Does Maintenance of Pulmonary Blood Flow Pulsatility at the Time of the Fontan Operation Improve Hemodynamic Outcome in Functionally Univentricular Hearts?

It is unclear whether residual anterograde pulmonary blood flow (APBF) at the time of Fontan is beneficial. Pulsatile pulmonary flow may be important in maintaining a compliant and healthy vascular circuit. We, therefore, wished to ascertain whether there was hemodynamic evidence that residual pulsatile flow at time of Fontan promotes clinical benefit. 106 consecutive children with Fontan completion (1999-2018) were included. Pulmonary artery pulsatility index (PI, (systolic pressure-diastolic pressure)/mean pressure)) was calculated from preoperative cardiac catheterization. Spectral analysis charted PI as a continuum against clinical outcome. The population was subsequently divided into three pulsatility subgroups to facilitate further comparison. Median PI prior to Fontan was 0.236 (range 0-1). 39 had APBF, in whom PI was significantly greater (median: 0.364 vs. 0.177, Mann-Whitney p < 0.0001). There were four early hospital deaths (3.77%), and PI in these patients ranged from 0.214 to 0.423. There was no correlation between PI and standard cardiac surgical outcomes or systemic oxygen saturation at discharge. Median follow-up time was 4.33 years (range 0.0273-19.6), with no late deaths. Increased pulsatility was associated with higher oxygen saturations in the long term, but there was no difference in reported exercise tolerance (Ross), ventricular function, or atrioventricular valve regurgitation at follow-up. PI in those with Fontan-associated complications or the requiring pulmonary vasodilators aligned with the overall population median. Maintenance of pulmonary flow pulsatility did not alter short-term outcomes or long-term prognosis following Fontan although it tended to increase postoperative oxygen saturations, which may be beneficial in later life.

Patient-Reported Outcomes Measurement Information System Outcome Measures and Mental Health in Orthopaedic Trauma Patients During Early Recovery.

OBJECTIVES: This study explored the relationships between negative affective states (depression and anxiety), physical/functional status, and emotional well-being during early treatment and later in recovery after orthopaedic trauma injury. DESIGN: This was a secondary observational analysis from a randomized controlled study performed at a Level-1 trauma center. PATIENTS: Patients with orthopaedic trauma (N = 101; 43.5 ± 16.4 years, 40.6% women) were followed from acute care to week 12 postdischarge. MAIN OUTCOME MEASURES: Patient-reported outcomes measurement information system measures of Physical Function, Psychosocial Illness Impact-Positive and Satisfaction with Social Roles and Activities and the Beck Depression Inventory-II and the State-Trait Anxiety Inventory were administered during acute care and at weeks 2, 6, and 12. Secondary measures included hospital length of stay, adverse readmissions, injury severity, and surgery number. RESULTS: At week 12, 20.9% and 35.3% of patients reported moderate-to-severe depression (Beck Depression Inventory-II score ≥20 points) and anxiety (State-Anxiety score ≥40 points), respectively. Depressed patients had greater length of stay, complex injuries, and more readmissions than those without. The study sample improved patient-reported outcomes measurement information system T-scores for Physical Function and Satisfaction with Social Roles and Activities by 40% and 22.8%, respectively (P < 0.0001), by week 12. Anxiety attenuated improvements in physical function. Both anxiety and depression were associated with lower Psychosocial Illness Impact-Positive scores by week 12. CONCLUSIONS: Although significant improvements in patient-reported physical function and satisfaction scores occurred in all patients, patients with depression or anxiety likely require additional psychosocial support and resources during acute care to improve overall physical and emotional recovery after trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Postinjury Inflammatory State and the Bone Marrow Response to Anemia.

