The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.

The Role of Chitosan and Graphene Oxide in Bioactive and Antibacterial Properties of Acrylic Bone Cements.

Acrylic bone cements (ABC) are widely used in orthopedics for joint fixation, antibiotic release, and bone defect filling, among others. However, most commercially available ABCs exhibit a lack of bioactivity and are susceptible to infection after implantation. These disadvantages generate long-term loosening of the prosthesis, high morbidity, and prolonged and expensive treatments. Due to the great importance of acrylic bone cements in orthopedics, the scientific community has advanced several efforts to develop bioactive ABCs with antibacterial activity through several strategies, including the use of biodegradable materials such as chitosan (CS) and nanostructures such as graphene oxide (GO), with promising results. This paper reviews several studies reporting advantages in bioactivity and antibacterial properties after incorporating CS and GO in bone cements. Detailed information on the possible mechanisms by which these fillers confer bioactive and antibacterial properties to cements, resulting in formulations with great potential for use in orthopedics, are also a focus in the manuscript. To the best of our knowledge, this is the first systematic review that presents the improvement in biological properties with CS and GO addition in cements that we believe will contribute to the biomedical field.

Non-biofilm-forming commensal Staphylococcus epidermidis isolates produce biofilm in the presence of trypsin.

Epidemiological studies comparing clinical and commensal Staphylococcus epidermidis isolates suggest that biofilm formation is a discriminant biomarker. A study showed that four non-biofilm-forming clinical S. epidermidis isolates could form an induced biofilm by trypsin treatment, suggesting that S. epidermidis can form biofilms in a protease-independent way and in a trypsin-induced way. In this study, the trypsin capacity to induce biofilm formation was evaluated in non-biofilm-forming S. epidermidis isolates (n = 133) in order to support this mechanism and to establish the importance of total biofilms (meaning the sum of protease-independent biofilm and trypsin-induced biofilm). Staphylococcus epidermidis isolates from ocular infections (OI; n = 24), prosthetic joint infections (PJI; n = 64), and healthy skin (HS-1; n = 100) were screened for protease-independent biofilm formation according to Christensen's method. The result was that there are significant differences (p < .0001) between clinical (43.2%) and commensal (17%) protease-independent biofilm producers. Meanwhile, non-biofilm-forming isolates were treated with trypsin, and biofilm formation was evaluated by the same method. The number of commensal trypsin-induced biofilm producers significantly increased from 17% to 79%. In contrast, clinical isolates increased from 43.2% to 72.7%. The comparison between clinical and commensal total biofilm yielded no significant differences (p = .392). A similar result was found when different isolation sources were compared (OI vs. HS-1 and PJI vs. HS-1). The genotype icaA- /aap+ was associated with the trypsin-induced biofilm phenotype; however, no correlation was observed between aap mRNA expression and the level of trypsin-induced biofilm phenotype. Studying another group of commensal S. epidermidis non-biofilm-forming isolates (HS-2; n = 139) from different body sites, it was found that 70 isolates (60.3%) formed trypsin-induced biofilms. In conclusion, trypsin is capable of inducing biofilm production in non-biofilm-forming commensal S. epidermidis isolates with the icaA- /aap+ genotype, and there is no significant difference in total biofilms when comparing clinical and commensal isolates, suggesting that total biofilms are not a discriminant biomarker.

Infecciones osteoarticulares en un hospital pediátrico de alta complejidad: epidemiología y características clínicas asociadas con bacteriemia / Osteoarticular infections in a tertiary care children's hospital: Epidemiology and clinical characteristics in association with bacteremia

