Search Results (810)

Background: Most patients with hypertension exhibit elevated and detectable levels of natriuretic peptides, particularly BNP and NT-proBNP, as well as troponin concentrations. However, the prognostic relevance of this finding has not been clearly established in patients who have hypertension without heart failure (HF). In this review, we aimed to evaluate the prognostic utility of BNP/NT-proBNP alongside troponin T/I for risk stratification in hypertensive patients, excluding those with HF. Methods: This systematic review was registered in PROSPERO (CRD42024552031). A systematic literature search was conducted using two online databases, Ovid Medline and Web of Science, to identify studies. Data retrieved from articles were used in line with the PRISMA statement guidelines. Participants were aged ≥ 18 years with hypertension. The primary end point was a major adverse cardiac event (MACE) and its individual components. Descriptive synthesis was performed, and data are presented in tabular form. Results: Seventeen studies (70,021 participants) were retrieved for analysis comprising eight prospective cohort studies, six randomized controlled trials, and three retrospective studies. The review evaluated cardiac biomarkers: BNP (n = 6), NT proBNP (n=9), troponin T (n = 4), and troponin I (n = 7). Studies predicted composite MACE (n = 8), all-cause mortality (n = 7), HF (n = 6), and atrial fibrillation (n = 3) outcomes. Cardiac biomarkers showed a strong association with reported outcomes. However, heterogeneity in biomarker thresholds and methodologies limited comparability. Conclusions: The obtained results suggest that elevated cardiac biomarkers BNP/NT-proBNP and troponin I are associated with significantly higher risk of MACE and are powerful predictors in clinical setting. However, large-scale studies are required to validate the robustness and prognostic utility of these biomarkers Full article

Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction. Methods: A novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies. Results: The Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems. Conclusions: This peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia. Full article

Background/Objectives: Pharmacovigilance aims to identify, assess, and minimize drug risks, with spontaneous reporting playing a central role. However, the high level of underreporting and the varying data quality are limitations that should be minimized through prospective cohort studies. Methods: Spontaneous reports reported to the Drug Commission of the German Medical Association (AkdÄ) over one year were compared with the adverse drug reaction (ADR) cases systematically recorded in hospital emergency departments. The frequencies of the demographic patient characteristics and the odds ratios, as the relationship between suspected and concomitant medication, were calculated. Results: In the spontaneous reports, cases were reported by patients a median of 12 years younger, and the group of older patients was less represented (10.8% versus 27.3% in the prospective cohort study). Within the study, cases with polypharmacy were documented significantly more often (a median of seven drugs [IQR 3;10] versus a median of two drugs [IQR 1;5] in the spontaneous reports). New drugs and drugs discussed in the media were frequently reported as causing ADRs, whereas drugs with an effect on the central nervous system were more often suspected in the emergency department setting. Conclusions: Both sources for ADRs provide complementary information that improves the detection of risk signals. The aim for the future is to further increase the awareness of spontaneous reports and to answer specific questions with the help of structured investigations. It is important to compare and validate the findings of spontaneous reports and investigations in regular intervals to improve drug safety. Full article

Background: Long-term follow-up after endovascular aortic repair (TEVAR) is crucial to detect adverse aortic remodeling, even with modern stent grafts offering enhanced flexibility and durability. Conventional imaging, based on diameter measurements, may fail to identify complications such as endograft migration. Methods: We conducted a longitudinal 3D geometric analysis of thoracic aortic and stent-graft evolution over 10 years in a patient treated for descending thoracic aortic aneurysm (DTAA) by endovascular treatment. A three-dimensional morphological analysis (length, tortuosity, angulation, and diameter) was carried out using advanced imaging software (EndoSize, MATLAB) to track aortic geometry and stent-graft behavior over time. A focused review of the literature on stent-graft migration, its risk factors, complications, and surveillance strategies was also performed. Results: This case illustrates how progressive geometric remodeling—including aortic elongation and increased tortuosity—can lead to delayed stent-graft migration and late type III endoleaks, with an elevated risk of rupture. The 3D analysis revealed early morphological changes that were undetectable using standard diameter-based follow-up. These observations are consistent with published data showing higher migration rates over time, particularly in tortuous anatomies. The literature review further emphasizes the clinical relevance of geometric surveillance, given the high rates of reintervention, morbidity, and mortality associated with stent-graft migration. Conclusions: This study underlines the importance of personalized and geometry-based surveillance after TEVAR. Advanced morphological assessment tools provide valuable insights for the early detection of complications and tailored patient management. Their integration into routine follow-up could help optimize long-term outcomes and prevent life-threatening events such as rupture. Full article

