Streptococcus pseudoporcinus bacteremia in a patient with skin and soft tissue infection. A case report and literature review.

Streptococcus pseudoporcinus is a beta-hemolytic Streptococcus species arranged in short chains, which was first described in 2006. In the last years, there have been several reports of human infections by this bacterium, with five skin and soft tissue infections identified. Herein, a case of S. pseudoporcinus skin and soft tissue infection in a patient, who also developed bacteremia and was successfully treated with intravenous antibiotics, is reported. A 67-year-old man with a history of diffuse large B-cell lymphoma presented to the emergency department because of fever, redness, swelling, and pain in the left lower limb. He was admitted to the medical ward, diagnosed with severe non-purulent skin and soft tissue infection, and treated empirically with intravenous piperacillin/tazobactam at 4.5 gr thrice daily and daptomycin at 10mg/kg once daily. Blood cultures were obtained before the initiation of the antibiotics and grew S. pseudoporcinus. Treatment was de-escalated to ceftriaxone at a dose of 2 gr once daily. He completed two weeks of intravenous antimicrobial treatment. S. pseudoporcinus is an emerging pathogen associated with skin and soft tissue infections, bacteremia, and other invasive, potentially life-threatening infections. Further investigation is warranted to clarify this microorganism's pathogenesis and biological significance.

Pseudomonas Bacteremia in a Tertiary Hospital and Factors Associated with Mortality.

Pseudomonas aeruginosa is the third most commonly identified cause among gram-negative microorganisms causing bloodstream infection (BSI) and carries a very high mortality, higher than that by other gram-negative pathogens. The aim of the present study was to assess the epidemiological and microbiological characteristics of patients with BSI by Pseudomonas spp. in a tertiary hospital, characterize the resistance rates of different Pseudomonas strains to the most clinically relevant anti-microbials, estimate the mortality rate, and identify factors independently associated with mortality. In total, 540 cultures from 419 patients sent to the microbiology department of the hospital during the 8-year period of the study were positive. Patients had a median age of 66 years, and 262 (62.5%) were male. The blood culture was drawn in the ICU in 201 of the patients (48%). The infection was hospital-acquired in 329 patients (78.5%) and the median hospital day when the blood culture was drawn was 15, with a range of 0 to 267 days. Median duration of stay in the hospital was 36 days, hospital mortality was 44.2% (185 patients), and 30-day mortality was 29.6% (124 patients). The most commonly isolated Pseudomonas species were P. aeruginosa followed by P. putida and P. oryzihabitans. There was a statistically significant reduction of P. aeruginosa isolation relative to non-aeruginosa Pseudomonas species in the post-COVID-19 era. Antimicrobial resistance of P. aeruginosa in clinically relevant antimicrobials with anti-pseudomonal activity was similar before and after the onset of the COVID-19 pandemic with the exception of gentamicin and tobramycin, with P. aeruginosa being more susceptible to these two antimicrobials in the post-COVID-19 era. Rates of multi-drug resistant (MDR), extensively-drug resistant (XDR), and difficult-to-treat (DTR) P. aeruginosa isolation were lower after the onset of the COVID-19 pandemic, even though a carbapenem-focused antimicrobial stewardship program had been implemented in the meantime. Increased age, ICU-acquisition of BSI, and more days in the hospital when positive blood culture was drawn were positively associated with 30-day mortality of patients with Pseudomonas BSI. The fact that rates of MDR, XDR, and DTR P. aeruginosa isolation were lower late in the study period, with a carbapenem-focused antimicrobial stewardship intervention being implemented in the meantime, further increases the understanding that implementation of antimicrobial stewardship interventions may halt the increase in antimicrobial resistance noted previously.

Overview of methods and available tools used in complex brain disorders.

