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In this work photonic energy from a high power xenon flash lamp is used for soldering thin chips on polyimide and polyester foil substrates using standard Sn-Ag-Cu lead free alloys. The absorption of the xenon light pulse leads to rapid heating of components and tracks up to temperatures above the solder melting temperature, while the temperature in the organic foil substrates remains low. Due to its high transparency the temperature in the delicate polyester foil remains low enough to avoid damage and allows fast soldering with standard lead-free alloys. The technology is fast and could be applied in-line in roll-to-roll fabrication of flexible electronics. In situ temperature measurements were performed and compared to finite element model predictions of the temperature in the chip during and after application of the photonic pulse. The accuracy of the model is within 10°C for the tested samples, which allows it to be used in developing photonic flash soldering compatible circuit designs. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) and arterial thrombosis (AT) are distinct yet closely related pathological processes. While traditionally considered separate entities, accumulating evidence suggests that they share common risk factors, such as inflammation and endothelial dysfunction (ED). This review explores the parallels and differences between venous and arterial thrombosis, with particular attention to the role of unprovoked VTE and its potential links to atherosclerosis and systemic inflammation. A key focus is the role of ED, which is emerging as a critical factor in thrombogenesis across both the venous and arterial systems. We examine the current methods for clinically detecting ED, including the use of biomarkers and advanced imaging techniques. Additionally, we discuss novel research avenues, such as the potential of endothelial colony-forming cells and other innovative methodologies, to further unravel the complex mechanisms of thrombosis. Finally, we propose future clinical scenarios where targeting endothelial health could pave the way for more effective prevention and treatment strategies in thrombosis management. [ABSTRACT FROM AUTHOR]

Background: Fungal infections are significant complications of severe coronavirus disease 2019 (COVID-19). Although various risk factors for poor outcomes in patients with COVID-19 have been identified, clinical and treatment factors associated with fungal infections in patients with severe COVID-19 remain unclear. This study aimed to elucidate clinical factors associated with fungal infections during severe COVID-19 treatment. Methods: This was a post hoc analysis of the J-RECOVER study, a multicenter retrospective observational study involving patients with COVID-19 who required admission at 66 hospitals between January and September 2020. Inclusion criteria were ages ≥ 18 years, COVID-19 diagnosis with reverse-transcription polymerase chain reaction, and treatment with mechanical ventilation (MV). Patients who received antifungal drugs before MV were excluded. Potential predictors were identified through univariate analysis of patient and treatment characteristics between patients with- and those without fungal infection, which was defined as antifungal agent use for ≥ 5 days. To account for facility-specific data clustering, generalized estimating equations (GEE) were employed as adjusted analyses to calculate the relative risks of potentially associated factors. Two sensitivity analyses were performed with modified definitions for the two groups: patients who received antifungal drugs for ≤ 4 days were excluded, and fungal infection was re-defined as antifungal drug use for ≥ 14 days. Results: Among 4,915 patients in the J-RECOVER study, 559 adults with COVID-19 who required MV were included. Fungal infections occurred in 57 (10.2%) patients. Univariate analyses identified age, age ≥ 65 years, D-dimer level, remdesivir use, steroid use, and duration of steroid therapy as potential predictors of fungal infections. Multivariate analysis using GEE on these six factors revealed that only the duration of steroid use was significantly associated with an increased risk of fungal infection (odds ratio [OR] for a day increase: 1.01; 95% confidence interval [CI]: 1.00–1.01; p < 0.001). The two sensitivity analyses similarly showed that the duration of steroid use was associated with fungal infection (odds ratio for a day increase: 1.01; 95% CI: 1.00–1.01; p < 0.001 for both). Conclusions: In patients with severe COVID-19 requiring MV, each additional day of steroid use was associated with prolonged use of antifungal medications for ≥ 5 days. [ABSTRACT FROM AUTHOR]