Introducción. Las infecciones osteoarticulares son una importante causa de morbilidad y pueden presentar bacteriemia. La epidemiología de estas infecciones se ha modificado en los últimos años. Objetivos. Describir las características epidemiológicas, clínicas y evolutivas de los niños con infecciones osteoarticulares y comparar los pacientes con bacteriemia con los que no la presentaron. Población y métodos. Cohorte retrospectiva. Se incluyeron pacientes menores de 18 años, admitidos en el Hospital Juan P. Garrahan entre el 1/1/2016 y el 31/12/2016 con sospecha de infecciones osteoarticulares en quienes se hubiese realizado artrocentesis y/o biopsia articular. Se excluyeron niños con patología previa. Se compararon las características clínicas y de laboratorio según tuvieran bacteriemia o no. Se utilizó Stata 10. Resultados. N: 62. La mediana de edad fue 59.5 meses (rango intercuartilo -RIC- 24-84). Presentaron fiebre 44 pacientes (70%). Predominaron las artritis (54 pacientes, 87%). Se identificó un agente etiológico en 29 pacientes (47%). Predominó Staphylococcus aureus (n: 20, 32%). Tuvieron bacteriemia 15 de ellos (24%). Recibieron clindamicina como tratamiento empírico 56 pacientes (90%). La mediana de tratamiento endovenoso fue 7 días (RIC 5-11) y de internación, 7 días (RIC 4-12). Los pacientes con bacteriemia tuvieron menor edad (26 meses vs. 60, p < 0,05), mayor valor de proteína C reactiva inicial (101 vs. 33 U/L, p < 0,05), menor valor de hemoglobina al ingresar (10,8 g/dl vs. 12.5 g/dl, p 0,04) y mayor frecuencia de fiebre (100% vs. 57%, p < 0,05). Conclusiones. Predominó Staphylococcus aureus. Los niños con bacteriemia tuvieron menor edad, mayor valor de proteína C reactiva, menos hemoglobina al ingresar y, más frecuentemente, fiebre.

Introduction. Osteoarticular infections are an important cause of morbidity and may present with bacteremia. The epidemiology has changed in recent years. Objectives. To describe the epidemiological, clinical, and evolutionary characteristics of children with osteoarticular infections and compare patients with and without bacteremia. Population and methods. Retrospective cohort. Patients younger than 18 years admitted between January 1st, 2016 and December 31st, 2016 suspected of osteoarticular infections who had undergone an arthrocentesis and/or joint biopsy were included. Clinical and laboratory characteristics were compared between patients with and without bacteremia. The Stata 10 software was used.Results. N: 62. Patients' median age was 59.5 months (interquartile range [IQR]: 24-84). Fever developed in 44 patients (70%). Arthritis predominated (54 patients, 87%). An etiologic agent was identified in 29 patients (47%). Staphylococcus aureus was prevalent (n: 20, 32%). Among these, 15 developed bacteremia (24%). Clindamycin was administered to 56 patients (90%) as empirical therapy. The median intravenous treatment duration was 7 days (IQR: 5-11) and the median length of stay, 7 days (IQR: 4-12). Patients with bacteremia were younger (26 months versus 60 months, p < 0.05), had a higher baseline C-reactive protein level (101 U/L versus 33 U/L, p < 0.05), a lower hemoglobin level at the time of admission (10.8 g/dL versus 12.5 g/dL, p = 0.04), and a higher frequency of fever (100% versus 57%, p < 0.05).Conclusions. Staphylococcus aureus was prevalent. Children with bacteremia were younger, had a higher C-reactive protein level, a lower hemoglobin level at the time of admission, and 100% presented fever

Osteoarticular infections in a tertiary care children's hospital: Epidemiology and clinical characteristics in association with bacteremia. / Infecciones osteoarticulares en un hospital pediátrico de alta complejidad: epidemiología y características clínicas asociadas con bacteriemia.

