Clinical Outcomes and Cost Analysis of Fibula Free Flaps: A Retrospective Comparison of CAD/CAM versus Conventional Technique.

(1) Background: A decrease in operative time can not only improve patient outcomes through a reduction in the risk of developing complications but can also result in cost savings. The aim of this study is to determine whether there an intraoperative time gain can be achieved by using the preoperative virtual planning of mandibular reconstruction using a free fibula flap compared with freehand plate bending and osteotomies. (2) Methods: A retrospective comparative study was carried out in the Oral and Maxillofacial Department of La Paz University Hospital, Madrid, Spain. The study compared 18 patients in the CAD/CAM group with 19 patients in the conventional freehand group. A comparison was made between the total surgical time, the comorbidities, and the hospital stay. The resource consumption was estimated using a cost analysis. (3) Results: Although CAD/CAM was a statistically more expensive procedure in the perioperative phase, no significant differences were observed in total health care costs between the two groups. There was a non-significant trend towards an increase in complications with conventional reconstruction plates compared to patient-specific plates (PSI). (4) Conclusions: CAD/CAM technology and a 3D printed cutting guide offer a significantly shorter surgical time, which is associated with a reduction in hospital days, PACU days, and complications. The cost of CAD/CAM technology is comparable to that of the conventional freehand technique.

Impact of Goal Directed Therapy in Head and Neck Oncological Surgery with Microsurgical Reconstruction: Free Flap Viability and Complications.

(1) Background: Surgical outcomes in free flap reconstruction of head and neck defects in cancer patients have improved steadily in recent years; however, correct anaesthesia management is also important. The aim of this study has been to show whether goal directed therapy can improve flap viability and morbidity and mortality in surgical patients. (2) Methods: we performed an observational case control study to analyse the impact of introducing a semi invasive device (Flo Trac®) during anaesthesia management to optimize fluid management. Patients were divided into two groups: one received goal directed therapy (GDT group) and the other conventional fluid management (CFM group). Our objective was to compare surgical outcomes, complications, fluid management, and length of stay between groups. (3) Results: We recruited 140 patients. There were no differences between groups in terms of demographic data. Statistically significant differences were observed in colloid infusion (GDT 53.1% vs. CFM 74.1%, p = 0.023) and also in intraoperative and postoperative infusion of crystalloids (CFM 5.72 (4.2, 6.98) vs. GDT 3.04 (2.29, 4.11), p < 0.001), which reached statistical significance. Vasopressor infusion in the operating room (CFM 25.5% vs. GDT 74.5%, p < 0.001) and during the first postoperative 24h (CFM 40.6% vs. GDT 75%, p > 0.001) also differed. Differences were also found in length of stay in the intensive care unit (hours: CFM 58.5 (40, 110) vs. GDT 40.5 (36, 64.5), p = 0.005) and in the hospital (days: CFM 15.5 (12, 26) vs. GDT 12 (10, 19), p = 0.009). We found differences in free flap necrosis rate (CMF 37.1% vs. GDT 13.6%, p = 0.003). One-year survival did not differ between groups (CFM 95.6% vs. GDT 86.8%, p = 0.08). (4) Conclusions: Goal directed therapy in oncological head and neck surgery improves outcomes in free flap reconstruction and also reduces length of stay in the hospital and intensive care unit, with their corresponding costs. It also appears to reduce morbidity, although these differences were not significant. Our results have shown that optimizing intraoperative fluid therapy improves postoperative morbidity and mortality.

Periprocedural Direct Oral Anticoagulant Management: The RA-ACOD Prospective, Multicenter Real-World Registry.

Introduction There is scarce real-world experience regarding direct oral anticoagulants (DOACs) perioperative management. No study before has linked bridging therapy or DOAC-free time (pre-plus postoperative time without DOAC) with outcome. The aim of this study was to investigate real-world management and outcomes. Methods RA-ACOD is a prospective, observational, multicenter registry of adult patients on DOAC treatment requiring surgery. Primary outcomes were thrombotic and hemorrhagic complications. Follow-up was immediate postoperative (24-48 hours) and 30 days. Statistics were performed using a univariate and multivariate analysis. Data are presented as odds ratios (ORs [95% confidence interval]). Results From 26 Spanish hospitals, 901 patients were analyzed (53.5% major surgeries): 322 on apixaban, 304 on rivaroxaban, 267 on dabigatran, 8 on edoxaban. Fourteen (1.6%) patients suffered a thrombotic event, related to preoperative DOAC withdrawal (OR: 1.57 [1.03-2.4]) and DOAC-free time longer than 6 days (OR: 5.42 [1.18-26]). Minor bleeding events were described in 76 (8.4%) patients, with higher incidence for dabigatran (12.7%) versus other DOACs (6.6%). Major bleeding events occurred in 17 (1.9%) patients. Bridging therapy was used in 315 (35%) patients. It was associated with minor (OR: 2.57 [1.3-5.07]) and major (OR: 4.2 [1.4-12.3]) bleeding events, without decreasing thrombotic events. Conclusion This study offers real-world data on perioperative DOAC management and outcomes in a large prospective sample size to date with a high percentage of major surgery. Short-term preprocedural DOAC interruption depending on the drug, hemorrhagic risk, and renal function, without bridging therapy and a reduced DOAC-free time, seems the safest practice.

