Patterns of musculoskeletal infection in childhood.

BackgroundLate preterm and early term infants are a large proportion of all births. Historically, outcomes were thought to be similar to those of full term infants, but recent evidence demonstrates worse outcomes. Although serious morbidity is less common than in very preterm infants, the impact of modest illness in large numbers of more mature neonates is significant, with 30–40% requiring neonatal unit (NNU) admission, primarily for respiratory disease. The SurfON trial aims to evaluate whether early surfactant therapy improves outcomes compared with expectant management in late preterm and early term infants with respiratory distress. The primary objectives are to compare neonatal hospital stay and incidence of severe respiratory failure, with secondary objectives assessing other perinatal outcomes and cost-effectiveness.MethodsThe SurfON trial is a multicentre, open-label, randomised controlled trial involving 45 UK NNUs, aiming to recruit 1522 infants over 30 months. Eligible infants are those born at 34+0 to 38+6 weeks’ gestation who require noninvasive respiratory support for respiratory distress within 24 h of birth. Infants are randomised in a 1:1 allocation ratio to either early surfactant therapy or expectant management. Infants randomised to the early surfactant therapy group will receive a single dose of CUROSURF®, a natural animal-derived surfactant. IMP administration reflects local site policy and procedure and may be completed by any clinician for whom this falls within their usual scope of practice, following confirmation of eligibility. The IMP is a commonly used drug in neonates and is being used in line with standard care. Side effects are uncommon and usually transient. Timing and dosage of IMP administration will be collected. Surfactant is a stock drug for all NNUs and will be administered and accounted for as per local practice.DiscussionEvidence-based guidance for the management of late preterm and early term infants is sparse, and no previous large randomised controlled trials have focused on this population. Management of respiratory distress in late preterm and early term infants varies. Some clinicians prefer early surfactant administration to prevent deterioration—78others delay treatment to avoid mechanical ventilation. This inconsistency highlights the need for trials to establish an evidence base. Unexpected neonatal morbidity and prolonged hospitalisation cause significant psychological distress for families, impacting breastfeeding and maternal well-being. High intensive care workload and associated costs pose challenges for the NHS (National Health Service). Evidence-based management could improve outcomes and reduce healthcare burdens.Trial registrationISRCTN 15915394. Registered on 20th February 2020 https://www.isrctn.com/ISRCTN15915394.

Musculoskeletal infection (MSKI) in children is a common cause of hospitalization in the pediatric population worldwide. Severity of disease is dependent upon the amount and type of tissue involved. Though common, pediatric MSKI diagnosis and treatment can be challenging. In this chapter, we have critically reviewed and summarized the evidence that underpin the current practice in the developed world. Evidence-based treatment guidelines applied by a multidisciplinary team resulted in better care of children with MSKI (Grade B). Non-contrasted MRI is the diagnostic modality of choice to distinguish isolated septic arthritis from adjacent infection (Grade B). Septic arthritis is the most common diagnosis with synovial fluid WBC counts between 25,000 and 75,000 cells/mm3 and can be adequately treated by both arthroscopy or traditional arthrotomy (Grade B). Acute haematogenous osteomyelitis (AHO) can be treated with short course of IV antibiotic, followed by oral antibiotic for 3–4 weeks (Grade B).

Osteomyelitis, defined as an inflammation of bone generally caused by a pyogenic organism, is a common disorder of childhood. Infection most commonly is caused by blood-borne bacteria that localize in the metaphysis. Trauma or surgery also may result in direct inoculation or implantation of bacteria into the bone, or an adjacent focus of infection might extend directly to the bone, resulting in osteomyelitis. The etiology of acute hematogenous osteomyelitis is not understood completely. Bacteremia in childhood occurs frequently, if not daily; thus, the presence of bacteria alone may not explain why infection begins. Recent trauma coincidental with a bacteremia has been postulated. The presence of an intercurrent illness (ie, chicken pox) or infection may introduce a larger number of organisms or different pathogenic bacteria into the system or alter the immune system, making the host more susceptible. An understanding of the anatomy of bone and the pathogenesis of osteomyelitis is essential to appreciate the protean manifestations of the disorder. Pathogenesis In acute hematogenous osteomyelitis, infection is localized in the metapahysis. The circulation of the bone predisposes this region to the infection. Epiphyseal and metaphyseaal blood supplies generally are separate. The blood supply to the metaaphysis originagtes when the nutrient arteries send small terminala branches that end at the growth plate.

