Hybrid closed-loop systems can help patients with extreme fear of hypoglycemia or hyperglycemia.

Fear of hypoglycemia and hyperglycemia can lead to inappropriate diabetes self-management and untoward health outcomes. We report two patients, representative of these opposite conditions, who benefited from hybrid closed-loop technology. In the patient with fear of hypoglycemia, time in range improved from 26 to 56% and the patient did not present with severe hypoglycemia. Meanwhile, the patient with hyperglycemia aversiveness had a drastic reduction in time below range, from 19 to 4%. We conclude that hybrid closed-loop technology was an effective tool for improvement of glucose values in two patients with fear of hypoglycemia and hyperglycemia aversiveness, respectively.

Usefulness of the Measurement of Serum Paraoxonase-1 Arylesterase Activity in the Diagnoses of COVID-19.

The development of inexpensive, fast, and reliable screening tests for COVID-19 is, as yet, an unmet need. The present study was aimed at evaluating the usefulness of serum arylesterase activity of paraoxonase-1 (PON1) measurement as a screening test in patients with different severity levels of COVID-19 infection. We included 615 COVID-19-positive patients who were classified as asymptomatic, mildly symptomatic, severely symptomatic, or fatally symptomatic. Results were compared with 50 healthy volunteers, 330 patients with cancer, and 343 with morbid obesity. Results showed PON1 activity greatly decreased in COVID-19 compared to healthy volunteers; a receiver operating characteristics plot showed a high diagnostic accuracy. The degree of COVID-19 severity did not influence PON1 levels. Our results indicated that PON1 determination was efficient for disease diagnosis, but not for prognosis. Furthermore, patients with obesity or cancer presented alterations similar to those of COVID-19 patients. As such, elevated levels of PON1 indicate the absence of COVID-19, but low levels may be present in various other chronic diseases. The assay is fast and inexpensive. We suggest that PON1 measurement could be used as an initial, high cut-off point screening method, while lower values should be confirmed with the more expensive nucleic acid amplification test.

Clinical performance of the Elecsys® anti-SARS-CoV-2 combined in an algorithm with two specific anti-IgG immunoassays for the evaluation of the serological response of patients with COVID-19 in a population with a high prevalence of infection.

BACKGROUND: Anti-SARS-CoV-2 antibodies have been used in the study of the immune response in infected patients. However, differences in sensitivity and specificity have been reported, depending on the method of analysis. The aim of the present study was to evaluate the diagnostic accuracy of an algorithm in which a high-throughput automated assay for total antibodies was used for screening and two semi-automated IgG-specific methods were used to confirm the results, and also to correlate the analytical results with the clinical data and the time elapsed since infection. METHODS: We studied 306 patients, some hospitalized and some outpatients, belonging to a population with a high prevalence of COVID-19. One-hundred and ten patients were classified as SARS-CoV-2 negative and 196 as positive by polymerase chain reaction. RESULTS: The algorithm and automated assay alone had a specificity and a positive predictive value of 100%, although the sensitivity and negative predictive value of the algorithm was higher. Both methods showed a good sensitivity from day 11 of the onset of symptoms in asymptomatic and symptomatic patients. The absorbance of the total antibodies was significantly higher in severely symptomatic than in asymptomatic or mildly symptomatic patients, which suggests the antibody level was higher. We found 15 patients who did not present seroconversion at 12 days from the onset of symptoms or the first polymerase chain reaction test. CONCLUSION: This study highlights the proper functioning of algorithms in the diagnosis of the immune response to COVID-19, which can help to define testing strategies against this disease.

First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain.

Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.

Dissemination of NDM-producing Klebsiella pneumoniae and Escherichia coli high-risk clones in Catalan healthcare institutions.

OBJECTIVES: To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain. METHODS: Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids. RESULTS: Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid. CONCLUSIONS: We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.

Accuracy of Flash Glucose Monitoring in Patients with Diabetes Mellitus on Hemodialysis and Its Relationship with Hydration Status.

