Is there a need to widely prescribe antibiotics in patients hospitalized with COVID-19?

BACKGROUND: Debate continues regarding the usefulness and benefits of wide prescription of antibiotics in patients hospitalized with coronavirus disease 2019 (COVID-19). METHODS: All patients hospitalized in the Infectious Diseases Department, Dijon University Hospital, Dijon, France between 27 February and 30 April 2020 with confirmed COVID-19 were included in this study. Clinical, biological and radiological data were collected, as well as treatment and outcome data. An unfavourable outcome was defined as death or transfer to the intensive care unit. Patient characteristics and outcomes were compared between patients who did and did not receive antibiotic therapy using propensity score matching. FINDINGS: Among the 222 patients included, 174 (78%) received antibiotic therapy. The univariate analysis showed that patients who received antibiotic therapy were significantly older, frailer and had more severe presentation at admission compared with patients who did not receive antibiotic therapy. Unfavourable outcomes were more common in patients who received antibiotic therapy [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.07-8.11; P = 0.04]. Multi-variate analysis and propensity score matching indicated that antibiotic therapy was not significantly associated with outcome (HR 1.612, 95% CI 0.562-4.629; P = 0.37). CONCLUSION: Antibiotics were frequently prescribed in this study and this was associated with more severe presentation at admission. However, antibiotic therapy was not associated with outcome, even after adjustment. In line with recent publications, such data support the need to streamline antibiotic therapy in patients with COVID-19.

Ultra-High Mass Resolution MALDI Imaging Mass Spectrometry of Proteins and Metabolites in a Mouse Model of Glioblastoma.

MALDI mass spectrometry imaging is able to simultaneously determine the spatial distribution of hundreds of molecules directly from tissue sections, without labeling and without prior knowledge. Ultra-high mass resolution measurements based on Fourier-transform mass spectrometry have been utilized to resolve isobaric lipids, metabolites and tryptic peptides. Here we demonstrate the potential of 15T MALDI-FTICR MSI for molecular pathology in a mouse model of high-grade glioma. The high mass accuracy and resolving power of high field FTICR MSI enabled tumor specific proteoforms, and tumor-specific proteins with overlapping and isobaric isotopic distributions to be clearly resolved. The protein ions detected by MALDI MSI were assigned to proteins identified by region-specific microproteomics (0.8 mm2 regions isolated using laser capture microdissection) on the basis of exact mass and isotopic distribution. These label free quantitative experiments also confirmed the protein expression changes observed by MALDI MSI and revealed changes in key metabolic proteins, which were supported by in-situ metabolite MALDI MSI.

An outbreak of Shewanella putrefaciens group in wild eels Anguilla anguilla L. favoured by hypoxic aquatic environments.

Microbiological analyses were conducted on wild eels from the L'Albufera Lake (Spain). A total of 174 individuals were collected in two surveys (i.e. year 2008 and autumn-winter 2014) among those caught by local fishermen into the lagoon. The prevalence of Shewanella putrefaciens group was 1.7% in 2008 and rose above 32% in 2014. It was due to an outbreak of shewanellosis that presented a morbidity rate of 64%. S. putrefaciens group strains were isolated as pure cultures from the sick eels that showed white ulcers surrounded by a reddish inflammation, damage of the mouth, extensive skin discoloration, exophthalmia, ascites and bad odour. The S. putrefaciens group was recovered from freshwater samples taken at the L'Albufera system, along autumn-winter 2015. Its counts significantly increased in freshwater parallel to hypoxia and temperature rising. Shewanellae strains were identified as S. putrefaciens and S. xiamenensis by 16S rRNA gene sequencing. These isolates recovered from sick eels or freshwater were virulent for European eel by IP challenge (LD50 106  CFU g-1 body weight). They also caused 30-38% cumulative mortality, in European eels challenged by a 2-h bath (107  CFU mL-1 ). These results suggest that shewanellosis could be transmitted through water highlighting the fact that hypoxic conditions increase this bacterium levels in water.

Fast and simultaneous determination of endocrine disrupting compounds by ultra-high performance liquid chromatography-tandem mass spectrometry.