RATIONALE: The pathophysiology of persistent injury-associated anemia is incompletely understood, and human data are sparse. OBJECTIVES: To characterize persistent injury-associated anemia among critically ill trauma patients with the hypothesis that severe trauma would be associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, and decreased erythropoiesis. METHODS: A translational prospective observational cohort study comparing severely injured, blunt trauma patients who had operative fixation of a hip or femur fracture (n = 17) with elective hip repair patients (n = 22). Bone marrow and plasma obtained at the index operation were assessed for circulating catecholamines, systemic inflammation, erythropoietin, iron trafficking pathways, and erythroid progenitor growth. Bone marrow was also obtained from healthy donors from a commercial source (n = 8). MEASUREMENTS AND MAIN RESULTS: During admission, trauma patients had a median of 625 ml operative blood loss and 5 units of red blood cell transfusions, and Hb decreased from 10.5 to 9.3 g/dl. Compared with hip repair, trauma patients had higher median plasma norepinephrine (21.9 vs. 8.9 ng/ml) and hepcidin (56.3 vs. 12.2 ng/ml) concentrations (both P < 0.05). Bone marrow erythropoietin and erythropoietin receptor expression were significantly increased among patients undergoing hip repair (23% and 14% increases, respectively; both P < 0.05), but not in trauma patients (3% and 5% increases, respectively), compared with healthy control subjects. Trauma patients had lower bone marrow transferrin receptor expression than did hip repair patients (57% decrease; P < 0.05). Erythroid progenitor growth was decreased in trauma patients (39.0 colonies per plate; P < 0.05) compared with those with hip repair (57.0 colonies per plate; P < 0.05 compared with healthy control subjects) and healthy control subjects (66.5 colonies per plate). CONCLUSIONS: Severe blunt trauma was associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, erythroid progenitor growth suppression, and persistent injury-associated anemia. Clinical trial registered with www.clinicaltrials.gov (NCT 02577731).

An integrated-delivery-of-care approach to improve patient reported physical function and mental wellbeing after orthopedic trauma: study protocol for a randomized controlled trial.

BACKGROUND: Orthopedic trauma injury impacts nearly 2.8 million people each year. Despite surgical improvements and excellent survivorship rates, many patients experience poor quality of life (QOL) outcomes years later. Psychological distress commonly occurs after injury. Distressed patients more frequently experience rehospitalizations, pain medication dependence, and low QOL. This study was developed to test whether an integrative care approach (IntCare; ten-step program of emotional support, education, customized resources, and medical care) was superior to usual care (UsCare). The primary aim was to assess patient functional QOL (objective and patient-reported outcomes) with secondary objectives encompassing emotional wellbeing and hospital outcomes. The primary outcome was the Lower Extremity Gain Scale score. METHODS/DESIGN: A single-blinded, single-center, repeated measures, randomized controlled study is being conducted with 112 orthopedic trauma patients aged 18-85 years. Patients randomized to the IntCare group have completed or are receiving a guided ten-step support program during acute care and at follow-up outpatient visits. The UsCare group is being provided the standard of care. Patient-reported outcomes and objective functional measures are collected at the hospital and at weeks 2, 6, and 12 and months 6 and 12 post surgery. The main study outcomes are changes in Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires of Physical Function quality of life, Satisfaction with Social Roles, and Positive-Illness Impact, Post-Traumatic Stress Disorder Check List, and the Tampa Scale of Kinesiophobia-11 from baseline to month 12. Secondary outcomes are changes in objective functional measures of the Lower Extremity Gain Scale, handgrip strength, and range of motion of major joints from week 2 to month 12 post surgery. Clinical outcomes include hospital length of stay, medical complications, rehospitalizations, psychological measures, and use of pain medications. A mixed model repeated measures approach assesses the main effects of treatment and time on outcomes, as well as their interaction (treatment × time). DISCUSSION: The results from this study will help determine whether an integrative care approach during recovery from traumatic orthopedic injury can improve the patient perceptions of physical function and emotional wellbeing compared to usual trauma care. Additionally, this study will assess the ability to reduce the incidence or severity of psychological distress and mitigate medical complications, readmissions, and reduction of QOL after injury. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02591472 . Registered on 28 October 2015.

Preexisting psychiatric illness worsens acute care outcomes after orthopaedic trauma in obese patients.