BACKGROUND: The use of flash-glucose monitoring system FreeStyle Libre (FSL) has demonstrated benefits in metabolic control and quality of life in different populations with diabetes mellitus (DM), being funded in many countries. Due to this, DM subjects on hemodialysis (HD) are using FSL despite the accuracy in this population being unclear. The aims of the present study are to assess the accuracy of FSL in DM subjects on HD, its relationship to hydration status, and patient satisfaction. MATERIAL AND METHODS: A prospective study in 16 patients with DM in a chronic HD program was conducted. Interstitial glucose values from FSL during a 14-day period were compared to capillary glucose measurements obtained at the same time. Hydration status was measured via bioimpedance spectroscopy. Satisfaction with FSL was obtained from an ad hoc satisfaction questionnaire. RESULTS: A total of 766 paired interstitial and capillary glucose levels were analyzed. A correlation coefficient of 0.936 was determined and a mean absolute relative difference (MARD) value of 23%, increasing to 29% during HD. MARD was not related to hydration status. Interstitial glucose values were lower during HD (100.1 ± 17 mg/dL) than within the 12 hours after (125.1 ± 39 mg/dL; P = .012) and the days without HD (134.2 ± 32 mg/dL; P = .001). Subjects showed high satisfaction with FSL. CONCLUSION: The accuracy of FSL in DM patients on HD is lower than in other populations, especially during HD sessions and is not related with the hydration status. Despite this, the degree of patient satisfaction with FSL is very high.

Inadequate Weight Gain According to the Institute of Medicine 2009 Guidelines in Women with Gestational Diabetes: Frequency, Clinical Predictors, and the Association with Pregnancy Outcomes.

BACKGROUND: In the care of women with gestational diabetes mellitus (GDM), more attention is put on glycemic control than in factors such as gestational weight gain (GWG). We aimed to evaluate the rate of inadequate GWG in women with GDM, its clinical predictors and the association with pregnancy outcomes. METHODS: Cohort retrospective analysis. OUTCOME VARIABLES: GWG according to Institute of Medicine 2009 and 18 pregnancy outcomes. Clinical characteristics were considered both as GWG predictors and as covariates in outcome prediction. STATISTICS: descriptive, multinomial and logistic regression. RESULTS: We assessed 2842 women diagnosed with GDM in the 1985-2011 period. GWG was insufficient (iGWG) in 50.3%, adequate in 31.6% and excessive (eGWG) in 18.1%; length of follow-up for GDM was positively associated with iGWG. Overall pregnancy outcomes were satisfactory. GWG was associated with pregnancy-induced hypertension, preeclampsia, cesarean delivery and birthweight-related outcomes. Essentially, the direction of the association was towards a higher risk with eGWG and lower risk with iGWG (i.e., with Cesarean delivery and excessive growth). CONCLUSIONS: In this cohort of women with GDM, inadequate GWG was very common at the expense of iGWG. The associations with pregnancy outcomes were mainly towards a higher risk with eGWG and lower risk with iGWG.

A Case of Aeromonas trota in an Immunocompromised Patient with Diarrhea.

According to recent literature, 95.4% of the Aeromonas strains associated with human clinical cases correspond to four species: Aeromonas caviae, Aeromonas dhakensis, Aeromonas veronii and Aeromonas hydrophila. However, other less prevalent species such as Aeromonas trota, are also described from clinical samples. Based on its low incidence, the latter species can be regarded as rare and it is the only Aeromonas species susceptible to ampicillin. From the taxonomic point of view, A. trota is considered a synonym of the species Aeromonas enteropelogenes. The objective of this study is to present a new clinical case associated with A. trota in order to increase the knowledge about this species. The strain was recovered from the feces of a 69-year-old patient with a diarrheal syndrome and peritoneal psammocarcinoma. The preliminary identification as Aeromonas sp. was obtained with the API 20E, but it was characterized as Aeromonas jandei and also as Aeromonas enteropelogenes with different scores with the matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Based on the sequence of the rpoD gene, it was confirmed to be A. trota. The antimicrobial resistance pattern showed that the strain was susceptible to ampicillin, penicillins in combination with beta-lactamase inhibitors, quinolones, carbapenems, aminoglycosides and cephalosporins, except cephalothin. In conclusion, the recognition of an Aeromonas strain susceptible to ampicillin should alert the clinical microbiologist of the possible involvement of this rare species. Furthermore, the MALDI-TOF database should be updated indicating that the species A. enteropelogenes, is a synonym of A. trota.

