude that while the genetic background investigation in AML offers important pieces of information regarding susceptibility to disease or prognosis, it is flow cytometry that is able to offer details of finesse in terms of NK numbers and phenotypes, necessary for an adequate individual evaluation of these patients.

The Impact of Bevacizumab and Chemotherapy on Quality of Life in Metastatic Colorectal Cancer Patients.

Health-related quality is of life of great importance in cancer care. This prospective study aimed to evaluate the impact of chemotherapy and bevacizumab on the activities of daily living, cancer symptoms, and general well-being in 59 metastatic colorectal cancer patients. We gathered information using the EORTC QLQ-C30 and QLQ-CR29 questionnaires. The paired sample t-test, MANOVA test, and Pearson's correlation test were used to analyze the presence of significant differences in mean scores before and after 6 months of treatment. The results revealed significant differences in the functioning and symptoms that influence patients' quality of life after 6 months of treatment: increased pain (p = 0.003), nausea and vomiting (p = 0.003), diarrhea (p = 0.021) and decreased appetite (p = 0.003). At the same time, there were several aspects that improved the quality of life. Increases in emotional function (p = 0.009), cognitive function (p = 0.033), and perception of body image (p = 0.026) were observed after 6 months of treatment. Elderly patients reported a higher frequency of stools (p = 0.028), and young patients had increased concerns about body perception (p = 0.047). Assessing the quality of life of metastatic colorectal cancer patients is an important way to identify and treat symptoms related to both cancer and therapy by establishing a holistic care plan and implementing measures to increase the quality of life.

Cytokines and Chemokines in Breastmilk of SARS-CoV-2 Infected or COVID-19 Vaccinated Mothers.

INTRODUCTION: The COVID-19 disease and anti-SARS-CoV-2 vaccination were accompanied by alterations in several inflammatory markers. The aim of our research was to check to what extent such cytokines are transferred to infants via the breastmilk of SARS-CoV-2-infected or vaccinated mothers. Thus, we wanted to check if breastfeeding is safe during SARS-CoV-2 infection or after COVID-19 mRNA-vaccination. MATERIAL AND METHOD: The Luminex Multiplexing Assay was used for quantifying 10 cytokine in the human breastmilk of SARS-CoV-2-infected or COVID-19-vaccinated mothers, compared with anti-SARS-CoV-2 IgG naïve mothers. Two milk samples were collected at 30 and 60 days either after the booster dose or afterthe onset of symptoms. A single milk sample was collected from the mothers within the control group. RESULTS: The cytokine concentrations were mostly found within the reference intervals for all mothers. The status of the vaccinated/infected mother, the age of the breastfed child, the parity of the mother and the maternal age were variation factors of the above-mentioned cytokine concentrations. The type of birth and the presence of IgG in the milk had no influence on these cytokine concentrations in milk. Furthermore, no statistically significant differences were recorded between the cytokine concentrations of the two milk samples. CONCLUSION: Our study provides data that support the safety of breastfeeding in the case of mild COVID-19 infection or after Pfizer or Moderna vaccinations.

A Rising Star of the Multimarker Panel: Growth Differentiation Factor-15 Levels Are an Independent Predictor of Mortality in Acute Heart Failure Patients Admitted to an Emergency Clinical Hospital from Eastern Europe.

(1) Background: Acute heart failure (HF) represents one of the most common yet extremely severe presentations in emergency services worldwide, requiring prompt diagnosis, followed by an adequate therapeutic approach, and a thorough risk stratification. Natriuretic peptides (NPs) are currently the most widely implemented biomarkers in acute HF, but due to their lack of specificity, they are mainly used as ruling-out criteria. Growth differentiation factor-15 (GDF-15) is a novel molecule expressing different pathophysiological pathways in HF, such as fibrosis, remodeling, and oxidative stress. It is also considered a very promising predictor of mortality and poor outcome. In this study, we aimed to investigate the GDF-15's expression and particularities in patients with acute HF, focusing mainly on its role as a prognosis biomarker, either per se or as part of a multimarker panel. (2) Methods: This unicentric prospective study included a total of 173 subjects, divided into 2 subgroups: 120 patients presented in emergency with acute HF, while 53 were ambulatory-evaluated controls with chronic HF. At admission, all patients were evaluated according to standard clinical echocardiography and laboratory panel, including the assessment of GDF-15. (3) Results: The levels of GDF-15 were significantly higher in patients with acute HF, compared to controls [596 (305−904) vs. 216 (139−305) ng/L, p < 0.01]. GDF-15 also exhibited an adequate diagnostic performance in acute HF, expressed as an area under the curve (AUC) of 0.883 [confidence interval (CI) 95%: 0.828−0.938], similar to that of NT-proBNP (AUC: 0.976, CI 95%: 0.952−1.000), or troponin (AUC: 0.839, CI 95%: 0.733−0.944). High concentrations of GDF-15 were significantly correlated with mortality risk. In a multivariate regression model, GDF-15 was the most important predictor of a poor outcome, superior to NT-proBNP or troponin. (4) Conclusions: GDF-15 proved to be a reliable tool in the multimarker assessment of patients with acute HF. Compared to the gold standard NT-proBNP, GDF-15 presented a similar diagnostic performance, doubled by a significantly superior prognostic value, making it worth being included in a standardized multimarker panel.

