Programmatic Approach to Increasing Osteopathic Medical Student Participation in Research: The TCOM Experience.

Providing medical students with a meaningful research-based educational experience will help them become exemplary physicians and informed consumers of medical research outcomes in the practice of evidence-based medicine. By participating in research projects during medical school, students have the opportunity to study specific fields that interest them in greater depth and develop their written and oral presentation skills. Studies indicate that students who have participated in research and scholarly activities during medical school are at an advantage when matching to their preferred residency. In this article, the authors outline programs and projects that provide opportunities for osteopathic medical students at the University of North Texas Health Science Center Texas College of Osteopathic Medicine to research concepts and conduct hypothesis-driven, hands-on research projects.

Requirements for Certification in Surgery: A Comparison of the American Board of Surgery and the American Osteopathic Board of Surgery.

In early 2014, the Accreditation Council for Graduate Medical Education, the American Osteopathic Association, and the American Association of Colleges of Osteopathic Medicine agreed to a memorandum of understanding describing a single accreditation system for graduate medical education in the United States. Although there are many benefits, such as consistent quality of graduate medical education, alignment of competency standards, alignment with policymakers' expectations, unification of voices on graduate medical education access and funding issues, and visibility of osteopathic medicine, there are also many challenges in creating a uniform system of graduate medical education. The authors review the pathways to initial certification for both the American Board of Surgery and the American Osteopathic Board of Surgery and discuss recertification and maintenance of certification.

Randomized trial of a dry-powder, fibrin sealant in vascular procedures.

OBJECTIVE: Topical hemostats are important adjuncts for stopping surgical bleeding. The safety and efficacy of Fibrocaps, a dry-powder, fibrin sealant containing human plasma-derived thrombin and fibrinogen, was evaluated in patients undergoing vascular surgical procedures. METHODS: In this single-blind trial (clinicaltrials.gov: NCT01527357), adult patients were randomized 2:1 to Fibrocaps plus gelatin sponge (Fibrocaps) vs gelatin sponge alone. Results are presented for the patient subset undergoing vascular procedures with suture hole bleeding. The primary efficacy endpoint compared time to hemostasis (TTH) over 5 minutes. Safety follow-up continued to day 29. RESULTS: A total of 175 patients were randomized and treated (Fibrocaps, 117; gelatin sponge, 58). Patients were predominately male (69%) and underwent arterial bypass (81%), arteriovenous graft formation (9%), or carotid endarterectomy (9%). Fibrocaps significantly reduced TTH compared with gelatin sponge (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.5-3.1; median TTH, 2 minutes; 95% CI, 1.5-2.5 vs 4 minutes; 95% CI, 3.0-5.0; P < .002). Significant reductions were also observed in patients receiving concomitant antiplatelet agents alone (HR, 2.8; 95% CI, 1.0-7.4; P = .03; n = 33), anticoagulants alone (HR, 2.0; 95% CI, 1.0-4.0; P = .04; n = 43), or both antiplatelet agents and anticoagulants (Fibrocaps vs gelatin sponge, HR, 2.3; 95% CI, 1.2-4.3; P = .008; n = 65). Incidences of common adverse events (procedural pain, nausea, constipation) were generally comparable between treatment arms. Anti-thrombin antibodies developed in 2% of Fibrocaps-treated patients and no-gelatin-sponge patients. CONCLUSIONS: Fibrocaps, a ready-to-use, dry-powder fibrin sealant, was well-tolerated and reduced TTH in patients undergoing vascular procedures, including those receiving antiplatelet agents and/or anticoagulants, demonstrating its safety and usefulness as an adjunct to hemostasis.

Fibrocaps for surgical hemostasis: two randomized, controlled phase II trials.

BACKGROUND: Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen, is being developed as an adjunct for surgical hemostasis. MATERIALS AND METHODS: Safety and efficacy of Fibrocaps applied directly or by spray device, in combination with gelatin sponge, was compared with that of gelatin sponge-alone in two randomized, single-blind controlled trials: FC-002 US (United States) and FC-002 NL (the Netherlands). A total of 126 adult patients were randomized (Fibrocaps: n = 47 [FC-002 US], n = 39 [FC-002 NL]; gelatin sponge alone: n = 23 [FC-002 US], n = 17 [FC-002 NL). One bleeding site was treated during a surgical procedure (n = 125). Time to hemostasis (primary end point) was measured, with a 28-d safety follow-up. Four surgical indications included hepatic resection (n = 58), spinal procedures (n = 37), peripheral vascular procedures (n = 30), and soft tissue dissection (n = 1). RESULTS: Mean (standard deviation) time to hemostasis was significantly shorter after Fibrocaps treatment than after gelatin sponge alone (FC-002 US: 1.9 [1.3] versus 4.8 min [3.1], P < 0.001; FC-002 NL: 2.2 [1.3] versus 4.4 min [3.1], P = 0.004). The incidence of hemostasis was greater after Fibrocaps compared with that of gelatin sponge alone within 3 min (FC-002 US: 83% versus 35%, P < 0.001; FC-002 NL: 77% versus 53%, P = 0.11), 5 min (94% versus 61%, P = 0.001; 95% versus 71%, P = 0.022), and 10 min (100% versus 78%, P = 0.003; 100% versus 82%, P = 0.025). Adverse events were consistent with surgical procedures performed and patients' underlying diseases and generally similar between treatment arms; most were mild or moderate in severity. Non-neutralizing antithrombin antibodies were detected in 5% of Fibrocaps-treated patients on day 29. CONCLUSIONS: Fibrocaps had good safety and efficacy profiles, supporting continuing clinical development as a novel fibrin sealant.

