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11 pages, 1311 KiB  
Case Report
Multisystemic Tuberculosis Masquerading as Aggressive Cardiac Tumor Causing Budd–Chiari Syndrome Disseminated to the Brain Resulting in Death of a Six-Year-Old Boy
by Eman S. Al-Akhali, Sultan Abdulwadoud Alshoabi, Halah Fuad Muslem, Fahad H. Alhazmi, Amirah F. Alsaedi, Kamal D. Alsultan, Amel F. Alzain, Awatif M. Omer, Maisa Elzaki and Abdullgabbar M. Hamid
Pathogens 2025, 14(8), 772; https://doi.org/10.3390/pathogens14080772 (registering DOI) - 5 Aug 2025
Abstract
Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control [...] Read more.
Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control and in lowering death rates at both individual and population levels. Although diagnostic methods have improved sufficiently in recent decades, TB can still present with ambiguous laboratory and imaging features. This ambiguity can lead to diagnostic pitfalls and potentially disastrous outcomes due to delayed diagnosis. In this article, we present a case of TB that was difficult to diagnose. The disease had invaded the mediastinum, right atrium, right coronary artery, and inferior vena cava (IVC), resulting in Budd–Chiari syndrome. This rare presentation created clinical, laboratory, and radiological confusion, resulting in a diagnostic dilemma that ultimately led to open cardiac surgery. The patient initially presented with progressive shortness of breath on exertion and fatigue, which suggested possible heart disease. This suspicion was reinforced by computed tomography (CT) imaging, which showed infiltrative mass lesions predominantly in the right side of the heart, invading the right coronary artery and IVC, with imaging features mimicking angiosarcoma. Although laboratory findings revealed an exudative effusion with lymphocyte predominance and elevated adenosine deaminase (ADA), the Gram stain was negative for bacteria, and an acid-fast bacilli (AFB) smear was also negative. These findings contributed to diagnostic uncertainty and delayed the confirmation of TB. Open surgery with excisional biopsy and histopathological analysis ultimately confirmed TB. We conclude that TB should not be ruled out solely based on negative Mycobacterium bacteria in pericardial effusion or AFB smear. TB can mimic aggressive tumors such as angiosarcoma or lymphoma with invasion of the surrounding tissues and blood vessels. Awareness of the clinical presentation, imaging findings, and potential diagnostic pitfalls of TB is essential, especially in endemic regions. Full article
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20 pages, 1291 KiB  
Review
Ultrasound Imaging Modalities in the Evaluation of the Dog’s Stifle Joint
by Anargyros T. Karatrantos, Aikaterini I. Sideri, Pagona G. Gouletsou, Christina G. Bektsi and Mariana S. Barbagianni
Vet. Sci. 2025, 12(8), 734; https://doi.org/10.3390/vetsci12080734 - 4 Aug 2025
Abstract
This review presents a comprehensive overview of various ultrasound imaging techniques employed in the evaluation of the canine knee joint. It critically analyzes studies conducted on both human and animal subjects, with a focus on the diagnostic accuracy of B-mode ultrasound, Doppler examination, [...] Read more.
This review presents a comprehensive overview of various ultrasound imaging techniques employed in the evaluation of the canine knee joint. It critically analyzes studies conducted on both human and animal subjects, with a focus on the diagnostic accuracy of B-mode ultrasound, Doppler examination, contrast-enhanced ultrasound, and elastography in both normal and pathological conditions. The review underscores the necessity of strict adherence to the protocols of each ultrasound modality and emphasizes the importance of a thorough understanding of the anatomical region to achieve optimal outcomes. The findings suggest that these ultrasound techniques can significantly enhance the diagnostic process, providing valuable insights into anatomy, size, blood supply, and tissue elasticity. Additionally, in cases where advanced imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) are cost-prohibitive or less accessible, ultrasound serves as a reliable alternative, delivering high diagnostic accuracy and critical information regarding mechanical changes in the joint and neovascularization. Full article
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10 pages, 2785 KiB  
Article
Integration of Genome and Epigenetic Testing in the Diagnostic Evaluation of Developmental Delay: Differentiating Börjeson–Forssman–Lehmann (BFLS) and White–Kernohan (WHIKERS) Syndromes
by Keri Ramsey, Supraja Prakash, Jennifer Kerkhof, Bekim Sadikovic, Susan White, Marcus Naymik, Jennifer Sloan, Anna Bonfitto, Newell Belnap, Meredith Sanchez-Castillo, Wayne Jepsen, Matthew Huentelman, Saunder Bernes, Vinodh Narayanan and Shagun Kaur
Genes 2025, 16(8), 933; https://doi.org/10.3390/genes16080933 (registering DOI) - 4 Aug 2025
Abstract
Background: More than 1500 genes are associated with developmental delay and intellectual disability, with variants in many of these genes contributing to a shared phenotype. The discovery of variants of uncertain significance (VUS) found in these genes during genetic testing can lead [...] Read more.
