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We assessed the vaccination effectiveness (VE) of a COVID-19 booster vaccine dose and the association between morbidity and absenteeism with COVID-19 booster vaccine receipt among healthcare personnel (HCP) in 2022–2023 in Greece. We followed 5752 HCP from November 14, 2022 through May 28, 2023 for episodes of absenteeism. Absenteeism for non-infectious causes, pregnancy leave, or annual leave was not recorded. Full vaccination was defined as a primary vaccination series plus one booster dose within the past six months. Multivariable regression models were used to estimate the association of full COVID-19 vaccination with the outcomes of interest. A total of 1029 episodes of absenteeism occurred during the study period (17.9 episodes per 100 HCP). The mean duration of absence per episode was 5.2 days, and the total duration of absence was 5237 days. COVID-19 was diagnosed in 736 (12.8 %) HCP, asymptomatic SARS-CoV-2 infection in 62 (1.1 %) HCP, and influenza in 95 (1.7 %) HCP. Overall, COVID-19, influenza, and asymptomatic SARS-CoV-2 infection accounted for 71.5 %, 9.2 %, and 6.0 % of episodes of absenteeism, respectively. Multivariable regression models indicated that fully vaccinated HCP were absent from work for shorter periods [adjusted odds ratio (aOR): 0.42; 95 % confidence interval (CI): 0.21–0.83], were less likely to develop COVID-19 [aOR: 0.37; 95 % CI: 0.17–0.81)], and were more likely to develop an asymptomatic SARS-CoV-2 infection (aOR: 5.90; 95 % CI: 1.27–27.45). The adjusted full VE against COVID-19 was 62.8 % (95 % CI: 18.6 %-83.0 %). COVID-19 remains a significant cause of morbidity and absenteeism among HCP. Full COVID-19 vaccination status conferred significant protection against COVID-19 and was associated with shorter periods of absence from work. [ABSTRACT FROM AUTHOR]

Iron plays an important role in the pathogenesis of infections, including invasive fungal infections (IFIs). Studies suggested that iron overload might represent an additional risk factor for IFIs among patients with hematological malignancies. We conducted a prospective, multi-center study amongst adult patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in transformation to determine whether baseline iron overload as measured using the bone marrow iron store (BMIS) score is an independent risk factor for the development of IFIs. We also measured baseline serum iron and ferritin levels. A total of 98 patients were enrolled (76 with AML) and were followed for 12 months. Twenty-two patients developed IFI during the follow-up period (invasive aspergillosis n = 16, candidemia n = 5, mucormycosis n = 1). A baseline BMIS score ≥ 3 indicated that iron overload was relatively common (38/98 patients, 38%), and its frequency was comparable between patients with no IFIs (31/76, 40.7%) and in those with IFIs (8/22, 36.4%). Univariate analysis showed that only the presence of AML was associated with increased risk for IFIs [OR (95% CI) 7.40 (1.05–325.42)]. Both univariate and multivariate analyses showed that an increased BMIS score (≥3) at baseline was not an independent risk factor for IFIs. Similarly, there was no difference in serum iron and ferritin between the two groups that had similar demographic characteristics. Indices of iron overload were not independent risk factors for IFIs in our cohort of Greek patients with newly diagnosed AML/MDS in transformation. [ABSTRACT FROM AUTHOR]

We assessed the impact of COVID-19 vaccination status and time elapsed since the last vaccine dose on morbidity and absenteeism among healthcare personnel (HCP) in the context of a mandatory vaccination policy. We followed 7592 HCP from November 15, 2021 through April 17, 2022. Full COVID-19 vaccination was defined as a primary vaccination series plus a booster dose at least six months later. There were 6496 (85.6 %) fully vaccinated, 953 (12.5 %) not fully vaccinated, and 143 (1.9 %) unvaccinated HCP. A total of 2182 absenteeism episodes occurred. Of 2088 absenteeism episodes among vaccinated HCP with known vaccination status, 1971 (94.4 %) concerned fully vaccinated and 117 (5.6 %) not fully vaccinated. Fully vaccinated HCP had 1.6 fewer days of absence compared to those not fully vaccinated (8.1 versus 9.7; p-value < 0.001). Multivariable regression analyses showed that full vaccination was associated with shorter absenteeism compared to not full vaccination (OR: 0.56; 95 % CI: 0.36–0.87; p-value = 0.01). Compared to a history of ≤ 17.1 weeks since the last dose, a history of > 17.1 weeks since the last dose was associated with longer absenteeism (OR: 1.22, 95 % CI:1.02–1.46; p-value = 0.026) and increased risk for febrile episode (OR: 1.33; 95 % CI: 1.09–1.63; p-value = 0.004), influenza-like illness (OR: 1.53, 95 % CI: 1.02–2.30; p-value = 0.038), and COVID-19 (OR: 1.72; 95 % CI: 1.24–2.39; p-value = 0.001). The COVID-19 pandemic continues to impose a considerable impact on HCP. The administration of a vaccine dose in less than four months before significantly protected against COVID-19 and absenteeism duration, irrespective of COVID-19 vaccination status. Defining the optimal timing of boosters is imperative. [ABSTRACT FROM AUTHOR]

