Gender-specific differences in haemostatic parameters and their influence on blood loss in bimaxillary surgery.

OBJECTIVE: The objectives of this prospective cohort study were to establish gender-related differences in blood loss and haemostatic profiles associated with bimaxillary surgery. In addition, we aimed to identify if any gender differences could be established which might help predict blood loss volume. MATERIALS AND METHODS: Fifty-four patients (22 males; 32 females) undergoing bimaxillary surgery for skeletal dentofacial deformities were eligible for inclusion. Blood samples were taken 1 day preoperatively and 48 h postoperatively for detailed gender-specific coagulation analysis incorporating global coagulation assays (endogenous thrombin potential) and specific coagulation parameters. Blood loss was measured at two different time points: (1) the end of surgery, visible intraoperative blood loss (IOB) using 'subtraction method'; and (2) 48 h postoperatively perioperative bleeding volume (CBL-48 h) using 'haemoglobin-balance method' and Nadler's formula. Correlation and regression analyses were performed to identify relevant parameters affecting the amount of blood loss. RESULTS: Significant differences in IOB and CBL-48 h were observed (p < 0.001). Men had higher IOB versus women, lacking statistical significance (p = 0.056). In contrast, men had significantly higher CLB-48 h (p = 0.019). Reduced CBL-48 h was shown to be most closely associated with the level of Antithrombin-III being decreased in females. CONCLUSIONS: Male gender is associated with higher IOB and CBL-48 compared with females. Gender does not affect IOB regarding haemostatic profile but does correlate strongly with procedure length. Conversely, CBL-48 is closely associated with gender-specific imbalances in the anticoagulant system. CLINICAL RELEVANCE: Knowledge of gender-related differences will help clinicians establish predictive factors regarding excessive blood loss in orthognathic surgery and identify at-risk patients.

ENDOTHELIN-1 AS A RISK FACTOR IN RETINAL VEIN OCCLUSION.

PURPOSE: Retinal vein occlusion (RVO) risk factors largely coincide with cardiovascular risk factors. Endothelin-1 (ET-1), the most potent vasoconstrictor with proinflammatory properties, is a known cardiovascular risk factor. In this study, we explore the role of serum ET-1 as a potential risk factor for RVO. METHODS: Endothelin-1 serum levels were measured in patients with RVO and control subjects. Samples were measured using the sandwich enzyme-linked immunosorbent assay for the quantitative determination of human big endothelin-1 (Biomedica Group, Austria). RESULTS: The study consisted of 147 RVO patients and 150 control subjects. Median serum ET-1 was significantly higher in RVO patients (0.26 pmol/L; range, 0.19-0.37 pmol/L) compared with control subjects (0.10 pmol/L; range, 0.05-0.22 pmol/L) (P < 0.0001) independent of the occlusion site. The difference remained significant after adjusting for arterial hypertension, diabetes mellitus, history of stroke, history of myocardial infarction, history of venous thromboembolism, glomerular filtration rate, and c-reactive protein. CONCLUSION: In conclusion, our results suggest that ET-1 is a potential risk factor for all types of RVO.

Is there a hidden blood loss in orthognathic surgery and should it be considered? Results of a prospective cohort study.

The aim of this prospective observational study was to investigate the parameter 'hidden blood loss' (HBL) in the context of orthognathic surgery, incorporating undetected bleeding volumes occurring intra- and postoperatively. Orthognathic bleeding volumes were recorded at three different time points. At the end of the operation the visible intraoperative blood loss (VBL) was measured. Additionally, the perioperative blood loss was calculated 24 h and 48 h postoperatively using the 'haemoglobin balance method'. Analysis of the HBL was based on the difference between the visible intraoperative blood loss (VBL) and calculated blood loss (CBL), determined 48 h after surgery. 82 patients (male 33, female 49) were included in this study, of whom 41 underwent bimaxillary surgery and of whom 41 underwent Bilateral Sagittal Split Osteotomy (BSSO). Statistically significant differences with reference to the absolute bleeding volumes were found when comparing the two treatment modalities. In terms of HBL, a bleeding volume of 287.2 ml (±265.9) in the bimaxillary group and 346.9 ml (±271.3) in the BSSO cohort was recorded. This accounted for 32.2% (bimaxillary surgery) and 62.6% (BSSO) of the CBL after 48 h (BIMAX vs. BSSO, p < 0.001). HBL is a valuable adjunct to record within the perioperative management of orthognathic surgery to further improve patient safety and postoperative outcomes.

