bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Deletions and Rewiring of the Transcriptome Underlying High Antimonite Resistance in Achromobacter sp. SMAs-55
Authors: Yu Yanshuang , Herzberg Martin , Pat-Espadas Aurora M. , Vinuesa Pablo , Feng Renwei , Rosen Barry , Amachi Seigo , Jia Xianbo , Rensing Christopher , Zhou Shungui
Published: December 2024

Microbes have been shown to adapt to stressful or even lethal conditions through displaying genome plasticity. However, how bacteria utilize the ability of genomic plasticity to deal with high antimony (Sb) stress has remained unclear. In this study, the spontaneous mutant strain SMAs-55 of Achromobacter sp. As-55 was obtained under antimonite (Sb(III)) stress. SMAs-55 displayed significantly increased Sb(III) resistance, but it lost the ability to oxidize arsenite (As(III)) by deleting an entire gene island containing genes encoding functions involved in As(III) oxidation, arsenic (As)/Sb resistance and phosphate transport. This study suggests that genetic plasticity has played an important role in As-55 adaption to Sb(III) stress. Transcriptomic analysis found that genes encoding functions involved in capsule polysaccharide synthesis, as well as functions correlated to stress adaptation, ATP production, and metabolism were more strongly expressed in SMAs-55. In addition, a lower intracellular Sb(III) accumulation in SMAs-55 was observed. These findings indicate that reduced uptake through increased capsule biosynthesis was an effective way for SMAs-55 to adapt to an environment displaying high levels of Sb. This study helps us to better understand the evolutionary processes enabling survival of microbes and microbial community in contaminated environments.
From Molecular to Radionuclide and Pharmacological Aspects in Transthyretin Cardiac Amyloidosis
Authors: Stanciu Silviu Marcel , Jurcut Ruxandra , Dragoi Galrinho Ruxandra , Stefani Constantin , Miricescu Daniela , Rusu Ioana Ruxandra , Prisacariu Georgiana Sabina , Mititelu Raluca
Published: December 2024

Amyloidosis is a rare pathology characterized by protein deposits in various organs and tissues. Cardiac amyloidosis (CA) can be caused by various protein deposits, but transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) are the most frequent pathologies. Protein misfolding can be induced by several factors such as oxidative stress, genetic mutations, aging, chronic inflammation, and neoplastic disorders. In ATTR cardiomyopathy (ATTR-CM), the amyloid fibrils can be found in the myocardium interstitial space and are associated with arrhythmias and heart failure. In pathological situations, the transthyretin (TTR) configuration is destroyed by proteolytic action, leading to monomers that further misfold and aggregate to form the amyloid fibrils. 99mTc-Pyrophosphate (99m-Tc-PYP), 99mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (99m-Tc-DPD) and 99m-Tc hydroxy-methylene-Dyphosphonate (99m-Tc-HMDP) are used to detect myocardium amyloid deposits due to their ability to detect calcium ions that are present in the amyloid fibrils through dystrophic calcification. ATTR-CM therapy acts on different stages of the amyloidogenic process, including liver TTR synthesis, TTR tetramer destabilization, and misfolding of the monomers. The main aim of this narrative review is to present ATTR-CM, starting with molecular changes regarding the protein misfolding process and radionuclide aspects and finishing with pharmacological approaches.
CircTEC Inhibits the Follicular Atresia in Buffalo (Bubalus bubalis) via Targeting miR-144-5p/FZD3 Signaling Axis
Authors: Cheng Juanru , Xing Qinghua , Pan Yu , Yang Yanyan , Zhang Ruimen , Shi Deshun , Deng Yanfei
Published: December 2024

The specific expression profile and function of circular RNA (circRNA) in follicular atresia remain largely unknown. Here, the circRNA expression profiles of granulosa cells derived from healthy follicles (HFs) and antral follicles (AFs) in buffalo were analyzed by RNA-seq, and the mechanism of a differentially expressed circRNA (DEcircRNA) circTEC regulating the granulosa cell function that affects follicular atresia was further explored. RNA-seq results showed that a total of 112 DEcircRNAs were identified. Among them, circTEC was highly expressed in HF, and its circular structure was confirmed by RNase R digestion assay, reversed PCR and Sanger sequencing. Functional experiments demonstrated that circTEC promotes the proliferation and steroid hormone synthesis of buffalo granulosa cells (bGCs), and it also inhibits their apoptosis. In-depth mechanism analysis showed that the expression level of circTEC in bGCs from AFs was adversely related to miR-144-5p and consistent with FZD3. CircTEC acts as an endogenous sponge of miR-144-5p to regulate the expression of the target gene FZD3 in AFs, which promotes the proliferation of bGCs and inhibits bGCs apoptosis, thereby inhibiting follicular atresia in buffalo. In summary, our study revealed the regulatory role of the circTEC/miR-144-5p/FZD3 axis during follicular atresia in buffalo. These results provided new insights into the biological mechanism underlying follicular atresia.
Recent Advances in the Search for Effective Anti-Alzheimer’s Drugs
Authors: Ogos Martyna , Stary Dorota , Bajda Marek
Published: December 2024

