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Article ; Online: Oral Antibiotics for Bacteremia and Infective Endocarditis

Gerasimos Eleftheriotis / Markos Marangos / Maria Lagadinou / Sanjay Bhagani / Stelios F. Assimakopoulos

Microorganisms, Vol 11, Iss 12, p

Current Evidence and Future Perspectives

2023 Volume 3004

Abstract: 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 ... ...

Abstract	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 This clinical approach, however, was based on low-quality data and outdated expert opinions.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.
Keywords	bacteremia ; endocarditis ; oral treatment ; Enterobacterales ; Staphylococcus ; Streptococcus ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Septic Tibial Nonunions on Proximal and Distal Metaphysis—A Systematic Narrative Review

Konstantinos Sidiropoulos / Andreas Panagopoulos / Konstantinos Tsikopoulos / Alkis Saridis / Stelios F. Assimakopoulos / Antonis Kouzelis / Ioannis N. Vrachnis / Panagiotis Givissis

Biomedicines, Vol 11, Iss 1665, p

2023 Volume 1665

Abstract: 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 ... ...

Abstract	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.
Keywords	septic nonunion ; infected metaphyseal tibia fractures ; surgical options ; efficiency ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS CoV-2-Induced Viral Sepsis

Stelios F. Assimakopoulos / Gerasimos Eleftheriotis / Maria Lagadinou / Vassilios Karamouzos / Periklis Dousdampanis / Georgios Siakallis / Markos Marangos

Microorganisms, Vol 10, Iss 1050, p

The Role of Gut Barrier Dysfunction

2022 Volume 1050

Abstract: 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 ... ...

Abstract	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.
Keywords	SARS-CoV-2 ; COVID-19 ; intestinal barrier ; microbiota ; tight junctions ; microbial translocation ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: “When,” “Where,” and “How” of SARS-CoV-2 Infection Affects the Human Cardiovascular System

Nicholas G. Kounis / Christos Gogos / Cesare de Gregorio / Ming-Yow Hung / Sophia N. Kounis / Efthymios P. Tsounis / Stelios F. Assimakopoulos / Soheila Pourmasumi / Virginia Mplani / George Servos / Periklis Dousdampanis / Panagiotis Plotas / Marina A. Michalaki / Grigorios Tsigkas / Gerasimos Grammatikopoulos / Dimitrios Velissaris / Ioanna Koniar

Balkan Medical Journal, Vol 41, Iss 1, Pp 7-

A Narrative Review

2024 Volume 22

Abstract: 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 ...

Abstract	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 ...
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Galenos Publishing House
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cramps during Hemodialysis

Periklis Dousdampanis / Konstantina Trigka / Ioannis Ntouvas / Stelios F Assimakopoulos / Carlos G Musso / Spyros Papadoulas

Saudi Journal of Kidney Diseases and Transplantation, Vol 30, Iss 4, Pp 985-

Are They Always Innocent?

2019 Volume 988

Abstract: 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 ... ...

Abstract	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.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Chemokines CXC, CC and C in the Pathogenesis of COVID-19 Disease and as Surrogates of Vaccine-Induced Innate and Adaptive Protective Responses

Mojgan Noroozi Karimabad / Gholamhossein Hassanshahi / Nicholas G. Kounis / Virginia Mplani / Pavlos Roditis / Christos Gogos / Maria Lagadinou / Stelios F. Assimakopoulos / Periklis Dousdampanis / Ioanna Koniari

Vaccines, Vol 10, Iss 8, p

2022 Volume 1299

Abstract: 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 ... ...

Abstract	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.
Keywords	CXC chemokines ; COVID-19 ; coronavirus ; CC chemokines ; virus ; Medicine ; R
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bile duct ligation in rats

Stelios F Assimakopoulos, Constantine E Vagianos

World Journal of Gastroenterology, Vol 15, Iss 1, Pp 121-

A reliable model of hepatorenal syndrome?

2009 Volume 123

Abstract: The two most widely used experimental models of advanced liver disease are the administration of carbon tetrachloride, and common bile duct ligation (BDL), however, neither has been systematically evaluated as a model of hepatorenal syndrome (HRS). The ... ...

Abstract	The two most widely used experimental models of advanced liver disease are the administration of carbon tetrachloride, and common bile duct ligation (BDL), however, neither has been systematically evaluated as a model of hepatorenal syndrome (HRS). The BDL model in rats, studied at diverse time points, induced a progressive renal dysfunction without structural changes in the kidney. The authors concluded that BDL is a good model for further studies of HRS and its treatment. However, the renal impairment observed at the acute phase of the BDL model is based on a different pathophysiology than that of HRS. Specifically, in acute obstructive jaundice, cholemia predominates over parenchymal liver disease (reversible at this stage without portal hypertension or cirrhosis) and independently induces negative inotropic and chronotropic effects on the heart, impaired sympathetic vasoconstriction response and profound natriuresis and diuresis that might lead to volume depletion. In addition, systemic endotoxemia contributes to the prerenal etiology of renal impairment and promotes direct nephrotoxicity and acute tubular necrosis. On the other hand, the renal failure observed in the chronic BDL model (with development of biliary cirrhosis, portal hypertension and ascites) shares pathophysiological similarities with HRS, but the accordance of the chronic BDL model to the diagnostic criteria of HRS (e.g. absence of spontaneous bacterial peritonitis, no renal function improvement after plasma volume expansion) should have been confirmed. In conclusion, we think that the BDL model is not suitable for the study of the natural history of HRS, but the chronic BDL model might be valid for the study of established HRS and its potential therapies.
Keywords	Obstructive jaundice ; Rats ; Bile duct ligation ; Hepatorenal syndrome ; Renal failure ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	616
Language	English
Publishing date	2009-01-01T00:00:00Z
Publisher	Baishideng Publishing Group Co. Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endotoxin Translocation and Gut Barrier Dysfunction Are Related to Variceal Bleeding in Patients With Liver Cirrhosis

Christos Triantos / Maria Kalafateli / Stelios F. Assimakopoulos / Katerina Karaivazoglou / Aikaterini Mantaka / Ioanna Aggeletopoulou / Panagiota I. Spantidea / Georgios Tsiaoussis / Maria Rodi / Hariklia Kranidioti / Dimitrios Goukos / Spilios Manolakopoulos / Charalambos Gogos / Dimitrios N. Samonakis / Georgios L. Daikos / Athanasia Mouzaki / Konstantinos Thomopoulos

Frontiers in Medicine, Vol

2022 Volume 9

Abstract: 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 ... ...

Abstract	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.
Keywords	cirrhosis ; variceal bleeding ; bacterial translocation ; intestinal barrier ; liver-gut axis ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Allergic Reactions to Current Available COVID-19 Vaccinations

Nicholas G. Kounis / Ioanna Koniari / Cesare de Gregorio / Dimitris Velissaris / Konstantinos Petalas / Aikaterini Brinia / Stelios F. Assimakopoulos / Christos Gogos / Sophia N. Kouni / George N. Kounis / GianFranco Calogiuri / Ming-Yow Hung

Vaccines, Vol 9, Iss 3, p

Pathophysiology, Causality, and Therapeutic Considerations

2021 Volume 221

Abstract: 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 ... ...

Abstract	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 ...
Keywords	allergy ; anaphylaxis ; COVID-19 ; Kounis syndrome ; vaccines ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A mysterious cause of stool ova

Stelios F Assimakopoulos / Konstantinos Thomopoulos / Markos Marangos

Saudi Journal of Gastroenterology, Vol 18, Iss 6, Pp 392-

2012 Volume 393

Keywords	Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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