Longitudinal Evaluation of Plasma Cytokine Levels in Patients with Invasive Candidiasis.

Interleukin (IL) 17A plays a decisive role in anti-Candida host defense. Previous data demonstrated significantly increased IL-17A values in candidemic patients. We evaluated levels and time courses of IL-17A, and other cytokines suggested to be involved in Candida-specific immunity (IL-6, IL-8, IL-10, IL-17F, IL-22, IL-23, interferon-γ, tumor necrosis factor-α, Pentraxin-related protein 3, transforming growth factor-ß) in patients with invasive candidiasis (IC) compared to bacteremic patients (Staphylococcus aureus, Escherichia coli) and healthy controls (from previous 4 days up to day 14 relative to the index culture (-4; 14)). IL-17A levels were significantly elevated in all groups compared to healthy controls. In IC, the highest IL-17A values were measured around the date of index sampling (-1; 2), compared to significantly lower levels prior and after sampling the index culture. Candidemic patients showed significantly higher IL-17A values compared to IC other than candidemia at time interval (-1; 2) and (3; 7). No significant differences in IL-17A levels could be observed for IC compared to bacteremic patients. Candidemic patients had higher IL-8, IL-10, IL-22, IFN-γ, PTX3 and TNF-α values compared to non-candidemic. Based on the limited discriminating competence between candidemia and bacteremia, IL-17A has to be considered a biomarker for blood stream infection rather than invasive Candida infection.

The impact of folate and vitamin B12 status on cognitive function and brain atrophy in healthy elderly and demented Austrians, a retrospective cohort study.

BACKGROUND: Dementia, and in particular Alzheimer's disease (AD), is a debilitating progressive disease with high prevalence in our society. Vitamin B12 and folate deficiency are potential modifiable risk factors. However, previous studies reported inconsistent results. RESULTS: The average concentrations of all biochemical markers were within the respective reference ranges. Cross-sectional and longitudinal analyses did not reveal significant associations between biochemical markers and cognitive function, global or regional brain volume, cortical thickness or cortical surface area, neither in controls nor in AD patients. CONCLUSIONS: Variations of direct and indirect markers of B12 and folate status are not associated with cognitive dysfunction and brain atrophy. METHODS: This retrospective study explored the association between biochemical markers of B12 and folate status, cognitive function and MRI-based brain atrophy in cognitive normal elderly (controls) and AD patients. Folate, total and active vitamin B12 and MMA were measured in blood samples from 378 controls and 217 AD patients. Neuropsychiatric tests capturing memory, executive function and visuopractical skills were performed in all participants. Brain atrophy was assessed by MRI in 155 controls and 217 AD patients. In a subset of participants cognitive testing (n=234) and MRI (n=182) was repeated after an average median between 1.25 and 6.25 years.

Diagnosis of acute intoxications in critically ill patients: focus on biomarkers - part 2: markers for specific intoxications.

In medical intensive care units, acute intoxications contribute to a large proportion of all patients. Epidemiology and a basic overview on this topic were presented in part one. The purpose of this second part regarding toxicological biomarkers in the ICU setting focuses on specific poisons and toxins. Following the introduction of anion and osmol gap in part one, it's relevance in toxic alcohols and other biomarkers for these poisonings are presented within this publication. Furthermore, the role of markers in the blood, urine and cerebrospinal fluid for several intoxications is evaluated. Specific details are presented, amongst others, for cardiovascular drug poisoning, paracetamol (acetaminophen), ethanol, pesticides, ricin and yew tree intoxications. Detailed biomarkers and therapeutic decision tools are shown for carbon monoxide (CO) and cyanide (CN-) poisoning. Also, biomarkers in environmental toxicological situations such as mushroom poisoning and scorpion stings are presented.

T2Candida magnetic resonance in patients with invasive candidiasis: Strengths and limitations.

