Research Spotlight

Martin, H. D., A. N. Khoury, R. Schroder, E. Johnson, J. Gomez-Hoyos, S. Campos and I. J. Palmer (2017). “Contribution of the pubofemoral ligament to hip stability: A biomechanical study.” Arthroscopy 33(2): 305-313.

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PURPOSE: To determine the isolated function of the pubofemoral ligament of the hip capsule and its contribution to hip stability in external/internal rotational motion during flexion greater than 30 degrees and abduction. METHODS: Thirteen hips from 7 fresh-frozen pelvis-to-toe cadavers were skeletonized from the lumbar spine to the distal femur with the capsular ligaments intact. Computed tomographic imaging was performed to ensure no occult pathological state existed, and assess bony anatomy. Specimens were placed on a surgical table in supine position with lower extremities resting on a custom-designed polyvinylchloride frame. Hip internal and external rotation was measured with the hip placed into a combination of the following motions: 30 degrees , 60 degrees , 110 degrees hip flexion and 0 degrees , 20 degrees , 40 degrees abduction. Testing positions were randomized. The pubofemoral ligament was released and measurements were repeated, followed by releasing the ligamentum teres. RESULTS: Analysis of the 2,106 measurements recorded demonstrates the pubofemoral ligament as a main controller of hip internal rotation during hip flexion beyond 30 degrees and abduction. Hip internal rotation was increased up to 438.9% (P < .001) when the pubofemoral ligament was released and 412.9% (P < .001) when both the pubofemoral and teres ligament were released, compared with the native state. CONCLUSIONS: The hypothesis of the pubofemoral ligament as one of the contributing factors of anterior inferior hip stability by controlling external rotation of the hip in flexion beyond 30 degrees and abduction was disproved. The pubofemoral ligament maintains a key function in limiting internal rotation in the position of increasing hip flexion beyond 30 degrees and abduction. This cadaveric study concludes previous attempts at understanding the anatomical and biomechanical function of the capsular ligaments and their role in hip stability.

McCullough, P. A., A. Vasudevan, M. Sathyamoorthy, J. M. Schussler, C. E. Velasco, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2017). “Urinary 11-dehydro-thromboxane b2 and mortality in patients with stable coronary artery disease.” Am J Cardiol: 2017 Jan [Epub ahead of print].

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Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (+/-SD) of 67 +/- 10 and 65 +/- 10 years, respectively. A positive linear trend for age was observed among tertiles of 11dhTxB2 (p trend = 0.01). Higher proportions of women (p = 0.001), chronic obstructive pulmonary disease (p trend = 0.0003), and heart failure (p trend = 0.003) were observed in the upper tertile of 11dhTxB2. Sixty-seven patients (14.9%) died over a median follow-up of 1,149 days and 87.5% of the deaths were due to cardiovascular causes. Twenty-six nonsurvivors (38.8%) were treated with P2Y12 receptor antagonists versus 161 survivors (42.2%; p = 0.61). By stepwise Cox proportional hazards analysis, we identified that patients in the middle (hazard ratio 7.14; 95% CI 2.46 to 20.68) and upper tertiles (hazard ratio 9.91; 95% CI 3.45 to 28.50) had higher risks for mortality after adjusting for age and co-morbidities. In conclusion, urinary concentration of 11dhTxB2 was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures.

Moreland, A. M., C. A. Santa Ana, J. R. Asplin, J. A. Kuhn, R. P. Holmes, J. A. Cole, E. A. Odstrcil, T. G. Van Dinter, Jr., J. G. Martinez and J. S. Fordtran (2017). “Steatorrhea and hyperoxaluria in severely obese patients before and after roux-en-y gastric bypass.” Gastroenterology: 2017 Jan [Epub ahead of print].

