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Background : Several significant associations between certain Human Leukocyte Antigen (HLA) alleles and myasthenia gravis (MG) subtypes were established in populations from Western Europe and North America and, to a lesser extent, from China and Japan. However, such data are scarcely available for Eastern Europe. This study aimed to analyze the associations of HLA Class I and II alleles with MG and its serological subtypes (with anti-acetylcholine receptor autoantibodies, RAch+MG, and double-seronegative, dSNMG) in myasthenic patients of Romanian descent. Methods: We consecutively enrolled adult Romanian unrelated myasthenic patients, which were genotyped by next-generation sequencing for HLA-A, -B, -C, -DRB1 and -DQB1. The descent-matched controls were represented by two separate groups of random normal subjects genotyped for the main five HLA loci at the two-digit and four-digit levels, respectively, collected from the Allele Frequency Net Database. Results: A total of 40 patients (females: 80.00%; median age at onset: 42.5 years, range: 1-78; RAch+MG: 75.00%; dSNMG: 22.50%) were included. We were able to confirm previously acknowledged allelic associations: positive for HLA-B*08, DRB1*14:54 and DRB1*16:01 and negative for DRB1*13. However, we found some potential novel significant positive associations between MG and the HLA-A*02:36, B*47, B*73, B*44:27 and B*57:02 alleles. All alleles positively associated with MG remained significantly associated with RAch+MG, regardless of the patients' clinical and thymic heterogeneity. We found significant positive associations between dSNMG and the HLA-B*47, B*44:27 and DRB1*14:54 alleles that are shared with RAch+MG. Conclusions: These results suggest both distinct and common etiopathogenic mechanisms between dSNMG and RAch+MG. Our study pioneers allele associations in Romanian MG patients.

This paper presents the obtaining and characterization of blends based on high-density polyethylene (HDPE) and plasticized starch. In addition to plasticized starch (28.8% w / w ), the compositions made also contained other ingredients, such as polyethylene-graft-maleic anhydride as a compatibilizer, ethylene propylene terpolymer elastomer, cross-linking agents, and nanoclay. Plasticized starch contains 68.6% w / w potato starch, 29.4% w / w glycerin, and 2% w / w anhydrous citric acid. Blends based on HDPE and plasticized starch were made in a Brabender Plasti-Corder internal mixer at 160 °C, and plates for testing were obtained using the compression method. Thermal analyses indicate an increase in the crystallization degree of the HDPE after the addition of plasticized starch. SEM micrographs indicate that blends are compatibilized, with the plasticized starch being well dispersed as droplets in the HDPE matrix. Samples show high hardness values (62-65° ShD), good tensile strength values (14.88-17.02 N/mm 2 ), and Charpy impact strength values (1.08-2.27 kJ/m 2 on notched samples, and 7.96-20.29 kJ/m 2 on unnotched samples). After 72 h of water immersion at room temperature, mixtures containing a compatibilizer had a mass variation below 1% and water absorption values below 1.7%. Upon increasing the water immersion temperature to 80 °C, the sample without the compatibilizer showed a mass reduction of -2.23%, indicating the dissolution of the plasticized starch in the water. The samples containing the compatibilizer had a mass variation of max 8.33% and a water absorption of max 5.02%. After toluene immersion for 72 h at room temperature, mass variation was below 8%.

IL-6 remains a key molecule of the cytokine storms characterizing COVID-19, exerting both proinflammatory and anti-inflammatory effects. Emerging research underscores the significance of IL-6 trans-signaling over classical signaling pathways, which has shifted the focus of therapeutic strategies. Additionally, the synergistic action of TNF-α and IFN-γ has been found to induce inflammatory cell death through PANoptosis, further amplifying the severity of cytokine storms. Long COVID-19 patients, as well as those with cytokine storms triggered by other conditions, exhibit distinct laboratory profiles, indicating the need for targeted approaches to diagnosis and management. Growing evidence also highlights the gut microbiota's crucial role in modulating the immune response during COVID-19 by affecting cytokine production, adding further complexity to the disease's immunological landscape. Targeted intervention strategies should focus on specific cytokine cutoffs, though accurate cytokine quantification remains a clinical challenge. Current treatment strategies are increasingly focused on inhibiting IL-6 trans-signaling, which offers promise for more precise therapeutic approaches to manage hyperinflammatory responses in COVID-19. In light of recent discoveries, this review summarizes key research findings on cytokine storms, particularly their role in COVID-19 and other inflammatory conditions. It explores emerging therapeutic strategies targeting cytokines like IL-6, TNF-α, and IFN-γ, while also addressing open questions, such as the need for better biomarkers to detect and manage cytokine storms. Additionally, the review highlights ongoing challenges in developing targeted treatments that mitigate hyperinflammation without compromising immune function, emphasizing the importance of continued research in this field.

A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term "mesenchymal cells" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Over the past four years, the COVID-19 pandemic has posed serious global health challenges. The severe form of disease and death resulted from the failure of immune regulatory mechanisms, closely highlighted by the dual proinflammatory cytokine and soluble immune checkpoint (sICP) storm. Identifying the individual factors impacting on disease severity, evolution and outcome, as well as any additional interconnections, have become of high scientific interest., Methods: In this study, we evaluated a novel panel composed of ten sICPs for the predictive values of COVID-19 disease severity, mortality and Delta vs. Omicron variant infections in relation to hyperinflammatory biomarkers. The serum levels of sICPs from confirmed SARS-CoV-2 infected patients at hospital admission were determined by Luminex, and artificial neural network analysis was applied for defining the distinct patterns of molecular associations with each form of disease: mild, moderate, and severe., Results: Notably, distinct sICP profiles characterized various stages of disease and Delta infections: while sCD40 played a central role in all defined diagrams, the differences emerged from the distribution levels of four molecules recently found and relatively less investigated (sCD30, s4-1BB, sTIM-1, sB7-H3), and their associations with various hematological and biochemical inflammatory biomarkers. The artificial neural network analysis revealed the prominent role of serum sTIM-1 and Galectin-9 levels at hospital admission in discriminating between survivors and non-survivors, as well as the role of specific anti-interleukin therapy (Tocilizumab, Anakinra) in improving survival for patients with initially high sTIM-1 levels. Furthermore, strong associations between sCD40 and Galectin-9 with suPAR defined the Omicron variant infections, while the positive match of sCD40 with sTREM-1 serum levels characterized the Delta-infected patients., Conclusions: Of importance, this study provides a comprehensive analysis of circulatory immune factors governing the COVID-19 pathology, and identifies key roles of sCD40, sTIM-1, and Galectin-9 in predicting mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paranga, Pavel-Tanasa, Constantinescu, Iftimi, Plesca, Miftode, Cianga and Miftode.)

This study investigates the combined treatment of secukinumab (SECU) and magnolol (MAGN) in a mouse model of LPS-induced ALI overlapped with allergic pulmonary inflammation, aiming to better understand the mechanism behind this pathology and to assess the therapeutic potential of this novel approach in addressing the severity of ALI. The combined treatment reveals intricate immunomodulatory effects. Both treatments inhibit IL-17 and promote M2 macrophage polarization, which enhances anti-inflammatory cytokine production such as IL-4, IL-5, IL-10, and IL-13, crucial for lung repair and inflammation resolution. However, the combination treatment exacerbates allergic responses and increases OVA-specific IgE, potentially worsening ALI outcomes. MAGN pretreatment alone demonstrates higher potency in reducing neutrophils and enhancing IFN-γ, suggesting its potential in mitigating severe asthma symptoms and modulating immune responses. The study highlights the need for careful consideration in therapeutic applications due to the combination treatment's inability to reduce IL-6 and its potential to exacerbate allergic inflammation. Elevated IL-6 levels correlate with worsened oxygenation and increased mortality in ALI patients, underscoring its critical role in disease severity. These findings offer valuable insights for the advancement of precision medicine within the realm of respiratory illnesses, emphasizing the importance of tailored therapeutic strategies.

