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Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), renin-aldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

Infection with SARS-CoV-2 and the resulting COVID-19 can cause both lung and kidney damage. SARS-CoV-2 can directly infect renal cells expressing ACE2 receptors, resulting in kidney damage, and acute kidney injury (AKI) has been reported in COVID-19 hospitalized patients. The pathophysiology of COVID-19-associated AKI is multifactorial. Local and systemic inflammation, immune system dysregulation, blood coagulation disorders, and activation of the renin-angiotensin-aldosterone system (RAAS) are factors that contribute to the development of AKI in COVID 19 disease. COVID-19 patients with kidney involvement have a poor prognosis, and patients with chronic kidney disease (CKD) infected with SARS-CoV-2 have an increased mortality risk. CKD patients with COVID-19 may develop end-stage renal disease (ESRD) requiring dialysis. In particular, patients infected with SARS-CoV-2 and requiring dialysis, as well as patients who have undergone kidney transplantation, have an increased risk of mortality and require special consideration. Nephrologists and infectious disease specialists face several clinical dilemmas in the prophylaxis and treatment of CKD patients with COVID-19. This entry presents recent data showing the effects of COVID-19 on the kidneys and CKD patients and the challenges in the management of CKD patients with COVID-19, and discusses treatment strategies for these patients.

Introduction. Critically ill COVID-19 patients hospitalized in intensive care units (ICU) are immunosuppressed due to SARSCoV-2-related immunological effects and are administered immunomodulatory drugs. This study aimed to determine whether these patients carry an increased risk of multi-drug resistant (MDR) and especially carbapenem-resistant Gram-negative (CRGN) bacterial infections compared to other critically ill patients without COVID-19. Materials and Methods. A prospective case-control study was conducted between January 2022 and August 2023. The ICU patients were divided into two groups (COVID-19 and non-COVID-19). Differences in the incidence of CRGN infections from Klebsiella pneumoniae, Acinetobacter spp., and Pseudomonas aeruginosa were investigated. In addition, an indicator of the infection rate of the patients during their ICU stay was calculated. Factors independently related to mortality risk were studied. Results. Forty-two COVID-19 and 36 non-COVID-19 patients were analyzed. There was no statistically significant difference in the incidence of CRGN between COVID-19 and non-COVID-19 patients. The infection rate was similar in the two groups. Regarding the aetiological agents of CRGN infections, Pseudomonas aeruginosa was significantly more common in non-COVID-19 patients (p=0.007). COVID-19 patients had longer hospitalisation before ICU admission (p=0.003) and shorter ICU length of stay (LOS) (p=0.005). ICU COVID-19 patients had significantly higher mortality (p

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

Background: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. Methods: Thirty-three patients with stage I–IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. Results: Patients with stage I–IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. Conclusion: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response.

Bacteremia and endocarditis are two clinical syndromes that, for decades, were managed exclusively with parenteral antimicrobials, irrespective of a given patient’s clinical condition, causative pathogen, or its antibiotic susceptibility profile. This clinical approach, however, was based on low-quality data and outdated expert opinions. When a patient’s condition has improved, gastrointestinal absorption is not compromised, and an oral antibiotic regimen reaching adequate serum concentrations is available, a switch to oral antibacterials can be applied. Although available evidence has reduced the timing of the oral switch in bacteremia to three days/until clinical improvement, there are only scarce data regarding less than 10-day intravenous antibiotic therapy in endocarditis. Many standard or studied oral antimicrobial dosages are smaller than the approved doses for parenteral administration, which is a risk factor for treatment failure; in addition, the gastrointestinal barrier may affect drug bioavailability, especially when the causative pathogen has a minimum inhibitory concentration that is close to the susceptibility breakpoint. A considerable number of patients infected by such near-breakpoint strains may not be potential candidates for oral step-down therapy to non-highly bioavailable antibiotics like beta-lactams; different breakpoints should be determined for this setting. This review will focus on summarizing findings about pathogen-specific tailoring of oral step-down therapy for bacteremia and endocarditis, but will also present laboratory and clinical data about antibiotics such as beta-lactams, linezolid, and fosfomycin that should be studied more in order to elucidate their role and optimal dosage in this context.

