Changes in pNFH Levels in Cerebrospinal Fluid and Motor Evolution after the Loading Dose with Nusinersen in Different Types of Spinal Muscular Atrophy.

Aim and Objectives: The objective of our retrospective study was to investigate the changes in pNFH levels in cerebrospinal fluid, which is a reliable marker of neuronal damage, after the loading dose of nusinersen in different types of spinal muscular atrophy. Materials and Methods: We analyzed the spinal muscular atrophy types, the number of copies of the SMN2 gene, and the progression of the motor status using specific motor function scales in a group of 38 patients with spinal muscular atrophy types 1, 2, and 3. Results: We found a significant inverse correlation between pNFH levels and patient age, progress on functional motor scales, and nusinersen administration. Our results also revealed that the neurofilament levels in the cerebrospinal fluid were higher in patients with 2 SMN2 copies than those with more than 2 copies, although the association was not statistically significant due to the abnormal distribution of the values. Conclusions: We identified several predictors of favorable evolution under nusinersen treatment, including spinal muscular atrophy type 1, children aged ≤ 30 months, and the presence of only 2 copies of SMN2. Our study provides important insights into the use of pNFH as a biomarker to monitor disease progression and responses to treatment in patients with spinal muscular atrophy.

Pulmonary Involvement in SARS-CoV-2 Infection Estimates Myocardial Injury Risk.

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represents a pathology with primary pulmonary involvement and multisystemic impact, including cardiovascular injuries. The present study aimed to assess the value of clinical, biochemical, and imaging factors in COVID-19 patients in determining the severity of myocardial involvement, and to create a model that can be used toevaluate myocardial injury risk based on clinical, biochemical and imaging factors. Materials and Methods: We performed an observational cohort study on 150 consecutive patients, evaluating their age, sex, hospitalization period, peripheral oxygen saturation (SpO2) in ambient air, systolic and diastolic blood pressure, heart rate, respiratory rate, biochemical markers of cardiac dysfunction (TnI, and NT-proBNP), inflammatory markers (C reactive protein (CRP), fibrinogen, serum ferritin, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα)), D-dimers, lactate dehydrogenase (LDH), myoglobin and radio-imaging parameters. All patients underwent computerized tomography chest scan in the first two days following admission. Results: We observed elevated heart and respiratory rates, higher systolic blood pressure, and a lower diastolic blood pressure in the patients with cardiac injury; significant differences between groups were registered in TnI, NT-proBNP, LDH, CRP, and D-dimers. For the radiological parameters, we found proportional correlations with the myocardial injury for the severity of lung disease, number of pulmonary segments with alveolar consolidation, number of pulmonary lobes with pneumonia, crazy paving pattern, type of lung involvement, the extent of fibroatelectatic lesions and the mediastinal adenopathies. Conclusions: Myocardial injury occurred in 12% of patients in the study group. Ground glass opacities, interstitial interlobular septal thickening (crazy paving pattern), fibroatelectasic lesions and alveolar consolidations on CT scan were correlated with myocardial injury. Routine lung sectional imaging along with non-specific biomarkers (LDH, D-dimers, and CRP) can be further valuable in the characterization of the disease burden, thus impacting patient care.

Mortality Predictors in Severe SARS-CoV-2 Infection.

