Mapping the path to excellence: Evaluation of the diagnostic and treatment tools for invasive fungal infections in the balkans.

BACKGROUND: In the Balkans, rising concerns about invasive fungal infections over the past decade stem from various factors. Primarily, there has been a notable uptick in immunocompromised individuals, including those with chronic illnesses like immunological and hematological diseases. Thus, it is essential to assess the region's laboratory capabilities and the availability of antifungals. This evaluation is vital for gauging the preparedness to diagnose and treat fungal infections effectively, thus minimizing their public health impact. METHODS: Data were collected via an online questionnaire targeting healthcare professionals specializing in relevant fields across diverse healthcare settings in Balkan countries. The survey covered various aspects, including diagnostic methods, imaging techniques, and available antifungal armamentarium. RESULTS: Responses were obtained from 50 institutions across the Balkans. While conventional diagnostic methods like microscopy (96 %) and culture (100 %) diagnostics were widely available, access to newer diagnostic tools such as molecular assays (61 %) were limited, often relying on outsourced services. Imaging modalities like ultrasound (100 %) and CT scans (93 %) were universally accessible. A variety of antifungal drugs were available, including amphotericin B formulations (80 %), echinocandins (79 %), and triazoles (100 %). However, access to newer agents like posaconazole (62 %) and isavuconazole (45 %) was inconsistent. Therapeutic drug monitoring (53 %) services were also limited. CONCLUSION: The study underscores the need for equitable access to diagnostic facilities and antifungal treatments across healthcare settings in the Balkan geographic region. Improving access to molecular diagnostic tools and essential antifungal drugs, as well as implementing therapeutic drug monitoring, would optimize the management of fungal infections in the region.

Disseminated cerebral cryptococcosis after silent West Nile virus infection in a patient with polycythemia vera: A case report and review of the literature.

Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with polycythemia vera. Following in 2018, he experienced an unknown-cause fever and headache. To establish the source of the symptoms, a magnetic resonance imaging scan of the brain was performed, which indicated meningeal and gyral-leptomeningeal thickening and several localized T2 hyperintense lesions measuring up to 10 × 14 mm in diameter. Cryptococcus neoformans was then cultivated from cerebrospinal fluid. Serum IgM antibodies against West Nile Virus were positive. After 8 weeks of treatment with amphotericin B and fluconazole, the overall condition improved, and the cerebrospinal fluid control culture became negative. The symptoms returned shortly after discontinuing antifungal therapy, necessitating the reintroduction of fluconazole. Currently, the patient is stable and responding positively to ruxolitinib. Here, it is demonstrated how a patient with polycythemia vera due to immunological weakness might develop disseminated cryptococcosis of the brain after West Nile virus infection.

Human infections by Hymenolepis diminuta in Europe: a case report and literature review.

We performed a review of published and gray literature of human Hymenolepis diminuta cases across Europe up to July 2022. Of all detectable publications and records, we further analyzed only those that contained demographic, clinical or epidemiological data regarding the infected subjects. Additionally, one case of hymenolepiasis in a 16-mo-old boy living in the urban part of Belgrade was included in the analysis. Published studies were based in 13/50 European countries and identified 104 laboratory-confirmed cases in total. Almost one-half (49%) of all cases originated from Mediterranean countries. Among symptomatic children, the infection most often manifested with diarrhea, abdominal pain, allergic reaction and behavioral changes. The diagnosis was made by the detection and identification of H. diminuta eggs or parts of strobila in stool samples, although cases of misdiagnosis were also reported. The parasite clearance was established with praziquantel or niclosamide, while the administration of albendazole or mebendazole led to unfavorable results. Future multicentric prospective studies focused on infection screening and the gathering of detailed sociodemographic and clinical data could provide an updated insight into the true distribution and characteristics of H. diminuta infection across Europe.

Molnupiravir's real-world effectiveness in COVID-19 outpatients at high risk of severe disease: a single-center study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic started in March 2020. Since then, there has been an urgent need for effective therapeutic methods to manage the disease. We aimed to assess the effectiveness of molnupiravir in reducing the need for hospitalization in at-risk, non-hospitalized COVID-19 patients. METHODOLOGY: This was a single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19, treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. RESULTS: The study was conducted between 15 December 2021 and 15 February 2022 and included 320 patients. Of these, 165 (51.6%) received treatment with molnupiravir. The study and control groups were similar in gender and age distribution. The study group had a higher proportion of vaccination (75.2% vs. 51%, p < 0.001). There was no statistically significant difference in presence of comorbidity within the groups. Majority of the patients who received molnupiravir did not require hospitalization; and this was statistically significant in comparison to control group (92.7 vs. 24.5%, p < 0.001). Oxygen supplementation was less frequently required in the study group compared to the control group (0.6% vs. 31%, p < 0.001). During the follow-up period of 12.12 ± 3.5 days, significantly less patients from the study group were admitted to the intensive care unit (p < 0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021; 95% CI 0.005-0.089; p < 0.001). CONCLUSIONS: Molnupiravir is an effective therapy in preventing the development of severe forms of COVID-19 and hospitalization.

