Safety and efficacy of G-CSF after allogeneic hematopoietic cell transplantation using post-transplant cyclophosphamide: clinical and in vitro examination of endothelial activation.

Since 2021 the use of G-CSF was implemented in allo-HCT with PTCY-based prophylaxis with the aim of shortening the aplastic phase and reducing infectious complications. This study investigates the effectiveness of this change in protocol performed at our institution. One-hundred forty-six adults undergoing allo-HCT with PTCY-based prophylaxis were included, and among them, 58 (40%) received G-CSF. The median of days to neutrophil engraftment was shorter in the G-CSF group (15 vs. 20 days, p < 0.001). Patients receiving G-CSF had a lower incidence of day +30 bacterial bloodstream infections (BSI) than the rest (20.7% vs. 47.7%, p < 0.001). GVHD, SOS, and TA-TMA incidences were comparable between groups, and using G-CSF did not impact on survival. Endothelial activation was investigated using EASIX and by the measurement of soluble biomarkers in cryopreserved plasma samples obtained on days 0, +7, +14 and +21 of 39 consecutive patients (10 received G-CSF) included in the study. EASIX, VWF:Ag, sVCAM-1, sTNFRI, ST2, REG3α, TM and NETs medians values were comparable in patients receiving G-CSF and those who did not. Compared with allo-HCT performed without G-CSF, the addition of G-CSF to PTCY-based allo-HCT accelerated neutrophil engraftment contributing on decreasing BSI incidence, and without inducing additional endothelial activation.

A voice and speech corpus of patients who underwent upper airway surgery in pre- and post-operative states.

Many research articles have explored the impact of surgical interventions on voice and speech evaluations, but advances are limited by the lack of publicly accessible datasets. To address this, a comprehensive corpus of 107 Spanish Castilian speakers was recorded, including control speakers and patients who underwent upper airway surgeries such as Tonsillectomy, Functional Endoscopic Sinus Surgery, and Septoplasty. The dataset contains 3,800 audio files, averaging 35.51 ± 5.91 recordings per patient. This resource enables systematic investigation of the effects of upper respiratory tract surgery on voice and speech. Previous studies using this corpus have shown no relevant changes in key acoustic parameters for sustained vowel phonation, consistent with initial hypotheses. However, the analysis of speech recordings, particularly nasalised segments, remains open for further research. Additionally, this dataset facilitates the study of the impact of upper airway surgery on speaker recognition and identification methods, and testing of anti-spoofing methodologies for improved robustness.

Exploring the Effects of Freeze-Dried Sourdoughs with Lactiplantibacillus pentosus 129 and Limosilactobacillus fermentum 139 on the Quality of Long-Fermentation Bread.

Sourdough production is a complex fermentation process. Natural sourdough fermentation without standardization causes great variability in microbial communities and derived products. Starter cultures have emerged as alternatives to natural fermentation processes, which could improve bakery quality and produce bioactive compounds. This study aimed to evaluate the impacts of freeze-drying on the production and viability of sourdoughs with Lactiplantibacillus pentosus 129 (Lp) and Limosilactobacillus fermentum 139 (Lf), as well as their effects on the quality of long-fermentation bread. These strains were selected based on their better performance considering acidification and exopolysaccharide production capacity. Sourdough with Lp and Lf were propagated until the 10th day, when physicochemical and microbiological parameters were determined. The produced sourdoughs were freeze-dried, and bread samples were produced. The freeze-drying process resulted in high survival rates and few impacts on the metabolic activity of Lp and Lf until 60 days of storage. Incorporating Lp and Lf improved the microbiological and physicochemical properties of sourdough and long-fermentation breads. Tested freeze-dried sourdoughs led to reduced bread aging (higher specific volume and decreased starch retrogradation) and increased digestibility. The results show the potential of the freeze-dried sourdoughs produced with Lp and Lf as innovative strategies for standardizing production protocols for the bakery industry, especially for producing long-term fermentation bread.

Increased blood draws for ultrasensitive ctDNA and CTCs detection in early breast cancer patients.

