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Background Diabetic patients with acute coronary syndromes (ACS) might benefit from tight glycemic control by means of insulin infusion. Nurse-implemented insulin infusion protocols (IIP) are available but none validated in patients with ACS admitted to a coronary care unit (CCU). Aims To assess feasibility, effectiveness and safety of a new nurse-managed IIP (Desio Diabetes Diagram, DDD) for intensive glucose control in patients with suspected ACS and known diabetes or blood glucose (BG) > 200 mg/dL. Methods and results To reach and maintain a target BG level of 100-139 mg/dL we adopted a nomogram based on the percent changes in the insulin infusion rate according to the current BG value and the percent change from previous BG level. Ninety-one consecutive patients (53 men, mean age 69.7 ± 11.2 years) were treated with DDD IIP. Baseline BG was 202.2 ± 86.8 mg/dL. The median time to achieve the target was 3 h (Q1-Q3 2-5 h). Afterwards target BG levels were maintained for 70.4 ± 15.9% of the time. During 5004 h of insulin infusion BG never fell below 40 mg/dL. Conclusions The nurse-managed DDD IIP was easily implemented in our CCU and permitted strict and safe glycemic control in hyperglycemic patients with ACS. [ABSTRACT FROM AUTHOR]

Rationale: Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive.Objectives: To prospectively determine the morphotype, immunophenotype, and cystic fibrosis transmembrane conductance regulator genotype in a large cohort with PNTM.Methods: We prospectively enrolled 63 patients with PNTM infection, each of whom had computerized tomography, echocardiogram, pulmonary function, and flow cytometry of peripheral blood. In vitro cytokine production in response to mitogen, LPS, and cytokines was performed. Anthropometric measurements were compared with National Health and Nutrition Examination Survey (NHANES) age- and ethnicity-matched female control subjects extracted from the NHANES 2001-2002 dataset.Measurements and Main Results: Patients were 59.9 (+/-9.8 yr [SD]) old, and 5.4 (+/-7.9 yr) from diagnosis to enrollment. Patients were 95% female, 91% white, and 68% lifetime nonsmokers. A total of 46 were infected with Mycobacterium avium complex, M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 vs. 161.0 cm; P < 0.001) and thinner (body mass index, 21.1 vs. 28.2; P < 0.001) than matched NHANES control subjects, and thinner (body mass index, 21.1 vs. 26.8; P = 0.002) than patients with disseminated nontuberculous mycobacterial infection. A total of 51% of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to that of healthy control subjects, including the IFN-gamma/IL-12 pathway. CD4(+), CD8(+), B, and natural killer cell numbers were normal. A total of 36% of patients had mutations in the cystic fibrosis transmembrane conductance regulator gene.Conclusions: Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects. [ABSTRACT FROM AUTHOR]

Mycolicibacterium hassiacum (homotypic synonym: Mycobacterium hassiacum ) represents an ungrouped thermotolerant rapidly growing mycobacteria (RGM) species occasionally associated with infections and disease in humans. In this report, we describe a case of pyogranulomatous dermatitis and panniculitis due to M. hassiacum in an immunocompetent adult cat. To the best of our knowledge, this represents the first report of M. hassiacum infection in animals. We also report the results of the in-depth genome characterization of the isolate using a combined short- and long-read whole-genome sequencing (WGS) approach. We observed the lack of acquired-resistance genes and no evidence of mutations in housekeeping genes associated with resistance to rifampicin and isoniazid. We detected some virulence factors in our isolate, such as some associated with the interaction of mycobacteria with host cells, and the presence of multiple copies of heavy metal resistance genes ( ars B, ars R, and ars L/ cad L). In conclusion, M. hassiacum should be included among the RGM species associated with feline subcutaneous atypical mycobacteriosis (SAM). A reliable and fast RGM laboratory identification and characterization is important not only for an accurate etiological diagnosis but also for a correct approach to SAM treatment options.