Introduction: Entry point selection, a crucial aspect of femoral antegrade nailing, can impact nail fit and consequently fracture reduction. In adults, the standard entry portals used are the piriformis fossa and the tip of the greater trochanter. Previous systematic reviews comparing the two techniques have not been limited to Randomized Controlled Trials (RCTs) and have not consistently included the same available RCTs., Materials and Methods: A systematic search of comparative studies regarding entry portal selection in femoral antegrade nailing was conducted on seven databases. Only Prospective RCTs comparing trochanteric and piriformis entry in the management of trochanteric or diaphyseal femur fractures were eligible for inclusion., Results: Ultimately, only 6 RCTs were found eligible for inclusion. Five of the six included studies reported on operative time. The resulting mean difference (MD) illustrated a significant decrease in operative time by approximately 21.26 min (95% CI  - 28.60 to  - 13.92, p < 0.001) using trochanteric entry. Fluoroscopy exposure was reported on by four studies, however, only two studies were included in the analysis due to different reporting methods. Trochanteric entry used significantly less fluoroscopy than piriformis entry (MD -50.33 s, 95% CI  - 84.441 to  - 16.22, p = 0. 004). No significant difference in malalignment rates, delayed union rates, nonunion rates, pain scores, or complication rates was found., Conclusion: The significant differences found in operating time and fluoroscopy time align with those in other studies. While we were not able to pool the data on functional outcome scores, none of the included studies found a significant difference in scores by their last follow-up. Both approaches demonstrate comparable functional outcomes and safety profiles, indicating the choice of entry point should be at the discretion of the surgeon based on technique familiarity and fracture characteristics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Previous work has demonstrated a deficiency in urology resident education when it comes to andrology and male infertility. We analyzed the top 100 most frequently cited and influential articles published on testosterone deficiency and its associated therapy, allowing trainees and clinicians to review and understand the characteristics of impactful literature for self-directed learning purposes., Methods: The ISI Web of Knowledge database was used to find articles on testosterone deficiency, hypogonadism, and replacement therapies. Relevant, peer-reviewed, English articles were included. Article details, including title, citation count, publication year, and more, were gathered. Articles were classified based on content (e.g. clinical outcomes, anatomy, and trends) using defined criteria., Results: The top 300 most cited were reviewed with 100 included. The most cited article had 774 citations, averaging 234 in the top 100. Publication years had peaks in 2003-2004 and 2006-2007. The US led in publications (56), followed by England (16), Germany (14), and Italy (13). Common affiliations included US Department of Veteran Affairs, Veterans Health Administration, RIC Research Education Clinical Center, and University of California System. Articles were categorized as LOE 2 (47), LOE 1 (22), and LOE 5 (21). Articles focused on clinical outcomes (71.7%), anatomy/biomechanics/physiology (14.1%), clinical guidelines (8.1%), and screening (4%). The " Journal of Clinical Endocrinology & Metabolism " published 26 of the top 100 cited articles., Conclusions: This analysis highlights influential articles regarding testosterone deficiency and management. The discussed articles have significant clinical and therapeutic implications for the practicing urologist which may bolster deficits in current resident education., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

(1) Background: Given its high cardiac specificity and its capacity to directly assess the cardiac function, cardiac myosin-binding protein (MyBP-C) is a promising biomarker in patients with acute heart failure (AHF). The aim of our study was to investigate the clinical utility of this novel marker for diagnosis and short-term prognosis in subjects with AHF. (2) Methods: We measured plasma levels of MyBP-C at admission in 49 subjects (27 patients admitted with AHF and 22 controls). (3) Results: The plasma concentration of MyBP-C was significantly higher in patients with AHF compared to controls (54.88 vs. 0.01 ng/L, p < 0.001). For 30-day prognosis, MyBP-C showed significantly greater AUC (0.972, p < 0.001) than NT-proBNP (0.849, p = 0.001) and hs-TnI (0.714, p = 0.047). In a multivariate logistic regression analysis, an elevated level of MyBP-C was the best independent predictor of 30-day mortality (OR = 1.08, p = 0.039) or combined death/recurrent 30-days rehospitalization (OR = 1.12, p = 0.014). (4) Conclusions: Our data show that circulating MyBP-C is a sensitive and cardiac-specific biomarker with potential utility for the accurate diagnosis and prognosis of AHF.

Neutrophils, known to be mobilized and activated in high amounts through Il-17 stimulation, are a key factor for clinical manifestation and imbalance of redox systems favoring a dominant oxidative state in both severe asthma and acute lung injury (f). The aim of this study was to evaluate in mice, the effect of Secukinumab (SECU) in a model of ovalbumin-induced asthma exacerbated with LPS administration to induce ALI, compared to dexamethasone (DEXA), already known for its benefit in both asthma and ALI. Results on cytokine levels for specific Th1, Th2 and Th17 revealed an interplay of immune responses. For Th1 effector cytokines in BALF, DEXA treatment increased TNF-α levels, but TNF-α was not modified by SECU; DEXA and SECU significantly decreased IFN-γ and IL-6 levels. For typical Th2 cytokines, DEXA significantly increased Il-4, Il-5 and Il-13 levels, while SECU significantly inhibited Il-5 levels. Both SECU and DEXA significantly decreased Il-17 levels. Cytokine level changes in lung tissue homogenate were partly similar to BALF cytokines. Conclusion: in addition to DEXA, SECU possesses the ability to modulate inflammatory cytokine release and to decrease Th17 responses in ALI overlapped on exacerbated asthma in mice.

Background: Since the introduction of electric-scooter (e-scooter) mobile applications, there has been a marked increase in e-scooter-related injury. On January 19, 2022, the City of Miami revoked permits to five major mobile applications for violation of safety protocols., Objectives: The purpose of our study was to assess the effects of this notice on the orthopedic patients seen at our corresponding Level I trauma center., Methods: Institutional Review Board approval was obtained for this study. A retrospective chart review was performed including all patients with orthopedic injuries at our Level I trauma center between July 19, 2021 and July 19, 2022. These dates include 6 months prior to and after the major e-scooter operators ceased use in Miami. SPSS statistical software version 28.0.0 (SPSS, IBM, Armonk, NY) was utilized for all statistical analysis., Results: There were 2558 patients in the prenotice cohort, and 2492 patients in the postnotice cohort. After the notice, there was a significant decrease in the number of patients that presented to our institution due to injuries caused by e-scooters (2.8% vs. 1.8% patients; p = 0.021). Patients with injuries caused by e-scooters had a significantly lower age (38 vs. 42, respectively; p = 0.034) and were more likely to be male (79.3% vs. 67.4% male, respectively; p = 0.007) than patients with other orthopedic injuries., Conclusion: This study demonstrates that the 2022 notice revoking the major mobile application operators from the City of Miami resulted in a significant decrease in the number of orthopedic cases due to e-scooter-related injury at the corresponding Level I trauma center., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Published by Elsevier Inc.)

Colorectal cancer (CRC) ranks as second most common cause of cancer-related deaths. The CRC management considerably improved in recent years, especially due to biological therapies such as bevacizumab. The lack of predictive or prognostic biomarkers remains one of the major disadvantages of using bevacizumab in the CRC management. We performed a prospective study to analyze the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) investigated by ELISA in 56 patients with metastatic CRC undergoing bevacizumab and chemotherapy between May 2019 and September 2021 at baseline and after one and six months of therapy. We showed that low levels of CypA at baseline and after one month of treatment were associated with better overall survival (OS) (42 versus 24 months, p = 0.029 at baseline; 42 versus 25 months, p = 0.039 after one month). For copeptin and Tie2, Kaplan-Meier curves showed no correlation between these biomarkers and OS or progression-free survival. When adjusting for baseline and post-treatment factors, a multivariate Cox analysis showed that low values of CypA at baseline and after one month of treatment were independent prognostic factors for OS and correlated with a better prognosis in metastatic CRC patients.

