bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Advanced Therapies for Primary Biliary Cholangitis: Insights from the Gut Microbiota–Bile Acid–Immunity Network
Authors: Guo Ziqi , He Kun , Pang Ke , Yang Daiyu , Lyu Chengzhen , Xu Haifeng , Wu Dong
Published: April 2024

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the effectiveness of conventional immunosuppressive therapy is disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut–liver axis emphasizes the interconnection between the gut and the liver, and evidence is increasing that gut microbiota and bile acids play an important role in the pathogenesis of cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Autoimmune cholangitis has the potential to be improved through immune system modulation. Considering the failure of conventional immunotherapies and the involvement of gut microbiota and bile acids in the pathogenesis, targeting immune factors associated with them, such as bile acid receptors, microbial-derived molecules, and related specific immune cells, may offer breakthroughs. Understanding the gut microbiota–bile acid network and related immune dysfunctions in PBC provides a new perspective on therapeutic strategies. Therefore, we summarize the latest advances in research of gut microbiota and bile acids in PBC and, for the first time, explore the possibility of related immune factors as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.
Shigella Vaccines: The Continuing Unmet Challenge
Authors: Lu Ti , Das Sayan , Howlader Debaki R. , Picking William D. , Picking Wendy L.
Published: April 2024

Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality in low-income regions; however, it is not confined to these regions and occurs in high-income nations when conditions allow. The ill effects of shigellosis are at their highest in children ages 2 to 5, with survivors often exhibiting impaired growth due to infection-induced malnutrition. The escalating threat of antibiotic resistance further amplifies shigellosis as a serious public health concern. This review explores Shigella pathology, with a primary focus on the status of Shigella vaccine candidates. These candidates include killed whole-cells, live attenuated organisms, LPS-based, and subunit vaccines. The strengths and weaknesses of each vaccination strategy are considered. The discussion includes potential Shigella immunogens, such as LPS, conserved T3SS proteins, outer membrane proteins, diverse animal models used in Shigella vaccine research, and innovative vaccine development approaches. Additionally, this review addresses ongoing challenges that necessitate action toward advancing effective Shigella prevention and control measures.
Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease
Authors: Saponjic Jasna , Mejías Rebeca , Nikolovski Neda , Dragic Milorad , Canak Asuman , Papoutsopoulou Stamatia , Gürsoy-Özdemir Yasemin , Fladmark Kari E. , Ntavaroukas Panagiotis , Bayar Muluk Nuray , Zeljkovic Jovanovic Milica , Fontán-Lozano Ángela , Comi Cristoforo , Marino Franca
Published: April 2024

Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results.
Ischemia–Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets
Authors: Lasorsa Francesco , Rutigliano Monica , Milella Martina , d’Amati Antonio , Crocetto Felice , Pandolfo Savio Domenico , Barone Biagio , Ferro Matteo , Spilotros Marco , Battaglia Michele , Ditonno Pasquale , Lucarelli Giuseppe
Published: April 2024

Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia–reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia–reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process.
H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma
Authors: Tinca Andreea Cătălina , Szoke Andreea Raluca , Lazar Bianca Andreea , Szász Emőke Andrea , Tomuț Alexandru Nicușor , Sabău Adrian Horațiu , Cocuz Iuliu-Gabriel , Cotoi Titiana-Cornelia , Niculescu Raluca , Chiorean Diana Maria , Ungureanu Ioana Ancuța , Turdean Sabin Gligore , Cotoi Ovidiu Simion
Published: April 2024

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.
Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review
Authors: Feier Catalin , Vonica Razvan , Faur Alaviana , Streinu Diana , Muntean Calin
Published: April 2024