Background and Objectives: The severe forms of SARS-CoV-2 pneumonia are associated with acute hypoxic respiratory failure and high mortality rates, raising significant challenges for the medical community. The objective of this paper is to present the importance of early quantitative evaluation of radiological changes in SARS-CoV-2 pneumonia, including an alternative way to evaluate lung involvement using normal density clusters. Based on these elements we have developed a more accurate new predictive score which includes quantitative radiological parameters. The current evolution models used in the evaluation of severe cases of COVID-19 only include qualitative or semi-quantitative evaluations of pulmonary lesions which lead to a less accurate prognosis and assessment of pulmonary involvement. Materials and Methods: We performed a retrospective observational cohort study that included 100 adult patients admitted with confirmed severe COVID-19. The patients were divided into two groups: group A (76 survivors) and group B (24 non-survivors). All patients were evaluated by CT scan upon admission in to the hospital. Results: We found a low percentage of normal lung densities, PaO2/FiO2 ratio, lymphocytes, platelets, hemoglobin and serum albumin associated with higher mortality; a high percentage of interstitial lesions, oxygen flow, FiO2, Neutrophils/lymphocytes ratio, lactate dehydrogenase, creatine kinase MB, myoglobin, and serum creatinine were also associated with higher mortality. The most accurate regression model included the predictors of age, lymphocytes, PaO2/FiO2 ratio, percent of lung involvement, lactate dehydrogenase, serum albumin, D-dimers, oxygen flow, and myoglobin. Based on these parameters we developed a new score (COV-Score). Conclusions: Quantitative assessment of lung lesions improves the prediction algorithms compared to the semi-quantitative parameters. The cluster evaluation algorithm increases the non-survivor and overall prediction accuracy.COV-Score represents a viable alternative to current prediction scores, demonstrating improved sensitivity and specificity in predicting mortality at the time of admission.

Pericardial Involvement in Severe COVID-19 Patients.

Background and Objectives: SARS-CoV-2 has an extensive tissue tropism due to its ability to attach to the surfaces of cells through different receptors, leading to systemic complications. In this article, we aim to present the prevalence of pericardial effusions in patients with severe COVID-19, to identify the risk factors/predictors for pericardial involvement, and to evaluate its impact on overall mortality. Materials and Methods: We enrolled 100 patients with severe COVID-19 in our observational cohort study and divided them in two groups: Group A (27 patients with pericardial effusion) and Group B (73 patients without pericardial effusion). We recorded demographic and lifestyle parameters, anthropometric parameters, clinical parameters, inflammation markers, respiratory function parameters, complete blood count, coagulation parameters, and biochemical serum parameters. All patients were evaluated by computer tomography scans within 48 h of admission. Results: The median age was 61 years in both groups and the male/female ratio was 3.5 vs. 2.8 in Group A vs. Group B. We identified mild pericardial effusion (3-4 mm) in 62.9% patients and moderate pericardial effusion (5-9 mm) in 37.1% patients, with a median value of 4 [3;6] mm. The patients with pericardial effusion presented with higher percentages of obesity, type-2 diabetes mellitus, arterial hypertension, and congestive heart failure, without statistical significance. Increased values in cardiac enzymes (myoglobin, CK, CK-MB) and LDH were statistically associated with pericardial effusion. The overall mortality among the participants of the study was 24% (24 patients), 33.3% in Group A and 20.8% in Group B. Conclusions: Pericardial effusion has a high prevalence (27%) among patients with severe forms of COVID-19 and was associated with higher mortality. Pericardial effusion in our study was not associated with the presence of comorbidities or the extent of lung involvement. Overall mortality was 60% higher in patients with pericardial effusion.

Predictors of Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection.

Background and Objectives: SARS-CoV-2 infection is frequently associated with pneumonia but has a broad tissue tropism also leading to systemic complications (hematologic, gastro-intestinal, cardiac, neurologic, etc.). In this study, we aim to evaluate the impact of COVID-19 infection on the liver and to identify the risk factors/predictors for liver injury at admission to the hospital. Materials and Methods: We performed a retrospective cohort study on 249 patients, divided into two Group A (157 patients with liver involvement) and Group B (92 patients without liver involvement). We recorded demographic and lifestyle parameters, anthropometric parameters, comorbidities, clinical parameters, inflammation markers, complete blood count, coagulation, and biochemical parameters. Lung parenchyma, liver dimensions, and morphology were evaluated by computer tomography (CT) scans. Results: Patients with liver involvement had higher heart and respiratory rates, lower oxygen saturation (SO2), and necessitated higher oxygen flow at admittance. We found higher serum levels of C-reactive protein, fibrinogen, ferritin, creatine kinase, lactate dehydrogenase (LDH), serum triglycerides, and lower values for serum albumin in Group A patients. The patients with liver involvement presented more extensive lung injury with higher percentages of alveolar, mixed, and interstitial lesions, an increase in liver dimensions, and lower density ranges for the liver parenchyma. The patients presented hepatocytolytic involvement in 26 cases (10.4% from the entire study population), cholestatic involvement in 63 cases (37.7% from the entire study population), and mixed liver involvement in 68 cases (37.7% from the entire study population). Conclusions: Liver involvement in COVID-19 patients is frequent, usually mild, and occurs mostly in male patients over 50 years old. Cholestatic and mixed liver injuries are more frequent than hepatocytolytic injuries. The severity of lung injury evaluated by CT scan, increased values of inflammatory markers, LDH, and low values of SO2 can be considered risk factors/predictors for liver injury at admission to the hospital.