Objective: The F508del mutation occurs in approximately 3.5% of Caucasian population of Northern Europe. Heterozygotes have increased risk for asthma and reduced pulmonary function. Allergic bronchopulmonary aspergillosis (ABPA) is more common in patients with cystic fibrosis (CF). We aimed to establish the frequency of F508del mutation in adult patients with ABPA. Methods: A retrospective matched case-control study of CF genotyped patients with ABPA seen at the National Aspergillosis Centre was undertaken. Key data were collected retrospectively from medical records, including respiratory comorbidities, total IgE, Aspergillus IgG and IgE, and immunoglobulins. Cystic fibrosis transmembrane regulator (CFTR) gene mutation analysis included multiplex PCR and sequencing. Results: From a cohort of 189 ABPA patients, 156 were screened for common mutations and variants in the CFTR gene. Eighteen were heterozygous for at least one CFTR mutation; 12 (7.7%) were heterozygous for the F508del, notably; 3 were heterozygous for the intron 8 5T variant; and 1 for an intronic variant of uncertain significance, c.3139 + 18C>T. Eight (67%) had asthma, 7 (58%) had CT-defined bronchiectasis, 4 (33%) hypergammaglobulinemia (>16 g/L), 3 (25%) sinusitis and 1 (8%) chronic pulmonary aspergillosis. Eight (67%) had elevated Aspergillus IgG antibodies (42-98 mg/L), and 8 (67%) had total IgE above 1,000 KIU/L. Two individuals heterozygous for the F508del mutation and the TG12T5 variant were diagnosed with CF, leading to a de novo CF discovery rate of 1.3%. Conclusions: In our ABPA patient cohort, the presence of the delta F508 mutation was higher than that seen in general population. Genetic counseling for CFTR genotyping might be appropriate for these patients. [ABSTRACT FROM AUTHOR]

Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance. [ABSTRACT FROM AUTHOR]

The prevalence of asymptomatic bacteriuria (AB) among women with autoimmune rheumatic diseases was not higher than that among age-matched controls. The presence of AB at baseline was not associated with higher risk for subsequent symptomatic urinary tract infections.Background. Data regarding the prevalence and clinical significance of asymptomatic bacteriuria (AB) in women with autoimmune rheumatic disease (ARD) are scarce.Methods. In this prospective, case-control study, consecutive female outpatients with ARD were screened for AB. For each patient, demographics, type, duration, and treatment of underlying ARD, and risk factors for urinary tract infection (UTI), were recorded. Age-matched women with endocrine disease, without any autoimmune disease, not receiving immunosuppressive agents were used as controls. Subjects were followed up for 1 year for the development of symptomatic UTI.Results. Two hundred sixty patients with ARD (mean age, 52.4 [standard deviation {SD}, 14.6] years) and 238 controls (mean age, 51.2 [SD, 16.5] years) were enrolled. The majority of patients with ARD (93.5%; 95% confidence interval [CI], 89.7%–95.9%) were receiving immunosuppressive agents. AB was detected in 24 patients with ARD (9.2%; 95% CI, 6.2%–13.4%) and in 22 controls (9.2%; 95% CI, 5.5%–12.9%) (P = 1.000). The most prevalent pathogen was Escherichia coli (16/24 [66%]). Independent predictors for AB among patients were diabetes (odds ratio [OR], 6.6; P = .008) and a longer ARD duration (>84 months; OR, 4.3; P = .018). During the 1-year follow-up, 9 patients with baseline AB remained persistently bacteriuric, whereas 11 were intermittently bacteriuric. Symptomatic UTI developed in 4 of 24 patients (16.7%; 95% CI, 6.1%–36.5%) with baseline AB vs 29 of 236 (12.3%; 95% CI, 8.6%–17.1%) without AB (P = .522).Conclusions. In our study, the prevalence of AB among women with ARD was not higher than that of controls, and AB was not associated with higher risk for symptomatic UTI. Risk factors for AB were longer duration of ARD and diabetes. [ABSTRACT FROM PUBLISHER]