Alzheimer’s disease, the most common form of dementia, is characterized by the deposition of amyloid plaques and neurofibrillary tangles in the brain, leading to the loss of neurons and a decline in a person’s memory and cognitive function. As a multifactorial disease, Alzheimer’s involves multiple pathogenic mechanisms, making its treatment particularly challenging. Current drugs approved for the treatment of Alzheimer’s disease only alleviate symptoms but cannot stop the progression. Moreover, these drugs typically target a single pathogenic mechanism, leaving other contributing factors unaddressed. Recent advancements in drug design have led to the development of multi-target-directed ligands (MTDLs), which have gained popularity for their ability to simultaneously target multiple pathogenic mechanisms. This paper focuses on analyzing the activity, mechanism of action, and binding properties of the anti-Alzheimer’s MTDLs developed between 2020 and 2024.
Towards Transparent Diabetes Prediction: Combining AutoML and Explainable AI for Improved Clinical Insights
Authors: Hasan Raza , Dattana Vishal , Mahmood Salman , Hussain Saqib
Published: December 2024

Diabetes is a global health challenge that requires early detection for effective management. This study integrates Automated Machine Learning (AutoML) with Explainable Artificial Intelligence (XAI) to improve diabetes risk prediction and enhance model interpretability for healthcare professionals. Using the Pima Indian Diabetes dataset, we developed an ensemble model with 85.01% accuracy leveraging AutoGluon’s AutoML framework. To address the “black-box” nature of machine learning, we applied XAI techniques, including SHapley Additive exPlanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME), Integrated Gradients (IG), Attention Mechanism (AM), and Counterfactual Analysis (CA), providing both global and patient-specific insights into critical risk factors such as glucose and BMI. These methods enable transparent and actionable predictions, supporting clinical decision-making. An interactive Streamlit application was developed to allow clinicians to explore feature importance and test hypothetical scenarios. Cross-validation confirmed the model’s robust performance across diverse datasets. This study demonstrates the integration of AutoML with XAI as a pathway to achieving accurate, interpretable models that foster transparency and trust while supporting actionable clinical decisions.
Integrated Pest Management of Wireworms in Potatoes: Use of Tolerant Varieties to Implement Damage Prevention
Authors: Lorenzo Furlan , Stefano Bona , Isadora Benvegnù , Valentina Cacitti , Fausto Govoni , Bruno Parisi
Published: December 2024

Wireworms (Agriotes spp., Coleoptera, Elateridae) are a major threat to potatoes, as are the current commercial standards for assessing potato damage. To reduce wireworm impacts on potato crops and comply with IPM legislation, we started research to assess the potential for new Italian 4x-breeding clones to reduce wireworm feeding on daughter tubers. Two sets of trials were carried out over a six-year period (2018–2023): in-field and in semi-natural conditions, with pots used to introduce a set number of reared wireworms. In the field trials, the varieties were planted in 4.8 × 9–12 m plots in a randomized-block layout with at least three replications. The same wireworm damage assessment was used for both sets of trials. The assessment involved counting all the erosions/scars caused by wireworm feeding activity. The prevalent wireworm species studied was Agriotes sordidus. Both sets of trials showed that some 4x-breeding clones were tolerant to wireworm attacks. The percentages of tubers damaged (any symptom) or with at least one ordinary/large hole was up to five times lower than in the commercial varieties. Glycoalkaloids and the caffeic acid content in tubers are considered to be the main cause of lower appetibility to wireworms.
New Insight on the Sublethal Effect of Bt-Cry1Ab in Spodoptera litura (Fabricius): Tissular Distribution of Cry1Ab, Ultrastructural Alterations and the Lysosomal Response
Authors: Wang Yan-Jue , Shen Ya-Qin , Xiao Ying-Dan , Yang Xue , Hao Shao-Peng , Liu Jian-Qiu , Yang Xiao-Xue , Mita Kazuei , Xu Ya-Jing
Published: December 2024

Bt has been applied as a gene source for insect-resistant transgenic crops, which represents efficient control of insect pests. In this study, we evaluated the pesticidal specificity of one Bt maize strain, DBN9936, that expresses Cry1Ab protein in Spodoptera litura larvae. The results showed that this Bt maize is active against the younger larvae while causing a sublethal effect on older larvae. To further assess the biological responses of S. litura under sublethal Cry1Ab exposure, the relative concentrations of Cry1Ab in different tissues of fifth instar larvae were investigated, indicating that Cry1Ab is transported along the gut and out of the body via excretion or into the hemocoel and lead to sequestration by molting. Furthermore, the result of ultrastructural observation in sublethal Cry1Ab-treated midgut, namely an increase in lysosome number, with the lysosomal activity activation simultaneously provides a strong indication that lysosome plays an active role in response to sublethal Cry1Ab exposure.
The Effects of Disturbance on Plant–Pollinator Interactions in the Native Forests of an Oceanic Island (Terceira, Azores)
Authors: Boieiro Mário , Ferreira Mariana , Ceia-Hasse Ana , Esposito Fabiana , Santos Renata , Pozsgai Gabor , Borges Paulo A. V. , Rego Carla
Published: December 2024

The native biodiversity of oceanic islands is threatened by human-driven disturbance and by the growing number of species introductions which often interfere with natural ecological processes. Here, we aim to evaluate the effect of anthropogenic disturbance on plant–pollinator interactions in the native forest communities of an oceanic island (Terceira, Azores, Portugal). We found that native species predominated in preserved sites compared to disturbed ones and that the extant plant–pollinator interactions were mostly dominated by generalist species. Dipterans, particularly hoverflies, emerged as the primary flower visitors, while introduced hymenopterans (Apis mellifera and Bombus terrestris) and native beetles were locally important, respectively, in disturbed and preserved sites. Human-driven disturbance seems to be responsible for the observed differences in flower abundance and species composition between sites and to drive changes in specific network metrics (namely nestedness, interaction strength asymmetry, and specialization), particularly in one of the study areas. Our findings also suggest that native generalist species provide ecological opportunities that can facilitate the establishment of introduced species through their broad interaction networks.
Honey Robbing: Causes, Impacts and Preventive Measures
Authors: Wang Xinyu , Huang Ting , Ji Quanzhi , Guo Jun , Zhao Yazhou
Published: December 2024