Comparative evaluation of aggressiveness traits in staphylococcal strains from severe infections versus nasopharyngeal carriage.

Despite their commensal status, staphylococci can become problematic pathogens expressing multiple and redundant virulence factors. This study aimed to evaluate aggressiveness markers comparatively in staphylococcal strains isolated from severe infections versus asymptomatic carriage in order to identify clinically relevant bacterial traits that could easily be detected in clinical practice and could be suggestive for particular host-pathogen interactions such as cyto-adhesion or biofilm formation, ultimately orienting the clinical decision-making process. We have used in vitro phenotypic methods to assess adhesion to and invasion of eukaryotic cells, biofilm development, and expression of soluble virulence factors in 92 Staphylococcus spp. strains. The adhesion index, invasion capacity, biofilm formation and expression of soluble factors did not differ significantly between clinical and commensal strains. The major bacterial traits we found to be significantly more prevalent in clinical staphylococci were the aggregative adhesion pattern (P = 0.012), cluster adhesion (P = 0.001) and tetrad morphology (P = 0.018). The aggregative adhesion pattern was correlated with higher cyto-adhesion (P < 0.001), higher invasion capacity (P = 0.003) and lower Carmeli scores (P = 0.002). Three major bacterial traits, namely tetrad morphology, aggregative adhesion pattern, and resistance to methicillin (acronym: TAM), can be used to compute an aggressiveness score (SAS) predictive of the staphylococcal strain's virulence and capacity to initiate and develop a biofilm-driven chronic infectious process versus a fulminant acute infection, in a susceptible host.

Characterization of oral involvement in acute graft-versus-host disease.

Acute graft-versus-host-disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). The purpose of this study was to characterize the oral features associated with aGVHD in patients who underwent HSCT between 1995 and 2010 and developed prominent oral aGVHD. Data was collected from patient medical records and analyzed descriptively. Twenty-one cases were identified, of which 5 (24%) demonstrated only oral features; the remaining 16 had variable involvement of skin (n = 14), liver (n = 7), and gut (n = 5). The median time to onset of any sign of aGVHD was 22 days (range, 8 to 154 days), and that for onset of oral aGVHD was 35 days (range, 11 to 159 days). Sites affected by nonspecific erythema and ulcerations included buccal mucosa (19 of 21; 90%) tongue (18 of 21; 86%; dorsum in 8), labial mucosa (16 of 21; 76%), palatal mucosa (15 of 21; 71%; hard palate in 7), and floor of mouth (7 of 21; 33%). Eight cases (38%) presented with lip ulceration and crusting. In addition to systemic therapies, topical solutions of dexamethasone, tacrolimus, and morphine were used for ancillary support. Oral features of aGVHD may be the initial manifestation and include nonspecific erythema and ulcerations of keratinized and nonkeratinized mucosa and lips. Intensive topical therapies may help reduce symptoms and promote healing.

MECHANISMS OF THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS.

Thrombotic events are highly prevalent in systemic lupus erythematosus (SLE). Antiphospholipid antibodies play an essential role in promoting thrombosis by activating several intracellular signaling pathways (TLR4, p38MAPK, NFkB) in platelets, monocytes and endothelial cells. New therapeutic opportunities might be offered by addressing these molecular targets. Chronic inflammatory status, the degree of disease activity and accelerated atherosclerosis are also responsible for the thrombotic phenotype in patients with SLE. The aim of this review is to highlight thrombosis mechanisms and to look for possible connection between SLE, antiphospholipid antibodies and cancer, especially myeloproliferative neoplasms.

