Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds.

BACKGROUND: The development of post-traumatic heterotopic ossification (HO) is a common, undesirable sequela in patients with high-energy (war-related) extremity injuries. While inflammatory and osteoinductive signaling pathways are known to be involved in the development and progression of post-traumatic HO, features of the structural microenvironment within which the ectopic bone begins to form remain poorly understood. Thus, increasing our knowledge of molecular and structural changes within the healing wound may help elucidate the pathogenesis of post-traumatic HO and aid in the development of specific treatment and/or prevention strategies. METHODS: In this study, we performed high-resolution microscopy and biochemical analysis of tissues obtained from traumatic war wounds to characterize changes in the structural microenvironment. In addition, using an electrospinning approach, we modeled this microenvironment to reconstitute a three-dimensional type I collagen scaffold with non-woven, randomly oriented nanofibers where we evaluated the performance of primary mesenchymal progenitor cells. RESULTS: We found that traumatic war wounds are characterized by a disorganized, densely fibrotic collagen I matrix that influences progenitor cells adhesion, proliferation and osteogenic differentiation potential. CONCLUSION: Altogether, these results suggest that the structural microenvironment present in traumatic war wounds has the potential to contribute to the development of post-traumatic HO. Our findings may support novel treatment strategies directed towards modifying the structural microenvironment after traumatic injury.

Incidence and Risk Factors of Acute Patellar Tendon Rupture, Repair Failure, and Return to Activity in the Active-Duty Military Population.

BACKGROUND: Patellar tendon ruptures have a reported incidence of 0.68 per 100,000 person-years in the general population. The epidemiology of surgically treated patellar tendon ruptures in the US military has yet to be reported, which would provide opportunity for identification of risk factors for these otherwise healthy and active patients. PURPOSE: To determine the incidence of patellar tendon rupture in the Military Health System (MHS) population and to analyze demographic patterns, surgical fixation methods, and rerupture rates. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: We utilized the MHS Data Repository (MDR) to identity active-duty military servicemembers surgically treated for patellar tendon rupture between 2010 and 2015. Records were reviewed for demographic information, injury characteristics, fixation technique, and occurrence of rerupture. Risk factors for rupture were calculated using Poisson regression based on population counts and demographic data obtained in the MDR. Risk factors for rerupture and return to duty were analyzed via univariate analysis and multivariate regression. RESULTS: A total of 504 operatively treated primary patellar tendon repairs in 483 patients were identified, with an overall incidence of 6 per 100,000 person-years. Mean age was 33.6 years (range, 17-54 years) and 98% of patients were male. Fixation method was 81% bone tunnels and 7% suture anchors, and 12% were unknown. Black race had a higher relative rate ratio for rupture compared with the race categories White (9.21; P < .0001) and Other (3.27; P < .0001). The rupture rate was higher in 35- to 44-year-old patients compared with those aged 18 to 24 years (P < .0001), 25 to 34 years (P < .0001), and 45 to 64 years (P = .004). Return to full previous level of activity occurred in 75.8% of patients, 14.6% returned to activity with limitations, and 9.5% were medically separated. The rerupture rate was 3%. Fixation method, tobacco usage, body mass index, and race were not significant risk factors for rerupture. CONCLUSION: The incidence of patellar tendon rupture in the US military population is substantially higher than has been reported in the civilian population. Among military personnel, men, Black servicemembers, and those aged 35 to 44 years were at highest risk for patellar tendon rupture. Three-quarters of patients were able to return to full activity without limitations. The rerupture rate was low and unaffected by fixation method.

Suture and Needle Characteristics in Orthopaedic Surgery.

There remains a dearth of research on and general knowledge with regard to materials used for wound closure and soft-tissue repair and approximation. Critical suture properties include physical configuration, fluid absorption and capillarity, caliber or diameter, tensile strength, torsion, absorbability, elasticity, plasticity, memory, coefficient of friction, and knot security. The optimal ranges of each of these characteristics remain undefined for most sutures and indications. Needle types and basic design characteristics affect suture passage and require further consideration with regard to specific suture-needle selection. Suture must perform its intended purpose with a minimum of undesirable reaction and infectious potential, adequate duration of efficacy, and adequate strength. However, stronger, or high tensile strength, suture is not always better because of the requisite increase in suture caliber as well as the potential for inadvertent tissue strangulation, possibly increasing inflammatory reactivity. Sometimes, we seek stable, watertight fascial closure; occasionally, strong and durable tendon repair; and other times, gentle, cosmetically friendly, skin eversion and opposition. A variety of common suture types differ in these critical characteristics and may be optimally utilized for contrasting, but sometimes overlapping, indications.

In vivo model of human post-traumatic heterotopic ossification demonstrates early fibroproliferative signature.