Thoracic splenosis more than 40 years after thoracoabdominal trauma.

Splenosis is a rare occurrence that is defined as autotransplantation of splenic tissue usually after splenic rupture due to trauma and subsequent splenectomy. Although splenosis most commonly occurs in the abdomen, the authors report a rare case of thoracic splenosis after remote thoracoabdominal trauma. A 62-year-old woman was found to have lower-lobe, pleural-based nodular lesions in juxtaposition to the posteromedial segment of the lung during workup for an abdominal hernia. Surgical excision of the mass confirmed the diagnosis of ectopic splenic tissue, and splenosis was diagnosed. This woman was among the rare 18% of people who are found to have splenosis in the intrathoracic space. In the workup of pulmonary nodules in patients with a history of trauma, splenosis should be a consideration.

Diagnosis and management of primary pulmonary leiomyosarcoma.

Leiomyosarcomas are cancers of smooth muscle cells that can arise from any location but occur most often in the uterus, retroperitoneum, or intraabdominal region. Primary leiomyosarcomas of the lung are extremely rare and are often diagnosed as a mass on routine chest radiography. Metastasis is uncommon and typically occurs late in the disease process, indicating the importance of early detection. Surgical excision is generally curative, offering patients optimal prognoses. The authors describe a 56-year-old asymptomatic man who was found to have a pulmonary mass on routine chest radiography. Further testing revealed a primary pulmonary leiomyosarcoma. The tumor was excised and postoperative osteopathic manipulative treatment was applied to help facilitate patient recovery. A brief discussion of the typical clinical presentation, prevalence, and medical management of these tumors is included.

Solitary fibrous pleural tumor.

Solitary fibrous pleural tumors are rare masses of mesenchymal origin that may be mistaken for mesothelioma. A positive staining of vimentin, negative staining of cytoplasmic keratin, and expression of the CD34 antigen can confirm the presence of a solitary fibrous pleural tumor. Although most tumors of this type are benign, they possess a malignant potential and thus should be excised. We report a case of a 63-year-old man who had an inconclusive biopsy of a lung lesion 15 years ago. Further testing after excision revealed a solitary fibrous pleural tumor. A brief discussion of the clinical presentation and incidence of these tumors is included.

Leukocyte-Aprotinin Atrial Fibrillation Study (LAFFS): Impact of Aprotinin and Leukofiltration on Atrial Fibrillation, Renal Insufficiency and Encephalopathy Post-Cardiopulmonary Bypass.

Purpose: Atrial fibrillation remains the leading postoperative complication following cardiopulmonary bypass. A randomized trial was undertaken to evaluate the effectiveness of leukocyte filtration and aprotinin, applied separately and in combination, on the incidence of post-operative atrial fibrillation. A secondary component of the study was the impact of these adjunct interventions on post-surgical renal and neurological dysfunction. Methods: A total of 1,220 patients undergoing primary isolated coronary artery bypass grafting were randomly assigned to one of four treatment groups. The control group (305 patients) received standard cardiopulmonary bypass with moderately hypothermic (34ºC) cardioplegic arrest. In the filtration group (310 patients) leukocyte reducing filters were incorporated into the bypass circuit and deployed strategically. The aprotinin group (285 patients) received full Hammersmith dose aprotinin. The combination therapy group (320 patients) received both aprotinin and leukocyte filtration. Results: The incidences of atrial fibrillation were 25% in the control group, 16% in the filtration group, 19% in the aprotinin group and 10% in the combination therapy group (P < 0.001). Renal dysfunction was detected in 3% of the control group, 2% of the filtration group, 8% of the aprotinin group, and 5% of the combination group (P < 0.005). Neurological dysfunction occurred in 2% of the control group, 2% of the filtration group, 1% of the aprotinin group, and 2% of the combination group (P = n.s.). Conclusions: Combination therapy with aprotinin and leukocyte filtration markedly reduced atrial fibrillation post-cardiopulmonary bypass, and was more effective than the individual treatments. Aprotinin treatment increased the incidence of renal dysfunction, and the addition of leukocyte filtration partially mitigated this detrimental effect of aprotinin. Thus, strategic leukocyte filtration augments aprotinin's anti-arrhythmic effects while suppressing its nephrotoxic sequelae.