Background: Current guidelines for treatment of Candida osteoarticular infections (COAIs) recommend a prolonged course of antifungal therapy (AFT) of 6 - 12 months. Based upon strategies developed at the Hospital for Special Surgery (HSS), we hypothesized that the duration of antifungal therapy may be substantially reduced for management of COAI. Methods: This was a retrospective chart review of cases of COAI treated at the HSS for the past 14 years. COAI was documented by open biopsy and direct culture in all cases. The mean (95% confidence interval, CI) duration of documented follow-up was 39 (16 - 61) months. Results: Among the 23 cases of COAI, the median age was 62 years (range 22 - 83 years) with 61% having no underlying condition. Orthopedic appliances, including joint prostheses and fracture hardware, were present in 74% of cases. All patients had COAI as the fi rst proven site of candidiasis. Candida albicans and Candida parapsilosis were the most common species. Hip, knee, foot, and ankle were the most common sites. All patients received aggressive surgical intervention followed by AFT administered for a mean (95% CI) duration of 45 (38 - 83) days. Systemic AFT consisted principally of fl uconazole alone (65%) or in combination with other agents (26%). Adjunctive intraoperative amphotericin B irrigation was used in 35%. Among eight cases of CAOI that required placement of a new prosthetic joint, all were successfully treated. There were no microbiologic failures. Conclusions: Candida osteoarticular infections may be successfully treated with substantially limited durations of AFT when combined with a thorough surgical approach. [ABSTRACT FROM AUTHOR]

In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs ≤ 1 µg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation. [ABSTRACT FROM AUTHOR]

Candida osteomyelitis most frequently presents subacutely with local symptoms but minimally elevated inflammatory biomarkers, hematogenous dissemination caused by C. albicans involving vertebrae in adults and femur/humerus in children, high relapse rate requiring extended therapy (median 3 months), and often surgical intervention.Background. The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood.Methods. Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases.Results. Median age was 30 years (range, ≤ 1 month to 88 years) with a >2:1 male:female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had ≥2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04–.25), rib, and sternum; for pediatric patients (≤18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4–48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response.Conclusions. Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6–12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome. [ABSTRACT FROM AUTHOR]

Summary Invasive fungal infections have emerged as a major cause of increased morbidity and mortality among severely immunosuppressed patients with haematological malignancy. Micafungin, a new member of the echinocandin class, is a valuable addition to the antifungal armamentarium of the 21st century as it is active against Candida species, Aspergillus species, and other unusual mycoses that frequently affect these high risk patients. Available data on the safety and efficacy of micafungin as prophylaxis, preemptive/empirical treatment, or treatment of documented invasive fungal infection in patients with haematological malignancies are summarized in this review. [ABSTRACT FROM AUTHOR]

Early diagnosis of invasive mucormycosis is important for timely therapeutic intervention, improved survival, and reduced morbidity. Given the importance of an accurate and rapid diagnosis of invasive mucormycosis to guide the timely initiation of amphotericin B and possible surgical intervention, a coordinated multidisciplinary approach of clinical assessment, diagnostic imaging, and laboratory assessment is necessary. Laboratory assessment for mucormycosis includes the conventional methods of direct examination and culture of tissue, respiratory secretions, bronchoalveolar lavage fluid, and other fluids. However, because conventional diagnostic tools are limited in their sensitivity, advanced molecular amplification systems, antigen detection assays, proteomic profiles, and metabolite detection may complement existing approaches to improve the rate of early diagnosis of invasive mucormycosis. [ABSTRACT FROM AUTHOR]

Abstract: We present 2 cases of HIV-related cryptococcal meningitis, persisting after 3 and 9 months, respectively, of standard treatment. Both patients were treated successfully with a salvage regimen consisting of the combination of liposomal amphotericin B (3 mg/kg), intravenous voriconazole, and subcutaneous recombinant interferon γ-1b (200 μg thrice weekly). Voriconazole was administered at an increased dose (5 mg/kg, twice daily) to overcome interactions with co-administered ritonavir. In both patients, resolution of clinical signs and symptoms, as well as sterilization of cerebrospinal fluid cultures occurred after 10 weeks of salvage therapy. No major side effects were encountered. At the end of treatment, both patients were placed on maintenance therapy with oral fluconazole; no recurrence has been observed after 4 years of follow-up. [Copyright &y& Elsevier]

