Sex and Ethnic Differences in 47 Candidate Proteomic Markers of Cardiovascular Disease: The Mayo Clinic Proteomic Markers of Arteriosclerosis Study

Cardiovascular disease (CVD) susceptibility differs between men and women and varies with ethnicity. This variability is not entirely explained by conventional CVD risk factors. We examined differences in circulating levels of 47 novel protein markers of CVD in 2561 men and women of African-American (AA) and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct sites.Participants (1,324 AAs, mean age 63.5 y, 71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships ascertained on the basis of hypertension. Solid-phase immunoassays and immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were used to measure the 47 protein markers in plasma or serum. Marker levels were log transformed and outliers were adjusted to within 4 SD. To identify markers independently associated with sex or ethnicity, we employed multivariable regression analyses that adjusted for conventional risk factors, prior history of CVD, medication use and lifestyle factors (physical activity, alcohol consumption and education). Generalized estimating equations were used to correct for intrafamilial correlations. After adjustment for the above covariates, female sex was associated with higher levels of 29 markers and lower levels of 6 markers. Female sex was independently associated with higher levels of several inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides, vasoconstrictor peptides and markers of calcification and thrombosis. AA ethnicity was associated with higher levels of 19 markers and lower levels of 6 markers, including higher levels of several inflammatory makers, higher leptin and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides, higher levels of vasoconstrictor-antidiuretic peptides and markers of calcification and thrombosis.Plasma levels of several novel protein markers of CVD differ significantly in the context of sex and ethnicity. These results have implications for individualized CVD risk assessment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Retrospective Chart Review of the Internal Brace Ligament Augmentation Repair in Conjunction with Open Broström Surgery in Ankle patients

Category: Arthroscopy, Sports Introduction/Purpose: The Broström is the most commonly used Lateral ligament repair for chronic instability, but there is growing evidence that a fairly large percentage will stretch out with time, resulting in recurrent instability. Due to the nature of the repair, rehabilitation is fairly slow, so as not to compromise the tissue during the maturation stage. Currently, the Internal Brace Ligament Augmentation Repair is an accepted augmentation method for management of a Broström procedure. However, to our knowledge, no formally collected outcome data on the procedure has been reported. Hypotheses Augmentation of the Broström repair with an Internal Brace would 1)allow accelerated rehabilitation and return to activity, 2)Will aid in long-term stability of the repair without a tendency to stretch out. Methods: Patients with lateral ankle instability repaired with a Broström and Internal Brace Augmentation were prospectively evaluated one-time post-operatively between 6 and 24 months. Patients with concomitant procedures other than debridement were excluded. Outcome measures included demographics; surgical time; AOFAS, FAAM, satisfaction, VAS scores; ROM, Raise Test, and calf strength compared to the contralateral limb; return to sports, and adverse events. Fifty five (55) patients were analyzed from two sites. The cohort includes 20 males and 35 females. 96% of the patients were non-smoking with an average BMI 27.7 ± 5.3 (range 20.6 to 43.8). Median age was 35 years (18 to 62 years). Six of the cases were revisions. Interestingly, 55% of the injuries resulted from severe sprains to the involved ankle from normal activities of daily living (ADL), while 45% were a result of sports injuries. The mean follow up time was 13.5 ± 6.5 months (range 6-27 months). Results: Average surgical time was 36±9 minutes (range 16-60minutes). The average postoperative VAS and Satisfaction scores were 0.9±1.5 and 9.1±2.0, respectively. The mean return to sports was 86 days (range 44-181). Average AOFAS score was 93.9±10.4. Thirty (55%) patients reported an ideal max score of 100. For the FAAM, current level of function in sports activities score was 90+ in 76% of subjects. Forty five (81%) patients were brace free with return to sport. The objective calf strength examination (actual girth measured) proved not significantly different from the contralateral limb; 38.9±4.5 cm and 38.7±4.4 cm (p=0.866). 89% had a negative anterior drawer. Ankle dorsiflexion comparisons were 9.4±2.8 cm (operative side) and 10.6±3.4 cm (contralateral); and ankle plantarflexion comparison (goniometer) 45.7±12.1degrees (operative side) and 45.9±12.7degrees (contralateral). Neither comparison showed a difference. Conclusion: The overall complication rate was < 3% without any reported adverse events. The results of the outcome measures and objective measurements suggest the Internal Brace Augmentation of Broström procedure is safe and efficacious

A Retrospective Review of Risk Factors and Conversion Rate of Transmetatarsal Amputations to Below or Above Knee Amputation