Complex brain disorders, including Alzheimer's dementia, sleep disorders, and epilepsy, are chronic conditions that have high prevalence individually and in combination, increasing mortality risk, and contributing to the socioeconomic burden of patients, their families and, their communities at large. Although some literature reviews have been conducted mentioning the available methods and tools used for supporting the diagnosis of complex brain disorders and processing different files, there are still limitations. Specifically, these research works have focused primarily on one single brain disorder, i.e., sleep disorders or dementia or epilepsy. Additionally, existing research initiatives mentioning some tools, focus mainly on one single type of data, i.e., electroencephalography (EEG) signals or actigraphies or Magnetic Resonance Imaging, and so on. To tackle the aforementioned limitations, this is the first study conducting a comprehensive literature review of the available methods used for supporting the diagnosis of multiple complex brain disorders, i.e., Alzheimer's dementia, sleep disorders, epilepsy. Also, to the best of our knowledge, we present the first study conducting a comprehensive literature review of all the available tools, which can be exploited for processing multiple types of data, including EEG, actigraphies, and MRIs, and receiving valuable forms of information which can be used for differentiating people in a healthy control group and patients suffering from complex brain disorders. Additionally, the present study highlights both the benefits and limitations of the existing available tools.

Candida Species Isolation from Hospitalized Patients with COVID-19-A Retrospective Study.

Coronavirus disease 2019 (COVID-19), a disease characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has so far led to hundreds of millions of infections and millions of deaths. Fungal infections are known to complicate COVID-19 patients and are associated with significant morbidity and mortality. The aim of this study was to assess the incidence of positive cultures for Candida spp. among patients hospitalized with COVID-19, describe their characteristics and identify factors associated with overall mortality in this patient population. Hospitalized COVID-19 patients with Candida spp. isolation were retrospectively assessed and their clinical, laboratory and microbiological characteristics were assessed and evaluated. In total, 69 patients with COVID-19 had a positive culture for Candida spp., representing a rate of 4.5% among all hospitalized COVID-19 patients. Their median age was 78 years (IQR 67-85 years) and 44.9% were male. Hospitalized patients with COVID-19 and Candida spp. isolation who died were older, were more likely to have a diagnosis of dementia, and had higher Charlson comorbidity index, higher Candida score and higher 4C score. Candida score was identified with a multivariate logistic regression analysis model to be independently associated with mortality. The most commonly identified Candida species was C. albicans, followed by C. tropicalis and C. glabrata and the most common source was the urine, even though in most cases the positive culture was not associated with a true infection. Thus, Candida score may be used in COVID-19 patients with isolation of Candida spp. from different body specimens for mortality risk stratification.

Infective Endocarditis by Moraxella Species: A Systematic Review.

Moraxella catarrhalis is the most clinically relevant species among Moraxella spp. For decades, it was considered to be part of the normal human flora in the upper respiratory tract. However, since the late 1970s, considerable evidence has proposed that M. catarrhalis is an important pathogen in the human respiratory tract. Even though Infective Endocarditis (IE) is rarely caused by Moraxella spp., these infections can be problematic due to the lack of experience in their management. The aim of this study was to systematically review all published cases of IE by Moraxella spp. A systematic review of PubMed, Scopus and Cochrane library (through 8 December 2021) for studies providing epidemiological, clinical, microbiological data as well as treatment data and outcomes of IE by Moraxella spp. was performed. A total of 27 studies, containing data for 31 patients, were included. A prosthetic valve was present in 25.8%. Mitral valve was the most commonly infected site. Fever, sepsis and embolic phenomena were the most common clinical presentations. Cephalosporins, aminoglycosides, aminopenicillins and penicillin were the most commonly used antimicrobials. Overall mortality was 12.9%.

Infective endocarditis by Serratia species: a systematic review.