Introduction: The rapid advancement of artificial intelligence (AI), particularly the development of Large Language Models (LLMs) such as Generative Pretrained Transformers (GPTs), has revolutionized numerous fields. The purpose of this study is to investigate the application of LLMs within the realm of orthopaedic in training examinations., Methods: Questions from the 2020-2022 Orthopaedic In-Service Training Exams (OITEs) were given to OpenAI's GPT-3.5 Turbo and GPT-4 LLMs, using a zero-shot inference approach. Each model was given a multiple-choice question, without prior exposure to similar queries, and their generated responses were compared to the correct answer within each OITE. The models were evaluated on overall accuracy, performance on questions with and without media, and performance on first- and higher-order questions., Results: The GPT-4 model outperformed the GPT-3.5 Turbo model across all years and question categories (2022: 67.63% vs. 50.24%; 2021: 58.69% vs. 47.42%; 2020: 59.53% vs. 46.51%). Both models showcased better performance with questions devoid of associated media, with GPT-4 attaining accuracies of 68.80%, 65.14%, and 68.22% for 2022, 2021, and 2020, respectively. GPT-4 outscored GPT-3.5 Turbo on first-order questions across all years (2022: 63.83% vs. 38.30%; 2021: 57.45% vs. 50.00%; 2020: 65.74% vs. 53.70%). GPT-4 also outscored GPT-3.5 Turbo on higher-order questions across all years (2022: 68.75% vs. 53.75%; 2021: 59.66% vs. 45.38%; 2020: 53.27% vs. 39.25%)., Discussion: GPT-4 showed improved performance compared to GPT-3.5 Turbo in all tested categories. The results reflect the potential and limitations of AI in orthopaedics. GPT-4's performance is comparable to a second-to-third-year resident and GPT-3.5 Turbo's performance is comparable to a first-year resident, suggesting the application of current LLMs can neither pass the OITE nor substitute orthopaedic training. This study sets a precedent for future endeavors integrating GPT models into orthopaedic education and underlines the necessity for specialized training of these models for specific medical domains., Competing Interests: None., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

A 24-year-old male, with a body mass index (BMI) of 31.7 and a previous open reduction and internal fixation (ORIF) of the left ankle seven years ago, presented to the emergency department with a peri-implant, comminuted fibula fracture with broken hardware and syndesmotic injury. The nature of the revision surgery made proper guidewire placement during fibular nailing difficult. Blocking wires assisted in ensuring proper guidewire placement. The patient was successfully managed with revision ORIF, fibular nailing, and syndesmotic fixation. Blocking wires are a helpful tool for achieving proper fracture alignment and stability during intramedullary nailing procedures and may be considered in fibular nailing situations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Acevedo et al.)

Introduction: The impact of anxiety and depression on outcomes in orthopaedic trauma surgery is a topic of growing research interest., Patients and Methods: Orthopaedic trauma patients often experience high rates of psychiatric disorders, with anxiety and depression being the most prevalent. Mental health disorders have been shown to increase the risk of negative surgical outcomes and morbidity. This narrative review seeks to summarize the current literature surrounding the impacts of anxiety and depression on orthopaedic trauma surgery outcomes., Discussion: There is a bidirectional relationship between chronic pain and mental health disorders, involving overlapping brain regions and neurotransmitter pathways. Anxiety and depression have been identified as predictors of negative surgical outcomes in orthopaedic trauma patients. Screening tools like the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Screener-7 (GAD-7), and Medical Outcomes Study 36-item Short Form (SF-36) can assess mental health status and help tailor interventions. Psychological distress, chronic pain, and traumatic limb amputation are factors that contribute to adverse mental health outcomes in orthopaedic trauma patients. Opioid use for pain management is common in orthopaedic surgery, but it can worsen symptoms of depression and lead to dependency. Non-opioid pain management strategies may improve postoperative outcomes by reducing the impact of opioid-exacerbated depression., Conclusion: Mental health interventions, both preoperative and postoperative, are crucial in optimizing surgical outcomes and improving patient quality of life. Multidisciplinary approaches that address both physical and mental health are recommended for orthopaedic trauma patients. Further research is needed to develop effective interventions for improving mental health outcomes in this patient population., Competing Interests: There are no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

With the incidence of primary total hip arthroplasty continuing to rise in the United States, the innovation behind improving current total hip arthroplasty systems inevitably grows with it-each new design potentially ushering in new flaws. We report a case of screw failure with the Arcos Modular Femoral Revision System-Trochanteric Bolt and Claw Technique in a 74-year-old male patient. The patient presented to the investigator's clinic for their 20-month follow-up evaluation of their complex right hip revision. Radiographs revealed failure of the screw attaching the claw plate to the stem resulting in dislodgement and relocation of the screw within the intra-articular cavity. The patient elected for nonsurgical management and will continue to be monitored. Consent by the patient involved in this case report was obtained., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Study Design: Retrospective review., Objective: This bibliometric review summarizes the publication trends and critical information about the most cited Proximal Junction Kyphosis (PJK) articles., Background: Data: Proximal junctional kyphosis is frequently diagnosed after spinal fusion surgery. However, there continues to be heavy debate regarding the definition, incidence, risk factors, and treatment of this disorder., Methods: Nine hundred eleven articles were found when searching The Web of Science database with the keywords "Proximal junctional kyphosis" and "proximal junctional failure." The 200 top-cited articles were reviewed and screened to ensure PJK was discussed. The articles were filtered based on the highest to lowest number of citations, and the top 50 articles were chosen. Inclusion criteria included articles that contained a discussion of PJK and outcomes after surgery. Exclusion criteria included articles without mentioning PJK, or that studied non-human subjects. The 50 most cited articles were sorted by level of evidence and their classification for analysis., Results: The 50 most cited articles in this study were published a total of 6056 times. These articles were cited 71-413 times in the literature, with publications from 1994 to 2018. Most of the top 50 articles (64%) were published in the USA. Specifically, HSS and Washington University are the institutions with the most contributions to the publication of the most cited articles on PJK (n = 16). Lenke was the author that contributed to most publications in the top 50 articles on PJK., Conclusion: This study provides a framework for the most cited articles published on PJK. Most articles on this topic were in the category of clinical outcomes (36%) and were of a level of evidence III (46%). Most of the top-cited articles came from the journal Spine (68%) and were published in the USA (64%). These top-cited papers are essential to understanding this critical trending topic in spine surgery., Level of Evidence: III., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

C-reactive protein (CRP) has been one of the most investigated inflammatory-biomarkers during the ongoing COVID-19 pandemics caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The severe outcome among patients with SARS-CoV-2 infection is closely related to the cytokine storm and the hyperinflammation responsible for the acute respiratory distress syndrome and multiple organ failure. It still remains a challenge to determine which of the hyperinflammatory biomarkers and cytokines are the best predictors for disease severity and mortality in COVID-19 patients. Therefore, we evaluated and compared the outcome prediction efficiencies between CRP, the recently reported inflammatory modulators (suPAR, sTREM-1, HGF), and the classical biomarkers (MCP-1, IL-1β, IL-6, NLR, PLR, ESR, ferritin, fibrinogen, and LDH) in patients confirmed with SARS-CoV-2 infection at hospital admission. Notably, patients with severe disease had higher serum levels of CRP, suPAR, sTREM-1, HGF and classical biomarkers compared to the mild and moderate cases. Our data also identified CRP, among all investigated analytes, to best discriminate between severe and non-severe forms of disease, while LDH, sTREM-1 and HGF proved to be excellent mortality predictors in COVID-19 patients. Importantly, suPAR emerged as a key molecule in characterizing the Delta variant infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paranga, Pavel-Tanasa, Constantinescu, Plesca, Petrovici, Miftode, Moscalu, Cianga and Miftode.)