The immunomodulating effects of repeated exposure to blood from multiple donors coupled with an immature immune system may predispose the preterm neonate to an increased incidence of infection in his first few months of life. To test this hypothesis, we compared lymphocyte phenotypes, serum IgG concentrations, and histories of infection and rehospitalization in neonates at 4 months corrected age. Two of the study groups were preterm infants who had been transfused with either frozen, deglycerolized or CMV-negative, gamma-irradiated blood. Control groups consisted of nontransfused term and preterm infants. There were no differences found in lymphocyte phenotypes or serum IgG concentrations of controls or transfused infants. No differences were found in the infection or rehospitalization incidence in the transfused infants as compared with nontransfused preterm neonates. We failed to show differences in immune parameters or in infection and rehospitalization rates of the preterm infants analysed. Alongside previously published reports, our data suggest that red cell transfusions have a minimal impact on the immature immune system of the neonate.

The aim of this prospective study was to evaluate the incidence of viral respiratory infection in hospitalized premature newborn infants and to assess the role of coronaviruses. All hospitalized premature infants with a gestational age less than or equal to 32 weeks were included. Tracheal or nasopharyngal specimens were studied by immunofluorescence for coronaviruses, respiratory syncytial virus, adenoviruses, influenza and parainfluenza viruses. Forty premature infants were included; 13 samples were positive in 10 newborns (coronaviruses n = 10; influenza 1 n= 2; adenovirus n= 1). None was positive at admission. All premature infants infected with coronaviruses had symptoms of bradycardia, apnea, hypoxemia, fever or abdominal distension. Chest X‐ray revealed diffuse infiltrates in two cases. However, no significant difference was observed between infected and non‐infected premature infants for gestational age, birth weight, duration of ventilation, age at discharge, incidence of apnea or bradycardia. Nosocomial respiratory tract infection with coronaviruses appears to be frequent. The clinical consequences should be evaluated in a larger population.

Cytomegalovirus infection occurs commonly during infancy. Postnatal infection in term infants is usually asymptomatic; however, infection in preterm infants can be associated with clinical manifestations during the neonatal period. Nevertheless, few studies to assess the frequency of cytomegalovirus infection in preterm infants have been performed outside of high-income countries. We analyzed the incidence of congenital and postnatal cytomegalovirus infection in a cohort of preterm infants. Cytomegalovirus infection was detected during the neonatal period in four of 178 infants; in three of them, the virus was detected during the first 3 weeks of life and, therefore, congenital infection was confirmed (1.7% incidence). Postnatal infection was detected in 44 (36.4%) of 121 infants who were assessed after discharge from the neonatal intensive care unit. Cytomegalovirus infection was significantly associated with the duration of breastfeeding. In addition, we characterized cytomegalovirus strains detected in infants together with sequences available at GenBank, based on sequences of the UL18 gene. Cytomegalovirus UL18-sequences clustered in five distinct clades (A-E), and sequences obtained from infants in our study were distributed in four of the five clades; 44.4% of these sequences were included in clade E. Breastfeeding duration was shorter on average (5.6 months) in infants with sequences in clade E compared to infants with sequences in the other three clades (8.2 months; p = .07). In conclusion, we provide information regarding the high incidence of cytomegalovirus infection in preterm infants. Further studies are warranted to assess if cytomegalovirus strain characteristics are associated with the risk of infection acquisition during infancy.

Chronic periodontitis is a chronic inflammatory disease of infectious origin involving destruction of the supporting structures of the teeth including ligament, bone and may lead to tooth loss. The pathogenesis of periodontitis involves inflammatory and immunological processes that elicit the production of cytokines, prostaglandins and in some cases, acute phase reagents, such as C-reactive protein (CRP). CP has been associated with elevated levels of CRP in otherwise systemically health. Moreover, periodontal treatment has been associated with reduction of CRP levels. In dialysis patients, increased CRP levels have been associated with increased risk for cardiovascular diseases in both continuous ambulatory peritoneal dialysis (CAPD) and in hemodialysis patients. Dialysis-associated inflammation may explain why approximately 30% of patients on renal replacement therapy (RRT) display markers of chronic inflammation. However, it is unknown why in some CKD patients without an evident concurrent inflammatory process also present laboratory signs of inflammation. It is possible that periodontitis may be a source of inflammation in CKD individuals. The aim ofthis review is to present the relations between CKD, atherosclerosis and periodontitis, emphatizing a possible influence of periodontitis on the inflammatory process in CKD patients. In conclusion, both PD and CKD are chronic inflammatory diseases, and the inflammatory mechanisms and host responses may be responsible for their endpoints. Non traditional risk factors, such as periodontitis, may be associated to the high mortality observed in CKD. Periodontitis is highly prevalent in the population and is associated with high levels of CRP and endothelial dysfunction, early predictors of atherosclerosis. Periodontal treatment may reduce the inflammatory process, reducing the incidence of atherosclerotic complications in patient with CKD.