Background: More than 1500 genes are associated with developmental delay and intellectual disability, with variants in many of these genes contributing to a shared phenotype. The discovery of variants of uncertain significance (VUS) found in these genes during genetic testing can lead to ambiguity and further delay in diagnosis and medical management. Phenotyping, additional genetic testing, and functional studies can all add valuable information to help reclassify these variants. Here we demonstrate the clinical utility of epigenetic signatures in prioritizing variants of uncertain significance in genes associated with developmental delay (DD) and intellectual disability (ID). Methods: Genome sequencing was performed in a male with developmental delay. He was found to have VUSs in both PHF6 and DDB1 genes, linked with Börjeson–Forssman–Lehmann syndrome (BFLS) and White–Kernohan syndrome (WHIKERS), respectively. These two disorders share a similar phenotype but have distinct inheritance patterns and molecular pathogenic mechanisms. DNA methylation profiling (DNAm) of whole blood was performed using the clinically validated EpiSign assay. Results: The proband’s methylation profile demonstrated a strong correlation with the BFLS methylation signature, supporting the PHF6 variant as a likely cause of his neurodevelopmental disorder. Conclusions: Epigenetic testing for disorders with distinct methylation patterns can provide diagnostic utility when a patient presents with variants of uncertain significance in genes associated with developmental delay. Epigenetic signatures can also guide genetic counselling and family planning. Full article
(This article belongs to the Special Issue Genetics and Genomics of Heritable Pediatric Disorders)
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12 pages, 677 KiB  
Review
Prognostic Utility of Arterial Spin Labeling in Traumatic Brain Injury: From Pathophysiology to Precision Imaging
by Silvia De Rosa, Flavia Carton, Alessandro Grecucci and Paola Feraco
NeuroSci 2025, 6(3), 73; https://doi.org/10.3390/neurosci6030073 - 4 Aug 2025
Abstract
Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a [...] Read more.
Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article
(This article belongs to the Topic Neurological Updates in Neurocritical Care)
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26 pages, 3179 KiB  
Review
Glioblastoma: A Multidisciplinary Approach to Its Pathophysiology, Treatment, and Innovative Therapeutic Strategies
by Felipe Esparza-Salazar, Renata Murguiondo-Pérez, Gabriela Cano-Herrera, Maria F. Bautista-Gonzalez, Ericka C. Loza-López, Amairani Méndez-Vionet, Ximena A. Van-Tienhoven, Alejandro Chumaceiro-Natera, Emmanuel Simental-Aldaba and Antonio Ibarra
Biomedicines 2025, 13(8), 1882; https://doi.org/10.3390/biomedicines13081882 - 2 Aug 2025
Viewed by 145
Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, [...] Read more.
Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy. Full article
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25 pages, 906 KiB  
Review
Evolution and Prognostic Variables of Cystic Fibrosis in Children and Young Adults: A Narrative Review
by Mădălina Andreea Donos, Elena Țarcă, Elena Cojocaru, Viorel Țarcă, Lăcrămioara Ionela Butnariu, Valentin Bernic, Paula Popovici, Solange Tamara Roșu, Mihaela Camelia Tîrnovanu, Nicolae Sebastian Ionescu and Laura Mihaela Trandafir
Diagnostics 2025, 15(15), 1940; https://doi.org/10.3390/diagnostics15151940 - 2 Aug 2025
Viewed by 200
Abstract
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, [...] Read more.
