Comparative bioinformatic analysis and biochemical characterization of digestive proteinases from Pacific whiting (Merluccius productus).

The hake fishery plays a crucial role due to its significant economic impact. The genus Merluccius includes 12 extant species found along the coasts of the Americas, Europe, and Africa. However, research on their digestive physiology and the enzymes involved in digestion, including proteases, remains limited. Proteases play a key role in protein digestion, a vital process for all living organisms. This study focused on screening the genomes of eight Merluccius spp. for eight specific proteases previously identified in Merluccius polli. Additionally, the study conducted biochemical analyses of proteases found in the stomach and intestine of Pacific whiting fish (Merluccius productus), comparing the results with the genomic findings. The analysis revealed that proteases across Merluccius spp. are conserved, although with slight variations, particularly in chymotrypsin and aspartic proteases. Biochemical characterization of M. productus identified at least three main proteases in the stomach, active at acidic pH, and at least seven proteases in the intestine, active at alkaline pH, as determined by electrophoresis. Further investigation, including specific inhibition studies, determination of molecular mass, and assessment of pH and temperature preferences for catalysis, revealed that one of the stomach proteases functioning at acidic pH likely belongs to the acid peptidase class, likely pepsin. Similarly, analysis of proteases active at alkaline pH indicated the presence of a chymotrypsin and a trypsin, consistent with genomic findings in M. productus. These results are important as they provide insights into the digestive physiology of Merluccius spp., contributing to a better understanding of their nutritional needs.

European Society of Clinical Microbiology and Infectious Diseases/European Committee on infection control clinical guidelines on pre-operative decolonization and targeted prophylaxis in patients colonized by multidrug-resistant Gram-positive bacteria before surgery.

SCOPE: The aim of these guidelines is to provide recommendations for decolonization and perioperative antibiotic prophylaxis (PAP) in multidrug-resistant Gram-positive bacteria (MDR-GPB) adult carriers before inpatient surgery. METHODS: These European Society of Clinical Microbiology and Infectious Diseases/European Committee on Infection Control guidelines were developed following a systematic review of published studies targeting methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, methicillin-resistant coagulase-negative Staphylococci, and pan-drug-resistant-GPB. Critical outcomes were the occurrence of surgical site infections (SSIs) caused by the colonizing MDR-GPB and SSIs-attributable mortality. Important outcomes included the occurrence of SSIs caused by any pathogen, hospital-acquired infections, all-cause mortality, and adverse events associated with the interventions, including resistance development to the agents used and the incidence of Clostridioides difficile infections. The last search of all databases was performed on 1 November 2023. The level of evidence and the strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included. RECOMMENDATIONS: The guideline panel reviewed the impact of decolonization, targeted PAP, and combined interventions (e.g. decolonization and targeted PAP) on the risk of SSIs and other outcomes in MDR-GPB carriers, according to the type of bacteria and type of surgery. We recommend screening for S. aureus before high-risk operations, such as cardiothoracic and orthopaedic surgery. Decolonization with intranasal mupirocin with or without a chlorhexidine bath is recommended in patients colonized with S. aureus before cardiothoracic and orthopaedic surgery and suggested in other surgeries. The addition of vancomycin to standard prophylaxis is suggested for MRSA carriers in cardiothoracic surgery, orthopaedic surgery, and neurosurgery. Combined interventions (e.g. decolonization and targeted prophylaxis) are suggested for MRSA carriers undergoing cardiothoracic and orthopaedic surgery. No recommendation could be made regarding screening, decolonization and targeted prophylaxis for vancomycin-resistant enterococci because of the lack of data. No evidence was retrieved for methicillin-resistant coagulase-negative Staphylococci and pan-drug-resistant-GPB. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship and infection control teams are warranted before implementing screening procedures or performing changes in PAP policy. Future research should focus on novel decolonizing techniques, on the monitoring of resistance to decolonizing agents and PAP regimens, and on standardized combined interventions in high-quality studies.

Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

Is an isolated positive sonication fluid culture in revision arthroplasties clinically relevant?

OBJECTIVES: The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection during follow-up compared with controls with a negative SFC. METHODS: This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections. All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study. RESULTS: A total of 95 cases (positive SFC) and 201 controls (negative SFC) were included. Infection during follow-up occurred in 12 of 95 cases (12.6%) versus 14 of 201 controls (7.0%) (p = 0.125). In all, 79.8% of cases were with treated with antibiotics (76/95). Of the non-treated cases, 89% (17/19) had a positive SFC with a low virulent microorganism. When solely analysing patients who were not treated with antibiotics, 16% of the cases (3/19) had an infection during follow-up versus 5% of the controls (9/173) (p = 0.08). DISCUSSION: Although not statistically significant, infections were almost twice as frequent in patients with an isolated positive SFC. These findings require further exploration in larger trials and to conclude about the potential benefit of antibiotic treatment in these cases.

Efficacy and safety of different antimicrobial DURATions for the treatment of Infections associated with Osteosynthesis Material implanted after long bone fractures (DURATIOM): Protocol for a randomized, pragmatic trial.

BACKGROUND: Infection associated with osteosynthesis material (IOM) is one of the most feared and challenging complications of trauma surgery and can cause significant functional loss, requiring multiple interventions and excessive consumption of antimicrobials. Evidence is needed about the best surgical procedure and the duration of antibiotic treatment according to the age of the implant or onset of infection symptoms, as it considers the biofilm formation and the state of fracture healing. There were not clinical trials evaluating the optimal duration of antibiotic therapy in IOM when implant is retained. Because there are antibiotics that have proven to be effective for the treatment of infection associated to implant, mainly in PJI, these antibiotics could be used in these infections. Investigating whether shorter duration of treatment is a priority in infectious diseases, as a way to reduce the exposure to antibiotics and help in controlling antimicrobial resistance and avoiding unnecessary adverse events and cost. We aim to describe the hypothesis, objectives, design, variables and procedures for a pragmatic randomized controlled trial comparing different durations of antibiotic treatment in IOM after long bone fractures treated with debridement and implant retention. METHODS AND DESIGN: This is a multicenter, open-label, non-inferiority, randomized, controlled, pragmatic phase 3 trial, comparing different durations of antibiotic treatment in IOM after long bone fractures treated with debridement and implant retention. Patients with microbiologically confirmed IOM will be included. Eligible patients are those older than 14 years, with early IOM (up to 2 weeks after the implant surgery) and delayed IOM (between 3 and 10 weeks after the implant surgery) with stabilized fracture and absence of bone exposure who sign the informed consent. Randomization will be 1:1 to receive a short-term antibiotic treatment (8 weeks in early IOM and 12 weeks in delayed IOM) or a long-term antibiotic treatment (12 weeks in early IOM or until fracture healing or implant removal in delayed IOM). The antibiotic treatment will be that used in routine practice by the specialist in infectious diseases. The primary outcome is the composited variable "cure" that includes clinical cure, radiological healing, and definitive soft tissue coverage, which will be evaluated in the test of cure at 12 months after the end of antibiotic therapy. Adverse events, resistance development during therapy and functional status will be collected. A total of 364 patients are needed to show a 10% non-inferiority margin, with 80% power and 5% one-sided significance level. DISCUSSION: If the hypothesis of non-inferiority of short vs. long antibiotic treatments is demonstrated, and the efficacy of antibiotics with less ecological impact in long treatments, the impact on reduction of bacterial resistance, toxicity and health costs will be observed. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05294796) on Jan 26th 2022 and at the European Union Drug Regulating Authorities Clinical Trials (EUDRACT) (2021-003914-38) on Jul 16th 2021. The Sponsor Study Code is DURATIOM.

Cutibacterium spp. Infections after Instrumented Spine Surgery Have a Good Prognosis Regardless of Rifampin Use: A Cross-Sectional Study.