The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates of up to 20 million prescriptions per year in the US until 2035. This systematic review aims to assess the incidence of thyroid cancer and detail the spectrum of adverse events associated with semaglutide, focusing on its implications for patient care. Through a systematic search of PubMed, Scopus, and Embase databases up to December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, with 7830 receiving semaglutide, were analyzed, with an additional number of 18 studies that were separately discussed because they reported data from the same RCTs. The review focused on thyroid cancer incidence, gastrointestinal symptoms, and other significant adverse events attributed to semaglutide. The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk. Adverse events were predominantly gastrointestinal, including nausea (2.05% to 19.95%) and diarrhea (1.4% to 13%). Nasopharyngitis and vomiting were also notable, with mean prevalences of 8.23% and 5.97%, respectively. Other adverse events included increased lipase levels (mean of 6.5%), headaches (mean prevalence of 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms (mean prevalence of 5.23%), dyspepsia (mean prevalence of 5.18%), and constipation (mean prevalence of 6.91%). Serious adverse events varied from 7% to 25.2%, highlighting the need for vigilant patient monitoring. These findings underscore the gastrointestinal nature of semaglutide’s adverse events, which, while prevalent, did not significantly deter from its clinical benefits in the treatment landscape. This systematic review provides a comprehensive assessment of semaglutide’s safety profile, with a focus on gastrointestinal adverse events and a low incidence of thyroid cancer. Despite the prevalence of gastrointestinal symptoms, semaglutide remains an efficacious option for managing diabetes and obesity. The detailed characterization of adverse events underscores the importance of monitoring and managing these effects in clinical practice, excluding the hypothesis of carcinogenesis.
Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice
Authors: Valls-Lacalle Laura , Consegal Marta , Ganse Freddy G. , Yáñez-Bisbe Laia , Pastor Javier , Ruiz-Meana Marisol , Inserte Javier , Benito Begoña , Ferreira-González Ignacio , Rodríguez-Sinovas Antonio
Published: April 2024

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 μL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.
Enhancing Methylene Blue Removal through Adsorption and Photocatalysis—A Study on the GO/ZnTiO3/TiO2 Composite
Authors: Jaramillo-Fierro Ximena , Cuenca Guisella
Published: April 2024

This study focuses on synthesizing and characterizing a graphene oxide/ZnTiO3/TiO2 (GO/ZTO/TO) composite to efficiently remove methylene blue (MB) from water, presenting a novel solution to address industrial dye pollution. GO and ZTO/TO were synthesized by the modified Hummers and sol–gel methods, respectively, while GO/ZTO/TO was prepared using a hydrothermal process. The structural and surface properties of the composite were characterized using various analytical techniques confirming the integration of the constituent materials and suitability for dye adsorption. The study revealed that GO/ZTO/TO exhibits an adsorption capacity of 78 mg g−1 for MB, with only a 15% reduction in adsorption efficiency until the fifth reuse cycle. Furthermore, the study suggests optimal adsorption near neutral pH and enhanced performance at elevated temperatures, indicating an endothermic reaction. The adsorption behavior fits the Langmuir isotherm, implying monolayer adsorption on homogeneous surfaces, and follows pseudo-second-order kinetics, highlighting chemical interactions at the surface as the rate-limiting step. The photocatalytic degradation of MB by GO/ZTO/TO follows pseudo-first-order kinetics, with a higher rate constant than that of GO alone, demonstrating the enhanced photocatalytic activity of the composite. In conclusion, GO/ZTO/TO emerges as a promising and sustainable approach for water purification, through an adsorption process and subsequent photocatalytic degradation.
Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress
Authors: Kapuy Orsolya
Published: April 2024

Dynamic regulation of the cellular proteome is mainly controlled in the endoplasmic reticulum (ER). Accumulation of misfolded proteins due to ER stress leads to the activation of unfolded protein response (UPR). The primary role of UPR is to reduce the bulk of damages and try to drive back the system to the former or a new homeostatic state by autophagy, while an excessive level of stress results in apoptosis. It has already been proven that the proper order and characteristic features of both surviving and self-killing mechanisms are controlled by negative and positive feedback loops, respectively. The new results suggest that these feedback loops are found not only within but also between branches of the UPR, fine-tuning the response to ER stress. In this review, we summarize the recent knowledge of the dynamical characteristic of endoplasmic reticulum stress response mechanism by using both theoretical and molecular biological techniques. In addition, this review pays special attention to describing the mechanism of action of the dynamical features of the feedback loops controlling cellular life-and-death decision upon ER stress. Since ER stress appears in diseases that are common worldwide, a more detailed understanding of the behaviour of the stress response is of medical importance.
How Artificial Intelligence Can Enhance the Diagnosis of Cardiac Amyloidosis: A Review of Recent Advances and Challenges
Authors: Kamel Moaz A. , Abbas Mohammed Tiseer , Kanaan Christopher N. , Awad Kamal A. , Baba Ali Nima , Scalia Isabel G. , Farina Juan M. , Pereyra Milagros , Mahmoud Ahmed K. , Steidley D. Eric , Rosenthal Julie L. , Ayoub Chadi , Arsanjani Reza
Published: April 2024