A rapid and sensitive analytical method for the simultaneous determination of thirteen endocrine disruptors (five phthalates, seven parabens, and bisphenol A) in a single chromatographic run has been developed for the first time. The separation method, based on ultra-high performance liquid chromatography (UHPLC), allows the separation of all compounds (including isobaric pairs) in less than 4.1 min. The fast polarity switching mode of the triple quadrupole mass spectrometer used enables the registration of positive (phthalates) and negative (parabens and BPA) ions in the same acquisition run. A Response Surface Methodology was used for the optimization of the method. The optimum elution program starts with 0.2 min in isocratic conditions (79.8% water; 20% acetonitrile, 0.2% ammonium formate 5mM at pH 10.2), then the content of acetonitrile is linearly increased in 2 min up to 42%, and later up to 98% in 1.1 min. The analytical characteristics of the developed method were satisfactory. The method is robust and showed a linear response with determination coefficients (R(2)) higher than 0.991 in the range 5.0-2000 pg on column (or higher) for all the compounds investigated. Instrumental intra- and inter-day precision (expressed as relative standard deviation) were lower than 12% for parabens and bisphenol A, and between 5.9% and 27% for phthalates. Instrumental detection and quantification limits (iLODs and iLOQs) were in the range of medium-high femtograms (270-1300 pg on column for iLODs). Finally, the suitability of the developed method was demonstrated through its application to the analysis of commercial personal care products (shower gels) without any sample treatment, only a simple dilution, being possible to determine the simultaneous presence of phthalates, parabens, and bisphenol A in almost all the gels analyzed.

Multidrug-resistant (MDR) Aeromonas recovered from the metropolitan area of Valencia (Spain): diseases spectrum and prevalence in the environment.

Aeromonas infections are rare in Europe and often related to traveller's diarrhoea. A total of 185 Aeromonas isolates from river water, fish and clinical sources, recovered during a 1-year period, were used to investigate the disease spectrum and impact of multidrug-resistant (MDR) strains. They were all identified by biochemical tests and 25% of them were also identified by sequencing of the 16S rRNA gene. The minimum inhibitory concentrations (MICs) of 21 antimicrobials were determined for all isolates by broth microdilution/E-strips methods, and susceptibility was assessed according to the Clinical and Laboratory Standards Institute (CLSI). Strains pathogenicity was determined by using Swiss Webster mice as the animal model. Aeromonas diseases had an incidence of around 20 cases/million inhabitants in the metropolitan area of Valencia (Spain). Acute gastroenteritis in children with no history of travel abroad was the main pathology. These cases were related to A. caviae, A. veronii biovar sobria, A. hydrophila and A. dhakensis. A significant incidence of A. caviae in humans was found, while the other species were equally present in clinical and environmental origins. A. jandaei, A. bestiarum and A. media had mainly an environmental distribution. The prevalence of MDR Aeromonas was maximal in clinical samples, and resistance phenotypes were significantly related to this source. 7.2% of environmental Aeromonas was resistant to at least five drugs; most of them were moderately virulent for mice and, in addition, belonged to clinically significant species. The present study demonstrates a diseases spectrum similar to that reported in tropical countries, and also that pathogenic and heavily MDR Aeromonas are present in environmental reservoirs. MDR Aeromonas from any source analysed were susceptible to aztreonam, netilmicin, cefotaxime, ceftazidime, cefepime and fluoroquinolones.

Novel strategy for the revalorization of olive (Olea europaea) residues based on the extraction of bioactive peptides.

This work proposes a new strategy for the revalorization of residual materials from table-olive and olive oil production based on the extraction of bioactive peptides. Enzymatic hydrolysates of olive seed protein isolate were prepared by treatment with five different proteases: Alcalase, Thermolysin, Neutrase, Flavourzyme and PTN. Although all hydrolysates presented antioxidant properties, Alcalase was the enzyme that yielded the hydrolysate with the highest antioxidant capacity. All hydrolysates showed antihypertensive capacity, obtaining IC50 values from 29 to 350 µg/ml. Thermolysin was the enzyme which yielded the hydrolysate with the highest ACE-inhibitory capacity. Hydrolysates were fractionated by ultrafiltration showing a high concentration of short chain peptides, which exhibited significantly higher antioxidant and antihypertensive capacities than fractions with higher molecular weights. Peptides in most active fractions were identified by LC-MS/MS, observing homologies with other recognized antioxidant and antihypertensive peptides. Finally, their antioxidant and antihypertensive capacities were evaluated after in vitro gastrointestinal digestion.

Presence of viruses in wild eels Anguilla anguilla L, from the Albufera Lake (Spain).