Multidrug-resistant Acinetobacter baumannii infections have become a threat for public health worldwide. The aim of the present study was to follow-up resistance patterns of Acinetobacter spp. bloodstream isolates in a Tertiary University Hospital over the last nine years, from 2014 to 2022. Susceptibility patterns were followed for the following antimicrobial agents: amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, imipenem, meropenem, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Minimal inhibitory concentration (MIC) values to ampicillin/sulbactam, cefepime, ceftazidime, minocycline, piperacillin/tazobactam were evaluated from 2020 to 2023. During the study period, 853 Acinetobacter spp. bloodstream infections (BSIs) were recorded, accounting for 5.36% of all BSIs. A. baumannii was isolated in 795 cases (93.2%), during the study period. Most BSIs were recorded in adult intensive care units (ICU) (46.2%) and medical wards (42%). Among A. baumannii isolates, 4.5% were multidrug-resistant, 84.7% were extensively drug-resistant, and 8.5% were pandrug-resistant. Resistance to carbapenems was over 95%. Resistance to tigecycline increased significantly during the last years of the study (2020–2022); A. baumannii isolates with MIC ≤ 2 μg/mL accounted for 28.5% of all isolates. Resistance to colistin exhibited an increasing pattern up to 42.2% in 2022. Increasing resistance rates and the evolution of pandrug-resistant isolates call for the urgent application of preventive and response actions.

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves’ disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD, is rarely observed post-COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post-viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED 10 days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids, and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.

Although coronavirus disease 2019 (COVID-19) is primarily associated with mild respiratory symptoms, a subset of patients may develop more complicated disease with systemic complications and multiple organ injury. The gastrointestinal tract may be directly infected by SARS-CoV-2 or secondarily affected by viremia and the release of inflammatory mediators that cause viral entry from the respiratory epithelium. Impaired intestinal barrier function in SARS-CoV-2 infection is a key factor leading to excessive microbial and endotoxin translocation, which triggers a strong systemic immune response and leads to the development of viral sepsis syndrome with severe sequelae. Multiple components of the gut immune system are affected, resulting in a diminished or dysfunctional gut immunological barrier. Antiviral peptides, inflammatory mediators, immune cell chemotaxis, and secretory immunoglobulins are important parameters that are negatively affected in SARS-CoV-2 infection. Mucosal CD4+ and CD8+ T cells, Th17 cells, neutrophils, dendritic cells, and macrophages are activated, and the number of regulatory T cells decreases, promoting an overactivated immune response with increased expression of type I and III interferons and other proinflammatory cytokines. The changes in the immunologic barrier could be promoted in part by a dysbiotic gut microbiota, through commensal-derived signals and metabolites. On the other hand, the proinflammatory intestinal environment could further compromise the integrity of the intestinal epithelium by promoting enterocyte apoptosis and disruption of tight junctions. This review summarizes the changes in the gut immunological barrier during SARS-CoV-2 infection and their prognostic potential.

