Effect of Dose on Intra-Articular Amikacin Sulfate Concentrations Following Intravenous Regional Limb Perfusion in Horses.

OBJECTIVE: To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. STUDY DESIGN: Randomized crossover experiment. ANIMALS: Six adult horses. METHODS: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period). Amikacin concentrations were quantified in synovial fluid collected from the middle carpal and metacarpophalangeal joints at 25 minutes, and 24, 36, and 48 hours after IVRLP. Minimum inhibitory concentrations (MIC) were determined from equine bacterial isolates and ability to reach target amikacin concentrations were compared. RESULTS: Overall, middle carpal joint amikacin concentrations were higher following IVRLP with 3 g amikacin compared to 2 g (P=.031), with significant differences at 25 minutes (P=.002) and 24 hours (P=.021). No differences were observed between doses in the metacarpophalangeal joint (P=.267). Target amikacin concentrations for Staphylococcus aureus and coagulase-negative staphylococci were achieved in middle carpal and metacarpophalangeal joints at 25 minutes with both dosages and for Escherichia coli and Actinobacillus spp. in the middle carpal joint at 25 minutes with 3 g. Target concentrations were not achieved for Enterococcus spp, Pseudomonas spp, or Streptococcus equi ssp. zooepidemicus. CONCLUSION: A 3 g amikacin dose is not justified in the majority of distal limb injuries, but should be reserved for isolates with an MIC higher than that achievable with a 2 g dose. Daily IVRLP may be necessary based on our results.

Foot and ankle characteristics in systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVE: To determine characteristics of the foot and ankle in people with systemic lupus erythematosus (SLE). METHODS: Medline, CINAHL, Sports-Discus, Scopus and Cochrane Library databases were searched up to January 2018. Studies reporting foot- and ankle-related outcomes in the following domains were included: vascular, neurological, musculoskeletal, cutaneous (skin and nail) or pain/function. The Quality Index tool was used to assess methodological quality. Where appropriate, odds ratio (OR) and mean difference meta-analyses were conducted for case-control studies; and pooled mean prevalence meta-analyses for studies assessing characteristics in SLE. RESULTS: Forty-nine studies were included with mean (range) quality scores of 75% (38-100%). Twenty-three studies assessed vascular characteristics, followed by musculoskeletal (n = 16), neurological (n = 11), cutaneous (n = 5) and pain/function (n = 4). Foot and ankle characteristics in people with SLE included impaired vascular supply, abnormal nerve function, musculoskeletal pathology, skin and nail pathology, and pain and functional disability. Twenty-four studies were included in meta-analyses. Pooled OR for abnormal ankle brachial index was 3.08 for SLE compared with controls. Pooled mean difference in brachial-ankle pulse-wave velocity between SLE and controls was significant (161.39 cm/s, P = 0.004). Pooled prevalence was 0.54 for intermittent claudication, 0.50 for Raynaud's phenomenon, 0.28 for chilblains, 0.00 for gangrene, 0.30 for hallux valgus, 0.15 for onychomycosis, 0.76 for history of foot pain, and 0.36 for current foot pain. CONCLUSION: People with SLE experience a wide range of foot and ankle manifestations. Published research highlights the impact of peripheral arterial disease, peripheral neuropathy, musculoskeletal deformity, skin and nail pathology and patient-reported foot pain and disability.

Neurovascular structures at risk with percutaneous fixation in tarsometatarsal fusion: A cadaveric study.

INTRODUCTION: First tarsometatarsal (TMT) joint fusion is routinely used for arthritis and deformities. Common fixation methods include a locking plate construct, cross-screws, or combinations of the two. Cross screws have proven effective for union and stability; however, there is a potential for harm to nearby neurovascular structures due to the nature of percutaneous insertion technique. This study assessed risk of damage to the superficial peroneal nerve with percutaneous TMT fusion. METHODS: Nine fresh-frozen cadaver specimens were included. A medial incision in the internervous plane was made for TMT joint preparation. Two crossed percutaneous wires followed by 4.0 cc screws were placed in the dorsal aspect of the proximal aspect of first metatarsal and in the medial cuneiform. Both were 10-15 mm from the TMT joint line. The dorsal aspect of the foot was dissected and examined for neurovascular interruptions, particularly branches of the superficial peroneal nerve. RESULTS: Results showed a mean distance of 4.33 mm from the proximal pin to the medial branch of the superficial peroneal nerve. The distal pin had a mean distance of 6.44 mm from the medial branch, with one pin 9 mm from the lateral branch. One incident of direct injury to the neurovascular bundle was observed. CONCLUSION: Preparing the joint from the medial side using a percutaneous approach is less invasive, but presents a relative risk for neuritis. Care should be taken during insertion of the percutaneous screw after TMT joint preparation for fusion. LEVEL OF EVIDENCE: Level V, cadaver study.

Mechanism of accumulation of 99mTc-sulesomab in inflammation.

UNLABELLED: 99mTc-Sulesomab, the Fab fragment of anti-NCA-90, is used as an in vivo granulocyte labeling agent for imaging inflammation. It is not clear to what extent it targets cells that have already migrated into the interstitial space of an inflammatory lesion as opposed to circulating cells. The contribution to signal of radioprotein diffusion in the setting of increased vascular permeability is also poorly documented. METHODS: We compared the local kinetics of (99m)Tc-sulesomab and (99m)Tc-labeled human serum albumin (HSA), which have similar molecular sizes, in 7 patients with orthopedic infection proven by clearly positive (111)In-leukocyte scintigraphy. (99m)Tc-Sulesomab and (99m)Tc-HSA were administered in sequence separated by an interval of 2-6 d. Images were obtained 1, 3, 4, and 6 h after injection, and multiple venous blood samples were obtained for blood clearance measurement. Patlak-Rutland (P-R) analysis was performed to measure lesion and control tissue protein clearance. Target-to-background tissue (T/Bkg) ratios were calculated for each radioprotein and compared with the T/Bkg ratio for (111)In-leukocytes. (99m)Tc-Sulesomab binding to granulocytes was measured in vitro and ex vivo and to primed and activated granulocytes in vitro. RESULTS: After intravenous injection, <5% of the circulating radioactivity was cell bound with both radioproteins so that the P-R curves could therefore be assumed to represent extravascular uptake of free protein. The blood clearance (mean +/- SD) of sulesomab was 23.4 +/- 11.7 mL/min, approximately 5 times greater than that of HSA, for which it was 4.8 +/- 3.1 mL/min. Likewise, clearance into the lesion of sulesomab was consistently higher than that of HSA, on average about 3 times as high. Nevertheless, the T/Bkg ratios for sulesomab and HSA were similar, except at 6 h when that of HSA (2.14 +/- 0.6) was higher than that of sulesomab (1.93 +/- 0.5; P approximately 0.01). Both values were considerably less than the T/Bkg ratio on the (111)In-leukocyte images, which, at 22 h, was 12.3 +/- 5.3. Moderate clearance of sulesomab, but not HSA, was seen in the control tissue. Granulocytes bound significantly more (99m)Tc-sulesomab in vitro when primed or activated. CONCLUSION: (a) Sulesomab does not localize in inflammation as a result of binding to circulating granulocytes; (b) sulesomab is cleared into inflammation nonspecifically via increased vascular permeability; nevertheless, it may be cleared after local binding to primed granulocytes or bind to activated, migrated extravascular granulocytes; and (c) HSA produces a similar or higher T/Bkg ratio than sulesomab because sulesomab is cleared into normal tissues and because image positivity in inflammation is significantly dependent on local blood-pool expansion.