T2Candida enables detection of five Candida species in whole blood within approximately 5 hours. Routinely drawn EDTA blood samples were prospectively stored and tested with T2Candida in patients with invasive candidiasis identified by routine index blood or sterile site cultures. T2Candida was compared to diagnostic blood and sterile site cultures and also performed with samples obtained prior and after collection of index cultures. T2Candida was evaluated with 133 samples of 32 patients with candidemia and 22 patients with deep-seated invasive candidiasis. In the candidemic group 28/32 (87.5%) patients had at least one positive T2Candida result at any time point. A total of 17/25 (68%) candidemic patients had a positive T2Candida sample that was drawn concurrently to the index blood culture. In the per patient analysis 17/18 (94.4%) candidemic patients with matched T2Candida samples and peripheral blood cultures at any timepoint had a positive T2Candida test. T2Candida revealed discordant Candida species identification in two candidemic patients. Six of 22 (27.3%) deep-seated IC patients had a positive T2Candida result. Despite advanced time-to-results the clinical value of T2Candida in diagnosing candidemia seems to be limited by missing blood culture positive cases. Positivity rates of T2Candida increased when serial T2Candida samples were tested. In patients with suspected deep-seated invasive candidiasis T2Candida might act as a blood based adjunct to sterile site cultures.

Diagnosis of acute intoxications in critically ill patients: focus on biomarkers - part 1: epidemiology, methodology and general overview.

Acute intoxications account for a significant proportion of the patient population in intensive care units and sedative medications, ethanol, illicit drugs, inhalable poisons and mixed intoxications are the most common causes. The aim of this article is to describe biomarkers for screening and diagnosis of acute intoxications in critically ill patients. For this purpose, a survey of the relevant literature was conducted, and guidelines, case reports, expert assessments, and scientific publications were reviewed. In critical care, it should always be attempted to identify and quantify the poison or toxin with the assistance of enzyme immunoassay (EIA), chromatography, and mass spectrometry techniques and this section is critically appraised in this publication. The principles for anion gap, osmol gap and lactate gap and their usage in intoxications is shown. Basic rules in test methodology and pre-analytics are reviewed. Biomarkers in general are presented in part one and biomarkers for specific intoxications including ethanol, paracetamol, cardiovascular drugs and many others are presented in part two of these publications.

Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and ß-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.

The impact of bacteremia on lipoprotein concentrations and patient's outcome: a retrospective analysis.

Bacteremia is a major clinical challenge requiring early treatment. Metabolic alterations occur during bacteremia, and accordingly plasma concentrations of lipoproteins LDL-C and HDL-C are substantially changed. We questioned whether bacteremia with Gram-negative versus Gram-positive bacteria causes contrasting changes of lipoprotein levels in order to differentiate between the 2-g stain types and if there is a relation with outcome parameters namely ICU-admission, 30-day mortality, duration of hospitalization. This is a retrospective dual-center cross-sectional study, including 258 patients with bacteremia. Plasma lipid levels were analyzed within 48 h to positive blood culture. Upon admission, HDL-C, LDL-C, and total cholesterol (p = 0.99) in plasma did not significantly differ between patients with Gram-negative and Gram-positive bacteremia, while significantly higher triglyceride concentrations were found in Gram-negative bacteremia (p < 0.05). 30-day mortality and ICU admission were associated with lower LDL-C and HDL-C concentrations as compared to survivors and non-ICU patients, and patients with HDL-C < 20 mg dl-1 and LDL-C < 55 mg dl-1 had a relative risk (RR) of 2.85 for ICU therapy requirement and RR = 2 of death within 30 days. Reduced HDL-C and LDL-C concentrations were associated with adverse patient's outcome in bacteremia. Discrimination between Gram-negative and Gram-positive pathogens upon lipoprotein patterns is unlikely.

Extracts of different pollen species and their effect on human tear fluid and an epithelial cell line.

PURPOSE: Hazelnut and birch pollen are known to destroy tear film components and attack ocular surface cells. We investigated further pollen species from different plant families, whether they show similar effects on human tear fluid and an epithelial cell line in vitro, to provide a broad basis for further research on pollen reactions affecting the tear film and ocular surface. MATERIALS AND METHODS: Regional pollen species from different plant families (Adoxaceae, Betulaceae, Fagaceae, Juglandaceae, Malvaceae, Oleaceae, Pinaceae, Plantaginaceae, Poaceae, Salicaceae, Sapindaceae) were collected. Their proteolytic activity was evaluated by Zymography. Human tear fluid and cells of an epithelial cell line were incubated with pollen extracts. Tear fluid was analyzed by Polyacrylamide gel electrophoresis (PAGE). Cytomorphology was assessed microscopically and cell viability by proliferation (MTS), water-soluble tetrazolium (WST-1) assay and the impedance-based xCELLigence real-time analysis (RTCA). RESULTS: Zymography revealed significant protease activity and PAGE showed the degradation of tear proteins by different pollen species. Cells incubated with pollen extracts presented dose- and time-dependent cytomorphological changes. MTS, WST-1, and RTCA revealed cytostatic as well as cytotoxic effects of pollen extracts. CONCLUSIONS: Pollen species from different plant families exert proteolytic activity and degrade human tear fluid as well as epithelial cells, which may play a crucial role in the pathogenesis of allergic and non-allergic reactions affecting the ocular surface.

