Convalescent Plasma Treatment of Patients Previously Treated with B-Cell-Depleting Monoclonal Antibodies Suffering COVID-19 Is Associated with Reduced Re-Admission Rates.

Patients receiving treatment with B-cell-depleting monoclonal antibodies, such as anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, either for hematological disease or another diagnosis, such as a rheumatological disease, are at an increased risk for medical complications and mortality from COVID-19. Since inconsistencies persist regarding the use of convalescent plasma (CP), especially in the vulnerable patient population that has received previous treatment with B-cell-depleting monoclonal antibodies, further studies should be performed in thisdirection. The aim of the present study was to describe the characteristics of patients with previous use of B-cell-depleting monoclonal antibodies and describe the potential beneficial effects of CP use in terms of mortality, ICU admission and disease relapse. In this retrospective cohort study, 39 patients with previous use of B-cell-depleting monoclonal antibodies hospitalized in the COVID-19 department of a tertiary hospital in Greece were recorded and evaluated. The mean age was 66.3 years and 51.3% were male. Regarding treatment for COVID-19, remdesivir was used in 89.7%, corticosteroids in 94.9% and CP in 53.8%. In-hospital mortality was 15.4%. Patients who died were more likely to need ICU admission and also had a trend towards a longer hospital stay, even though the last did not reach statistical significance. Patients treated with CP had a lower re-admission rate for COVID-19 after discharge. Further studies should be performed to identify the role of CP in patients with treatment with B-cell-depleting monoclonal antibodies suffering from COVID-19.

Infective endocarditis by Actinomyces species: a systematic review.

Actinomycosis, is a slowly progressive infection that may mimic malignancy due to the invasiveness of tissues and the ability to form sinus tracts. Infective Endocarditis (IE) is a rare disease with significant morbidity and mortality. Interestingly, even though there are scarce data of IE by Actinomyces spp. in the literature, a review adequately summarizing all available evidence on the topic in a systematic way is lacking. The aim of this study was to systematically review all cases of IE by Actinomyces spp. in the literature and describe the epidemiology, microbiology, clinical characteristics, treatment and outcomes of this infection. A systematic review of PubMed, Scopus and Cochrane library (through 19 August 2021) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of IE by Actinomyces spp. was performed. A total of 31 studies providing data for 31 patients were included. A prosthetic valve was present in 12.9%, while the most common microorganism was A. meyeri. Aortic valve was the most commonly infected intracardiac site, followed by the mitral valve. Diagnosis was most commonly performed with transesophageal echocardiography, while the diagnosis was made at autopsy in 16.1%. Penicillin, cephalosporins and aminopenicillins were the most commonly used antimicrobials. Clinical cure was noted in 80.6%, while mortality was 19.4%. Development of heart failure was associated with mortality by IE. This systematic review thoroughly describes IE by Actinomyces and provides information on epidemiology, clinical presentation, treatment and outcomes.

Hydropneumothorax as a complication of necrotizing pneumonia.

Introduction: Hydropneumothorax with a bronchopleural fistula is an infrequent but severe complication of necrotizing pneumonia associated with high morbidity and mortality. Few cases in the adult population have been reported. Case report: This is a case of a 76-year-old male patient who developed pneumonia caused by Pseudomonas aeruginosa and Klebsiella pneumoniae complicated by hydropneumothorax. He was managed conservatively with chest tube placement but denied surgical management and eventually died despite initial improvement. Conclusions: Early recognition and appropriate management of pneumonia complications, such as hydropneumothorax, including thoracic surgeon interventions, are crucial as this complication can be fatal. Factors like the patient's overall status, preferences, and comorbidities may have a crucial effect on clinical decisions and outcomes.

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.

COVID-19 Disease and Vaccination: Knowledge, Fears, Perceptions and Feelings of Regret for Not Having Been Vaccinated among Hospitalized Greek Patients Suffering SARS-CoV-2 Infection.