Honey robbing, which typically occurs during times of food scarcity, is a perilous foraging strategy for bee colonies and presents a formidable challenge in the realm of beekeeping. This article provides a comprehensive and multifaceted exploration of honey robbing, including the morphology, behavioral traits, timing, and scope of this phenomenon. This exploration elucidates the specific manifestations of honey robbing, offering readers a deeper understanding of its various facets. Next, this article investigates the root causes of honey robbing by examining both abiotic and biotic factors. The resulting harms are outlined, and corresponding preventive and control measures are suggested. Finally, the article succinctly summarizes the current obstacles in research related to honey robbing and outlines promising avenues for future exploration. The objective of this study was to elucidate the occurrence mechanism of honey robbing, ultimately aiming to contribute to the sustainable growth of the beekeeping industry.
Platelets, Biomarkers of Coagulation and Fibrinolysis, and Early Coronary Stent Thrombosis
Authors: Galli Lukas , Sator Alexander , Schauer Stephanie , Bräu Konstantin , Bernhard Johannes , Hengstenberg Christian , Gangl Clemens , Hemetsberger Rayyan , Roth Christian , Berger Rudolf , Krychtiuk Konstantin A. , Speidl Walter S.
Published: December 2024

Background/Objectives: Acute stent thrombosis (ST) is a rare yet severe complication following percutaneous coronary intervention (PCI). Herein, we investigated the possible association between routinely available coagulation and fibrinolysis markers with early ST. Methods: Within a single-center registry, we investigated the association between the preprocedural platelet count, plasma levels of fibrinogen and D-Dimer, and the incidence of early ST in the first 30 days after PCI. Results: Out of 10,714 consecutive patients who underwent PCI using drug-eluting stents (DESs), the preprocedural platelet count, fibrinogen, and D-Dimer measurements were available in 6337, 6155, and 956 patients, respectively. Fifty-eight patients (0.92%) experienced an early ST within 30 days after PCI. Compared with those without ST, patients with early ST showed significantly elevated preprocedural platelet counts (p < 0.05) and fibrinogen levels (p < 0.05). D-Dimer levels were not associated with early ST. Patients in the fifth quintile of platelet count had a significantly increased risk for early ST (HR 2.43; 95% CI 1.43–4.14; p = 0.001) compared with patients in the lower four quintiles. In addition, patients in the fifth quintile of fibrinogen also had a significantly increased risk for early ST (HR 1.86; 95% CI 1.07–3.26; p < 0.05) compared with patients in the lower four quintiles. These associations were independent of clinical risk factors, the number of stents, the presence of acute coronary syndromes, and white blood cell count. Conclusions: Preprocedural platelet counts and fibrinogen plasma levels can identify patients at elevated risk of early ST after implantation of DESs in addition to procedure-level and device-related risk factors.
Beyond Longer Intervals: Advocating for Regular Treatment of Neovascular AMD
Authors: Gilligan Alexandra K. , Ramsey David J.
Published: December 2024

Personalizing the management of neovascular age-related macular degeneration (nAMD) poses significant challenges for practicing retina specialists and their patients. This commentary addresses some of these complexities, particularly those that arise in the context of an expanding array of intravitreal agents targeting vascular endothelial growth factor (VEGF) and related retinal disease targets. Many of these newer agents approved by the Food and Drug Administration (FDA) for the treatment of nAMD have labeling that indicates that they can provide non-inferior visual outcomes when compared head-to-head with previously available treatments and can be used at significantly extended dosing intervals in some patients. It can be difficult to know if patients should be transitioned to these agents, especially those who are doing well on existing therapies. Although offering extended intervals may be appropriate for some patients with excellent disease control, retina specialists know that undertreatment risks the loss of visual acuity (VA). It can also be challenging for clinicians to interpret the results delivered by clinical trial treatment protocols compared with what is likely to occur in real-world office settings. Many retina specialists use less liberal treatment paradigms than employed in clinical study protocols and consequently many patients experience shorter injection intervals. Since VA is most closely linked to quality of life, it should be prioritized compared with other endpoints. The authors advocate for maintaining consistent treatment schedules dictated by disease control instead of switching therapies even in the presence of small amounts of macular fluid that may occur with longer injection intervals.
Medical Costs and Economic Impact of Hyperkalemia in a Cohort of Heart Failure Patients with Reduced Ejection Fraction
Authors: López-López Andrea , Regueiro-Abel Margarita , Paredes-Galán Emilio , Johk-Casas Charigan Abou , Vieitez-Flórez José María , Elices-Teja Juliana , Armesto-Rivas Jorge , Franco-Gutiérrez Raúl , Ríos-Vázquez Ramón , González-Juanatey Carlos
Published: December 2024