Timely diagnosis of musculoskeletal infections is essential to prevent severe complications of this disease. Important symptoms that lead to the diagnosis include high fever, malaise, local pain and loss of function of the involved extremity. In the case of arthritis, swelling of the affected joint may develop quickly in the course of disease. Imaging techniques include ultrasound and MRI. Both are useful in determining the exact site of infection. Infectious parameters, C-reactive protein and/or sedimentation rate of erythrocytes (ESR) are used in following disease activity during treatment. The gold standard for diagnosing musculoskeletal infection is microbiological isolation of the organism. Bone-biopsy of an involved metaphysis or aspiration of joint-fluid gives the highest chance of a positive culture. Usually S. aureus is the causative micro-organism, although specific underlying diseases may predispose to other bacterial infections. Antibiotic treatment is aimed at the most likely causative micro-organism. In some instances surgical treatment is necessary, especially in cases of focal and chronic osteomyelitis and when the adjacent joint is involved in the inflammatory process. Collaboration between paediatrician and orthopaedic surgeon is essential to achieve the best treatment for the patient.

IntroductionStrains of Panton-Valentine leukocidin-producing Staphylococcus aureus producing a new pattern of disease have emerged worldwide. Infection with these bacteria typically presents as a life-threatening infection of soft tissues and bones, and may cause potentially devastating consequences.Case presentationWe report a case of osteoarticular infection caused by Panton-Valentine leukocidin-producing Staphylococcus aureus. A 12-year-old Caucasian girl presented with acute osteomyelitis of the tibia associated with toxic shock syndrome, which was complicated by an unexpected spontaneous ankle arthrodesis.ConclusionsOsteoarticular infections due to Panton-Valentine leukocidin-producing Staphylococcus aureus appear to be severe, and are characterized by their tendency to evolve towards serious complications. This case highlights the need for early and aggressive surgical procedures in conjunction with appropriate antimicrobial therapy and regular long-term follow-up.

Infectious Risk of Continuous Peripheral Nerve Blocks

BackgroundPreterm infants have immature gastrointestinal tracts and poor immunity. In this study, the effects of Lactobacillus reuteri DSM 17938 first on early feeding tolerance, growth, and second on infection prevention in preterm infants were evaluated.MethodsOne hundred fourteen formula-fed preterm infants with a gestational age between 30 weeks and 37 weeks, and a birth weight between 1500 and 2000 g were enrolled; 57 in the intervention and 57 in the control group:the intervention group was given a dose of 1 × 108 colony-forming units (5 drops) of L. reuteri DSM 17938 once daily, beginning with the first feeding until discharge. The control group did not receive probiotics. Early feeding tolerance (as time to full enterla feeding and number of reflux), growth, incidences of sepsis, localized infection, NEC, and adverse effects were recorded for both groups.ResultsThe number of Daily reflux episodes (times/d) was lower (2.18 ± 0.83 vs. 3.77 ± 0.66, P < 0.01) and time to full enteral feedings (120 mL/kg/d) (9.95 ± 2.46 d vs. 13.80 ± 3.47 d, P < 0.05) was shorter in the intervention group. Average daily weight gain (14.55 ± 3.07 g/d vs. 10.12 ± 2.80 g/d), head circumference increas e(0.0760 ± 0.0157 cm/d vs. 0.0681 ± 0.0108 cm/d), and body length increase (0.1878 ± 0.0151 cm/d vs. 0.1756 ± 0.0166 cm/d) of the intervention group were higher (P < 0.01). There were no significant differences in the incidences of sepsis (4.44% vs. 8.33%), localized infection (6.67% vs. 8.33%), or NEC (2.22% vs. 10.42%) between the 2 groups (P > 0.05). The number of daily defecations (times/d) in the intervention group was higher (3.08 ± 0.33 vs. 2.29 ± 0.20, P < 0.01) and the length of hospital stay was shorter than that in the control group (20.60 ± 5.36 d vs. 23.75 ± 8.57 d, P < 0.05). No adverse effects were noted among the infants receiving L. reuteri.ConclusionL. reuteri may be an useful tool in improving early feeding tolerance in preterm infants, promoting growth, increasing the frequency of defecation, and shortening the length of hospital stay.Trial registrationChiCTR, ChiCTR1900025590. Registered 1 February 2019- Retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx.