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.
Prognostic Value of Standard Heart Failure Medication in Patients with Cardiac Transthyretin Amyloidosis
Authors: aus dem Siepen Fabian , Hein Selina , Hofmann Eva , Nagel Christian , Schwarting Stéphanie K. , Hegenbart Ute , Schönland Stefan O. , Weiler Markus , Frey Norbert , Kristen Arnt V.
Published: April 2024

Introduction: Cardiac transthyretin amyloidosis (ATTR) is a progressive, fatal disease leading to heart failure due to accumulation of amyloid fibrils in the interstitial space and may occur as a hereditary (ATTRv) or wild-type (ATTRwt) form. Guidelines recommend the use of ACE inhibitors (ACEis) and beta-blockers (BBs) as heart failure therapy (HFT) in all patients with symptomatic heart failure and reduced ejection fraction, independent of the underlying etiology. However, the prognostic benefit of ACEis and BBs in ATTR has not been elucidated in detail yet. We thus sought to retrospectively investigate the outcome of patients with ATTRwt or ATTRv under HFT. Methods: Medical records of 403 patients with cardiac ATTR (ATTRwt: n = 268, ATTRv: n = 135) were screened for long-term medication as well as clinical, laboratory, electrocardiographic and echocardiographic data. Patients were assessed between 2005 and 2020 at the University Hospital Heidelberg. Kaplan–Meier analysis was used to analyze potential differences in survival among different subgroups. Results: The mean follow-up was 28 months. In total, 43 patients (32%) with ATTRv and 140 patients (52%) with ATTRwt received HFT. Survival was significantly shorter in patients receiving HFT in ATTRv (46 vs. 83 months, p = 0.0007) vs. non-HFT. A significantly better survival was observed in patients with comorbidities (coronary artery disease, arterial hypertension) and HFT among ATTRwt patients (p = 0.004). No significant differences in survival were observed in the other subgroups. Conclusions: Survival analysis revealed a potential benefit of HFT in patients with ATTRwt and cardiac comorbidities such as coronary artery disease and/or arterial hypertension. In contrast, HFT should be used with caution in patients with ATTRv.
A Study on the Sense of Parental Competence, Health Locus of Control and Levels of Anxiety, Depression and Somatization in Parents of Children with Type 1 Diabetes: Evidence on a Possible Relationship
Authors: Carosi Arcangeli Ivonne , Celia Giovanna , Girelli Laura , Fioretti Chiara , Cozzolino Mauro
Published: April 2024

Background: Parents of children with chronic conditions face challenges that go beyond basic care and parenting responsibilities. Parents’ experiences can be influenced by perceived stress, emotional experiences, feelings of helplessness, low sense of self-efficacy, anxiety and depression, reducing their quality of life. It is therefore not surprising that parents of children with chronic illnesses are more likely to experience stress, anxiety and depression than parents of healthy children. A prevalent chronic condition is type 1 diabetes. Methods: Parents (31 with children with type 1 diabetes diagnosis and 71 with children without chronic illness) were recruited to complete the measures of the Brief Symptom Inventory-18 (BSI-18), the Parent Health Locus of Control (PHLOC) and Parenting Sense of Competence (PSOC). Results: Significant differences in depression and internal locus of control were found; there was a positive correlation between internal LOC and efficacy in both samples; furthermore, there was a negative correlation between somatization and satisfaction in the experimental group. Conclusions: The ongoing experiences and challenges faced daily make parents perceive themselves as capable. Active involvement in supporting and managing the needs of child with type 1 diabetes could be a source of empowerment for the parent, contributing to the maintenance of their sense of competence. It is important, therefore, to consider the well-being and perception of the parent at a personal level, regardless of the child’s situation.
Application of Biomarkers in Obese Infertile Women: A Genetic Tool for a Personalized Treatment
Authors: Voros Charalampos , Bananis Kyriakos , Papapanagiotou Angeliki , Pouliakis Abraham , Mavriki Konstantina , Gkaniatsos Ioannis , Daskalaki Maria Anastasia , Prokopakis Ioannis , Tsimpoukelis Charalampos , Koulakmanidis Aristotelis-Marios , Darlas Menelaos , Anysiadou Sofia , Daskalakis Georgios , Domali Ekaterini
Published: April 2024