Background/Objectives: Hyperkalemia is a common electrolyte disorder in patients with heart failure and reduced ejection fraction (HFrEF). Renin-angiotensin-aldosterone system inhibitors (RAASi) have been shown to improve survival and decrease hospitalization rates, although they may increase the serum potassium levels. Hyperkalemia has significant clinical and economic implications, and is associated with increased healthcare resource utilization. The objective of the study was to analyze the management of hyperkalemia and the associated medical costs in a cohort of patients with HFrEF. Methods: An observational, longitudinal, retrospective, single-center retrospective study was conducted in patients with HFrEF who started follow-up in a heart failure unit between 2010 and 2021. Results: The study population consisted of 1181 patients followed-up on for 64.6 ± 38.8 months. During follow-up, 11,059 control visits were conducted, documenting 438 episodes of hyperkalemia in 262 patients (22.2%). Of the hyperkalemia episodes, 3.0% required assistance in the Emergency Department, 1.4% required hospitalization, and only 0.2% required admission to the Intensive Care Unit. No episode required renal replacement therapy. Reduction or withdrawal of RAASi was necessary in 69.9% of the hyperkalemia episodes. The total cost of the 438 hyperkalemia episodes was €89,178.82; the expense during the first year accounted for 48.8% of the total cost. Conclusions: Hyperkalemia is frequent in patients with HFrEF. It is often accompanied by a modification of treatment with RAASi. Hyperkalemia generates substantial costs in terms of healthcare resources and medical care, especially during the first year.
Modelling Intra-Sinus Fluid Movements and Drainage Through Computational Fluid Dynamics Before and After Maxillary Sinus Augmentation: A Simulation-Based Pilot Study
Authors: Güldiken Sarıkaya İpek Necla , Tekin Alperen , Suda Fatih , Çukurova Yilmaz Zeynep Gülen , Özcan Mutlu
Published: December 2024

Objectives: Sinus lifting, a procedure to augment bone in the maxilla, may cause complications such as sinusitis due to impaired drainage. This study aimed to assess how sinus lifting impacts airflow in the sinus cavity, which is essential for patients undergoing dental implants. Using computational fluid dynamics (CFD), this research analyzed airflow changes after sinus floor elevation, offering insights into the aerodynamic consequences of the procedure. Methods: Digital modeling and CFD analysis were performed using patient cone-beam computed tomography data. Three different sinus elevation scenarios, each with varying implant heights, were simulated. Airflow simulations were conducted to assess how reshaping the sinus cavity affects aerodynamics and airflow dynamics. Nasal resistance, calculated through pressure drops and flow rates, and wall shear stress, indicating potential mucosal damage, were evaluated. Results: Although some airflow changes occurred post-surgery, the implants primarily affected the front and rear of the elevated area, with little impact being seen on air entry points. Conclusions: Maxillary sinus lifting for dental implant placement may impair sinus drainage, especially at higher elevations, increasing the risk of mucosal damage due to intensified airflows in the reduced sinus volume. A more uniform, simplified intra-sinus structure may enhance fluid dynamics and reduce complications.
Assessment of Iron Metabolism and Inflammation in Children with Cerebral Palsy
Authors: Orhan Ozhan , Gokdemir Gul Sahika
Published: December 2024

Background/Objectives: Cerebral palsy (CP) is a motor disorder resulting from brain damage that is common in childhood. Iron is vital for the body’s basic functions. Iron metabolism disorders and inflammation contribute to the neurological complications seen in CP. The purpose of this research was to ascertain the association and correlation between markers of inflammation and iron metabolism in children with CP. Methods: A total of 181 children diagnosed with CP and 111 typically developing children were retrospectively included in the study. Demographic data, blood parameters, C-reactive protein, iron, total iron binding capacity, and inflammation markers were evaluated. Results: C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immuno-inflammatory index (SII) levels of CP children were found to be statistically significantly higher than those of control group children (p < 0.05). Iron (Fe) and ferritin levels were lower in the CP group, while total iron binding capacity (TIBC) was higher. Spearman correlation analysis showed significant correlations between iron, ferritin and TIBC and SII. Conclusions: Iron deficiency and chronic inflammation are associated with the pathophysiology of CP in patients with CP, and therefore it is important to monitor markers of iron metabolism and inflammation in these patients.
Impact of BRAF and MEK Inhibitors on Gingival Hyperplasia in Melanoma Patients—A Case Report
Authors: Veljovic Tanja , Djuric Milanko , Gusic Ivana , Vuckovic Nada , Ramic Bojana , Mirnic Jelena
Published: December 2024

Background: Although BRAF inhibitors, such as vemurafenib, produce a marked response in patients with advanced melanoma with a BRAF V600 mutation, they eventually develop resistance to this treatment. To address this issue, vemurafenib is increasingly combined with the MEK inhibitor cobimetinib, leading to improved response rates and enhanced survival. However, this treatment modality is associated with numerous side effects. We present a case of gingival hyperplasia in a patient treated with vemurafenib, along with the strategy adopted for the management of this condition, and the impact of subsequent cobimetinib administration on its severity. Methods: The 59-year-old male patient in the focus of this report presented at the Department of Periodontology at the Medical Faculty, University of Novi Sad, in 2019, complaining of gingival overgrowth and bleeding. The patient reported persistent gum swelling during the preceding six months, which he ascribed to the use of vemurafenib, 960 mg twice daily, since 2018, when this medication was prescribed as a part of malignant melanoma treatment. Detailed clinical examination revealed significant gingival overgrowth around all present teeth, affecting the vestibular as well as the oral sides. The patient underwent thorough scaling and root planing, followed by the surgical removal of hyperplastic gingiva. After gingivectomy, the patient was scheduled for follow-up visits at one-month intervals. Six months after gingivectomy, vemurafenib dose was reduced to 720 mg twice daily, and cobimetinib was introduced at 60 mg per day. Results: The treatment protocol adopted in this study, combined with cobimetinib administration, stabilized the gingiva condition in this patient. However, due to his overall poor oral hygiene, gingiva remained inflamed and edematous, but was no longer hyperplastic and hyperkeratotic in appearance. Conclusions: This case underscores the importance of recognizing and adequately addressing this complication, as its adverse effect on a patient’s quality of life can potentially compromise treatment protocol adherence.
Deferred Lateral Margin Control in the Surgical Treatment of Genital Paget’s Disease and Lentiginous Vulvar Melanoma
Authors: Redondo Pedro
Published: December 2024