Rethinking Aspergillosis in the Era of Microbiota and Mycobiota.

Aspergillosis encompasses a wide range of clinical conditions based on the interaction between Aspergillus and the host. It ranges from colonization to invasive aspergillosis. The human lung provides an entry door for Aspergillus. Aspergillus has virulence characteristics such as conidia, rapid growth at body temperature, and the production of specific proteins, carbohydrates, and secondary metabolites that allow A. fumigatus to infiltrate the lung's alveoli and cause invasive aspergillosis. Alveolar epithelial cells play an important role in both fungus clearance and immune cell recruitment via cytokine release. Although the innate immune system quickly clears conidia in immunocompetent hosts, A. fumigatus has evolved multiple virulence factors in order to escape immune response such as ROS detoxifying enzymes, the rodlet layer, DHN-melanin and toxins. Bacterial co-infections or interactions can alter the immune response, impact Aspergillus growth and virulence, enhance biofilm formation, confound diagnosis, and reduce treatment efficacy. The gut microbiome's makeup influences pulmonary immune responses generated by A. fumigatus infection and vice versa. The real-time PCR for Aspergillus DNA detection might be a particularly useful tool to diagnose pulmonary aspergillosis. Metagenomics analyses allow quick and easy detection and identification of a great variety of fungi in different clinical samples, although optimization is still required particularly for the use of NGS techniques. This review will analyze the current state of aspergillosis in light of recent discoveries in the microbiota and mycobiota.

Global prevalence, mortality, and main characteristics of HIV-associated pneumocystosis: A systematic review and meta-analysis.

The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.

Seroprevalence and risk factors of Toxoplasma gondii infection among pregnant women.

INTRODUCTION: Toxoplasma gondii is an obligate intracellular parasite affecting a broad range of warm-blooded animals, including humans. Infection acquired during pregnancy can be transmitted to the fetus and leading to serious problems such as spontaneous abortion, stillbirth, or severe mental and/or physical handicaps in the child. The purpose of this study was to investigate the seroprevalence of Toxoplasma infection and related risk factors in pregnant woman. METHODOLOGY: The study enrolled 1200 serum samples of pregnant women from February-November 2017. Then the samples were tested for the presence of anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. RESULTS: Out of the 1200 samples, 381 (31.7%) and 41 (3.4%) subjects were positive for IgG and IgM Ab, respectively. Among the evaluated risk factors, the seroprevalence of Toxoplasma infection was not related to the occupation in a significant way. However significant relationship was observed with factors such as; contact with soil, cats, consumption of raw washed vegetables, and washed hands before meals. CONCLUSIONS: According to the results, more than two-thirds of pregnant women are susceptible to Toxoplasma infection, hence training health care programs should be provided to prevent infection.

Chronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease.

Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.

Multifactorial action of lavender and lavandin oils against filamentous fungi.

AIMS: In this study, five essential oils (EOs) from different species of Lavandula hybrida abrialis, for Lavandula hybrida R.C., Lavandula hybrida 'super A', Lavandula hybrida 'super Z' and Lavandula vera and its hybrids Lavender were evaluated against 26 dust-isolated fungal strains from North Africa. METHODS AND RESULTS: The composition of the different EOs was determined from volume to dry weight. The photochemical analyses were performed via gas chromatography (GC). The cytotoxic effect of five lavender EOs on human epithelial colorectal adenocarcinoma cells (Caco-2) cell line was done. A total of 26 strains of filamentous fungi including Aspergillus spp., Botrytis cinerea, Ceriporia spp., Fusarium spp. and Penicillium glabrum were isolated from sand dust samples via molecular diagnostic tool of PCR. Fungal strains with the lowest minimal lethal concentration (MLC) were Penicillium glabrum, Ceriporia spp. and a strain of Aspergillus spp. CONCLUSIONS: More studies are needed to verify the activity of this EO against more different fungal species, and determine the active ingredients.Significance and impact of study: MIC of the antifungal efficacy relating to EOs was evaluated. The EOs tests showed no cytotoxic effect at very low concentrations, ranging from 0.03% (IC50 0.9132 mg/mL) (L. hybrid Abrialis) to 0.001% (IC50 1.631 mg/mL) (L. hybrid R.C.).