Infection after spinal instrumentation (IASI) by Cutibacterium spp. is being more frequently reported. The aim of this study was to analyse the incidence, risk factors, clinical characteristics, and outcome of a Cutibacterium spp. IASI (CG) compared with non-Cutibacterium IASI (NCG) infections, with an additional focus on the role of rifampin in the treatment. All patients from a multicentre, retrospective, observational study with a confirmed IASI between January 2010 and December 2016 were divided into two groups: (CG and NCG) IASI. Baseline, medical, surgical, infection treatment, and follow-up data were compared for both groups. In total, 411 patients were included: 27 CG and 384 NCG. The CG patients were significantly younger. They had a longer median time to diagnosis (23 vs. 13 days) (p = 0.025), although 55.6% debuted within the first month after surgery. Cutibacterium patients were more likely to have the implant removed (29.6% vs. 12.8%; p = 0.014) and received shorter antibiotic regimens (p = 0.014). In 33% of Cutibacterium cases, rifampin was added to the baseline therapy. None of the 27 infections resulted in treatment failure during follow-up regardless of rifampin use. Cutibacterium spp. is associated with a younger age and may cause both early and late IASIs. In our experience, the use of rifampin to improve the outcome in the treatment of a Cutibacterium spp. IASI is not relevant since, in our series, none of the cases had therapeutic failure regardless of the use of rifampin.

ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery.

SCOPE: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery. METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development. RECOMMENDATIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study.

OBJECTIVES: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions. METHODS: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort. RESULTS: In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort. DISCUSSION: Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study.

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( n = 57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n = 16 ), Pseudomonas aeruginosa ( n = 14 ; XDR 50 %), Klebsiella spp. ( n = 7 ), Enterobacter spp. ( n = 9 ), Acinetobacter spp. ( n = 5 ), Proteus mirabilis ( n = 3 ), Serratia marcescens ( n = 2 ) and Stenotrophomonas maltophilia ( n = 1 ). The prevalence of ESBL (extended-spectrum ß -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n = 37 ; 64.9 %) were treated with a combination including carbapenems ( n = 32 ) and colistin ( n = 11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p = 0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age > 60  years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p = 0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p = 0.024 ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

Prognosis of unexpected positive intraoperative cultures in arthroplasty revision: A large multicenter cohort.

BACKGROUND: The positive-intraoperative-cultures-type prosthetic joint infection (PIOC-PJI) is considered when surgical cultures yield microorganisms in presumed aseptic arthroplasty revisions. Herein we assess the risk factors for failure in the largest cohort of PIOC-PJI patients reported to date. METHODS: A retrospective, observational, multicenter study was performed during 2007-2017. Surgeries leading to diagnose PIOC-PJI included only one-stage procedures with either complete or partial prosthesis revision. Failure was defined as recurrence caused by the same microorganism. RESULTS: 203 cases were included (age 72 years, 52% females). Coagulase-negative staphylococci (n = 125, 62%) was the main etiology, but some episodes were caused by virulent bacteria (n = 51, 25%). Prosthesis complete and partial revision was performed in 93 (46%) and 110 (54%) cases, respectively. After a median of 3.4 years, failure occurred in 17 episodes (8.4%, 95%CI 5.3-13.1). Partial revision was an independent predictor of failure (HR 3.63; 95%CI 1.03-12.8), adjusted for gram-negative bacilli (GNB) infection (HR 2.68; 95%CI 0.91-7.89) and chronic renal impairment (HR 2.40; 95%CI 0.90-6.44). Treatment with biofilm-active antibiotics (rifampin/fluoroquinolones) had a favorable impact on infections caused by staphylococci and GNB. CONCLUSION: Overall prognosis of PIOC-PJI is good, but close follow-up is required in cases of partial revision and in infections caused by GNB.

Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial.

PURPOSE: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture. METHODS: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. PRIMARY OUTCOME: early-PJI after HHA. RESULTS: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10]). CONCLUSIONS: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.

Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study.