Tuberculosis (TB) affects humans and other animals, and it is caused by bacteria within the Mycobacterium tuberculosis complex (MTBC). In this study, we report the characterisation of Mycobacterium pinnipedii that caused a TB case in a sea lion ( Otaria flavescens ) kept in an Italian zoo. The animal died due to severe, progressive disorders involving the respiratory and gastro-enteric systems and the skin. At necropsy, typical gross lesions referable to a TB generalised form were found. In particular, nodular granulomatous lesions were detected in the lungs and several lymph nodes, and colonies referable to Mycobacterium spp. were isolated from lung, mesenteric, and mediastinal lymph nodes. The isolate was identified by PCR as a MTBC, had a spoligotype SB 1480 ("seal lineage"), and was characterised and characterised by whole-genome sequencing analysis confirming that the MTBC involved was M. pinnipedii . The analysis of the resistome and virulome indicated the presence of macrolide and aminoglycoside resistance genes intrinsic in M. tuberculosis [ erm-37 and aac (2')-Ic] and confirmed the presence of the region of difference 1 (RD1), harbouring the esx A and esx B virulence genes, differently from its closest taxon, M. microti . As for other MTCB members, M. pinnipedii infection can spill over into non-pinniped mammalian species; therefore, zoological gardens, veterinary practitioners, and public health officers should be aware of the hazard posed by tuberculosis from marine mammals. Since the isolate under study, as well as all available genomes of M. pinnipedii investigated in this study retains almost all the M. tuberculosis virulence genes, it could indeed cause infection, lesions, and disease in other animal species, including humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Alba, Caprioli, Cocumelli, Eleni, Diaconu, Donati, Ianzano, Sorbara, Stravino, Cerini, Boniotti, Zanoni, Franco and Battisti.)

Purpose: To investigate changes in the corneal volume, corneal densitometry and pachymetry of young myopes wearing over-night orthokeratology (OK) contact lenses., Methods: The medical records of 28 right eyes of young myopes wearing OK between 2013 and 2018 were reviewed retrospectively. The baseline refractive error, best corrected visual acuities at baseline and uncorrected visual acuity at the most recent visit were recorded. Corneal volume of the central 10 mm cornea; densitometry at central, nasal and temporal cornea; and pachymetry along the horizontal and vertical meridians were collected from the Pentacam® HR at baseline, after one night of lens wear, and at the latest visit., Results: The mean age of subjects was 12.03 ± 3.80 years at the time of OK lens fitting and wore OK overnight for a mean duration of 666 days (range 206-1736 days). The baseline spherical equivalent refractive error was -3.03 ± 1.56 D (range -1.00 to -6.00 D). The corneal volume increased significantly after OK wear (p = 0.001). Corneal densitometry increased after OK wear, but the change did not reach statistical significance (p = 0.113). Pachymetry in the central cornea did not change significantly across all visits (p > 0.05) but increased significantly in the mid-peripheral regions of the cornea. Baseline refractive error was not found to be correlated with the changes in corneal volume, corneal densitometry, or pachymetry., Conclusion: The increase in corneal volume and densitometry and no significant change in the central corneal thickness may indicate the presence of corneal oedema from long-term OK wear. The baseline refraction was not correlated with the changes in corneal volume, densitometry or pachymetry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

The increasing prevalence of pESI(like)-positive, multidrug-resistant (MDR) S. Infantis in Europe is a cause of major concern. As previously demonstrated, the pESI(like) megaplasmid is not only a carrier of antimicrobial resistant (AMR) genes (at least tet, dfr, and sul genes), but also harbours several virulence and fitness genes, and toxin/antitoxin systems that enhance its persistence in the S. Infantis host. In this study, five prototype pESI(like) plasmids, of either CTX-M-1 or CTX-M-65 ESBL-producing strains, were long-read sequenced using Oxford Nanopore Technology (ONT), and their complete sequences were resolved. Comparison of the structure and gene content of the five sequenced plasmids, and further comparison with previously published pESI(like) sequences, indicated that although the sequence of such pESI(like) 'mosaic' plasmids remains almost identical, their structures appear different and composed of regions inserted or transposed after different events. The results obtained in this study are essential to better understand the plasticity and the evolution of the pESI(like) megaplasmid, and therefore to better address risk management options and policy decisions to fight against AMR and MDR in Salmonella and other food-borne pathogens. Graphical representation of the pESI-like plasmid complete sequence (ID 12037823/11). Block colours indicate the function of the genes: red: repB gene; pink: class I integrons (IntI); yellow; mobile elements; blue: resistance genes; green: toxin/anti-toxin systems; grey: mer operon; light green: genes involve in conjugation., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Carbapenemase-producing Enterobacterales (CPE) are considered a major public health issue. In the frame of the EU Harmonized AMR Monitoring program conducted in Italy in 2021, 21 epidemiological units of fattening pigs (6.98%; 95% CI 4.37-10.47%; 21/301) and four epidemiological units of bovines <12 months (1.29%; 95% CI 0.35-3.27%, 4/310) resulted positive to OXA-48-like-producing E. coli ( n  = 24 OXA-181, n  = 1 OXA-48). Whole Genome Sequencing (WGS) for in-depth characterization, genomics and cluster analysis of OXA-181-(and one OXA-48) producing E. coli isolated, was performed. Tracing-back activities at: (a) the fattening holding of origin of one positive slaughter batch, (b) the breeding holding, and (c) one epidemiologically related dairy cattle holding, allowed detection of OXA-48-like-producing E. coli in different units and comparison of further human isolates from fecal samples of farm workers. The OXA-181-producing isolates were multidrug resistant (MDR), belonged to different Sequence Types (STs), harbored the IncX and IncF plasmid replicons and multiple virulence genes. Bioinformatics analysis of combined Oxford Nanopore Technologies (ONT) long reads and Illumina short reads identified bla OXA-181 as part of a transposon in IncX1, IncX3, and IncFII fully resolved plasmids from 16 selected E. coli, mostly belonging to ST5229, isolated during the survey at slaughter and tracing-back activities. Although human source could be the most likely cause for the introduction of the bla OXA-181 -carrying IncX1 plasmid in the breeding holding, concerns arise from carbapenemase OXA-48-like-producing E. coli spreading in 2021 in Italian fattening pigs and, to a lesser extent, in veal calf holdings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carfora, Diaconu, Ianzano, Di Matteo, Amoruso, Dell'Aira, Sorbara, Bottoni, Guarneri, Campana, Franco, Alba and Battisti.)