BackgroundThe management of infected metaphyseal nonunion of the tibia is devastating, especially when associated with significant bone loss, poor soft tissues, draining sinuses, axial deformity, knee or ankle joint stiffness, limb discrepancy, and multiresisted pathogens. A systematic review, performed recently by the primary investigators but not yet published, yielded the lack of studies in the field and the huge heterogeneity of the presented results. We found several bias and controversies such as no clear definition of the exact part of the tibia where the nonunion was located, the pathogen causing the fracture-related infection, the number of previous interventions and time to presentation, and the exact type of treatment methods including the use of muscle flaps or bone grafting. Time to final union as a functional score is another important but missing data. ObjectiveThe proposed study is designed to evaluate a sufficient number of patients with infected metaphyseal tibial nonunions using various general health, functional, and bone scores. MethodsThis prospective clinical trial study, with a minimum follow-up period of 36 months, focuses on the effectiveness of the Ilizarov method after radical nonunion debridement and targeted antibiotic therapy in patients with infected metaphyseal tibial nonunions. The primary outcomes would be the definite healing of nonunion and infection-free results. Secondary outcomes would be limb alignment and discrepancy, alteration in the patient’s quality of life, and functional results. A power analysis calculated a minimum of 11 patients to obtain statistical power, but we aim to include at least 25 patients. Limb discrepancy, clinical validation of infection eradication and fracture healing, radiographic validation, and patient-reported outcome measures will be highlighted and correlated. Statistical analysis of the results will offer data missing from the literature so far. Measurements are scheduled at specific times for each patient: preoperatively, 3 and 6 months postoperatively, 1 month after Ilizarov frame removal, and once per semester afterward until the end of the follow-up period (minimum 36 months). Laboratory evaluation will be assessed once per month. Any complication will be reported and treated when it occurs. ResultsThe trial has already started. It was funded in June 2020. As of May 2022, 19 participants have been recruited and no major complications have been noticed yet. Data analysis will be performed after data collection ends, and results will be published afterward. ConclusionsAn infected metaphyseal tibial nonunion is a rare condition with limited treatment options and many controversies. There is no consensus in the literature about the best treatment strategy, and this lack of evidence should be fulfilled. Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 30905788; https://www.isrctn.com/ISRCTN30905788 International Registered Report Identifier (IRRID)DERR1-10.2196/39319

Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets.

Background: Infected nonunion of the tibia represents a challenging complication for orthopedic surgeons and poses a major financial burden to healthcare systems. The situation is even more compounded when the nonunion involves the metaphyseal region of long bones, a rare yet demanding complication due to the poor healing potential of infected cancellous bone; this is in addition to the increased likelihood of contamination of adjacent joints. The purpose of this study was to determine the extent and level of evidence in relation to (1) available treatment options for the management of septic tibial metaphyseal nonunions; (2) success rates and bone healing following treatment application; and (3) functional results after intervention. Methods: We searched the MEDLINE, Embase, and CENTRAL databases for prospective and retrospective studies through to 25 January 2021. Human-only studies exploring the efficacy of various treatment options and their results in the setting of septic, quiescent, and metaphyseal (distal or proximal) tibia nonunions in the adult population were included. For infection diagnosis, we accepted definitions provided by the authors of source studies. Of note, clinical heterogeneity rendered data pooling inappropriate. Results: In terms of the species implicated in septic tibial nonunions, staphylococcus aureus was found to be the most commonly isolated microorganism. Many authors implemented the Ilizarov external fixation device with a mean duration of treatment greater than one year. Exceptional or good bone and functional results were recorded in over 80% of patients, although the literature is scarce and possible losses of the follow-up were not recorded. Conclusion: A demanding orthopedic condition that is scarcely studied is infected metaphyseal tibial nonunion. External fixation seems promising, but further research is needed. Systematic Review Registration: PROSPERO No. CRD42020205781.

BackgroundBacterial infections are associated with the risk of variceal bleeding through complex pathophysiologic pathways.ObjectivesThe primary objective of the present case-control study was to investigate the role of bacterial translocation and intestinal barrier dysfunction in the pathogenesis of variceal bleeding. A secondary objective was to determine independent predictors of key outcomes in variceal bleeding, including bleeding-related mortality.MethodsEighty-four (n = 84) consecutive patients participated in the study, 41 patients with acute variceal bleeding and 43 patients with stable cirrhosis, and were followed up for 6 weeks. Peripheral blood samples were collected at patient admission and before any therapeutic intervention.ResultsChild-Pugh (CP) score (OR: 1.868; p = 0.044), IgM anti-endotoxin antibody levels (OR: 0.954; p = 0.016) and TGF-β levels (OR: 0.377; p = 0.026) were found to be significant predictors of variceal bleeding. Regression analysis revealed that albumin (OR: 0.0311; p = 0.023), CRP (OR: 3.234; p = 0.034) and FABP2 levels (OR:1.000, p = 0.040), CP score (OR: 2.504; p = 0.016), CP creatinine score (OR: 2.366; p = 0.008), end-stage liver disease model (MELD), Na (OR: 1.283; p = 0.033), portal vein thrombosis (OR: 0.075; p = 0.008), hepatocellular carcinoma (OR: 0.060; p = 0.003) and encephalopathy (OR: 0.179; p = 0.045) were significantly associated with 6-week mortality.ConclusionsBacterial translocation and gut barrier impairment are directly related to the risk of variceal bleeding. Microbiota-modulating interventions and anti-endotoxin agents may be promising strategies to prevent variceal bleeding.

