Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model

Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Comparison of ventricular drainage in poor grade patients after intracranial hemorrhage

Abstract

Objectives: The selection of patients and treatment criteria for acute hydrocephalus and intracranial pressure (ICP) after intracranial hemorrhage remains unclear. In general neurosurgical practice, there is a tendency to use external ventricular drainage (EVD) for the patients. This study was undertaken to analyse the complications and efficiency of the different treatment modalities.

Methods: The effects, complications and outcome of ventricular drainage on high ICP and hydrocephalus were analysed retrospectively in 109 patients with intracranial hemorrhage. All the patients were assessed using the Glasgow Coma Scale, computed tomography and ICP monitoring. We excluded patients over the GCS of 8. All patients underwent a procedure for ICP monitoring plus ventricular cerebrospinal fluid (CSF) drainage. Sixty-one patients were managed with one (single) EVD system; 12 patients needed two EVD systems consecutively, while 23 patients underwent an EVD procedure followed by permanent ventriculoperitoneal (VP) shunt insertion. Thirteen patients were treated only by VP shunt for ventricular drainage. The infection rate and outcome 9 months after hemorrhage were analysed.

Results: The infection rates were 8.1% in the one-EVD group, 33.3% in the two-EVD group (one EVD versus two EVD, p<0.05), 8.6% in the EVD-VP group and 7.7% in the VP shunt group. The mortality rates were 73.7% in the one-EVD group, 83.8% in the two-EVD group, 47.8% (p<0.05) in the EVD-VP group and 53.8% (p<0.01) in the VP shunt group.

Discussion: This study indicates that single and short-term use of EVD and/or early VP shunting are associated with a low risk of infection. Furthermore, early VP shunting may protect the brain from the irregular control of intracranial hypertension and may allow more time for resolution of CSF circulation and significantly lowers the mortality rates.     

Inhibition of bacterial and leukocyte adhesion under shear stress conditions by material surface chemistry

Biomaterial-centered infections, initiated by bacterial adhesion, persist due to a compromised host immune response. Altering implant materials with surface modifying endgroups (SMEs) may enhance their biocompatibility by reducing bacterial and inflammatory cell adhesion. A rotating disc model, which generates shear stress within physiological ranges, was used to characterize adhesion of leukocytes and Staphylococcus epidermidis on polycarbonate-urethanes and polyetherurethanes modified with SMEs (polyethylene oxide, fluorocarbon and dimethylsiloxane) under dynamic flow conditions. Bacterial adhesion in the absence of serum was found to be mediated by shear stress and surface chemistry, with reduced adhesion exhibited on materials modified with polydimethylsiloxane and polyethylene oxide SMEs. In contrast, bacterial adhesion was enhanced on materials modified with fluorocarbon SMEs. In the presence of serum, bacterial adhesion was primarily neither material nor shear dependent. However, bacterial adhesion in serum was significantly reduced to 10% compared to adhesion in serum-free media. Leukocyte adhesion in serum exhibited a shear dependency with increased adhesion occurring in regions exposed to lower shear-stress levels of 7 dyne/cm². Additionally, polydimethylsiloxane and polyethylene oxide SMEs reduced leukocyte adhesion on polyether-urethanes. In conclusion, these results suggest that surface chemistry and shear stress can mediate bacterial and cellular adhesion. Furthermore, materials modified with polyethylene oxide SMEs are capable of inhibiting bacterial adhesion, consequently minimizing the probability of biomaterial-centered infections.     

共刺激分子在复感儿中医分型中的表达研究

[目的]通过观察反复呼吸道感染(RRTI)非急性感染期肺脾气虚、肺脾气阴两虚型患儿(简称"复感儿")T细胞CD8+CD28+的表达,探讨两个证型T淋巴细胞亚群的表达特点及临床意义,为RRll的中医辨证提供可能的物质基础及客观依据.[方法]选择RRTI非急性期肺脾气虚、肺脾气阴两虚患儿各30例,运用流式细胞仪对RRTI患...     