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Inherited/Genetic Diseases)
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11 pages, 577 KiB  
Article
New Method for the Determination of Lamotrigine in Human Saliva Using SPE-LC-DAD
by Ewelina Dziurkowska, Aleksandra Michalak, Alina Plenis and Maciej Dziurkowski
Molecules 2025, 30(15), 3237; https://doi.org/10.3390/molecules30153237 - 1 Aug 2025
Viewed by 135
Abstract
(1) Background: The concentration of lamotrigine, an antiepileptic drug very often used in bipolar disorder, is most often determined in the blood, with many inconveniences. An alternative may be to use saliva as a diagnostic material for this purpose. The development of a [...] Read more.
(1) Background: The concentration of lamotrigine, an antiepileptic drug very often used in bipolar disorder, is most often determined in the blood, with many inconveniences. An alternative may be to use saliva as a diagnostic material for this purpose. The development of a method to determine lamotrigine in saliva as a biological material significantly improves patient comfort during sampling. The developed method uses solid-phase extraction for the isolation of the drug from saliva for the first time. (2) Methods: This study aimed to develop a method to determine lamotrigine in saliva using solid-phase extraction (SPE) for isolation and liquid chromatography with a diode array detector (LC-DAD) for quantitative analysis. (3) Results: The method was validated by determining its linearity in the concentration range 10–2000 ng/mL (R2 > 0.99), and the intra- and inter-day precision expressed as coefficient of variation (CV%) did not exceed 15%. (4) Conclusions: The developed method was used to determine the salivary concentration of lamotrigine in patients treated with the studied compound, confirming its usefulness in bipolar disorder (BD). Full article
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13 pages, 1697 KiB  
Article
Enhanced Diagnostic Accuracy for Septic Arthritis Through Multivariate Analysis of Serum and Synovial Biomarkers
by Hyung Jun Park, Ji Hoon Jeon, Juhyun Song, Hyeri Seok, Hee Kyoung Choi, Won Suk Choi, Sungjae Choi, Myung-Hyun Nam, Dong Hun Suh, Jae Gyoon Kim and Dae Won Park
J. Clin. Med. 2025, 14(15), 5415; https://doi.org/10.3390/jcm14155415 - 1 Aug 2025
Viewed by 163
Abstract
Background: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), [...] Read more.
Background: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), and presepsin, in distinguishing septic from non-septic arthritis. Methods: Thirty-one patients undergoing arthrocentesis were included. Patients were categorized into septic and non-septic arthritis groups. Synovial fluid and serum samples were analyzed for five biomarkers. Diagnostic performance was assessed by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Synovial WBC demonstrated the highest diagnostic performance among single biomarkers (AUC = 0.837, p = 0.012). Among novel biomarkers, PTX3 showed the highest accuracy and sensitivity. The serum CRP and synovial WBC combination yielded an AUC of 0.853, with 100% sensitivity, 68.0% specificity, 42.9% PPV, and 100% NPV. Adding all three novel biomarkers to this combination increased the AUC to 0.887 (p = 0.004), maintaining 100% sensitivity and NPV. When individually added, PTX3 achieved 100% sensitivity and NPV, while presepsin showed the highest specificity (96.0%), PPV (75.0%), and accuracy (87.1%). Conclusions: Serum CRP and synovial WBC remain essential biomarkers for diagnosing septic arthritis; however, combining them with PTX3, IL-6, and presepsin improved diagnostic accuracy. PTX3 is best suited for ruling out septic arthritis due to its high sensitivity and NPV, whereas presepsin is more useful for confirmation, given its specificity and PPV. These results support a tailored biomarker approach aligned with diagnostic intent. Full article
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10 pages, 479 KiB  
Article
Evaluation of a Simplified Upper Arm Device for Vacuum-Assisted Collection of Capillary Blood Specimens
by Ulrich Y. Schaff, Bradley B. Collier, Gabriella Iacovetti, Mitchell Peevler, Jason Ragar, Nicolas Tokunaga, Whitney C. Brandon, Matthew R. Chappell, Russell P. Grant and Greg J. Sommer
Diagnostics 2025, 15(15), 1935; https://doi.org/10.3390/diagnostics15151935 - 31 Jul 2025
Viewed by 257
Abstract
Background/Objectives: Conventional blood collection can be challenging in a non-clinical or home-based setting. In response, vacuum-assisted lancing devices for capillary blood collection (typically from the upper arm) have gained popularity to broaden access to diagnostic testing. However, these devices are often costly relative [...] Read more.