This study investigates links between CART and leptin gene expression, FSH receptor Asn680Ser polymorphism, and reproductive hormones in morbidly obese patients under 40 years old, facing infertility, and undergoing bariatric surgery. A total of 29 women were included in this study. A hormonal profile along with detection of CART and leptin gene expression was evaluated before and after bariatric surgery. Additionally, the presence or absence of Asn680Ser of the FSHR gene was studied. Following bariatric surgery, a mean reduction in BMI (16.03 kg/m2) was observed in all women. FSH levels preoperatively varied significantly among genotypes, with medians of 8.1, 9.5, and 10.3 for individuals without polymorphism, heterozygotes, and homozygotes, respectively (p = 0.0408). Post surgery, marginal differences in FSH levels were observed (5.8, 7.1, and 8.2, respectively) (p = 0.0356). E2 and LH levels exhibited no significant genotype-based differences pre and post surgery. Presurgical E2 levels were 29.6, 29.8, and 29.6, respectively (p = 0.91634), while postsurgical levels were 51.2, 47.8, and 47 (p = 0.7720). LH levels followed similar patterns. Our findings highlight bariatric surgery’s positive impact on BMI reduction and its potential connection to genetic markers, hormones, and infertility. This suggests personalized treatments and offers a valuable genetic tool for better fertility outcomes in obese individuals.
Hypophosphatasia Presenting as a Chronic Diffuse Pain Syndrome with Extra-Articular Calcifications
Authors: Lehane Florence , Malaise Olivier , Von Frenckell Christian , Otto Bernard , Docampo Elisa , Ribbens Clio
Published: April 2024

Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is well known in pediatrics with typical presentations in children, but mild forms can also be present in adults and are difficult to detect. We present the case of a 50-year-old woman referred for pain management, with a previous diagnosis of fibromyalgia. The association of clinical features (diffuse pain syndrome, early dental loosening, personal history of two fractures with osteoporosis, and family history of osteoporosis) with radiographic (heterotopic calcifications of the yellow and interspinous lumbar ligaments) and biological (low levels of total alkaline phosphatase) indices was suggestive of hypophosphatasia, which was confirmed by genetic analysis. We review and discuss the association between hypophosphatasia, musculoskeletal pain, and calcium pyrophosphate deposition and the importance of raising the diagnosis of adult-onset hypophosphatasia when facing these two rheumatologic entities.
Assessment of Risk Factors for Acute Kidney Injury with Machine Learning Tools in Children Undergoing Hematopoietic Stem Cell Transplantation
Authors: Musiał Kinga , Stojanowski Jakub , Augustynowicz Monika , Miśkiewicz-Migoń Izabella , Kałwak Krzysztof , Ussowicz Marek
Published: April 2024

Background: Although acute kidney injury (AKI) is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT), its prophylaxis remains a clinical challenge. Attempts at prevention or early diagnosis focus on various methods for the identification of factors influencing the incidence of AKI. Our aim was to test the artificial intelligence (AI) potential in the construction of a model defining parameters predicting AKI development. Methods: The analysis covered the clinical data of children followed up for 6 months after HSCT. Kidney function was assessed before conditioning therapy, 24 h after HSCT, 1, 2, 3, 4, and 8 weeks after transplantation, and, finally, 3 and 6 months post-transplant. The type of donor, conditioning protocol, and complications were incorporated into the model. Results: A random forest classifier (RFC) labeled the 93 patients according to presence or absence of AKI. The RFC model revealed that the values of the estimated glomerular filtration rate (eGFR) before and just after HSCT, as well as methotrexate use, acute graft versus host disease (GvHD), and viral infection occurrence, were the major determinants of AKI incidence within the 6-month post-transplant observation period. Conclusions: Artificial intelligence seems a promising tool in predicting the potential risk of developing AKI, even before HSCT or just after the procedure.
Hospital Incidence and Treatment Outcomes of Patients with Aneurysms and Dissections of the Iliac Artery in Switzerland—A Secondary Analysis of Swiss DRG Statistics Data
Authors: Bozalka Roland , Menges Anna-Leonie , Zimmermann Alexander , Meuli Lorenz
Published: April 2024