Simple Summary: The research aims to evaluate the diagnostic performance of low-dose chest CT (LDCCT) in detecting pulmonary infections in neutropenic patients with hematologic malignancies. Driven by concerns over radiation exposure in high-risk patients undergoing standard chest CT scans (SDCCT), the research investigates whether LDCCT, with reduced radiation and noise reduction algorithms, matches SDCCT in image quality and diagnostic accuracy. Involving 164 neutropenic patients with 256 CT exams, the study scrutinizes specific radiological criteria linked to pulmonary infections. The researchers analyzed objective parameters (such as image noise and attenuation levels), subjective evaluations (image quality, noise, and artifacts), and diagnostic performance. The findings reveal a 47% reduction in radiation dose with LDCCT but a lower diagnostic performance, especially in detecting consolidation and ground glass opacities. The authors caution against relying solely on LDCCT for initial assessments in patients with hematologic malignancies, emphasizing the importance of further research to optimize diagnostic protocols. The study aimed to assess the image quality and diagnostic performance of low-dose Chest Computed Tomography (LDCCT) in detecting pulmonary infections in patients with hematologic malignancies. A total of 164 neutropenic patients underwent 256 consecutive CT examinations, comparing 149 LDCCT and 107 Standard-Dose Chest CT (SDCCT) between May 2015 and June 2019. LDCCT demonstrated a 47% reduction in radiation dose while maintaining acceptable image noise and quality compared to SDCCT. However, LDCCT exhibited lower sensitivity in detecting consolidation (27.5%) and ground glass opacity (64.4%) compared to SDCCT (45.8% and 82.2%, respectively) with all the respective p-values from unadjusted and adjusted for sex, age, and BMI analyses being lower than 0.006 and the corresponding Odds Ratios of detection ranging from 0.30 to 0.34. Similar trends were observed for nodules ≥3 mm and ground glass halo in nodules but were not affected by sex, age and BMI. No significant differences were found for cavitation in nodules, diffuse interlobular septal thickening, pleural effusion, pericardial effusion, and lymphadenopathy. In conclusion, LDCCT achieved substantial dose reduction with satisfactory image quality but showed limitations in detecting specific radiologic findings associated with pulmonary infections in neutropenic patients compared to SDCCT. [ABSTRACT FROM AUTHOR]

Background. Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. Methods. We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases. Results. Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28-84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin. Conclusions. Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. Results: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07–0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01–0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. Conclusion: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death. [ABSTRACT FROM AUTHOR]

We estimated vaccine effectiveness (VE) of full (booster) vaccination against severe outcomes in hospitalized COVID-19 patients during the Delta and Omicron waves. The study extended from November 15, 2021 to April 17, 2022. Full vaccination was defined as a primary vaccination plus a booster ≥ 6 months later. We studied 1138 patients (mean age: 66.6 years), of whom 826 (72.6 %) had ≥ 1 comorbidity. Of the 1138 patients, 75 (6.6 %) were admitted to intensive care unit (ICU), 64 (5.6 %) received mechanical ventilation, and 172 (15.1 %) died. There were 386 (33.9 %) fully vaccinated, 172 (15.1 %) partially vaccinated, and 580 (51 %) unvaccinated patients. Unvaccinated patients were absent from work for longer periods compared to partially or fully vaccinated patients (mean absence of 20.1 days versus 12.3 and 17.3 days, respectively; p-value = 0.03). Compared to unvaccinated patients, fully vaccinated patients were less likely to be admitted to ICU [adjusted relative risk (ARR: 0.49; 95 % CI: 0.29–0.84)], mechanically ventilated (ARR: 0.43; 95 % CI: 0.23–0.80), and die (ARR: 0.57; 95 % CI: 0.42–0.78), while they were hospitalized for significantly shorter periods (ARR: 0.79; 95 % CI: 0.70–0.89). The adjusted full VE was 48.8 % (95 % CI: 42.7 %-54.9 %) against ICU admission, 55.4 % (95 % CI: 52.0 %-56.2 %) against mechanical ventilation, and 22.6 % (95 % CI: 7.4 %-34.8 %) against death. For patients with ≥ 3 comorbidities, VE was 56.2 % (95 % CI: 43.9 %-67.1 %) against ICU admission, 60.2 % (95 % CI: 53.7 %-65.4 %) against mechanical ventilation, and 43.9 % (95 % CI: 19.9 %-59.7 %) against death. Full (booster) COVID-19 vaccination conferred protection against severe outcomes, prolonged hospitalization, and prolonged work absenteeism. [ABSTRACT FROM AUTHOR]