Adipokines, and not vitamin D, associate with antibody immune responses following dual BNT162b2 vaccination within individuals younger than 60 years.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to a global health outbreak known as the COVID-19 pandemic which has been lasting since March 2020. Vaccine became accessible to people only at the beginning of 2021 which greatly helped reducing the mortality rate and severity of COVID-19 infection afterwards. The efficacy of vaccines was not fully known and studies documenting the immune responses following vaccination are continuing to emerge. Recent evidence indicate that natural infection prior vaccination may improve the antibody and cellular immune responses, while little is known about the factors influencing those processes. Here we investigated the antibody responses following BNT162b2 vaccination in relation to previous-infection status and age, and searched for possible biomarkers associated with the observed changes in immune responses. We found that the previous-infection status caused at least 8-times increase in the antibody titres, effect that was weaker in people over 60 years old and unaltered by the vitamin D serum levels. Furthermore, we identified adiponectin to positively associate with antibody responses and negatively correlate with pro-inflammatory molecules (MCP-1, factor D, CRP, PAI-1), especially in previously-infected individuals.

Autoimmune myasthenia gravis after COVID-19 in a triple vaccinated patient.

Despite a well characterized mechanism, myasthenia gravis (MG) remains a dilemma in terms of etiology. Several case reports and series of cases suggest a potential cause-effect relation between SARS-CoV-2 infection or vaccination and MG. We present the case of an autoimmune MG occurring post Covid-19 in an elderly male, vaccinated with three doses of the BNT162b2/Pfizer-BioNTech vaccine. The 78-year-old male was admitted in the Neurology Clinic in early November 2021 with double vision, bilateral ptosis, dysphonia and dysphagia, 16 days after receiving a third dose of the BNT162b2/Pfizer-BioNTech SARS-CoV-2 vaccine and 12 days after testing positive for SARS-CoV-2 infection. The symptoms began to emerge at 9 days after COVID-19 diagnosis. Clinical neurological examination included ice-pack test and intramuscular neostigmine, both with positive results. Myasthenia gravis positive diagnosis was confirmed by slow repetitive nerve stimulation and abnormally increased serum levels of antibodies against acetylcholine receptors. Due to patient's refusal of further hospitalization, he was discharged with therapy recommendations. Under treatment with oral pyridostigmine, but no oral corticosteroid due to therapeutic noncompliance, the patient was readmitted two months later with aggravated symptoms. The myasthenic crisis was successfully treated with intravenous immunoglobulins, corticosteroid therapy and oral pyridostigmine. The novelty of the current case resides in the fact that, to the best of our knowledge, appears to be the first case of MG clinically manifested after COVID-19 infection in a fully vaccinated patient.

Antiangiogenic Drug-Induced Proteinuria as a Prognostic Factor in Metastatic Colorectal Cancer.

Treatment with bevacizumab is known to cause adverse events such as proteinuria and hypertension, amongst others. However, while bevacizumab-induced hypertension has been linked to increased overall survival (OS), data on proteinuria are controversial. We performed a retrospective analysis to observe the influence of adverse events developed during treatment with bevacizumab and chemotherapy on the OS in patients with metastatic colorectal cancer (mCRC). Kaplan-Meier and log-rank analyses were used to assess differences in OS, and hazard ratios (HR) were estimated using Cox models. Out of the 3497 mCRC patients admitted to our center between 2014 and 2019, 150 met the criteria for inclusion in our analysis. Out of these, 50.7% experienced proteinuria and had reached a longer OS (40 versus 25 months, p = 0.015) and progression-free survival (15 versus 12 months, p = 0.039). The following groups were identified as having a lower risk of death: patients with proteinuria (HR 0.589; 95% CI 0.402-0.863; p = 0.007), one metastatic site (HR 0.533; 95% CI 0.363-0.783; p = 0.001), and non-metastatic stage at diagnosis (HR 0.459; 95% CI 0.293-0.720; p = 0.001). Patients with anemia and diabetes had an increased risk of death. Proteinuria emerges as a useful prognostic factor in mCRC patients undergoing bevacizumab-based systemic therapy, and it could be easily integrated into the decision-making process, thus allowing physicians to further individualize systemic treatments.