The influence of electromagnetic radiation on the measurement behaviour of the triggerfish® contact lens sensor.

BACKGROUND: To assess a possible signal drift, noise and influences of electromagnetic radiation on the measurement behaviour of the Triggerfish® contact lens sensor, which might be mistaken as IOP fluctuations. METHODS: Contact lens sensors (Triggerfish®, SENSIMED AG, Lausanne, Switzerland) were fixed in a water bath. To reduce any external electromagnetic impulses, all plugs were removed from the sockets, no lights were switched on and no electronic devices, except a temperature logger were left in the test room. For 24 h signal drift, noise and the influences of a cordless telephone (Ascom d43 DECT Handset, EU DECT 1880-1900 MHz, Ascom Wireless, Baar, Switzerland), a smartphone (Sony Xperia Go ST27i, Sony Corporation, Tokyo, Japan) and a computer (Hewlett-Packard ProBook 650 15,6″ - D9S33AV, Hewlett-Packard Inc., Palo Alto, USA) on the measuring profile were analysed. RESULTS: Twenty-four-hour measurements without provoked external electromagnetic impulses yielded a profile without any signal drift and 8.2 mV eq noise. During the activation of the cordless telephone a maximum measurement variation of 3.2 mV eq. (4.1-7.3), smartphone 1.8 mV eq. (4.7-6.5) and computer 1.4 mV eq. (6.3-7.7) were observed. CONCLUSIONS: During 24-h measurements there was no signal drift and a very low noise. Patients concerned about electronic devices possibly interfering with the measurements of the contact lens sensor, can be informed, that the use of their cordless telephone, smartphone or computer does not cause any problems. The amount of the signal noise might help to define actual IOP fluctuations. Temperature fluctuations might influence the measuring profile.

Diagnosis of invasive aspergillosis in hematological malignancy patients: Performance of cytokines, Asp LFD, and Aspergillus PCR in same day blood and bronchoalveolar lavage samples.

BACKGROUND: Aspergillus spp. induce elevated levels of several cytokines. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/tests for invasive aspergillosis (IA). METHODS: This cohort study included 106 prospectively enrolled (2014-2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both, serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, ß-D-glucan, and cytokines that have shown significant associations with IA before. RESULTS: Among 106 cases, 11 had probable IA, and 32 possible IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed better performance in BALF versus blood, with the exception of serum interleukin (IL)-8 which was the most reliable blood biomarker. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) showed promise for differentiating probable IA from no IA. CONCLUSIONS: High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA.

Decreased viability and proliferation of CHANG conjunctival epithelial cells after contact with ultraviolet light-irradiated pollen.

CONTEXT: Contact with pollen is the major reason for the development of allergic symptoms on the ocular surface leading to a significant increase of allergic diseases worldwide. Environmental changes such as increased ultraviolet (UV) radiation and air pollution are discussed as contributory causes for this increase. OBJECTIVE: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells. MATERIALS AND METHODS: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system. RESULTS: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen. DISCUSSION AND CONCLUSIONS: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells.

Levels of interleukin (IL)-6 and IL-8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis.

Aspergillus spp. have been shown to induce T-helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case-control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014-2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at -70°C for retrospective determination of cytokines. IL-6 and IL-8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL-10 (P = .059). In multivariate conditional logistic regression analysis, IL-10 remained a significant predictor of IPA in serum and IL-8 among BALF cytokines. In conclusion, levels of IL-6 and IL-8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL-10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.

Galactomannan testing and Aspergillus PCR in same-day bronchoalveolar lavage and blood samples for diagnosis of invasive aspergillosis.