Background/Objectives: Several studies investigated the risk factors for severe COVID-19-related outcomes. Early identification and proper treatment of COVID-19 patients who may develop severe pneumonia are crucial. The aim of this study was to detect the importance of the laboratory parameters for risk prediction of severe pneumonia in COVID-19 patients. Methods: This retrospective cohort study included COVID-19 patients' laboratory parameters at admission. Biochemical, hematological, coagulation, and inflammatory parameters values were compared between the non-severe and severe groups. Results: A total of 534 COVID-19 patients were screened, and 472 of them were included in this study. The mean age of patients was 64 (±3.1) years; 242 (51.3%) were men. A total of 204 (43.2%) patients were diagnosed as severe cases. The independent predictors of severe illness were C-reactive peptide, Eosinophil, neutrophil–lymphocyte ratio, interleukin-6, and lactate dehydrogenase. These parameters were named as CENIL scores from 0 to 5 points. The findings of this study indicate that these biomarkers identified tend to increase progressively with disease severity in severe COVID-19 patients. Additionally, the CENIL risk score identified a specific cut-off value of 3, highlighting it as a critical threshold for identifying patients at high risk of severe COVID-19 progression. Conclusions: In this study, we identified biomarkers—including CRP, eosinophil count, NLR, IL-6, and LDH—named as CENIL risk score that can help predict the likelihood of severe disease at diagnosis. Clinicians may be more vigilant regarding the development of severe disease in patients with high CENIL risk scores, guided by clinical and radiological findings. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) can lead to various multisystem disorders, including thrombotic microangiopathy (TMA). We present here eight patients with COVID-19-associated TMA who were treated at our center. Our aim was to summarize the demographic and clinical characteristics of the patients and discuss the possible role of COVID-19. One patient presented with thrombotic thrombocytopenic purpura (TTP) and seven with atypical hemolytic–uremic syndrome (aHUS.) Most patients had no obvious symptoms of COVID-19, and TMA occurred after viremia. Two patients had concomitant non-COVID-19-related triggers for TMA: exposure to tacrolimus and everolimus; first presentation of antiphospholipid syndrome. The patient with TTP was treated with therapeutic plasma exchange (TPE), steroids and caplacizumab, resulting in complete hematologic recovery. Six patients with aHUS were treated with TPE with or without steroids, four of whom received a C5 complement inhibitor and one an intravenous immunoglobulin. One patient with aHUS was treated with a C5 complement inhibitor and a steroid. We observed one partial and one complete recovery of renal function, while five patients experienced renal failure. There were no deaths. We believe that COVID-19 may act as a trigger for TMA in patients who have either pre-existing endothelial injury or an underlying predisposition to complement activation, and may also trigger autoimmune diseases. As a consequence of the different underlying pathophysiologies, the treatment of COVID-19-associated TMA requires a specific approach based on the subtype of the syndrome and possible concomitant triggers. [ABSTRACT FROM AUTHOR]

Viral infections in humans often cause excessive inflammation. In some viral infections, inflammation can be serious and even fatal, while in other infections it can promote viral clearance. Viruses can escape from the host immune system via regulating inflammatory pathways, thus worsening the illness. MicroRNAs (miRNAs) are tiny non-coding RNA molecules expressed within diverse tissues as well as cells and are engaged in different normal pathological and physiological pathways. Emerging proof suggests that miRNAs can impact innate and adaptive immunity, inflammatory responses, cell invasion, and the progression of viral infections. We discuss some intriguing new findings in the current work, focusing on the impacts of different miRNAs on host inflammatory responses and virus-mediated inflammation. A better understanding of dysregulated miRNAs in viral infections could improve the identification, prevention, and treatment of several serious diseases. [ABSTRACT FROM AUTHOR]

Aim: to investigate the content of eNOS in the blood serum of patients with coronavirus disease (COVID-19) with pneumonia in association with hemostatic parameters and to determine its prognostic value in assessing the risk of oxygen dependence and death. Material and methods. There were 123 patients with COVID-19 with pneumonia under observation. All patients were examined and treated in accordance with the Order of the Ministry of Health of Ukraine No. 722 dated 28.03.2020. The eNOS content in the patients’ serum was determined by enzyme-linked immunosorbent assay. Results. It was found that the content of eNOS in the blood serum of patients with COVID-19 with pneumonia at the time of hospitalization was 9.0 [7.0; 12.0] days lower (p < 0.001) than in healthy subjects. The development of oxygen dependence in patients with COVID-19 with pneumonia was accompanied by worsening of endothelial dysfunction and procoagulant changes, which was confirmed by a decrease in the content of eNOS in the blood serum (p < 0.001), an increase in the level of fibrinogen (p < 0.05) and D-dimer (p < 0.05). The threshold level of eNOS in the blood serum ≤327.09 pg/ml (AUC = 0.861, p < 0.001) was predictive of the onset of oxygen dependence. In patients with COVID-19 with pneumonia who subsequently died, at the time of hospitalization, eNOS levels were lower (p < 0.001) than in patients who recovered, which was combined with a higher level of D-dimer (p < 0.05) and its more frequent increase (p = 0.04) compared with patients who recovered. The eNOS content in the blood serum of patients with COVID-19 with pneumonia was correlated (p < 0.05) not only with the lethal outcome of the disease, but also with the formation of thrombotic complications, which occurred more often in patients with COVID-19 with pneumonia in the event of an adverse outcome (p = 0.0001). The threshold level of eNOS in the blood serum ≤201.75 pg/ml (AUC = 0.892, p < 0.001) was indicative of a high probability of death. Conclusion. The eNOS content in the blood serum of patients with COVID-19 pneumonia at the time of hospitalization is lower (p < 0.001) than in healthy individuals, and the degree of its decrease depends on the severity of the disease, the development of oxygen dependence and the subsequent outcome of this disease. Limiting levels of eNOS in the blood serum of patients with COVID-19 pneumonia, which are important for predicting the risk of developing oxygen dependence and fatal outcome of the disease, have been established. [ABSTRACT FROM AUTHOR]