Polyphasic identification of three new species in Alternaria section Infectoriae causing human cutaneous infection.

BACKGROUND: Cutaneous phaeohyphomycosis is an emerging disease in immunocompromised patients, being Alternaria one of the most common genera reported as a causative agent. Species identification is not carried out mainly due to the complexity of the genus. Analysis of the ITS barcode has become standard for fungal identification, but in Alternaria it is only able to discriminate among species-groups or sections. METHODS: We present three cases of cutaneous infection caused by Alternaria isolates morphologically identified as belonging to section Infectoriae. They have been morphologically characterised and phylogenetically delineated with five molecular markers (ITS, ATPase, gapdh, rpb2 and tef1). RESULTS: Mycotic infections have been diagnosed by repeated cultures and histopathological examination in two of the cases. The polyphasic approach has allowed to delineate three new species of Alternaria section Infectoriae, that is A anthropophila, A atrobrunnea and A guarroi. ATPase has been the only locus able to discriminate most of the species (29 out of 31) currently sequenced in this section, including A infectoria the commonest reported species causing alternariosis. Susceptibility test showed different antifungal patterns for the three species, although terbinafine was the most active in vitro drug against these fungi. CONCLUSIONS: The ATPase gene is recommended as an alternative barcode locus to identify Alternaria clinical isolates in section Infectoriae. Our results reinforce the relevance of identification of Alternaria isolates at the species level and the necessity to carry out antifungal susceptibility testing to determine the most adequate drug for treatment.

Fungal Olecranon Bursitis in an Immunocompetent Patient by Knoxdaviesia dimorphospora sp. nov.: Case Report and Review.

Bursitis is a common medical condition that can occur either with or without infection. We present a case of fungal olecranon bursitis in an immunocompetent individual caused by the new species Knoxdaviesia dimorphospora. It is a dematiaceous filamentous fungus characterized by the production of two different conidia: hyaline and cylindrical, which rise up from phialidic conidiogenous cells located in the upper part of differentiated and unbranched conidiophores, and pale brown and ellipsoidal conidia produced by phialidic conidiogenous cells which are born directly on hyphae. In addition to its morphological peculiarities, the novelty of the fungus was confirmed by sequence analysis of the internal transcribed spacer (ITS) regions and D1/D2 domains of the 28S of the nuclear rRNA gene. The fungal infection was confirmed by cytological examination and repeated cultures. The infection was resolved by surgical debridement and drainage, and the patient presented a complete functional recovery 3 months later. The in vitro antifungal susceptibility to this new human opportunist is provided, terbinafine being the drug with the most potent activity.

Antimicrobial susceptibility, virulence potential and sequence types associated with Arcobacter strains recovered from human faeces.

PURPOSE: The genus Arcobacter includes bacteria that are considered emergent pathogens because they can produce infections in humans and animals. The most common symptoms are bloody and non-bloody persistent diarrhea but cases with abdominal cramps without diarrhea or asymptomatic cases have also been described as well as cases with bacteremia. The objective was to characterize Arcobacter clinical strains isolated from the faeces of patients from three Spanish hospitals. METHODOLOGY: We have characterized 28 clinical strains (27 of A. butzleri and one of A. cryaerophilus) isolated from faeces, analysing their epidemiological relationship using the multilocus sequence typing (MLST) approach and screening them for their antibiotic susceptibility and for the presence of virulence genes.Results/Key findings. Typing results showed that only one of the 28 identified sequence types (i.e. ST 2) was already present in the MLST database. The other 27 STs constituted new records because they included new alleles for five of the seven genes or new combinations of known alleles of the seven genes. All strains were positive for the ciaB virulence gene and sensitive to tetracycline. However, 7.4 % of the A. butzleri and A. cryaerophilus strains showed resistance to ciprofloxacin. CONCLUSION: The fact that epidemiological unrelated strains show the same ST indicates that other techniques with higher resolution should be developed to effectively recognize the infection source. Resistance to ciprofloxacin, one of the antibiotics recommended for the treatment of Arcobacter intestinal infections, demonstrated in 10.7 % of the strains, indicates the importance of selecting the most appropriate effective treatment.