Background: Malnutrition is a prevalent but underrecognized condition in cardiovascular disease (CVD) patients, associated with adverse outcomes including longer hospitalizations, higher readmission rates, and increased mortality. Traditional measures such as body mass index (BMI) often fail to detect malnutrition, especially in patients with fluid retention, sarcopenia, or obesity. Methods: This review critically examines current tools used to assess nutritional status in CVD populations. Screening instruments such as Nutritional Risk Screening 2002 (NRS 2002), Mini Nutritional Assessment (MNA, MNA-SF), Malnutrition Universal Screening Tool (MUST), Subjective Global Assessment (SGA), and the Controlling Nutritional Status (CONUT) score are discussed, alongside diagnostic frameworks including the Global Leadership Initiative on Malnutrition (GLIM) criteria. The role of body composition assessment, particularly bioelectrical impedance analysis (BIA) and phase angle (PA), is also highlighted. Results: These tools differ in diagnostic performance and applicability, with many influenced by the pathophysiological features of CVD, such as inflammation, altered fluid balance, and pharmacotherapy. GLIM criteria provide a standardized two-step approach, combining phenotypic and etiologic factors, but require further validation in cardiology settings. Conclusions: A tailored, multimodal approach could be recommended: initial screening followed by confirmatory assessment using GLIM criteria and objective measures of muscle mass or cellular integrity. Clinicians should be aware of tool-specific limitations and interpret findings in the context of CVD-specific challenges. Full article

Background/Objectives: Heart disease affects 0.1% to 4% of pregnant women, with congenital heart defects being the leading cause in developed countries. While maternal mortality is generally low, pre-existing cardiac conditions substantially increase adverse outcome risks. This report describes the multidisciplinary management of a pregnant patient with a bicuspid aortic valve, severe aortic stenosis, and ascending aortic ectasia. Case Presentation: A 34-year-old pregnant woman, asymptomatic but at high risk (World Health Organization Class III) for hemodynamic decompensation, was closely monitored throughout gestation. At 36 weeks, intrauterine growth restriction was detected, prompting an elective cesarean delivery at 38 weeks. Postpartum, the patient developed pre-eclampsia, which was managed successfully. Imaging revealed progressive aortic dilation, leading to surgical aortic valve replacement and ascending aorta reduction plasty. Post-operatively, atrioventricular reentrant tachycardia from an unrecognized accessory pathway developed; medical therapy effectively controlled the arrhythmia after failed catheter ablation. One year later, both mother and child remained in good health. Discussion: This case illustrates the complexity of managing pregnancy in women with congenital heart disease and significant aortic pathology. The physiological changes of pregnancy can exacerbate underlying lesions, necessitating individualized risk assessment, vigilant monitoring, and timely intervention. Conclusions: A multidisciplinary approach involving cardiology, obstetrics, anesthesiology, and genetics is essential to optimize outcomes for pregnant women with significant heart disease. As advances in care allow more women with congenital heart defects to reach childbearing age, structured care pathways remain vital for ensuring safe pregnancies and long-term cardiovascular health. Full article

Background: High-risk chromosomal abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH) have a well-established adverse prognostic impact in multiple myeloma (MM). It is increasingly recognized that the coexistence of two or more HRCAs identifies a particularly poor-risk subgroup, often referred to as double- or multiple-hit MM. However, there is currently no consensus on its definition. Methods: We retrospectively analyzed a multicenter cohort of 1122 newly diagnosed MM patients from 2008 to 2019. Double-hit MM was defined as the coexistence of at least two of the following four HRCAs: t(14;16), gain(1q), del(17p), and del(1p). Based on this definition, we constructed a novel prognostic model, the HBDH (Institute of Hematology & Blood Diseases Hospital) double-hit model, and assessed its prognostic value for progression-free survival (PFS) and overall survival (OS). Results: According to the HBDH model, double-hit patients showed significantly inferior outcomes compared to non-double-hit patients, with median PFS of 20.6 vs. 53.3 months (p < 0.001) and median OS of 40.2 vs. 84.2 months (p < 0.001). The addition of del(13q), t(4;14), or t(11;14) did not improve the prognostic performance of the model. Importantly, the HBDH model was independent of the International Staging System (ISS), elevated LDH, and advanced age. Conclusions: The HBDH double-hit model identifies a subset of ultra-high-risk MM patients carrying at least two major HRCAs, providing a simple and robust framework for prognostic stratification and a potential reference for future biologically driven treatment approaches. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy. Full article