Background: Pilomatrixoma is an uncommon benign skin neoplasm originating from the hair follicle. Here, we report a rare case of giant and atypical proliferating pilomatrixoma affecting the eyelid. Case presentation: A 47-year-old male presented with a solitary, giant mass on his left upper eyelid, which had recently shown progressive enlargement. The lesion appeared well-circumscribed with a firm consistency, and measuring 7 × 10 cm. Orbital computed tomography scan revealed no intraorbital extension. The lesion was surgically excised. Histopathological examination identified the mass as an atypical proliferating pilomatrixoma, characterized by a minimal infiltrating margin of the deep plane and focal cytological atypia of the basaloid cells. No recurrence was observed up to one year postoperatively. Conclusions: Pilomatrixoma is a rare periocular tumor with potential for malignant transformation, often mimicking other lesions in this region. Therefore, any enlarging masses in this area should be excised for histopathological evaluation to rule out malignancy. [ABSTRACT FROM AUTHOR]

Twelve patients managed with supracricoid partial laryngectomies (SCPLs) after failed laryngeal radiation therapy (RT) were evaluated. None of the recurrent tumors were amenable to vertical or horizontal partial laryngectomy. Results were analyzed for tracheostomy decannulation, oral alimentation, morbidity, local control, and survival. Major complications included perichondritis (2 patients), laryngeal stenosis (2 patients), and pneumonia from aspiration (1 patient). Mucocutaneous fistula and cricoarytenoid joint ankylosis were not encountered. Margins of resection were uninvolved in all cases. The Kaplan-Meier 3-year actuarial survival and local control estimate was 83.3%. Salvage total laryngectomy allowed for an overall 100% local control rate and a 75% laryngeal preservation rate. This preliminary report suggests that, in patients with failed laryngeal RT not amenable to vertical or horizontal partial laryngectomy, the SCPL procedures should be discussed before advocating salvage total laryngectomy. Further series analyzing the role and limitations of the various SCPL procedures after failed laryngeal RT are warranted. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation. We investigated the impact of UFH dose during ECMO therapy at the coagulation–inflammation interface level, focusing on complement activation and changes in circulating large EV (lEV) subsets. In a post hoc analysis of a multicenter randomized controlled trial comparing two anticoagulation management algorithms, we examined lEV levels and complement activation in 23 veno-venous-ECMO patients stratified by UFH dose. Blood samples were collected at different time points and grouped into three phases of ECMO therapy: initiation (day 1), mid (days 3–4), and late (days 6–7). Immunoassays detected complement activation, and flow cytometry analyzed lEV populations with an emphasis on mitochondria-carrying subsets. Patients receiving <15 IU/kg/h UFH exhibited higher levels of the complement activation product C5a and soluble terminal complement complex (sC5b-9). Lower UFH doses were linked to increased endothelial-derived lEVs, while higher doses were associated with elevated RBC-derived and mitochondria-positive lEVs. Our findings suggest the potential theranostic relevance of EV detection at the coagulation–inflammation interface. Further research is needed to standardize EV detection methods and validate these findings in larger ECMO patient cohorts. [ABSTRACT FROM AUTHOR]

High-risk acute myeloid leukemia has been associated with a poor outcome. Hematopoietic stem cell transplantation (HSCT) represents the only curative option for eligible patients. Relapse after HSCT is a dramatic event with poor chances of survival. With the aim of reducing the rate of post-HSCT relapse, maintenance treatment has been investigated in this setting. Results from clinical trials suggest an advantage in the use of a maintenance strategy; however, standardized guidelines are not yet available due to the lack of prospective clinical trials. In this review, we have reported the most important strategies adopted as post-HSCT maintenance, highlighting their efficacy, but the current research also opens questions. [ABSTRACT FROM AUTHOR]

Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other drugs with varying mechanisms of action (MoAs). Furthermore, multidrug treatment against COVID-19 is an ongoing topic and merits further investigation. Method/Objectives. We assessed the efficacy of multidrug treatment against SARS-CoV-2 in reconstituted human nasal epithelia, using combinations of molnupiravir and nirmatrelvir as a baseline, adding suboptimal concentrations of either GS-441524 or ivermectin, attempting to increase overall antiviral activity while lowering the overall therapeutic dose. Results. Nirmatrelvir combined with molnupiravir, GS-441524, or ivermectin at suboptimal concentrations show increased antiviral activity compared to single treatment. No triple combinations showed improved inhibition of SARS-CoV-2 replication beyond what was observed for double treatments. Conclusions. In general, we observed that the addition of a third compound is not beneficial for antiviral activity, while various double combinations exhibit increased antiviral activity over single treatment. [ABSTRACT FROM AUTHOR]

Background: The high complexity of systemic autoimmune diseases (SADs) has hindered precise management. This study aims to investigate heterogeneity in SADs. Methods: We applied a joint cluster analysis, which jointed multiple correspondence analysis and k-means, to immunomarkers and measured the heterogeneity of clusters by examining differences in immunomarkers and clinical manifestations. The electronic health records of patients who received an antinuclear antibody test and were diagnosed with SADs, namely systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were retrieved between 2001 and 2016 from hospitals in Taiwan. Results: With distinctive patterns of immunomarkers, a total of 11,923 patients with the three SADs were grouped into six clusters. None of the clusters was composed only of a single SAD, and these clusters demonstrated considerable differences in clinical manifestation. Both patients with SLE and SS had a more dispersed distribution in the six clusters. Among patients with SLE, the occurrence of renal compromise was higher in Clusters 3 and 6 (52% and 51%) than in the other clusters (p < 0.001). Cluster 3 also had a high proportion of patients with discoid lupus (60%) than did Cluster 6 (39%; p < 0.001). Patients with SS in Cluster 3 were the most distinctive because of the high occurrence of immunity disorders (63%) and other and unspecified benign neoplasm (58%) with statistical significance compared with the other clusters (all p < 0.05). Conclusions: The immunomarker-driven clustering method could recognise more clinically relevant subgroups of the SADs and would provide a more precise diagnosis basis. [ABSTRACT FROM AUTHOR]

Background: Facial nerve injury (FNI) is the most common complication of parotid surgery and manifests as FN paralysis. The use of intraoperative facial nerve monitoring (IFNM) is becoming an established intraoperative aid for surgeons, assisting in the identification of the location and dissection of the facial nerve trunk or branches. The postoperative outcomes of parotid surgery with and without monitoring have been addressed in only a limited number of studies. Objective: The objective of this study is to evaluate the incidence of postoperative paralysis in patients undergoing extracapsular dissection (ED) for benign parotid tumors concerning the use or non-use of IFNM. Materials and Methods: The retrospective study was conducted at the Maxillo-Facial Department of the Magna Graecia University of Catanzaro. The patients were divided into two groups: Group 1 consisted of patients who underwent surgery without IFNM (1 January 2015 to 31 December 2018); Group 2, on the other hand, consisted of patients who underwent surgery with IFNM (1 January 2019 to 31 December 2022). Group 2 employed the Nerve Integrity Monitor (Medtronic's NIM®). To classify the FN function, we employed the modified House–Brackmann classification system. To evaluate the dependence between the "use of IFNM" and "postoperative paralysis", a descriptive analysis was conducted, including applying the Chi-squared test and calculating the Pearson correlation. Subsequently, a binary logistic regression model was applied to further evaluate the correlation between the latter. The level of statistical significance was set at p < 0.05. Results: A total of 276 patients were included in the study: 120 subjects were assigned to Group 1 (43.5%, comprising 60 men and 60 women) and 156 subjects were assigned to Group 2 (56.5%, comprising 93 men and 63 women). In 91.7% of the cases (n. 253, precisely 105 in Group 1 and 148 in Group 2), no FNI occurred. In 8.33% of the cases (n. 23, specifically 15 in Group 1 and 8 in Group 2), postoperative paralysis was observed. Of these subjects, only two in Group 1 had permanent paralysis (8.69%); therefore, 91.31% had transient paralysis. As a result, 91.31% of the subjects exhibited transient paralysis. In the case of FNI, 78% of the cases involved the marginal mandibular branch (n. 18), 13% involved the temporo-zygomatic branch (n. 3), and 7% involved more than one branch (n = 2). The results of the multivariable binary logistic regression analysis demonstrated that the use of IFNM was a statistically significant influencing factor, with an estimated reduction in postoperative paralysis of approximately 62% (OR 0.378; 95% CI: 0.155–0.92). In Group 2, the occurrence of transient complications was significantly reduced (OR 0.387; 95% CI: 0.149–1.002 with p < 0.05). Discussion and Conclusions: The use of IFNM in the ED for benign parotid tumors significantly reduces the rate of FNI and, consequently, postoperative FN paralysis. On the other hand, the use of monitoring systems must not replace the experience and anatomical knowledge of the surgeon. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease's severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction. Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections. Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative. This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19. [ABSTRACT FROM AUTHOR]

Complement and extracellular vesicles (EVs) association with thrombogenic tendencies is acknowledged, but limited evidence exists for their link to COVID-19 venous thromboembolism. This study aims to examine the relationship between pulmonary embolism and the expression of complement and other proteins related to thrombogenesis in severe Covid-19 patients. We included prospectively 207 severe COVID-19 patients and retrospectively screened for pulmonary embolism (PE). This analysis comprises 20 confirmed PE cases and 20 matched patients without PE. Blood samples taken at the admission in the intensive care unit were analyzed for complement using ELISA. EVs derived from neutrophils, endothelium, or platelets, as well carrying complement or tissue factor were analyzed using flow cytometry. Complement levels were markedly elevated, with a notable increase in C3a and Terminal Complement Complex. The most prevalent EV population was identified as tissue factor (TF)-carrying EVs which peaked in patients with PE during ICU days 4–9. However, for both the complement and analyzed EV populations, no statistically significant differences were found between the patients who developed pulmonary embolism and those who did not. In conclusion, complement factors and EVs expressing tissue factor, along with EVs derived from endothelial cells and platelets, are elevated in severe COVID-19 patients, regardless of the presence of pulmonary embolism. However, the involvement of complement and procoagulant EVs in peripheral plasma in the development of pulmonary embolism is still unclear and requires further investigation. [ABSTRACT FROM AUTHOR]

Platelet-derived extracellular vesicles (pEVs) are emerging as pivotal players in numerous physiological and pathological processes, extending beyond their traditional roles in hemostasis and thrombosis. As one of the most abundant vesicle types in human blood, pEVs transport a diverse array of bioactive molecules, including growth factors, cytokines, and clotting factors, facilitating crucial intercellular communication, immune regulation, and tissue healing. The unique ability of pEVs to traverse tissue barriers and their biocompatibility position them as promising candidates for targeted drug delivery and regenerative medicine applications. Recent studies have underscored their involvement in cancer progression, viral infections, wound healing, osteoarthritis, sepsis, cardiovascular diseases, rheumatoid arthritis, and atherothrombosis. For instance, pEVs promote tumor progression and metastasis, enhance tissue repair, and contribute to thrombo-inflammation in diseases such as COVID-19. Despite their potential, challenges remain, including the need for standardized isolation techniques and a comprehensive understanding of their mechanisms of action. Current research efforts are focused on leveraging pEVs for innovative anti-cancer treatments, advanced drug delivery systems, regenerative therapies, and as biomarkers for disease diagnosis and monitoring. This review highlights the necessity of overcoming technical hurdles, refining isolation methods, and establishing standardized protocols to fully unlock the therapeutic potential of pEVs. By understanding the diverse functions and applications of pEVs, we can advance their use in clinical settings, ultimately revolutionizing treatment strategies across various medical fields and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplant (ASCT) remains the only treatment option for patients with high-risk acute myeloid leukemia (AML). Recurrence of leukemic cells after ASCT represents a dramatic event associated with a dismal outcome, with a 2-year survival rate of around 20%. Adoptive cell therapy (ACT) is a form of cell-based strategy that has emerged as an effective therapy to treat and prevent post-ASCT recurrence. Lymphocytes are the principal cells used in this therapy and can be derived from a hematopoietic stem cell donor, the patient themselves, or healthy donors, after being engineered to express the chimeric antigen receptor (CAR-T and UniCAR-T). In this review, we discuss recent advances in the established strategy of donor lymphocyte infusion (DLI) and the progress and challenges of CAR-T cells. [ABSTRACT FROM AUTHOR]

Case summary: A 6-year-old female spayed domestic shorthair cat was presented with a 7-month history of a subcutaneous mass on the dorsal nasal surface. A CT examination revealed the presence of a nasal dermoid sinus cyst with a nasal bone defect. The cyst was excised and an autologous fascia lata graft was used for reconstruction. The dorsal nasal bone was reconstituted and no compromise of respiratory function was reported in the long-term outcome. No short-term complications were observed at the 2-week follow-up. No long-term complications or recurrence were observed at the 2- and 12-month follow-ups. Fascia lata grafting appears to be an effective method for repairing a nasal bone defect after surgical excision of a nasal dermoid sinus cyst in cats. It is inexpensive and the tissue is easily harvested and provides good functional and cosmetic results. Relevance and novel information: To the authors' knowledge, this is the first report that evaluates the effectiveness of repairing a nasal bone defect after dermoid sinus cyst excision in a cat using an autologous fascia lata graft. [ABSTRACT FROM AUTHOR]

Background: Understanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic. Methods: A retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements. Results: Overall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26-130) mg/L, whereas the eosinophil count was 10 (0-60)/mm³. Eosinophil count normalization (=100/mm³) by day 2 correlated significantly with decreased oxygen needs (<2 L) with hazard ratio (HR) = 3.7 [1.1-12.9] (p = 0.04). Likewise, CRP < 80 mg/L was associated with reduced oxygen requirements (p < 0.001). Predictors, including underlying chronic respiratory disease, exhibited a trend toward a negative association (p = 0.06). Conclusion: The study highlights the relationship between eosinophil count and CRP, with implications for predicting oxygen weaning during COVID-19. Further research is warranted to explore the relevance of these biomarkers in other respiratory infections. [ABSTRACT FROM AUTHOR]

The acute exudative phase of acute respiratory distress syndrome (ARDS), a severe form of respiratory failure, is characterized by alveolar damage, pulmonary oedema, and an exacerbated inflammatory response. There is no effective treatment for this condition, but based on the major contribution of inflammation, anti‐inflammatory strategies have been evaluated in animal models and clinical trials, with conflicting results. In COVID‐19 ARDS patients, interleukin (IL)‐1 and IL‐6 receptor antagonists (IL‐1Ra and IL‐6Ra, kineret and tocilizumab, respectively) have shown some efficacy. Moreover, we have previously developed novel peptides modulating IL‐1R and IL‐6R activity (rytvela and HSJ633, respectively) while preserving immune vigilance and cytoprotective pathways. We aimed to assess the efficacy of these novel IL‐1Ra and IL‐6Ra, compared to commercially available drugs (kineret, tocilizumab) during the exudative phase (day 7) of bleomycin‐induced acute lung injury (ALI) in mice. Our results first showed that none of the IL‐1Ra and IL‐6Ra compounds attenuated bleomycin‐induced weight loss and venous PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ increase. Histological analyses and lung water content measurements also showed that these drugs did not improve lung injury scores or pulmonary oedema, after the bleomycin challenge. Finally, IL‐1Ra and IL‐6Ra failed to alleviate the inflammatory status of the mice, as indicated by cytokine levels and alveolar neutrophil infiltration. Altogether, these results indicate a lack of beneficial effects of IL‐1R and IL‐6R antagonists on key parameters of ALI in the bleomycin mouse model. What is the central question of this study?There is no effective pharmacological treatment for the acute respiratory distress syndrome (ARDS), which has an important inflammatory component: what is the efficacy of novel interleukin‐1/6 receptor antagonists, compared to commercially available antagonists, for resolution of ARDS parameters in vivo?What is the main finding and its importance?The novel and commercial antagonists failed to improve key parameters of the acute phase of ARDS in an animal model of severe acute lung injury. Complementary/alternative strategies favouring epithelial repair or oedema resorption are needed to improve the resolution of ARDS, after severe alveolar damage. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPL) are both laboratory evidence and causative factors for a broad spectrum of clinical manifestations of antiphospholipid syndrome (APS), with thrombotic and obstetric events being the most prevalent. Despite the aPL-triggered vasculopathy nature of APS, vasculitic-like manifestations rarely exist in APS and mainly appear associated with other concurrent connective tissue diseases like systemic lupus erythematous. Several studies have characterized pulmonary capillaritis related to pathogenic aPL, suggesting vasculitis as a potential associated non-thrombotic manifestation. Here, we describe a 15-year-old girl who develops hepatic infarction in the presence of highly positive aPL, temporally related to prior non-severe COVID- 19 infection. aPL-related hepatic vasculitis, which has not been reported before, contributes to liver ischemic necrosis. Immunosuppression therapy brings about favorable outcomes. Our case together with retrieved literature provides supportive evidence for aPL-related vasculitis, extending the spectrum of vascular changes raised by pathogenic aPL. Differentiation between thrombotic and vasculitic forms of vascular lesions is essential for appropriate therapeutic decision to include additional immunosuppression therapy. We also perform a systematic review to characterize the prevalence and clinical features of newonset APS and APS relapses after COVID-19 for the first time, indicating the pathogenicity of aPL in a subset of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is an uncommon, but potentially disabling or even deadly, thrombotic microangiopathy with a well-studied mechanism of ADAMTS13 deficiency or dysfunction. While established treatments are largely effective, the standard ADAMTS13 testing required to definitively diagnose TTP may cause delays in diagnosis and treatment, highlighting the need for rapid and effective diagnostic methods. Additionally, the heterogeneous presentation and varied inciting events of TTP suggest more variation in its mechanism than previously thought, implying three potential pathways rather than the accepted two. The recent discovery of ADAMTS13 conformation as a potential contributor to TTP in addition to the proposal of using the absolute immature platelet count (A-IPC) as a biomarker, present novel areas for monitoring and treatment. A-IPC in particular may serve as a more rapid and accurate diagnostic test to distinguish TTP from non-TTP TMAs and to monitor treatment response and relapse. These considerations highlight the need to further study TTP in order to improve best practices and patient care. [ABSTRACT FROM AUTHOR]

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia. [ABSTRACT FROM AUTHOR]

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: the recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time. [ABSTRACT FROM AUTHOR]

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies. [ABSTRACT FROM AUTHOR]

Inkjet printing represents a disruptive additive manufacturing technology that has emerged as an innovative approach to generate customized lithium-ion batteries by tailored dispersions. However, electrode dispersions cause a complex non-Newtonian behavior which hampers the processability. This paper demonstrates a novel procedure for an a priori evaluation of the printability of aqueous graphite dispersions. Therefore, dispersions with a varying active material content were prepared and the printability was examined through a characterization of the drop formation and the drop deposition behavior. While the drop formation was observed by in-situ monitoring, the drop deposition was analyzed in ex-situ test setups. The rheological properties were systematically determined to calculate nondimensional numbers that describe the dispensing behavior. Consequently, their capability to predict the stability of the drop formation was evaluated. The results revealed that a graphite dispersion with a content of 2 m% allowed for a stable drop formation. No splashing occurred on the substrate during the drop deposition and sufficient wetting can be assumed due to a contact angle of below 90 ∘ . Conclusions were drawn to further enhance the active material content. Due to the universality of the proposed approach, it is expected to be applicable to different dispersion systems. [ABSTRACT FROM AUTHOR]

Printing electronics is emerging as one of the fastest-growing engineering technologies that are increasingly used and reliable. It provides an alternative to manufacturing electronics devices based on silicon compounds. This article discusses its challenges, problems, and ways of obtaining desired features efficiently and inexpensively. The influence of the most important parameters of the drop-on-demand (DOD) inkjet printing process on the quality of the conductive layers, together with the results of their ageing tests, is illustrated and discussed in terms of their applicability to general-purpose electronics circuits. [ABSTRACT FROM AUTHOR]