PURPOSE: Pre-existing psychiatric illness, illicit drug use, and alcohol abuse adversely impact patients with orthopaedic trauma injuries. Obesity is an independent factor associated with poorer clinical outcomes and discharge disposition, and higher hospital resource use. It is not known whether interactions exist between pre-existing illness, illicit drug use and obesity on acute trauma care outcomes. PATIENTS AND METHODS: This cohort study is from orthopaedic trauma patients prospectively measured over 10 years (N = 6353). Psychiatric illness, illicit drug use and alcohol were classified by presence or absence. Body mass index (BMI) was analyzed as both a continuous and categorical measure (<30 kg/m2 [non-obese], 30-39.9 kg/m2 [obese] and ≥40 kg/m2 [morbidly obese]). Main outcomes were the number of acute care services provided, length of stay (LOS), discharge home, hospital readmissions, and mortality in the hospital. RESULTS: Statistically significant BMI by pre-existing condition (psychiatric illness, illicit drug use) interactions existed for LOS and number of acute care services provided (ß values 0.012-0.098; all p < 0.05). The interaction between BMI and psychiatric illness was statistically significant for discharge to locations other than home (ß = 0.023; p = 0.001). DISCUSSION: Obese patients with orthopaedic trauma, particularly with preexisting mental health conditions, will require more hospital resources and longer care than patients without psychiatric illness. Early identification of these patients through screening for psychiatric illness and history of illicit drug use at admission is imperative to mobilize the resources and provide psychosocial support to facilitate the recovery trajectory of affected obese patients.

Comparison of cannulated screws with FiberWire or stainless steel wire for patella fracture fixation: A pilot study.

PURPOSE: This pilot study tested whether FiberWire provides similar protection to steel wire against repair displacement in patella fractures. METHODS: Thirteen cadaver knees were cyclically loaded with 10 cycles (0-90° flexion) and fracture displacement was recorded. Fixation methods were also tested in load to failure (>3 mm displacement). RESULTS: There was no difference between wire types in fracture displacement (1.4 mm ± 0.33 mm vs 1.2 mm ± 0.34 mm, respectively; p = 0.418) or in the load to failure (714.7 N ± 110.9 N vs 744.5 N ± 92.8 N, respectively; p = 0.360). CONCLUSION: FiberWire provides similar protection to steel wire against repair displacement after fixation of patellar fractures.

Design and implementation of a system-based course in musculoskeletal medicine for medical students.

BACKGROUND: The amount of time devoted to musculoskeletal medicine in the typical undergraduate curriculum is disproportionately low compared with the frequency of musculoskeletal complaints that occur in a general practice. Consequently, whether because of the quantity or quality of the education, the competence level of graduating physicians regarding musculoskeletal problems is inadequate. Our purposes were to design a self-contained, system-based course in musculoskeletal medicine for medical students in the preclinical years and to measure the level of competence achieved by a class of first-year medical students who took the course. METHODS: The course was formulated by faculty from the departments of orthopaedic surgery, anatomy, and rheumatology and included elements of both objectives-based and problem-centered curricular models. The clinical lectures were preceded by pertinent anatomy lectures and dissections to provide a context for the clinical information. The lectures on basic science were designed to rationalize and explicate clinical practices. Small-group activities were incorporated to permit engagement of the students in critical thinking and problem-solving. A general musculoskeletal physical examination was taught in two two-hour-long small-group sessions with the orthopaedic residents serving as instructors. Cognitive competency was evaluated with use of comprehensive anatomy laboratory and written examinations, the latter of which included a validated basic competency examination in musculoskeletal medicine. Process-based skills were evaluated in the small-group meetings and in a timed, mock patient encounter in which each student's ability to perform the general musculoskeletal physical examination was assessed. RESULTS: The course lasted six weeks and consisted of forty-four lecture hours, seventeen hours of small-group meetings, and twenty-eight hours of anatomy laboratory. The average student score on the basic competency examination was 77.8%, compared with 59.6% for a historical comparison group (p < 0.05). Each student demonstrated the ability to adequately perform a general musculoskeletal physical examination in twenty minutes. The survey of student opinion after the course indicated a high level of student satisfaction. CONCLUSIONS: The main features of the course were: (1) an emphasis on both cognitive and process-based knowledge; (2) more contact hours and broader content than in previously described courses in musculoskeletal medicine; (3) the use of small groups to focus on problem-solving and physical examination competencies; (4) basic-science content directly related to clinical goals. These features might be used at other institutions that employ a system-based curriculum for the preclinical years to help improve competence in musculoskeletal medicine.