Background: It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. Methods: A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor^®, Dicofarm, Rome, Italy) in a dose of 6 × 10⁹ colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. Results: Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Conclusion: Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations.

For many health care providers, an umbilical venous catheter (UVC) may be a contraindication for skin-to-skin contact (SSC). Our aim was to compare the frequency of adverse events between preterm infants who were on SSC with UVC and those who remained in an incubator. Prospective observational study in newborns less than 35 weeks gestation. UVC-related adverse events were compared between neonates who performed SSC and those who did not. The incidence of catheter-related displacement, leak, loss, hemorrhage, malfunction, and bloodstream infection was studied. From 226 patients, 171 performed SSC with UVC. Their first contact was earlier than in those who remained in an incubator (SSC-UVC, 29 hours [interquartile range (IQR): 21-53] vs. no SSC-UVC, 132 hours [IQR: 96-188]; p < 0.001). Both groups were similar in gestational age (SSC-UVC, 30 weeks vs. no SSC-UVC, 30.3 weeks; p = 0.331) and birth weight (SSC-UVC, 1,285 g vs. no SSC-UVC, 1,355 g; p = 0.2). Studied complications were not more frequent in patients who performed SSC. In fact, although it was not statistically significant, a lower overall incidence of adverse events (SSC-UVC, 13.5% vs. no SSC-UVC, 20%; p = 0.237) and catheter-related bloodstream infection (SSC-UVC, 4.7% vs. no SSC-UVC, 10.9%; p = 0.111) was observed in this group. SSC with a UVC is a safe procedure and there are no more complications in newborns who perform SSC compared to those who remain in the incubator. Due to its demonstrated benefits, SSC should be promoted in premature newborns regardless of the presence of a UVC. · SSC in preterm infants with UVCs is safe.. · Early SSC does not increase UVC-related bloodstream infection.. · Early SSC should be promoted in stable patients regardless of the presence of a UVC..

Septic arthritis is the infection of native or prosthetic joints. In native joints, bacterial infection is commonly caused by Staphylococcus aureus through haematogenous spread. Prompt recognition is essential to prevent destruction of articular cartilage. Diagnosis is confirmed by microbiological studies on joint aspirate but preliminary results can be negative. Treatment consists of surgical washout followed by antibiotics. Prosthetic joint infections are managed by washout with retention of prosthesis or two-stage revision depending on the time since initial surgery. Acute osteomyelitis is infection of bone caused often by haematogenous spread but can result from contamination of deep wounds, ulcers or previous surgery (internal fixation of fractures). Symptoms might be nonspecific and therefore a thorough history helps reach the diagnosis. MRI and bone scan identify the affected bony segment but diagnosis is confirmed through histological studies from biopsies. Treatment consists of intravenous antibiotics but surgical drainage might be required when antibiotherapy fails.

Severe injury and infection are associated with autonomic dysfunction. The realization that a dysregulation in autonomic function may predispose a host to excessive inflammatory processes has renewed interest in understanding the role of central nervous system (CNS) in modulating systemic inflammatory processes. Assessment of heart rate variability (HRV) has been used to evaluate systemic abnormalities and as a predictor of the severity of illness. Dissecting the relevance of neuroimmunomodulation in controlling inflammatory processes requires an understanding of the multiscale interplay between CNS and the immune response. A vital enabler in that respect is the development of a systems-based approach that integrates data across multiple scales, and models the emerging host response as the outcome of interactions of critical modules. Thus, a multiscale model of human endotoxemia, as a prototype model of systemic inflammation in humans, is proposed that integrates processes across the host from the cellular to the systemic host response level. At the cellular level interacting components are associated with elementary signaling pathways that propagate extracellular signals to the transcriptional response level. Further, essential modules associated with the neuroendocrine immune crosstalk are considered. Finally, at the systemic level, phenotypic expressions such as HRV are incorporated to assess systemic decomplexification indicative of the severity of the host response. Thus, the proposed work intends to associate acquired endocrine dysfunction with diminished HRV as a critical enabler for clarifying how cellular inflammatory processes and neural-based pathways mediate the links between patterns of autonomic control (HRV) and clinical outcomes.