Early breast cancer patients often experience relapse due to residual disease after treatment. Liquid biopsy is a methodology capable of detecting tumor components in blood, but low concentrations at early stages pose challenges. To detect them, next-generation sequencing has promise but entails complex processes. Exploring larger blood volumes could overcome detection limitations. Herein, a total of 282 high-volume plasma and blood-cell samples were collected for dual ctDNA/CTCs detection using a single droplet-digital PCR assay per patient. ctDNA and/or CTCs were detected in 100% of pre-treatment samples. On the other hand, post-treatment positive samples exhibited a minimum variant allele frequency of 0.003% for ctDNA and minimum cell number of 0.069 CTCs/mL of blood, surpassing previous investigations. Accurate prediction of residual disease before surgery was achieved in patients without a complete pathological response. A model utilizing ctDNA dynamics achieved an area under the ROC curve of 0.92 for predicting response. We detected disease recurrence in blood in the three patients who experienced a relapse, anticipating clinical relapse by 34.61, 9.10, and 7.59 months. This methodology provides an easily implemented alternative for ultrasensitive residual disease detection in early breast cancer patients.

Cereus jamacaru DC. (mandacaru) fruit as a source of lactic acid bacteria with in vitro probiotic-related characteristics and its protective effects on Pediococcus pentosaceus during lyophilization and refrigeration storage.

This study isolated and identified autochthonous lactic acid bacteria (LAB) from mandacaru fruit and evaluated their potential probiotic and technological aptitudes in vitro, as well as the protective effects of freeze-dried mandacaru fruit on the most promising LAB isolate during lyophilization and refrigeration storage. Initially, 212 colonies were isolated from mandacaru fruit, and 34 were preliminarily identified as LAB. Thirteen isolates identified by 16S-rRNA sequencing as Pediococcus pentosaceus were negative for DNase, gelatinase, hemolytic, and biogenic amine production. The selected isolates showed proteolytic activity, diacetyl and exopolysaccharide production, and good tolerance to different NaCl concentrations while having low cellular hydrophobicity and antagonistic activity against pathogens. The survival of isolates sharply decreased after 3 h of exposure to pH 2 and had a good tolerance to 1 % bile salt. A principal component analysis selected P. pentosaceus 57 as the most promising isolate based on the examined technological and probiotic-related physiological properties. This isolate was lyophilized with mandacaru fruit and stored under refrigeration for 90 days. P. pentosaceus 57 lyophilized with mandacaru fruit had high viable cell counts (9.69 ± 0.03 log CFU/mL) and >50 % of physiologically active cells at 90 days of refrigeration storage. The results indicate that mandacaru fruit is a source of P. pentosaceus with aptitudes to be explored as potential probiotic and technological characteristics of interest for the food industry, besides being a good candidate for use in lyophilization processes and refrigeration storage of LAB due to its cryoprotective effects.

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Identification of a novel gene signature related to prognosis and metastasis in gastric cancer.

BACKGROUND: Gastric Cancer (GC) presents poor outcome, which is consequence of the high incidence of recurrence and metastasis at early stages. GC patients presenting recurrent or metastatic disease display a median life expectancy of only 8 months. The mechanisms underlying GC progression remain poorly understood. METHODS: We took advantage of public available GC datasets from TCGA using GEPIA, and identified the matched genes among the 100 genes most significantly associated with overall survival (OS) and disease free survival (DFS). Results were confirmed in ACRG cohort and in over 2000 GC cases obtained from several cohorts integrated using our own analysis pipeline. The Kaplan-Meier method and multivariate Cox regression analyses were used for prognostic significance and linear modelling and correlation analyses for association with clinic-pathological parameters and biological hallmarks. In vitro and in vivo functional studies were performed in GC cells with candidate genes and the related molecular pathways were studied by RNA sequencing. RESULTS: High expression of ANKRD6, ITIH3, SORCS3, NPY1R and CCDC178 individually and as a signature was associated with poor prognosis and recurrent disease in GC. Moreover, the expression of ANKRD6 and ITIH3 was significantly higher in metastasis and their levels associated to Epithelial to Mesenchymal Transition (EMT) and stemness markers. In line with this, RNAseq analysis revealed genes involved in EMT differentially expressed in ANKRD6 silencing cells. Finally, ANKRD6 silencing in GC metastatic cells showed impairment in GC tumorigenic and metastatic traits in vitro and in vivo. CONCLUSIONS: Our study identified a novel signature involved in GC malignancy and prognosis, and revealed a novel pro-metastatic role of ANKRD6 in GC.