Purpose: To evaluate the agreement of central corneal thickness (CCT) measurement between Scheimpflug imaging and ultrasound (U/S) pachymetry in keratoconic eyes, and investigate factors that affect the agreement., Methods: This post hoc analysis within a prospective, observational non-randomised study preformed at the Kensington Eye Institute, Toronto, Ontario, Canada, included crosslinking candidates with progressive keratoconus (KC). Main outcome measures were the agreement of CCT measurement between Scheimpflug imaging (Pentacam Oculus, Wetzlar, Germany) and U/S pachymetry (PachPen 24-5100, Accutome Inc., Malvern, Pennsylvania, USA), and factors that affect the agreement., Results: A total of 794 keratoconic eyes of 456 subjects with a mean age of 27.6±8.0 years (69.7% males and 49.6% right eyes) were included. Agreement between devices was moderate (intraclass correlation coefficient: 74.9%, Bland-Altman limits of agreement: -48.5 μm to +62.5 μm). In a multivariable analysis, cone decentration (p<0.001, coefficient +10.13 [+6.73 to +13.53 95% CIs]) and Kmax (p<0.001, coefficient +0.68 [+0.46 to +0.90 95% CIs]) were significantly associated (both clinically and statistically) with the level of agreement between the devices; the discrepancy in CCT between the devices increased on average by 10.13 μm for every mm of cone decentration, and by 6.8 μm for every 10D of Kmax. Age, corneal astigmatism and spherical equivalent were statistically but not clinically significant factors affecting agreement., Conclusion: The agreement of CCT measurement between Scheimpflug imaging and U/S pachymetry in KC was moderate. To ensure the safety of crosslinking in keratoconic corneas, Scheimpflug and U/S CCT measurements should not be used interchangeably, especially in steep corneas and corneas with decentred cones., Competing Interests: Competing interests: MM is a paid consultant for Eye Yon Medical and Lapidot Medical. CC has received support from Alcon Laboratories Inc, Allergan, Bausch & Lomb, Santen, Shire, Tearlab, Labtician Thea, and Johnson & Johnson. AS has been a paid consultant for Abbott Medical Optics, AbbVie, Alcon Laboratories Inc, Allergan, Bausch & Lomb, Santen Inc, Shire, Acqueous, and Labtician Thea. DR has received support from Alcon Laboratories Inc and Johnson & Johnson. TR has been a paid consultant for Alcon Laboratories Inc, Johnson & Johnson, and AbbVie., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the development and report psychometric properties of the Contact Lens Risk Survey (CLRS) to identify patients at risk for soft contact lens-related complications., Methods: Psychometric properties of the CLRS, a web-based survey with branching logic, were determined using data from 5 multi-site fieldings (n = 1059), including re-fielding to sub groups. Responses from participants with and without an active red eye were used to identify risk factors of a red eye event and calculate an overall risk score. A 6th fielding of the CLRS (n = 171) was used to assess discriminate validity., Results: Participants needed 11-12 min to complete the survey with a negligible difference by age. Internal consistency was excellent (Cronbach's α ≥ 0.70) for 3 of the 5 constructs identified by factor analysis. Twelve of the 17 survey items exhibited excellent within-subject repeatability (Kappa ≥ 0.61). Between-subject agreement, assessed in 18-25 year olds, was high for the majority of items, suggesting good generalizability across different populations of SCL wearers. The ability of the model using individual items of the CLRS to discriminate Controls and participants with a red eye was good with an area under the curve of 0.779., Conclusion: The CLRS tool is a repeatable and valid instrument to standardize documentation of demographic, behavior, and exposure factors which appear to drive the greatest risk of a contact lens related red eye event., (Copyright © 2020 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Significance: Cytokine and protease analysis revealed relative changes in the post-lens tear film of scleral lenses with low and high limbal clearances. Results from this study indicate that midperipheral lens fit is an important fitting feature that can impact the inflammatory response of a keratoconic eye., Purpose: The purpose of this study was to investigate changes in levels of inflammatory mediators in the post-lens tear film of keratoconic scleral lens wearers with varying limbal clearance designs., Methods: Twenty-two keratoconic eyes were fitted with two sets of scleral lenses that were consistent in lens diameter and central sagittal depth but varied in limbal clearance by approximately 50 μm. Lenses were worn in a randomly assigned order for a 