BACKGROUND: The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality. METHODS: In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model. FINDINGS: Three distinct phenotypes were derived in the derivation cohort (n=2667)-phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])-and reproduced in the internal validation cohort (n=1368)-phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4-4·3) for patients with phenotype A, 30·5% (28·5-32·6) for patients with phenotype B, and 60·7% (53·7-67·2) for patients with phenotype C (log-rank test p<0·0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5·3% [95% CI 3·4-8·1] for phenotype A, 31·3% [28·5-34·2] for phenotype B, and 59·5% [48·8-69·3] for phenotype C; external validation cohort: 3·7% [2·0-6·4] for phenotype A, 23·7% [21·8-25·7] for phenotype B, and 51·4% [41·9-60·7] for phenotype C). INTERPRETATION: Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated. FUNDING: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

How to Handle Concomitant Asymptomatic Prosthetic Joints During an Episode of Hematogenous Periprosthetic Joint Infection, a Multicenter Analysis.

BACKGROUND: Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered. METHODS: In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005-2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded. RESULTS: We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a "missed" PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%). CONCLUSIONS: During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.

Caracterización de las leucemias en niños en Cuba (2006-2015) / Characterization of leukemias in Cuban children (2006-2015)

Introducción: La leucemia es el cáncer más frecuente en edades pediátricas. La leucemia linfoide aguda (LLA) representa el 23 por ciento de los diagnósticos de cáncer en niños menores de 15 años y el 75 por ciento de todas las leucemias. Más del 90 por ciento de las leucemias mieloides agudas (LMA) en la niñez son agudas y el resto son crónicas. Objetivo: Caracterizar las leucemias agudas de la edad pediátrica en Cuba. Métodos: Estudio descriptivo, longitudinal y retrospectivo. La muestra fue de 799 niños de toda Cuba, los cuales fueron atendidos en los siete hospitales pediátricos acreditados en el país para el tratamiento de leucemias agudas, entre enero 2006 y diciembre de 2015. Como medida de resumen para las variables cuantitativas se utilizaron la media y desviación estándar. Para todas las variables cualitativas se calcularon los porcentajes de cada grupo. Resultados: Las tasas de incidencia fueron de 2,9 x 100 000 niños. El 95 por ciento fueron leucemias agudas (70,6 por ciento linfoides), con el 34,9 por ciento de leucemia promielocíticas (LPM) en las LMA. Predominó el sexo masculino y la edad promedio al diagnóstico fue de 7,1 años. El porcentaje de remisión completa en las LLA fue de 91 por ciento y en las LMA, de 66,7 por ciento. La frecuencia de recaídas de la enfermedad fue de 25,1 por ciento en las LLA, 13,7 por ciento en las LPM y 45 por ciento en las otras mieloides. La sobrevida global y libre de eventos fue de 89 por ciento y 63 por ciento en los niños con LLA, 64 por ciento y 62 por ciento en la LPM, 38 por ciento y 36 por ciento en la LMA no promielocítica, respectivamente. Conclusiones: La frecuencia y distribución etaria de las leucemias en niños cubanos son similares a lo descrito a nivel. Los resultados del tratamiento en las leucemias agudas de manera general pueden considerarse como buenos(AU)