Category: Diabetes Introduction/Purpose: Despite the presence of several studies examining the conversion from transmetatarsal amputation (TMA) to a more proximal amputation, few studies identified the possible predictors of failure. The objective of this study is to examine the rate of conversion of transmetatarsal amputation to below or above knee amputation, and to identify the risk factors for conversion. Methods: A retrospective cohort study was performed examining 71 transmetatarsal amputations performed by a single group of foot and ankle subspecialists within a single specialty group between October 1 2005 and August 25 2015. Demographic information and comorbidities were recorded, as were complications, readmission rate, and rate of conversion to a more proximal amputation. Results: Of the 71 patients who underwent transmetatarsal amputation during the study period, 74.7% progressed to a revision amputation or more proximal amputation at a mean of 9.7 months, but a median of only 3.2 months. 87.3% progressed to below knee amputation, 9.9% underwent revision transmetatarsal amputation, and 2.8% received an above knee amputation. Of the patients who progressed to more proximal amputation, 88.2% had diabetes mellitus, 72.4% had a pre-operative ulceration, and 81.7% had peripheral neuropathy. Only 52.7% had diagnosed peripheral vascular disease, 38.1% had a history of renal disease, and 35% were smokers. Conclusion: Transmetatarsal amputation has an extremely high short-term reamputation rate with the vast progressing to a below knee amputation. Comorbidities such as diabetes mellitus, neuropathy, and history of ulceration are often found in these patients, while renal and peripheral vascular disease as well as tobacco abuse are not necessarily present. This high rate of reamputation may bring into question the efficacy of performing transmetatarsal amputation as opposed to a more proximal amputation as a definitive procedure when lower extremity amputation is required

What Is the Rate of Recurrence of Peroneal Groove Deepening for Subluxation/Dislocation

Category: Sports Introduction/Purpose: Peroneal tendon subluxation is an uncommon, yet well-known, condition that can occur after injury to the lateral ankle. The diagnosis can be difficult and is often missed or delayed. This may lead to recurrent or chronic subluxation or dislocation. Surgical management is often recommended, both in the acute and subacute setting. Multiple different surgical procedures have been described ranging from soft tissue repair to fibular groove deepening procedures. Soft tissue procedures alone may be inadequate to treat this pathology, especially in the case of shallow peroneal grooves. Multiple fibular groove deepening techniques have been described, although the population size in each study has been low. This investigation will evaluate the largest cohort of patients undergoing fibular groove deepening for peroneal subluxation or dislocation. Methods: Forty-four patients (Age 39.3 +/- 15.6, BMI 27.9 +/- 5.9) who underwent fibular groove deepening without concomitant bony procedures were able to return to clinic with a minimum two year follow-up. Demographic and operative data was collected via chart review. A standing CT scan, physical examination and functional outcome data was collected at the time of the office visit. The primary outcome was revision surgery. Secondary outcomes included radiographic findings(depth of groove), physical examination data (subluxation/dislocation, strength, ROM) and functional scores(FAAM). Results: 44 patients who underwent isolated peroneal groove deepening were enrolled. Rate of revision surgery was 3/44. CT scan showed an average depth on the operative side of (4.4 mm +/- 2.6) compared to (0.6 mm +/- 1.9) on the contralateral side. On physical exam 5% had objective subluxation, 2% dislocation, 84% had full strength to eversion. The median dorsiflexion and plantarflexion range of motion was 14 (0,100) and 40 (15,155) degrees, respectively. FAAM scores for ADL and Sports were (88.6% +/- 16.4% and 71.7% +/- 20.5%, respectively). 84% of patients would undergo the operation again. Conclusion: Our results show that peroneal groove deepening has a low recurrence rate but results in decreased strength and modest decreases in plantar flexion. The majority of patients were satisfied and would have the operation again. There was low incidence revision surgery (7%), and postoperative dislocation (2%). This is the first study to our knowledge that looked at postoperative CT scans. We showed that deepening is preserved and in our study increased peroneal groove depth by 3.8 mm on average