Background/Objectives: Aneurysms and dissections of the iliac artery (ADIAs) are significant vascular conditions often associated with aortic pathologies. Despite their importance, reports on isolated iliac artery pathologies are rare. This study aimed to investigate the epidemiology of ADIA in Switzerland including treatment incidence and hospital outcomes. Methods: A retrospective analysis of diagnosis-related group (DRG) statistics from 2011 to 2018 in Switzerland was conducted, identifying all cases of ADIA while excluding those with concomitant treatment of aortic pathologies. Age-standardized incidence rates and treatment outcomes were assessed, with multivariable logistic regression performed to identify factors associated with hospital mortality. Results: From 2011 to 2018, 1037 ADIA cases were hospitalized in Switzerland. Incidence rates for elective treatment were significantly higher in men than women, increasing in men from 1.5 to 2.4 cases per 100,000 men (p = 0.007), while remaining stable in women at around 0.2 cases per 100,000 women. Acute treatment incidence rates were lower but still higher in men, at 0.9 cases per 100,000 men and 0.2 cases per 100,000 women. Crude hospital mortality rates were lower for endovascular repair than open surgical repair in both elective (0.8% vs. 3.1%, p = 0.023) and emergency treatment (6.7% vs. 18.4%, p = 0.045). Multivariable analysis showed that endovascular repair was associated with significantly reduced hospital mortality compared to open repair (OR 0.27, 95%-CI: 0.10 to 0.66, p = 0.006). Conclusions: This nationwide study of iliac artery pathologies shows that the treatment incidence was about 10 times higher in men than in women for elective procedures, but only about five times higher for emergency treatment. Endovascular procedures were associated with significantly lower hospital mortality than open procedures, while hospital mortality rates were comparable for men and women.
A Novel Approach to Facial Reanimation and Restoration Following Radical Parotidectomies
Authors: Pannuto Lucia , Soh Jun Yi , Duah-Asante Kwaku , Shaharan Shazrinizam , Ward Joseph , Bisase Brian S. , Norris Paul , Koshima Isao , Nduka Charles , Kannan Ruben Yap
Published: April 2024

Background: Parotidectomies are indicated for a variety of reasons. Regardless of the indication for surgery, facial reanimation may be required because of facial nerve sacrifice or iatrogenic damage. In these cases, facial restoration performed concurrently with ablative surgery is considered the gold standard, and delayed reanimation is usually not attempted. Methods: A retrospective review of all patients who underwent parotidectomies from 2009 to 2022 in a single institution was performed. Indications, surgical techniques, and outcomes of an algorithmic template were applied to these cases using the Sunnybrook, Terzis scores, and Smile Index. A comparison was made between immediate vs. late repairs. Results: Of a total of 90 patients who underwent parotidectomy, 17 (15.3%) had a radical parotidectomy, and 73 (84.7%) had a total or superficial parotidectomy. Among those who underwent complete removal of the gland and nerve sacrifice, eight patients (47.1%) had facial restoration. There were four patients each in the immediate (n = 4) and late repair (n = 4) groups. Surgical techniques ranged from cable grafts to vascularized cross facial nerve grafts (sural communicating nerve flap as per the Koshima procedure) and vascularized nerve flaps (chimeric vastus lateralis and anterolateral thigh flaps, and superficial circumflex perforator flap with lateral femoral cutaneous nerve). Conclusions: The algorithm between one technique and another should take into consideration age, comorbidities, soft tissue defects, presence of facial nerve branches for reinnervation, and donor site morbidity. While immediate facial nerve repair is ideal, there is still benefit in performing a delayed repair in this algorithm.
Evolution of the Transforaminal Lumbar Interbody Fusion (TLIF): From Open to Percutaneous to Patient-Specific
Authors: Drossopoulos Peter N. , Ononogbu-uche Favour C. , Tabarestani Troy Q. , Huang Chuan-Ching , Paturu Mounica , Bardeesi Anas , Ray Wilson Z. , Shaffrey Christopher I. , Goodwin C. Rory , Erickson Melissa , Chi John H. , Abd-El-Barr Muhammad M.
Published: April 2024

The transforaminal lumbar interbody fusion (TLIF) has seen significant evolution since its early inception, reflecting advancements in surgical techniques, patient safety, and outcomes. Originally described as an improvement over the posterior lumbar interbody fusion (PLIF), the TLIF began as an open surgical procedure, that notably reduced the need for the extensive neural retractation that hindered the PLIF. In line with the broader practice of surgery, trending toward minimally invasive access, the TLIF was followed by the development of the minimally invasive TLIF (MIS-TLIF), a technique that further decreased tissue trauma and postoperative complications. Subsequent advancements, including Trans-Kambin’s Triangle TLIF (percLIF) and transfacet LIF, have continued to refine surgical access, minimize surgical footprint, and reduce the risk of injury to the patient. The latest evolution, as we will describe it, the patient-specific TLIF, is a culmination of the aforementioned adaptations and incorporates advanced imaging and segmentation technologies into perioperative planning, allowing surgeons to tailor approaches based on individual patient anatomy and pathology. These developments signify a shift towards more precise methods in spine surgery. The ongoing evolution of the TLIF technique illustrates the dynamic nature of surgery and emphasizes the need for continued adaptation and refinement.
Autoimmune and Non-Autoimmune Comorbidities in Myasthenic Patients of East-European Descent: A Case–Control Study
Authors: Croitoru Cristina Georgiana , Pavel-Tanasa Mariana , Cuciureanu Dan Iulian , Hodorog Diana Nicoleta , Cianga Petru
Published: April 2024

