Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

BACKGROUND: Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. RESULTS: Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. CONCLUSION: We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

Conformational Manifold Sampled by Two Short Linear Motif Segments Probed by Circular Dichroism, Vibrational, and Nuclear Magnetic Resonance Spectroscopy.

Disordered protein segments called short linear motifs (SLiM) serve as recognition sites for a variety of biological processes and act as targeting signals, modification, and ligand binding sites. While SLiMs do not adopt one of the known regular secondary structures, the conformational distribution might still reflect the structural propensities of their amino acid residues and possible interactions between them. In the past, conformational analyses of short peptides provided compelling evidence for the notion that individual residues are less conformationally flexible than locally expected for a random coil. Here, we combined various spectroscopies (NMR, IR, vibrational, and UV circular dichroism) to determine the Ramachandran plots of two SLiM motifs, i.e., GRRDSG and GRRTSG. They are two representatives of RxxS motifs that are capable of being phosphorylated by protein kinase A, an enzyme that plays a fundamental role in a variety of biological processes. Our results reveal that the nearest and non-nearest interactions between residues cause redistributions between polyproline II and ß-strand basins while concomitantly stabilizing extended relative to turn-forming and helical structures. They also cause shifts in basin positions. With increasing temperature, ß-strand populations become more populated at the expense of polyproline II. While molecular dynamics simulations with Amber ff14SB and CHARMM 36m force fields indicate residue-residue interactions, they do not account for the observed structural changes.

How do salt and lipids affect conformational dynamics of Aß42 monomers in water?

It is well established that amyloid ß-protein (Aß) self-assembly is involved in triggering of Alzheimer's disease. On the other hand, evidence of physiological function of Aß interacting with lipids has only begun to emerge. Details of Aß-lipid interactions, which may underlie physiological and pathological activities of Aß, are not well understood. Here, the effects of salt and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids on conformational dynamics of Aß42 monomer in water are examined by all-atom molecular dynamics (MD). We acquired six sets of 250 ns long MD trajectories for each of the three lipid concentrations (0, 27, and 109 mM) in the absence and presence of 150 mM salt. Ten replica trajectories per set are used to enhance sampling of Aß42 conformational space. We show that salt facilitates long-range tertiary contacts in Aß42, resulting in more compact Aß42 conformations. By contrast, addition of lipids results in lipid-concentration dependent Aß42 unfolding concomitant with enhanced stability of the turn in the A21-A30 region. At the high lipid concentration, salt enables the N-terminal region of Aß42 to form long-range tertiary contacts and interact with lipids, which results in formation of a parallel ß-strand. Aß42 forms stable lipid-protein complexes whereby the protein is adhered to the lipid cluster rather than embedded into it. We propose that the inability of Aß42 monomer to get embedded into the lipid cluster may be important for facilitating repair of leaks in the blood-brain barrier without penetrating and damaging cellular membranes.

Do molecular dynamics force fields accurately model Ramachandran distributions of amino acid residues in water?

Molecular dynamics (MD) is a powerful tool for studying intrinsically disordered proteins, however, its reliability depends on the accuracy of the force field. We assess Amber ff19SB, Amber ff14SB, OPLS-AA/M, and CHARMM36m with respect to their capacity to capture intrinsic conformational dynamics of 14 guest residues x (=G, A, L, V, I, F, Y, DP, EP, R, C, N, S, T) in GxG peptides in water. The MD-derived Ramachandran distribution of each guest residue is used to calculate 5 J-coupling constants and amide I' band profiles to facilitate a comparison to spectroscopic data through reduced χ2 functions. We show that the Gaussian model, optimized to best fit the experimental data, outperforms all MD force fields by an order of magnitude. The weaknesses of the MD force fields are: (i) insufficient variability of the polyproline II (pPII) population among the guest residues; (ii) oversampling of antiparallel at the expense of transitional ß-strand region; (iii) inadequate sampling of turn-forming conformations for ionizable and polar residues; and (iv) insufficient guest residue-specificity of the Ramachandran distributions. Whereas Amber ff19SB performs worse than the other three force fields with respect to χ2 values, it accounts for residue-specific pPII content better than the other three force fields. Additional testing of residue-specific RSFF1 and Amber ff14SB combined with TIP4P/2005 on six guest residues x (=A, I, F, DP, R, S) reveals that residue specificity derived from protein coil libraries or an improved water model alone do not result in significantly lower χ2 values.

Non-invasive phrenic nerve stimulation to avoid ventilator-induced diaphragm dysfunction in critical care.