A virological analysis was conducted on wild eels from the Albufera Lake (Spain). A total of 179 individuals at different growth stages were collected in two different surveys (2004 and 2008). Presence of anguillid herpesvirus (AngHV-1), aquabirnavirus and betanodavirus was confirmed by PCR procedures in both surveys, although the number of detections was clearly higher in 2008 (83% of the eels analysed resulted positive for virus presence). AngHV-1 was the viral agent most frequently detected, followed by aquabirnaviruses. Betanodaviruses were detected by the first time in wild eels, and although the detections were only made by nested PCR, high percentage of positives were achieved. In addition, in 2008, seven aquabirnaviruses were isolated. Phylogenetic analysis performed using partial sequences of both genomic segments of aquabirnaviruses indicated that the seven isolates could be typed as WB (genogroup I) on the basis of segment A sequences, but when segment B was used six of them clustered with C1 strain (genogroup V) and one was typed as Ab (genogroup II). These results indicate natural reassortment between different strains of aquabirnaviruses in the eels. Although betanodaviruses were not isolated in cell culture, the analysis of the sequence of the nested PCR product indicated that they clustered with SJNNV genotype. The diversity of viral agents and the high level of viral detections suggest that viral infections may play a more prominent role in the decline of the European eel than initially thought.

Vegetable foods: a cheap source of proteins and peptides with antihypertensive, antioxidant, and other less occurrence bioactivities.

Despite less explored than foods from animal origin, plant derived foods also contain biologically active proteins and peptides. Bioactive peptides can be present as an independent entity in the food or, more frequently, can be in a latent state as part of the sequence of a protein. Release from that protein requires protein hydrolysis by enzymatic digestion, fermentation or autolysis. Different methodologies have been used to test proteins and peptides bioactivities. Fractionation, separation, and identification techniques have also been employed for the isolation and identification of bioactive proteins or peptides. In this work, proteins and peptides from plant derived foods exerting antihypertensive, antioxidant, hypocholesterolemic, antithrombotic, and immunostimulating capacities or ability to reduce food intake have been reviewed.

Analysis of olive allergens.

Olive pollen is one of the most important causes of seasonal respiratory allergy in Mediterranean countries, where this tree is intensely cultivated. Besides this, some cases of contact dermatitis and food allergy to the olive fruit and olive oil have been also described. Several scientific studies dealing with olive allergens has been reported, being the information available about them constantly increasing. Up to date, twelve allergens have been identified in olive pollen while just one allergen has been identified in olive fruit. This review article describes considerations about allergen extraction and production, also describing the different methodologies employed in the physicochemical and immunological characterization of olive allergens. Finally, a revision of the most relevant studies in the analysis of both olive pollen and olive fruit allergens is carried out.

Multiresistant waterborne pathogens isolated from water reservoirs and cooling systems.

AIMS: To determine the incidence of multiple antibiotic-resistant strains of the emergent human pathogens Legionella pneumophila, Pseudomonas aeruginosa and mesophilic Aeromonas species among those isolated from water reservoirs and industrial cooling systems. METHODS AND RESULTS: Water from four natural water reservoirs and four industrial cooling towers was sampled for 1 year period. The total heterotrophs, mesophilic Aeromonas, Pseudomonas spp. and Legionella spp. counts were performed as recommended by standard procedures, and the sensitivity of the isolates to 27 antibiotics was tested. A total of 117 Aeromonas, 60 P. aeruginosa and 15 L. pneumophila strains were isolated and identified by means of biochemical tests and DNA probes. 46.4% of Aeromonas, and 100% of P. aeruginosa isolates presented multiple resistance. Legionella pneumophila strains were generally sensitive to the drugs used. CONCLUSIONS: Antibiotic-resistant pathogenic bacteria belonging to P. aeruginosa and mesophilic Aeromonas species are common in natural aquatic environments. Thus, the risk of waterborne diseases owing to domestic and industrial uses of freshwater should be re-examined from the increase of bacterial resistance point of view. SIGNIFICANCE AND IMPACT OF THE STUDY: These data confirm the emergence of bacteria resistant to antibiotics in aquatic environments.

Carcinoma de endometrio y ovario sincrónicos / Synchronous primary cancers of the endometrium and ovary

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Synchronous primary cancers of the endometrium and ovary are found in 10% of women with ovarian cancer and 5% of women with endometrial cancer. The classification into synchronous primary cancers or metastasis has different consequences in the prognosis and treatment. But this classification is still difficult. We describe four cases from our service. Endometrioid cancers are the most frequent and have the best prognosis. The median age of the patients is younger than patients with metastasic tumours and the most common sign or symtom is abnormal uterine bleeding. Treatment is still controversial (AU)

Factores asociados a la prevalencia del asma bronquial en la infancia y la adolescencia / Factors associated with the prevalence of bronchial asthma in childhood and adolescence