Acinetobacter baumannii (AB) has evolved over the last decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in the intensive care unit (ICU). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant AB. We retrospectively evaluated the characteristics, treatment regimens and outcomes of twenty patients with pan-drug resistant (PDR) AB primary bacteremia hospitalized in the ICU of the University General Hospital of Patras, during a two-year period (October 2020–September 2022). The 28-day mortality reached 50%. Between survivors and non-survivors, no differences were found regarding age, gender, and Charlson comorbidity index (CCI). However, non-survivors had higher APACHE II scores and higher prevalence of septic shock and COVID-19 infection. A significantly higher percentage in the survivor group received Fosfomycin as part of the combination regimen. Inclusion of fosfomycin in the combination therapeutic regimen was associated with significantly better survival as compared to non-fosfomycin-containing regimens. In view of the increasing prevalence of PDR-AB infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, the observed survival benefit with fosfomycin inclusion in the therapeutic regimen merits further validation in larger prospective studies.

Background: Ceftazidime/avibactam (CZA) is a new option for the treatment of KPC-producing Klebsiella pneumoniae. The aim of this study was to determine resistance patterns and carbapenemase genes among K. pneumoniae (CP-Kp) bacteremic isolates before and after CZA introduction. Methods: K. pneumoniae from blood cultures of patients being treated in a Greek university hospital during 2015–21 were included. PCR for blaKPC, blaVIM, blaNDM and blaOXA-48 genes was performed. Results: Among 912 K. pneumoniae bacteremias: 725 (79.5%) were due to carbapenemase-producing isolates; 488 (67.3%) carried blaKPC; 108 (14.9%) blaVIM; 100 (13.8%) blaNDM; and 29 (4%) carried a combination of blaKPC, blaVIM or blaNDM. The incidence of CP-Kp bacteremias was 59 per 100,000 patient-days. The incidence of CP-Kp changed from a downward pre-CZA trend to an upward trend in the CZA period (p = 0.007). BSIs due to KPC-producing isolates showed a continuous downward trend in the pre-CZA and CZA periods (p = 0.067), while BSIs due to isolates carrying blaVIM or blaNDM changed from a downward trend in the pre-CZA to an upward trend in the CZA period (p < 0.001). Conclusions: An abrupt change in the epidemiology of CP-Kp was observed in 2018, due to the re-emergence of VIM-producing isolates after the suppression of KPC-producing ones via the use of CZA.

Cramps are very common in hemodialysis (HD) patients. A high ultrafiltration rate and volume contraction have been implicated in the pathogenesis, but the underlying mechanism is not yet fully elucidated. We present a male HD patient with cramps during his session, attributed to acute limb ischemia due to thrombosis of a common femoral artery aneurysm (CFAA). The true CFAAs are extremely rare, but the pseudoaneurysms (or false aneurysms) are less uncommon resulting after femoral catheterization for diagnostic and therapeutic procedures. This aneurysm was eccentric in shape which in conjunction with the patient’s history of femoral catheterization strongly suggests us to consider it a pseudoaneurysm. Although the patient was operated with the clinical suspicion of arterial embolism due to atrial fibrillation and the subtherapeutic anticoagulation, no embolus was found in the aneurysm. We want to emphasize that the presence of cramps is not always innocent, simply attributed to HD. Rarely, it may result from or mask severe and devastating acute leg ischemia caused by thrombosis of a CFAA. Notably, the thrombosis of a CFAA (true or false) is an extremely rare condition. We suggest all the HD patients with a history of femoral cannulation to undergo a vascular ultrasound in the related femoral artery at least once, to manage and to prevent the complications.