INTRODUCTION: Osteoarticular infections are an important cause of morbidity and may present with bacteremia. The epidemiology has changed in recent years. OBJECTIVES: To describe the epidemiological, clinical, and evolutionary characteristics of children with osteoarticular infections and compare patients with and without bacteremia. POPULATION AND METHODS: Retrospective cohort. Patients younger than 18 years admitted between January 1st, 2016 and December 31st, 2016 suspected of osteoarticular infections who had undergone an arthrocentesis and/or joint biopsy were included. Clinical and laboratory characteristics were compared between patients with and without bacteremia. The Stata 10 software was used. RESULTS: N: 62. Patients' median age was 59.5 months (interquartile range [IQR]: 24-84). Fever developed in 44 patients (70%). Arthritis predominated (54 patients, 87%). An etiologic agent was identified in 29 patients (47%). Staphylococcus aureus was prevalent (n: 20, 32%). Among these, 15 developed bacteremia (24%). Clindamycin was administered to 56 patients (90%) as empirical therapy. The median intravenous treatment duration was 7 days (IQR: 5-11) and the median length of stay, 7 days (IQR: 4-12). Patients with bacteremia were younger (26 months versus 60 months, p < 0.05), had a higher baseline C-reactive protein level (101 U/L versus 33 U/L, p < 0.05), a lower hemoglobin level at the time of admission (10.8 g/dL versus 12.5 g/dL, p = 0.04), and a higher frequency of fever (100% versus 57%, p < 0.05). CONCLUSIONS: Staphylococcus aureus was prevalent. Children with bacteremia were younger, had a higher C-reactive protein level, a lower hemoglobin level at the time of admission, and 100% presented fever.

INTRODUCCIÓN: Las infecciones osteoarticulares son una importante causa de morbilidad y pueden presentar bacteriemia. La epidemiología de estas infecciones se ha modificado en los últimos años. OBJETIVOS: Describir las características epidemiológicas, clínicas y evolutivas de los niños con infecciones osteoarticulares y comparar los pacientes con bacteriemia con los que no la presentaron. POBLACIÓN Y MÉTODOS: Cohorte retrospectiva. Se incluyeron pacientes menores de 18 años, admitidos en el Hospital Juan P. Garrahan entre el 1/1/2016 y el 31/12/2016 con sospecha de infecciones osteoarticulares en quienes se hubiese realizado artrocentesis y/o biopsia articular. Se excluyeron niños con patología previa. Se compararon las características clínicas y de laboratorio según tuvieran bacteriemia o no. Se utilizó Stata 10. RESULTADOS: N: 62. La mediana de edad fue 59.5 meses (rango intercuartilo -RIC- 24-84). Presentaron fiebre 44 pacientes (70%). Predominaron las artritis (54 pacientes, 87%). Se identificó un agente etiológico en 29 pacientes (47%). Predominó Staphylococcus aureus (n: 20, 32%). Tuvieron bacteriemia 15 de ellos (24%). Recibieron clindamicina como tratamiento empírico 56 pacientes (90%). La mediana de tratamiento endovenoso fue 7 días (RIC 5-11) y de internación, 7 días (RIC 4-12). Los pacientes con bacteriemia tuvieron menor edad (26 meses vs. 60, p < 0,05), mayor valor de proteína C reactiva inicial (101 vs. 33 U/L, p < 0,05), menor valor de hemoglobina al ingresar (10,8 g/dl vs. 12.5 g/dl, p 0,04) y mayor frecuencia de fiebre (100% vs. 57%, p < 0,05). CONCLUSIONES: Predominó Staphylococcus aureus. Los niños con bacteriemia tuvieron menor edad, mayor valor de proteína C reactiva, menos hemoglobina al ingresar y, más frecuentemente, fiebre.

Clinical and epidemiological characteristics of septic arthritis of the hip, 2006 to 2012, a seven-year review.

OBJECTIVE: To epidemiologically characterize the population treated at our orthopedic clinic with a diagnosis of septic arthritic of the hip between 2006 and 2012. METHODS: Fifteen patients diagnosed with septic arthritis of the hip between 2006 and 2012 were retrospectively evaluated. The patients' clinical and epidemiological characteristics were surveyed; a sensitivity profile relating to the microorganisms that caused the infections and the complications relating to the patients' treatment and evolution were identified. RESULTS: Septic arthritis was more common among males. Most diagnoses were made through positive synovial fluid cultures, after joint drainage was performed using the Smith-Petersen route. Among the comorbidities found, the most prevalent were systemic arterial hypertension, diabetes mellitus, and human immunodeficiency virus. The pathological joint conditions diagnosed prior to joint infection were osteoarthrosis and developmental dysplasia of the hip. The infectious agent most frequently isolated was Staphylococcus aureus. From the clinical and laboratory data investigated, 53.33% of the cases presented with fever, and all except one patient presented with increased measures in inflammation tests. Gram staining was positive in only 26.66% of the synovial fluid samples analyzed. Six patients presented with joint complications after treatment was administered. CONCLUSION: S. aureus is the most common pathogen in acute infections of the hip in our setting. Factors such as clinical comorbidities are associated with septic arthritis of the hip. Because of the relatively small number of patients, given that this is a condition of low prevalence, there was no statistically significant correlation in relation to worse prognosis for the disease.

