Clinical Perspective Research Articles

Predictors of reading comprehension and profiling of poor readers in Croatian: educational and clinical perspectives

Predictors of reading comprehension and profiling of poor readers in Croatian: educational and clinical perspectives

Dual-energy CT in musculoskeletal imaging: technical considerations and clinical applications.

Dual-energy CT stands out as a robust and innovative imaging modality, which has shown impressive advancements and increasing applications in musculoskeletal imaging. It allows to obtain detailed images with novel insights that were once the exclusive prerogative of magnetic resonance imaging. Attenuation data obtained by using different energy spectra enable to provide unique information about tissue characterization in addition to the well-established strengths of CT in the evaluation of bony structures. To understand clearly the potential of this imaging modality, radiologists must be aware of the technical complexity of this imaging tool, the different ways to acquire images and the several algorithms that can be applied in daily clinical practice and for research. Concerning musculoskeletal imaging, dual-energy CT has gained more and more space for evaluating crystal arthropathy, bone marrow edema, and soft tissue structures, including tendons and ligaments. This article aims to analyze and discuss the role of dual-energy CT in musculoskeletal imaging, exploring technical aspects, applications and clinical implications and possible perspectives of this technique.

Clinical and kinematic characterization of parkinsonian soft signs in essential tremor.

Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms.

The dark side of drug repurposing. From clinical trial challenges to antimicrobial resistance: analysis based on three major fields

Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields—cardiovascular, cancer, and diabetes—and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.

Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression

Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature and the subsets of these conditions have changed frequently over time, and despite the fact that, in the last classification, they lost their autonomous entity status and became disease qualifiers, the recognition of this feature remains of major importance. Furthermore, in recent years, extensive studies focusing on clonal hematopoiesis and germline variants shed light on the mechanisms of positive pressure underpinning the rise of driver gene mutations in t-MN. In this manuscript, we aim to review the evolution of defining criteria and characteristics of t-MN from a clinical and biological perspective, the advances in mechanistic aspects of malignant progression and the challenges in prevention and management.

Luteinizing hormone supplementation in controlled ovarian stimulation: the Iran Delphi consensus

IntroductionNumerous consensus documents worldwide address luteinizing hormone (LH) supplementation in controlled ovarian stimulation, yet to the best of our knowledge, only one consensus paper has been published in the Arab region. This study presents a Delphi consensus by seven Iranian infertility experts, offering real-world clinical perspectives. The aim was to develop evidence-based opinions on LH's role alongside FSH in various aspects of assisted reproductive technology (ART), including LH levels, monitoring, r-hLH use, and suggested activity.MethodsEmploying the Delphi consensus approach, the Iran consensus unfolded in three steps. In Step 1, eight out of 10 statements gained approval, while two unclear statements were removed. In Step 2, the 20-member extended panel voted on the remaining eight statements.ResultsOnly one (statement 3) lacked consensus (55% agreement), prompting a modification. The revised statement (noted as statement 3′) obtained an 83% agreement.DiscussionThe clinical perspectives included in this consensus complement clinical guidelines and policies that help further improve treatment outcomes, especially for patients with FSH and LH deficiencies.

Global Approach to Follow-Up of Celiac Disease

Celiac disease, an autoimmune disorder induced by the ingestion of gluten, affects approximately 1.4% of the population. Gluten damages the villi of the small intestine, producing symptoms such as abdominal pain, bloating and a subsequent loss of nutrient absorption, causing destabilization of the nutritional status. Moreover, gluten can trigger extra intestinal symptoms, such as asthma or dermatitis, but also mental disorders such as depression or anxiety. Moreover, people suffering from celiac disease sometimes feel misunderstood by society, mainly due to the lack of knowledge about the disease and the gluten-free diet. Thus, the treatment and follow-up of patients with celiac disease should be approached from different perspectives, such as the following: (1) a clinical perspective: symptomatology and dietary adherence monitorization; (2) nutritional assessment: dietary balance achievement; (3) psychological assistance: mental disorders avoidance; and (4) social inclusion: educating society about celiac disease in order to avoid isolation of those with celiac disease. The aim of this narrative review is to gain deep insight into the different strategies that currently exist in order to work on each of these perspectives and to clarify how the complete approach of celiac disease follow-up should be undertaken so that the optimum quality of life of this collective is reached.