Heparin-Binding Protein (HBP), Neutrophil Gelatinase-Associated Lipocalin (NGAL) and S100 Calcium-Binding Protein B (S100B) Can Confirm Bacterial Meningitis and Inform Adequate Antibiotic Treatment.

The empirical administration of antibiotics for suspected bacterial meningitis denotes a poor bacterial stewardship. In this context, the use of biomarkers can distinguish between bacterial and viral infections before deciding treatment. Our study assesses how levels of heparin-binding protein (HBP), neutrophil gelatinase-associated lipocalin (NGAL), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) and in blood can promptly confirm bacterial etiology and the need for antibiotic treatment. The CSF and blood levels of HBP, NGAL, S100B, and NSE of 81 patients with meningitis were measured and analyzed comparatively. Statistical sensitivity, specificity, and positive and negative predictive values were evaluated. CSF levels of HBP and NGAL and the blood level of S100B in the bacterial meningitis group were significantly higher (p < 0.05). The area under curve (AUC) for predicting bacterial meningitis was excellent for the CSF level of HBP (0.808 with 93.54% sensitivity and 80.64% specificity), good for the CSF level of NGAL (0.685 with 75.00% sensitivity and 65.62% specificity), and good for the blood level of S100B (0.652 with 65.90% sensitivity and 57.14% specificity). CSF levels of HBP and NGAL, as well as the blood level of S100B, could help discriminate between bacterial and viral meningitis before considering antibiotic treatment.

Acceptability of Human Papilloma Virus Self-Sampling for Cervical Cancer Screening in a Cohort of Patients from Romania (Stage 2).

(1) Background: Low patient's adherence to conventional cervical cancer screening methods determined the need to take into consideration alternative approaches, and vaginal HPV self-sampling is one of them. We aimed to evaluate, using an online survey, the Romanian women's acceptability of vaginal HPV self-sampling. (2) Methods: A 13-questions online survey was distributed on three Facebook groups, and the results were summarized. (3) Results: Despite of good educational background, 10.8% (n = 60) of the respondents did not know what a Pap smear is, and 33% (n = 183) were not informed about the free national cervical cancer screening program. Multivariate analysis revealed an increased likelihood of vaginal self-sampling acceptance among respondents who did not know about Pap test (OR: 7.80; 95%CI: 1.062−57.431; p = 0.021), national cervical cancer screening program (OR: 1.96; 95%CI: 1.010−3.806; p = 0.02), HPV infection (OR: 7.35; 95%CI: 3.099−17.449; p< 0.001) or HPV test (OR: 1.67; 95%CI: 0.950−2.948; p = 0.03). Moreover, women who did not previously undergo a cervical cancer screening program were more likely to accept the new screening method (OR: 1.62; 95%CI: 0.878−3.015; p = 0.04). (4) Conclusions: Our results showed high acceptability rates of vaginal HPV self-sampling among participants.

Anti-RBD IgA and IgG Response and Transmission in Breast Milk of Anti-SARS-CoV-2 Vaccinated Mothers.

The appearance of the severe acute respiratory syndrome virus-2 (SARS-CoV-2) has had a significant impact on the balance of public health and social life. The data available so far show that newborns and young children do not develop severe forms of COVID-19, but a small proportion of them will still need hospitalization. Even though young children represent an important vector of the infection, vaccination at such a young age was not yet considered. Thus, the question of whether potentially protective antibodies against SARS-CoV-2 could be provided to them via breast milk or across the placenta, as "passive immunity", still stands. MATERIALS AND METHODS: Between January-July 2021, we have conducted a prospective study that aimed to measure the immunoglobulin (Ig) A and IgG anti-SARS-CoV-2 titers in the breast milk of 28 vaccinated lactating mothers, sampled at 30 and 60 days after the second dose of the anti-SARS-CoV-2 Pfizer or Moderna mRNA vaccines. Anti-RBD reactive IgA and IgG antibodies were detected and quantified by a sandwich enzyme-linked immunosorbent assay. RESULTS: Anti-RBD IgA and IgG were present in all breast milk samples, both in the first and in the second specimens, without a significant difference between those two. The anti-RBD IgA titers were approximately five-times higher than the anti-RBD IgG ones. The anti-RBD IgA and IgG titers were correlated with the infants' age, but they were not correlated with the vaccine type or mother's age. The anti-RBD IgA excreted in milk were inversely correlated with the parity number. CONCLUSIONS: Anti-SARS-CoV-2 IgA and IgG can be found in the milk secretion of mothers vaccinated with mRNA vaccines and, presumably, these antibodies should offer protection to the newborn, considering that the antibodies' titers did not decrease after 60 days. The antibody response is directly proportional to the breastfed child's age, but the amount of anti-RBD IgA decreases with the baby's rank. The antibody response did not depend on the vaccine type, or on the mother's age.

