H Vessel Formation as a Marker for Enhanced Bone Healing in Irradiated Distraction Osteogenesis.

In the setting of bone defects, the injured vasculature and loss of hemodynamic inflow leads to hematoma formation and low oxygen tension which stimulates vascular expansion through the HIf-1α pathway. Most importantly, this pathway upregulates sprouting of type H vessels (CD31hiEmcnhi vessels). H vessels engage in direct interaction with perivascular osteoprogenitor cells (OPCs), osteoblasts, and preosteoclasts of bone formation and remodeling. This angiogenic-osteogenic coupling leads to synchronous propagation of vascular and bony tissue for regenerative healing. A growing body of literature demonstrates that H vessels constitute a large portion of bone's innate capacity for osteogenic healing. We believe that CD31hiEmcnhi vessels play a role in bone healing during distraction osteogenesis (DO). DO is a procedure that utilizes traction forces to facilitate induction of endogenous bone formation and regeneration of surrounding soft tissues such as skin, muscle, tendon, and neurovascular structures. While the H vessel response to mechanical injury is adequate to facilitate healing in normal healthy tissue, it remains inadequate to overcome the devastation of radiation. We posit that the destruction of CD31hiEmcnhi vessels plays a role in precluding DO's effectiveness in irradiated bone defect healing. We aim, therefore, to recapitulate the normal pathway of bony healing by utilizing the regenerative capacity of H vessels. We hypothesize that using localized application of deferoxamine (DFO) will enhance the H vessel-mediated vasculogenic response to radiation damage and ultimately enable osteogenic healing during DO. This discovery could potentially be exploited by developing translational therapeutics to hopefully accelerate bone formation and shorten the DO consolidation period, thereby potentially expanding DO's utilization in irradiated bone healing. Sprague-Dawley rats were divided into three groups: DO, radiation with DO (xDO), and radiation with DO and DFO implantation (xDODFO). Experimental groups received 35 Gy of radiation. All groups underwent DO. The treatment group received injections into the osteotomy site, every other day, beginning on postoperative day (POD) 4 of DFO. Animals were sacrificed on POD 40. For immunohistochemical analysis, mandibles were dissected and fixed in 4% paraformaldehyde for 48 hours, decalcified in Cal-Ex II for 2 days, dehydrated through graded ethanol of increasing concentration, and then embedded in paraffin. Samples were cut into 7-µm thick longitudinally oriented sections including the metaphysis and diaphysis. CD31 and Emcn double immunofluorescent staining were performed to evaluate the extent of CD31hiEmcnhi vessel formation. Bone sections were then stained with conjugated antibodies overnight at 4°C. Nuclei were stained with Hoechst. Slides were also double stained with Osterix and CD31 to study the quantity of H vessel-mediated recruitment of OPCs to accelerate bone healing. Images were acquired with a Nikon Ti2 widefield microscope and analyzed in NIS- Elements Advanced Research 5.41.02 software. The abundance of type H vessels is represented by the area fraction of CD31 + Emcn+ vessel area inside the regenerate sample. OPC concomitant proliferation into the distraction gap is represented by the area fraction of Osterix+ cell area inside of the regenerate sample. There were 6× more type H vessels in DO groups than in xDO groups. Localized DFO significantly increased the abundance of type H vessels of irradiated DO animals compared to xDO by 15× ( p = 0.00133531). Moreover, the DO and xDODFO groups with higher abundance of type H vessels also demonstrated better angiogenesis and osteogenesis outcomes. Interestingly, xDODFO groups doubled the quantity of H vessel formation compared to DO, indicating a supraphysiologic response ( p = 0.044655055). Furthermore, H vessel-mediated recruitment of OPCs mimicked the described H vessel formation trend in our study groups. Irradiated DO groups contained 3× less OPCs compared to DO controls. DFO treatment to xDO animals remediated irradiation damage by containing 12× Osterix+ cells. Finally, DFO treatment of irradiated animals quadrupled osteoprogenitor recruitment into the distraction gap compared to DO controls. In this study, we developed a novel approach to visualize CD31hiEmcnhi in paraffin sections to study DO regeneration. Normal DO demonstrated a significant upregulation of H vessel formation and associated angiogenic-osteogenic coupling. Radiation severely decreased H vessel formation along with an associated significant diminution of new bone formation and nonunion. DFO administration, however, resulted in vascular replenishment and the restoration of high quantities of CD31hiEmcnhi and OPCs, recapitulating the normal process of bony regeneration and repair. DFO treatment remediated new bone formation and bony union in irradiated fields associated with increased H vessel angiogenic-osteogenic coupling. While further studies are required to optimize this approach, the results of this study are incredibly promising for the long-awaited translation of localized DFO into the clinical arena.