Background/Objectives: Some skin tumors can extend beyond their clinical appearance. This presents an additional challenge, especially when the affected area is the genital region, which is more difficult for both the patient and the physician to access and monitor due to its location and anatomical characteristics. The treatment of these lesions is complex, and literature postulates Mohs surgery as the best therapeutic option. Methods: We describe our experience in two patients with the resection of vulvar lentiginous melanoma and genital extramammary Paget’s disease, using a method of deferred lateral margin control in the surgical treatment. Results: The “spaghetti technique”(ST) initially removing a small strip from all lateral margins of the lesion, which is then closed directly while awaiting the paraffin histological result. In a second stage, the tumors within those margins are removed, and immediate reconstruction is performed. The final oncological and functional result was satisfactory, with no notable side effects. Conclusions: This method is suited for large, poorly defined superficial tumors in the genital, perineal, and perianal regions, where a frozen section study would be slow and burdensome for the patient and surgeon. The ST preserves healthy tissue and can be performed by any surgeon and pathologist without additional training, and is more comfortable for patients, avoiding prolonged open wounds during multiple steps of tumor excision.
Assessing Malignant Risk in B3 Breast Lesions: Clinical Insights and Implications
Authors: D’Archi Sabatino , Carnassale Beatrice , Accetta Cristina , Belli Paolo , De Lauretis Flavia , Di Guglielmo Enrico , Di Leone Alba , Franco Antonio , Gambaro Elisabetta , Magno Stefano , Moschella Francesca , Natale Maria , Sanchez Alejandro Martin , Scardina Lorenzo , Silenzi Marta , Masetti Riccardo , Franceschini Gianluca
Published: December 2024

Background/Objectives: B3 breast lesions, characterized by uncertain malignant potential, pose a significant challenge for clinicians. With the increasing use of preoperative biopsies, there is a need for careful management strategies, including watchful waiting, vacuum-assisted excision (VAE), and surgery. This study aims to assess the concordance between preoperative biopsy findings and postoperative histology, with a focus on evaluating the positive predictive value (PPV) for malignancy in B3 lesions. Methods: Over a seven-year period, 305 patients preoperatively diagnosed with B3 lesions were treated at the Multidisciplinary Breast Center of “Fondazione Policlinico Universitario Agostino Gemelli IRCCS” in Rome. All cases were reviewed at multidisciplinary meetings involving surgeons, radiologists, histopathologists, and oncologists. Preoperative diagnoses were obtained by ultrasound-guided core needle biopsies (CNBs) or stereotactic-guided vacuum-assisted biopsies (VABs). The radiological features were assessed using the Breast Imaging Reporting and Data System (BIRADS), and discrepancies between radiological and pathological findings were recorded. The biopsy results were compared with the postoperative histological findings to calculate the PPV for malignancy. Results: Of the 305 B3 lesions biopsied, 242 were confirmed as B3 on the final histological examination, resulting in a concordance rate of 79.3%. A total of 63 cases were upgraded to malignancy on postoperative histology, yielding a cumulative upgrade rate of 20.7%. The PPV for malignancy was 31.5% for atypical ductal hyperplasia (ADH), 27.6% for lobular neoplasia (LN), 22.9% for papillary lesions (PLs), 12.1% for flat epithelial atypia (FEA), 10.4% for radial scar (RS), and 10.3% for phyllodes tumors (PTs). Conclusions: Our findings demonstrate that the cumulative PPV for B3 lesions, as well as the PPV for each subtype, are consistent with the existing literature. The factors influencing the PPV include the use of CNB versus VAB, discordance between the BIRADS and biopsy results, the presence of atypia in the biopsy sample, the presence of microcalcifications on mammography, mass lesions identified on MRI, and the extent of the lesion. These factors should be considered in the personalized management of B3 lesions, potentially leading to more targeted and less invasive approaches in the future.
Hormonal Function of Undescended Testes Before Orchidopexy in Prepubertal Boys
Authors: Walczak-Jędrzejowska Renata , Niedzielski Jerzy , Slowikowska-Hilczer Jolanta , Nowak Maciej , Marchlewska Katarzyna
Published: December 2024

Background/Objectives: The hormonal aspect of undescended testes (UDTs) in prepubertal boys, i.e., after mini-puberty, is poorly understood. The aim of this study was to evaluate the hormonal function of UDTs before orchidopexy in prepubertal boys and its correlation with testicular parameters. Methods: The study included 90 prepubertal boys (0.9–8.8 years) with UDTs and 57 age-matched boys with testes in the scrotum (control). The testicular volume (TV), testicular atrophy index (TAI), and testicular growth potential (TGP) of the UDTs were assessed before orchidopexy and 18–24 months after. The analysis included FSH, LH, T, DHT, E2, Inh B, INSL3, and AMH levels. Results: The UDT group demonstrated a significantly higher FSH level and lower Inh B/FSH ratio than controls. Boys with UDTs aged under six years exhibited significantly higher FSH and LH levels and lower Inh B/FSH and T/LH ratios. The TV level of descended and undescended testes, both before and after surgery, was significantly positively related to T and DHT levels, but negatively with Inh B, INSL3 levels, Inh B/AMH, and Inh B/FSH. Conclusions: Hormonal evaluation of the hypothalamus–pituitary–testicular axis and Sertoli and Leydig cell function in prepubertal boys (after mini-puberty) may predict the further development and function of UDTs and may serve as a diagnostic tool in testicular descent disorder.
The Value of Body Plethysmography (sGaw) in the Assessment of Airway Hyperreactivity in Cough Variant Asthma
Authors: Karamarkovic Lazarusic Natasa , Popovic-Grle Sanja , Tolic Ena , Stajduhar Anamarija , Bozinovic Renata , Pavlisa Gordana
Published: December 2024