(1) Background: Acute heart failure (HF) represents a complex clinical syndrome burdened by increased mortality and a high rate of systemic complications. Although natriuretic peptides (e.g., NT-proBNP) currently represent the diagnostic and prognostic gold standard in acute HF, those molecules do not accurately reflect all the pathophysiological mechanisms involved in the progression of this pathology when determined independently. Therefore, the current paradigm tends to focus on a multi-marker approach for the risk stratification of patients with acute HF. Syndecan-1 is a less studied biomarker in cardiovascular diseases; its assessment in patients with acute HF being potentially able to reflect the myocardial pathological changes, such as fibrosis, inflammation, endothelial dysfunction or global wall stress. (2) Methods: We conducted a single center prospective study that enrolled 173 patients (120 patients admitted for acute HF, compared to 53 controls with stable chronic HF). A complete standardized clinical, echocardiography and laboratory evaluation was performed at admission, including serum samples for the determination of syndecan-1 by the enzyme-linked immunosorbent assay (ELISA) method. (3) Results: The serum concentration of syndecan-1 was significantly higher in patients with acute HF, compared to controls [121.4 (69.3-257.9) vs. 72.1 (41.4-135.8) ng/mL, p = 0.015]. Syndecan-1 was a significant predictor for the diagnosis of acute HF, expressed by an area under the curve (AUC) of 0.898, similar to NT-proBNP (AUC: 0.976) or cardiac troponin (AUC: 0.839). Moreover, syndecan-1 was independently associated with impaired kidney and liver function at admission, being also a predictor for early, subclinical organ dysfunction in patients with normal biological parameters at admission. When included in the multi-marker model, syndecan-1 levels influenced mortality more significantly than NT-proBNP or troponin. A multivariable regression including syndecan-1, NT-proBNP and troponin provided additional prognostic value compared to each independent biomarker. (4) Conclusions: Syndecan-1 can be considered a promising novel biomarker in acute HF, exhibiting adequate diagnostic and prognostic value. Additionally, syndecan-1 can be used as a surrogate biomarker for non-cardiac organ dysfunction, as its highs levels can accurately reflect early acute kidney and liver injury.

The development of the modern society imposes a fast-growing demand for new advanced functional polymer materials. To this aim, one of the most plausible current methodologies is the end-group functionalization of existing conventional polymers. If the end functional group is able to polymerize, this method enables the synthesis of a molecularly complex, grafted architecture that opens the access to a wider range of material properties, as well as tailoring the special functions required for certain applications. In this context, the present paper reports on α-thienyl-ω-hydroxyl-end-groups functionalized oligo-(D,L-lactide) ( Th-PDLLA ), which was designed to combine the polymerizability and photophysical properties of thiophene with the biocompatibility and biodegradability of poly-(D,L-lactide). Th-PDLLA was synthesized using the path of "functional initiator" in the ring-opening polymerization (ROP) of (D,L)-lactide, assisted by stannous 2-ethyl hexanoate (Sn(oct) 2 ). The results of NMR and FT-IR spectroscopic methods confirmed the Th-PDLLA 's expected structure, while the oligomeric nature of Th-PDLLA , as resulting from the calculations based on 1 H-NMR data, is supported by the findings from gel permeation chromatography (GPC) and by the results of the thermal analyses. The behavior of Th-PDLLA in different organic solvents, evaluated by UV-vis and fluorescence spectroscopy, but also by dynamic light scattering (DLS), suggested the presence of colloidal supramolecular structures, underlining the nature of the macromonomer Th-PDLLA as an "shape amphiphile". To test its functionality, the ability of Th-PDLLA to work as a building block for the synthesis of molecular composites was demonstrated by photoinduced oxidative homopolymerization in the presence of diphenyliodonium salt (DPI). The occurrence of a polymerization process, with the formation of a thiophene-conjugated oligomeric main chain grafted with oligomeric PDLLA, was proven, in addition to the visual changes, by the results of GPC, 1 H-NMR, FT-IR, UV-vis and fluorescence measurements.

Introduction: Multisystem injuries affecting vasculature and nerves can be detrimental sequelae of knee dislocations (KDs). The purpose of this study was to provide an update of the current literature since the conducted search used in the publication of Medina et al on May 3, 2013, to evaluate (1) the frequency of vascular and neurologic injury after KD, (2) the frequency with which surgical intervention was conducted for vascular injury in this setting, and (3) the frequency with which each imaging modality was used to detect vascular injury., Methods: A two-author screening process was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the MEDLINE database. Frequency of vascular injury, surgical intervention, and amputation after KD were analyzed. Diagnostic modalities used in the acute-care setting were also evaluated., Results: Nineteen articles were analyzed for a total of 37,087 KDs. Of these, 10.7% sustained vascular injuries and 19.6% sustained nerve injuries. Overall, 62.2% of patients with vascular injury underwent surgical repair and 2.2% limbs resulted in amputation. Angiography was the most frequently used diagnostic modality (91.7%)., Discussion: This review updates our understanding on the clinical implications of KDs including frequency of vascular injury (10.7%), amputation (2.2%), and nerve injuries (19.6%). Compared with prior literature, there was an increased prevalence of KD1 (32.4%) and lateral KDs (80.4%). Most vascular injuries after KD undergo surgical repair (62.2%)., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Factoring a 2048-bit number using Shor's algorithm, when accounting for error correction, reportedly requires 400,000 qubits. However, it is well known that there is yet much time before we will have this many qubits in the same local system. This is why we propose a protocol for distributed quantum computation applicable to small register devices, specifically for the distribution of controlled unitary gates, the key element in the construction of every quantum computation algorithm. We leverage quantum sharing of partial results to obtain a parallel processing scheme, allowing for the first time the quantum distribution of very large gates with thousands of inputs using only small register devices with tens of qubits. In this way, we improve all previous controlled unitary gate distribution approaches, obtaining surprising results. The impact is quantified for recent milestone hardware realizations of quantum processors., (© 2022. The Author(s).)

Introduction: The COVID-19 disease and anti-SARS-CoV-2 vaccination were accompanied by alterations in several inflammatory markers. The aim of our research was to check to what extent such cytokines are transferred to infants via the breastmilk of SARS-CoV-2-infected or vaccinated mothers. Thus, we wanted to check if breastfeeding is safe during SARS-CoV-2 infection or after COVID-19 mRNA-vaccination., Material and Method: The Luminex Multiplexing Assay was used for quantifying 10 cytokine in the human breastmilk of SARS-CoV-2-infected or COVID-19-vaccinated mothers, compared with anti-SARS-CoV-2 IgG naïve mothers. Two milk samples were collected at 30 and 60 days either after the booster dose or afterthe onset of symptoms. A single milk sample was collected from the mothers within the control group., Results: The cytokine concentrations were mostly found within the reference intervals for all mothers. The status of the vaccinated/infected mother, the age of the breastfed child, the parity of the mother and the maternal age were variation factors of the above-mentioned cytokine concentrations. The type of birth and the presence of IgG in the milk had no influence on these cytokine concentrations in milk. Furthermore, no statistically significant differences were recorded between the cytokine concentrations of the two milk samples., Conclusion: Our study provides data that support the safety of breastfeeding in the case of mild COVID-19 infection or after Pfizer or Moderna vaccinations.