Introduction: Leukemia is the most frequent cancer in pediatric ages. Acute lymphoid leukemia (ALL) accounts for 23 percent of cancer diagnoses in children at ages under 15 years and 75 percent of all leukemias. More than 90 percent of childhood acute myeloid leukemias (AML) are acute and the rest are chronic. Objective: To characterize acute leukemias in pediatric age in Cuba. Methods: Descriptive, longitudinal and retrospective study. The sample was 799 children from all over Cuba, who were treated in any of the country's seven pediatric hospitals accredited for the treatment of acute leukemias, between January 2006 and December 2015. As a summary measure for the quantitative variables, the mean and standard deviation were used. For all qualitative variables, the percentages of each group were calculated. Results: Incidence rates were 2.9 per 100,000 children. 95 percent were acute leukemias (70.6 percent lymphoid), with 34.9 percent corresponding to promyelocytic leukemia (PML) in AML. The male sex predominated and the average diagnosis age was 7.1 years. The percentage of complete remission in ALL was 91 percent, and 66.7 percent in AML. The frequency of disease relapse was 25.1 percent in ALL, 13.7 percent in LPM, and 45 percent in other myeloid leukemias. Overall and event-free survival was 89 percent and 63 percent in children with ALL, 64 percent and 62 percent in LPM, 38 percent and 36 percent in non-promyelocytic AML, respectively. Conclusions: Frequency and age distribution of leukemias in Cuban children are similar to that described worldwide. The results of treatment in acute leukemias in general can be considered as good(AU)

Lower Success Rate of Débridement and Implant Retention in Late Acute versus Early Acute Periprosthetic Joint Infection Caused by Staphylococcus spp. Results from a Matched Cohort Study.

BACKGROUND: Surgical débridement, antibiotics and implant retention (DAIR) is currently recommended by international guidelines for both early acute (postsurgical) and late acute (hematogenous) periprosthetic joint infections (PJIs). However, due to a different pathogenesis of infection, a different treatment strategy may be needed. QUESTIONS/PURPOSES: (1) Compared with early acute PJIs, are late acute PJIs associated with a higher risk of DAIR failure? (2) When stratified by microorganism, is the higher risk of failure in late acute PJI associated with Staphylocococcus aureus infection? (3) When analyzing patients with S. aureus infection, what factors are independently associated with DAIR failure? METHODS: In this multicenter observational study, early acute and late acute PJIs treated with DAIR were retrospectively evaluated and matched according to treating center, year of diagnosis, and infection-causing microorganism. If multiple matches were available, the early acute PJI diagnosed closest to the late acute PJI was selected. A total of 132 pairs were included. Treatment success was defined as a retained implant during follow-up without the need for antibiotic suppressive therapy. RESULTS: Late acute PJIs had a lower treatment success (46% [60 of 132]) compared with early acute PJIs (76% [100 of 132]), OR 3.9 [95% CI 2.3 to 6.6]; p < 0.001), but the lower treatment success of late acute PJIs was only observed when caused by Staphylococcus spp (S. aureus: 34% versus 75%; p < 0.001; coagulase-negative staphylococci: 46% versus 88%; p = 0.013, respectively). On multivariable analysis, late acute PJI was the only independent factor associated with an unsuccessful DAIR when caused by S. aureus (OR 4.52 [95% CI 1.79 to 11.41]; p < 0.001). CONCLUSIONS: Although DAIR seems to be a successful therapeutic strategy in the management of early acute PJI, its use in late acute PJI should be reconsidered when caused by Staphylococcus spp. Our results advocate the importance of isolating the causative microorganism before surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Different Microbial Etiology of Prosthetic Joint Infections according to Route of Acquisition and Time after Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms.

The aim of our study was to characterize the etiology of prosthetic joint infections (PJIs)-including multidrug-resistant organisms (MDRO)-by category of infection. A multicenter study of 2544 patients with PJIs was performed. We analyzed the causative microorganisms according to the Tsukayama's scheme (early postoperative, late chronic, and acute hematogenous infections (EPI, LCI, AHI) and "positive intraoperative cultures" (PIC)). Non-hematogenous PJIs were also evaluated according to time since surgery: <1 month, 2-3 months, 4-12 months, >12 months. AHIs were mostly caused by Staphylococcus aureus (39.2%) and streptococci (30.2%). EPIs were characterized by a preponderance of virulent microorganisms (S. aureus, Gram-negative bacilli (GNB), enterococci), MDROs (24%) and polymicrobial infections (27.4%). Conversely, coagulase-negative staphylococci (CoNS) and Cutibacterium species were predominant in LCIs (54.5% and 6.1%, respectively) and PICs (57.1% and 15.1%). The percentage of MDROs isolated in EPIs was more than three times the percentage isolated in LCIs (7.8%) and more than twice the proportion found in AHI (10.9%). There was a significant decreasing linear trend over the four time intervals post-surgery for virulent microorganisms, MDROs, and polymicrobial infections, and a rising trend for CoNS, streptococci and Cutibacterium spp. The observed differences have important implications for the empirical antimicrobial treatment of PJIs.

