Picomets: Assessing single and few cell metastases in melanoma sentinel lymph node biopsies.

BACKGROUND: Lymph node involvement is a significant prognostic factor for melanoma. Both number of positive nodes and disease burden within a lymph node affects survival. However, the significance of few tumor cells within a single node and subsequent optimal management remains without consensus. We investigated the implications of minimal nodal disease on clinical outcomes. METHODS: We reviewed 752 patients who underwent lymph node sampling at time of primary melanoma resection at our institution over 15 years. We deemed patients who had 1 node with 1 to 4 atypical cells staining positive for either Melan-A or Sox-10 as having "picomets." We examined the initial clinicopathological features, subsequent management, and outcomes. RESULTS: Thirty-three patients (4%) met criteria for having picomets. The most common number of positively staining atypical cells was 1 (n = 13). Nodal staging at initial pathology review varied, and overall stage ranged from IA to IIIC. Four patients underwent further therapy, none of whom had recurrent disease. Of the 29 patients undergoing observation/surveillance only, 5 had disease recurrence (17%). CONCLUSION: Although patients with picomets had better outcomes than historical stage matched cohorts, a small subset had recurrent disease. Staging patients with picomets as "N0" may not reflect the true negative prognostic significance of picomets. A larger population of patients meeting picomets criteria is needed to draw further conclusions.

Intraoperative Site Vancomycin Powder Application in Infected Diabetic Heel Ulcers With Calcaneal Osteomyelitis.

BACKGROUND: Intraoperative site application of vancomycin powder has been found to be beneficial in foot and ankle surgery among diabetic patients undergoing elective procedures. However, there are concerns for risks such as selection of multidrug-resistant bacteria, local tissue irritation, and increased wound complications. The clinical utility of intraoperative site vancomycin powder application in infected diabetic foot ulcer surgery is unknown. We aimed to report the clinical outcomes of partial or total calcanectomy for diabetic heel ulcer (DHU) and determine if intraoperative site application of vancomycin powder placement at the time of wound closure leads to improved clinical outcomes. METHODS: A current procedural terminology query (CPT 28120: partial excision bone; talus or calcaneus) was run that identified 35 patients representing 38 calcanectomies performed secondary to infected DHU with calcaneal osteomyelitis. An initial group of 25 patients did not receive intraoperative site vancomycin powder, whereas the following 13 cases received intraoperative site vancomycin powder. Demographics, clinical characteristics, comorbidities, operative complications, unexpected return to the operating room (RTOR), and revision amputations were recorded for each patient. Average follow-up was 26.1 (6.5-51.6) months. RESULTS: There was a significantly higher rate of RTOR among the vancomycin powder cohort (VANC) relative to the no-vancomycin cohort (No-VANC) (84.6% vs 36.0%, P = .038). Of the 13 VANC patients, 3 healed the wound and did not require RTOR, 2 underwent below-knee amputation (BKA), 2 received irrigation and debridement (I&D), and 6 underwent revision or total calcanectomies. Of the 25 No-VANC patients, 17 healed the wound, 4 underwent BKAs, 1 received an I&D, and 2 required revision or total calcanectomy. There was a trend toward increased rates of revision calcanectomy and BKA among the VANC cohort, but this was not statistically significant (61.5% vs 28.0%, P = .079). CONCLUSION: Partial or total calcanectomies for the management of infected DHU resulted in an overall healing rate of 50.0%, unplanned RTOR and revision calcanectomy rate of 39.5%, and a limb salvage rate of 82.6%. We found no clinical benefit with the intraoperative site application of vancomycin powder. LEVEL OF EVIDENCE: Level III, retrospective case control study.

Loss of Gas6 and Axl signaling results in extensive axonal damage, motor deficits, prolonged neuroinflammation, and less remyelination following cuprizone exposure.

The TAM (Tyro3, Axl, and MerTK) family of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and ProS1, are important for innate immune responses and central nervous system (CNS) homeostasis. While only Gas6 directly activates Axl, ProS1 activation of Tyro3/MerTK can indirectly activate Axl through receptor heterodimerization. Therefore, we generated Gas6-/- Axl-/- double knockout (DKO) mice to specifically examine the contribution of this signaling axis while retaining ProS1 signaling through Tyro3 and MerTK. We found that naïve young adult DKO and WT mice have comparable myelination and equal numbers of axons and oligodendrocytes in the corpus callosum. Using the cuprizone model of demyelination/remyelination, transmission electron microscopy revealed extensive axonal swellings containing autophagolysosomes and multivesicular bodies, and fewer myelinated axons in brains of DKO mice at 3-weeks recovery from a 6-week cuprizone diet. Analysis of immunofluorescent staining demonstrated more SMI32+ and APP+ axons and less myelin in the DKO mice. There were no significant differences in the number of GFAP+ astrocytes or Iba1+ microglia/macrophages between the groups of mice. However, at 6-weeks cuprizone and recovery, DKO mice had increased proinflammatory cytokine and altered suppressor of cytokine signaling (SOCS) mRNA expression supporting a role for Gas6-Axl signaling in proinflammatory cytokine suppression. Significant motor deficits in DKO mice relative to WT mice on cuprizone were also observed. These data suggest that Gas6-Axl signaling plays an important role in maintaining axonal integrity and regulating and reducing CNS inflammation that cannot be compensated for by ProS1/Tyro3/MerTK signaling.