Evidence-based surgery for laparoscopic appendectomy: A stepwise systematic review.

INTRODUCTION: Appendectomy is a common emergency surgery performed globally. Despite the frequency of laparoscopic appendectomy, consensus does not exist on the best way to perform each procedural step. We identified literature on key intraoperative steps to inform best technical practice during laparoscopic appendectomy. METHODS: Research questions were framed using the population, indication, comparison, outcome (PICO) format for 6 key operative steps of laparoscopic appendectomy: abdominal entry, placement of laparoscopic ports, division of mesoappendix, division of appendix, removal of appendix, and fascial closure. These questions were used to build literature queries in PubMed, EMBASE, and the Cochrane Library databases. Evidence quality and certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) definitions. RESULTS: Recommendations were rendered for 6 PICO questions based on 28 full length articles. Low quality evidence favors direct trocar insertion for abdominal entry and establishment of pneumoperitoneum. Single port appendectomy results in improved cosmesis with unclear clinical implications. There was insufficient data to determine the optimal method of appendiceal stump closure, but use of a specimen extraction bag reduces rates of superficial surgical site infection and intra-abdominal abscess. Port sites made with radially dilating trocars are less likely to necessitate closure and are less likely to result in port site hernia. When port sites are closed, a closure device should be used. CONCLUSION: Key operative steps of laparoscopic appendectomy have sufficient data to encourage standardized practice.

Prospective study of short-term quality-of-life after traumatic rib fractures.

BACKGROUND: Postdischarge convalescence after traumatic rib fractures remains unclear. We hypothesized that patients with rib fractures, even as an isolated injury, have associated poor quality of life (QoL) after discharge. METHODS: We prospectively enrolled adult patients at our level I trauma center with rib fractures between July 2019 and January 2020. We assessed QoL at 1 and 3 months after discharge using the Trauma-specific Quality-of-Life (T-QoL; 43-question survey evaluating five QoL domains on a 4-point Likert scale, where 4 indicates optimal and 1, worst QoL) and supplementary questionnaires. We used generalized estimating equations to assess T-QoL score trends over time and effect of age, sex, injury pattern, self-perceived injury severity, and Injury Severity Score. RESULTS: We enrolled 139 patients (108 completed the first and 93 completed both surveys). Three months after discharge, 33% of patients were not working at preinjury capacity, and 7% were still using opioid analgesia. Suffering rib fractures mostly impacted recovery and resilience (T-QoL score, mean [robust standard error] at 1 month, 2.7 [0.1]; 3 months, 3.0[0.1]) and physical well-being domains (1 month, 2.5 [0.1]; 3 months, 2.9[0.1]). Quality of life improved over time across all domains. Compared with patients who perceived their injuries as mild/moderate, patients who perceived their injuries as severe/very severe reported worse T-QoL scores across all domains. In contrast, Injury Severity Score did not affect QoL. Patients 65 years or older (-0.6 [0.1]) and women (-0.6 [0.2]) reported worse functional engagement compared with those 65 years or older and men, respectively. CONCLUSION: We found that patients with traumatic rib fractures experience suboptimal QoL after discharge. Quality of life improved over time, but even 3 months after discharge, patients reported challenges performing activities of daily living, slower-than-expected recovery, and not returning to work at preinjury capacity. Perception of injury severity had a large effect on QoL. Patients with rib fractures may benefit from close short-term follow-up. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Safety of Foregoing Operation for Small Bowel Obstruction in the Virgin Abdomen: Systematic Review and Meta-Analysis.

Our objective was to assess the safety of foregoing surgery in patients without abdominopelvic surgery history presenting with small bowel obstruction (SBO). Classic dogma has counseled early surgical intervention for SBO in the virgin abdomen-patients without abdominopelvic surgery history-given their presumed higher risk of malignant or potentially catastrophic etiologies compared with those who had undergone previous abdominal operations. The term virgin abdomen was coined before widespread use of CT, which now elucidates many SBO etiologies. Despite recent efforts to re-evaluate clinical management standards, the prevalence of SBO etiologies in the virgin abdomen and the current management landscape (nonoperative vs operative) in these patients remain unclear. Our random-effects meta-analysis of 6 studies including 442 patients found the prevalence of malignant etiologies in patients without abdominopelvic surgery history presenting with SBO varied from 7.7% (95% CI 3.0 to 14.1) to 13.4% (95% CI 7.6 to 20.3) on sensitivity analysis. Most malignant etiologies were not suspected before surgery. De novo adhesions (54%) were the most common etiology. More than half of patients underwent a trial of nonoperative management, which often failed. Subgroups of patients likely have variable risk profiles for underlying malignant etiologies, yet no study had consistent follow-up data and we did not find convincing evidence that foregoing operative management altogether in this population can be generally recommended.