全层缝合在预防阑尾炎术后切口感染中的应用

目的：探讨全层缝合在预防阑尾炎术后切口感染的治疗效果。方法：将皮肤、皮下组织、腹外斜肌腱膜全层褥式缝合(腹膜不予缝合)。结果：56例患者无一例感染，也未发现近期并发症。结论：此方法对预防切口感染有较好疗效，且能缩短手术时间，操作简单，建议值得临床应用。     

The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61–15.04) and 11.55 (95% CI, 8.91–14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38–2.11) and 1.42 (95% CI, 0.49–2.36), and of all-cause death was 4.06 (95% CI, 2.50–5.61) and 3.96 (95% CI, 2.41–5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs–treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Chronic Systemic Infection of Mice with Leishmania infantum Leads to Increased Bone Mass

Vector-borne infections of humans with the protozoan parasite Leishmania (L.) infantum can cause a systemic and potentially lethal disease termed visceral leishmaniasis. In the corresponding mouse model, an intravenous infection with L. infantum leads to the persistence of parasites in various organs, including bone marrow (BM). Considering the anatomical proximity between the BM and the cortical bone, we investigated whether a chronic infection with L. infantum affected bone homeostasis. Unexpectedly, chronic infection with L. infantum caused an increase in bone mass in mice. In vivo, an increased number of osteoblasts and osteocytes and a decreased maturation of osteoclasts characterized the phenotype. Confocal laser scanning fluorescence microscopy confirmed the infection of BM macrophages but also revealed the presence of parasites in osteoclasts. In vitro, mature osteoclasts took up L. infantum parasites. However, infection of osteoclast progenitors abolished their differentiation and function. In addition, secretory products of infected BM–derived macrophages inhibited the maturation of osteoclasts. Both in vitro and in vivo, infected macrophages and osteoclasts showed an enhanced expression of the anti-osteoclastogenic chemokine CCL5 (RANTES). Neutralization of CCL5 prevented the inhibition of osteoclast generation seen in the presence of culture supernatants from L. infantum-infected macrophages. Altogether, our study shows that chronic infection with Leishmania increases bone mass by inducing bone formation and impairing osteoclast differentiation and function. © 2022 American Society for Bone and Mineral Research (ASBMR).     

速肤保的主要药效及安全性研究

本文探讨了外用新中成药速肤保的主要药效及安全性。实验结果表明:速肤保具有如下药理作用:1.对创伤感染常见的病原菌和条件致病菌均有不同程度的抗菌作用;2.有一定的抗炎作用。能抑制巴豆油混合致炎液所致的小鼠耳肿胀,抑制大鼠蛋清性足肿胀,对二甲苯所致小鼠毛细血管通透性增高有拮抗作用,能减少小鼠烫伤组织的含水量;3.有一定的镇痛作用。能抑制醋酸所致的小鼠扭体反应,提高小鼠痛阈,减轻热刺激所致的疼痛;4.有一定的止血作用。能缩短小鼠的出血时间。实验还证明,速肤保对小鼠无明显毒性作用,对新西兰大白兔正常及损伤皮肤均无明显刺激性,对豚鼠皮肤亦未产生过敏反应。本实验结果为速肤保的有效性和安全性提供了一定的药理学依据。     

Beta-thromboglobulin and platelet counts - effect of malignancy, infection, age and obesity

Plasma levels of beta-thromboglobulin (BTG) and platelet count were studied in 69 control subjects, 19 patients with operable abdominal malignancy, and 9 patients with acute bacterial infection. In control subjects there was a significant rise in BTG and fall in platelet count with age, and a negative correlation of BTG with obesity. BTG and platelet count were normal in patients with operable malignancy, but significantly increased in patients with acute bacterial infection. These effects must be considered in studies of BTG and thrombosis.     

Continuous positive pressure ventilation in children with bronchopneumonia

The application of a small end-expiratory pressure of 5 cmH2O to the assisted ventilation of nineteen children (mean age 19 months) with bronchopneumonia was compared with intermittent positive pressure ventilation. Within 1 h of introducing continuous positive pressure ventilation the alveolar-to-arterial oxygen gradient was reduced in most patients, with an increase in functional residual capacity and a decrease in total pulmonary blood shunt. Physiological dead space was also reduced, a feature not observed in other studies, and the significance of this finding is discussed. The use of continuous positive pressure ventilation in broncho-pulmonary infection was shown to be effective even at small pressures, and can be recommended especially for patients requiring long-term ventilation.