Is topical antibiotic use necessary to prevent surgical site infection following oculoplastic surgery?

PURPOSE: To assess whether oculoplastic surgeries can be performed without any topical and systemic antibiotics, in a "100% antibiotic free" fashion. METHOD: We conducted a multicenter retrospective study between November 2017 and December 2022. Patients who underwent an oculoplastic procedure were screened. Patients who received preoperative or postoperative systemic antibiotics were excluded. Intraoperative IV antibiotics were allowed. Patients were divided into two groups: those who were treated with local antibiotics ointments (LATB group) and those who were treated without local antibiotics ointments (LATB free group) postoperatively. The primary outcome was the incidence of surgical site infections (SSI). The relationship between the use of local antibiotics and the occurrence of SSI was assessed using Fisher's exact test. The alpha risk was set to 5% and two-tailed tests were used. RESULTS: Among the 947 procedures included, 617 were included in the LATB group and 330 in the LATB free group. 853 and 80 procedures were classified Altemeier class 1 (clean) and class 2 (clean-contaminated) surgeries, respectively. Overall, 310 (32.73%) procedures were performed without any systemic nor topical antibiotics (100% antibiotic free fashion). SSI occured in four (4/617; 0.65%) and five (5/330; 1.52%) procedures in the LATB and LATB free group respectively, without any statistical difference between the groups (p = 0.290). A subgroup analysis was carried out by excluding the procedures performed under prophylactic intraoperative intravenous antibiotics and did not reveal any statistical difference between the two groups (p = 0.144). All SSI patients were treated with systemic antibiotics with favorable outcomes. Postoperative wound dehiscence was the only risk factor associated with postoperative SSI (p = 0.002). CONCLUSION: This study suggests that performing a "100% antibiotic free" oculoplastic surgery without systemic and topical antibiotics is reasonable in Altemeier class 1 and class 2 procedures.

Acute Pyelonephritis with Bacteremia in an 89-Year-Old Woman Caused by Two Slow-Growing Bacteria: Aerococcus urinae and Actinotignum schaalii.

Aerococcus urinae is an aerobic Gram-positive coccus that grows as tiny alpha-hemolytic colonies. Actinotignum schaalii is a slow-growing facultative anaerobic Gram-positive rod. These bacteria are part of the urogenital microbiota of healthy patients, but can also be involved in urinary tract infections (UTIs), particularly in elderly men and young children. Because A. urinae and A. schaalii are fastidious and are difficult to identify with phenotypic methods, they are underestimated causes of UTIs. Their growth is slow and requires a blood-enriched medium incubated under an anaerobic or 5% CO2 atmosphere for 48 h and from 24 to 48 h for A. schaalii and A. urinae, respectively. Furthermore, accurate identification is only possible using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or molecular-based methods. In rare cases, these bacteria can be responsible for invasive infections. We describe, here, an unusual case of bacteremic UTI caused by both A. schaalii and A. urinae in an 89-year-old woman. She presented with dyspnea, and bacteriuria was noted. This challenging clinical and microbiological diagnosis was made in our laboratory by Gram staining urine with a leucocyte count >50/µL and/or a bacterial count >14/µL urinary culture on a blood agar plate. After 10 days of antimicrobial treatment consisting of 2 g amoxicillin PO t.i.d., the patient was discharged with a complete clinical and biological recovery. A. schaalii and A. urinae are probably still underestimated causes of UTIs. Microbiologists could consider the presence of these two bacteria using appropriate culture and identification methods in cases where a positive direct examination of urine reveals small Gram-positive rods or cocci, where undocumented UTIs are present in elderly patients, but also where a urinary dipstick is negative for nitrites and is associated with leukocyturia.

Lesson from the COVID-19 pandemic lockdown: A major change of hospital-diagnosed bacteremia epidemiology.