Background: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether 18F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop 18F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis. Methods: A total of 22 rabbits were studied. In 20 animals, the right tibia was inoculated intraoperatively with S. aureus. Two control animals were inoculated with normal saline. A needle was placed in the tibia as a foreign body. Infection was allowed to develop for 21 days when 18F-FDG PET/CT was performed, the needle was removed, and bone specimens were cultured to confirm infection. Antimicrobial therapy with daptomycin was initiated in all successfully infected animals for 1, 3, or 6 weeks. Following completion of treatment, a second 18F-FDG PET/CT was performed, animals were euthanized, and infected tibias were harvested for quantitative cultures and histology. A positive scan was defined as 18F-FDG signal activity greater in the infected tibia than that of the contralateral non-infected control tibia. Therapeutic response was measured by the change of Background: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether 18F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop 18F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis. Methods: A total of 22 rabbits were studied. In 20 animals, the right tibia was inoculated intraoperatively with S. aureus. Two control animals were inoculated with normal saline. A needle was placed in the tibia as a foreign body. Infection was allowed to develop for 21 days when 18F-FDG PET/CT was performed, the needle was removed, and bone specimens were cultured to confirm infection. Antimicrobial therapy with daptomycin was initiated in all successfully infected animals for 1, 3, or 6 weeks. Following completion of treatment, a second 18F-FDG PET/CT was performed, animals were euthanized, and infected tibias were harvested for quantitative cultures and histology. A positive scan was defined as 18F-FDG signal activity greater in the infected tibia than that of the contralateral non-infected control tibia. Therapeutic response was measured by the change of Background: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether 18F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop 18F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis. Methods: A total of 22 rabbits were studied. In 20 animals, the right tibia was inoculated intraoperatively with S. aureus. Two control animals were inoculated with normal saline. A needle was placed in the tibia as a foreign body. Infection was allowed to develop for 21 days when 18F-FDG PET/CT was performed, the needle was removed, and bone specimens were cultured to confirm infection. Antimicrobial therapy with daptomycin was initiated in all successfully infected animals for 1, 3, or 6 weeks. Following completion of treatment, a second 18F-FDG PET/CT was performed, animals were euthanized, and infected tibias were harvested for quantitative cultures and histology. A positive scan was defined as 18F-FDG signal activity greater in the infected tibia than that of the contralateral non-infected control tibia. Therapeutic response was measured by the change of 18F-FDG signal activity in the infected tibia. Results: All successfully infected animals (n= 14), with microbiologically and/or histologically confirmed osteomyelitis, had positive 18F-FDG PET/CT scans, while the two control animals had negative scans despite the presence of the foreign body [mean maximum standardized uptake value (SUVmax) (±SD) values 2.96 (±0.80) vs. 1 (±1.10), respectively, P = 0.04]. In the 14 successfully infected animals, the mean SUVmax was significantly higher in the infected compared to the uninfected tibia (P< 0.0001). A SUVmax of 1.4, when used as a cutoff for infection, yielded a diagnostic accuracy of 93 %. At the end of treatment, successfully treated animals and saline controls had a negative 18F-FDG PET/CT scan (n =4), while animals with persistent infection despite treatment (n = 12) had a positive 18F-FDG PET/CT scan (SUVmax 1.0-3.0) (p < 0.001). SUVmax values were significantly reduced after 42 days of treatment from 3.15 ± 0.5 (day 7) to 1.71 ± 0.37 (day 42) (p = 0.05). Conclusions: 18F-FDG PET/CT scan is a sensitive and specific tool in therapeutic monitoring of experimental foreign-body osteomyelitis. F-FDG signal activity in the infected tibia. Results: All successfully infected animals (n= 14), with microbiologically and/or histologically confirmed osteomyelitis, had positive 18F-FDG PET/CT scans, while the two control animals had negative scans despite the presence of the foreign body [mean maximum standardized uptake value (SUVmax) (±SD) values 2.96 (±0.80) vs. 1 (±1.10), respectively, P = 0.04]. In the 14 successfully infected animals, the mean SUVmax was significantly higher in the infected compared to the uninfected tibia (P< 0.0001). A SUVmax of 1.4, when used as a cutoff for infection, yielded a diagnostic accuracy of 93 %. At the end of treatment, successfully treated animals and saline controls had a negative 18F-FDG PET/CT scan (n =4), while animals with persistent infection despite treatment (n = 12) had a positive 18F-FDG PET/CT scan (SUVmax 1.0-3.0) (p < 0.001). SUVmax values were significantly reduced after 42 days of treatment from 3.15 ± 0.5 (day 7) to 1.71 ± 0.37 (day 42) (p = 0.05). Conclusions: 18F-FDG PET/CT scan is a sensitive and specific tool in therapeutic monitoring of experimental foreign-body osteomyelitis. F-FDG signal activity in the infected tibia. Results: All successfully infected animals (n= 14), with microbiologically and/or histologically confirmed osteomyelitis, had positive 18F-FDG PET/CT scans, while the two control animals had negative scans despite the presence of the foreign body [mean maximum standardized uptake value (SUVmax) (±SD) values 2.96 (±0.80) vs. 1 (±1.10), respectively, P = 0.04]. In the 14 successfully infected animals, the mean SUVmax was significantly higher in the infected compared to the uninfected tibia (P< 0.0001). A SUVmax of 1.4, when used as a cutoff for infection, yielded a diagnostic accuracy of 93 %. At the end of treatment, successfully treated animals and saline controls had a negative 18F-FDG PET/CT scan (n =4), while animals with persistent infection despite treatment (n = 12) had a positive 18F-FDG PET/CT scan (SUVmax 1.0-3.0) (p < 0.001). SUVmax values were significantly reduced after 42 days of treatment from 3.15 ± 0.5 (day 7) to 1.71 ± 0.37 (day 42) (p = 0.05). Conclusions: 18F-FDG PET/CT scan is a sensitive and specific tool in therapeutic monitoring of experimental foreign-body osteomyelitis. [ABSTRACT FROM AUTHOR]