2-week period each. At each follow-up visit, immediately after lens removal, tear samples were collected with a microcapillary tube (10 μL, 0.5 mm in diameter) from the bowl of the inverted scleral lens. Tear cytokine and protease analysis was performed using a multiplex electrochemiluminescent array (Meso Scale Discovery, Rockville, MD) instrument. Levels of interleukins 1, 6, and 8; tumor necrosis factor α; and matrix metalloproteinases 1 and 9 were compared and analyzed., Results: Levels of interleukin 1β, tumor necrosis factor α, and matrix metalloproteinase 1 increased with high limbal clearance (P = .01, .006, and .02, respectively). No change in interleukins 6 and 8 levels was found (P > .05). A decrease in matrix metalloproteinase 9 was noted in post-lens tear film of scleral lenses with high limbal clearance (P = .10)., Discussion: Relative changes in the cytokine and protease levels were found when comparing low and high limbal clearance, indicating that the midperipheral lens fit is an important feature that can impact the inflammatory response of the keratoconic eye., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Purpose: To test the Contact Lens Assessment in Youth Contact Lens Risk Survey (CLRS) scoring algorithm in soft contact lens (SCL) wearers presenting with SCL-related adverse events and healthy matched controls., Methods: This prospective case-control study compared CLRS responses in SCL wearers presenting with symptomatic red eyes (Cases) with age-, sex- and site-matched healthy SCL wearers (Controls) at six locations across North America. Responses to individual questions from Cases and Controls were analyzed using either the Pearson, Mantel-Haenszel chi-square, or Fisher's exact test. Differences in the CLRS scores were compared using t-tests., Results: A total of 171 SCL wearers were enrolled (n = 57 Cases, 114 Controls). Cases were adjudicated to consensus and classified as contact lens-related serious and significant (S&S) or non-serious events. S&S Cases scored significantly higher on the CLRS (56.1 ± 11.1) than either their matched Controls (44.3 ± 11.1) (P <  0.001) or the non-Serious Cases (44.8± 12.8 P =  0.002). Scores of non-serious Cases were not significantly different than scores of their Controls (43.4 ± 10.7, P = 0.33) CONCLUSIONS: The CLRS scoring algorithm discriminated between SCL wearers presenting with S&S CL-related adverse events from healthy SCL wearers and those with non-serious events. This survey and scoring system could help practitioners identify patients at greatest risk for CL-related adverse events and support targeted interventions aimed at reducing risk behaviors., (Copyright © 2020 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to characterize the central epithelial thickness (CET) of penetrating keratoplasty corneal specimens obtained from patients with keratoconus (KC) and correlate the histological patterns with their clinical history., Methods: Ex vivo histological imaging was performed to measure CET and total corneal thickness (TCT) in 56 patients with KC. Microscopic slides from penetrating keratoplasty corneal specimens, stained with hematoxylin and eosin were evaluated using bright field microscopy. CET and TCT were measured, and morphological features were studied. Clinical history regarding duration of KC prior to surgery and length of and tolerance to contact lens wear were compared and analyzed., Results: The microscopic slides of all patients available for follow up (n=48) were analyzed and CET and TCT were measured. The histological evaluation revealed 3 distinctive epithelial patterns. Pattern 1 with central hypertrophic and hydropic changes (n=19) measured 70.89±25.88μm in CET and 308.63±100.74μm in TCT; Pattern 2 (n=14) had not changed, similar to normal epithelium CET and TCT measuring 36.5±7.02μm and 260.14±87.93μm respectively. Pattern 3 (n=15) demonstrated thinner central epithelium characterized by atrophy and focal hydropic changes measuring 19.93±4.60μm and 268.00±79.39μm in CET and TCT respectively (all p<0.0001). The presence of Pattern 2 characterized by similar to normal CET was correlated with the duration of the condition (R=0.600, p=0.030). There was a significant difference in the length of CL wear comparing those with patterns 1 and 2 versus 3 (least no. of CL years) (p=0.05 and p=0.33 respectivelly)., Conclusions: Patients with advanced disease have various central corneal epithelial changes detected with histology. Although each central epithelial pattern type was distinctive comparing the 3 patterns, there was no correlation with years of CL wear but only with the duration of the condition., (Copyright © 2020 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)