OBJECTIVES: When the COVID-19 pandemic reached France early in 2020, the enforced nationwide lockdown deeply altered lifestyle as well as hospital processes and modalities of care. The aim of the study was to evaluate the impact during the lockdown of the first epidemic wave on the epidemiology of bacteremia in one French University Hospital. PATIENTS AND METHODS: Retrospective cohort study including adult patients with positive blood culture between 23rd March to 24th May 2020. The clinical-microbiological characteristics were compared with those of the period from 25th March to 26th May 2019. The data were adjusted to the number of hospitalizations (h). RESULTS: In 2020, 189 bacteremia were diagnosed from 1939 vials (9658 hospitalizations, 10911 emergency room consultations) compared to 143 from 1976 vials (14797 hospitalizations, 16493 emergency room consultations) recorded in 2019. The incidence of bacteremia increased up to 19.7 per 1000h in 2020 vs 9.7 in 2019 (p < 0.001). The main differences (2020 vs 2019) were: Staphylococcus aureus bacteremia (2.4 vs 1.0/1000h, p = 0.012), polymicrobial bacteremia (2.2 vs 0.9/1000h p = 0.013) and Gram-negative bacteremia (8.9 vs 4.3/1000h, p < 0.01). Conversely, Streptococcus pneumoniae incidence decreased (0 vs 0.47/1000h, p = 0.047). The standardized incidence ratio calculation confirmed these results. CONCLUSION: The lockdown and the impact of the first wave of the Covid-19 pandemic on the health system resulted in increased hospital-diagnosed bacteremia and decreased pneumococcal bacteremia. Disruption and overload of ICUs, lockdown with preventive control measures, and decrease in human-to-human interaction may have been the main reasons.

24/7 workflow for bloodstream infection diagnostics in microbiology laboratories: the first step to improve clinical management.

OBJECTIVES: We aimed to evaluate the impact of an uninterrupted workflow regarding blood cultures on turnaround time and antibiotic prescription. METHODS: Monomicrobial episodes of bacteremia were retrospectively evaluated before and after a continuous 24/7 workflow was implemented in our clinical microbiology laboratory (pre- and post-intervention periods; PREIP and POSTIP). Primary outcome was the time from specimen collection to the first change in antibiotic therapy. Secondary outcomes included the time from specimen collection to effective antibiotic therapy and to antibiotic susceptibility testing results (or turnaround time), as well as hospital length of stay and all-cause mortality at 30 days. RESULTS: A total of 548 episodes of bacteremia were included in the final analysis. There was no difference in PREIP and POSTIP regarding patient characteristics and causative bacteria. In POSTIP, the mean time to the first change in antibiotic therapy was reduced by 10.4 h (p<0.001). The time to effective antibiotic therapy and the turnaround time were respectively reduced by 4.8 h (p<0.001) and 5.1 h (p=0.006) in POSTIP. There was no difference in mean hospital length of stay or mortality between the two groups. CONCLUSIONS: Around the clock processing of blood cultures allows for a reduction in turnaround time, which in turn reduces the delay until effective antibiotic therapy prescription.

Evaluation of an Antibiotic Susceptibility Testing Method on Enterobacterales-Positive Blood Cultures in Less Than 8 h Using the Rapid Mueller-Hinton Diffusion Method in Conjunction with the SIRscan 2000 Automatic Reading Device.

Enterobacterales bloodstream infections are life-threatening and require rapid, targeted antibiotherapy based on antibiotic susceptibility testing (AST). A new method using Muller-Hinton Rapid-SIR (MHR-SIR) agar (i2a, Montpellier, France) allows complete direct AST (dAST) to be read from positive blood culture bottles (BCBs) for all Enterobacterales species after 6-8 h of incubation. We evaluated (i) the performance of dAST from positive BCBs on MHR-SIR agar using two different inoculum protocols; (ii) the categorical agreement between dAST results obtained with MHR-SIR agar vs. those obtained with Muller-Hinton (MH) agar; and (iii) the ability of the MHR-SIR medium to detect ß-lactam resistant Enterobacterales. Finally, we estimated the saved turnaround time (TAT) with MHR-SIR compared with MH agar in our 24/7 laboratory. Our results showed that the most suitable inoculation protocol for dAST on MHR-SIR agar was 1 drop of BCB/5 mL H2O. For monomicrobial Enterobacterales BCBs, dAST performed on MHR-SIR medium showed 99.3% categorical agreement with AST on MH agar. Furthermore, MHR-SIR agar allows early detection of ß-lactam resistance mechanisms, including AmpC hyperproduction, extended-spectrum ß-lactamase, and carbapenemase. Finally, TAT reduction in our 24/7 laboratory was 16 h, enabling a significantly faster provision of antibiotic advice.

Spontaneous Bacterial Peritonitis: The Incremental Value of a Fast and Direct Bacterial Identification from Ascitic Fluids Inoculated in Blood Culture Bottles by MALDI-TOF MS for a Better Management of Patients.

