Prediction of post-interventional physical function in diabetic foot ulcer patients using patient reported outcome measurement information system (PROMIS).

BACKGROUND: Infected diabetic foot ulcer (DFU) patients present with an impaired baseline physical function (PF) that can be further compromised by surgical intervention to treat the infection. The impact of surgical interventions on Patient Reported Outcomes Measurement Information System (PROMIS) PF within the DFU population has not been investigated. We hypothesize that preoperative PROMIS scores (PF, Pain Interference (PI), Depression) in combination with relevant clinical factors can be utilized to predict postoperative PF in DFU patients. METHODS: DFU patients from a single academic physician's practice between February 2015 and November 2018 were identified (n = 240). Ninety-two patients met inclusion criteria with complete follow-up and PROMIS computer adaptive testing records. Demographic and clinical factors, procedure performed, and wound healing status were collected. Spearman's rank correlation coefficient, Chi-Squared tests and multidimensional modelling were applied to all variables' pre- and postoperative values to assess patients' postoperative PF. RESULTS: The mean age was 60.5 (33-96) years and mean follow-up was 4.7 (3-12) months. Over 70 % of the patients' initial PF were 2-3 standard deviations below the US population (n = 49; 28). Preoperative PF (p < 0.01), PI (p < 0.01), Depression (p < 0.01), CRF (p < 0.02) and amputation level (p < 0.04) showed significant univariate correlation with postoperative PF. Multivariate model (r = 0.55) showed that the initial PF (p = 0.004), amputation level (p = 0.008), and wound healing status (p = 0.001) predicted postoperative PF. CONCLUSIONS: Majority of DFU patients present with poor baseline PF. Preoperative PROMIS scores (PF, PI, Depression) are predictive of postoperative PROMIS PF in DFU patients. Postoperative patient's physical function can be assessed by PFpostoperative = 29.42 + 0.34 (PFinitial) - 5.87 (Not Healed) - 2.63 (Amputation Category). This algorithm can serve as a valuable tool for predicting post-operative physical function and setting expectations.

Distinct vasculotropic versus osteotropic features of S. agalactiae versus S. aureus implant-associated bone infection in mice.

Osteomyelitis is a devastating complication of orthopaedic surgery and commonly caused by Staphylococcus aureus (S. aureus) and Group B Streptococcus (GBS, S. agalactiae). Clinically, S. aureus osteomyelitis is associated with local inflammation, abscesses, aggressive osteolysis, and septic implant loosening. In contrast, S. agalactiae orthopaedic infections generally involve soft tissue, with acute life-threatening vascular spread. While preclinical models that recapitulate the clinical features of S. aureus bone infection have proven useful for research, no animal models of S. agalactiae osteomyelitis exist. Here, we compared the pathology caused by these bacteria in an established murine model of implant-associated osteomyelitis. In vitro scanning electron microscopy and CFU quantification confirmed similar implant inocula for both pathogens (~105 CFU/pin). Assessment of mice at 14 days post-infection demonstrated increased S. aureus virulence, as S. agalactiae infected mice had significantly greater body weight, and fewer CFU on the implant and in bone and adjacent soft tissue (p < 0.05). X-ray, µCT, and histologic analyses showed that S. agalactiae induced significantly less osteolysis and implant loosening, and fewer large TRAP+ osteoclasts than S. aureus without inducing intraosseous abscess formation. Most notably, transmission electron microscopy revealed that although both bacteria are capable of digesting cortical bone, S. agalactiae have a predilection for colonizing blood vessels embedded within cortical bone while S. aureus primarily colonizes the osteocyte lacuno-canalicular network. This study establishes the first quantitative animal model of S. agalactiae osteomyelitis, and demonstrates a vasculotropic mode of S. agalactiae infection, in contrast to the osteotropic behavior of S. aureus osteomyelitis.

Evolving concepts in bone infection: redefining "biofilm", "acute vs. chronic osteomyelitis", "the immune proteome" and "local antibiotic therapy".

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast, S. aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.