BACKGROUND: The relationship between the tissue injury healing response and development of heterotopic ossification (HO) is poorly understood. Here we compare a rat blast model and human traumatized muscle from a blast injury to study the early signatures of osteogenesis and fibrosis during the formation of HO. METHODS: Rat and human tissues were characterized using histology, scanning electron microscopy, immunohistochemistry, as well as gene and protein expression analysis. Additionally, animals and humans were assessed radiographically for HO formation following injury. RESULTS: Markers of bone formation were dramatically increased in tissue samples from both humans and rats, and both displayed increased fibroproliferative regions within the injured tissues and elevated expression of markers of tissue fibrosis such as TGF-ß1, Fibronectin, SMAD3 and PAI-1. Markers of inflammation and fibrosis (ACTA, TNFα, BMP1 and BMP3) were elevated at the RNA level in both rat and human samples. By day 42, bone formation in the rat blast model appeared similar in radiographs compared to human patients who progressed to develop post-traumatic HO. CONCLUSIONS: Our data demonstrates that a similar early fibrotic response is evident in both the rat blast model and the human tissues following a traumatic injury and demonstrates the relevance of this animal model for future translational studies.

Fascia iliaca blockade with the addition of liposomal bupivacaine vs. plain bupivacaine for perioperative pain management following hip arthroscopy.

PURPOSE: A newer formulation of bupivacaine, encapsulated within carrier molecules, has garnered attention for its role in providing extended post-operative analgesia. The purpose was to evaluate the addition of liposomal bupivacaine to fascia iliaca blockade during hip arthroscopy. METHODS: Retrospective cohort study of patients undergoing hip arthroscopy with a pre-operative fascia iliaca blockade with either liposomal bupivacaine (Group 1; 266mg + 20 cc 0.5% plain bupivacaine) or bupivacaine (Group 2; 40 cc 0.25% plain bupivacaine). All patients received standardized pre-operative oral pain medications. The primary outcome was the defense veteran pain rating scale (DVPRS). Secondary outcomes included duration of hospital admission, PACU opioid use, PACU pain scores, and duration of nerve blockade. RESULTS: Thirty-eight males and 30 females, mean age of 33 years (range 14-56). There was no difference in pre-operative DVPRS between the groups (n.s.). There was no difference in post-operative DVPRS pain scores at POD0 (3.7 vs. 3.9, n.s.), POD1 (4.2 vs. 3.8, n.s.), POD2 (4.2 vs. 3.7, n.s.), POD3 (3.9 vs. 3.7, n.s.) or POD14 (2.2 vs. 2.4, n.s.). Group 1 trended towards longer mean total hospital admission time (872 vs. 822 min, n.s.), and greater mean morphine equivalents administered in the PACU (33 vs. 29 mg, n.s.). 68% of patients in group 1 reported continued anterior thigh numbness at POD3, compared to 34% in group 2 (p = 0.008). CONCLUSIONS: Despite the advertised benefits of prolonged post-operative analgesia using liposomal bupivacaine, there were no significant differences in post-operative pain scores or PACU opioid consumption. Our results support that acceptable pain scores are successfully achieved at all time periods with the use of multimodal analgesia including fascia iliaca blockade despite the type of pain medication administered. LEVEL OF EVIDENCE: III.

Outcomes of Hip Arthroscopy in the Older Adult: A Systematic Review of the Literature.

BACKGROUND: The indications for hip preservation surgery have expanded to include treatment of hip pathology in older adults. While several studies have examined the efficacy of hip arthroscopy in the setting of osteoarthritis, there has been no review of outcomes in older adults. PURPOSE: To review the outcomes of hip arthroscopy in older adults and identify factors associated with treatment failures. STUDY DESIGN: Systematic review. METHODS: PubMed, EMBASE, and the Cochrane Library were searched through March 2016 for studies reporting outcomes of primary hip arthroscopy in patients older than 40 years. Inclusion in the review was based on age, patient-reported outcome (PRO) measures, and duration of follow-up. Two authors screened the results and extracted data for use in this review. Standardized mean difference was calculated to estimate effect size for PRO scores within studies. RESULTS: Eight studies with 401 total patients undergoing hip arthroscopy for femoroacetabular impingement (FAI) or labral tears were included in this review. Seven of the 8 studies reported favorable PRO scores and significant postoperative improvement with moderate to large effect size. The included studies demonstrated a trend toward higher effect sizes with an increasing percentage of labral repair compared to isolated labral debridement. The complication rate was comparable to that of previous reports involving younger patients; however, the overall reoperation rate was 20.8%. Conversion to hip arthroplasty ranged from 0% to 30%, with an overall conversion rate of 18.5% at a mean time of 17.5 months following arthroscopy. The most common risk factors for conversion to arthroplasty were low preoperative PRO scores and advanced arthritis. CONCLUSION: Hip arthroscopy appears to be a safe and efficacious treatment for labral tears and FAI in older patients who do not have significant underlying degenerative changes. However, in this population, there is a significant proportion of patients who eventually require hip arthroplasty. Outcomes may be affected by type of treatment (ie, labral debridement vs repair). Additional high-quality studies are needed to understand how these factors affect outcomes.