Background: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether 18F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop 18F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis. Methods: A total of 22 rabbits were studied. In 20 animals, the right tibia was inoculated intraoperatively with S. aureus. Two control animals were inoculated with normal saline. A needle was placed in the tibia as a foreign body. Infection was allowed to develop for 21 days when 18F-FDG PET/CT was performed, the needle was removed, and bone specimens were cultured to confirm infection. Antimicrobial therapy with daptomycin was initiated in all successfully infected animals for 1, 3, or 6 weeks. Following completion of treatment, a second 18F-FDG PET/CT was performed, animals were euthanized, and infected tibias were harvested for quantitative cultures and histology. A positive scan was defined as 18F-FDG signal activity greater in the infected tibia than that of the contralateral non-infected control tibia. Therapeutic response was measured by the change of 18F-FDG signal activity in the infected tibia. Results: All successfully infected animals (n = 14), with microbiologically and/or histologically confirmed osteomyelitis, had positive 18F-FDG PET/CT scans, while the two control animals had negative scans despite the presence of the foreign body [mean maximum standardized uptake value (SUVmax) (±SD) values 2.96 (±0.80) vs. 1 (±1.10), respectively, P = 0.04]. In the 14 successfully infected animals, the mean SUVmax was significantly higher in the infected compared to the uninfected tibia (P < 0.0001). A SUVmax of 1.4, when used as a cutoff for infection, yielded a diagnostic accuracy of 93 %. At the end of treatment, successfully treated animals and saline controls had a negative 18F-FDG PET/CT scan (n = 4), while animals with persistent infection despite treatment (n = 12) had a positive 18F-FDG PET/CT scan (SUVmax 1.0–3.0) (p < 0.001). SUVmax values were significantly reduced after 42 days of treatment from 3.15 ± 0.5 (day 7) to 1.71 ± 0.37 (day 42) (p = 0.05). Conclusions: 18F-FDG PET/CT scan is a sensitive and specific tool in therapeutic monitoring of experimental foreign-body osteomyelitis. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant. [ABSTRACT FROM AUTHOR]