Endothelial Dysfunction as a Key Link between Cardiovascular Disease and Frailty: A Systematic Review.

Background: Frailty is increasingly recognized as a significant health concern, particularly due to its association with cardiovascular pathologies. This study aims to examine how vascular endothelial dysfunction, a known premorbid stage in the pathophysiology of cardiovascular diseases, contributes to the link between cardiovascular illness and frailty. Methods: The inclusion criteria allowed us to focus on original clinical research articles published in English between January 2014 and January 2024, which reported quantitative assessments of the relationship between frailty and vascular endothelial dysfunction. Excluded from the study were systematic literature reviews, meta-analyses, editorials, conference articles, theses, methodological articles, and studies using animal or cell culture models. Searches were conducted of electronic databases, including Scopus, ScienceDirect, and Medline, up to 22 January 2024. The risk of bias was assessed using the Joanna Briggs Institute's critical appraisal tools. The methods used to present and synthesize the results involved data extraction and categorization based on biomolecular and clinical findings of endothelial dysfunction. Results: Following the application of the inclusion and exclusion criteria, a total of 29 studies were identified. Vascular endothelial dysfunction was associated with increased frailty phenotypes, and we also identified SGLT-2 inhibitors' potential role as an anti-fragility treatment that affects endothelial dysfunction. This study found that the physical and biomolecular markers of endothelial dysfunction are associated with frailty measures and have predictive value for incident frailty. Furthermore, some studies have shown inflammation to have an impact on endothelial dysfunction and frailty, and an innovative age-related chronic inflammation measure has been proven to predict frailty scores. Conclusions: The current evidence suggests an association between endothelial dysfunction and frailty, highlighting the need for further research to elucidate the underlying mechanisms.

Fractal Analysis in Neurodegenerative Diseases.

Neurodegenerative diseases are defined by progressive nervous system dysfunction and death of neurons. The abnormal conformation and assembly of proteins is suggested to be the most probable cause for many of these neurodegenerative disorders, leading to the accumulation of abnormally aggregated proteins, for example, amyloid ß (Aß) (Alzheimer's disease and vascular dementia), tau protein (Alzheimer's disease and frontotemporal lobar degeneration), α-synuclein (Parkinson's disease and Lewy body dementia), polyglutamine expansion diseases (Huntington disease), or prion proteins (Creutzfeldt-Jakob disease). An aberrant gain-of-function mechanism toward excessive intraparenchymal accumulation thus represents a common pathogenic denominator in all these proteinopathies. Moreover, depending upon the predominant brain area involvement, these different neurodegenerative diseases lead to either movement disorders or dementia syndromes, although the underlying mechanism(s) can sometimes be very similar, and on other occasions, clinically similar syndromes can have quite distinct pathologies. Non-Euclidean image analysis approaches such as fractal dimension (FD) analysis have been applied extensively in quantifying highly variable morphopathological patterns, as well as many other connected biological processes; however, their application to understand and link abnormal proteinaceous depositions to other clinical and pathological features composing these syndromes is yet to be clarified. Thus, this short review aims to present the most important applications of FD in investigating the clinical-pathological spectrum of neurodegenerative diseases.

COVID-19 associated pulmonary embolism: clinical, biochemical and CT imaging findings.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represented a disruptive pathology that emerged in late 2019 with profound implications ranging from individual health to health systems and world economy. Our study aimed to evaluate clinical, biochemical and computerized tomography (CT) parameters values in determining the severity of pulmonary embolism (PE) associated with COVID-19. METHODS: We performed an observational cohort study evaluating demographic, clinical, biochemical, coagulation markers, as well as CT imaging parameters. RESULTS: In our study on 186 patients with COVID-19, we found that 31 patients (16,66%) had pulmonary embolism. Significant correlations for the patients with PE were detected in C-reactive protein, lactate dehydrogenase, serum ferritin, IL-6, serum myoglobin, NT-proBNP, D-dimers, serum proteins, transaminases as well as white cell blood counts. Patients with pulmonary embolism had a more severe lung involvement, with thrombi distribution mainly involving the lower lobes. CONCLUSION: Early identification of PE is an important step for timely and efficient treatment in the intensive care management of COVID-19 patients. Our study showed that high plasmatic values of lactate dehydrogenase, ferritin, IL-6, white blood cells and D-dimers and low proteins serum levels are strongly linked with COVID-19-associated pulmonary embolism.