Left Ventricular Unloading in Extracorporeal Membrane Oxygenation: A Clinical Perspective Derived from Basic Cardiovascular Physiology.

To present an abridged overview of the literature and pathophysiological background of adjunct interventional left ventricular unloading strategies during veno-arterial extracorporeal membrane oxygenation (V-A ECMO). From a clinical perspective, the mechanistic complexity of such combined mechanical circulatory support often requires in-depth physiological reasoning at the bedside, which remains a cornerstone of daily practice for optimal patient-specific V-A ECMO care. Recent conventional clinical trials have not convincingly shown the superiority of V-A ECMO in acute myocardial infarction complicated by cardiogenic shock as compared with medical therapy alone. Though, it has repeatedly been reported that the addition of interventional left ventricular unloading to V-A ECMO may improve clinical outcome. Novel approaches such as registry-based adaptive platform trials and computational physiological modeling are now introduced to inform clinicians by aiming to better account for patient-specific variation and complexity inherent to V-A ECMO and have raised a widespread interest. To provide modern high-quality V-A ECMO care, it remains essential to understand the patient's pathophysiology and the intricate interaction of an individual patient with extracorporeal circulatory support devices. Innovative clinical trial design and computational modeling approaches carry great potential towards advanced clinical decision support in ECMO and related critical care.

Unraveling the Immunogenetics of STAT Proteins: Clinical Perspectives on Gain-of-Function and Loss-of-Function Variants.

Signal Transducer and Activator of Transcription (STAT) proteins play pivotal roles in immune regulation. The dysregulation of these proteins, attributed to both gain-of-function (GOF) and loss-of-function (LOF) variants, has emerged as a substantial and intricate area of research. This comprehensive review delves into the intricate details of the diverse clinical spectrum associated with STAT variants and the immunological findings linked to these genetic alterations. Although this review does not encompass the treatment of each individual disease, we discuss investigative approaches ranging from immunophenotyping assessment to evaluation of STAT protein activity. These investigations play a crucial role in identifying affected patients and understanding the complexities of STAT.

Investigation of triticeal cartilage anatomy in forensic autopsy cases.

This study aims to determine the presence and morphology of triticeal cartilage (TrC) through autopsy cases and to examine its relationship with age, gender, and height, thus contributing to clinical practices and forensic perspective. Our study was conducted on a total of 84 autopsy cases between the ages of 20-90years who came to Tokat Forensic Medicine Institute. The laryngeal region was palpated to determine whether TrC was present. The dimensions of the TrC and the length of the upper horn of thyroid cartilage (UHThC) were measured with precise digital calipers, and its weight was measured with an accurate digital scale. The presence of TrC was identified in 56% of the autopsy cases examined. The prevalence of TrC was higher in males (61.9%) than in females (23.1%). It was determined to be bilateral in 45% of the cases and unilateral in 11%. TrCs had a cylindrical shape in 68.2%, an oval shape in 25.8%, and a pyramidal shape in 5.8%. The average weight of TrC was 67.93 ± 33.91mg on the right side and 72.67 ± 32.23mg on the left. As the individual's height increased, the weight of TrC increased (p < 0.001). Additionally, there was a strong positive correlation between the lengths of TrC and UHThC and the individual's height (p < 0.001). TrC may be confused with UHThC fractures. Therefore, we believe that knowledge of the presence and morphology of TrC will contribute to clinical approaches and forensic cases, especially in relation to the neck region.

Precocious puberty and skyrocketing obesity rates among children: a contemporary clinical perspective on the co-occurrence

Precocious puberty and skyrocketing obesity rates among children: a contemporary clinical perspective on the co-occurrence

Examination of Ulcero-Proliferative Lesions of Oropharynx and Oral Cavity- A Clinical Perspective

