In vitro laboratory infection research in orthopaedics:Why,when,and how

The musculoskeletal system involves multiple tissues which are constantly exposed to being exposed to various biological and mechanical stimuli.As such,isolating and studying a particular system from a complex human clinical environment is not always a realistic expectation.On top of that,recruitment limitations,in addition to the nature of orthopaedic interventions and their associated cost,sometimes preclude consideration of human trials to answer a clinical question.Therefore,in this mini review,we sought to rationalize the rapid evolution of biomedical research at a basic scientific level and explain why the perception of orthopaedic conditions has fundamentally changed over the last decades.In more detail,we highlight that the number of orthopaedic in vitro publications has soared since 1990.Last but not least,we elaborated on the minimum requirements for conducting a scientifically sound infection-related laboratory experiment to offer valuable information to clinical practitioners.We also explained the rationale behind implementing molecular biology techniques,ex vivo experiments,and artificial intelligence in this type of laboratory research.

Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: A preliminary study

AIM To evaluate the ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition.METHODS Twenty healthy Italian volunteers, eight males and twelve females, participated in the study. Ten subjects took a sachet containing 4 × 109 colony-forming units(CFU) of Bifidobacterium longum BB536 and 109 CFU of Lactobacillus rhamnosus HN001, 30 min before breakfast(pre-prandial administration), while ten subjects took a sachet of probiotic product 30 min after breakfast(post-prandial administration). The ability ofLactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize human gut microbiota was assessed by means of quantitative real-time PCR, while changes in gut microbiota composition were detected by using Ion Torrent Personal Genome Machine.RESULTS Immediately after 1-mo of probiotic administration, B. longum BB536 and L. rhamnosus HN001 load was increased in the majority of subjects in both preprandial and post-prandial groups. This increase was found also 1 mo after the end of probiotic oral intake in both groups, if compared to samples collected before probiotic consumption. At phyla level a significant decrease in Firmicutes abundance was detected immediately after 1-mo of B. longum BB536 and L. rhamnosus HN001 oral intake. This reduction persisted up to 1 mo after the end of probiotic oral intake together with a significant decrease of Proteobacteria abundance if compared to samples collected before probiotic administration. Whereas, at species level, a higher abundance of Blautia producta, Blautia wexlerae and Haemophilus ducrey was observed, together with a reduction of Holdemania filiformis, Escherichia vulneris, Gemmiger formicilis and Streptococcus sinensis abundance. In addition, during follow-up period we observed a further reduction in Escherichia vulneris and Gemmiger formicilis, together with a decrease in Roseburia faecis and Ruminococcus gnavus abundance. Conversely, the abundance of Akkermansia muciniphila was increased if compared to samples collected at the beginning of the experimental time course CONCLUSION B. longum BB536 and L. rhamnosus HN001 showed the ability to modulate the gut microbiota composition, leading to a significant reduction of potentially harmful bacteria and an increase of beneficial ones. Further studies are needed to better understand the specific mechanisms involved in gut microbiota modulation.

Predicting lower limb periprosthetic joint infections: A review of risk factors and their classification

AIM To undertook a systematic review to determine factors that increase a patient's risk of developing lower limb periprosthetic joint infections(PJI).METHODS This systematic review included full-text studies that reviewed risk factors of developing either a hip or knee PJI following a primary arthroplasty published from January 1998 to November 2016. A variety of keywords were used to identify studies through international databases referencing hip arthroplasty, knee arthroplasty, infection, and risk factors. Studies were only included if they included greater than 20 patients in their study cohort, and there was clear documentation of the statistical parameter used; specifically P-value, hazard ratio, relative risk, or/and odds ratio(OR). Furthermore a quality assessment criteria for the individual studies was undertaken to evaluate the presence of record and reporting bias. RESULTS Twenty-seven original studies reviewing risk factors relating to primary total hip and knee arthroplasty infections were included. Four studies(14.8%) reviewed PJI of the hip, 3(11.21%) of the knee, and 20(74.1%) reviewed both joints. Nineteen studies(70.4%) were retrospective and 8(29.6%) prospective. Record bias was identified in the majority of studies(66.7%). The definition of PJI varied amongst the studies but there was a general consensus to define infection by previously validated methods. The most significant risks were the use of preoperative high dose steroids(OR = 21.0, 95%CI: 3.5-127.2, P < 0.001), a BMI above 50(OR = 18.3, P < 0.001), tobacco use(OR = 12.76, 95%CI: 2.47-66.16, P= 0.017), body mass index below 20(OR = 6.00, 95%CI: 1.2-30.9, P = 0.033), diabetes(OR = 5.47, 95%CI: 1.77-16.97, P = 0.003), and coronary artery disease(OR = 5.10, 95%CI: 1.3-19.8, P = 0.017).CONCLUSION We have highlighted the need for the provider to optimise modifiable risk factors, and develop strategies to limit the impact of non-modifiable factors.

Viral infections in orthopedics: A systematic review and classification proposal

BACKGROUND Although the impact of microbial infections on orthopedic clinical outcomes is well recognized,the influence of viral infections on the musculoskeletal system might have been underestimated.AIM To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.METHODS We searched MEDLINE,Cochrane Central Register of Controlled Trials(CENTRAL),the Reference Citation Analysis(RCA),and Scopus for completed studies published before January 30,2021,to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries.Quality assessment was performed using SYRCLE's risk of bias tool for animal studies,Moga score for case series,Wylde score for registry studies,and Newcastle-Ottawa Scale for case-control studies.RESULTS Six human and four animal studies were eligible for inclusion in the qualitative synthesis.Hepatitis C virus was implicated in several peri-and post-operative complications in patients without cirrhosis after major orthopedic surgery.Herpes virus may affect the integrity of lumbar discs,whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.CONCLUSION Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis.Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms.Therefore,based on our literature search,the proposed clinical and pathogenetic classification scheme is as follows:(1)Viral infections of bone or joint;(2)Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues;and(3)Viral infection as a risk factor for post-surgical bacterial infection.

Rationalising animal research synthesis in orthopaedic literature

Systematic reviews in orthopaedic literature are frequently criticised for offering inconsistent conclusions.On top of that,high-quality randomized human evidence on crucial orthopaedic topics is more often than not lacking.In this situation,pooling animal literature could offer an excellent insight into unanswered critical clinical questions,thus potentially improving healthcare.In this paper,we sought to present the rationale and basic principles governing meta-analysis of animal research.More specifically,we elaborated on the available evidence-based methods to achieve a scientifically sound animal data synthesis.In addition,we discussed result interpretation,strength of recommendations and clinical implications based on the results of these meta-analytic modalities.