Ovulation rate and cycle characteristics in a subsequent clomiphene citrate cycle after stair-step protocol.

OBJECTIVE: To determine the ovulation rate after ovulation induction with clomiphene citrate (CC) in women who had previously been ovulatory after a stair-step (CC-SS) ovulation induction. DESIGN: Retrospective cohort. SETTING: University-based tertiary fertility center. PATIENT(S): 61 anovulatory patients <40 years of age with polycystic ovary syndrome who underwent ovulation induction with a CC-SS protocol and a subsequent CC cycle. INTERVENTION(S): Ovulation induction with CC. MAIN OUTCOME MEASURE(S): Ovulation rates and cycle characteristics. RESULT(S): Of 61 patients who underwent a subsequent CC cycle, 15 (25%) failed to ovulate at the previously ovulatory dose. Of those 15 patients, 13 (86.7%) ovulated after an increase in dose. The total number of follicles ≥15 mm (2.8 ± 1.2 vs. 1.6 ± 0.7) and peak estradiol (E2) levels (604 ± 272 pg/mL vs. 447 ± 218 pg/mL) were statistically significantly higher in the CC-SS cycle compared with the subsequent CC cycle, respectively. The endometrial lining was statistically significantly thinner in the CC-SS than the CC cycle (7.8 ± 1.8 vs. 9.2 ± 2.7, respectively). CONCLUSION(S): The majority of patients who ovulate after a CC-SS protocol will ovulate after taking the previously ovulatory CC dose in a subsequent cycle. Those who do not ovulate will likely ovulate with a further increase in CC dose.

Maternal and neonatal outcomes after gonadotropin-releasing hormone agonist trigger for final oocyte maturation in patients undergoing in vitro fertilization.

OBJECTIVE: To compare the rate of congenital anomalies, obstetrical complications, and neonatal complications in antagonist cycles where either GnRH agonist (GnRHa) or hCG was used for final oocyte maturation. DESIGN: Retrospective cohort study. SETTING: University-based tertiary fertility center. PATIENT(S): Three hundred ninety-two women under 40 years of age who underwent controlled ovarian stimulation using a GnRH antagonist protocol and who had final oocyte maturation triggered with either a GnRHa or hCG that resulted in pregnancy and delivery after 16 weeks' gestation. INTERVENTION(S): GnRHa versus hCG trigger of final oocyte maturation. MAIN OUTCOME MEASURE(S): Congenital anomaly rates, obstetrical complications, and neonatal complications. RESULT(S): There were no significant differences in the rate of congenital anomalies between GnRHa and hCG trigger (6.6 vs. 9.2%). There were also no differences in the maternal complications (27.6 vs. 20.8%) or neonatal complications (19.7 vs. 20.0%) between the GnRHa trigger and hCG trigger groups. CONCLUSION(S): GnRHa trigger does not affect the rate of congenital anomalies or obstetrical or neonatal complications and remains a viable option in the prevention of ovarian hyperstimulation syndrome.

Arteriovenous malformation of the uterus after a midtrimester loss: a case report.

BACKGROUND: Arteriovenous malformations (AVMs) of the uterus are rare but potentially life-threatening lesions. The typical presentation includes intermittent, heavy and profuse vaginal bleeding, often refractory to medical therapy. CASE: We present the case of a 25-year-old woman presenting 18 months after a 22-week pregnancy loss complicated by a postpartum curettage for retained placenta. The patient's initial symptoms included irregular and extremely heavy vaginal bleeding. Several transfusions of packed red blood cells were required because of severe anemia. On transfer to our institution, evaluation with ultrasound and hysteroscopy revealed a large AVM in the fundus of the uterus, apparently fed by both the right and left uterine arteries. After 2 embolization procedures of the uterine arteries, the patient experienced a recurrence of her symptoms, requiring definitive treatment with a hysterectomy. CONCLUSION: AVMs of the uterus are a rare cause of vaginal bleeding. AVMs should be considered in the differential diagnosis for the patient with bleeding refractory to medical management and a history of prior uterine surgery. Although unsuccessful in our case, uterine artery embolization remains a viable treatment option, particularly in patients wishing to retain their reproductive capacity.