Prevalence of Cryptosporidium and microsporidial infection in HIV-infected individuals.

BACKGROUND: Microsporidia and Cryptosporidium are obligate intracellular protozoa. These medically important species are recognized as opportunistic organisms in intestinal complications in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. METHODS: The current cross-sectional study was designed and conducted from August 2016 to August 2017 to determine intestinal Cryptosporidium and microsporidia spp. in HIV-infected individuals from the Behavioral Diseases Counseling Center, Tabriz, Iran, by modified acid-fast and modified trichrome staining and nested polymerase chain reaction (PCR) and real-time PCR. RESULTS: Of 100 HIV-infected persons, 21.0% (95% confidence interval [CI] 13.0 to 30.0) and 18.0% (95% CI 11.0 to 26.0) were identified as Cryptosporidium and microsporidia, respectively, by the microscopic method. Of these 100 HIV-infected persons, 18.0% (95% CI 11.0 to 26.0) and 14.0% (95% CI 7.0 to 22.0) were positive for Cryptosporidium and microsporidia, respectively, by the molecular method. The predominant species of microsporidia in patients was Enterocytozoon bieneusi (85.7% [95% CI 57.0 to 98.0]) and Encephalitozoon cuniculi (14.3% [95% CI 1.7 to 42.0]), which were found by quantitative real-time PCR and its high-resolution melting tool. CONCLUSIONS: As far as we know, this study is the first to estimate the prevalence of infection with Cryptosporidium and microsporidia among HIV-infected persons in northwest of Iran. The prevalence of intestinal microsporidiosis and cryptosporidiosis in this area in HIV-infected people was higher than the global prevalence of infection among immunocompromised patients. In addition to the need for further studies to prove protozoan pathogenicity in the aforementioned group, preventive measures should be considered.

Seasonal Variation in Fungi in Beach Sand in Summertime: Stintino (Italy).

BACKGROUND: The goal of this study was to monitor the microbial biodiversity in beach sand that is heavily visited by tourists during the summer, and to determinate whether the high presence of bathers (around 5000 per day) can modify sand microbial composition. METHODS: Between 2016 and 2020, 150 sand samples were collected from nine different points at La Pelosa beach in Sardinia, Italy. Non-culturing methods were used; DNA extraction and meta-barcode sequencing were performed. All samples were analyzed with sequencing methods for 16S and ITS sequences. RESULTS: Fungal genera differ on the three beaches and in the winter/summer zones. The ITS sequence showed the most common presence of Candida during summer and Paradendryphiella in the winter. The greatest diversity was found in the dune during winter, while in other parts of the beach, there are differences between bacteria and fungi, particularly in the wash zone during the winter, with high diversity for 16S sequences but low diversity for ITS sequences. CONCLUSIONS: It appears reasonable that the sands, even on non-urban beaches, should be included in health monitoring programs in addition to the waters, and that access to them should be regulated by limiting the number of bathers with the aim of reducing the presence of pathogenic fungal species.

Myositis-specific autoantibodies in a non-traveler, patient from a non-endemic country, with Plasmodium vivax malaria.

INTRODUCTION: Autoantibodies (AAb) are a hallmark of immune-mediated inflammatory diseases. Malaria is a parasitic disease caused by Plasmodium protozoa. Individuals with malaria may present with a wide range of symptoms. It is frequently linked to the development of different AAb. CASE DESCRIPTION: A 35-year-old male presented with repeated episodes of fever, malaise, myalgia, dark urine, and yellowish sclera. Initial diagnostic workup revealed severe Coombs-positive anemia, increased C-reactive protein, and procalcitonin, pathological liver tests, high concentration of serum IgE, IgG, IgM, IgA, positive antinuclear antibodies (ANA), and positive antineutrophil cytoplasmatic antibodies (ANCA). In addition, myositis-specific antibodies directed to polymiositis-scleroderma 75 protein (PmScl75), threonyl-tRNA synthetase (PL-7), alanyl-tRNA synthetase (PL-12), Mi-2 antigen (Mi-2), Ku DNA helicase complex (Ku), signal recognition particle (SRP), and antiaminoacyl tRNA synthetase (EJ) were detected. The patient was suspected of having systemic lupus erythematosus and sent to the Clinic of Allergy and Immunology for further evaluation and treatment. A peripheral blood film examined by the hematologist during an episode of fever revealed intra-erythrocytic parasitic forms of Plasmodium vivax (P. vivax). After being diagnosed with P. vivax malaria, he was transferred to the Clinic for Infective and Tropical Diseases. The therapy consisted of artesunate/mefloquine and prednisone led to a complete clinical recovery and autoantibodies gradually disappeared. CONCLUSIONS: Malaria would not normally be considered during the initial diagnostic workup in a non-traveler and a patient from a non-endemic country. However, a thorough parasitic evaluation in patients presenting with a broad range of autoantibodies might be of particular importance.