Limosilactobacillus fermentum Strains as Novel Probiotic Candidates to Promote Host Health Benefits and Development of Biotherapeutics: A Comprehensive Review.

Fruits and their processing by-products are sources of potentially probiotic strains. Limosilactobacillus (L.) fermentum strains isolated from fruit processing by-products have shown probiotic-related properties. This review presents and discusses the results of the available studies that evaluated the probiotic properties of L. fermentum in promoting host health benefits, their application by the food industry, and the development of biotherapeutics. The results showed that administration of L. fermentum for 4 to 8 weeks promoted host health benefits in rats, including the modulation of gut microbiota, improvement of metabolic parameters, and antihypertensive, antioxidant, and anti-inflammatory effects. The results also showed the relevance of L. fermentum strains for application in the food industry and for the formulation of novel biotherapeutics, especially nutraceuticals. This review provides evidence that L. fermentum strains isolated from fruit processing by-products have great potential for promoting host health and indicate the need for a translational approach to confirm their effects in humans using randomized, double-blind, placebo-controlled trials.

Effects of Simulated Gastrointestinal Conditions on Combined Potentially Probiotic Limosilactobacillus fermentum 296, Quercetin, and/or Resveratrol as Bioactive Components of Novel Nutraceuticals.

This study evaluated the effects of simulated gastrointestinal conditions (SGIC) on combined potentially probiotic Limosilactobacillus fermentum 296 (~ 10 log CFU/mL), quercetin (QUE, 160 mg), and/or resveratrol (RES, 150 mg) as the bioactive components of novel nutraceuticals. Four different nutraceuticals were evaluated during exposure to SGIC and analyzed the plate counts and physiological status of L. fermentum 296, contents and bioaccessibility of QUE and RES, and antioxidant capacity. Nutraceuticals with QUE and RES had the highest plate counts (4.94 ± 0.32 log CFU/mL) and sizes of live cell subpopulations (28.40 ± 0.28%) of L. fermentum 296 after SGIC exposure. An index of injured cells (Gmean index, arbitrary unit defined as above 0.5) indicated that part of L. fermentum 296 cells could be entered the viable but nonculturable state when the nutraceuticals were exposed to gastric and intestinal conditions while maintaining vitality. The nutraceuticals maintained high contents (QUE ~ 29.17 ± 0.62 and RES ~ 23.05 mg/100 g) and bioaccessibility (QUE ~ 41.0 ± 0.09% and RES ~ 67.4 ± 0.17%) of QUE and RES, as well as high antioxidant capacity (ABTS assay ~ 88.18 ± 1.16% and DPPH assay 75.54 ± 0.65%) during SGIC exposure, which could be linked to the protective effects on L. fermentum 296 cells. The developed nutraceuticals could cross along the gastrointestinal tract with high concentrations of functioning potentially probiotic cells and bioavailable phenolic compounds to exert their beneficial impacts on consumer health, being an innovative strategy for the co-ingestion of these bioactive components.

An In Vitro Study of the Impacts of Sweet Potato Chips with Potentially Probiotic Levilactobacillus brevis and Lactiplantibacillus plantarum on Human Intestinal Microbiota : Impacts of potato chips with probiotics on intestinal microbiota.