COVID-19 is one of the progressive viral pandemics that originated from East Asia. COVID-19 or SARS-CoV-2 has been shown to be associated with a chain of physio-pathological mechanisms that are basically immunological in nature. In addition, chemokines have been proposed as a subgroup of chemotactic cytokines with different activities ranging from leukocyte recruitment to injury sites, irritation, and inflammation to angiostasis and angiogenesis. Therefore, researchers have categorized the chemotactic elements into four classes, including CX3C, CXC, CC, and C, based on the location of the cysteine motifs in their structures. Considering the severe cases of COVID-19, the hyperproduction of particular chemokines occurring in lung tissue as well as pro-inflammatory cytokines significantly worsen the disease prognosis. According to the studies conducted in the field documenting the changing expression of CXC and CC chemokines in COVID-19 cases, the CC and CXC chemokines contribute to this pandemic, and their impact could reflect the development of reasonable strategies for COVID-19 management. The CC and the CXC families of chemokines are important in host immunity to viral infections and along with other biomarkers can serve as the surrogates of vaccine-induced innate and adaptive protective responses, facilitating the improvement of vaccine efficacy. Furthermore, the immunogenicity elicited by the chemokine response to adenovirus vector vaccines may constitute the basis of vaccine-induced immune thrombotic thrombocytopaenia.

A considerable proportion of patients with severe COVID-19 meet Sepsis-3 criteria and share common pathophysiological mechanisms of multiorgan injury with bacterial sepsis, in absence of secondary bacterial infections, a process characterized as “viral sepsis”. The intestinal barrier exerts a central role in the pathophysiological sequence of events that lead from SARS-CoV-2 infection to severe systemic complications. Accumulating evidence suggests that SARS-CoV-2 disrupts the integrity of the biological, mechanical and immunological gut barrier. Specifically, microbiota diversity and beneficial bacteria population are reduced, concurrently with overgrowth of pathogenic bacteria (dysbiosis). Enterocytes’ tight junctions (TJs) are disrupted, and the apoptotic death of intestinal epithelial cells is increased leading to increased gut permeability. In addition, mucosal CD4(+) and CD8(+) T cells, Th17 cells, neutrophils, dendritic cells and macrophages are activated, and T-regulatory cells are decreased, thus promoting an overactivated immune response, which further injures the intestinal epithelium. This dysfunctional gut barrier in SARS-CoV-2 infection permits the escape of luminal bacteria, fungi and endotoxin to normally sterile extraintestinal sites and the systemic circulation. Pre-existing gut barrier dysfunction and endotoxemia in patients with comorbidities including cardiovascular disease, obesity, diabetes and immunosuppression predisposes to aggravated endotoxemia. Bacterial and endotoxin translocation promote the systemic inflammation and immune activation, which characterize the SARS-CoV-2 induced “viral sepsis” syndrome associated with multisystemic complications of severe COVID-19.

Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed to reveal the pathophysiology, prevalence, clinical manifestation, correlation and treatment of COVID-19, anaphylaxis with profuse hypotension, Kounis acute coronary syndrome and thrombotic events post vaccination. Results: The same key immunological pathophysiology mechanisms and cells seem to underlie COVID-19 cardiovascular complications and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, plaque rupture and microthrombi formation, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. COVID-19-interrelated vaccine excipients as polysorbate, polyethelene glycol (PEG) and trometamol constitute potential allergenic substances. Conclusion: Better acknowledgement of the pathophysiological mechanisms, clinical similarities, multiorgan complications of COVID-19 or other viral infections as dengue and human immunodeficiency viruses along with the action of inflammatory cells inducing the Kounis syndrome could identify better immunological approaches for prevention, treatment of the COVID-19 pandemic as well as post-COVID-19 vaccine adverse reactions.

Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactions that are encountered rarely, but can cause serious complications. The allergic responses caused by vaccines can stem from activation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. The type IV allergic reactions initiate 48 h after vaccination and demonstrate their peak between 72 and 96 h. Non-IgE-mediated mast cell degranulation via activation of the complement system and via activation of the Mas-related G protein-coupled receptor X2 can also induce allergic reactions. Reactions are more often caused by inert substances, called excipients, which are added to vaccines to improve stability and absorption, increase solubility, influence palatability, or create a distinctive appearance, and not by the active vaccine itself. Polyethylene glycol, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID-19 vaccines, are excipients mostly incriminated for allergic reactions. This review will summarize the current state of knowledge of immediate and delayed allergic reactions in the currently available vaccines against COVID-19, together with the general and specific therapeutic considerations. These considerations include: The incidence of allergic reactions and deaths under investigation with the available vaccines, application of vaccination in patients with mast cell disease, patients who developed an allergy during the first dose, vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, deaths associated with COVID-19 vaccination, and questions arising in managing of this current ordeal. Careful vaccine-safety surveillance over time, in conjunction with the elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy. Allergists’ expertise in proper diagnosis and treatment of allergic reactions is vital for the screening of high-risk individuals.

In recent years, due to the dramatic increase in and global spread of bacterial resistance to a number of commonly used antibacterial agents, many studies have been directed at investigating drugs whose primary therapeutic purpose is not antimicrobial action. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, it is important to understand these antimicrobial effects and their potential clinical implications. Numerous studies report the antibacterial activity of non-steroidal anti-inflammatory drugs, local anaesthetics, phenothiazines such as chlorpromazine, levomepromazine, promethazine, trifluoperazine, methdilazine and thioridazine, antidepressants, antiplatelets and statins. Several studies have explored a possible protective effect of statins inreducing the morbidity and mortality of many infectious diseases. Various non-antibiotic agents exhibit antimicrobial activity via multiple and different mechanisms of action. Further studies are required in the field to further investigate these antimicrobial properties in different populations. This is of paramount importance in the antimicrobial resistance era, where clinicians have limited therapeutic options to combat problematic infections.

Background. Intestinal mucosal barrier dysfunction in liver cirrhosis and its implicated mechanisms is of great clinical importance because it is associated with the development of serious complications from diverse organs through promotion of systemic endotoxemia.Aim. The present study was designed to investigate whether enterocytes’ proliferation, apoptosis and intestinal oxidative stress are altered in the intestinal mucosa of patients with compensated and decompensated liver cirrhosis.Material and methods. Twelve healthy controls (group A) and twenty four cirrhotic patients at a compensated (n = 12, group B) or decompensated condition (n = 12, group C) were subjected to duodenal biopsy. In intestinal specimens mucosal apoptotic and mitotic activity and their ratio were recorded by means of morphological assessment and mucosal lipid hydroperoxides were measured. Plasma endotoxin concentration, an index of gut barrier function, was also determined.Results. Cirrhotic patients presented significantly higher serum endotoxin concentrations as compared to healthy controls (P < 0.001), whilst endotoxemia was higher in decompensated disease (P < 0.05 vs. compensated cirrhosis). Intestinal mucosal mitotic count was significantly lower in patients with compensated and decompensated cirrhosis compared to controls (P < 0.01, respectively), whilst a trend towards increased apoptosis was recorded. The mitotic/apoptotic ratio was significantly reduced in groups B (P < 0.05) and C (P < 0.01) as compared to controls. Intestinal lipid peroxidation was significantly increased in decompensated cirrhotics (P < 0.001 vs. groups A and B).Conclusions. The present study demonstrates for the first time that human liver cirrhosis is associated with decreased intestinal mucosal proliferation and proliferation/apoptosis ratio even at early stages of cirrhosis and increased intestinal oxidative stress in advanced liver disease.