BACKGROUND: The development of vaccines against COVID-19 has greatly altered the natural course of this infection, reducing the disease's severity and patients' hospitalization. However, hesitancy against vaccination remains an obstacle in the attempt to achieve appropriate herd immunity that could reduce the spread of SARS-CoV-2. The aim of this study was to investigate the perceptions and attitudes of COVID-19 patients hospitalized during the fourth pandemic wave in two Greek hospitals and assess whether their experience had changed their intentions regarding vaccination against COVID-19. METHODS: This is a cross-sectional, questionnaire-based survey, conducted from 31 August 2021 to 18 February 2022 in the COVID-19 departments of two tertiary care hospitals. The questionnaire included questions regarding the patients' educational level, knowledge and beliefs regarding SARS-CoV-2, personal protection measures, beliefs regarding vaccination, vaccination status, reasons for not been vaccinated against SARS-CoV-2, feelings of regret for not been vaccinated, and willingness to be vaccinated in the future. All adult patients with COVID-19 were eligible, regardless of their vaccination status against SARS-CoV-2. RESULTS: In total, 162 patients agreed and participated in the study, with 97% of them suffering severe COVID-19. Their median age was 56 years, and 59.9% (97 patients) were male. Among them, 43.8% had been vaccinated against COVID-19. When unvaccinated patients were asked the reasons for not being vaccinated, the most frequent responses were that they were waiting for more scientific data, due to uncertainty about long-term consequences of the vaccine, and their fear of thrombosis. When at discharge, unvaccinated hospitalized COVID-19 patients were asked whether they would get vaccinated if they could turn time back, and 64.7% of them replied positively. CONCLUSIONS: The study reveals several patients' fears and misconceptions and suggests that there is room for implementing measures that could reduce knowledge gaps allowing for improvement of vaccination rates against COVID-19.

Visceral Varicella-Zoster Virus Infection Presenting with Severe Abdominal Pain without a Rash in a Patient with Psoriatic Arthritis Treated with Infliximab Biosimilar and Steroids: A Case Report.

Visceral herpes zoster following reactivation of dormant varicella-zoster virus can rarely occur, usually in highly immunosuppressed patients, and may present with abdominal pain without the relevant rash. In the absence of skin manifestations, diagnosis of visceral herpes zoster is extremely difficult, while computed tomography may reveal isolated periarterial fat stranding. We describe a rare case of visceral herpes zoster in a medically immunocompromised adult with psoriatic arthritis, who presented with acute abdomen, was diagnosed based on computed tomography findings and subsequent serum polymerase chain reaction results, and was appropriately treated with an uneventful recovery. This case underlines the significance of considering varicella-zoster virus infection as a cause of severe abdominal pain even in the absence of rash in this setting, and highlights the potential role of appropriately performed computed tomography in such unusual and complex cases, where early diagnosis and initiation of treatment is extremely important for a favorable outcome.

Candida parapsilosis endocarditis. Report of cases and review of the literature.

INTRODUCTION: Infective endocarditis (IE) due to Candida species is a rare disease representing about 1-2% of all IE cases and carries a high mortality rate. Given the rarity of the disease, there are no clear guidelines on the type and duration of antifungal therapy. Thus, long-term or even life-long antifungal treatment is commonly used. CASE REPORT: We report two patients with prosthetic valve C. parapsilosis IE and persistent candidemia that failed conservative treatment and ultimately developed heart failure. They underwent prosthetic valve replacement and prolonged antifungal treatment with favorable outcome. DISCUSSION: Candida IE commonly occurs in the setting of underlying malignancy, chronic liver disease, previous endocarditis, previous antimicrobial exposure, previous abdominal surgery, intravenous drug use, presence of a central venous catheter, and previous cardiac surgery. Both present patients had undergone a cardiac surgery and had a prosthetic heart valve, while one patient had an underlying autoimmune disease that could be associated with higher risk of IE. In both patients transthoracic ultrasound failed to diagnose IE. In our patients, conservative treatment alone was not enough to control the infection, thus, both patients underwent valve replacement and were subsequently treated with antifungals for 6 weeks. Furthermore, both patients were put on long-term antifungal suppression treatment. CONCLUSIONS: Given the absence of controlled randomized trials, the treatment of Candida endocarditis mostly relies on experts' opinion, and, thus, future studies focusing on the type and duration of antifungal treatment are required.