Confronting a New Challenge in Plastic Surgery: MDR Infections in Patients with Chronic Wounds.

BACKGROUND: The presence of a wound can be anywhere from non-problematic to life-threatening on a severity spectrum, with bacterial infection and resistance playing a major role in the development of chronicity, delaying wound healing. Wound colonization with multiple organisms and the limited number of effective antibiotics place a heavy burden on the healthcare system, with patients going through multiple surgeries during a prolonged hospitalization time. By analyzing the resistance patterns of pluri-bacterial populations and the approach used in managing complex cases, we aim to improve the protocols applied in caring for chronic wounds in our practice and share our experiences and observations. METHODS: We designed a retrospective study on 212 diabetic and non-diabetic patients, aiming to evaluate the course of chronic wound treatment in our practice. We focused on the impact that MDR bacteria and diabetes have on surgical outcomes and their role in the healing process. RESULTS: Patients who received empiric antibiotic therapy before being admitted eventually presented with multiple MDR bacteria compared to those who did not receive antibiotics (p = 0.014). The presence of at least one MDR bacteria in the wound bed was associated with ulcers reaching bone (p = 0.02) and was positively correlated with the number of surgeries performed (p < 0.001). Diabetes played a significant role in surgery-related complications (p = 0.02) and hospitalization time (p < 0.001). CONCLUSIONS: Proper management of chronic wounds requires a comprehensive, multidisciplinary approach and a thorough understanding of antibiotic usage. To address this need, we have developed and implemented a chronic wound treatment protocol in our clinic, with the goal of discharging patients once their ulcers have been treated and closed. A key summary of the protocol presented is to reduce the incidence of MDR bacteria and improve the patient's quality of life.

Exploring an Innovative Approach: Integrating Negative-Pressure Wound Therapy with Silver Nanoparticle Dressings in Skin Graft Procedures.

BACKGROUND: Skin grafting is a helpful instrument in a plastic surgeon's arsenal. Several types of dressings were designed to facilitate the process of graft integration. Negative-pressure wound therapy is a proven dressing method, enhancing graft survival through several mechanisms: aspiration of secretions, stimulation of neoangiogenesis, and promotion of an anti-inflammatory environment. Silver nanoparticle dressings also bring multiple benefits by bearing an antimicrobial effect and providing a humid medium, which are favorable for epithelialization. The combination of NPWT (negative-pressure wound therapy) with AgNPs (silver nanoparticles) has not been widely studied. MATERIALS AND METHODS: This study aimed to compare the outcomes of silver nanoparticle sheets with the combination of negative-pressure wound therapy and silver nanoparticle dressings. We conducted a comparative prospective study on 80 patients admitted to the Plastic Surgery Department of "Prof. Dr. Agrippa Ionescu" Emergency Clinical Hospital between 1st of January 2020 and 31st of December 2022. The study population was randomized to receive either silver nanoparticle dressings or negative-pressure wound therapy (NPWT) combined with silver nanoparticle dressings. Various parameters were monitored, including patient comorbidities and graft-related data such as defect etiology, graft integration, and graft size. Dressings were changed, and graft status was evaluated at 7, 10, and 14 days postoperatively. Additionally, baseline C-reactive protein (CRP) levels were measured before surgery and 7, 10, and 14 days postoperatively. RESULTS: The study demonstrated an enhanced integration of skin grafts at all evaluation stages when employing NPWT combined with AgNPs, particularly evident 10 days post operation. Significant variations in graft integration were also observed based on factors such as diabetes, cardiovascular disease, graft size, or the origin of the grafted defect. Moreover, dynamic C-reactive protein monitoring showed a statistically significant decrease in CRP levels 10 days post operation among patients treated with NPWT in conjunction with silver dressing, consistent with the nearly complete integration of skin grafts at this evaluation threshold. CONCLUSION: Several factors influence the postoperative evolution of split-skin grafts. Postoperative dressings target local factors to enhance graft integration further. Our research demonstrated that the innovative combination of NPWT-assisted dressings, complemented by a silver nanoparticle sheet, resulted in improved benefits for graft integration and the alleviation of systemic inflammation.