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BACKGROUND: Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat, which can produce hyperphagic steatorrhea. The primary objective of the study was to determine whether urine oxalate excretion correlates with elements of fat balance in severely obese patients before and after RYGB. METHODS: Fat balance and urine oxalate excretion were measured simultaneously in 26 severely obese patients before and one year after RYGB, while patients consumed their usual diet. At these time points, stool and urine samples were collected. Steatorrhea and hyperoxaluria were defined as fecal fat >7 g/day and urine oxalate >40 mg/day. Differences were evaluated using paired 2-tailed t tests. RESULTS: Prior to RYGB, 12 of 26 patients had mild to moderate steatorrhea. Average urine oxalate excretion was 61 mg/day; there was no correlation between fecal fat and urine oxalate excretion. After RYGB, 24 of 26 patients had steatorrhea and urine oxalate excretion averaged 69 mg/day, with a positive correlation between fecal fat and urine oxalate excretions (r = 0.71, p < 0.001). For each 10 g/day increase in fecal fat output, fecal water excretion increased only 46 mL/day. CONCLUSION: Steatorrhea and hyperoxaluria were common in obese patients before bypass, but hyperoxaluria was not caused by excess unabsorbed fatty acids. Hyperphagia, obesity, or metabolic syndrome could have produced this previously unrecognized hyperoxaluric state by stimulating absorption or endogenous synthesis of oxalate. Hyperoxaluria after RYGB correlated with steatorrhea and was presumably caused by excess fatty acids in the intestinal lumen. Because post-bypass steatorrhea caused little increase in fecal water excretion, most patients with steatorrhea did not consider themselves to have diarrhea. Before and after RYGB, high oxalate intake contributed to the severity of hyperoxaluria.

Muller, D. W., R. S. Farivar, P. Jansz, R. Bae, D. Walters, A. Clarke, P. A. Grayburn, R. C. Stoler, G. Dahle, K. A. Rein, M. Shaw, G. M. Scalia, M. Guerrero, P. Pearson, S. Kapadia, M. Gillinov, A. Pichard, P. Corso, J. Popma, M. Chuang, P. Blanke, J. Leipsic and P. Sorajja (2017). “Transcatheter mitral valve replacement for patients with symptomatic mitral regurgitation: A global feasibility trial.” J Am Coll Cardiol 69(4): 381-391.

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BACKGROUND: Symptomatic mitral regurgitation (MR) is associated with high morbidity and mortality that can be ameliorated by surgical valve repair or replacement. Despite this, many patients with MR do not undergo surgery. Transcatheter mitral valve replacement (TMVR) may be an option for selected patients with severe MR. OBJECTIVES: This study aimed to examine the effectiveness and safety of TMVR in a cohort of patients with native valve MR who were at high risk for cardiac surgery. METHODS: Patients underwent transcatheter, transapical delivery of a self-expanding mitral valve prosthesis and were examined in a prospective registry for short-term and 30-day outcomes. RESULTS: Thirty patients (age 75.6 +/- 9.2 years; 25 men) with grade 3 or 4 MR underwent TMVR. The MR etiology was secondary (n = 23), primary (n = 3), or mixed pathology (n = 4). The Society of Thoracic Surgeons Predicted Risk of Mortality was 7.3 +/- 5.7%. Successful device implantation was achieved in 28 patients (93.3%). There were no acute deaths, strokes, or myocardial infarctions. One patient died 13 days after TMVR from hospital-acquired pneumonia. Prosthetic leaflet thrombosis was detected in 1 patient at follow-up and resolved after increased oral anticoagulation with warfarin. At 30 days, transthoracic echocardiography showed mild (1+) central MR in 1 patient, and no residual MR in the remaining 26 patients with valves in situ. The left ventricular end-diastolic volume index decreased (90.1 +/- 28.2 ml/m2 at baseline vs. 72.1 +/- 19.3 ml/m2 at follow-up; p = 0.0012), as did the left ventricular end-systolic volume index (48.4 +/- 19.7 ml/m2 vs. 43.1 +/- 16.2 ml/m2; p = 0.18). Seventy-five percent of the patients reported mild or no symptoms at follow-up (New York Heart Association functional class I or II). Successful device implantation free of cardiovascular mortality, stroke, and device malfunction at 30 days was 86.6%. CONCLUSIONS: TMVR is an effective and safe therapy for selected patients with symptomatic native MR. Further evaluation of TMVR using prostheses specifically designed for the mitral valve is warranted. This intervention may help address an unmet need in patients at high risk for surgery.

Nizamutdinov, D., S. DeMorrow, M. McMillin, J. Kain, S. Mukherjee, S. Zeitouni, G. Frampton, P. C. Bricker, J. Hurst and L. A. Shapiro (2017). “Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury.” Sci Rep 7: 40112

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Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action.