Spontaneous bacterial peritonitis (SBP) is a severe infection that requires fast and accurate antibiotic therapy to improve the patient outcome. Direct bacterial identification using MALDI-TOF mass spectrometry from ascitic fluid inoculated in blood culture bottles (BCBs) could therefore improve patients' management. We evaluated the impact of the implementation of this method for the treatment of patients. Our identification protocol was performed on 136 positive BCBs collected from 61 patients between December 2018 and December 2020. The therapeutic impact of our protocol was evaluated using a before (2015-2016) and after (2019-2020) case-control study in two populations of 41 patients diagnosed with SBP and treated with antibiotics. The decrease in time to first identification and the optimization of antibiotic therapy following communication of the identification result were evaluated. Our protocol allowed us to identify 78% of bacteria in ascitic fluids. The transmission of the direct identification allowed the introduction or adaption of the antibiotic therapy early in 37% of SBP, with a mean decrease in time to first antibiotic change of 17 h. Our direct identification protocol for positive inoculated ascitic fluids is fast, reliable and inexpensive. Its routine integration into a microbiology laboratory allows the early introduction of appropriate antibiotic therapy and improves the management of patients with SBP.

Clindamycin Efficacy for Cutibacterium acnes Shoulder Device-Related Infections.

Clindamycin is an antibiotic with high bioavailability and appropriate bone diffusion, often proposed as an alternative in guidelines for C. acnes prosthetic joint infections. We aimed to evaluate the efficacy of clindamycin in the treatment of C. acnes shoulder implant joint infections (SIJI). METHODS: A retrospective analysis was conducted at the University Hospital of Nice (France) between 2010 and 2019. We included patients with one shoulder implant surgical procedure and at least one C. acnes positive sample. We selected the C. acnes SIJI according to French and international recommendations. The primary endpoint was favorable outcome of C. acnes SIJI treatment after at least 1-year follow-up in the clindamycin group compared to another therapeutic group. RESULTS: Forty-eight SIJI were identified and 33 were treated with clindamycin, among which 25 were treated with monotherapy. The median duration of clindamycin antibiotherapy was 6 weeks. The average follow-up was 45 months; one patient was lost to follow-up. Twenty-seven patients out of 33 (82%) were cured with clindamycin, compared to 9/12 (75%) with other antibiotics. The rate of favorable outcomes increased to 27/31 (87%) with clindamycin and to 9/10 (90%) for other antibiotics when no septic revision strategies were excluded (P = 1.00). CONCLUSIONS: The therapeutic strategy based on one- or two-stage revision associated with 6 weeks of clindamycin seems to be effective.

Bacillus cereus Invasive Infections in Preterm Neonates: an Up-to-Date Review of the Literature.

Bacillus cereus group species are widespread, Gram-positive, spore-forming environmental bacteria. B. cereus sensu stricto is one of the major causes of food poisoning worldwide. In high-risk individuals, such as preterm neonates, B. cereus infections can cause fatal infections. It is important to note that the phenotypic identification methods commonly used in clinical microbiology laboratories make no distinction between B. cereus sensu stricto and the other members of the group (Bacillus anthracis excluded). As a result, all the invasive infections attributed to B. cereus are not necessarily due to B. cereus sensu stricto but likely to other closely related species of the B. cereus group. Next-generation sequencing (NGS) should be used to characterize the whole genome of the strains belonging to the B. cereus group. This could confirm whether the strains involved in previously reported B. cereus invasive infections preferentially belong to formerly known or emerging individual species. Moreover, infections related to B. cereus group species have probably been overlooked, since their isolation in human bacteriological samples has for a long time been regarded as an environmental contaminant of the cultures. Recent studies have questioned the emergence or reemergence of B. cereus invasive infections in preterm infants. This review reports our current understanding of B. cereus infections in neonates, including taxonomical updates, microbiological characteristics, bacterial identification, clinical features, host-pathogen interactions, environmental sources of contamination, and antimicrobial resistance.

Complete Circular Genome Sequences of Three Bacillus cereus Group Strains Isolated from Positive Blood Cultures from Preterm and Immunocompromised Infants Hospitalized in France.

We report here the complete genome sequences of three Bacillus cereus group strains isolated from blood cultures from premature and immunocompromised infants hospitalized in intensive care units in three French hospitals. These complete genome sequences were obtained from a combination of Illumina HiSeq X Ten short reads and Oxford Nanopore MinION long reads.

Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review.