Diagnostic and Therapeutic Particularities of Symptomatic Melanoma Brain Metastases from Case Report to Literature Review.

The recent introduction of immunotherapy and targeted therapy has substantially enriched the therapeutic landscape of metastatic melanoma. However, cerebral metastases remain unrelenting entities with atypical metabolic and genetic profiles compared to extracranial metastases, requiring combined approaches with local ablative treatment to alleviate symptoms, prevent recurrence and restore patients' biological and psychological resources for fighting malignancy. This paper aims to provide the latest scientific evidence about the rationale and timing of treatment, emphasizing the complementary roles of surgery, radiotherapy, and systemic therapy in eradicating brain metastases, with a special focus on the distinct response of intracranial and extracranial disease, which are regarded as separate molecular entities. To illustrate the complexity of designing individualized therapeutic schemes, we report a case of delayed BRAF-mutant diagnosis, an aggressive forearm melanoma, in a presumed psychiatric patient whose symptoms were caused by cerebral melanoma metastases. The decision to administer molecularly targeted therapy was dictated by the urgency of diminishing the tumor burden for symptom control, due to potentially life-threatening complications caused by the flourishing of extracranial disease in locations rarely reported in living patients, further proving the necessity of multidisciplinary management.

The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view.

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-ß, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.

Insulin resistance and adipokines serum levels in a caucasian cohort of hiv-positive patients undergoing antiretroviral therapy: a cross sectional study.

BACKGROUND: Insulin resistance is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy. Cytokines secreted by adipose tissue (adipokines) are linked to insulin sensitivity. The present study is aimed to assess the prevalence of insulin resistance (IR) and its association with several adipokines, in a non-diabetic Romanian cohort of men and women with HIV-1 infection, undergoing combination antiretroviral therapy (cART). METHODS: A cross-sectional study was conducted in an unselected sample of 89 HIV-1-positive, non-diabetic patients undergoing stable cART for at least 6 months. Metabolic parameters were measured, including fasting plasma insulin, and circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Insulin resistance was estimated by measuring the Quantitative Insulin Sensitivity Check Index (QUICKI), using a cut-off value of 0.33. A linear regression model was fitted to QUICKI to test the association of IR and adipokines levels. RESULTS: A total of 89 patients (aged 18-65, median: 28 years) including 51 men (57.3%) and 38 women (42.7%) were included in the study. Fifty nine patients (66.3%) were diagnosed with IR based on QUICKI values lower than the cut-off point. IR prevalence was 72.5% in men and 57.6% in women. The presence of the IR was not influenced by either the time of the HIV diagnosis or by the duration of cART. Decreased adiponectin and increased serum triglycerides were associated with increased IR in men (R=0.43, p=0.007). Hyperleptinemia in women was demonstrated to be associated with the presence of IR (R=0.33, p=0.03). CONCLUSIONS: Given the significant prevalence of the IR in our young non-diabetic cohort with HIV infection undergoing antiretroviral therapy reported in our study and the consecutive risk of diabetes and cardiovascular events, we suggest that the IR management should be a central component of HIV-infection therapeutic strategy. As adipokines play major roles in regulating glucose homeostasis with levels varying according to the sex, we suggest that further studies investigating adipokines should base their analyses on gender differences.