 Introduction Patients often present with ulcero-proliferative lesions of the oropharynx and oral cavity in the outpatient department (OPD). These lesions have a negative impact on the patients' health, so it's critical to make an accurate diagnosis and administer the right care.  Aim of the Study: To determine the proportion of patients who exhibit different ulcero-proliferative lesions clinical characteristics in the oropharynx and oral cavity.  Patients and Methodology: This is prospective study done at Department of ENT, Guntur Medical College, spanning a period of 18 months. This study included patients with ulcero- membranous lesions in the oropharynx and oral cavity, regardless of age. This study excluded Patients who had radiation therapy soon before developing the illness and who had traumatic injuries but no infection. Detailed history including personal, family and medical history were noted. Local and general examination was done. Selected patients were subjected to investigations like routine blood investigations, gram stain, albert’s stain, KOH mount, culture and sensitivity, peripheral smear, serology, FNAC, HPE, USG, chest x ray, CT neck, MRI.  Results In the current study, men dominated women (65.69%) and the most prevalent age group participating was 41–60 years old (45.09%). The most typical symptoms of the throat were odynophagia, burning sensation, dysphagia, and throat pain. 5.9% of the patients had nose issues and 14.7% had associated ear complaints. General symptoms included fever in 10.7% of cases, weight loss in 23.5%, general weakness in 15.6% of cases, and skin lesions in 6.9% of cases. Systemic disorders such as HIV was present in 3.9%, hypertension in 25.4%, and diabetes in 34.3% of cases. Risk factors include chewing tobacco (17.6%), drinking alcohol (14.7%), smoking (43.1%), and having previously been exposed to radiation (0.9%). The tongue was the most frequently afflicted site in this study (44.1%), followed by the palate (29.4%), the buccal mucosa (15.6%), the tonsils (8.8%), the lips (7.8%), the alveolus (2.9%), and the RMT (1.9%). Neoplastic etiology accounted for 41.1% of the total etiology discovered. It was followed by inflammatory (31.3%), infectious (20.5%), and miscellaneous (6.8%) etiologies. 52.9% of patients had conservative care, 36.2% had oncosurgery team treatment through surgery, and 10.7% had radiation therapy. Of the patients with neoplastic etiology, 10.7% had radiation therapy.  Conclusion: The incidence of cancers rises in the adult population with increased habits like smoking and chewing nicotine in any form. A high degree of suspicion is required when treating oral ulcers, particularly those that are chronic. The gold standard for confirming the diagnosis is always a biopsy and a histopathological examination.

Unveiling Promising Neuroimaging Biomarkers for Schizophrenia Through Clinical and Genetic Perspectives.

Schizophrenia is a complex and serious brain disorder. Neuroscientists have become increasingly interested in using magnetic resonance-based brain imaging-derived phenotypes (IDPs) to investigate the etiology of psychiatric disorders. IDPs capture valuable clinical advantages and hold biological significance in identifying brain abnormalities. In this review, we aim to discuss current and prospective approaches to identify potential biomarkers for schizophrenia using clinical multimodal neuroimaging and imaging genetics. We first described IDPs through their phenotypic classification and neuroimaging genomics. Secondly, we discussed the applications of multimodal neuroimaging by clinical evidence in observational studies and randomized controlled trials. Thirdly, considering the genetic evidence of IDPs, we discussed how can utilize neuroimaging data as an intermediate phenotype to make association inferences by polygenic risk scores and Mendelian randomization. Finally, we discussed machine learning as an optimum approach for validating biomarkers. Together, future research efforts focused on neuroimaging biomarkers aim to enhance our understanding of schizophrenia.

4D flow MRI: value and clinical perspectives in patients with pathology of the heart and great vessels. A review

The study of blood flow is becoming a new trend in cardiology and cardiovascular surgery. Based on the literature and our own data, a review is presented on the use of 4D flow in diseases of the heart and blood vessels. The main state of the question about the features of the application of the technique in various pathologies of the cardiovascular system is described in detail, the priorities, limitations and promising directions of the technique application are considered taking into account the goals of practical medicine. The review consists of two parts. The first is devoted to general issues, limitations of the technique, and issues of 4D flow mapping in patients with lesions of the great vessels. In the second part, the emphasis is on the use of 4D flow magnetic resonance imaging in the study of intraventricular blood flow and the application of the technique in congenital heart and vascular diseases.

Combining predominant polarity and affective spectrum concepts in bipolar disorder: towards a novel theoretical and clinical perspective

This is an overview of recent advances on predominant polarity conceptualization in bipolar disorder (BD). Current evidence on its operationalized definitions, possible contextualization within the affective spectrum, along with its epidemiological impact, and treatment implications, are summarized. Predominant polarity identifies three subgroups of patients with BD according to their mood recurrencies: (i) those with depressive or (ii) manic predominance as well as (iii) patients without any preponderance (‘nuclear’ type). A predominant polarity can be identified in approximately half of patients, with similar rates for depressive and manic predominance. Different factors may influence the predominant polarity, including affective temperaments. More generally, affective disorders should be considered as existing on a spectrum ranging from depressive to manic features, also accounting for disorders with ‘ultrapredominant’ polarity, i.e., unipolar depression and mania. While mixed findings emerge on its utility in clinical practice, it is likely that the construct of predominant polarity, in place of conventional differentiation between BD-I and BD-II, may be useful to clarify the natural history of the disorder and select the most appropriate interventions. The conceptualization of predominant polarity seems to reconcile previous theoretical views of both BD and affective spectrum into a novel perspective. It may provide useful information to clinicians for the early identification of possible trajectories of BD and thus guide them when selecting interventions for maintenance treatment. However, further research is needed to clarify the specific role of predominant polarity as a key determinant of BD course, outcome, and treatment response.

Abstract PO3-27-03: PROMISE Study: Pre-Operatory MRI is not Effective. A Systematic review of impact of magnetic resonance imaging on surgery-decision and clinical outcomes in women with breast cancer

Abstract Background: The use of magnetic resonance imaging (MRI) in patients with breast cancer before surgery has been a subject of ongoing debate and discussion. The role of MRI as a preoperative tool to guide surgical decision-making remains controversial. Some studies suggest that MRI may improve the detection of additional tumors or assess the extent of disease, while others discuss that it may lead to increased false-positive findings and unnecessary interventions. The potential benefits and potential harms of incorporating MRI into the preoperative assessment of breast cancer patients continue to be topics of research and clinical interest. Clarifying the impact of preoperative MRI on surgical outcomes is crucial to inform evidence-based practices and optimize patient care. Until present, there is no pooled analyses from randomized clinical trials perspective of the clinical impact regarding the routine use of MRI. Objectives: This study aims to conduct metanalysis of randomized controlled trials (RCT) to investigate the association between preoperative MRI and surgical outcomes in women with newly diagnosed invasive breast cancer, providing evidence-based recommendations for clinical practice. Methods: A comprehensive search of electronic databases including PubMed, Medline, Embase, Ovid, Cochrane Library, and Web of Science was conducted by three independent researchers from inception to May 2023. The inclusion and exclusion criteria were based on Cochrane's principles. Relevant data from eligible studies were extracted. A systematic evaluation and meta-analysis were performed using the fixed-effects model to estimate the pooled risk ratio (RR) and 95% CI. Results: Out of 21 studies found, 6 were RCTs and 15 observational comparative studies. The results showed that in RCT preoperative MRI significantly reduce the rate of immediate breast conservative surgery (RR=0.94, 95%CI 0.91~0.96, I2=0%) and increase the mastectomy rate (RR=1.88, 95%CI 1.48~2.38, I2=86%). There wasn’t any change in reoperations rates (RR=0,87, 95%CI 0.71~1.07, I2=72%). Only 1 trial reported data on survival, showing no difference between groups. Conclusion: From RCT standpoint, the evidence suggests that preoperative MRI for newly diagnosed invasive breast cancer may not be beneficial to the patients by increasing rate of mastectomy with no survival benefit and that should be considered when offering as a routine practice to patients with breast cancer before surgery. Forest plot of mastectomy as an outcome Forest plot of re-operation as an outcome Citation Format: Andre Mattar, Andressa Amorim, Evandro Mateus, Fabio Bagnoli, Felipe Zerwes, Francisco Pimentel Cavalcante, Guilherme Novita, Lincon Mori, Marcelo Madeira, Marina Diogenes, Marcelo Antonini, Lucas Okumura. PROMISE Study: Pre-Operatory MRI is not Effective. A Systematic review of impact of magnetic resonance imaging on surgery-decision and clinical outcomes in women with breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-03.