Background/Objectives: Conventional blood collection can be challenging in a non-clinical or home-based setting. In response, vacuum-assisted lancing devices for capillary blood collection (typically from the upper arm) have gained popularity to broaden access to diagnostic testing. However, these devices are often costly relative to the reimbursement rate for common laboratory testing panels. This study describes the design and evaluation of Comfort Draw™, a simplified and economical vacuum-assisted capillary blood collection device. Methods: Comfort Draw™ was evaluated by 12 participants in a preliminary study and by 42 participants in a follow-up study. Metrics assessed included the following: vacuum pressure of the device, skin temperature generated by the Comfort Draw prep warmer, blood collection volume, and analytical accuracy (for 19 common serum-based analytes). Results: Acceptable blood volume (>400 µL) and serum volume (>100 µL) were collected by Comfort Draw in 85.5% and 95.1% of cases, respectively. Seventeen of the nineteen analytes examined were within CLIA acceptance limits compared to matched venous samples. Self-reported pain scores associated with Comfort Draw collection averaged 0.39 on a scale from 0 to 10. Conclusions: In this preliminary clinical study, Comfort Draw was found to be a valid and relatively painless method for collecting capillary blood specimens. The device’s simple design and lower cost could enable broader applications compared to more complex alternative capillary blood collection devices. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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24 pages, 624 KiB  
Systematic Review
Integrating Artificial Intelligence into Perinatal Care Pathways: A Scoping Review of Reviews of Applications, Outcomes, and Equity
by Rabie Adel El Arab, Omayma Abdulaziz Al Moosa, Zahraa Albahrani, Israa Alkhalil, Joel Somerville and Fuad Abuadas
Nurs. Rep. 2025, 15(8), 281; https://doi.org/10.3390/nursrep15080281 - 31 Jul 2025
Viewed by 126
Abstract
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping [...] Read more.
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article
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13 pages, 1001 KiB  
Review
Old and New Definitions of Acute Respiratory Distress Syndrome (ARDS): An Overview of Practical Considerations and Clinical Implications
by Cesare Biuzzi, Elena Modica, Noemi De Filippis, Daria Pizzirani, Benedetta Galgani, Agnese Di Chiaro, Daniele Marianello, Federico Franchi, Fabio Silvio Taccone and Sabino Scolletta
Diagnostics 2025, 15(15), 1930; https://doi.org/10.3390/diagnostics15151930 - 31 Jul 2025
Viewed by 274
Abstract
Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early [...] Read more.
Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO2/FiO2 ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article
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36 pages, 1583 KiB  
Review
SARS-CoV-2 Pneumonia: Advances in Diagnosis and Treatment
by Olga Adriana Caliman-Sturdza, Iuliana Soldanescu and Roxana Elena Gheorghita
Microorganisms 2025, 13(8), 1791; https://doi.org/10.3390/microorganisms13081791 - 31 Jul 2025
Viewed by 270
Abstract
The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious [...] Read more.
The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: SARS-CoV-2 and COVID-19)
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10 pages, 1604 KiB  
Article
Anifrolumab Attenuates Follicular Helper T Cell Activation in Patients with Systemic Lupus Erythematosus
by Ádám Diós, Ágnes Gyetvai, Gábor Papp and Tünde Tarr
Int. J. Mol. Sci. 2025, 26(15), 7397; https://doi.org/10.3390/ijms26157397 - 31 Jul 2025
Viewed by 316
Abstract
Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects [...] Read more.
Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects of inhibited type I IFN signaling on circulating follicular helper T subsets (TFH), follicular regulatory T cells (TFR), and B lymphocyte subpopulations, reflecting the ongoing germinal center reactions in SLE patients. Peripheral blood samples were obtained from ten SLE patients before the initiation of anifrolumab treatment, and at months 6 and 12 of the intervention period. Flow cytometry analysis was performed to assess the frequencies of circulating TFH cell subsets, TFR cells, and certain B cell subpopulations. Serological parameters, including autoantibody levels and complement components, were determined as part of the routine diagnostic evaluation. We observed a significant and sustained reduction in the percentage of activated circulating TFH cells. Notably, the frequency of CXCR3CCR6+ TFH17 cells decreased, whereas the proportion of CXCR3+CCR6 TFH1 cells increased significantly. Furthermore, the proportion of the IgDCD27 double-negative B lymphocytes was also significantly reduced. These findings suggest that anifrolumab therapy attenuates TFH cell activation, which may contribute to its clinical efficacy by modulating germinal center responses in SLE. Full article
(This article belongs to the Special Issue Drug Therapy of Systemic Lupus Erythematosus)
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32 pages, 12213 KiB  
Review
Capacitive Sensors for Label-Free Detection in High-Ionic-Strength Bodily Fluids: A Review
by Seerat Sekhon, Richard Bayford and Andreas Demosthenous
Biosensors 2025, 15(8), 491; https://doi.org/10.3390/bios15080491 - 30 Jul 2025
Viewed by 268
Abstract
Capacitive sensors are platforms that enable label-free, real-time detection at low non-perturbing voltages. These sensors do not rely on Faradaic processes, thereby eliminating the need for redox-active species and simplifying system integration for point-of-care diagnostics. However, their sensitivity in high-ionic-strength solutions, such as [...] Read more.
Capacitive sensors are platforms that enable label-free, real-time detection at low non-perturbing voltages. These sensors do not rely on Faradaic processes, thereby eliminating the need for redox-active species and simplifying system integration for point-of-care diagnostics. However, their sensitivity in high-ionic-strength solutions, such as bodily fluids, is limited due to a reduced Debye length and non-specific interactions. The present review highlights advances in material integration, surface modification, and signal enhancement techniques to mitigate the challenges of deploying capacitive sensors in biofluids (sweat, saliva, blood, serum). This work further expands on the promise of such sensors for advancing liquid biopsies and highlights key technical challenges in translating capacitive systems to clinics. Full article
(This article belongs to the Special Issue Novel Designs and Applications for Electrochemical Biosensors)
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5 pages, 628 KiB  
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Infrared Photography: A Novel Diagnostic Approach for Ocular Surface Abnormalities Due to Vitamin A Deficiency
by Hideki Fukuoka and Chie Sotozono
Diagnostics 2025, 15(15), 1910; https://doi.org/10.3390/diagnostics15151910 - 30 Jul 2025
Viewed by 242
Abstract
Vitamin A deficiency (VAD) remains a significant cause of preventable blindness worldwide, with ocular surface changes representing early manifestations that require prompt recognition and treatment. Conventional examination methods are capable of detecting advanced changes; however, subtle conjunctival abnormalities may be overlooked, potentially delaying [...] Read more.
Vitamin A deficiency (VAD) remains a significant cause of preventable blindness worldwide, with ocular surface changes representing early manifestations that require prompt recognition and treatment. Conventional examination methods are capable of detecting advanced changes; however, subtle conjunctival abnormalities may be overlooked, potentially delaying the administration of appropriate interventions. We herein present the case of a 5-year-old Japanese boy with severe VAD due to selective eating patterns. This case demonstrates the utility of infrared photography as a novel diagnostic approach for detecting and monitoring conjunctival surface abnormalities. The patient exhibited symptoms including corneal ulcers, night blindness, and reduced visual acuity. Furthermore, blood tests revealed undetectable levels of vitamin A (5 IU/dL), despite relatively normal physical growth parameters. Conventional slit-lamp examination revealed characteristic sandpaper-like conjunctival changes. However, infrared photography (700–900 nm wavelength) revealed distinct abnormal patterns of conjunctival surface folds and keratinization that were not fully appreciated on a routine examination. Following high-dose vitamin A supplementation (4000 IU/day), complete resolution of ocular abnormalities was achieved within 2 months, with infrared imaging objectively documenting treatment response and normalization of conjunctival surface patterns. This case underscores the potential for severe VAD in developed countries, particularly in the context of dietary restrictions, thereby underscoring the significance of a comprehensive dietary history and a meticulous ocular examination. Infrared photography provides a number of advantages, including the capacity for non-invasive assessment, enhanced visualization of subtle changes, objective monitoring of treatment response, and cost-effectiveness due to the use of readily available equipment. This technique represents an underutilized diagnostic modality with particular promise for screening programs and clinical monitoring of VAD-related ocular manifestations, potentially preventing irreversible visual loss through early detection and intervention. Full article
(This article belongs to the Collection Interesting Images)
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