BACKGROUND: Diaphragm muscle atrophy during mechanical ventilation begins within 24 h and progresses rapidly with significant clinical consequences. Electrical stimulation of the phrenic nerves using invasive electrodes has shown promise in maintaining diaphragm condition by inducing intermittent diaphragm muscle contraction. However, the widespread application of these methods may be limited by their risks as well as the technical and environmental requirements of placement and care. Non-invasive stimulation would offer a valuable alternative method to maintain diaphragm health while overcoming these limitations. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. Respiratory pressure and flow, diaphragm electromyography and mechanomyography, and ultrasound visualization were used to assess the diaphragmatic response to stimulation. The electrode positions and stimulation parameters were systematically varied in order to investigate the influence of these parameters on the ability to induce diaphragm contraction with non-invasive stimulation. RESULTS: We demonstrate that non-invasive capture of the phrenic nerve is feasible using surface electrodes without the application of pressure, and characterize the stimulation parameters required to achieve therapeutic diaphragm contractions in healthy volunteers. We show that an optimal electrode position for phrenic nerve capture can be identified and that this position does not vary as head orientation is changed. The stimulation parameters required to produce a diaphragm response at this site are characterized and we show that burst stimulation above the activation threshold reliably produces diaphragm contractions sufficient to drive an inspired volume of over 600 ml, indicating the ability to produce significant diaphragmatic work using non-invasive stimulation. CONCLUSION: This opens the possibility of non-invasive systems, requiring minimal specialist skills to set up, for maintaining diaphragm function in the intensive care setting.

Pediatric Odontogenic and Maxillofacial Bone Pathology: A Global Analysis.

BACKGROUND: Although pathology in the maxillary and mandibular bones is rare in young patients, the differential diagnosis is broad. The World Health Organization (WHO) updated its classification of maxillofacial bone pathology in 2017. Using these updated guidelines, a systematic review of common maxillofacial bone lesions in the pediatric population was performed. METHODS: A PubMed search was conducted capturing English language articles from inception to July 2020. Thirty-one articles were identified that described the frequency of maxillofacial bone pathology. Data were extracted and organized using the WHO 2017 classification of odontogenic and maxillofacial bone tumors. Prevalence data were analyzed among diagnostic categories and geographical regions. The SAS version 9.4 was used to complete statistical analyses. RESULTS: The articles included patients from birth to a maximum age of 14 to 19 years. The most common odontogenic cysts included radicular cyst (42.7%) and dentigerous cyst (39.0%) followed by odontogenic keratocyst (15.0%). Among odontogenic bone tumors, odontoma (49.3%) was most common followed by ameloblastoma (29.1%). The most common nonodontogenic bone tumor was fibrous dysplasia (42.4%), and the most common malignant bone tumor was osteosarcoma (75.0%). Significant variations were found by geographic region, with dentigerous cyst more common than radicular cyst, and ameloblastoma more common than odontoma in African and Asian countries (P < 0.0001). CONCLUSIONS: This systematic review uses the WHO 2017 guidelines to classify common odontogenic and nonodontogenic maxillofacial bone lesions around the world. Pathogenesis, presentation, and available treatment options for the most common maxillofacial bone lesions are reviewed.

Short peptides as predictors for the structure of polyarginine sequences in disordered proteins.

Intrinsically disordered proteins and intrinsically disordered regions are frequently enriched in charged amino acids. Intrinsically disordered regions are regularly involved in important biological processes in which one or more charged residues is the driving force behind a protein-biomolecule interaction. Several lines of experimental and computational evidence suggest that polypeptides and proteins that carry high net charges have a high preference for extended conformations with average end-to-end distances exceeding expectations for self-avoiding random coils. Here, we show that charged arginine residues even in short glycine-capped model peptides (GRRG and GRRRG) significantly affect the conformational propensities of each other when compared with the intrinsic propensities of a mostly unperturbed arginine in the tripeptide GRG. A conformational analysis based on experimentally determined J-coupling constants from heteronuclear NMR spectroscopy and amide I' band profiles from vibrational spectroscopy reveals that nearest-neighbor interactions stabilize extended ß-strand conformations at the expense of polyproline II and turn conformations. The results from molecular dynamics simulations with a CHARMM36m force field and TIP3P water reproduce our results only to a limited extent. The use of the Ramachandran distribution of the central residue of GRRRG in a calculation of end-to-end distances of polyarginines of different length yielded the expected power law behavior. The scaling coefficient of 0.66 suggests that such peptides would be more extended than predicted by a self-avoiding random walk. Our findings thus support in principle theoretical predictions.

Anatomic Subunit Approach to Composite Reconstruction of Facial Gunshot Wounds.