Body composition, adipokines, FGF23-Klotho and bone in kidney transplantation: Is there a link?

BACKGROUND: Kidney transplantation-associated mineral and bone disorder (KT-MBD) still represents a black box on the long-term due to scarce available data. We aimed to investigate the impact of non-classical bone regulating factors (body composition, adipokines, inflammatory markers, fibroblast growth factor 23-FGF23 and α-Klotho) in long-standing kidney transplant (KT) recipients compared to the general population. METHODS: Our cross-sectional study, enrolling 59 KT patients and age, sex and body mass index-matched healthy general population volunteers, assessed the predictive role of the body composition, serum adipokines (leptin, adiponectin, resistin), inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and parathyroid hormone (PTH)-FGF23/α-Klotho axis upon bone mineral density (BMD) and osteocalcin, using correlation and linear multiple regression. RESULTS: The 59 KT recipients (mean transplantation span of 57.7 ± 7.2 months) had similar body composition but significantly lower BMD (p < 0.01) compared to the general population group. Total lean mass was independently associated with BMD in both groups. In KT patients, age, time spent on dialysis and PTH were the main negative independent predictors of BMD, after adjusting for possible confounders. Resistin and α-Klotho also negatively predicted lumbar bone density (p < 0.001), while adiponectin and α-Klotho positively predicted osteocalcin levels (p < 0.001) in KT recipients, independently of inflammatory markers. No significant associations were found between FGF23 and bone parameters in any of the groups. CONCLUSIONS: Age, PTH, time on dialysis and lean mass are among the main bone density predictors in long-standing KT patients. The bone impact of adipokine dysregulation and of α-Klotho merits further investigations in KT-MBD. Preserving lean mass for improved bone outcomes should be part of KT-MBD management on the long-term.

The Influence of Socioeconomic Status on the Prognosis and Profile of Patients Admitted for Acute Heart Failure during COVID-19 Pandemic: Overestimated Aspects or a Multifaceted Hydra of Cardiovascular Risk Factors?

Background: Heart failure (HF) is a complex clinical syndrome that represents a great burden on public health systems due to its increased prevalence, disability and mortality rates. There are multiple triggers that can induce or aggravate a preexisting HF, socioeconomic status (SES) emerging as one of the most common modifiable risk factors. Our study aimed to analyze the influence of certain SES indicators on the outcome, clinical aspects and laboratory parameters of patients with HF in North-Eastern Romania, as well as their relationship with other traditional cardiovascular risk factors. Methods: We conducted a prospective, single-center study comprising 120 consecutively enrolled patients admitted for acute HF. The evaluation of individual SES was based upon a standard questionnaire and evidence from official documents. Results: the patients' age ranged between 18 and 94 years; Out of 120 patients, 49 (40.8%) were women and 71 (59.2%) were men, residing in rural 59 (49.2%) or urban 61 (50.8%) areas. 14.2% were university graduates, while 15.8% had only attended primary school. The majority of the patients are or were employed in the service sector (54.5%), followed by industry (29.2%) and agriculture (20%). The mean monthly income was 306.1 ± 177.4 euro, while the mean hospitalization cost was 2471.8 ± 2073.8 euro per patient. The individual income level was positively correlated with urban area of residence, adequate household sanitation facilities and healthcare access, and negatively associated with advanced age and previous hospitalizations due to HF. However, the individual financial situation was also positively correlated with the increased prevalence of certain cardiovascular risk factors, such as arterial hypertension, anemia or obesity, but not with total cholesterol or male gender. Concerning the direct impact of a poor economic status upon prognosis in the setting of acute HF, our results showed no statistically significant differences concerning the in-hospital or at 1-month follow-up mortality rates. Rather than inducing a direct impact on the short-term outcome, these findings concerning SES indicators are meant to enhance the implementation of policies aimed to provide adequate healthcare for people from all social layers, with a primary focus on modifiable cardiovascular risk factors.

A Novel Paradigm Based on ST2 and Its Contribution towards a Multimarker Approach in the Diagnosis and Prognosis of Heart Failure: A Prospective Study during the Pandemic Storm.

BACKGROUND: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians' interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. METHODS: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. RESULTS: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). CONCLUSIONS: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.