En los países desarrollados, la enfermedad alérgica es una de las enfermedades crónicas más frecuente; afecta entre un 15 y 30% de la población. Numerosos son los estudios epidemiológicos que se ocupan de las enfermedades alérgicas, y en especial del asma bronquial; cabe resaltar entre ellos el Estudio ISAAC (International Study of Asthma and Allergies in Childhood). Muchos son los trabajos que posteriormente han utilizado la metodología, ISAAC para estudiar diferentes factores asociados a las enfermedades alérgicas. Aprovechando esta metodología, estudiamos los diferentes factores de riesgo asociados al asma bronquial en la infancia y la adolescencia. Se estudiaron dos grupos de edad de diferentes colegios:3.194 niños de 5 a 8 años de edad y 3.526 de 12 a 15 años. Además del Cuestionario ISAAC Fase I, se empleó un cuestionario adicional con el objetivo de analizar diferentes factores de riesgo. De los resultados obtenidos, se puede concluir que ser varón, tener antecedentes familiares de asma, síntomas de rinitis, infecciones respiratorias, necesidad de excluir algún alimento de la dieta y sibilancias o tos con el ejercicio son factores de riesgo asociados al asma bronquial, y que deben ser valorados con el fin de establecer un diagnóstico precoz. Pese a no encontrar asociación con exposición al humo del tabaco, se debe indicar su evitación, dada la influencia de iniciarse en este hábito entre los adolescentes y su asociación entonces al asma

Allergies are among the most common chronic diseases in developed countries, affecting 15% to 30% of the population. There are numerous epidemiological studies dealing with allergic diseases, especially with bronchial asthma; of particular interest is the ISAAC study (International Study of Asthma and Allergies in Childhood). Many subsequent studies have used the ISAAC method to study the factors associated with allergic diseases. Using this same approach, we studied different risk factors associated with bronchial asthma in childhood and adolescence. Two age groups from different schools were studied: 3,194 children in the 5 to 8-year-old group and 3,526 in the 12 to 15-year-old group. In addition to the ISAAC Phase I questionnaire, a second questionnaire was analyzed in order to evaluate different risk factors. From the results obtained, we can conclude that male sex, a family history of asthma, rhinitis symptoms, respiratory infections, the need to exclude some food from the diet, and exercise-induced wheezing or coughing are risk factors associated with bronchial asthma and should be assessed to establish an early diagnosis. Although we found no association with exposure to tobacco smoke, its avoidance is recommended given the influence of the smoking habit among adolescents and its association with asthma

Surgically repaired massive rotator cuff tears: MRI of tendon integrity, muscle fatty degeneration, and muscle atrophy correlated with intraoperative and clinical findings.

OBJECTIVE: Our goal in this study was to evaluate by means of MRI the clinical significance of tendon integrity, muscle fatty degeneration, and muscle atrophy in surgically repaired massive rotator cuff tears and to correlate these and other prognostic factors with intraoperative and clinical findings. MATERIALS AND METHODS: Twenty-eight surgically proven massive rotator cuff tears were retrospectively included in the study. Twenty-two patients underwent complete repair, and six patients underwent partial repair. Preoperative and postoperative clinical assessment was performed by using the University of California at Los Angeles score. Preoperative and postoperative MRI studies were evaluated for the presence and extent of rotator cuff tear and for the degree of fatty degeneration and atrophy of the rotator cuff muscles. RESULTS: At a mean 44.4 months' follow-up, 20 patients (71.4%) had a favorable result. A total of 25 patients (89.2%) showed postoperative full-thickness rotator cuff tear, 19 of which were reruptures. A sagittal preoperative rotator cuff tear of less than or equal to 34 mm showed a specificity of 100% for predicting a favorable outcome. A coronal postoperative rotator cuff tear of less than or equal to 34 mm showed a specificity of 85.7% and a positive predictive value of 92.9% for predicting a favorable outcome. A postoperative fatty degeneration of infraspinatus muscle less than or equal to 2 had a specificity of 87.5% and a positive predictive value of 90.9% for predicting a favorable outcome. CONCLUSION: Open repair of massive rotator cuff tears may reach a favorable outcome in a significant proportion of patients, despite a high rate of recurrent or residual tears. Oblique coronal sizes of the recurrent or residual tear of less than or equal to 34 mm and postoperative fatty degenerations of infraspinatus muscle of less than or equal to 2 may allow a favorable outcome.

Rabdomiolisis secundaria a la administración de succinilcolina / Rhabdomyolysis after succinylcholine administration

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Analgesic effect of intra-articular ketorolac in knee arthroscopy: comparison of morphine and bupivacaine.