Background: As the life expectancy of patients with myasthenia gravis (MG) is improving, so the number of comorbidities continues to rise, with a potentially significant impact on the overall morbidity and mortality. The main aim of the study was to assess comorbidities of MG in a group of patients of East-European descent. Methods: We retrospectively compared 185 adult myasthenic patients with 895 sex- and age-matched controls, admitted from January 2013 to December 2021. Results: Of these patients, 60% had late-onset MG (LOMG), with a clear predominance of women in both the LOMG and early-onset (EOMG) types; and 23.8% of the patients had a radiological description consistent with thymoma. All myasthenic patients had at least one comorbidity; 20 (10.8%) of the patients associated at least one autoimmune comorbidity. Obesity (p < 0.01), type 2 diabetes (p < 0.0001), cerebrovascular diseases (p < 0.0001), essential hypertension (p < 0.01), and cardiac arrythmias (p < 0.0001) were more frequent in patients than in the control group. The granulocyte-to-lymphocyte ratio was higher in the myasthenic patients compared to the controls (p < 0.01 for LOMG). Discussion: We, thus, suggest a common chronic low-grade inflammatory background as a possible connection between MG subtypes and some of these apparently unconnected comorbidities. Conclusions: The East-European origin of the patients offered a different social and cultural angle of a disease studied mainly on populations of West-European and Asian descent.
Comparing the Real-World and Clinical Trial Bleeding Rates Associated with Oral Anticoagulation Treatment for Atrial Fibrillation
Authors: Gue Ying , Bloomfield Dan , Freedholm Debra , Lip Gregory Y. H.
Published: April 2024

Background The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOACs). However, it comes with an increased risk of bleeding, and therefore, counselling patients on their individual risks is important. Although the majority of patients initiated on DOACs have been represented within the clinical trials, some cohorts are under-represented in whom clinicians cannot practice evidence-based medicine. Methods Utilising the pooled clinical trial (CT) data sourced from Medidata Enterprise Data Store, five recent open-label industry-sponsored AF trials were compared with real-world data (RWD) sourced from the HealthVerity™ Marketplace with the occurrence of bleeding events as the primary outcome of interest. Results A total of 64,421 patients were included in the analysis, with 3207 patients from the clinical DOAC trials and 61,214 patients from the RWD cohort. Overall, the patients from the RWD cohort had more co-morbidities, were older (72.2 ± 11.9 vs. 65.3 ± 10.7 years old, p < 0.001), had higher mean CHA2DS2VASc (3.98 ± 1.9 vs. 2.87 ± 1.73, p < 0.001), and HAD-BLED scores (2.13 ± 1.02 vs. 1/04 ± 0.93, p < 0.001) when compared to the trial data. When comparing the incidence of the first major bleed at 12 months post-treatment initiation, rates in the RWD cohort were significantly higher (10.69 vs. 18.97 per 100 person-years). The impact of co-morbidities such as age, CHA2DS2VASc, and HAD-BLED scores was similar in both cohorts; however, there was an under-representation of older females and more co-morbid patients within the clinical trial cohort. Conclusions DOAC-treated patients have a higher bleeding incidence rate in the RWD cohort than in clinical trials. This can be explained by the older patient age group with more complex medical h istories and higher HAS-BLED scores. The under-representation of higher-risk patients and lower proportion of females within clinical trials should be addressed to better translate clinical trial data into real-world clinical practice.
Early Experience with Prone Lateral Interbody Fusion in Deformity Correction: A Single-Institution Experience
Authors: Bartlett Alyssa M. , Dibble Christopher F. , Sykes David A. W. , Drossopoulos Peter N. , Wang Timothy Y. , Crutcher Clifford L. , Than Khoi D. , Bhomwick Deb A. , Shaffrey Christopher I. , Abd-El-Barr Muhammad M.
Published: April 2024