• We assessed the impact of Pfizer-BioNTech vaccine on HCP morbidity and absenteeism. • We found 11.8 absenteeism episodes per 100 unvaccinated and 4.7 per 100 vaccinated HCP. • The mean duration of absence was 11.9 days in unvaccinated and 6.9 days in vaccinated HCP. • Vaccine effectiveness was 94.16% against COVID-19 and 66.42% against absenteeism. • Vaccination significantly reduced morbidity, COVID-19, absenteeism and duration of absenteeism. Healthcare personnel (HCP) are prioritized for coronavirus disease 2019 (COVID-19) vaccination to protect them and non-disruptive provision of healthcare services. We assessed the impact of the Pfizer-BioNTech vaccine on morbidity and absenteeism among HCP. We studied 7445 HCP in five tertiary-care hospitals in Greece from November 15, 2020 through April 18, 2021. A total of 910 episodes of absenteeism and 9695 days of absence were recorded during the entire study period. Starting from January 4, 2021, 4823/7445 HCP (64.8%) were fully or partially vaccinated. Overall, 535 episodes of absenteeism occurred from January 4, 2021 through April 18, 2021, including 309 (57.76%) episodes among 2622 unvaccinated HCP and 226 (42.24%) episodes among 4823 vaccinated HCP (11.8 versus 4.7 episodes of absenteeism per 100 HCP, respectively; p-value < 0.001). The mean duration of absenteeism was 11.9 days among unvaccinated HCP compared with 6.9 days among vaccinated HCP (p-value < 0.001). Unvaccinated HCP more frequently developed acute respiratory infection, influenza-like illness, and COVID-19 (p-values < 0.001 for all comparisons). Vaccine effectiveness for fully vaccinated HCP was estimated at 94.16% [confidence interval (CI): 88.50%-98.05%) against COVID-19, 83.62% (CI: 73.36%-90.38%) against SARS-CoV-2 infection (asymptomatic or COVID-19), and 66.42% (CI: 56.86%-74.15%) against absenteeism. The COVID-19 pandemic had a considerable impact on healthcare workforce. The Pfizer-BioNTech vaccine significantly reduced morbidity, COVID-19, absenteeism and duration of absenteeism among HCP during a period of high SARS-CoV-2 circulation in the community. It is expected that HCP vaccination will protect them and healthcare services and contain healthcare costs. [ABSTRACT FROM AUTHOR]

• Educational intervention combined with a non-compulsory antifungal stewardship (AFS) program had a significant impact on overuse and misuse of antifungal agents • The major errors in prescribing antifungals were suboptimal selection of antifungal agent, inappropriate dosage and duration of treatment • The AFS program resulted in a significant decrease in the consumption of AFs, mainly polyenes and echinocandins and in a significant reduction of the acquisition costs • Audits of the antifungals use are essential for selecting the targets for intervention Objectives: To assess the impact of an antifungal stewardship (AFS) program on appropriate use, consumption and acquisition costs of antifungals, and on clinical outcomes (in-hospital-mortality, in-hospital-length-of-stay). Methods: The study was conducted at a 535-bed tertiary-care hospital and had three consecutive periods. A) Observational period (10 months): all antifungal prescriptions were prospectively evaluated. B) Educational intervention to increase the awareness on proper antifungals use. C) Implementation of a non-compulsory AFS program (10 months) based on prospective audit and feedback. Interrupted time series analysis has been used to assess the impact of the intervention. Results: During the pre-interventional period 198 AF prescriptions for 147 patients, have been evaluated compared to 181 prescriptions in 138 patients during the AFS period. Statistical analysis showed a significant immediate drop of inappropriate prescriptions after intervention with a significantly declining trend thereafter, and a significant drop of the total consumption of antifungals immediately after the intervention with a significant declining trend thereafter. All-cause, in-hospital- mortality was stable during the pre-intervention period with a significant declining trend after the AFS program implementation, although no immediate intervention effect could be established. Comparison of pre-and post-interventional periods showed significant reduction in acquisition costs (-26.8%, p <0.001) but no difference regarding the total number of bed-days (107,654 vs. 102,382), and mean length of hospital-stay (5.19 vs. 4.96 days, p =NS). Conclusions: The implementation of a non-compulsory AFS program resulted in significant improvement in the quality of prescriptions and reduction in antifungals consumption and acquisitions costs, without affecting the overall in-hospital-mortality and mean in-hospital-length-of-stay. [ABSTRACT FROM AUTHOR]