This study formulated sweet potato chips with powdered potentially probiotic Levilactobacillus brevis (SPLB) and Lactiplantibacillus plantarum (SPLP) and evaluated their impacts on human intestinal microbiota during 48 h of in vitro colonic fermentation. L. brevis and L. plantarum kept high viable cell counts (> 6 log CFU/g) on sweet potato chips after freeze-drying and during 60 days of storage. SPLB and SPLP had satisfactory quality parameters during 60 days of storage. SPLB and SPLP increased the relative abundance of Lactobacillus ssp./Enterococcus spp. (3.84-10.22%) and Bifidobacterium spp. (3.25-12.45%) and decreased the relative abundance of Bacteroides spp./Prevotella spp. (8.56-2.16%), Clostridium histolyticum (8.23-2.33%), and Eubacterium rectale/Clostridium coccoides (8.07-1.33%) during 48 h of in vitro colonic fermentation. SPLB and SPLP achieved high positive prebiotic indexes (> 8.24), decreased pH values and sugar contents, and increased lactic acid and short-chain fatty acid production, proving selective stimulatory effects on beneficial bacterial groups forming the intestinal microbiota. The results showed that SPLB and SPLP have good stability and high viable cell counts of L. brevis and L. plantarum when stored under room temperature and caused positive impacts on human intestinal microbiota, making them potentially probiotic non-dairy snack options.

Technical substitutability of recycled materials in life cycle Assessment: A comprehensive review and framework for quantification.

In evaluating environmental sustainability with methodologies like life cycle assessment (LCA), recycling is usually credited for avoiding impacts from virgin material production. Consequently, the LCA results are influenced by the manner in which the substitutability of virgin by recycled materials is estimated. This study reviews how the scientific community assesses the technical substitutability of recycled materials in LCA. Accordingly, 49 peer-reviewed papers were in-depth analysed, considering aspects such as materials studied, type of substitution, recycled material (rMaterial) application, and life cycle stages (LCSs) where substitution was evaluated. The results show that 49% of the papers investigated material substitutability through technical and economic aspects. 51% of the articles did not consider the final application of the rMaterial. Plastics were the most studied material, and mass was the most used property to quantify technical substitutability. Certain materials were more analysed in specific LCSs (e.g., metals in the natural resource extraction stage). As 51% of the papers developed a new approach for substitutability calculation, this shows that substitutability is still a concept in development. It was noticed in 33% of the papers that substitutability values were taken from external sources, and in some cases were used without considering whether they were representative for a specific case. Aspects such as harmonization, transparency, and consideration of the application of recycled materials, therefore, require more attention in substitutability evaluation. Based on the results, a step-wise framework to measure technical substitutability at different LCSs was developed to guide researchers in including substitutability in LCA studies.

Transoral Flexible Laser Surgery of the Larynx with Blue Laser.

INTRODUCTION: Laser surgery of the larynx is currently the standard of clinical practice in a multitude of procedures. Lasers with photoangiolytic properties have a wide application in endolaryngeal lesions. One of their most prominent features is the ability to coagulate blood vessels, reducing unwanted tissue damage. Our objective is to expose the uses of the blue laser (445 nm) in the larynx. MATERIAL AND METHODS: A retrospective study was carried out including 47 patients treated with blue photoangiolytic laser from October 2021 to January 2023 at a university hospital. Demographic data, type of lesion presented, date of intervention and scope of the procedure, as well as the parameters of the laser used, were recorded. The number of sessions received per patient, the result and complications were also collected. RESULTS: A total of 47 patients with laryngeal lesions were treated, including vascular angiomas, laryngeal sulcus vocali, vocal cord polyps, Reinke's edemas, laryngeal papillomatoses, subglottic stenosis, laryngeal synechiae, subglottic granulomas, glottic scars, vocal fold leukoplakias, laryngeal dysplasias and tracheostomal granulomas. The mean age was 52.5 years, and 64.3% of the patients were women. The range of power used in the resective surgeries was 2-10 Watts with a 20-millisecond window. The average number of sessions received was 2.1 (range 1-4). A satisfactory situation was obtained in 45 of the 47 patients treated (95.75%), and an evident decrease in lesions was seen in the remaining two. There was no evidence of any complications directly derived from the use of the blue laser. Twenty-seven cases (54%) were treated exclusively in-office. CONCLUSIONS: The blue laser is safe and effective in the treatment of a wide range of laryngeal pathologies. Its advantages include its portability, its photoangiolytic qualities as well as its ability to vaporize tissue in contact mode, which can treat subepithelial vessels or resect lesions.