Background/Objectives: Lateral spine surgery offers effective minimally invasive deformity correction, but traditional approaches often involve separate anterior, lateral, and posterior procedures. The prone lateral technique streamlines this process by allowing single-position access for lateral and posterior surgery, potentially benefiting from the lordosing effect of prone positioning. While previous studies have compared prone lateral to direct lateral for adult degenerative diseases, this retrospective review focuses on the outcomes of adult deformity patients undergoing prone lateral interbody fusion. Methods: Ten adult patients underwent single-position prone lateral surgery for spine deformity correction, with a mean follow-up of 18 months. Results: Results showed significant improvements: sagittal vertical axis decreased by 2.4 cm, lumbar lordosis increased by 9.1°, pelvic tilt improved by 3.3°, segmental lordosis across the fusion construct increased by 12.2°, and coronal Cobb angle improved by 6.3°. These benefits remained consistent over the follow-up period. Correlational analysis showed a positive association between improvements in PROs and SVA and SL. When compared to hybrid approaches, prone lateral yielded greater improvements in SVA. Conclusions: Prone lateral surgery demonstrated favorable outcomes with reasonable perioperative risks. However, further research comparing this technique with standard minimally invasive lateral approaches, hybrid, and open approaches is warranted for a comprehensive evaluation.
Validation of an Inhaled Therapy Beliefs Questionnaire in Patients with Chronic Obstructive Pulmonary Disease
Authors: Muñoz-Cobos Francisca , Aguiar-Leiva Virginia P. , Argüello-Suárez Carmen , Colacicchi Paula , Calleja-Cartón Luis Antonio , Leiva-Fernández Francisca
Published: April 2024

Background: To carry out a validation questionnaire that assesses beliefs about inhaled treatments in patients with chronic obstructive pulmonary disease (COPD), as knowing patients’ beliefs could help to improve medication adherence and health outcomes. Methods: We evaluated data from 260 COPD patients from electronic medical record databases from five primary healthcare centers, in a descriptive, cross-sectional study with a sample size calculated for a 10-item questionnaire, with an estimated Cronbach’s alpha of 0.70 and a 95% confidence level. Study participants were selected via systematic random sampling. Variables: Ten-item Inhaled Therapy Beliefs Questionnaire, CCTI-Questionnaire v.2.0, time for completion, age, sex, educational level, spirometry severity (GOLD criteria), exacerbations (previous year), characteristics of inhaled treatment, and smoking habit. A two-year follow-up in a subsample of 77 patients from one health center was utilized. The Morisky–Green test, pharmacy dispensing data, test–retest (kappa coefficient), and an exploratory analysis of the adherence–belief relationship (ji-squared) were measured. Results: The 10-item questionnaire showed good viability (3 min completion time) when performed face-to-face or telephonically; its psychometric properties were acceptable, with an internal consistency (Cronbach’s alpha) score of 0.613. Three factors explained 47.58% of the total variance (p < 0.0001): use (factor 1), effects (factor 2), and objectives (factor 3) of inhalers. The two-year follow-up ultimately considered 58 out of the 77 patients (10 deceased, 4 unlocated, 2 mistakes, 2 no inhaled treatment, and 1 withdrawal). Non-adherence was 48.3% in terms of the Morisky–Green test; 31% in terms of pharmacy dispensing data; and 40.4% considering both methods. There was low test–retest reliability, indicated by items 4, 8, and 9 of the CCTI-Questionnaire (Kappa = 0.4, 0.26, and 0.34; p-value < 0.0001, 0.008, and 0.001, respectively). There was mild correlation between beliefs and adherence. Conclusions: The ten-item CCTI-Questionnaire v.2.0 demonstrated acceptable psychometric properties regarding feasibility, reliability, and content validity.
Malignancy in Abdominal Wall Endometriosis: Is There a Way to Avoid It? A Systematic Review
Authors: Alaert Julie , Lancelle Mathilde , Timmermans Marie , Tanos Panayiotis , Nisolle Michelle , Karampelas Stavros
Published: April 2024