Effects of changes in central blood volume on carotid-vasomotor baroreflex sensitivity at rest and during exercise.

The purpose of this investigation was to examine whether the effect of changes in central blood volume on carotid-vasomotor baroreflex sensitivity at rest was the same during exercise. Eight men (means +/- SE: age 26 +/- 1 yr; height 180 +/- 3 cm; weight 86 +/- 6 kg) participated in the present study. Sixteen Torr of lower body negative pressure (LBNP) were applied to decrease central venous pressure (CVP) at rest and during steady-state leg cycling at 50% peak O2 uptake (104 +/- 20 W). Subsequently, infusions of 25% human serum albumin solution were administered to increase CVP at rest and during exercise. During all protocols, heart rate, arterial blood pressure, and CVP were recorded continuously. At each stage of LBNP or albumin infusion, the maximal gain (G(max)) of the carotid-vasomotor baroreflex function curve was measured using the neck pressure and neck suction technique. LBNP reduced CVP and increased the G(max) of the carotid-vasomotor baroreflex function curve at rest (+63 +/- 25%, P = 0.006) and during exercise (+69 +/- 19%, P = 0.002). In contrast to the LBNP, increases in CVP resulted in the G(max) of the carotid-vasomotor baroreflex function curve being decreased at rest -8 +/- 4% and during exercise -18 +/- 5% (P > 0.05). These findings indicate that the relationship between CVP and carotid-vasomotor baroreflex sensitivity was nonlinear at rest and during exercise and suggests a saturation load of the cardiopulmonary baroreceptors at which carotid-vasomotor baroreflex sensitivity remains unchanged.

Cardiopulmonary baroreflex is reset during dynamic exercise.

The purpose of this study was to examine the hypothesis that the operating point of the cardiopulmonary baroreflex resets to the higher cardiac filling pressure of exercise associated with the increased cardiac filling volumes. Eight men (age 26 +/- 1 yr; height 180 +/- 3 cm; weight 86 +/- 6 kg; means +/- SE) participated in the present study. Lower body negative pressure (LBNP) was applied at 8 and 16 Torr to decrease central venous pressure (CVP) at rest and during steady-state leg cycling at 50% peak oxygen uptake (104 +/- 20 W). Subsequently, two discrete infusions of 25% human serum albumin solution were administered until CVP was increased by 1.8 +/- 0.6 and 2.4 +/- 0.4 mmHg at rest and 2.9 +/- 0.9 and 4.6 +/- 0.9 mmHg during exercise. During all protocols, heart rate, arterial blood pressure, and CVP were recorded continuously. At each stage of LBNP or albumin infusion, forearm blood flow and cardiac output were measured. During exercise, forearm vascular conductance increased from 7.5 +/- 0.5 to 8.7 +/- 0.6 U (P = 0.024) and total systemic vascular conductance from 7.2 +/- 0.2 to 13.5 +/- 0.9 l.min(-1).mmHg(-1) (P < 0.001). However, there was no significant difference in the responses of both forearm vascular conductance and total systemic vascular conductance to LBNP and the infusion of albumin between rest and exercise. These data indicate that the cardiopulmonary baroreflex had been reset during exercise to the new operating point associated with the exercise-induced change in cardiac filling volume.

Hemodynamic effects of osteopathic manipulative treatment immediately after coronary artery bypass graft surgery.

CONTEXT: Coronary artery bypass graft (CABG) surgery is a common procedure for patients with coronary artery disease. The physiologic effects of postoperative osteopathic manipulative treatment (OMT) following CABG have not been documented previously. OBJECTIVE: To determine the effects of OMT on cardiac hemodynamics post-CABG surgery. DESIGN: Pilot prospective clinical study (N=29). SETTING AND PATIENTS: Treatment subjects (n=10) undergoing CABG surgery were recruited for postoperative OMT. The primary assessment compared, pre-OMT versus post-OMT, measurements of thoracic impedance, mixed venous oxygen saturation (SvO2), and cardiac index. Records of control subjects (n=19) who underwent CABG surgery--but who did not receive OMT--were assessed for SvO2 and cardiac index at 1 hour and 2 hours postsurgery. INTERVENTION: Immediately following CABG surgery (< or = 2 h), OMT was provided to subjects to alleviate anatomic dysfunction of the rib cage caused by median sternotomy and to improve respiratory function. This adjunctive treatment occurred while subjects were completely anesthetized. RESULTS: A post-OMT increase in thoracic impedance (P < or = .02) in OMT subjects demonstrated that central blood volume was reduced after OMT, suggesting an improved peripheral circulation. Mixed venous oxygen saturation also increased (P < or = .005) after OMT. These increases were accompanied by an improvement in cardiac index (P < or = .01). Comparisons of postoperative measurements in OMT subjects versus those in control subjects revealed statistically significant differences for SvO2 (P < or = .005) and cardiac index (P < or = .02) between the two groups. CONCLUSION: The observed changes in cardiac function and perfusion indicated that OMT had a beneficial effect on the recovery of patients after CABG surgery. The authors conclude that OMT has immediate, beneficial hemodynamic effects after CABG surgery when administered while the patient is sedated and pharmacologically paralyzed.

The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise.

We examined the relationship between changes in cardiac output and middle cerebral artery mean blood velocity (MCA V(mean)) in seven healthy volunteer men at rest and during 50% maximal oxygen uptake steady-state submaximal cycling exercise. Reductions in were accomplished using lower body negative pressure (LBNP), while increases in were accomplished using infusions of 25% human serum albumin. Heart rate (HR), arterial blood pressure and MCA V(mean) were continuously recorded. At each stage of LBNP and albumin infusion was measured using an acetylene rebreathing technique. Arterial blood samples were analysed for partial pressure of carbon dioxide tension (P(a,CO2). During exercise HR and were increased above rest (P < 0.001), while neither MCA V(mean) nor P(a,CO2) was altered (P > 0.05). The MCA V(mean) and were linearly related at rest (P < 0.001) and during exercise (P = 0.035). The slope of the regression relationship between MCA V(mean) and at rest was greater (P = 0.035) than during exercise. In addition, the phase and gain between MCA V(mean) and mean arterial pressure in the low frequency range were not altered from rest to exercise indicating that the cerebral autoregulation was maintained. These data suggest that the associated with the changes in central blood volume influence the MCA V(mean) at rest and during exercise and its regulation is independent of cerebral autoregulation. It appears that the exercise induced sympathoexcitation and the change in the distribution of between the cerebral and the systemic circulation modifies the relationship between MCA V(mean) and .

Sympathetic cardiac influence and arterial blood pressure instability.

Previous studies have suggested that sympathetic cardiac blockade enhances baroreflex function, whereas parasympathetic blockade diminishes baroreflex sensitivity and elicits arterial blood pressure (ABP) instability. The aim of this project was to test the hypothesis that sympathetic cardiac blockade was beneficial in maintaining ABP stability during orthostatic challenge. In 8 young healthy subjects, measurements were taken before and after sympathetic cardiac blockade (beta1-adrenoceptor blockade via metoprolol) in combination with or without parasympathetic blockade (atropine) at rest and during lower body negative pressure (LBNP). Arterial blood samples were obtained to evaluate plasma renin activity (PRA) and norepinephrine (NE). Power spectral analyses were performed on heart rate (HR) and ABP variability. LBNP -50 Torr significantly decreased systolic blood pressure (SBP, -6+/-3 mm Hg) and increased PRA (from 0.72+/-0.23 to 1.75+/-0.24 ng ml(-1) h(-1)) and NE (from 1.02+/-0.11 to 2.13+/-0.32 pg ml(-1)). Low frequency (LF, 0.04-0.12 Hz) SBP and diastolic blood pressure (DBP) variability were significantly augmented by LBNP (4.1+/-1.6 vs. 10.8+/-3.0 mm Hg2, and 3.1+/-1.0 vs. 7.9+/-1.9 mm Hg2, respectively). Following metoprolol, arterial baroreflex sensitivity (assessed by the slope of HR interval to SBP during injection with 1 mug kg(-1) phenylephrine) increased significantly (9.9+/-2.2 to 19.6+/-4.1 ms mm Hg(-1)). With beta1-adrenoceptor blockade, LBNP still decreased SBP (-10+/-2 mm Hg) and increased NE, but did not significantly augment PRA (0.59+/-0.22 vs. 1.03+/-0.18 ng ml(-1) h(-1)), or LF SBP and DBP variability (3.3+/-0.6 vs. 5.7+/-1.3 mm Hg2, and 3.1+/-0.7 vs. 5.4+/-1.1 mm Hg2, respectively). The increased PRA during LBNP remained non-significant following metoprolol combined with atropine, whereas the augmented LF SBP (2.6+/-0.7 vs. 9.9+/-2.8 mm Hg2) and DBP (2.5+/-0.7 vs. 11.1+/-3.0 mm Hg2) variability were significantly accentuated compared to both metoprolol alone and control conditions, accompanied by a greater delta SBP (-17+/-7 mm Hg) and significantly diminished baroreflex gain (0.91+/-0.05 ms/mm Hg). These data suggested that removal of sympathetic cardiac influence improved cardiovascular stability as indicated by a diminished LF ABP variability, which was related to an enhanced cardiac responsiveness.