In recent years galactomannan antigen testing (GM) and also Aspergillus PCR have become increasingly important for diagnosis of invasive aspergillosis (IA). Whether or not these tests need to be performed with bronchoalveolar lavage fluid (BALF; i.e., primary site of infection), or testing of blood samples is sufficient, remains, however, a matter of debate. We evaluated the diagnostic performance of GM ELISA, and Aspergillus PCR by using BALF samples and blood samples obtained at the same day from a total of 53 immunocompromised patients (16 with probable/proven IA and 37 with no evidence of IA according to the revised EORTC/MSG criteria; 38 patients with hematological malignancies were prospectively enrolled at the Medical University of Graz, Austria, 15 patients with mixed underlying diseases at the Mannheim University Hospital). Patients with possible IA were excluded from this analysis. A total of 34/53 (64%) of all patients and 12/16 (75%) of patients with probable/proven IA received mold-active antifungal prophylaxis/therapy at the time of the BALF procedure. Sensitivities of GM and Aspergillus PCR were 38% and 44% in BALF, and 31% and 0% in blood, respectively. Best sensitivity (75%) for detecting proven/probable IA was achieved when BALF Aspergillus PCR, BALF GM (>1.0 ODI), BALF-culture and serum-GM (>0.5 ODI) were combined (specificity 95%). In conclusion, sensitivities of the evaluated diagnostic tests-when interpreted on their own-were low in BALF and even lower in blood, sensitivities increased markedly when diagnostic tests were combined.

Road and rail traffic noise induce comparable extra-aural effects as revealed during a short-term memory test.

To examine extraaural effects as induced by 20 min of road (ROAD) and 20 min of rail (RAIL) traffic noise with same loudness (75 dBA), a laboratory study was carried out. The study (N = 54) consisted of 28 high and 26 low-annoyed healthy individuals as determined by a traffic annoyance test. To control attention, all individuals performed a nonauditory short-term memory test during the noise exposures. A within-subject design, with phases of ROAD, RAIL, and CALM (memory test only), alternated by phases of rest, was defined. Heart rate (HR), systolic blood pressure (sBP), total peripheral resistance (TPR), as well as three autonomic variables, preejection period (PEP), 0.15-0.4 Hz high-frequency component of HR variability (HF), and salivary stress biomarker alpha amylase (sAA) were measured. In relation to CALM, HR increased (RAIL +2.1%, ROAD +2.5%), sBP tended to increase against the end of noise exposure, PEP decreased (RAIL -0.7%, ROAD -0.8%), HF decreased (RAIL -3.4%, ROAD -2.9%), and sAA increased (RAIL +78%, ROAD +69%). No differences were found between RAIL and ROAD, indicating that both noise stressors induced comparable extraaural effects. Factor annoyance showed significant during CALM. Here a reduced sympathetic drive (higher PEP values) combined with an increased vascular tone (higher TPR values) was found at the high-annoyed subgroup.

Characterisation of Candida within the Mycobiome/Microbiome of the Lower Respiratory Tract of ICU Patients.

Whether the presence of Candida spp. in lower respiratory tract (LRT) secretions is a marker of underlying disease, intensive care unit (ICU) treatment and antibiotic therapy or contributes to poor clinical outcome is unclear. We investigated healthy controls, patients with proposed risk factors for Candida growth in LRT (antibiotic therapy, ICU treatment with and without antibiotic therapy), ICU patients with pneumonia and antibiotic therapy and candidemic patients (for comparison of truly invasive and colonizing Candida spp.). Fungal patterns were determined by conventional culture based microbiology combined with molecular approaches (next generation sequencing, multilocus sequence typing) for description of fungal and concommitant bacterial microbiota in LRT, and host and fungal biomarkes were investigated. Admission to and treatment on ICUs shifted LRT fungal microbiota to Candida spp. dominated fungal profiles but antibiotic therapy did not. Compared to controls, Candida was part of fungal microbiota in LRT of ICU patients without pneumonia with and without antibiotic therapy (63% and 50% of total fungal genera) and of ICU patients with pneumonia with antibiotic therapy (73%) (p<0.05). No case of invasive candidiasis originating from Candida in the LRT was detected. There was no common bacterial microbiota profile associated or dissociated with Candida spp. in LRT. Colonizing and invasive Candida strains (from candidemic patients) did not match to certain clades withdrawing the presence of a particular pathogenic and invasive clade. The presence of Candida spp. in the LRT rather reflected rapidly occurring LRT dysbiosis driven by ICU related factors than was associated with invasive candidiasis.