Introduction With the advances in critical care, the incidence of post intubation tracheal stenosis is increasing. Tracheal resection and anastomosis have been the gold standard for the management of grades III and IV stenosis. Scientific evidence from the literature on the determining factors and outcomes of surgery is not well described. Objective This study was aimed at determining the influence of tracheostoma site on the surgical outcomes and postoperative quality of life of patients undergoing tracheal resection anastomosis. Methods Thirteen patients who underwent tracheal resection and anastomosis during a period of 3 years were followed up prospectively for 3 months to determine the degree of improvement in their quality of life postsurgery by comparing the pre and postoperative validated Tamil/vernacular version of RAND SF-36 scores and Medical Research Council (MRC) dyspnea score. Results As per preoperative computed tomography (CT), the mean length of stenosis was found to be 1.5 cm while the mean length of trachea resected was 4.75 cm. We achieved a decannulation rate of 61.53%. There was an estimated loss of 3.20 +/− 1.90 cm of normal trachea from the lower border of the stenosis until the lower border of the stoma that was lost during resection. Analysis of SF-36 and MRC dyspnea scores revealed significant improvement in the domains of physical function postoperatively in comparison with the preoperative scores (p < 0.05). Conclusion Diligent placement of tracheostomy in an emergency setting with respect to the stenotic segment plays a pivotal role in minimizing the length of the resected segment of normal trachea. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions. Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells. Coronavirus disease 2019 (COVID-19) disease is caused by infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of host cells in the respiratory system and various extra-pulmonary tissue/organs, resulting in complications of multiple organ systems. As the cell surface receptor, angiotensin-converting enzyme 2 (ACE2) mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19. Recent studies have found that ACE2 can be released with EVs, which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology. In addition, ACE2, neprilysin (NEP), and thimet oligopeptidase (TOP) are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7, the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease. This review summarizes the recent research progress regarding EV-associated ACE2, NEP, and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease. [ABSTRACT FROM AUTHOR]

Introduction: Wound closure methods have evolved, attributed to the armamentarium including the synthetic sutures, staples, surgical adhesive tapes and, most recently, the cyanoacrylate tissue adhesives. Cyanoacrylates have shown promising results in terms of aesthetic outcomes in other fields of surgery. The aim of this study is to compare the aesthetic value of Dermabond over Ethilon suture when used in case of facial surgical incisions. The purpose of this study was to demonstrate the efficacy of Dermabond for wound closure in the head-and-neck region. Materials and Methods: This study involved 20 subjects undergoing maxillofacial surgery. In 10 subjects, skin closure was done with conventional suturing (Ethilon) and other 10 subjects with tissue glue (2-octyl cyanoacrylate). Observations regarding skin closure time and scar assessment were made, and their results were compared. Results: The mean time for closure in the Dermabond group was 217.2 ± 42.0 s and for Ethilon suture group was 383.3 ± 140.2 s. Dermabond was significantly better than Ethilon sutures at both 1 month and 3 months with P = 0.001 and P < 0.001, respectively. For Dermabond, the average score improved from 8.2 ± 2.5 at 1 month to 6.1 ± 1.6 at the 3rd month. The improvement was statistically significant (P = 0.001) for Ethilon sutures; the average score improved from 12.0 ± 1.2 at 1 month to 10.2 ± 2.0 at 3rd month. The improvement was statistically significant (P = 0.038). Discussion: Adhesive glue appears to be superior to conventional suturing in clean elective surgeries. It is a safe and effective method of skin closure with less operative time and better cosmesis of the scar. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is a prevalent hematological malignancy (HM) characterized by inherent immunodeficiency, which is further pronounced by disease-directed therapy. The COVID-19 pandemic has had devastating outcomes, and although its impact has diminished over time, it continues to be a cause of significant morbidity and mortality, particularly among immunodeficient patients. Summary: In this review, we describe mechanisms of immune dysfunction in CLL in relation to COVID-19, provide an overview of the clinical outcomes of the disease in this patient population, and identify risk factors associated with severe morbidity and mortality. Additionally, we acknowledge the influence of the rapidly evolving landscape of new disease variants. The review further delineates the humoral and cellular responses to vaccination and their clinical efficacy in preventing COVID-19 in CLL patients. Moreover, we explore potential approaches to enhance these immune responses. Pre- and post-exposure prophylaxis strategies are discussed, along with description of common agents in the treatment of the disease in both outpatient and inpatient setting. Throughout the review, we emphasize the interplay between novel therapies for CLL and COVID-19 outcomes, prevention, and treatment and describe the impact of COVID-19 on the utilization of these novel agents. This information has the potential to guide clinical decision making in the management CLL patients. Key Messages: CLL patients are at risk for severe COVID-19 infection. Vaccinations and COVID-19 directed therapy have improved outcomes in patients with CLL, yet clinical challenges persist. [ABSTRACT FROM AUTHOR]

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The use of prophylactic antibiotics in the context of septorhinoplasty (SRP) is a frequently debated topic among plastic surgeons. Most surgeons routinely use antibiotics to prevent the dreaded physical and psychological morbidity of postoperative infections, although this practice is controversial. With antimicrobial resistance becoming a global threat, however, optimizing antibiotic prescribing is essential. The current evidence would suggest that the rate of postoperative infection is low and routine antibiotic use is unnecessary in SRP surgery. Rates range from 0.5 to 2% in simple SRP surgery, majority of which are minor nasal infections which respond to oral antibiotics and do not require hospital admission. In cases of complex SRP, defined as revision cases or where grafts or implants have been utilized, infection rates can be much higher with an incidence of 7 to 11%, and as such utilization of antibiotics is reasonable. When considering the regime to be utilized, a single preoperative dose of intravenous antibiotics has the same efficacy in reducing the incident of postoperative infection as a postoperative 7-day course of oral antibiotics. In the authors' practice, all patients receive a single intravenous dose of antibiotics on induction, and in the case of utilization of a graft from a nonnasal site, this is complimented with an oral course of postoperative antibiotics. With this approach, infections rates are at the lowest range of available published literature. [ABSTRACT FROM AUTHOR]