OBJECTIVES: Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition. METHODS: All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed. RESULTS: Seventeen patients were included. Bacteria were identified in 16 cases: Staphylococcus aureus (n = 10), including methicillin-resistant S. aureus (n = 1); and coagulase-negative staphylococci (n = 10), including methicillin-resistant Staphylococcus epidermidis (n = 4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0-476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%. CONCLUSION: Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity.

Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient's evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Nocardia takedensis: a newly recognized pathogen responsible for skin and soft tissue infections.

Nocardia takedensis was first isolated in 2005, from soil in Japan. We report here two cases of lymphangitis in France (2012-2017) caused by N. takedensis both occurring after skin injury while gardening, which enabled its inoculation. The two patients were immunocompromised and successfully treated by an antimicrobial agent active on the isolated strain, trimethoprim-sulfamethoxazole and amoxicillin-clavulanic acid for patient one and patient two, respectively. Our study along with previous ones supports the idea of a newly recognized cutaneous opportunistic pathogen and reinforces the recommendation of using gloves during soil exposure for immunocompromised patients. Lastly, according to data found in the literature, we would recommend trimethoprim-sulfamethoxazole as an efficient empirical antibiotic therapy in case of cutaneous infection caused by N. takedensis.

French national cohort of first use of dalbavancin: A high proportion of off-label use.

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.

Co-culture of Methanobrevibacter smithii with enterobacteria during urinary infection.

BACKGROUND: Urinary tract infections are known to be caused by bacteria, but the potential implications of archaea have never been studied in this context. METHODS: In two different university hospital centres we used specific laboratory methods for the detection and culture of archaeal methanogens in 383 urine specimens prospectively collected for diagnosing urinary tract infection (UTI). FINDINGS: Methanobrevibacter smithii was detected by quantitative PCR and sequencing in 34 (9%) of the specimens collected from 34 patients. Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Enterococcus faecium and mixed cultures were detected along with M. smithii in eighteen, six, three, one and six urine samples, respectively. Interestingly, using our specific culture method for methanogens, we also isolated M. smithii in 31 (91%) of the 34 PCR positive urine samples. Genotyping the 31 isolates using multispacer sequence typing revealed three different genotypes which have been previously reported in intestinal microbiota. Antibiotic susceptibility testing found the 31 isolates to be in vitro susceptible to metronidazole (MIC: 1 mg/L) but resistant to fosfomycin, sulfamethoxazole-trimethoprim, amoxicillin-clavulanate and ofloxacin, commonly used to treat bacterial UTI. Finally, 19 (54%) of the 34 patients in whose urine samples M. smithii was detected were diagnosed with UTIs, including cystitis, pyelonephritis and prostatitis. INTERPRETATION: Our results show that M. smithii is part of the urinary microbiota of some individuals and could play a role in community-acquired UTI in association with enteric bacteria. FUND: This study was supported by IHU Méditerranée Infection, Marseille, France.

Direct Identification of 80 Percent of Bacteria from Blood Culture Bottles by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Using a 10-Minute Extraction Protocol.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry is not widely used to identify bacteria directly from positive blood culture bottles (BCBs) because of overlong protocols. The objective of this work was to develop and evaluate a simple extraction protocol for reliable identification from BCBs. The 10-min protocol was applied over a 5-month period. Direct identifications on day 0 were compared with those obtained from colonies on day 1 [log(score) of ≥2]. We evaluated a range of seven log(score) thresholds on day 0 from 1.4 to 2.0 to find the lower confidence score that provides the higher percentage of direct identifications without loss of accuracy. With a log(score) threshold of ≥1.5 at day 0, our protocol allowed us to identify 80% of bacteria in 632 BCBs (96% of Enterobacteriaceae, 95% of Staphylococcus aureus, 92% of enterococci, and 62% of streptococci). At least one bacterial species of the mixture was identified in 77% of the polymicrobial samples. The rapidity and reliability of the protocol were factors in its adoption for routine use, allowing us to save up to 24 h in identifying 80% of the bacteria in the BCBs and, thus, to supply useful information to adapt antibiotic therapy when necessary. We currently provide reliable daily direct identifications of staphylococci, enterococci, Enterobacteriaceae, Pseudomonas aeruginosa, and beta-hemolytic streptococci.

Virulence Analysis of Bacillus cereus Isolated after Death of Preterm Neonates, Nice, France, 2013.

After the deaths of 2 preterm neonates with Bacillus cereus systemic infection in the same intensive care unit, we investigated the pathogenic potential of this bacterium. Genetic and virulence analysis indicated the neonates were infected with 2 different strains with a virulence potential similar to environmental strains, indicating likely patient immune response failure.

Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation.

The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation. In addition, several mutations located in the ankyrin domain displayed a dramatic reduction in Rac1 ubiquitylation associated with a decrease of colony formation in soft agar. 3D structure modelling of the 7 ankyrin-repeats coupled to functional analysis identified a surface epitope centered on one of the mutated residue, Gly-175, which is critical for controlling Rac1 binding and ubiquitylation. We also identified a role for the MID domain in conferring the specificity of association of HACE1 to the active form of Rac1. Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation.

First isolation of Clostridium indolis in a patient with chronic osteitis: a case report and literature review of human infections related to Clostridium saccharolyticum group species.

Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.

Epidemic spread of Pandoraea pulmonicola in a cystic fibrosis center.

BACKGROUND: Pandoraea spp. are recently discovered bacteria, mainly recovered from cystic fibrosis (CF) patients, but their epidemiology and clinical significance are not well known. We describe an epidemic spread of Pandoraea pulmonicola from 2009 in our CF center, involving 6 out of 243 CF patients. METHODS: Bacterial identification used amplified ribosomal DNA restriction analysis (ARDRA), MALDI-TOF mass spectrometry (MALDI-TOF MS) and 16S rDNA gene sequencing. The clonal link between strains was assessed with pulsed field gel electrophoresis (PFGE) using XbaI. Clinical data were gathered for all patients. RESULTS: The index case was chronically colonized since 2000. The main hypothesis for this bacterial spread was a droplet cross-transmission, due to preventive measures not being strictly followed. Antibiotic susceptibility testing revealed resistance to beta-lactams, ciprofloxacin and colistin. However, there was susceptibility to trimethoprim-sulfamethoxazole. All patients were chronically colonized with Pseudomonas aeruginosa, and the acquisition of P. pulmonicola resulted in chronic colonization in all patients. Three patients died, and two patients remained clinically stable, whereas one patient had a decline in lung function. CONCLUSIONS: This study, which is the first to describe an epidemic spread of P. pulmonicola, notes the potential transmissibility of this bacterial species and the need for infection control measures.

RNY-derived small RNAs as a signature of coronary artery disease.

BACKGROUND: Data from next generation sequencing technologies uncovered the existence of many classes of small RNAs. Recent studies reported that small RNAs are released by cells and can be detected in the blood. In this report, we aimed to discover the occurrence of novel circulating small RNAs in coronary artery disease (CAD). METHODS: We used high-throughput sequencing of small RNAs from human and mouse apoptotic primary macrophages, and analyzed the data by empirical Bayes moderated t-statistics to assess differential expression and the Benjamini and Hochberg method to control the false discovery rate. Results were then confirmed by Northern blot and RT-qPCR in foam cells and in two animal models for atherosclerosis, namely ApoE(-/-) and Ldlr(-/-) mouse lines. Quantitative RT-PCR to detect identified small RNAs, the RNY-derived small RNAs, was performed using sera of 263 patients with CAD compared to 514 matched healthy controls; the Student t-test was applied to statistically assess differences. Associations of small RNAs with clinical characteristics and biological markers were tested using Spearman's rank correlations, while multivariate logistic regressions were performed to test the statistical association of small RNA levels with CAD. RESULTS: Here, we report that, in macrophages stimulated with pro-apoptotic or pro-atherogenic stimuli, the Ro-associated non-coding RNAs, called RNYs or Y-RNAs, are processed into small RNAs (~24-34 nt) referred to as small-RNYs (s-RNYs), including s-RNY1-5p processed from RNY1. A significant upregulation of s-RNY expression was found in aortic arches and blood plasma from ApoE(-/-) and Ldlr(-/-) mice and in serum from CAD patients (P <0.001). Biostatistical analysis revealed a positive association of s-RNY1-5p with hs-CRP and ApoB levels; however, no statistical interaction was found between either of these two markers and s-RNY1-5p in relation to the CAD status. Levels of s-RNY1-5p were also independent from statin and fibrate therapies. CONCLUSION: Our results position the s-RNY1-5p as a relevant novel independent diagnostic biomarker for atherosclerosis-related diseases. Measurement of circulating s-RNY expression would be a valuable companion diagnostic to monitor foam cell apoptosis during atherosclerosis pathogenesis and to evaluate patient's responsiveness to future therapeutic strategies aiming to attenuate apoptosis in foam cells in advanced atherosclerotic lesions.