Clinical, biochemical and pulmonary CT imaging features for hepatobiliary involvement in COVID-19.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a viral disease with primary pulmonary involvement and systemic impact. This article aims to assess the importance of clinical, biological, demographic and radioimaging parameters in COVID-19 patients in characterizing the incidence and severity of the hepatobiliary involvement. Methods: We performed an observational cohort study on 132 consecutive patients, evaluating their demographics, hospitalization period, peripheral oxygen saturation (SpO2) in the ambient air, as well as biochemical markers of hepatobiliary involvement: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), gamma-glutamyl transferase (GGT), serum albumin, total serum proteins, D-dimers; coagulation tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR); inflammatory markers: fibrinogen, serum ferritin, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis alpha (TNF-α). Hepatobiliary involvement was further stratified by type of affection pattern: hepatocytolysis, cholestasis or mixed type. All patients received a computerized tomography (CT) chest scan in the first or second day of hospital admission. Results: We observed lower SaO2 and longer hospitalization days in patients with hepatobiliary involvement, as well as longer coagulation times (PT and INR), lower serum albumin and higher serum ferritin (p<0.05). No significant correlations have been found between the degree or type of pattern of lung involvement as seen on CT scans performed and biochemical liver changes. Conclusions: Hepatobiliary involvement occurred in 72% of patients in the study group, associated with longer hospitalization period, prolonged coagulation parameters, lower serum albumin levels, raised serum ferritin and CRP levels. Cholestatic and mixed types of injury were associated with higher ferritin levels, while mixed type alone presented higher D-dimers levels compared with the cholestatic or hepatocytolysis groups. No significant correlation was found between lung involvement by CT evaluation and hepatobiliary involvement.

Coagulation Disorders in Sepsis and COVID-19-Two Sides of the Same Coin? A Review of Inflammation-Coagulation Crosstalk in Bacterial Sepsis and COVID-19.

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have focused on SARS-CoV-2 pathogenesis and treatment. Significant progress has been made in this regard and coagulation disturbances were once again found to underlie some of the most serious adverse outcomes of SARS-CoV-2 infection, such as acute lung injury and multiorgan dysfunction. In the attempt of untangling the mechanisms behind COVID-19-associated coagulopathy (CAC), a series of similarities with sepsis-induced coagulopathy (SIC) became apparent. Whether they are, in fact, the same disease has not been established yet. The clinical picture of CAC shows the unique feature of an initial phase of intravascular coagulation confined to the respiratory system. Only later on, patients can develop a clinically significant form of systemic coagulopathy, possibly with a consumptive pattern, but, unlike SIC, it is not a key feature. Deepening our understanding of CAC pathogenesis has to remain a major goal for the research community, in order to design and validate accurate definitions and classification criteria.

Extremely Rare Type of Breast Cancer-Dedifferentiated Breast Liposarcoma-Diagnosis and Treatment.

Primary liposarcoma of the breast is an uncommon soft tissue malignant tumor, comprising only 0.003% of all malignant breast tumors. The main differential diagnosis of this mass consists of malignant phyllodes tumor and metaplastic breast carcinoma. The objective of this paper is to report a case of dedifferentiated breast liposarcoma, therapeutic approach and outcome. We present a case of a 79-year-old woman complaining of a large mass in her left breast which had increased in size over the last 6 months. Physical examination revealed an enlarged left breast, and a total body CT scan showed a large tumor in contact with the musculature of the anterior thoracic wall, with no metastatic lesions. The histopathology report of a fine needle biopsy described a high-grade sarcoma. The Oncological Tumor Board recommended neoadjuvant radiotherapy sessions and reevaluation by MRI and CT scans. The patient underwent radical mastectomy with latissimus dorsi myo-cutaneous flap reconstruction. The final histopathology diagnosis was a grade 3 dedifferentiated liposarcoma (FNCLCC), with certain response to radiotherapy and positive MDM2, CDK4 markers. The postoperative period was uneventful; 12 months after surgery, the follow-up CT scan showed multiple pulmonary lesions with metastatic characteristics. Liposarcoma is a very rare type of breast cancer, and the most important treatment for breast sarcoma is surgery, the role of axillary lymph node removal, chemotherapy and radiotherapy still being controversial. Considering such cases are scarce and the development of surgical guidelines is difficult, reporting any new case is crucial.

Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and glial cells in aging and stroke.

Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology.