Faculty Bibliography

BACKGROUND:Limb lengthening with external fixation is performed to treat patients with leg length discrepancy or short stature. Although the procedure has a high rate of success, one potential drawback from limb lengthening is the amount of time spent in the fixation device while regenerate bone consolidates. Although some studies have assessed different treatment modalities, there has not been a study that has systematically evaluated whether low intensity pulsed ultrasound (LIPUS) or pulsed electromagnetic fields (PEMF) have significant effects on regenerate bone growth. The purpose of this study was to evaluate these two non-pharmacological treatment options to stimulate regenerate bone, and to assess whether they affect the treatment time in limb lengthening. METHODS:Utilizing the electronic databases Medline, Embase and Ovid, we performed a literature search for studies describing the application of LIPUS or PEMF following limb lengthening. With the aid of a statistical software package, Forest-Plots were generated to compare the differences in bone healing index with and without the use of regenerate bone stimulation. RESULTS:A total of 7 studies assessed these two bone stimulation modalities in a cohort of 153 patients. Overall, the mean healing index was 11.7 days/cm faster when using bone stimulation that in the comparison cohorts (33.7 vs 45.4 day, standardized mean difference of 1.16; p = 0.003). CONCLUSION/CONCLUSIONS:Amongst the drawbacks from limb lengthening is the relatively high rate of non- and delayed-union. Several methods, both pharmacological and non-pharmacological, have been investigated for their potential to stimulate the growth of regenerate bone. After systematically evaluating the limited and heterogeneous current literature, we found that LIPUS and PEMF both decreased the time for bone healing (healing index in days/cm) of the newly formed regenerate bone in an adequately selected cohort of patients that underwent limb lengthening. However, a high number of complications should be noted, which could be attributed to the lengthening procedure or to the additional bone stimulation. PROSPERO REGISTRATION NUMBER/UNASSIGNED:CRD42016039024.

The Patient Protection and Affordable Care Act will have a dramatic impact on Academic Medical Centers (AMC) across many fronts. The expansion of Medicaid and creation of healthcare exchanges to compete with existing commercial payers will alter the current payer-mix seen at AMC's. While prior studies have analyzed this impact at a hospital level, we evaluated these changes in payer-mix on three distinct internal medicine service lines by modeling out their effect on overall contribution margin (CM) for each service line using actual hospital data collected from a tertiary-care, urban AMC. We performed a sensitivity analysis to account for varying rates of participation in the newly created exchanges using 33, 50, and 100% take-up rates to simulate the unknown migration of current commercial patients to exchanges in addition to a threshold analysis. We found that despite an increase in CM from Medicaid expansion, the negative impact on CM from commercial patients migrating to exchange plans at all three take-up rates caused an overall loss in CM across all three service lines ranging from $215 020 to $1 482 597. Threshold points ranged from 19 to 37% across service lines. Our results reveal that the key drivers to determining the impact on CM is ultimately driven by what exchange rates will be set at as well as how many current commercial patients transition to the newly created exchanges

Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was carried out on 20 rats that were divided into two groups, a control group (n = 10) and an EESD group (n = 10). All the rats underwent a perforator flap surgery, after which post-operative abdominal compressions of EESD were given to the EESD group for seven days, while the control group received saline. Flap survival percentages were determined after seven days, and were found to be significantly higher in the EESD group than in the control group. Results of laser Doppler flowmetry (LDF) showed that perforator flaps in the EESD group had higher perfusion values than those of the control group. The flap tissues were stained with hematoxylin and eosin, followed by immunohistochemical evaluation. Superoxide dismutase (SOD) expression and micro-vessel development markedly increased in the EESD group, while malondialdehyde (MDA) levels decreased. This is the first study to investigate the effect of sanguis draconis on perforator flap survival. Our results demonstrate that sanguis draconis can improve perforator flap survival in rats by promoting microvessel regeneration and blood perfusion.

BACKGROUND:Cardiovascular disease (CVD) rates are increased in HIV. The degree to which myocyte injury, strain, and fibrosis occur prior to clinical disease and relate to coronary plaque in HIV is unknown. OBJECTIVE:To investigate newer cardiac biomarkers of subclinical myocyte injury [high-sensitivity troponin T (hs-cTnT)], strain (amino terminal proB-type natriutretic peptide), fibrosis (soluble ST2, Galectin-3), and vascular inflammation (oxidized LDL, lipoprotein-associated phospholipase A2) in HIV-infected individuals and non-HIV controls and relate these to coronary plaque by cardiac computed tomography angiography. DESIGN/METHODS:Observational. METHODS:Markers were investigated in 155 HIV-infected and 70 non-HIV-infected participants without known CVD and with low traditional CVD risk and related to cardiac computed tomography angiography data. RESULTS:Age, sex, and race did not differ between the groups. Hs-cTnT [3.1 (3.0, 6.4) vs. 3.0 (3.0, 4.0) ng/l, P = 0.03], Galectin-3 [13.5 (10.6, 18.1) vs. 11.6 (9.9, 14.5) ng/ml, P = 0.002], and soluble ST2 [31.5 (24.5, 41.5) vs. 28.3 (20.2, 33.5) ng/ml, P = 0.01] were significantly higher in HIV-infected participants vs. CONTROLS/METHODS:Detectable hs-cTnT (seen in 50% of HIV participants) related to the overall presence of plaque [odds ratio (OR) 2.3, P = 0.01] and particularly to coronary calcium (OR for Agatston calcium score > 0, 3.3, P = 0.0008 and OR for calcified plaque 7.4, P = 0.01) in HIV, but not in non-HIV. CONCLUSION/CONCLUSIONS:Subclinical myocyte injury is observed among young, asymptomatic HIV-infected individuals with low traditional cardiac risk factors. In the setting of HIV infection, the presence of detectable cardiac troponin is strongly associated with coronary plaque, particularly calcified plaque among an asymptomatic group. Future studies are needed to assess if early subclinical injury marked by hs-cTnT predicts plaque progression and cardiac events in HIV.

BACKGROUND: The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of anti-tuberculosis drugs. OBJECTIVES: To determine the optimal molecular approach needed, we sought to create a comprehensive catalogue of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance. METHODS: We developed and validated molecular inversion probes for DNA capture and deep sequencing of 28 drug resistance loci in M.tuberculosis. We used the probes for targeted sequencing of a geographically diverse set of 1397 clinical M.tuberculosis isolates with known drug resistance phenotypes. We identified a minimal set of mutations to predict resistance to first- and second-line anti-tuberculosis drugs and validated our predictions in an independent dataset. We constructed and piloted a web-based database that provides public access to the sequence data and prediction tool. RESULTS: The predicted resistance to rifampicin and isoniazid exceeded 90% sensitivity and specificity, but was lower for other drugs. The number of mutations needed to diagnose resistance is large and for the 13 drugs studied it was 238 across 18 genetic loci. CONCLUSION: These data suggest that a comprehensive M.tuberculosis drug resistance diagnostic will need to allow for a high dimension of mutation detection. They also support the hypothesis that currently unknown genetic determinants, potentially discoverable by whole genome sequencing, encode resistance to second-line TB drugs.

BACKGROUND: Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply-demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. METHODS: Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n=255) or myonecrosis without definite MI (n=220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. RESULTS: Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p=0.41). At discharge, only 43% of patients received aspirin and statin therapy. CONCLUSIONS: Type 2 MI and myonecrosis occur frequently in the setting of supply-demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients.

IMPORTANCE/OBJECTIVE:The in vivo effect of pilocarpine hydrochloride on the Schlemm canal may help explain its pharmacologic mechanism of action and better indicate its clinical use. OBJECTIVE:To investigate the effect of pilocarpine on the structure of the Schlemm canal in vivo in healthy eyes and eyes with glaucoma. DESIGN, SETTING, AND PARTICIPANTS/METHODS:In this case-control study, healthy individuals and patients with open-angle glaucoma were prospectively enrolled between September 1, 2013, and June 30, 2014, after a complete ophthalmologic examination at a tertiary glaucoma referral practice. Eighty-one serial, horizontal, enhanced depth imaging optical coherence tomographic B-scans (interval between B-scans, approximately 35 µm) of the nasal corneoscleral limbus were performed before and 1 hour after topical administration of pilocarpine, 1%, in 1 eye of healthy volunteers and pilocarpine, 2%, in 1 eye of patients with glaucoma. Fifty B-scans in the overlapping area (circumferential length, approximately 1.7 mm) between the 2 sets of serial scans (before and after pilocarpine administration) were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The cross-sectional area of the Schlemm canal was measured in each selected B-scan. Volume of the Schlemm canal was calculated using commercially available 3-dimensional reconstruction software. MAIN OUTCOMES AND MEASURES/METHODS:Mean cross-sectional area of the Schlemm canal. RESULTS:Enhanced depth imaging optical coherence tomographic scans of the Schlemm canal were performed successfully before and after administration of pilocarpine, 1%, in 9 healthy eyes (9 individuals) and pilocarpine, 2%, in 10 eyes with glaucoma (10 patients) (mean [SD] age, 31.9 [7.8] and 68.7 [13.2] years, respectively). Following pilocarpine administration, mean (SD) intraocular pressure decreased from 14.3 (1.3) to 13.7 (1.1) mm Hg in healthy eyes (P = .004) and from 17.5 (6.0) to 16.6 (6.1) mm Hg in eyes with glaucoma (P = .01). The mean (SD) cross-sectional area of the Schlemm canal increased by 21% (4667 [1704] to 5647 [1911] µm2) in healthy eyes (P < .001) and by 24% (3737 [679] to 4619 [692] µm2) in eyes with glaucoma (P < .001) (mean difference in percent increase, 2.2%; 95% CI, -8.5% to 12.9%). The mean (SD) volume of the Schlemm canal in the overlapping area increased from 8 004 000 (2 923 000) to 9 685 000 (3 277 000) µm3 in healthy eyes (P < .001) and from 6 468 000 (1 170 000) to 7 970 000 (1 199 000) µm3 in eyes with glaucoma (P < .001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:These data suggest that pilocarpine expands the Schlemm canal in eyes with and without glaucoma. No differences in the effect were identified between the 2 groups. Enhanced depth imaging optical coherence tomography may be useful in investigating the effect of pharmacologic agents on the Schlemm canal.

BACKGROUND & AIMS: National hepatitis C virus (HCV) screening guidelines recommended 1-time testing of persons born between 1945 and 1965. METHODS: We performed a retrospective study to compare care milestones achieved by HCV-infected patients identified by birth cohort versus risk-based screens. RESULTS: We determined the proportions of patients newly identified with HCV infection who met care milestones (viral load, referral to and evaluation by a specialist, offer of treatment, initiation of treatment, and sustained viral response) and the time it took to reach them. We found no differences in HCV care milestones for patients identified via birth cohort testing versus risk-based screening. Overall, only 43% of HCV antibody-positive patients were referred to care, and less than 4% started treatment. The time to each care milestone was lengthy and varied greatly; treatment was initiated in a median of 308 days. CONCLUSIONS: Although birth cohort testing will likely increase identification of patients with HCV infection, it does not seem to increase the number of patients that meet management milestones. New methods are needed to increase access to care and establish efficient models of health care delivery.