Patients with autoimmune rheumatic diseases (ARDs) are at increased risk for pneumococcal infections and should be vaccinated against Streptococcus pneumoniae. Data on the rates of pneumococcal vaccination among patients with ARDs in Southern Europe are scarce. Here, we estimate the pneumococcal vaccination rate in patients living in Greece with ARDs, explore the patients' awareness regarding vaccination, and try to recognize factors that influence the vaccine uptake. Between October 2015 and September 2016, a structured questionnaire was provided to all consecutive patients with ARDs attending one outpatient clinic of our department. The survey included parameters concerning patients' demographics, underlying ARD and immunosuppressive medications, other comorbidities, vaccine type, knowledge about infection risk and necessity of vaccination. Univariate and multivariate analyses were performed to study any association of these factors with the vaccination uptake. Overall, 395 patients with ARDs (30.13% aged >65 years and 78.99% female) participated in our survey. The most frequent ARD was rheumatoid arthritis (43.04%); 40.51% of patients were receiving biologic agents and 44.56% steroids. Pneumococcal vaccination rate was 49.37%, while 45.06% of patients have been vaccinated during the last five years and only 8.21% of them had a second pneumococcal vaccine, as per national guidelines. The decision of vaccination was significantly influenced by the patient's age (>65 years) (p < 0.001) and the complete awareness of reasons for being vaccinated (p < 0.001), but not by presence of comorbidities, the type of ARD or administration of a biologic agent. The main reason for no vaccination was that it was not suggested by the caring physician (82.50%). In our cohort of patients with ARDs the pneumococcal vaccination was suboptimal. Better understanding of the significance of vaccination by the patient and suggestion for vaccination by the caring physician will improve vaccination uptake and optimize the clinical benefits among patients with ARDs. [ABSTRACT FROM AUTHOR]

Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes. [ABSTRACT FROM AUTHOR]

We assessed the value of conventional culture, vial culture, and broad-range PCR of the sonication fluid (SF), individually or in combinations, for the diagnosis of prosthetic joint infection (PJI). We studied 114 consecutive patients (median age:72.5 years, males: 28.07%) undergoing removal of a total knee or hip prosthesis. By non-microbiologic criteria, 87 patients had aseptic failure, and 27 PJI. All patients had periprosthetic tissue culture, sonication of prosthesis, and study of SF by conventional and vial culture, and PCR. Compared to tissue culture, each test was significantly more sensitive and less specific. If only one test was positive, the sensitivity was 88.46% and specificity 64.29%. If all three SF tests were positive, sensitivity, and NPV were decreasing (34.6% and 80.23%), but specificity and PPV were increasing up to 98.57% and 90.9%, respectively, outperforming tissue culture. A triple negative test practically excluded PJI. [ABSTRACT FROM AUTHOR]

Background: Our aim was to investigate the aortic distensibility (AD) of the ascending aorta and carotid artery intima-media thickness (c-IMT) in HIV-infected patients compared to healthy controls. Methods: One hundred and five HIV-infected patients (86 males [82%], mean age 41 ± 0.92 years), and 124 age and sex matched HIV-1 uninfected controls (104 males [84%], mean age 39.2 ± 1.03 years) were evaluated by high-resolution ultrasonography to determine AD and c-IMT. For all patients and controls clinical and laboratory factors associated with atherosclerosis were recorded. Results: HIV- infected patients had reduced AD compared to controls: 2.2 ± 0.01 vs. 2.62 ± 0.01 10-6 cm2 dyn-1, respectively (p < 0.001). No difference was found in c-IMT between the two groups. In multiadjusted analysis, HIV infection was independently associated with decreased distensibility (beta -0.45, p < 0.001). Analysis among HIV-infected patients showed that patients exposed to HAART had decreased AD compared to HAART-naïve patients [mean (SD): 2.18(0.02) vs. 2.28(0.03) 10-6 cm2 dyn-1, p = 0.01]. In multiadjusted analysis, increasing age and exposure to HAART were independently associated with decreased AD. Conclusion: HIV infection is independently associated with decreased distensibility of the ascending aorta, a marker of subclinical atherosclerosis. Increasing age and duration of exposure to HAART are factors further contributing to decreased AD. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment. Case presentation: We present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2nd line chemotherapy with gemcitabine. Conclusions: Polymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment. [ABSTRACT FROM AUTHOR]