The Sultanate of Oman boasts remarkable biodiversity, exemplified by such species as the Arabian leopard (Panthera pardus nimr) and the Arabian oryx (Oryx leucoryx), national symbols that highlight the extensive conservation efforts required to protect the country’s natural heritage. During decades, Omani authorities have taken significant measures to safeguard wildlife and preserve the natural environment. A sanctuary dedicated to the reintroduction of the Arabian Oryx, after extinction in nature in 1972, was established in 1980 in the Al Wusta Governorate under the patronage of the Royal Diwan and currently administrated by the recently established Environment Authority. During the almost 40 years since the reintroduction and the creation of the sanctuary, the oryx population has grown slowly but constantly. In 2021, the sanctuary hosted 738 oryx, allowing the start of the reintroduction of the species into the natural environment. Small groups of animals were released into the wild in selected areas. No animal health adverse events were recorded, and mortality was generally due to injuries received as a consequence of fighting, in particular during mating season. Standard veterinary care, including control of internal and external parasites, was regularly provided. In some occasions, immunization against certain diseases, such as clostridial infections, pasteurellosis, or mycoplasmosis, was also applied. In 2023, an FMD outbreak in cattle reported in Dhofar, about 500 km from the Al Wusta sanctuary, motivated specific prophylactic actions to prevent the risk of diffusion to oryx. From December 2023 to January 2024, an immunization program was undertaken using an FMD vaccine against serotypes A, O, and SAT 1, mostly in male oryx, while pregnant oryx were avoided for abortion risk due to handling. The following year, in January 2025, a severe outbreak occurred in oryx herds held in the sanctuary. The rapid onset and the spread of clinical symptoms among animals (100% morbidity in the second day after the first appearance of signs in some individuals) were suggestive of a highly contagious disease. The animals suffered from severe depression and inappetence, rapidly followed by abundant salivation, erosions of the oral mucosa and tongue, and diarrhea, with a short course characterized by prostration and death of the animal in the most severe cases. Therapeutical attempts (administration of antibiotics and rehydration) were mostly ineffective. Laboratory investigations (ELISA and PCR) ruled out contagious bovine pleuropneumonia (CBPP), Johne’s disease and Peste des petits ruminants (PPR). Both serology and antigen detection showed positiveness to foot-and-mouth disease (FMD). Out of a total population of 669 present in the sanctuary at the beginning of the outbreak, 226 (33.78%) oryx died. Despite the vaccinal status, the 38.49% of dead animals resulted being vaccinated against FMD. Taking into account the incalculable value of the species, the outbreak represented a very dangerous event that risked wiping out the decades of conservation efforts. Therefore, all the available means, such as accrued biosecurity and adequate prophylaxis, should be implemented to prevent the recurrence of such health risks. The delicate equilibrium of wild fauna in Oman requires study and support for an effective protection, in line with the national plan “Vision 2040”, targeting the inclusion of the Sultanate within the 20 best virtuous countries for wildlife protection. Full article

Background/Objectived: Daratumumab is an anti-CD38 monoclonal antibody used in the treatment of multiple myeloma. Its use interferes with the indirect antiglobulin test (IAT). Treatment of reagent red blood cells (RBCs) with dithiothreitol (DTT) is one of the most validated techniques to resolve this interference. The objective of this study is to evaluate the rate of alloimmunization in transfused patients receiving daratumumab and the occurrence of hemolytic transfusion reactions. Materials and Methods: We conducted a single-center, retrospective, descriptive analysis of all patients treated with daratumumab at our institution from October 2016 to April 2024. For daratumumab-treated patients requiring RBC transfusions, an IAT with DTT-pretreated RBCs (DTT-IAT) was performed using the automated Orthovision system. Transfusion was administered only with a previous negative DTT-IAT while respecting Rh and Kell phenotyping. We assessed the transfusion profile of our patient cohort, including their rates of alloimmunization before and after daratumumab initiation, as well as the incidence of hemolytic complications. Additionally, a literature review was performed on reported alloimmunization rates in daratumumab-treated patients. Results: Among all patients, 106 received RBC and/or platelet transfusions after starting daratumumab. Four had known pre-existing alloantibodies. None developed new alloantibodies or experienced hemolytic complications while receiving anti-CD38 therapy. There were four cases of false-positive DTT-IAT due to residual drug interference or technical variability, in which no alloantibodies or adverse transfusion reactions were detected. Conclusions: Patients receiving daratumumab exhibit a low risk of alloimmunization. This may be partly explained by adherence to Rh and Kell phenotyping and daratumumab’s immunosuppressive effects on alloantibody production. These results support the conclusion that an extended red blood cell phenotype or genotype before starting daratumumab could be omitted if a fast and reliable technique for pretransfusion testing (such as automated DTT-IAT) is available 24 h. Full article