Serratia species are facultative anaerobes, non-spore-forming, motile Gram-negative bacteria. Serratia spp. are currently thought to cause a variety of infections, such as bacteremia, urinary tract infections, and pneumonia, as well as other, less common infections, including ocular infections or skin and soft tissue infections. On the other hand, Infective Endocarditis (IE) is an infrequent disease with notable morbidity and mortality. Even though IE is rarely caused by Serratia spp., these infections can be quite problematic due to the lack of experience in their management. This study aimed to systematically review all published cases of IE by Serratia spp. in the literature. A systematic review of PubMed, Scopus, and Cochrane library (through 13th May 2021) for studies providing epidemiological, clinical, microbiological data as well as data on treatment and outcomes of IE by Serratia spp. was performed. In total, 50 studies, containing data for 72 patients, were included. A prosthetic valve was present in 18.1%. The mitral valve was the most commonly infected site, followed by the aortic valve. The diagnosis was facilitated by transthoracic echocardiography in 34.7%, while the diagnosis was set at autopsy in 22.4%. Fever, sepsis, and embolic phenomena were the most common clinical presentations, followed by heart failure. Aminoglycosides, cephalosporins, and carbapenems were the most commonly used antimicrobials. Clinical cure was noted only in 53.5%, while overall mortality was 47.2%. Having surgery along with antimicrobial treatment was independently associated with reduced overall mortality. IE by Serratia spp. was more likely to be associated with intravenous drug use, and to present with heart failure and embolic phenomena compared to IE by other non-HACEK Gram-negative bacilli, while mortality was also higher in IE by Serratia spp.

Endocarditis in Liver Transplant Recipients: A Systematic Review.

Infective Endocarditis (IE) is associated with significant mortality. Interestingly, IE in patients with liver transplantation has not been adequately described. The aim of this review was to systematically review all published cases of IE in liver transplant recipients and describe their epidemiology, microbiology, clinical characteristics, treatment and outcomes. A systematic review of PubMed, Scopus and Cochrane Library (through 2 January 2021) for studies providing epidemiological, clinical, microbiological, treatment data and outcomes of IE in liver transplant recipients was conducted. A total of 39 studies, containing data for 62 patients, were included in the analysis. The most common causative pathogens were gram-positive microorganisms in 69.4%, fungi in 25.8%, and gram-negative microorganisms in 9.7% of cases, while in 9.3% IE was culture-negative. The aortic valve was the most commonly infected valve followed by mitral, tricuspid and the pulmonary valve. Aminoglycosides, vancomycin and aminopenicillins were the most commonly used antimicrobials, and surgical management was performed in half of the cases. Clinical cure was noted in 57.4%, while overall mortality was 43.5%. To conclude, this systematic review thoroughly describes IE in liver transplant recipients and provides information on epidemiology, clinical presentation, treatment and outcomes.

Endocarditis in kidney transplant recipients: a systematic review.

Infective Endocarditis (IE) carries significant mortality. Bacteremia, which is a predisposing factor for IE, occurs more frequently in immunocompromised individuals. Interestingly, IE in kidney transplant recipients has not been adequately described. The aim of this study was to systematically review all published cases of IE in kidney transplant recipients and describe their epidemiology, microbiology, clinical characteristics, treatment and outcomes. A systematic review of PubMed (through 13th December 2019) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of IE in kidney transplant recipients was performed. A total of 60 studies, containing data of 117 patients, were included in the analysis. The most common causative pathogens were gram-positive microorganisms in 57.4%, gram-negative microorganisms in 14.8%, fungi in 20%, while in 18.9% of cases, IE was culture-negative. Aortic valve was the most commonly infected valve followed by mitral, tricuspid and the pulmonary valve. Diagnosis was set with a transthoracic ultrasound in half the cases, followed by transesophageal ultrasound and autopsy. Fever was present in most cases, while embolic phenomena were noted in two out of five cases. Aminoglycosides, cephalosporins and aminopenicillins were the most commonly used antimicrobials, and surgical management was performed in one out of three cases. Clinical cure was noted in 60.9%, while overall mortality was 45.3%. To conclude, this systematic review thoroughly describes IE in kidney transplant recipients and provides information on epidemiology, clinical presentation, treatment and outcomes. Moreover, it identifies the emerging role of Enterococci, gram-negatives and fungi in IE in this population.