Clinical and epidemiological characteristics of septic arthritis of the hip, 2006 to 2012, a seven-year review

OBJECTIVE: To epidemiologically characterize the population treated at our orthopedic clinic with a diagnosis of septic arthritic of the hip between 2006 and 2012. METHODS: Fifteen patients diagnosed with septic arthritis of the hip between 2006 and 2012 were retrospectively evaluated. The patients' clinical and epidemiological characteristics were surveyed; a sensitivity profile relating to the microorganisms that caused the infections and the complications relating to the patients' treatment and evolution were identified. RESULTS: Septic arthritis was more common among males. Most diagnoses were made through positive synovial fluid cultures, after joint drainage was performed using the Smith-Petersen route. Among the comorbidities found, the most prevalent were systemic arterial hypertension, diabetes mellitus, and human immunodeficiency virus. The pathological joint conditions diagnosed prior to joint infection were osteoarthrosis and developmental dysplasia of the hip. The infectious agent most frequently isolated was Staphylococcus aureus. From the clinical and laboratory data investigated, 53.33% of the cases presented with fever, and all except one patient presented with increased measures in inflammation tests. Gram staining was positive in only 26.66% of the synovial fluid samples analyzed. Six patients presented with joint complications after treatment was administered. CONCLUSION: S. aureus is the most common pathogen in acute infections of the hip in our setting. Factors such as clinical comorbidities are associated with septic arthritis of the hip. Because of the relatively small number of patients, given that this is a condition of low prevalence, there was no statistically significant correlation in relation to worse prognosis for the disease. .

[Treatment failure due to acquisition of antibiotic resistance: report of two clinical cases]. / Fallo terapéutico por resistencia antibacteriana intra-tratamiento, a propósito de dos casos clínicos.

OBJECTIVE: We describe two cases of treatment failure due to intra-treatment acquisition of antibiotic resistant microorganisms with the aim of highlighting the possible molecular mechanisms by which treatment failure occurred. PATIENTS AND METHODS: We analyzed the clinical histories and the isolates obtained from 2 patients, one with a urinary tract infection (UTI) by E. coli, initially treated with cefuroxim (to which the isolate was susceptible), and another with osteoarthritis (OA) treated initially with meropenem plus vancomycin, developing K. pneumoniae susceptible to meropenem. During treatment, in both patients, resistant microorganisms were isolated, and empirical therapy was modified, initially with ceftriaxone and afterwards meropenem in case 1, and adding amikacin in case 2. Both strains (per patient) were compared by PFGE and resistance genes were sought by PCR. RESULTS: Regarding the UTI, the initial strain acquired an IncFIB SHV-5-producing plasmid. In the OA case, the initial susceptible strain was substituted by a CTX-M-9 and AadB-AadA2-Aac(6')Ib-producing K. pneumoniae.

[Metastatic infections in children with Staphylococcus aureus bacteremia]. / Localización metastásica en niños con bacteriemia por Staphylococcus aureus.

Staphylococcus aureus is one of the most common infectious agents in children. It causes a broad spectrum of infections ranging from trivial to severe life-threatening presentations. The possibility of complications in case of Staphylococcus aureus bacteremia (SAB) appears to be high, being described in up to 43% of cases in adult patients. However, metastatic infections seems to be less frequent in pediatric patients. There is no agreement on when or to whom complementary tests should be requested to rule them out. The aim of this study is to describe the frequency and characteristics of secondary impacts of SAB identified at "Hospital Gutierrez" in a period of two years, and assess potential risk factors for their occurrence. Metastatic infection rate was 15.8%. The main risk factor was the persistence of positive blood cultures more than 48 hours.