(1) Background: Acute heart failure (HF) represents one of the most common yet extremely severe presentations in emergency services worldwide, requiring prompt diagnosis, followed by an adequate therapeutic approach, and a thorough risk stratification. Natriuretic peptides (NPs) are currently the most widely implemented biomarkers in acute HF, but due to their lack of specificity, they are mainly used as ruling-out criteria. Growth differentiation factor-15 (GDF-15) is a novel molecule expressing different pathophysiological pathways in HF, such as fibrosis, remodeling, and oxidative stress. It is also considered a very promising predictor of mortality and poor outcome. In this study, we aimed to investigate the GDF-15’s expression and particularities in patients with acute HF, focusing mainly on its role as a prognosis biomarker, either per se or as part of a multimarker panel. (2) Methods: This unicentric prospective study included a total of 173 subjects, divided into 2 subgroups: 120 patients presented in emergency with acute HF, while 53 were ambulatory-evaluated controls with chronic HF. At admission, all patients were evaluated according to standard clinical echocardiography and laboratory panel, including the assessment of GDF-15. (3) Results: The levels of GDF-15 were significantly higher in patients with acute HF, compared to controls [596 (305−904) vs. 216 (139−305) ng/L, p < 0.01]. GDF-15 also exhibited an adequate diagnostic performance in acute HF, expressed as an area under the curve (AUC) of 0.883 [confidence interval (CI) 95%: 0.828−0.938], similar to that of NT-proBNP (AUC: 0.976, CI 95%: 0.952−1.000), or troponin (AUC: 0.839, CI 95%: 0.733−0.944). High concentrations of GDF-15 were significantly correlated with mortality risk. In a multivariate regression model, GDF-15 was the most important predictor of a poor outcome, superior to NT-proBNP or troponin. (4) Conclusions: GDF-15 proved to be a reliable tool in the multimarker assessment of patients with acute HF. Compared to the gold standard NT-proBNP, GDF-15 presented a similar diagnostic performance, doubled by a significantly superior prognostic value, making it worth being included in a standardized multimarker panel.

The incidence of primary and revision total knee arthroplasty (TKA) is increasing worldwide. Heterotopic ossification is a common and concerning complication of TKA. There are few described cases of severe heterotopic ossification after revision TKA and no known cases of heterotopic ossification causing functional ankylosis after revision TKA. We describe a case of extensive heterotopic ossification in a patient who underwent right TKA for extensive adhesions and stiffness. After early range of motion improvement postoperatively, the patient discontinued a physical therapy regimen. The patient presented 13 years after revision TKA with radiographically evidenced severe heterotopic ossification resulting in a functional ankylosis. The patient elected for nonsurgical management. This case demonstrates a delayed finding of severe heterotopic ossification. The case prompted an applied literature review of several topics: heterotopic ossification as a complication of revision arthroplasty, the contribution of autoimmune and inflammatory conditions to heterotopic ossification; the use of medication, radiation, and physical therapy as prophylaxis against heterotopic ossification; and the range of treatment strategies for severe heterotopic ossification at the knee joint. Consent by the patient involved in this case report was obtained., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: A growing number of patients use the internet to learn about their conditions and management options, but there may exist a disconnect between the readability of online education materials and a patient's health literacy. This issue is of particular relevance for shoulder conditions, where even with traumatic injuries (eg, clavicle fracture, shoulder dislocation), treatment is discretionary, directed primarily at quality of life, and therefore highly preference-sensitive.The purpose of this study was to utilize multiple readability algorithms to calculate the readability of the American Academy of Orthopaedic Surgeons (AAOS) patient education materials pertaining to diseases and conditions of the shoulder., Methods: Online patient education articles from the AAOS pertaining to diseases and conditions of the shoulder were reviewed. The articles were modified for analysis using Readability Pro and readability scores were computed using the following 9 algorithms: Flesch-Kincaid Grade Level, Flesch Reading Ease, Gunning Fog Index, Coleman-Liau Index, Simple Measure of the Gobbledygook Index (SMOG), Automated Readability Index, FORCAST, and New Dale and Chall Index. A list of suggested word changes to improve the readability of included articles was compiled from Readable Pro. The average number of illustrations (images and/or videos) included per article was documented., Results: Twenty-eight articles were included for analysis. For each of the algorithms studied, the average scores were as follows: Flesch Kincaid Grade Level was 8.8 ± .8 [range, 7.2-10.2]; recommended score: ≤ 8.0, Flesch Reading Ease 54.3 ± 5.3 [range, 45.3-64.1]; recommended score: ≥ 60, Gunning Fog 10.8 ± 1.2 [range, 8.3-13.1]; recommended score: ≤ 8.0, Coleman-Liau 11.2 ± .9 [range, 9.2-12.9]; recommended score: ≤8.0, SMOG index 11.4 ± .8 [range, 9.2-12.9]; recommended score: ≤ 8.0 , Automated Readability Index 8.4 ± .8 [range, 6.9-10.0]; recommended score: ≤ 8.0, FORCAST 11.2 ± .4 [range, 10.2-12.0]; recommended score: ≤ 9.0, and New Dale and Chall Index 5.8 ± .5 [range, 4.9-7.2 recommended score: ≤ 6.0-6.9]. The average number of illustrations per article was 4.5 ± 3.1 [range, 1-14]., Conclusion: The readability of most patient education materials from the AAOS pertaining to diseases and conditions of the shoulder is higher than recommended across a variety of algorithms. Efforts to revise the readability of online education materials are important to facilitate shared decision-making, particularly in practice settings where most decisions are preference-sensitive., (© 2022 The Author(s).)

Background: Medial collateral ligament (MCL) injury is a common orthopaedic knee injury with a plethora of published articles regarding evaluation, treatment, and outcome., Purpose: To perform a comprehensive bibliometric analysis of the 50 most cited articles in MCL research., Study Design: Cross-sectional study., Methods: We performed a keyword search of the Institute for Scientific Information's Web of Knowledge database for the identification of articles published before September 2021 encompassing the MCL. The conducted search yielded 9534 articles. The results were then filtered using predetermined guidelines and criteria, and the 50 most cited articles were selected for analysis. Extracted data included title, authors, citation count, year of publication, topic, journal, article type, country of origin, and level of evidence., Results: The selected 50 articles ranged from 1976 to 2013. The largest proportion was classified as having level 4 evidence (n = 12; 24%). The majority of the articles were published in the decade from 2000 to 2009 (n = 17; 34%), followed by 1990 to 1999 (n = 16; 32%). The mean raw citation score per article was 133 (range, 74-422). The most popular topic discussed was surgical technique and outcome (n = 14; 28%), followed by anatomy and biomechanics (n = 13; 26%)., Conclusion: This study provides a comprehensive and objective measure of the most cited articles on MCL research. Knowledge of the characteristics of these most influential articles improves the understanding of MCL injury and can guide discussion for future research., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: L.D.K. has received education payments from Southern Edge Othopaedics and speaking fees and royalties from Arthrex. M.G.B. has received education payments, consulting fees, and speaking fees from Arthrex and hospitality payments from Smith & Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Introduction: Performing total knee arthroplasty (TKA) without the use of tourniquet is gaining popularity. However, performing a "tourniquetless TKA" has a variety of meanings regarding the timing and application of a tourniquet and associated techniques. The purpose of this systematic review was to evaluate the literature and more accurately define "tourniquetless TKA.", Methods: A systematic review following PRISMA guidelines was performed of the PubMed, Web of Science, and Cochrane databases for articles published from 2016 to 2021. Inclusion criteria included papers that used "tourniquetless" or a similar term to describe their TKA procedure, original clinical studies, English language, and full-text studies., Results: A total of 1,096 studies were identified, of which 84 full text studies with 9,349 total patients were included. Overall, 17 (20.2%) of the studies performing tourniquetless TKA never applied a tourniquet, 17 (20.2%) applied a tourniquet but kept it deflated throughout the entire procedure, 2 (2.4%) applied a tourniquet and inflated during cementation only, and 48 (57.1%) did not specify. Ultimately, of the studies that did specify tourniquet use, only 17 studies (47.2%) truly never applied a tourniquet throughout the procedure. A review of 7 recommended techniques to control blood loss in tourniquetless TKA found that no one technique was performed in more than 10.6% of patients., Conclusion: Variation in the definition of tourniquetless TKA and the utilization of augmented techniques to control blood loss remains. We propose the terms "tourniquetless" for no tourniquet application, "tourniquet-available" for tourniquet applied but kept deflated throughout surgery, and "tourniquet-assisted" for tourniquet inflation during cementation only. These terms can help better differentiate the literature, guide surgeons as they transition to tourniquetless TKA, and assist in the development of more definitive protocols for tourniquetless TKA., Competing Interests: Senior author VH declares paid consultation for Stryker, Pfizer, and Consensus, as well as roles as a voting member of the AAHKS International Committee and Editor of JBJS CME. No other authors have any financial disclosures nor declare any conflicts of interest., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to a global health outbreak known as the COVID-19 pandemic which has been lasting since March 2020. Vaccine became accessible to people only at the beginning of 2021 which greatly helped reducing the mortality rate and severity of COVID-19 infection afterwards. The efficacy of vaccines was not fully known and studies documenting the immune responses following vaccination are continuing to emerge. Recent evidence indicate that natural infection prior vaccination may improve the antibody and cellular immune responses, while little is known about the factors influencing those processes. Here we investigated the antibody responses following BNT162b2 vaccination in relation to previous-infection status and age, and searched for possible biomarkers associated with the observed changes in immune responses. We found that the previous-infection status caused at least 8-times increase in the antibody titres, effect that was weaker in people over 60 years old and unaltered by the vitamin D serum levels. Furthermore, we identified adiponectin to positively associate with antibody responses and negatively correlate with pro-inflammatory molecules (MCP-1, factor D, CRP, PAI-1), especially in previously-infected individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pavel-Tanasa, Constantinescu, Cianga, Anisie, Mereuta, Tuchilus and Cianga.)