A biomechanical study of bankart lesion fixation - biodegradable ArthroRivet tack vs. suture repair.

Bioabsorbable fixation is commonly used in soft tissue procedures performed in the shoulder. ArthroRivettrade mark tacks (referred to as rivets here), made from a copolymer of 82% poly-L-lactic acid and 18% polyglycolic acid, were developed for the Bankart procedure. Although a previous in vivo study demonstrated favorable comparison of the fixation strength and absorption characteristics of this device with that of polyglyconate bioabsorbable tacks, there have been no published biomechanical studies of this rivet in the shoulder. Fourteen shoulders were harvested from fresh-frozen cadavers of average age 74 years (46-89). Biomechanical testing was performed by measuring the energy, or work, required to anteriorly displace the humeral head 6 mm from the glenoid. Each shoulder was tested intact, vented, and before and after repair of a simulated Bankart lesion at 0, 45, and 90 degrees of abduction with and without maximal external rotation. Overall, the average work required ranged from 54.7 N-mm to 178.27 N-mm. Although the biomechanical performance of the rivet, based on resistance to anterior displacement of the humeral head, was indistinguishable from that of the suture repair, the statistical power of the test was low due to the large variance in the cadaver specimens. The results, in general, correlated well with those of previously published studies, suggesting the suitability of the bioabsorbable rivet for use in Bankart repair.

Hyperglycemia induced oxidative stress in type-1 and type-2 diabetic patients with and without nephropathy.

Diabetes mellitus is associated with hyperglycemia, hyperlipoproteinaemia and oxidative stress at cellular level. The aim of the present study was to determine the relationship between anti-oxidative system of cells and hyperglycemia induced reactive oxygen species (ROS) in type-1 and type-2 diabetic patients with and without nephropathy. ROS are anihilated by an intracellular enzymatic system such as glutathione peroxidase (GPx) and catalase and the reduced glutathione (GSH) is the major antioxidant of erythrocytes and plasma. Total of 200 diabetic patients and 50 of normal healthy control individuals were recruited for the present study. Erythrocytes and plasma activities of GPx, catalase and GSH were measured as a part of anti-oxidative system and TBARS for the marker of oxidative stress in type-1 diabetes mellitus (T1DM), type-2 diabetic mellitus (T2DM), type-1 diabetes with nephropathy (T1DN) and type-2 diabetes with nephropathy (T2DN) patients. GPx, catalase and GSH activity was significantly decreased, whereas TBARS level was significantly increased in both type-1 and type-2 diabetic groups with and without nephropathy than the normal healthy individuals. T1DM patients had shown decreased level of GSH and activity of anti-oxidative enzymes than T2 DM patients, whereas TBARS level was higher in T1DM than T2DM patients, suggesting that T1DM patients are more prone to secondary complications such as nephropathy than T2DM patients. Obtained results have shown positive correlation of GSH with GPx and catalase activity in erythrocytes and plasma, whereas, negative correlation was observed between TBARS and catalase in erythrocytes and plasma indicative of the relationship of various anti-oxidative enzymes and key antioxidant such as GSH in erythrocytes and plasma responsible for increased oxidative stress.

Grafting long bone fractures with demineralized bone matrix putty enriched with bone marrow: pilot findings.

In this pilot study, the preliminary effectiveness of a composite graft consisting of demineralized bone matrix (DBM) putty (Grafton DBM) and aspirated bone marrow was evaluated for treating long bone fractures. Patients were ssigned randomly to treatment with the DBM putty composite (n = 10) or iliac crest autograft (n = 8), and had a minimum of 12 months of radiographic follow-up. Ninety percent of DBM patients (9/10) achieved full bone formation compared to 75% of autograft patients (6/8) (P = .41). Additionally, all 10 DBM patients were healed compared with 63% of autograft patients (5/8) (P = .07). These findings suggest that DBM putty enriched with bone marrow may be comparable to autograft for treating long bone fractures.