Background/Objectives: Cough variant asthma (CVA) is characterized by nonspecific symptoms and normal spirometric values, which makes diagnosis challenging. To diagnose CVA it is necessary to document airway hyperreactivity (AHR). The aim of our study was to evaluate the diagnostic value of body plethysmography in the assessment of AHR using the methacholine challenge test (MCT). Methods: In CVA-suspected patients, a bronchodilation test (BDT), an MCT with spirometry, and body plethysmography were performed. The MCT was considered positive if there was a 20% decrease in forced expiratory volume in 1 s from the baseline value (PC20FEV1) or a 40% reduction in specific conductance (PC40sGaw) after inhaling methacholine of concentration < 8 mg/mL. Sensitivity and specificity were generated for different cut off points of sGaw (PC40sGaw, PC45sGaw, PC50sGaw). Anti-asthma treatment was started for those with proven AHR. The diagnosis of asthma was made after one year of follow-up based on the response to treatment. Results: AHR was diagnosed in 83.5% (91/109) of patients by either a BDT, PC20FEV1, or PC40sGaw. After one year of follow-up, asthma was confirmed in 76 patients. The sensitivities of the BDT, PC20FEV1, and PC40sGaw were 25%, 64%, and 97%, respectively. The specificities of the BDT, PC20FEV1 and PC40sGaw were 94%, 88%, and 67%, respectively. The sensitivities for a PC45sGaw and PC50sGaw were 88% and 63%, and the specificities were 82% and 91%, respectively. Conclusions: Body plethysmography is a valuable tool in the assessment of AHR in CVA, with the best sensitivity-to-specificity ratio found at a PC45sGaw.
Cangrelor in Patients Undergoing Percutaneous Coronary Intervention After Out-of-Hospital Cardiac Arrest
Authors: Ferlini Marco , Raone Luca , Bendotti Sara , Currao Alessia , Primi Roberto , Bongiorno Andrea , Fava Cristian , Dall’Oglio Laura , Adamo Marianna , Ghiraldin Daniele , Marino Marcello , Dossena Cinzia , Baldo Andrea , Maffeo Diego , Kajana Vilma , Affinito Silvia , Baldi Enrico , De Luca Leonardo , Savastano Simone
Published: December 2024

Background: Cangrelor provides rapid platelet inhibition, making it a potential option for out-of-hospital cardiac arrest (OHCA) survivors undergoing percutaneous coronary intervention (PCI). However, clinical data on its use after OHCA are limited. This study investigates in-hospital outcomes of cangrelor use in this population. Methods: We conducted a prospective, observational study involving OHCA patients from the Lombardia CARe Registry (January 2015–December 2022) who underwent PCI in seven centers in Northern Italy. Propensity score (PS) matching compared patients who received cangrelor to those who did not. Logistic regression tested associations between cangrelor and discharge outcomes. Results: Of 612 OHCA patients admitted, 414 (67.4%) underwent PCI with known antithrombotic therapy, of whom 34 (8.2%) received cangrelor. Radial access was more common in the cangrelor group, which also had a higher troponin peak and a final TIMI flow grade of 3. Survival at discharge was 82.4% in the cangrelor group, compared to 65.3% in the no-cangrelor group (p = 0.043). Univariable logistic regression showed that cangrelor use was associated with higher survival at discharge (OR 2.5; 95% CI: 1.1–6.1, p = 0.049). After multiple PS matchings, cangrelor remained associated with better survival (OR 2.07; 95% CI: 1.16–2.98). Major bleeding rates were higher in the cangrelor group, even after adjusting for baseline bleeding risk (OR: 7.0; 95% CI: 2.9–17.0; p < 0.001). Conclusions: In OHCA patients undergoing PCI, cangrelor use was linked to improved in-hospital survival but higher major bleeding, suggesting a potential net clinical benefit.
Echocardiography in the Ventilated Patient: What the Clinician Has to Know
Authors: Delle Femine Fiorella Chiara , D’Arienzo Diego , Liccardo Biagio , Pastore Maria Concetta , Ilardi Federica , Mandoli Giulia Elena , Sperlongano Simona , Malagoli Alessandro , Lisi Matteo , Benfari Giovanni , Russo Vincenzo , Cameli Matteo , D’Andrea Antonello
Published: December 2024