Background: Hip resurfacing arthroplasty is an accepted treatment option for young patients presenting with osteoarthritis of the hip. The purpose of this review was to evaluate and identify the top 50 most-cited articles pertaining to hip resurfacing, to help clinicians identify influential articles and navigate the literature more effectively., Material and Methods: Clarivate Analytics Web of Science was used to identify all articles related to hip resurfacing. The screening was based on the number of citations for each article. The final list of articles was further reviewed, and further data including manuscript title, authors, total citation count, year of publication, journal, country of origin, and level of evidence were extracted., Results: The most-cited publication was "Pseudotumors associated with metal-on-metal hip resurfacings", which was cited 704 times. The average total number of citations per publication was 203. The most prolific publication year was 2008 with 8 publications, and the most recent article was published in 2012. The journals with the most attributable publications were Journal of Bone and Joint Surgery and Clinical and Orthopedic Related Research ., Conclusions: This review provides a comprehensive analysis of the most-cited articles pertaining to hip resurfacing., Level of Evidence: III., (© 2022 The Authors.)

Background: This study aims to identify the most frequently cited articles published in the Journal of Arthroplasty ( JOA ) and to analyze the trends in the content and contributors of the literature within the journal., Methods: The 100 most cited articles published in the JOA were accessed using the Scopus database. The number of citations, year of publication, level of evidence (LOE), article type, country of origin, and contributing institution were each recorded for each article., Results: The United States (63%) was the most prolific publishing nation. The 1990s (30%) and 2000s (47%) were the most productive decades. The most common article category was clinical outcomes (33%), followed by technical note (16%) and biomechanics (14%). The plurality of the top 100 articles were well-designed case-control or cohort studies of LOE II (46%) followed by LOE V (32%) and LOE I (11%)., Conclusions: Using citation analysis, the most influential articles in the JOA were comprehensively and objectively analyzed. The most popular fields of research involved clinical outcomes (33%) and technical note (16%), both of which increase an article's likelihood of being highly cited. Knowledge of the most influential articles in the JOA allows for appreciation of current and potential future areas of literature regarding diagnosis, management, and outcome of a patient undergoing arthroplasty., (© 2022 The Authors.)

Background and Objectives: Cytokines are cell-signaling proteins whose identification may serve as inflammatory markers or early indicators for progressive disease. The aim of our study was to quantify several cytokines in aqueous humor (AH) and their correlations with biochemical parameters in diabetic eyes with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: A total of 62 eyes from 62 patients were included in the study: 37 eyes from nondiabetic patients (group 1), 13 diabetic eyes with no retinopathy changes (group 2) and 12 diabetic eyes with early and moderate NPDR (group 3). AH samples were collected during uneventful cataract surgery. The cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, TNF-α and VEGF were quantified using multiplex bead-based immunoassay. Due to unreliable results, IL-1β, TNF-α, IL-10 and IL-12 were excluded. Concentrations were compared between groups. Biochemical parameters (fasting blood sugar, glycated hemoglobin, C-reactive protein) and the duration of diabetes were recorded. Results: VEGF levels were significantly different between groups (p = 0.001), while levels of IL-6, IL-8, IP-10 and MCP-1 were comparable across all groups (p > 0.05). IL-6 concentration correlated with VEGF in group 1 (rho = 0.651, p = 0.003) and group 3 (rho = 0.857, p = 0.007); no correlation could be proved between IL-6, IL-8, IP-10, MCP-1 or VEGF and biochemical parameters. Duration of diabetes was not correlated with the cytokine levels in groups 2 and 3. The receiver operating characteristic (ROC) curve revealed that VEGF concentrations could discriminate early and moderate NPDR from diabetes, with an area under the curve (AUC) of 0.897 (p = 0.001, 95% CI = 0.74−1.0). Conclusions: Diabetes mellitus induces significant intraocular changes in the VEGF expression in diabetic patients vs. normal subjects, even before proliferative complications appear. VEGF was increasingly expressed once the diabetes progressed from no retinopathy to early or moderate retinopathy.

Purpose: Commercially available smartphone apps and wearable devices have proven valuable in a variety of clinical settings, yet their utility in measuring physical activity and monitoring patient status following total knee arthroplasty (TKA) remains unclear., Methods: A systematic review was performed to assess the evidence supporting the use of smartphone apps and wearable devices to assist rehabilitation interventions following TKA. A search was conducted in the PubMed, Cochrane, Medline, and Web of Science databases in September 2021., Results: One hundred and seventy-six studies were retrieved, of which 15 met inclusion criteria, including 6 randomized control trials. Four of these studies utilized smartphone apps, seven utilized wearable devices, and four utilized a combination of both. A total of 1607 TKA patients participated in the included studies. For primary outcomes, three reported on device accuracy, three on recovery prediction, two on functional recovery, two on physical activity promotion, two on patient compliance, two on pain control, and one on healthcare utilization., Conclusion: Commercially available smartphone apps and wearable devices were shown to capably monitor physical activity and improve patient engagement following TKA, making them potentially viable adjuncts or replacements to traditional rehabilitation programs. Components of interventions such as step goals, app-based patient engagement platforms, and patient-specific benchmarks for recovery may improve effectiveness. However, future research should focus on the economics of implementation, long-term outcomes, and optimization of compliance and accuracy when using these devices.