Hemophagocytic lymphohistiocytosis syndrome associated with Epstein-Barr infection in an immunocompetent patient. A case study.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening rare disease resulting from the uncontrolled activation of the immune system, leading to unrestrained cytokine release and macrophage activation. It can be either hereditary or acquired due to infections, hematological disease or malignancy. CASE REPORT: We present the case of a 19-year old woman that presented with high fever and acute cholestatic hepatitis. She was initially admitted to the Gastroenterology department and the following days she developed respiratory distress and multiorgan insufficiency that necessitated intubation and support in the Intensive Care Unit. Fever, splenomegaly, hypertriglyceridemia, increased ferritin levels and hemophagocytosis in the bone marrow were found, thus, fulfilling the criteria of hemophagocytic lymphohistiocytosis. Laboratory examination was notable for positive serology (IgM and IgG) and PCR for EBV in the serum. An extensive workup including virology and immunologic workup, blood cultures, a CT of the thorax and the abdomen and a bone marrow biopsy did not reveal any cause of secondary HLH other than the EBV infection. The patient was treated with high dose corticosteroids and intravenous immunoglobulins with slow resolution of her symptoms. CONCLUSIONS: In patients with EBV infection who exhibit persistent high fever and unresponsiveness to antibiotics, the possibility of HLH should be considered. Early diagnosis and rapid initiation of appropriate treatment may avert an unfavorable outcome.

BCMA (TNFRSF17) Induces APRIL and BAFF Mediated Breast Cancer Cell Stemness.

Recent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL (TNFSF13), and BAFF (TNFSF13B), which are type II membrane proteins, released in active forms by proteolytic cleavage and are primarily involved in B-lymphocyte maturation, have also been associated with tumor growth and aggressiveness in several solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition, migration, and stemness of breast cancer cells. Our findings show that both molecules increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by increasing the expression of pluripotency genes such as ALDH1A1, KLF4, and NANOG. These effects are mediated by their common receptor BCMA (TNFRSF17) and the JNK signaling pathway. Interestingly, transcriptional data analysis from breast cancer cells and patients revealed that androgens can increase APRIL transcription and subsequently, in an autocrine/paracrine manner, enhance its pluripotency effect. In conclusion, our data suggest a possible role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased.

Tamoxifen induces a pluripotency signature in breast cancer cells and human tumors.

Tamoxifen is the treatment of choice in estrogen receptor alpha breast cancer patients that are eligible for adjuvant endocrine therapy. However, ∼50% of ERα-positive tumors exhibit intrinsic or rapidly acquire resistance to endocrine treatment. Unfortunately, prediction of de novo resistance to endocrine therapy and/or assessment of relapse likelihood remain difficult. While several mechanisms regulating the acquisition and the maintenance of endocrine resistance have been reported, there are several aspects of this phenomenon that need to be further elucidated. Altered metabolic fate of tamoxifen within patients and emergence of tamoxifen-resistant clones, driven by evolution of the disease phenotype during treatment, appear as the most compelling hypotheses so far. In addition, tamoxifen was reported to induce pluripotency in breast cancer cell lines, in vitro. In this context, we have performed a whole transcriptome analysis of an ERα-positive (T47D) and a triple-negative breast cancer cell line (MDA-MB-231), exposed to tamoxifen for a short time frame (hours), in order to identify how early pluripotency-related effects of tamoxifen may occur. Our ultimate goal was to identify whether the transcriptional actions of tamoxifen related to induction of pluripotency are mediated through specific ER-dependent or independent mechanisms. We report that even as early as 3 hours after the exposure of breast cancer cells to tamoxifen, a subset of ERα-dependent genes associated with developmental processes and pluripotency are induced and this is accompanied by specific phenotypic changes (expression of pluripotency-related proteins). Furthermore we report an association between the increased expression of pluripotency-related genes in ERα-positive breast cancer tissues samples and disease relapse after tamoxifen therapy. Finally we describe that in a small group of ERα-positive breast cancer patients, with disease relapse after surgery and tamoxifen treatment, ALDH1A1 (a marker of pluripotency in epithelial cancers which is absent in normal breast tissue) is increased in relapsing tumors, with a concurrent modification of its intra-cellular localization. Our data could be of value in the discrimination of patients susceptible to develop tamoxifen resistance and in the selection of optimized patient-tailored therapies.