Use of Liposomal Bupivacaine in Major Ankle and Hindfoot Surgery

Category: Ankle Introduction/Purpose: Nearly 40% of patients undergoing ambulatory orthopedic surgery experience moderate-to-severe pain at home in spite of analgesic medication.As a result, a multimodal approach consisting of oral opioid agents and regional analgesics are recommended.Regional anesthesia is considered the primary anesthetic modality and adjunct to post-operative pain control following foot and ankle surgery, however it is not without potential complication.An ideal analgesic would provide long-term pain relief without resulting in a transiently weak or insensate limb. Extended-release liposomal bupivacaine-based analgesics as been approved by the FDA for anesthetic injection and have been shown to provide extended pain relief and decrease opioid use after bunionectomy, compared with placebo. This prospective study has been designed to evaluate the effect of surgeon applied liposomal bupivacaine on post-operative pain in patients undergoing major ankle and hindfoot surgery. Methods: 28 patients who were scheduled to undergo ankle arthrodesis, a tibiotalocalcaneal arthrodesis, hindfoot arthrodesis including, or a flatfoot procedure were enrolled prospectively. Prior to surgerypatients received a single shot popliteal block and at the conclusion of the case received 20cc of liposomal bupivacaine mixed with 10cc of normal saline injected at the surgical site. VAS pain scale at PACU admission and discharge, narcotic use, anti-emetic use, length of time in PACU and any complications were documented. A take home questionnaire documenting oral narcotic use, VAS pain scales at different intervals throughout the day, patient satisfaction with post surgical pain relief, as well as any complications for the day of surgery up to post op day 3 was completed. Patient satisfaction with post surgical pain relief and complications were also recorded at the patient’s first post- operative visit. Results: 28 total patients were enrolled ( Average age 55.6, Range 20-80). Post operatively 18/28 patients (64%) rated their satisfaction as >4 (on a five-point scale). Greatest increase in VAS pain scores was seen from DOS to POD1 at 4:00 PM. Satisfaction with pain control was most strongly associated on POD3 at midday with a negative correlation (R= -0.68). Patients took the least amount of pain medications on DOS (28.83 mg) with an average total morphine equivalents consumed from DOS to POD3 of 236.68 mg. There were no complications associated with application of liposomal bupivacaine, this included postoperative wound complications, skin necrosis and persistent paresthesias. Conclusion: Extended-release liposomal bupivacaine-based analgesics when utilizedduring major ankle or hindfoot surgery did not provide complete pain relief as demonstrated by the sharp rise in pain scores seen after the resolution of the analgesic effect of the popliteal block. However it seemed that the effect of liposomal bupivacaine did contribute to lower pain scores at the conclusion of the period of efficacy, as there was no further rise in pain complaints after POD1 and lowest pain scores were seen on POD3. Application of liposomal bupivacaine appears to be safe without an increase in complications, wound problems or adverse reactions

The Use of Cryo-Preserved Umbilical Cord Plus Amniotic Membrane Tissues in the Resection of Tarsal Coalition

Category: Hindfoot Introduction/Purpose: Tarsal coalition can be a common underlying cause of painful flatfoot deformity in adolescent and adult patient populations. When conservative options fail, surgical resection becomes the mainstay of treatment. Adequate resection leaves a void, often filled with bone wax, fat graft or adjacent muscle or tendon. Interposition grafting is designed to provide a physical barrier between the ends of the excised segment and deter recurrence or bony overgrowth. No definitive graft choice has been shown to be superior to another. The goal of this study was to evaluate the use commercially available umbilical cord plus amniotic membrane tissues as an interposition graft with functional and radiological outcomes at one year follow-up. Methods: Retrospective review was performed of patients who had resection of tarsal coalition at our institution. Patients who had interposition of umbilical cord plus amniotic membrane tissues (Amniox Medical, Atlanta GA) at the site of the resection were included in this review. Postoperative data collection included VAS scores, Foot Function index scores, and radiographic review. Radiographic review included postoperative CT scans in all patients. Assessment of hindfoot ROM was noted on physical examination at last follow up visit. Results: Fourteen patients (8 male and 6 female; median age 28.5 years at time of evaluation) were enrolled in the study. Of these patients, 7 were calcaneonavicular coalitions and 7 were talonavicular coalitions. Average follow up occurred at 18 months (range 9-32 months). Interposition of umbilical cord plus amniotic membrane tissues was performed at the site of the resection. Median improvement in pain visual analog score (VAS) was 89.75%, with no post-operative infection or wound complications. Post-operative CT scan review demonstrated evidence of osteoarthritis in two patients (one at talonavicular and one subtalar joint). Four of 14 patients (29%) were found to have recurrence at follow-up. The median post-operative Foot Function Index score was 46 (range 30-110) and 64% of patients had improvement in range of motion. Conclusion: Based on radiological and functional outcomes at an average 19 month follow up, the interposition of umbilical cord plus amniotic membrane tissues after tarsal coalition resection appears to be a viable option in treating these patients. No adverse reactions were found and recurrence rate was noted to be 29%