The empirical administration of antibiotics for suspected bacterial meningitis denotes a poor bacterial stewardship. In this context, the use of biomarkers can distinguish between bacterial and viral infections before deciding treatment. Our study assesses how levels of heparin-binding protein (HBP), neutrophil gelatinase-associated lipocalin (NGAL), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) and in blood can promptly confirm bacterial etiology and the need for antibiotic treatment. The CSF and blood levels of HBP, NGAL, S100B, and NSE of 81 patients with meningitis were measured and analyzed comparatively. Statistical sensitivity, specificity, and positive and negative predictive values were evaluated. CSF levels of HBP and NGAL and the blood level of S100B in the bacterial meningitis group were significantly higher (p < 0.05). The area under curve (AUC) for predicting bacterial meningitis was excellent for the CSF level of HBP (0.808 with 93.54% sensitivity and 80.64% specificity), good for the CSF level of NGAL (0.685 with 75.00% sensitivity and 65.62% specificity), and good for the blood level of S100B (0.652 with 65.90% sensitivity and 57.14% specificity). CSF levels of HBP and NGAL, as well as the blood level of S100B, could help discriminate between bacterial and viral meningitis before considering antibiotic treatment.

(1) Background: Low patient’s adherence to conventional cervical cancer screening methods determined the need to take into consideration alternative approaches, and vaginal HPV self-sampling is one of them. We aimed to evaluate, using an online survey, the Romanian women’s acceptability of vaginal HPV self-sampling. (2) Methods: A 13-questions online survey was distributed on three Facebook groups, and the results were summarized. (3) Results: Despite of good educational background, 10.8% (n = 60) of the respondents did not know what a Pap smear is, and 33% (n = 183) were not informed about the free national cervical cancer screening program. Multivariate analysis revealed an increased likelihood of vaginal self-sampling acceptance among respondents who did not know about Pap test (OR: 7.80; 95%CI: 1.062−57.431; p = 0.021), national cervical cancer screening program (OR: 1.96; 95%CI: 1.010−3.806; p = 0.02), HPV infection (OR: 7.35; 95%CI: 3.099−17.449; p< 0.001) or HPV test (OR: 1.67; 95%CI: 0.950−2.948; p = 0.03). Moreover, women who did not previously undergo a cervical cancer screening program were more likely to accept the new screening method (OR: 1.62; 95%CI: 0.878−3.015; p = 0.04). (4) Conclusions: Our results showed high acceptability rates of vaginal HPV self-sampling among participants.

Background: Bibliometric analysis is a useful tool for measuring the scholarly impact of a topic. To date, there is no such review analyzing the characteristics and trends of publications focused on revision total hip arthroplasty (rTHA). The purpose of this study is to use bibliometric analysis to comprehensively analyze the 50 most cited articles in rTHA research., Methods: This is a cross-sectional study that used the ISI Web of Knowledge database to identify articles published before September 2021. Articles were sorted in descending order by number of citations and those with a focus of rTHA were identified. Of these, the top 50 most cited articles were carried forward for evaluation., Results: The 2000s (50%) and the 1990s (32%) had the greatest volume of contribution. 9 of the top 10 most cited articles were published in the 2000s. The highest impact article had 4702 citations. The level of evidence (LOE) published with the greatest frequency was LOE II (40%) followed by LOE III and LOE IV both recording 24%. The Journal of Bone and Joint Surgery-American Volume had the greatest productivity (46%) followed by The Journal of Bone and Joint Surgery-British Volume (18%). The United States was the country with the highest number of contributions to this list with 56% followed by England (12%), and Sweden and Canada both with 8%., Conclusion: The most impactful articles focusing on rTHA research were comprehensively and objectively analyzed. The most common article type was clinical outcomes (46%) followed by natural history/epidemiology (24%) and surgical technique (16%). While this topic is highly studied with significant level of evidence to support the studies, there is a lack of influential research regarding imaging and clinical guidelines. This analysis can be used by researchers to develop further discussions and build research questions., Competing Interests: The authors report no conflicts of interest., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Introduction: and Importance: Anterior dislocation of a prosthetic knee is rarely encountered. Acute vascular injury following anterior prosthetic dislocation has only been reported once in the literature with extremely poor outcomes., Case Presentation: The authors report the case of a 70-year-old woman who presented with anterior prosthetic knee dislocation after a fall from slipping. After closed reduction, CT angiography found transection and active extravasation of the left popliteal artery. An emergent fasciotomy and popliteal bypass were performed with concurrent external fixation of the joint. Recovery was complicated by bacteremia requiring eventual explant of total knee arthroplasty (TKA)., Clinical Discussion: We report the only case of successful vascular repair after acute vascular injury from traumatic anterior prosthetic dislocation. External fixation of the knee allowed for better stabilization of the joint and preservation of the repaired vascular injury; however, it carries a risk for infection, as seen in this case., Conclusions: While there are no clear guidelines for management, we highlight the importance of rapid diagnosis with CT angiography and shared decision making with the vascular surgery team to repair the injury and stabilize the joint., Competing Interests: None declared., (© 2022 The Authors.)

The appearance of the severe acute respiratory syndrome virus-2 (SARS-CoV-2) has had a significant impact on the balance of public health and social life. The data available so far show that newborns and young children do not develop severe forms of COVID-19, but a small proportion of them will still need hospitalization. Even though young children represent an important vector of the infection, vaccination at such a young age was not yet considered. Thus, the question of whether potentially protective antibodies against SARS-CoV-2 could be provided to them via breast milk or across the placenta, as "passive immunity", still stands., Materials and Methods: Between January-July 2021, we have conducted a prospective study that aimed to measure the immunoglobulin (Ig) A and IgG anti-SARS-CoV-2 titers in the breast milk of 28 vaccinated lactating mothers, sampled at 30 and 60 days after the second dose of the anti-SARS-CoV-2 Pfizer or Moderna mRNA vaccines. Anti-RBD reactive IgA and IgG antibodies were detected and quantified by a sandwich enzyme-linked immunosorbent assay., Results: Anti-RBD IgA and IgG were present in all breast milk samples, both in the first and in the second specimens, without a significant difference between those two. The anti-RBD IgA titers were approximately five-times higher than the anti-RBD IgG ones. The anti-RBD IgA and IgG titers were correlated with the infants' age, but they were not correlated with the vaccine type or mother's age. The anti-RBD IgA excreted in milk were inversely correlated with the parity number., Conclusions: Anti-SARS-CoV-2 IgA and IgG can be found in the milk secretion of mothers vaccinated with mRNA vaccines and, presumably, these antibodies should offer protection to the newborn, considering that the antibodies' titers did not decrease after 60 days. The antibody response is directly proportional to the breastfed child's age, but the amount of anti-RBD IgA decreases with the baby's rank. The antibody response did not depend on the vaccine type, or on the mother's age.

Background Social media use among scholars and journals is growing and has augmented the academic impact of published articles in several areas of medicine. However, the influence of social media postings on academic citations of shoulder and elbow surgery publications is not known. In this study, we sought (1) to quantify the adoption of Twitter use for the dissemination of research publications by three prominent shoulder and elbow surgery journals and (2) to determine the correlation between Twitter mentions and academic citations in shoulder and elbow surgery publications. Methodology A total of 396 original research articles from three shoulder and elbow surgery journals (Journal of Shoulder and Elbow Surgery (JSES), Shoulder & Elbow, and JSES International) published in 2018 were assessed 34 to 45 months after print publication. For each article, the total number of Twitter mentions were obtained using Altmetric Bookmarklet and grouped into those tweeted by authors, an official outlet, or a third party. Article citation data was obtained using the Google Scholar search engine. Pearson correlation was used to determine the association between the number of Twitter mentions and citation count. Results Of all articles, 51% (202/396) had at least one Twitter mention. Of all Twitter mentions, 12.7% (367/2,879) occurred within the first week of online publication dates, while 51.5% (1,482/2,879) occurred between online and print publication dates. Articles mentioned on Twitter had 1.3-fold more Google Scholar citations (17.7 ± 15.2) than articles with no Twitter mentions (14.0 ± 15.7) (p = 0.017). The number of Twitter mentions had a weakly positive correlation with academic citation count (r = 0.25; p < 0.001). No significant difference in academic citation rates was found between articles tweeted by authors or official outlets when compared to articles tweeted by a third party only (p = 0.97 and p = 0.34, respectively). Conclusions Approximately half of shoulder and elbow surgery publications are shared on Twitter, with the majority of the activity occurring prior to their print publication date. The finding that tweeted articles have more academic citations within three years of release suggests that social media activity seems to amplify the academic impact of shoulder and elbow surgery publications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sudah et al.)

