A wide array of benefits has been attributed to metformin. These include attenuation of abnormal glucose metabolism (diabetes treatment and prevention), weight neutrality or weight loss, improvement in the pathophysiologic components of metabolic syndrome (insulin resistance, subclinical inflammation, and endothelial dysfunction), lipid-lowering properties, cardiovascular protection, and antineoplastic potential. Metformin itself is not a nephrotoxic drug. Initially appointed as the safest hypoglycemic agent in chronic kidney disease, its use has been limited in these patients because of the perceived risk of lactic acidosis. A fear perpetuated by numerous case reports in which it is implicated. Current guidelines stipulate that it must be used with caution in estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute. Identified risk factors for metformin-associated lactic acidosis include acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock. Treatment may include supportive care and dialysis techniques. On the other hand, it is likely that the use of metformin would be beneficial in many with chronic kidney disease according to the advantages associated with attenuation of metabolic syndrome and cardiovascular protection. The reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment raises the question of limitation of its use in these patients.

Background Two-stage exchange arthroplasty remains the most popular option for the treatment of chronic periprosthetic joint infection (PJI). Determining infection eradication and optimal timing of reimplantation can be challenging. Information to allow for a truly informed evidence-based decision is scarce. Methods We conducted a critical review of available evidence on the presently available tests to help determine timing of reimplantation. Results Serology is traditionally used to follow up patients after the first stage. Despite tradition mandates waiting for normal inflammatory markers, there is actually no evidence that they correlate with persistent infection. The role of synovial fluid investigation between stages is also explored. Cultures lack sensitivity and neither differential leukocyte counts nor alternative biomarkers have proven to be accurate in identifying persistent infection with a spacer in situ. We also examined the evidence regarding the optimal time interval between resection and reimplantation and whether there is evidence to support the implementation of a two week “antibiotic holiday” prior to proceeding with reimplantation. Finally, wound healing and other important factors in this setting will be discussed. Conclusion Currently there are no accurate metrics to aid in the decision on the optimal timing for reimplantation. Decision must therefore rely on the resolution of clinical signs and down trending serological and synovial markers.

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