Distal tibiofibular syndesmosis fixation: a cadaveric, simulated fracture stabilization study comparing bioabsorbable and metallic single screw fixation.

Metal screws that are used for ruptured tibiofibular syndesmosis repair are often removed within 3 months of placement, suggesting the utility of bioabsorbable screws. A biomechanical study was performed to compare fixation of a simulated syndesmosis separation with a 5-mm oriented copolymer bioabsorbable (82:18 poly-L-lactic acid/poly-glycolic acid) versus a stainless steel screw. Eight pairs of cadaveric lower-leg specimens were cleaned and a pronation external rotation-type injury was created in each. The syndesmosis was fixed with a single, tricortical bioabsorbable screw in 1 ankle and a metal screw in the contralateral ankle (matched pairs). Sequential testing of the specimens showed that torsional stiffness of the fixed, relative to intact, specimens was nearly equivalent (0.730 +/- 0.260 for copolymer, 0.770 +/- 0.300 for stainless steel; P = .401). Application of 1000 cycles of axial load (90 to 900 N) resulted in a significant decrease ( P < .0001) in axial stiffness for each fixation method, but the relative decrease was equivalent for both ( P = .211). Failure torque (17.8 +/- 8.3 N.m copolymer, 21.0 +/- 11.5 N.m stainless steel; P = .238) and angle of rotation at failure (47.9 +/- 13.6 degrees copolymer, 42.0 +/- 11.5 degrees stainless steel; P = .199) were also nearly equivalent. It appears that the 5.0-mm diameter copolymer screw is biomechanically equivalent to the 5.0-mm diameter stainless steel screw for repair of syndesmosis disruption.

Increased intercellular communication through gap junctions may contribute to progression of osteoarthritis.

Our aim was to support the hypothesis of a specific association between gap junctions in synovial tissue and the presence of osteoarthritis, as evidenced by differences between osteoarthritis and non-osteoarthritis synovia in the number of gap junctions, the amount of gap-junction protein, and the amount of enzymatic activity produced through a pathway mediated by gap-junction intercellular communication. An average of 4.41 gap junctions were found per 100 cells counted in the osteoarthritis synovia, compared with 1.00 in the controls. The amount of the gap-junction protein connexin 43 in synovial lining cells was approximately 50% greater in patients with osteoarthritis. Synovial lining cells from patients with osteoarthritis produced matrix metalloproteinases constitutively and, at higher levels, in response to stimulation by interleukin-1 beta. In both cases, intercellular communication through gap junctions was shown to be critical to the ability of the cells to secrete matrix metalloproteinases. Overall, the results indicated that gap junctions between synovial lining cells were altered significantly in patients with osteoarthritis, as a consequence of the disease process or as part of the causal chain. In either case, gap junctions seem to be a rational therapeutic target.

Cranial base approaches to intracranial aneurysms in the subarachnoid space.

The use of cranial base approaches to aneurysm surgery is illustrated by means of patient examples. Over a 9-year period, cranial base approaches were used to expose and treat 38 aneurysms involving the anterior communicating artery complex, proximal internal carotid artery, basilar artery, or vertebral artery. The approaches included orbital osteotomy, orbitozygomatic osteotomy, petrous apicectomy, presigmoid petrosectomy, and extreme lateral transcondylar methods. Complications related to the approaches included one partial ptosis and two cerebrospinal fluid leaks, which resolved with treatment. The technique of three-dimensional computed tomographic angiography was useful in delineating the vascular anatomy and its relation to the cranial base structures. This helped the surgeon plan the appropriate approach to the aneurysm. Cranial base approaches, used selectively, can provide improved exposure of deep-seated aneurysms and large or giant aneurysms, while minimizing brain retraction.

Infiltration of the carotid artery by cavernous sinus meningioma.