Background: Veno venous Extra Corporeal Membrane Oxygenation (vvECMO) is associated with frequent hematological ECMO-related complications needing ECMO circuit change. Microvesicles (MVs) interplay during the thrombosis-fibrinolysis process. The main objective of the study was to identify subpopulations of MVs associated with indications of early vvECMO circuit change. Methods: This is a prospective observational monocenter cohort study. Blood gas was sampled on the ECMO circuit after the membrane oxygenator to measure the PO2 post oxy at inclusion, day 3, day 7 and the day of ECMO circuit removal. Blood samples for MV analysis were collected at inclusion, day 3, day 7 and the day of ECMO circuit removal. MV subpopulations were identified by flow cytometry. Results: Nineteen patients were investigated. Seven patients (37%) needed an ECMO circuit change for hemolysis (n = 4), a pump thrombosis with fibrinolysis (n = 1), persistent thrombocytopenia with bleeding (n = 1) and a decrease of O2 transfer (n = 1). Levels of leukocyte and endothelial MVs were significantly higher at inclusion for patients who thereafter had an ECMO circuit change (p = 0.01 and p = 0.001). The areas under the received operating characteristics curves for LeuMVs and EndoMVs sampled the day of cannulation and the need for ECMO circuit change were 0.84 and 0.92, respectively. PO2 post oxy did not significantly change except for in one patient during the ECMO run. Conclusions: Our pilot study supports the potential interest of subpopulations of microvesicles early associated with hematological ECMO-related complications. Our results warrant further studies. [ABSTRACT FROM AUTHOR]

Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet–leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we characterized TF-positive extracellular vesicles (EVs) and their cellular origin in 12 patients suffering from severe COVID-19 (time course, 134 samples overall) and 25 healthy controls. EVs exposing phosphatidylserine (PS) were characterized by flow cytometry. Their cellular origin was determined by staining with anti-CD41, anti-CD45, anti-CD235a, and anti-CD105 as platelet, leukocyte, red blood cell, and endothelial markers. We further investigated the association of EVs with TF, platelet factor 4 (PF4), C-reactive protein (CRP), and high mobility group box-1 protein (HMGB-1). COVID-19 patients showed higher levels of PS-exposing EVs compared to controls. The majority of these EVs originated from platelets. A higher amount of EVs in patient samples was associated with CRP, HMGB-1, PF4, and TF as compared to EVs from healthy donors. In COVID-19 samples, 16.5% of all CD41+ EVs displayed the leukocyte marker CD45, and 55.5% of all EV aggregates (CD41+CD45+) co-expressed TF, which reflects the interaction of platelets and leukocytes in COVID-19 on an EV level. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) represent nanometer-sized, subcellular spheres, that are released from almost any cell type and carry a wide variety of biologically relevant cargo. In severe cases of coronavirus disease 2019 (COVID-19) and other states of systemic pro-inflammatory activation, EVs, and their cargo can serve as conveyors and indicators for disease severity and progression. This information may help distinguish individuals with a less severe manifestation of the disease from patients who exhibit severe acute respiratory distress syndrome (ARDS) and require intensive care measures. Here, we investigated the potential of EVs and associated miRNAs to distinguish normal ward patients from intensive care unit (ICU) patients (N = 10/group), with 10 healthy donors serving as the control group. Blood samples from which plasma and subsequently EVs were harvested by differential ultracentrifugation (UC) were obtained at several points in time throughout treatment. EV-enriched fractions were characterized by flow cytometry (FC), nanoparticle tracking analysis (NTA), and qPCR to determine the presence of selected miRNAs. Circulating EVs showed specific protein signatures associated with endothelial and platelet origin over the course of the treatment. Additionally, significantly higher overall EV quantities corresponded with increased COVID-19 severity. MiR-223-3p, miR-191-5p, and miR-126-3p exhibited higher relative expression in the ICU group. Furthermore, EVs presenting endothelial-like protein signatures and the associated miR-126-3p showed the highest area under the curve in terms of receiver operating characteristics regarding the requirement for ICU treatment. In this exploratory investigation, we report that specific circulating EVs and miRNAs appear at higher levels in COVID-19 patients, especially when critical care measures are indicated. Our data suggest that endothelial-like EVs and associated miRNAs likely represent targets for future laboratory assays and may aid in clinical decision-making in COVID-19. [ABSTRACT FROM AUTHOR]

Background: The treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C. Methods: We included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher's exact tests. Results: Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS. Conclusions: In patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay. [ABSTRACT FROM AUTHOR]