The growing success of oncologic therapies has led to a significant improvement in patient survival; however, this has been accompanied by an increasing incidence of cardiovascular adverse events, particularly cancer therapy-related cardiac dysfunction (CTRCD). Among these, left ventricular impairment represents a major concern due to its potential to compromise both cardiac and oncologic outcomes. This review provides an in-depth overview of the cardiotoxic adverse events associated with several classes of anticancer agents. Particular focus is given to the molecular mechanisms involved in myocardial injury, such as oxidative stress, mitochondrial dysfunction, calcium dysregulation, endothelial reticulum stress, autophagy, and apoptosis. In parallel, established and emerging cardioprotective strategies, from conventional to newer therapeutic approaches, are explored. The role of advanced imaging modalities, as well as cardiac biomarkers, is discussed in the context of early detection and monitoring of subclinical cardiac injury. Finally, the integration of pharmacogenomics and epigenetics is considered as a promising avenue to personalize risk stratification and preventive therapy. By elucidating the complex interplay between cancer treatments and cardiovascular health, this review underscores the importance of a multidisciplinary, precision medicine approach to optimizing the care of patients undergoing potentially cardiotoxic therapies. Full article

Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8 million cases. Pregnant women represent a particularly vulnerable population requiring tailored approaches to the prevention, diagnosis, and treatment of tuberculosis. SARS-CoV-2 infection may have impacted existing clinical protocols. Implementing updated methods of tuberculosis prevention, diagnosis, and treatment in pregnant women could help reduce adverse maternal and fetal outcomes. The aim of this review was to explore potential modifications in tuberculosis management among pregnant women in the post-COVID-19 era, including co-infection with SARS-CoV-2. Methods: A review was conducted, incorporating a systematic literature search across major international databases, including Medline, PubMed, Web of Science, Scopus, and Google Scholar. The search covered publications released between December 2019 and September 2024 and used targeted keywords such as “COVID-19” OR “SARS-CoV-2”, “tuberculosis” OR “TB” OR “latent tuberculosis infection” OR “pulmonary tuberculosis”, and “pregnancy” OR “pregnant women”. Results: Pregnant women living with HIV are at increased risk of developing tuberculosis, which can negatively affect both maternal and perinatal outcomes. Screening for tuberculosis is recommended for all HIV-positive pregnant women, even in the absence of clinical symptoms. Notably, immunological testing before and during pregnancy facilitates the timely and safe detection of tuberculosis infection, enabling preventive and therapeutic interventions during any stage of gestation and the early postpartum period, for the benefit of both mother and child. Drug–drug interactions play a significant role in tuberculosis management, both among anti-tuberculosis agents and with medications for comorbid conditions. Current knowledge of the pharmacokinetics and pharmacodynamics of antituberculosis agents, coupled with therapeutic drug monitoring, supports the development of individualized and effective treatment regimens, which are particularly critical for pregnant patients. Recommendations for managing tuberculosis in pregnant women after COVID-19 infection include measuring D-dimer levels, performing echocardiography, and consulting cardiologists to prevent treatment-related complications. Conclusions: Pregnant women represent a distinct subgroup of tuberculosis patients requiring individualized management. Changes observed in tuberculosis progression and treatment responses in pregnant women before and after SARS-CoV-2 infection should inform therapeutic choices, especially in cases of drug-resistant tuberculosis treated with bedaquiline. COVID-19 has been associated with increased cardiovascular risk, which may heighten the likelihood of adverse drug reactions in this population, especially given the limited therapeutic options. Further research is required to assess the long-term outcomes of latent tuberculosis infection in pregnant women and to evaluate the safety and efficacy of novel regimens for drug-resistant TB during pregnancy. Full article