Heart and lung sharing the same anatomical space are influenced by each other. Spontaneous breathing induces dynamic changes in intrathoracic pressure, impacting cardiac function, particularly the right ventricle. In intensive care units (ICU), mechanical ventilation (MV) and therefore positive end-expiratory pressure (PEEP) are often applied, and this inevitably influences cardiac function. In ventilated patients, the use of positive pressures leads to an increase in intrathoracic pressure and, consequently, to a reduction in the right ventricular preload and thus cardiac output. The clinician working in the intensive care unit must be able to assess the effects MV has on the heart in order to set it up appropriately and to manage any complications. The echocardiographic evaluation of the ventilated patient has the main purpose of studying the right ventricle; in fact, they are the ones most affected by PEEP. It is therefore necessary to assess the size, thickness, and systolic function of the right ventricle. In the mechanically ventilated patient, it may be difficult to assess the volemic status and fluid responsiveness, in fact, the study of the inferior vena cava (IVC) is not always reliable in these patients. In patients with MV, it is preferable to assess fluid responsiveness with dynamic methods such as the end-expiration occlusion (EEO) test, passive leg raise (PLR), and fluid challenge (FC). The study of the diaphragm is also essential to identify possible complications, manage weaning, and provide important prognostic information. This review describes the basis for echocardiographic evaluation of the mechanically ventilated patient with the aim of supporting the clinician in managing the consequences of MV for heart–lung interaction.
Local Recurrence of Premalignant and Early Malignant Rectal Polyps Treated by TEM—A Single-Center Experience
Authors: Khalifa Muhammad , Gingold-Belfer Rachel , Issa Nidal
Published: December 2024

Background: Transanal endoscopic microsurgery (TEM) is a minimally invasive approach for excising rectal polyps, particularly those with high-grade dysplasia (HGD) or early-stage rectal cancer (T1). This study aimed to evaluate the recurrence risk and its associated factors in patients treated with TEM for HGD and T1 rectal tumors. Methods: A retrospective review was conducted on 79 patients who underwent TEM for rectal lesions at Rabin Medical Center-Hasharon Hospital from 2005 to 2019. Data collected included demographics, tumor characteristics, and follow-up outcomes, with specific focus on tumor size, resection margins, mucin production, and distance from anal verge (AV). Separate and unified analyses were performed to assess the recurrence risk factors for both HGD and T1 patients. Results: Sixty-three patients were included in the final analysis. In the unified analysis, larger tumor size was significantly associated with increased recurrence risk (OR = 2.27, p = 0.028), and mucin production was a strong predictor of recurrence in the T1 group and combined analysis (p = 0.0012 and p = 0.014, respectively). Distance from AV demonstrated a borderline association with recurrence (p = 0.053). Conclusions: Larger tumor size and mucin production are significant predictors of recurrence in TEM-treated rectal polyps. Personalized follow-up and postoperative management are essential for patients with these risk factors to reduce the recurrence risk.
Refining Stroke Risk Assessment in Patients with Device-Detected Atrial Fibrillation
Authors: Sjøholm-Christensen Andreas , Tojaga Nedim , Brandes Axel
Published: December 2024

Clinical atrial fibrillation (AF) is a well-established major risk factor for stroke and systemic embolism. Pivotal trials have shown that treatment with oral anticoagulation reduces the risk of stroke and systemic embolism in clinical AF with a simultaneous increase in the risk of major bleeding. To help balance the risk of stroke and bleeding in clinical AF, different prediction models including biomarkers and clinical features have been validated. Device-detected AF (DDAF) is also associated with an increased risk of stroke and systemic embolism, but not to the same extent as clinical AF. Two large randomised studies have found significant stroke risk reduction with direct oral anticoagulation in DDAF patients, yet also a significantly increased risk of major bleeding. To date, the question remains how to balance the thromboembolic risk reduction with oral anticoagulation and the increased risk of bleeding in patients with DDAF and to identify the right patients who may benefit from oral anticoagulant treatment.
Calcified Amorphous Tumor and Granulomatosis with Polyangiitis—Case Report and Systematic Review of the Literature
Authors: Suleiman Mathieu N. , Agaimy Abbas , Dewald Oliver , Kaemmerer-Suleiman Ann-Sophie , Mellert Fritz , Weyand Michael , Harig Frank
Published: December 2024

Background: Calcified amorphous tumor (CAT) is a rare, mostly incidental tumor-like cardiac lesion of unknown histogenesis. Current imaging modalities do not differentiate between CAT and other masses. As it can be a source for embolization, surgical excision of CAT is mandatory. CAT in patients with Granulomatosis with polyangiitis (GPA) is exceedingly rare. Methods: This systematic literature review was prompted by the case of a CAT in a patient with GPA. The search of all types of studies in two databases (PubMed and Scopus) was conducted through November 2024 to identify the relevant studies. Results: Nine studies were included describing cases of patients being diagnosed with GPA and a cardiac mass. All included patients had a histopathological examination of the either biopsied or surgically resected mass. Only one case reported a CAT. In our case, the patient was diagnosed with GPA through a kidney biopsy, whereas a cardiac mass in the right atrium was diagnosed by echocardiography during evaluation for possible kidney transplantation. One year later a progression was observed, and the mass was resected. The histopathological examination revealed a CAT. The patient could be successfully discharged in a good clinical condition. Conclusions: This systematic literature search and case report highlight the importance of regular echocardiographic examination in patients with GPA. Moreover, surgical excision is crucial for the diagnosis and for further therapy planning, regardless of whether the mass is neoplastic or not.
Absorbable Powder Haemostat Use in Minimally Invasive Thoracic Surgery
Authors: Ricciardi Sara , Patel Akshay Jatin , Alunni Fegatelli Danilo , Volpi Sara , Femia Federico , Petrella Lea , Bille Andrea , Cardillo Giuseppe
Published: December 2024