Intracranial meningiomas are known to infiltrate surrounding structures such as the calvaria and dural sinuses, and the brain itself. The issue of whether meningiomas invade major intracranial arteries is of clinical importance, particularly in the case of meningiomas of the cavernous sinus. If a meningioma has not invaded the carotid artery wall, complete tumor removal may be accomplished with careful dissection from the carotid artery; however, if the tumor has infiltrated the wall of the carotid artery, complete removal may require sacrifice of the artery. To determine whether cavernous sinus meningiomas invade the carotid artery, the authors retrospectively reviewed the histopathology of 19 consecutively treated individuals whose carotid artery was sacrificed during removal of a meningioma involving the cavernous sinus. Patients were selected for carotid artery resection based on preoperative magnetic resonance imaging studies demonstrating complete encasement of the artery. Reconstruction of the carotid artery was planned depending on the results of preoperative balloon test occlusion with blood flow determinations. None of the 19 patients had pathological evidence of malignant tumor. Eight individuals (42%) were found to have infiltration of the carotid artery by meningioma. In five cases, focal involvement of the adventitia of the carotid artery wall was noted and, in three, the vessel was infiltrated up to the tunica muscularis. In no case was the tunica muscularis invaded by tumor. Thus, meningiomas of the cavernous sinus do infiltrate the internal carotid artery and, in order to completely resect these lesions and effect a surgical cure, it may be necessary to sacrifice the carotid artery with or without reconstruction.

Assessing brain stem function.

Intraoperative neurophysiologic monitoring provides objective measures of nervous system function that are of value when operating in proximity to the brain stem. Real-time measurements of function can be correlated to operative manipulations in order to reduce the risk of damage in critically important regions. Techniques for evaluating brain stem function clinically and electrophysiologically are presented along with their applications during surgery of the brain stem.

Substitution of serine for alpha 1(I)-glycine 844 in a severe variant of osteogenesis imperfecta minimally destabilizes the triple helix of type I procollagen. The effects of glycine substitutions on thermal stability are either position of amino acid specific.

Recent reports have demonstrated that a series of probands with severe osteogenesis imperfecta had single base mutations in one of the two structural genes for type I procollagen that substituted amino acids with bulkier side chains for glycine residues and decreased the melting temperature of the triple helix. Here we demonstrate that the type I procollagen synthesized by cultured fibroblasts from a proband with a severe form of osteogenesis imperfecta consisted of normal molecules and molecules over-modified by post-translational reactions. The thermal stability of the intact type I collagen was normal as assayed by protease digestion under conditions in which a decrease in thermal stability was previously observed with eight other substitutions for glycine in the alpha 1(I) chain. In contrast, the thermal stability of the one-quarter length B fragment generated by digestion with vertebrate collagenase was decreased by 2-3 degrees C under the same conditions. Nucleotide sequencing of cDNAs and genomic DNA established that the proband had a substitution of A for G in one allele of the pro alpha 1(I) gene that converted the codon for alpha 1-glycine 844 to a codon for serine. The results also established that the alpha 1-serine 844 was the only mutation that could account for the decrease in thermal stability of the collagenase B fragment. There are at least two possible explanations for the failure of the alpha 1-serine 844 substitution to decrease the thermal stability of the collagen molecule whereas eight similar mutations decreased the melting temperature. One possibility is that the effects of glycine substitutions are position specific because not all glycine residues make equivalent contributions to cooperative blocks of the triple helix that unfold in the predenaturation range of temperatures. A second possible explanation is that substitutions of glycine by serine have much less effect on the stability of protein than the substitutions by arginine, cysteine, and aspartate previously studied.

Biogenic amines and some metals in brain of cadmium-exposed diabetic rats.

Diabetic rats (alloxan diabetes) were exposed to cadmium (2 mg kg-1 i.p.) daily for 21 days to investigate the levels of blood glucose, biogenic amines and iron, copper, zinc and cadmium in the brain. Cadmium exposure to diabetic rats produced a significant exacerbation in the hyperglycemic effect and accumulation of cadmium in the blood compared with that observed after diabetes or cadmium exposure alone. The elevation in the levels of brain dopamine and 5-hydroxytryptamine were also more pronounced in cadmium-exposed diabetic rats compared with either cadmium exposure or diabetes alone. Cadmium exposure to diabetic rats also produced significant changes in the concentrations of copper in the blood. These results indicated enhanced cadmium toxicity in diabetic rats.