Diagnosis of Chronic Pulmonary Aspergillosis: Clinical, Radiological or Laboratory?

Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40-50%. The disease is characterized by slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient's condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA.

Systematic review and meta-analysis of the global prevalence of sexually transmitted infections in people living with HIV and associated risk factors.

People living with HIV (PLWH) constitute a vulnerable population for acquiring additional sexually transmitted infections (STIs). This study was conducted to provide a summary of the evidence on the global prevalence of STIs in PLWH with an emphasis on infectious agents, diagnostic methods, and related risk factors. PubMed, Scopus, and Web of Science were systematically searched to include records published from January 01, 1990, to January 31, 2022, and the Google Scholar search engine was used to check the search strategy. In total, 132 eligible studies reporting STIs in PLWH were included, enrolling subjects from 35 countries across five continents. The pooled proportion of STIs was estimated to be 30.23% (95% CI, 26.1-34.45%) in PLWH and 20.01% (95% CI, 17.17-23.01%) in HIV-negative patients. Our meta-analysis indicated that in PLWH, the pooled OR of STIs compared to HIV-negatives was 1.77 (95% CI: 1.58-1.98) (p < 0.0001). The pooled OR of STIs by viral infectious agents was highest in PLWH (52.19% [95% CI: 43.88-60.43]) compared with fungal (22.19% [95% CI: 15.64-29.53]), bacterial (19.07% [95% CI: 13.59-26.63]), and parasitic (14.05% [95% CI: 11.88-16.38]) infections. Our findings show that there is a rather significant frequency of STIs among PLWH. This study highlights the need for new programs for the detection, treatment, and prevention of STIs in this at-risk population.

Induction of TLR5, IRAK1, and NF-κB expression by Trichomonas vaginalis in cervical cancer cell (HeLa) and normal human vaginal epithelial cell (HVECs) lines.

INTRODUCTION: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. METHODOLOGY: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using ß-actin as a housekeeping control. RESULTS: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). CONCLUSIONS: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways.

Predictors for Prolonged Hospital Stay Solely to Complete Intravenous Antifungal Treatment in Patients with Candidemia: Results from the ECMM Candida III Multinational European Observational Cohort Study.

BACKGROUND: To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). METHODS: Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. FINDINGS: Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 - 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 - 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 - 0.45; p < 0.03). INTERPRETATION: Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis.

European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study.

The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.

Assessment of chronic rhinosinusitis severity indicators: radiological and clinical perspective.

INTRODUCTION: Chronic rhinosinusitis (CRS) is inflammation of the nasal cavity and paranasal sinus mucosa. The aim of this study was to examine which of the available radiological and clinical parameters is the best indicator of the CRS severity. METHODOLOGY: In order to classify CRS, we used both a subjective assessment tool such as SNOT-22 questionnaire, as well as an objective tool such as clinical examination. We introduced three forms of CRS (mild, moderate and severe). Within these groups, we evaluated the computerized tomography (CT) parameters used as an indicator of bone remodeling, the Lund-Mackay score (LMS), CT properties of the soft tissue content in the maxillary sinuses, presence of nasal polypus (NP), presence of fungal infection and parameters indicating allergic status. RESULTS: Frequencies of NP, positive eosinophil count, presence of fungi, areas of high attenuation, and duration of CRS and LMS significantly increased with the increased severity of CRS. Anterior wall thickness and density increased in the severe forms of CRS in the group assessed by SNOT-22. Positive correlation was detected between LMS and maximal density of sinus content and between duration of CRS and anterior wall thickness. CONCLUSIONS: Morphological changes of sinus wall detected in CT could be a useful indicator of CRS severity. Changes in bone morphology are more likely to occur in patients with longer-lasting CRS. The presence of fungi, allergic inflammation of any origin and nasal polypus potentiates more severe forms of CRS both clinically and subjectively.

Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study.

BACKGROUND: The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. METHODS: In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. FINDINGS: 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04-1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05-1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals. INTERPRETATION: Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay. FUNDING: Scynexis.

Corrigendum to "Pneumocystis pneumonia in COVID-19 patients: A comprehensive review" [Heliyon 9(2) (February 2023) e13618].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13618.].