This prospective study assessed the postoperative analgesic effect of intra-articular ketorolac, morphine, and bupivacaine during arthroscopic outpatient partial meniscectomy. Group 1 patients (n=20) received postoperative injection of 60 mg intra-articular ketorolac, group 2 patients (n=20) 10 cc intra-articular bupivacaine 0.25%, group 3 patients (n=20) 1 mg intra-articular morphine diluted in 10 cc saline, and group 4 patients (n=20, controls) only 10 cc saline. We evaluated the postoperative analgesic effect (period measured from the end of the surgery until further analgesia was demanded), the level of postoperative pain (by visual analog scale 1, 2, 3, 12, and 24 h after surgery), and the need for additional pain medication (during the first 24 h after surgery). The best analgesic effect was in patients treated with intra-articular ketorolac, and this was statistically significant in: postoperative analgesic effect and the need for additional pain medication immediately after surgery, and after 24 h. No complications were found related to the intra-articular treatment. We conclude that 60 mg intra-articular ketorolac provides better analgesic effect than 10 cc intra-articular bupivacaine 0.25% or 1 mg intra-articular morphine.

Secretion of haemolysins and proteases by Aeromonas hydrophila EO63: separation and characterization of the serine protease (caseinase) and the metalloprotease (elastase).

AIMS: To determine the haemolysins and proteases excreted by the virulent strain EO63 of Aeromonas hydrophila grown in complex media and to then fractionate and characterize them, in particular those with elastolytic activity. METHODS AND RESULTS: The amount of haemolytic and proteolytic activity in EO63 culture supernatants was dependent on the culture media used. In all media, haemolysins appeared during the phase of active growth and haemolytic activity decreased quickly thereafter, as previously described for aerolysin. In contrast, proteases were mainly released during the stationary phase. Serine protease activity in EO63 culture supernatants was four times greater than that caused by metalloproteases. Two main proteases were partially purified from EO63 culture supernatants by isoelectrophoresis: a serine protease (68 kDa) active against casein; a mixture of different protein bands (60, 44 and 31 kDa) representing a thermostable metalloprotease active against elastin and casein. This metallo-elastase was also inhibited by dithiothreitol and showed a pH optimum of 8.0. Both exoenzymes were toxic for eels at LD50 doses of 1.1 and 3.5 microg (g fish)(-1), respectively. CONCLUSIONS: A serine caseinase and a metallo-elastase may play a role in the pathogenicity of EO63 for eels. These toxins are excreted in vitro by EO63 in the ratio of 4:1 during the stationary phase of growth. Strain EO63 also produced beta-haemolysins in vitro which could correspond to aerolysin. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the purification of a metallo-elastase excreted by a wild-type A. hydrophila strain.

Rotura masiva del manguito de los rotadores. Resultados del tratamiento quirúrgico / Massive rupture of the rotator cuff. Results of surgical treatment

Objetivo: Evaluar de forma retrospectiva los resultados clínicos de 25 pacientes diagnosticados de rotura masiva del manguito de los rotadores tratados quirúrgicamente, de forma consecutiva. Pacientes: La serie está compuesta por 13 hombres y 12 mujeres con una edad media de 57 años. La indicación para el tratamiento quirúrgico ha sido el dolor importante después de un período de tratamiento conservador superior a 3 meses. El diagnóstico de rotura masiva se ha realizado en el momento de la intervención quirúrgica cuando el tamaño de la rotura, en su diámetro mayor ha sido = 5 cm. Se han excluido aquellos pacientes con rotura masiva del manguito con excentricidad de la cabeza humeral respecto a la glenoides por subluxación proximal con signos de artropatía secundaria a lesión del manguito. Se ha realizado una descompresión del espacio subacromial a cielo abierto mediante la técnica de Neer y reparación de la lesión después de movilización de los extremos tendinosos siguiendo un proceso sistemático, sutura tendinosa por convergencia de márgenes y sutura al troquíter mediante anclajes óseos. Los pacientes se han evaluado desde el punto de vista clínico mediante la escala de UCLA con un seguimiento mínimo de 1 año. Resultados: Antes de la intervención la puntuación media fue de 11,6; mientras que en la revisión fue de 32,2 (13 resultados excelentes, 8 buenos, 3 regulares y 1 malo). Los 3 pacientes que tenían un antecedente traumático de luxación glenohumeral obtuvieron los peores resultados. Conclusiones: Con el tratamiento quirúrgico de las roturas masivas del manguito de los rotadores puede obtenerse un nivel de resultados satisfactorios parecido a los obtenidos con el tratamiento de lesiones de menor tamaño. (AU)