Expert Study: Utility of an Automated Bolus Advisor System in Patients with Type 1 Diabetes Treated with Multiple Daily Injections of Insulin-A Crossover Study.

OBJECTIVE: This study was designed to assess the impact of the use of an automated bolus advisor (ABA) on glycemic control, quality of life, and satisfaction in adult patients with type 1 diabetes mellitus treated with multiple daily injections of insulin. MATERIALS AND METHODS: A crossover, prospective, randomized, controlled, multicenter study of 36 weeks duration was conducted. Patients were randomized to start in either control phase (CP) using a traditional blood glucose meter to calculate insulin doses (Accu-Chek(®) Aviva Nano; Roche Diagnostics, Indianapolis, IN) or intervention phase (IP) using an ABA meter (Accu-Chek Aviva Expert; Roche Diagnostics) and switched to the other phase after a washout period. Each phase was 12 weeks in duration. RESULTS: Significant glycated hemoglobin (HbA1c) reduction was observed in both phases (CP, initial HbA1c of 8.05 ± 0.7%, final HbA1c of 7.59 ± 0.7% [P < 0.001]; IP, initial HbA1c of 8.13 ± 1%, final HbA1c of 7.61 ± 0.8% [P < 0.001]). Although the trend was to a higher HbA1c reduction in IP, no statistically significant differences were observed between phases (CP, HbA1c -0.39%; IP, HbA1c -0.52% [P = 0.8]). During IP, the number of daily glucose measurements was greater (4.28 ± 1.2 vs. 4.01 ± 1.1 [P < 0.006]), the rate of postprandial hypoglycemia was lower, and an improvement in quality of life and higher satisfaction were observed. CONCLUSIONS: In this first crossover study comparing the use of an ABA with the standard usual care, the use of an ABA was effective and well accepted. Furthermore, reduction in hypoglycemic events, improvement in adherence and quality of life, and higher treatment satisfaction were observed.

A preliminary study of paraoxonase-1 in infected patients with an indwelling central venous catheter.

OBJECTIVES: Identification of biochemical markers to diagnose bloodstream infections in patients with a central venous catheter (CVC) inserted is an active research pursuit. Paraoxonase-1 (PON1) is an enzyme participating in the innate immune system protecting against toxic substances and infectious agents. We investigated the relationships between serum PON1 alterations and the characteristics of infection in a group of patients with a CVC implant. METHODS: Patients (n=114) who had had an inserted CVC removed because of infection or because the usefulness was at an end, and 407 healthy volunteers were recruited. In all participants we measured serum PON1 lactonase and paraoxonase activities, PON1 concentration and genetic polymorphisms, together with levels of the chemokine (C-C motif) ligand 2 (CCL2), procalcitonin and C-reactive protein (CRP). RESULTS: Patients with an acute concomitant infection (ACI) had higher CCL2, CRP and procalcitonin concentrations than the control group, together with lower paraoxonase and lactonase activities and specific activities. The areas under the curve of the receiver operating characteristic plots for paraoxonase and lactonase specific activities in the discrimination between patients with or without and ACI were 0.81 (0.73-0.89) and 0.81 (0.71-0.89), respectively, indicating the high diagnostic accuracy of these parameters. CONCLUSION: This preliminary study suggests that the measurement of PON1 may be useful as a tool for the diagnosis of ACI in patients with an indwelling CVC.

Paraoxonases as potential antibiofilm agents: their relationship with quorum-sensing signals in Gram-negative bacteria.