The best African plant-derived antibacterial products for clinical perspectives: The state-of-the-art

Background: The global burden of bacterial infections remains a serious health concern. In the present review, we have summarized the best botanicals and phytochemicals from the flora of Africa that deserve clinical studies to develop novel antibacterial drugs to combat enterobacteria, Pseudomonas aeruginosa, Gram-positive bacteria, and mycobacteria. Methods: Data were retrieved from scientific databases such as PubMed, Scopus, ScienceDirect, Google Scholar, and Web of Science using the keywords “African country and plant and antibacterial” and plants or phytochemicals with outstanding antibacterial activities following established cutoff point standards were selected. Results: The identified botanicals were from Acacia polyacantha, Alchornea floribunda, Artemisia abyssinica, Beilschmiedia acuta, Eriosema glomeratum, Harungana madagascariensis, Macaranga capensis, Macaranga conglomerata, Macaranga kilimandscharica, Mangifera indica, Piper nigrum, Piptadeniastrum africanum, and Uapaca togoensis. The phytochemicals identified included 2-(4-hydroxyphenyl)-ethyltriacontanoate (1), 1,3,5,6-tetrahydroxyxanthone (2), 1,3,5,7-tetrahydroxyxanthone (3), 8,8-bis-(dihydroconiferyl) diferulate (4), 2-hydroxy-3-methoxy-9,10-dioxo-9,10-dihydroanthracene-1-carbaldehyde (5), allanxanthone D (6), angusticornin B (7), bartericin A (8), diospyrone (9), dorsmanin C (10), gancaonin Q (11), isobavachalcone (12), isoliquiritigenin (13), laburnetin (14), O1-demethyl-3',4'-deoxy-psorospermi-3',4' diol (15), plumbagin (16), and vismiaquinone (17). Conclusion: These plant-derived products deserve clinical investigations to develop novel antibacterial agents to combat bacterial infections.

E-44 | Clinical Perspectives on Valvular and Subclinical Leaflet Thrombosis after Transcatheter Aortic Valve Replacement: Insights from the US FDA MAUDE Database

E-44 | Clinical Perspectives on Valvular and Subclinical Leaflet Thrombosis after Transcatheter Aortic Valve Replacement: Insights from the US FDA MAUDE Database

Cancer Nanovaccines: Nanomaterials and Clinical Perspectives.

Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state-of-the-art in cancer nanovaccine development, elucidating innovative strategies and technologies employed in their design. It explores both preclinical and clinical advancements, emphasizing key studies demonstrating their potential to elicit robust anti-tumor immune responses. The study encompasses various facets, including integrating biomaterial-based nanocarriers for antigen delivery, adjuvant selection, and the impact of nanoscale properties on vaccine performance. Detailed insights into the complex interplay between the tumor microenvironment and nanovaccine responses are provided, highlighting challenges and opportunities in optimizing therapeutic outcomes. Additionally, the study presents a thorough analysis of ongoing clinical trials, presenting a snapshot of the current clinical landscape. By curating the latest scientific findings and clinical developments, this study aims to serve as a comprehensive resource for researchers and clinicians engaged in advancing cancer immunotherapy. Integrating nanotechnology into vaccine design holds immense promise for revolutionizing cancer treatment paradigms, and this review provides a timely update on the evolving landscape of cancer nanovaccines.

Natural Products Act as Game-Changer Potentially in Treatment and Management of Sepsis-Mediated Inflammation: A Clinical Perspective

BackgroundSepsis, a life-threatening condition resulting from uncontrolled host responses to infection, poses a global health challenge with limited therapeutic options. Due to high heterogeneity, sepsis lacks specific therapeutic drugs. Additionally, there remains a significant gap in the clinical management of sepsis regarding personalized and precise medicine. PurposeThis review critically examines the scientific landscape surrounding natural products in sepsis and sepsis-mediated inflammation, highlighting their clinical potential. MethodsFollowing the PRISMA guidelines, we retrieved articles from PubMed to explore potential natural products with therapeutic effects in sepsis-mediated inflammation. Results434 relevant in vitro and in vivo studies were identified and screened. Ultimately, 55 studies were obtained as the supporting resources for the present review. We divided the 55 natural products into three categories: those influencing the synthesis of inflammatory factors, those affecting surface receptors and modulatory factors, and those influencing signaling pathways and the inflammatory cascade. ConclusionNatural products' potential as game-changers in sepsis-mediated inflammation management lies in their ability to modulate hallmarks in sepsis, including inflammation, immunity, and coagulopathy, which provides new therapeutic avenues that are readily accessible and capable of undergoing rapid clinical validation and deployment, offering a gift from nature to humanity. Innovative techniques like bioinformatics, metabolomics, and systems biology offer promising solutions to overcome these obstacles and facilitate the development of natural product-based therapeutics, holding promise for personalized and precise sepsis management and improving patient outcomes. However, standardization, bioavailability, and safety challenges arise during experimental validation and clinical trials of natural products.