Background: Malignant-associated abdominal wall endometriosis (AWE) is a rare pathology, likely to occur in 1% of scar endometriosis. The objectives of this study were to update the evidence on tumor degeneration arising from AWE to notify about the clinical characteristics, the different treatments offered to patients and their outcomes. Methods: A comprehensive systematic review of the literature was conducted. PubMed, Embase and Cochrane Library databases were used. Prospero (ID number: CRD42024505274). Results: Out of the 152 studies identified, 63 were included, which involved 73 patients. The main signs and symptoms were a palpable abdominal mass (85.2%) and cyclic pelvic pain (60.6%). The size of the mass varied between 3 and 25 cm. Mean time interval from the first operation to onset of malignant transformation was 20 years. Most common cancerous histological types were clear cell and endometrioid subtypes. Most widely accepted treatment is the surgical resection of local lesions with wide margins combined with adjuvant chemotherapy. The prognosis for endometriosis-associated malignancy in abdominal wall scars is poor, with a five-year survival rate of around 40%. High rates of relapse have been reported. Conclusions: Endometrial implants in the abdominal wall should be considered as preventable complications of gynecological surgeries. Special attention should be paid to women with a history of cesarean section or uterine surgery.
Clinical Correlates of In-Hospital Mortality in Patients Undergoing Inferior Vena Cava Filter Placement for Acute Deep Vein Thrombosis
Authors: Porceddu Enrica , Talerico Rosa , Ciasca Gabriele , Cammà Giulia , Di Santo Riccardo , Peri Matilde , Cina Alessandro , Pola Roberto , Porfidia Angelo
Published: April 2024

Background: It is reasonable to place an Inferior Vena Cava Filter (IVCF) when an acute deep vein thrombosis (DVT) of the lower limbs occurs in a patient with absolute contraindication to therapeutic anticoagulation. An additional potential reason for placing an IVCF is the need to stop therapeutic anticoagulation in a patient with acute DVT who must undergo urgent non-deferrable surgery. However, IVCFs are often used outside of such established indications and many authors argue about their actual utility, especially in terms of survival. In this retrospective study, we looked for clinical correlates of in-hospital mortality among patients who underwent IVCF placement, limiting our analysis to the cases for which a correct indication to IVCF placement existed. Methods: We retrospectively analyzed the electronic database of our University Hospital, searching for consecutive hospitalized patients who had acute DVT and underwent IVCF placement because of an established contraindication to therapeutic anticoagulation and/or because it was necessary to stop anticoagulation due to urgent surgery. The search covered the period between 1 January 2010 and 31 December 2020. Results: The search resulted in the identification of 168 individuals. An established contraindication to therapeutic anticoagulation was present in 116 patients (69.0%), while urgent non-deferrable surgery was the reason for IVCF placement in 52 patients (31.0%). A total of 24 patients (14.3%) died during the same hospital stay in which the IVCF was placed. Mortality rate was significantly higher in patients with a contraindication to anticoagulation than in patients who underwent IVCF placement because of urgent surgery (19.0% vs. 3.8%, OD 5.85 vs. 0.17). In-hospital mortality was also significantly higher among patients with chronic kidney disease and those who needed blood cell transfusion during hospitalization. Conclusions: This study provides novel information on clinical correlates of in-hospital mortality among patients with acute DVT who undergo IVCF. Prospective observational studies are needed to substantiate these findings.
Cytokine Dynamics in Acute Pancreatitis: The Quest for Biomarkers from Acute Disease to Disease Resolution
Authors: Malheiro Filipa , Ângelo-Dias Miguel , Lopes Teresa , Martins Catarina Gregório , Borrego Luis Miguel
Published: April 2024

Background: Acute pancreatitis (AP) is an inflammatory disease of the pancreas with incompletely known pathogenic mechanisms. This study aimed to explore the temporal changes in serum cytokines in patients with AP and to assess the association of these changes with disease severity. Methods: Fifty patients hospitalized with AP were enrolled, and their serum cytokine levels were analyzed at four different time points. A healthy control (HC) group of 30 outpatients was included. Results: AP patients showed increased levels of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, and monocyte chemoattractant protein (MCP)-1 at admission when compared with HC. IL-6, VEGF, and EGF remained elevated 1 month after hospitalization and 6 months after discharge. Conclusions the Bedside Index of Severity in Acute Pancreatitis (BISAP) and severity classification of the revised Atlanta classification system, IL-6 and VEGF, determined 48 h after hospitalization, were the two cytokines consistently elevated in the most severe patients. Increased levels of IL-4, IL-6, IL-10, and TNF-alpha at admission and MCP-1 48 h after admission are also related to the length of hospital stay. Conclusions: Our study highlights the role cytokines play in the pathogenesis of AP and can be useful in the development of future drug trials for AP.