The property of many bacteria to form biofilms constitutes a major health problem. Bacteria living in biofilms have a very high resistance to antibiotics. Biofilms may develop at a certain locations with the participation of secreted molecules, termed quorum-sensing signals, when a sufficient density of bacterial growth occurs. In Gram-negative bacteria, acyl homoserine lactones (AHL) have been identified as major quorum-sensing signals. The paraoxonases (PONs) constitute a family of enzymes comprising 3 members (PON1, PON2, and PON3) that have lactonase activity and are able to hydrolyze AHL. In this minireview, we summarize some existing basic knowledge on PON genetics, biochemistry, and function and describe recent research that reports evidence of the important roles that they may play in the organism's defense against biofilm formation. Finally, we propose some lines of future research that could be very productive.

In vitro and in vivo antifungal susceptibilities of the Mucoralean fungus Cunninghamella.

We have determined the in vitro activities of amphotericin B (AMB), voriconazole, posaconazole (PSC), itraconazole (ITC), ravuconazole, terbinafine, and caspofungin against five strains of Cunninghamella bertholletiae and four of Cunninghamella echinulata. The best activity was shown by terbinafine against both species (MIC range = 0.3 to 0.6 µg/ml) and PSC against Cunninghamella bertholletiae (MIC = 0.5 µg/ml). We have also evaluated the efficacies of PSC, ITC, and AMB in neutropenic and diabetic murine models of disseminated infection by Cunninghamella bertholletiae. PSC at 40, 60, or 80 mg/kg of body weight/day was as effective as AMB at 0.8 mg/kg/day in prolonging survival and reducing the fungal tissue burden in neutropenic mice. PSC at 80 mg/kg/day was more effective than AMB at 0.8 mg/kg/day in reducing the fungal load in brain and lung of diabetic mice. Histological studies revealed an absence of fungal elements in organs of mice treated with either AMB at 0.8 mg/kg/day or PSC at 60 or 80 mg/kg/day in both models. ITC showed limited efficacy in both models. PSC could be a therapeutic option for the treatment of systemic infections caused by Cunninghamella bertholletiae.

Antifungal therapy in a murine model of disseminated infection by Cryptococcus gattii.

We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.

Evaluation of the Neo-Sensitabs diffusion method for determining the antifungal susceptibilities of Cryptococcus gattii isolates, using three different agar media.

The Neo-Sensitabs diffusion method was evaluated for determining the antifungal susceptibilities of 30 Cryptococcus gattii isolates to amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC) and voriconazole (VRC). Three different culture media, Müeller-Hinton (MH), RPMI 1640 (RPMI) and Antibiotic medium 3 (AM3), all supplemented with 2% of glucose and 0.5 microg/ml of methylene blue, were tested. The tests were repeated three times on different days at three incubation times (48, 72 and 96 h). Results were compared with those obtained with the CLSI M27-A2 broth microdilution method. The degree of reproducibility of the diffusion test was 100% for VRC and ITC, 98.3-100% for AMB and 43.3-73.3% for FLC. The best reproducibility was observed at 48 h of incubation and no important differences among media were observed at any of the incubation times assayed. Between Neo-Sensitabs and the reference method, VRC showed the best agreement and ITC the worst in all conditions tested (100% and 56.7%, respectively). AMB showed a high agreement between the two methods (93.3% to 96.7%) but Neo-Sensitabs assay failed to detect resistant isolates (discrepancy classified as "very major error") in all times of incubation assayed. Only agreement between both methods for FLC was clearly affected by incubation time and media used, the best results being achieved at 48 h of incubation when MH and RPMI (80.0%, in both media) were used.

Use of random amplified microsatellites to type isolates from an outbreak of nosocomial aspergillosis in a general medical ward.

Numerous patients were diagnosed with aspergillosis in a nosocomial outbreak caused by Aspergillus fumigatus and Aspergillus flavus. Thirty-three isolates of the former and 28 isolates of the latter were collected from the hospital environment and from the patients and studied for genetic relatedness by random amplified microsatellites (RAMS) analysis, in which two polymorphic regions were tested. Twenty-eight genotypes of A. fumigatus and 23 genotypes of A. flavus were identified. Four patients were infected by two isolates with the same genotype as the environmental isolates. One clinical genotype was shared by three patients and another was shared by two patients. We found that RAMS was useful for fingerprinting Aspergillus spp.