Background: Significant intraoperative and postoperative blood loss are rare but possibly life-threatening complications after lung resection surgery either during open or minimally invasive procedures. Microporous Polysaccharide Haemospheres (ARISTA™AH) have demonstrated time-efficient haemostasis, lower postoperative blood volumes and a lower blood transfusion requirement, without any identified adverse events across other specialities. The primary aim of our study was to evaluate the impact of ARISTA™AH on short-term postoperative outcomes in thoracic surgery. Our secondary aim was to compare ARISTA™AH with other commonly used haemostatic agents. Methods: We retrospectively reviewed a prospectively collected database of consecutive early-stage lung cancer patients surgically treated in two European centres (October 2020–December 2022). Exclusion criteria included open surgery, patients with coagulopathy/anticoagulant medication, major intraoperative bleeding, non-anatomical lung resection and age <18 years. The cohort was divided into five groups according to the haemostatic agent that was used. Propensity score matching was used to estimate the effect of ARISTA™AH on various intra- and postoperative parameters (continuous and binary outcome modelling). Results: A total of 482 patients (M/F:223/259; VATS 97/RATS 385) with a mean age of 68.9 (±10.6) years were analysed. In 253 cases, ARISTA™AH was intraoperatively used to control bleeding. This cohort of patients had a significant reduction in total drain volume by 135 mls (standard error 53.9; p = 0.012). The use of ARISTA™AH did reduce the average length of a hospital stay (−1.47 days) and the duration of chest drainage (−0.596 days), albeit not significantly. In the ARISTA™AH group, we observed no postoperative bleeding, no blood transfusion requirement, no 30-day mortality and no requirement for redo surgery. The use of ARISTA™AH significantly reduced the odds of postoperative complications, as well as the need for transfusion and redo surgery. Conclusions: Our data showed that Microporous Polysaccharide Haemospheres are a safe and effective haemostatic device. Their use has a positive effect on the short-term postoperative outcomes of patients surgically treated for early-stage lung cancer.
Could Pulsed Wave Tissue Doppler Imaging Solve the Diagnostic Dilemma of Right Atrial Masses and Pseudomasses? A Case Series and Literature Review
Authors: Sonaglioni Andrea , Nicolosi Gian Luigi , Muti-Schünemann Giovanna Elsa Ute , Lombardo Michele , Muti Paola
Published: December 2024

Even if rarely detected, right atrial (RA) masses represent a diagnostic challenge due to their heterogeneous presentation. Para-physiological RA structures, such as a prominent Eustachian valve, Chiari’s network, and lipomatous atrial hypertrophy, may easily be misinterpreted as pathological RA masses, including thrombi, myxomas, and vegetations. Each pathological mass should always be correlated with adequate clinical, anamnestic, and laboratory data. However, the differential diagnosis between pathological RA masses may be challenging due to common constitutional symptoms, as in the case of vegetations and myxoma, which present with fever and analogous complications such as systemic embolism. The implementation of transthoracic echocardiography (TTE) with pulsed wave (PW) tissue Doppler imaging (TDI) may improve the visualization and differentiation of intracardiac masses through different color coding of the pathological structure compared to surrounding tissue. More remarkably, PW-TDI can provide a detailed assessment of the specific pattern of motion of each intracardiac mass, with important clinical implications. Specifically, a TDI-derived pattern of incoherent motion is typical of right-sided thrombi, myxomas, and vegetations, whereas right-sided pseudomasses are generally associated with a TDI pattern of concordant motion synchronous with the cardiac cycle. An increased TDI-derived mass peak antegrade velocity may represent an innovative marker of the embolic potential of mobile right-sided pathological masses. During the last two decades, only a few authors have used TTE implemented with PW-TDI for the characterization of intra-cardiac masses’ morphology and mobility. Herein, we report two clinical cases of totally different right-sided cardiac masses diagnosed using a multimodality imaging approach, including PW-TDI, followed at our institution. The prevalence and physiopathological characteristics of the most relevant RA masses and pseudomasses encountered in clinical practice are described in the present narrative review. In addition, we will discuss the principal clinical applications of PW-TDI and its potential value in improving the differential diagnosis of pathological and para-physiological right-sided cardiac masses.
The Crooked Nose—Surgical Algorithm in Post-Traumatic Patient—Evaluation of Surgical Sequence
Authors: Jadczak Marcin , Krzywdzińska Sandra , Rozbicki Paweł , Jurkiewicz Dariusz
Published: December 2024

Background: A crooked nose is a challenge for a surgeon performing rhinoplasty. When performed correctly, rhinoseptoplasty aligns the nasal framework, restores nasal patency, and achieves facial symmetry. The key to this procedure is to dissect all the structures of the nasal framework, mobilize, reposition, and stabilize them. Aim: This study aims to discuss the quality of life after the rhinoseptoplasty and principles of treating a post-traumatic crooked nose with a view to improving the predictability and reliability of rhinoplasty procedures involving this challenging problem. Methods: The study compared the results of the Rhinoplasty Outcome Evaluation (ROE) and the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) through statistical analysis. Results: Considering the structural deformities that lead to a crooked nose, the open approach seems to be preferred during a rhinoseptoplasty of a post-traumatic, crooked nose. When reconstructing the nasal septum, it is always necessary to leave the required amount of cartilage to provide nasal support and to secure the septum to the nasal spine. Osteotomies are important for fixing a crooked nose. The preoperative values for ROE were significantly lower before surgery than after surgery (8.7 vs. 20.2), while for SCHNOS, the postoperative values were statistically significantly lower compared to the preoperative values (46.0 vs. 9.1). Conclusions: Properly planned and performed surgery improves the functional and aesthetic outcomes in patients after rhinoseptoplasty.