Best Clinical Practice in Botulinum Toxin Treatment for Children with Cerebral Palsy

Botulinum toxin A (BoNT-A) is considered a safe and effective therapy for children with cerebral palsy (CP), especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS) of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.     

Changing world of neutrophils

Neutrophilic granulocytes are no longer regarded as cells involved only in the last phase of the immune response with one single—although vitally important—task: engulfing and killing of microorganisms marked by immunoglobulin or complement fragments. In recent years, it was shown that neutrophils are actively involved in initiation and organization of the adaptive immune response by releasing various cytokines, interacting with all major types of immune cells, regulating their own lifespan, and participating in the anaphylactic reaction and in several classically nonimmune functions such as hemostasis, atherogenesis, and even insulin resistance. The antibacterial effect is no longer restricted to killing and destruction of microorganisms sequestered in the phagosomal space. Bacteriostasis also occurs at certain locations of the extracellular space, by formation of neutrophil extracellular traps (NETs) that were shown in the last 2 years to have a significant role in the prevention of dissemination of microorganisms. Extracellular vesicles represent a recently discovered form of intercellular communication carried out both by lipids, proteins, and nucleic acids. In this review, we also summarize the role of neutrophil-derived extracellular vesicles in modifying the function of other cell types as well as their direct antibacterial effect that differs significantly from mechanisms applied either by neutrophils or by the NETs.     

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6–20.7) and 32.3 (95% CI 27.3–38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58–5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.     

Colonic anastomotic healing in the context of altered macrophage function and endotoxemia

Purpose  

Prevention of perioperative activation of intestinal muscularis macrophages is a promising intervention to avoid post-traumatic gastrointestinal tract dysfunction. However, impaired macrophage function could have deleterious consequences on anastomotic healing, especially in complications aggravating the healing process itself, such as infectious problems either as preexisting local inflammation or infection (e.g., complicated diverticulitis) or endotoxemia due to early postoperative infections (e.g., pneumonia). Aim of this study was to investigate colonic anastomotic healing in macrophage-depleted mice in the presence of endotoxemia.