Cardiotoxicidad tardía por antraciclinas usadas en el tratamiento de la leucemia linfoblástica aguda en la edad pediátrica / Late cardiotoxicity by anthracyclines used for treatment of acute lymphoblastic leukemia in pediatric age

Introducción: las leucemias linfoblásticas agudas diagnosticadas en la edad prediátrica se tratan con antraciclinas con buenos resultados. Sin embargo estos fármacos producen cardiotoxicidad, lo que limita su uso. Objetivo: identificar las alteraciones subclínicas de cardiotoxicidad tardía causadas por las antraciclinas usadas en los enfermos de leucemia linfoblástica aguda en edad pediátrica.Método: se realizó un preexperimento con posprueba entre septiembre de 2015 y diciembre de 2016. La población en estudio estuvo constituida por 18 enfermos tratados en el Departamento de Oncología del Hospital Pediátrico de Camagüey, a los que se les realizó electrocardiograma y ecocardiograma bidimensional, Doppler y de flujo en color y se calculó la dosis acumulada de antraciclinas en mg/m2 de superficie corporal.Resultados: predominó el sexo femenino (61,11 por ciento), la casi totalidad de los pacientes tenían 10 o más años de edad, 83,33 por ciento presentó signos de cardiotoxicidad tardía. Prevalecieron las alteraciones electrocardiográficas (86,67 por ciento) por taquicardia sinusal, sobre las ecocardiográficas (13,33 por ciento) por incremento del diámetro diastólico del ventrículo izquierdo. Se identificó cardiotoxicidad incluso en los que recibieron dosis más bajas (180 mg/m2 y 240 mg/m2) y en todos los que recibieron el tratamiento por dos años o más. Los signos ecocardiográficos aparecieron con las dosis más elevadas (600 mg/m2 a 720 mg/m2) mientras los signos electrocardiográficos se presentaron para las demás dosis de la droga.Conclusiones: las alteraciones electrocardiográficas predominaron sobre las ecocardiográficas. La cardiotoxicidad se presentó cuando el tiempo de exposición a la droga fue corto y las dosis eran bajas(AU)

Introduction: the acute lymphoblastic leukemias diagnosed in prediatric age are treated with anthracyclines which offers good results. However, these drugs produce cardiotoxicity, which limits their use.Objective : to identify the subclinical alterations of late cardiotoxicity caused by anthracyclines used in patients with acute lymphoblastic leukemia in pediatric age.Method: a preexperiment was carried out with post-test between September 2015 and December 2016. The population under study was constituted by the 18 patients treated in the Oncology Department of the Pediatric Hospital in Camagüey, who underwent an electrocardiogram and two-dimensional echocardiogram, Doppler and color flow, and calculated the cumulative dose of anthracyclines in mg/m2 of body surface area.Results: the female sex predominated (61,11 percent), almost all patients were 10 or more years old, 83,33 percent showed signs of late cardiotoxicity. Electrocardiographic alterations prevailed (86,67 percent) due to sinus tachycardia, on echocardiography (13,33 percent) due to an increase in diastolic diameter of the left ventricle. Cardiotoxicity was identified even in those who received the lowest dose (180 mg/m2 and 240 mg/m2 ) and in all those who received the treatment for two years or more. The echocardiographic signs appeared with the highest doses (600 mg/m2 to 720 mg/m2) while the electrocardiographic signs appeared for the other doses of the drug.Conclusions: the electrocardiographic alterations prevailed over echocardiography. Cardiotoxicity occurred even when the time of exposure to the drug was short and the doses were low(AU)