Osteoarthritis in the neonate: risk factors and outcome.

OBJECTIVES: The aim of this study was to identify the clinical, radiological, and bacteriological features, risk factors, and outcome of neonates with bone and joint infections. STUDY DESIGN: Observational, retrospective, and analytical study of 77 patients less than 2 months of age, admitted to a tertiary neonatal intensive care unit (NICU) with the diagnosis of bone or joint infection, based on clinical, radiological, and microbiological criteria. RESULTS: Seventy-seven patients with 99 acute osteoarthritis foci in a 16 year period were included in the study. Risk factors for infection could be identified in 69% of the patients. The hip was the most frequent. Staphylococcus aureus was the main isolated microorganism. Twenty-nine infants (38%) had sequelae. Hip involvement, culture positive, and Staphylococcus aureus isolation were risk factors associated with sequelae. CONCLUSION: Osteoarticular infection is unusual in the neonate; however it is associated with an elevated incidence of sequelae. This mandates for a high degree of suspicion to diagnose this potentially disabling entity.

Osteoarthritis in the neonate: risk factors and outcome

OBJECTIVES: The aim of this study was to identify the clinical, radiological, and bacteriological features, risk factors, and outcome of neonates with bone and joint infections. STUDY DESIGN: Observational, retrospective, and analytical study of 77 patients less than 2 months of age, admitted to a tertiary neonatal intensive care unit (NICU) with the diagnosis of bone or joint infection, based on clinical, radiological, and microbiological criteria. RESULTS: Seventy-seven patients with 99 acute osteoarthritis foci in a 16 year period were included in the study. Risk factors for infection could be identified in 69 percent of the patients. The hip was the most frequent. Staphylococcus aureus was the main isolated microorganism. Twenty-nine infants (38 percent) had sequelae. Hip involvement, culture positive, and Staphylococcus aureus isolation were risk factors associated with sequelae. CONCLUSION: Osteoarticular infection is unusual in the neonate; however it is associated with an elevated incidence of sequelae. This mandates for a high degree of suspicion to diagnose this potentially disabling entity.

Sporothrix schenckii infection presented as monoarthritis: report of two cases and review of the literature.

Septic arthritis demands early diagnosis and correct treatment if the function of the joint is to be restored. Sometimes, as in fungal infection, signs and symptoms may be mild and the diagnosis delayed. Nevertheless, the outcome of fungal arthritis is severe and usually causes joint disability. The authors report two patients with chronic monoarthritis due to Sporothrix schenckii infection diagnosed by synovial fluid cultures. Their clinical presentation, laboratory and image findings, and their treatment and follow-up are analyzed and compared to previously reported cases. These cases illustrate the differential diagnosis of monoarthritis in immunocompetent adults and picture clinical features that could lead to early diagnosis and proper treatment.

[Cellulitis in pediatrics. Diagnostic and therapeutic considerations]. / Celulitis en pediatría. Consideraciones diagnósticas y terapéuticas.

The clinical histories of 180 cases of cellulitis or phlegmona diffusa were studied at the Hospital de Pediatría del Centro Medico Nacional. The disease prevailed in infants and preschool children. Staphylococcus aureus was the etiological agent most frequently found, but with the presence of enterobacteriaceae in 39% of patients under 2 years of age. One third of the children with cellulitis showed one or several complications. Lethality reached 5% (9 cases), but always related to septicemia from S. aureus. In 14.4%, osteoarthritis was present; frequently there was: fever for over 5 days in spite of adequate treatment, a history of late initiation of the antimicrobial drug (over 1 week) and phlogosis or functional limitation. The radiological picture that shows the bony lesion was evident only after two weeks. One half these cases remained with sequelae. Considerations are made on the adequate plans for antibiotic treatment and the early diagnosis of the osteoarticular complication.