Solid organ transplant recipients (SOTRs) are at high risk of severe coronavirus disease 2019 (COVID-19), therefore early treatment of mild infections is crucial to prevent increased morbidity and mortality. The effectiveness of early treatment in SOTRs has yet to be fully characterized due to the emergence of new SARS-CoV-2 variants and to COVID-19 vaccination implementation. The aim of this single-center retrospective study is to evaluate the outcomes, safety and impact on SARS-CoV-2 viral load kinetics of COVID-19 early treatment in SOTRs. The study includes 80 SOTRs with a laboratory-confirmed diagnosis of symptomatic SARS-CoV-2 infection enrolled between January and October 2022 and treated with either monoclonal antibodies or antivirals. All patients received COVID-19 vaccination and 68.8% of them showed detectable levels of anti-spike (S) antibodies. The occurrence of clinical events (hospitalization, intensive care unit admission, or death) was assessed within 30 days after treatment initiation. The quantification of SARS-CoV-2 viral load were performed at baseline and at day-7. The rate of hospitalization was 2.5% [0.3–9%] and no deaths occurred. All patients completed treatment with no serious adverse events. Median viral load decrease was 0.48 [0.26–0.69] log₂ cycle threshold (ct) values, with no significant differences between SOTRs treated with monoclonal antibodies and those treated with antivirals. Viral load decrease was significantly associated with positive anti-s serology at baseline ($\beta$ = 0.196, p = 0.01), number of days between symptom onset and treatment ($\beta$ = 0.05, p = 0.03) and the number of comorbidities ($\beta$ = −0.05, p = 0.03). We provide evidence of real-world effectiveness of early therapy in SOTRs infected with SARS-CoV-2 and demonstrate the relevant role of humoral response to vaccination in enhancing early viral load decay during treatment. Full article

Acacia mearnsii De Wild. has been introduced to over 150 countries for its economic value. However, it easily escapes from plantations and establishes monospecific stands across plains, hills, valleys, and riparian habitats, including protected areas such as national parks and forest reserves. Due to its negative ecological impact, A. mearnsii has been listed among the world’s 100 worst invasive alien species. This species exhibits rapid stem growth in its sapling stage and reaches reproductive maturity early. It produces a large quantity of long-lived seeds, establishing a substantial seed bank. A. mearnsii can grow in different environmental conditions and tolerates various adverse conditions, such as low temperatures and drought. Its invasive populations are unlikely to be seriously damaged by herbivores and pathogens. Additionally, A. mearnsii exhibits allelopathic activity, though its ecological significance remains unclear. These characteristics of A. mearnsii may contribute to its expansion in introduced ranges. The presence of A. mearnsii affects abiotic processes in ecosystems by reducing water availability, increasing the risk of soil erosion and flooding, altering soil chemical composition, and obstructing solar light irradiation. The invasion negatively affects biotic processes as well, reducing the diversity and abundance of native plants and arthropods, including protective species. Eradicating invasive populations of A. mearnsii requires an integrated, long-term management approach based on an understanding of its invasive mechanisms. Early detection of invasive populations and the promotion of public awareness about their impact are also important. More attention must be given to its invasive traits because it easily escapes from cultivation. Full article

This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in 19 samples, while 29 samples exceeded established maximum residue levels (MRLs). Acute and chronic dietary risks were assessed for both adults and children. Although individual hazard quotients (HQs) for adults and children remained below the threshold of concern (HQ < 1), the cumulative acute risk reached up to 63.1% of the Acute Reference Dose (ARfD) for children and 51.1% ARfD for adults, with ginger and celery posing the highest risks. Similarly, cumulative chronic risks remained below the safety threshold, with the Acceptable Daily Intake (ADI) percentages reaching a maximum of 5.9% ADI for adults and increased vulnerability of 11.0% ADI among children. Monte Carlo simulations were applied to account for variability and uncertainty in chronic exposure estimates. The hazard index (HI) results showed that adverse health effects for both population groups remained within acceptable safety limits (HI < 1), although higher susceptibility was observed in children. Sensitivity analysis identified body weight and vegetable consumption rates as the most influential factors affecting chronic risk variability. Full article