Ligand-Independent Activation of Aryl Hydrocarbon Receptor and Attenuation of Glutamine Levels by Natural Deep Eutectic Solvent.

Natural deep eutectic solvents (NADESs) are emerging sustainable alternatives to conventional organic solvents. Beyond their role as laboratory solvents, NADESs are increasingly explored in drug delivery and as therapeutics. Their increasing applications notwithstanding, our understanding of how they interact with biomolecules at multiple levels - metabolome, proteome, and transcriptome - within human cell remain poor. Here, we deploy integrated metabolomics, proteomics, and transcriptomics to probe how NADESs perturb the molecular landscape of human cells. In a human cell line model, we found that an archetypal NADES derived from choline and geranic acid (CAGE) significantly altered the metabolome, proteome, and transcriptome. CAGE upregulated indole-3-lactic acid and 4-hydroxyphenyllactic acid levels, resulting in ligand-independent activation of aryl hydrocarbon receptor to signal the transcription of genes with implications for inflammation, immunomodulation, cell development, and chemical detoxification. Further, treating the cell line with CAGE downregulated glutamine biosynthesis, a nutrient rapidly proliferating cancer cells require. CAGE's ability to attenuate glutamine levels is potentially relevant for cancer treatment. These findings suggest that NADESs, even when derived from natural components like choline, can indirectly modulate cell biology at multiple levels, expanding their applications beyond chemistry to biomedicine and biotechnology.

Spontaneous fermentation improves the physicochemical characteristics, bioactive compounds, and antioxidant activity of acerola (Malpighia emarginata D.C.) and guava (Psidium guajava L.) fruit processing by-products.

This study aimed to investigate the effects of spontaneous fermentation on physicochemical characteristics, bioactive compounds, and antioxidant activity of acerola and guava fruit industrial by-products. Viable cell counts of lactic acid bacterial (LAB) in acerola and guava by-products were ≥ 5.0 log CFU/mL from 24 h up to 120 h of fermentation. Fermented acerola and guava by-products had increased luminosity and decreased contrast. Contents of total soluble solids and pH decreased, and titrable acidity increased in acerola and guava by-products during fermentation. Ascorbic acid contents decreased in acerola by-product and increased in guava by-product during fermentation. Different phenolic compounds were found in acerola and guava by-products during fermentation. Fermented acerola and guava by-products had increased contents of total flavonoids, total phenolics, and antioxidant activity. The contents of total flavonoids and total phenolics positively correlated with antioxidant activity in fermented acerola and guava by-products. These results indicate that spontaneous fermentation could be a strategy to improve the contents of bioactive compounds and the antioxidant activity of acerola and guava by-products, adding value and functionalities to these agro-industrial residues.

Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy.

Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance. Single-cell RNA-sequencing analysis reveals that RANO diminishes the abundance of the therapy-resistant NGFRhi neural crest stem cell subpopulation. Moreover, by rewiring the methionine salvage pathway, RANO enhances melanoma immunogenicity through increased antigen presentation and interferon signalling. Combination of RANO with anti-PD-L1 antibodies strongly improves survival by increasing antitumour immune responses. Altogether, we show that RANO increases the efficacy of targeted melanoma therapy through its effects on FAO and the methionine salvage pathway. Importantly, our study suggests that RANO could sensitize BRAFi-resistant tumours to immunotherapy. Since RANO has very mild side-effects, it might constitute a therapeutic option to improve the two main strategies currently used to treat metastatic melanoma.

Laryngotracheal Complications after Intubation for COVID-19: A Multicenter Study.