Background: Kidney transplantation-associated mineral and bone disorder (KT-MBD) still represents a black box on the long-term due to scarce available data. We aimed to investigate the impact of non-classical bone regulating factors (body composition, adipokines, inflammatory markers, fibroblast growth factor 23-FGF23 and α-Klotho) in long-standing kidney transplant (KT) recipients compared to the general population., Methods: Our cross-sectional study, enrolling 59 KT patients and age, sex and body mass index-matched healthy general population volunteers, assessed the predictive role of the body composition, serum adipokines (leptin, adiponectin, resistin), inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and parathyroid hormone (PTH)-FGF23/α-Klotho axis upon bone mineral density (BMD) and osteocalcin, using correlation and linear multiple regression., Results: The 59 KT recipients (mean transplantation span of 57.7 ± 7.2 months) had similar body composition but significantly lower BMD (p < 0.01) compared to the general population group. Total lean mass was independently associated with BMD in both groups. In KT patients, age, time spent on dialysis and PTH were the main negative independent predictors of BMD, after adjusting for possible confounders. Resistin and α-Klotho also negatively predicted lumbar bone density (p < 0.001), while adiponectin and α-Klotho positively predicted osteocalcin levels (p < 0.001) in KT recipients, independently of inflammatory markers. No significant associations were found between FGF23 and bone parameters in any of the groups., Conclusions: Age, PTH, time on dialysis and lean mass are among the main bone density predictors in long-standing KT patients. The bone impact of adipokine dysregulation and of α-Klotho merits further investigations in KT-MBD. Preserving lean mass for improved bone outcomes should be part of KT-MBD management on the long-term., (© 2021. Italian Society of Nephrology.)

Background : Heart failure (HF) is a complex clinical syndrome that represents a great burden on public health systems due to its increased prevalence, disability and mortality rates. There are multiple triggers that can induce or aggravate a preexisting HF, socioeconomic status (SES) emerging as one of the most common modifiable risk factors. Our study aimed to analyze the influence of certain SES indicators on the outcome, clinical aspects and laboratory parameters of patients with HF in North-Eastern Romania, as well as their relationship with other traditional cardiovascular risk factors. Methods : We conducted a prospective, single-center study comprising 120 consecutively enrolled patients admitted for acute HF. The evaluation of individual SES was based upon a standard questionnaire and evidence from official documents. Results : the patients' age ranged between 18 and 94 years; Out of 120 patients, 49 (40.8%) were women and 71 (59.2%) were men, residing in rural 59 (49.2%) or urban 61 (50.8%) areas. 14.2% were university graduates, while 15.8% had only attended primary school. The majority of the patients are or were employed in the service sector (54.5%), followed by industry (29.2%) and agriculture (20%). The mean monthly income was 306.1 ± 177.4 euro, while the mean hospitalization cost was 2471.8 ± 2073.8 euro per patient. The individual income level was positively correlated with urban area of residence, adequate household sanitation facilities and healthcare access, and negatively associated with advanced age and previous hospitalizations due to HF. However, the individual financial situation was also positively correlated with the increased prevalence of certain cardiovascular risk factors, such as arterial hypertension, anemia or obesity, but not with total cholesterol or male gender. Concerning the direct impact of a poor economic status upon prognosis in the setting of acute HF, our results showed no statistically significant differences concerning the in-hospital or at 1-month follow-up mortality rates. Rather than inducing a direct impact on the short-term outcome, these findings concerning SES indicators are meant to enhance the implementation of policies aimed to provide adequate healthcare for people from all social layers, with a primary focus on modifiable cardiovascular risk factors.

Background: There is a paucity of literature about return to play (RTP) for golf protocols following cervical and lumbar fusions. The timing of return to this sport is a common question among patients. The aim of this review was to analyze and report the current protocols for RTP following cervical and lumbar spinal fusion., Methods: A systematic search was conducted using the following databases: MEDLINE, PubMed, Web of Science, Scopus, and Google Scholar. A 3-step, multiauthor screening process was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included peer-reviewed and published prospective, case-control, cohort, case series, or review articles. Studies had to pertain to RTP for golf following instrumented cervical or lumbar spinal fusion to be included., Results: Three articles met inclusion criteria: 2 retrospective survey-based cohort studies and 1 survey-based case series study. All studies included a minimum of 1 year of follow-up. Of patients, 71.6% (n = 51) were able to RTP following surgery; 54.3%-80% were able to RTP at a similar or improved level of play as preoperatively. Postoperative pain reduction was noted in 2 articles., Conclusions: Most golfers are able to RTP within 12 months following cervical or lumbar spinal fusion. Patients generally reported decreased lower back pain and leg pain postoperatively. Following cervical or lumbar fusion, many golfers are able to RTP at the same or an increased frequency compared with preoperatively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians' interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value., Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach., Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 ( r (120) = 0.20, p < 0.002)., Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.

This paper proposes a strategy to overcome the threats posed to connectivity-preserving synchronization of Euler-Lagrange networks by time-varying delays and bounded actuation. It first introduces a suitable distributed negative gradient plus damping injection controller, based on which it establishes that the local connectivity of time-delay Euler-Lagrange networks can be preserved by appropriately regulating the interagent connections and increasing the damping injection locally. Yet, actuator saturation may impede the proper modulation of the interagent connections and the injection of sufficient damping and, thus, may threaten the maintenance of connectivity. This paper then develops an indirect coupling control framework which integrates the bounded actuation constraints into the control design. The framework endows every agent with a virtual proxy and couples initially adjacent agents through their virtual proxies. The interproxy couplings then tackle the time-varying delays while the agent-proxy couplings account for the saturation of actuators. Lyapunov-Krasovskii analysis proves that the indirect coupling strategy can drive time-delay Euler-Lagrange networks with bounded actuation to connectivity-preserving synchronization by limiting the energy of the agent-proxy and interproxy couplings according to the actuation constraints. Experiments with Geomagic Touch haptic robots validate the proposed designs compared to a conventional proportional plus damping controller.

The coexistence of stable limit cycles and chaotic attractors has already been observed in some 3D dynamical systems. In this paper we show, using the T-system, that unstable limit cycles and chaotic attractors can also coexist. Moreover, by completing the characterization of the existence of invariant algebraic surfaces and their associated global dynamics, we give a better understanding on the disappearance of the strange attractor and the limit cycles of the studied system., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Constantinescu D et al.)

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second most common cause of cancer-related death globally. This type of liver cancer is frequently detected at a late stage by current biomarkers because of the high clinical and biological heterogeneity of HCC tumours. From a plethora of molecules and cellular compounds, small nanoparticles with an endosomal origin are valuable cancer biomarkers or cargos for novel treatments. Despite their small sizes, in the range of 40-150 nm, these particles are delimited by a lipid bilayer membrane with a specific lipid composition and carry functional information-RNA, proteins, miRNAs, long non-coding RNAs (lncRNAs), or DNA fragments. This review summarizes the role of exosomal microRNA (miRNA) species as biomarkers in HCC therapy. After we briefly introduce the exosome biogenesis and the methods of isolation and characterization, we discuss miRNA's correlation with the diagnosis and prognosis of HCC, either as single miRNA species, or as specific panels with greater clinical impact. We also review the role of exosomal miRNAs in the tumourigenic process and in the cell communication pathways through the delivery of cargos, including proteins or specific drugs.