New techniques and recommendations in the management of free flap surgery for head and neck defects in cancer patients.

Free flap surgery is the gold standard surgical treatment for head and neck defects in cancer patients. Outcomes have improved considerably, probably due to recent advances in surgical techniques. In this article, we review improvements in the parameters traditionally used to optimize hematocrit levels and body temperature and to prevent vasoconstriction, and describe the use of cardiac output-guided fluid management, a technique that has proved useful in other procedures. Finally, we review other parameters used in free flap surgery, such as clotting/platelet management and nutritional optimization.

Identification and characterization of novel IGFBP5 interacting protein: evidence IGFBP5-IP is a potential regulator of osteoblast cell proliferation.

Insulin-like growth factor binding protein-5 (IGFBP5) is a multifunctional protein, which acts not only as a traditional binding protein, but also functions as a growth factor independent of IGFs to stimulate bone formation. It has been predicted that the intrinsic growth factor action of IGFBP5 involves binding of IGFBP5 to a putative receptor to induce downstream signaling pathways and/or nuclear translocation of IGFBP5 to influence transcription of genes involved in osteoblast cell proliferation/differentiation. Our study indentified proteins that bound to IGFBP5 using IGFBP5 as bait in a yeast two-hybrid screen of the U2 human osteosarcoma cell cDNA library. One of the clones that interacted strongly with the bait under high-stringency conditions corresponded to a novel IGFBP5 interacting protein (IGFBP5-IP) encoded by a gene that resides in mouse chromosome 10. The interaction between IGFBP5-IP and IGFBP5 is confirmed by in vitro coimmunoprecipitation studies that used pFlag and IGFBP5 polyclonal antibody, and cell lysates overexpressing both IGFBP5-IP and IGFBP5. Northern blot and RT-PCR analysis showed that the IGFBP-IP is expressed in both untransformed normal human osteoblasts and in osteosarcoma cell lines, which are known to produce IGFBP5. To determine the roles of IGFBP5-IP, we evaluated the effect of blocking the expression of IGFBP5-IP on osteoblast proliferation. We found that using a IGFBP5-IP-specific small interfering-hairpin plasmid resulted in a decrease in both basal and IGFBP5-induced osteoblast cell proliferation. On the basis of these findings, we predict that IGFBP5-IP may act as intracellular mediator of growth promoting actions of IGFBP5 and perhaps other osteoregulatory agents in bone cells.

Effects of secreted frizzled-related protein 3 on osteoblasts in vitro.

UNLABELLED: To examine if sFRP3s act as decoy receptors for Wnt, we examined the effects of recombinant sFRP3 on mouse osteoblast proliferation and differentiation. We found that sFRP3 unexpectedly increased osteoblast differentiation, suggesting it may act through other mechanisms besides acting as a decoy receptor for Wnt's. INTRODUCTION: Secreted frizzled-related proteins (sFRPs) are a truncated form of frizzled receptor, missing both the transmembrane and cytosolic domains. Because previous studies have shown that sFRPs bind and act as decoy receptors for Wnt proteins that promote osteoblast differentiation, we postulated that sFRP3 acts as an inhibitor of osteoblast differentiation. MATERIALS AND METHODS: We examined the effects of mouse recombinant sFRP3 and/or Wnt-3A on cell proliferation and differentiation using MC3T3-E1 mouse osteoblasts and primary cultures of mouse bone marrow stromal cells. We evaluated the effects of sFRP3 on beta-catenin levels using Western immunoblot analyses. RESULTS: We found that sFRP3 suppressed osteoblast cell number in a dose-dependent manner that was the result of a decrease in proliferation and not because of an increase in apoptosis. Surprisingly, sFRP3 increased osteoblast differentiation, which could not be explained based on sFRP3 acting as a decoy receptor for stimulatory Wnt's. Furthermore, sFRP3 did not inhibit Wnt3A-induced increase in alkaline phosphatase (ALP) activity. Wnt3A, but not sFRP3 treatment, increased cellular beta-catenin levels, and sFRP3 failed to block Wnt3A-induced increase in cellular beta-catenin levels. Treatment with endostatin, an agent known to degrade beta-catenin, did not inhibit sFRP3-induced increase in ALP activity. sFRP1, like sFRP3, inhibited proliferation and stimulated ALP activity in MC3T3-E1 mouse osteoblasts. CONCLUSIONS: Based on our findings, we conclude that sFRP3 decreased osteoblast proliferation and unexpectedly increased parameters of osteoblast differentiation. Based on our findings, we propose that sFRP3 may stimulate differentiation through a beta-catenin-independent pathway in addition to its previously known function as a decoy receptor for Wnt's.