Fungal endocarditis in transplant recipients: A systematic review.

BACKGROUND: Invasive fungal infections remain a major cause of morbidity and mortality in transplant recipients. Moreover, Fungal Infective Endocarditis (FIE) is a rare infection that carries a higher mortality than bacterial IE in normal host, while in transplant recipients may be even higher. The purpose of this study was to systemically review all published cases of FIE in solid organ and allogeneic bone marrow transplant recipients, describe the epidemiology, microbiology, clinical characteristics, treatment and outcomes of these infections, and to identify risk factors for mortality by FIE. METHODS: A systematic review of PubMed, Scopus and Cochrane Library (through 20 May 2020) for studies providing epidemiological, clinical, microbiological and treatment data and outcomes of FIE in transplant recipients was performed. RESULTS: A total of 60 studies, containing data of 72 patients, were included. The most common transplants were those of the kidney and the liver, while the commonest causative pathogen was Aspergillus. Mitral valve was the commonest infected intracardiac site, followed by mural endocardium. Diagnosis was made with transthoracic echocardiography in 44.3%, while the diagnosis was made at autopsy in 37.3%. Embolic phenomena were the commonest clinical presentation, followed by fever, heart failure and endophthalmitis. Amphotericin B, voriconazole and caspofungin were the commonest antifungals used for treatment of FIE. Clinical cure was noted in 26.9%, while overall mortality was 78.6%. Amphotericin B or caspofungin use was negatively associated with overall mortality. CONCLUSIONS: This systematic review thoroughly describes IE in transplant recipients and provides information on epidemiology, clinical presentation, treatment and outcomes.

Kodamaea ohmeri infections in humans: A systematic review.

BACKGROUND: Kodamaea ohmeri, previously known as Pichia ohmeri or Yamadazyma ohmeri, belongs to the Saccharomycetaceae family and the Ascomycetae class, is the telomorphic form of C guilliermondii var. membranaefaciens and is frequently mistaken for Candida, as they belong to the same family. It has been isolated from environmental sources, such as sand, pools, seawater and fruits, while the last decades it is recognised as a rare pathogen that causes life-threatening infections in humans. The purpose of this study was to systemically review all published cases of K ohmeri infections in the literature and describe the epidemiology, microbiology, antimicrobial susceptibility, treatment and outcomes of these infections in humans. METHODS: Systematic review of PubMed (through 27th December 2019) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of K ohmeri infections. RESULTS: A total of 35 studies, containing data of 44 patients, were included in the analysis. The most common K ohmeri infections were those of the bloodstream, infective endocarditis and onychomycosis. Previous antibiotic use, presence of a central venous catheter, parenteral nutrition and cancer were very common among patients. Mortality was high in the case of fungemias but low for other types of infections. Amphotericin B and fluconazole are the most common agents used for treatment, even though alarming MICs for fluconazole were noted. CONCLUSIONS: This systematic review thoroughly describes infections by K ohmeri and provides information on their epidemiology, clinical presentation, microbiology, antibiotic resistance patterns, treatment and outcomes.

Gastrointestinal perforation: clinical and MDCT clues for identification of aetiology.

Gastrointestinal tract (GIT) perforation is a common medical emergency associated with considerable mortality, ranging from 30 to 50%. Clinical presentation varies: oesophageal perforations can present with acute chest pain, odynophagia and vomiting, gastroduodenal perforations with acute severe abdominal pain, while colonic perforations tend to follow a slower progression course with secondary bacterial peritonitis or localised abscesses. A subset of patients may present with delayed symptoms, abscess mimicking an abdominal mass, or with sepsis.Direct multidetector computed tomography (MDCT) findings support the diagnosis and localise the perforation site while ancillary findings may suggest underlying conditions that need further investigation following primary repair of ruptured bowel. MDCT findings include extraluminal gas, visible bowel wall discontinuity, extraluminal contrast, bowel wall thickening, abnormal mural enhancement, localised fat stranding and/or free fluid, as well as localised phlegmon or abscess in contained perforations.The purpose of this article is to review the spectrum of MDCT findings encountered in GIT perforation and emphasise the MDCT and clinical clues suggestive of the underlying aetiology and localisation of perforation site.

Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes.

Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61-0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82-1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43-0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.

The P274S Mutation of Lecithin-Cholesterol Acyltransferase (LCAT) and Its Clinical Manifestations in a Large Kindred.

RATIONALE & OBJECTIVE: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 2 (related) index patients with clinically apparent FLD were initially identified. 110 of 122 family members who consented to genetic analysis were also studied. PREDICTORS: Demographic and laboratory parameters (including lipid profiles and LCAT activity) and full sequence analysis of the LCAT gene. Kidney histologic examination was performed with samples from 6 participants. OUTCOMES: Cardiovascular and renal events during a median follow-up of 12 years. Estimation of annual rate of decline in glomerular filtration rate. ANALYTICAL APPROACH: Analysis of variance, linear regression analysis, and Fine-Gray competing-risk survival analysis. RESULTS: 9 homozygous, 57 heterozygous, and 44 unaffected family members were identified. In all affected individuals, full sequence analysis of the LCAT gene revealed a mutation (c.820C>T) predicted to cause a proline to serine substitution at amino acid 274 (P274S). Homozygosity caused a complete loss of LCAT activity. Kidney biopsy findings demonstrated lipid deposition causing glomerular basement membrane thickening, mesangial expansion, and "foam-cell" infiltration of kidney tissue. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with worse kidney outcomes. Estimated glomerular filtration rate deteriorated among homozygous family members at an average annual rate of 3.56 mL/min/1.73 m2. The incidence of cardiovascular and renal complications was higher among homozygous family members compared with heterozygous and unaffected members. Mild thrombocytopenia was a common finding among homozygous participants. LIMITATIONS: The presence of cardiovascular disease was mainly based on medical history. CONCLUSIONS: The P274S LCAT mutation was found to cause FLD with renal involvement. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with a worse renal prognosis.

SGLT2 inhibitors and cardioprotection: a matter of debate and multiple hypotheses.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. Two trials have shown significant reductions of cardiovascular (CV) events with empagliflozin and canagliflozin, which could not be attributed solely to their antidiabetic effects. The aim of the review is the critical presentation of suggested mechanisms/hypotheses for the SGLT2 inhibitors' cardioprotection. The search of the literature revealed many possible cardioprotective mechanisms, because SGLT2 inhibitors (i) increase natriuresis and act as diuretics with unique properties leading to a reduction in preload and myocardial stretch (the diuretic hypothesis); (ii) decrease blood pressure and afterload (the blood pressure lowering hypothesis), (iii) favor the production of ketones, which can act as a 'superfuel' in the cardiac and renal tissue (the 'thrifty substrate' hypothesis), (iv) improve many metabolic variables (the metabolic effects hypothesis), (v) exert many anti-inflammatory effects (the anti-inflammatory effects hypothesis), (vi) can act through the angiotensin II type II receptors in the context of simultaneous renin-angiotensin-aldosterone-system (RAAS) blockade leading to vasodilation and positive inotropic effects (the RAAS hypothesis), (vii) directly decrease the activity of the upregulated in heart failure Na+-H+ exchanger in myocardial cells leading to restoration of mitochondrial calcium handling in cardiomyocytes (the sodium hypothesis). Additionally, some SGLT2 inhibitors exhibit also SGLT1 inhibitory action possibly resulting in an attenuation of oxidative stress in ischemic myocardium (the SGLT1 inhibition hypothesis). Thus, many mechanisms have been suggested (and possibly act cumulatively) for the cardioprotective effects of SGLT2 inhibitors.