Surgical pathology

This chapter focuses on surgical pathology. Pathology forms the basis for understanding surgical management. The chapter outlines key concepts that are relevant to the surgical patient and highlights key pathogenesis factors and clinical points. It deals with cellular injury; inflammation; hypersensitivity reactions; wound healing; ulcers; cysts, sinuses, and fistulae; atherosclerosis; thromboembolic disease; gangrene and capillary ischaemia; neoplasia; carcinogenesis; tumours; and tumour markers. Moreover, it examines the grading and staging of a tumour, and discusses surgically important bacteria, viruses, surgical site infections, soft tissue and bone infections, bleeding and coagulation, and anaemia and polycythaemia. Other infections in the surgical patient include nosocomial (healthcare acquired) infections, infective diarrhoea, urinary tract infection (UTI), and pelvic inflammatory disease (PID).

Bone infection: a clinical priority for clinicians, scientists and educators

Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection.

Efficacy of Nano-Encapsulated Daptomycin in an Experimental Methicillin-Resistant Staphylococcus aureus (MRSA) Bone and Joint Infection Model

S. aureus bone infections remain a therapeutic challenge, leading to long and expensive hospitalizations. Systemic antibiotic treatments are inconsistently effective due to insufficient penetration into the infectious site. In an osteomyelitis model, the single local administration of nanoparticle-encapsulated daptomycin allows sterilization of the infectious sites after 4 and 14 days of treatment, while daily systemic treatment of daptomycin for 4 days was not effective. These results demonstrate the great interest of this local antibiotic treatment.

The Effect of Needle Tract Nursing Methods to Reduce Needle Tract Infection in Patients with Indwelling Percutaneous Bone Puncture

Percutaneous bone piercing needles are used in orthopedics, which play the role of needle fixation. Needle tract infection is a common complication during the use of percutaneous bone needles. How to prevent needle tract infection is an important topic, so it is necessary to explore better needle tract care methods during percutaneous bone needle indwelling, to provide a basis for clinical work. Based on this, the purpose of this article is to study the effects of needle tract nursing methods for patients with indwelling percutaneous bone puncture needle infections. In this article, through an overview of percutaneous bone needle tract infection, on this basis, a detailed analysis of its occurrence, causes, and main influencing factors are carried out. Experimental studies have shown that the incidence of needle tract infections is 23.64%, mainly mild needle tract infections. Mild needle tract infections account for 84.62% of all needle tract infections, of which grade 1 needle tract infections account for 50.00 of mild needle tract infections. Severe needle tract infections accounted for 15.38% of all needle tract infections. All severe needle tract infections were grade 4 needle tract infections. No patients had bone infections or osteomyelitis.

IgG4-specific responses in patients with Staphylococcus aureus bone infections are not predictive of postoperative complications

The most prevalent pathogen in bone infections is Staphylococcus aureus; its incidence and severity are partially determined by host factors. Prior studies showed that anti-glucosaminidase (Gmd) antibodies are protective in animals, and 93.3 % of patients with culture-confirmed S. aureus osteomyelitis do not have anti-Gmd levels > 10 ng/mL in serum. Infection in patients with high anti-Gmd remains unexplained. Are anti-Gmd antibodies in osteomyelitis patients of the non-opsonising, non-complement-fixing IgG4 isotype? The relative amounts of IgG4 and total IgG against Gmd and 7 other S. aureus antigens: iron-surface determinants (Isd) IsdA, IsdB, and IsdH, amidase (Amd), α-haemolysin (Hla), chemotaxis inhibitory protein from S. aureus (CHIPS), and staphylococcal-complement inhibitor (SCIN) were determined in sera from healthy controls (Ctrl, n = 92), osteomyelitis patients whose surgical treatment resulted in infection control (IC, n = 95) or an adverse outcome (AD, n = 40), and post-mortem (PM, n = 7) blood samples from S. aureus septic-death patients. Anti-Gmd IgG4 levels were generally lower in infected patients compared to controls; however, levels among the infected were higher in AD than IC patients. Anti-IsdA, IsdB and IsdH IgG4 levels were increased in infected patients versus controls, and Jonckheere-Terpstra tests of levels revealed an increasing order of infection (Ctrl < IC < AD < PM) for anti-Isd IgG4 antibodies and a decreasing order of infection (Ctrl > IC > AD > PM) for anti-autolysin (Atl) IgG4 antibodies. Collectively, this does not support an immunosuppressive role of IgG4 in S. aureus osteomyelitis but is consistent with a paradigm of high anti-Isd and low anti-Atl responses in these patients.

Specific Bacterial Immunotherapy in Treating Chronic Osteomyelitis

The immunological experience is treating osteomyelitis chronic forms at the Istituto Putti in Cortina starts in 1963 by introducing immunotherapy, applied by the progressive administration in growing doses of a staphylococci pool, that had been collected from some patients with bone infections by the same germ and then inactivated in an aqueous solution suspension. This therapy is coadjutant of antibiotics, surgical and hyperbaric therapy and not substitutive of these. This study ascertained indeed a reduction of the phagocytic activity as a whole, and especially the opsonisation activity It has been thought therefore that in immunotherapy more factors are involved; their principal property is to reduce the allergising effect and therefore to desensitise vs. the germ proteins and to increase the phagocytic activity. This condition, neither whose entity nor its lasting may be defined, does not appear to be unlimited. Obviously this desensitisation can be obtained also by the right antibiotic choice that, as already said mainly in acute forms, may develop their bactericidal properties and sterilise the focus. In the chronic forms it is possible to provoke this mechanism by carrying out a surgical toilette that restores the vascularization and stimulation conditions needed for a correct antibiotic action. Checks upon immuno-stimulation treatment termination clearly showed corresponding results between laboratory deficit corrected and clinical conditions bettering. The casuistry is based on 50 patients with hematogenic osteomyelitis, all under the age of 16, age at which the growth plate is still active, and 117 post-traumatic septic non-union, where this term was adopted for cases that showed a lack of non-solidification at 6 months after trauma. We have expressly made a distinction between hematogenic and post-traumatic forms, since the relationships between bacterial counts vs. host response do differ.

Staphylococci planktonic and biofilm environments differentially affect macrophage immune activation and osteoclastogenic differentiation.

Implant-related bone infections are a major complication in orthopedic surgery that lead to inflammation and bone destruction. Bacterial biofilm formation on the implant is discussed to polarize the immune response towards tolerance and to facilitate bacterial persistence. In addition to their role in the early immune response, macrophages are osteoclast precursor cells. Therefore, macrophages can link inflammation and RANKL-mediated osteoclastogenic bone destruction. We investigated the influence of Staphylococcus aureus (SA) and epidermidis (SE) biofilm formation on immune function and osteoclastogenesis using RAW264.7 cells and conditioned media (CM) of planktonic and biofilm cultures in the presence and absence of the osteoclastogenic transcription factor RANKL. Analysis of immune cell activation, metabolic activity and osteoclast formation revealed that a planktonic environment causes a pro-inflammatory response. This was also partially induced by biofilm CM. Simultaneous stimulation with CM and RANKL suppressed osteoclast formation in favor of a long-term immune activation. While the early macrophage response towards CM was dominated by glycolysis, the CM and RANKL approach shifted metabolism towards increased mitochondrial biomass and activity. This was most evident in biofilm CM. We further showed that planktonic CM effects are mediated through activation of TLR signaling and induction of IFN-β production. In biofilm CM, high lactate levels seem to significantly contribute to the modulation of macrophages. Our results can contribute to find targets for therapeutic intervention that restore an effective pro-inflammatory immune response, which could help to control implant-related bone infections.