Many of the patients with COVID-19 have suffered respiratory distress requiring prolonged endotracheal intubation (ETI) resulting in laryngotracheal complication with an impact on breathing, phonation, and swallowing. Our aim is to describe laryngeal injuries diagnosed after ETI in patients with COVID-19 in a multicentre study. METHODS: A prospective descriptive observational study was conducted from January 2021 to December 2021, including COVID-19 patients with laryngeal complications due to ETI diagnosed in several Spanish hospitals. We analyzed the epidemiological data, previous comorbidities, mean time to ICU admission and ETI, need for tracheostomy, mean time on invasive mechanical ventilation until tracheostomy or weaning, mean time in ICU, type of residual lesions, and their treatment. RESULTS: We obtained the collaboration of nine hospitals during the months of January 2021 to December 2021. A total of 49 patients were referred. Tracheostomy was performed in 44.9%, being late in most cases (more than 7-10 days). The mean number of days of ETI until extubation was 17.63 days, and the main post-intubation symptoms were dysphonia, dyspnea, and dysphagia, in 87.8%, 34.7%, and 42.9%, respectively. The most frequent injury was altered laryngeal mobility, present in 79.6%. Statistically, there is a greater amount of stenosis after late ETI and after delayed tracheostomy, not observing the data with the immobility alterations. CONCLUSION: The mean number of days of ETI was long, according to the latest guidelines, with the need for several cycles of pronation. This long ETI may have had an impact on the increase of subsequent laryngeal sequelae, such as altered laryngeal mobility or stenosis.

Effects of supplementation of tropical fruit processing by-products on lipid profile, retinol levels and intestinal function in Wistar rats.

Fruits agro-industrial by-products may have a great variety of bioactive compounds that promote health. Thus, the effects of supplementation with acerola, cashew and guava processing by-products for 28 days on retinol level, lipid profile and on some aspects related to intestinal function in rats were investigated. The animals supplemented with different fruit by-products presented similar weight gain, faecal pH values and intestinal epithelial structures; however, they showed higher moisture and Lactobacillus spp. and Bifidobacterium spp. counts in faeces compared to the control group. Supplementation with the cashew by-product decreased the blood glucose, acerola and guava by-products reduced serum lipid levels and all fruit by-products tested increased serum and hepatic retinol. The results indicated that acerola and guava by-products possess a potential hypolipidemic effect. The three fruit by-products increase the hepatic retinol deposition and the faecal populations of beneficial bacterial groups and modulated aspects of intestinal function. The findings of this study can contribute to sustainable fruticulture and support future clinical studies with the supplementation of by-products.

Persistent Dysphonia in Hospitalized COVID-19 Patients.

INTRODUCTION: The main objective of this study is to estimate the prevalence of persistent dysphonia in hospitalised COVID-19 patients. METHODS: Data were collected from those COVID-19 patients who, during the months of March to April 2020, were hospitalised in ward or intensive care unit at the University Hospital of Fuenlabrada. Patients with dysphonia prior to SARS-CoV-2 were excluded. Informed consent was obtained orally by a telephone call, as well as clinical and epidemiological data. Patients who reported persistent dysphonia were assessed using the Voice Handicap Index 10, the maximum phonation time, the s/z ratio and a fibrolaryngoscope examination. Patients who reported persistent dysphagia were assessed with the Eating Assessment Tool 10. RESULTS: A total of 79 patients were included in the study (48 men and 31 women). 10 ICU patients (25%) and 4 ward patients (10,3%) had dysphonia at least 3 months after hospital discharge, but no association was found between ICU admission and the presence of persistent dysphonia (P = 0.139). Persistent dysphonia in patients admitted to the ICU is associated with persistent dysphagia (P = 0.002), also the age of patients with persistent dysphonia is significantly higher than the age of non-dysphonic patients (P = 0.046). The most frequent exploratory finding was vocal cord paresis/paralysis (60.4%). CONCLUSION: This is one of the first studies to show that persistence of dysphonia may be a consequence of COVID-19, so further studies are needed to assess the evolution and prognosis of these patients and the possible association of dysphonia with the severity of the disease.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.