ABSTRACT: With a rise in gun violence in the United States, surgeons are tasked with effectively managing penetrating facial trauma. The purpose of this study is to assess methods used for successful composite reconstruction of each anatomical facial subunit following penetrating trauma. A retrospective chart review was performed in subjects undergoing craniofacial reconstruction following penetrating trauma. Reconstructive methods were analyzed through operative reports. Subjects were categorized by anatomical subunit reconstructed (mandible, maxilla (malar complex and roof/palate), orbit, and cranium) and method of reconstruction (open reduction internal fixation only, bone graft, free flap, implant, and tissue expansion). Thirty-six subjects underwent reconstruction for penetrating facial trauma. Involved subunits include 24 mandible, 11 malar complex, 13 palate, 18 orbit, and 11 cranium. Predominate reconstruction method was open reduction internal fixation only for mandible (45.8%), bone grafting for malar complex (81.8%), implant for orbit (66.7%) and cranium (63.6%), and local tissue rearrangement for palate (84.6%). The predominate bone graft donor site was iliac for mandible (42.9%), rib for malar complex (36.3%) and orbit (40.0%), and frontal bone for cranium (42.8%). The predominate free flap was osteocutaneous for all mandible, orbit, and cranium and 7 of 10 (70.0%) palate reconstructions. Tissue expansion was used in all subunits except cranium. In conclusion, bone grafting, implants, free tissue transfer, and tissue expansion are all viable reconstruction options for penetrating trauma. There is no single approach to use, and decisions regarding definitive reconstruction method should be based upon anatomical subunit involved and the size/area of defects.

Cartilage Grafting Outcomes in Intermediate and Definitive Cleft Rhinoplasty.

OBJECTIVE: To compare cartilage grafting outcomes in intermediate versus definitive cleft rhinoplasty. DESIGN: A retrospective chart review was conducted. The χ2 and Fisher exact tests were used for statistical analyses. Results were considered statistically significant at P < .05. PARTICIPANTS: All subjects who underwent revision cleft rhinoplasties between July 2011 and June 2019 were included. Subjects with syndromic conditions were excluded. RESULTS: A total of 46 subjects with a cleft nose deformity underwent 65 rhinoplasty procedures. The ages averaged 17 years (range 5-50) with 34 (73.9%) males and 12 (26.1%) females. In the intermediate group, 6 (28.6%) subjects required cartilage grafting as part of 6 cleft rhinoplasties, whereas 15 (71.4%) subjects underwent a total of 26 cleft rhinoplasties that did not require grafting. In the definitive group, 18 (76%) subjects required cartilage grafting over 21 cleft rhinoplasties, whereas 7 (24%) subjects underwent a total of 9 cleft rhinoplasties where cartilage grafting was not required. The difference between the number of subjects requiring cartilage grafting in the intermediate versus the definitive group was statistically significant (P = .007). Ear concha and nose were the most frequently used cartilage donor sites, with no observed complications. CONCLUSIONS: Cartilage grafting was significantly more common in the definitive rhinoplasty group. Intermediate cleft rhinoplasty during the 5- to 13-year age period was effective, with a low-risk profile. In our experience, ear concha and nose were the preferred cartilage donor sites, with effective results and an excellent safety profile.

COVID-19 Pandemic and its Impact on Craniofacial Surgery.

In late 2019, a novel coronavirus strain, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), also known as coronavirus disease 2019 (COVID-19), triggered a global pandemic as the virus spread from the Wuhan Province, China, across all continents. Although infrequent, severe respiratory infection and death caused by SARS-CoV-2 is disproportionately high amongst healthcare providers such as craniofacial surgeons who work in the head and neck region. Factors this impact SARS-CoV-2 transmission include: (1) high viral loads in the mucosa of the oral and nasopharynx, (2) limited and/or imprecise disease screening/confirmation testing, (3) access to and appropriate use of personal protective equipment (PPE).

Surgical Decision-Making in Microvascular Reconstruction of Composite Scalp and Skull Defects.

OBJECTIVES: Microvascular reconstruction of composite scalp and skull defects requires careful planning of both cranial bone and soft-tissue coverage. The current body of literature has yet to identify a "best practice" approach to achieve these goals. METHODS: A retrospective chart review was performed. Patients with composite defects who underwent combined microvascular surgery of the scalp and skull were included over a 6-year period. Reconstructions were classified by: microvascular flap, cranioplasty, timing of cranioplasty (primary or delayed), and exposure to radiation. RESULTS: Forty-five microvascular flaps were performed for 36 patients. Fasciocutaneous flaps were more likely to experience complications than other microvascular flaps (50.0% versus 8.6%, P = 0.008). Forty of the 50 patients (80%) underwent cranioplasty, including 19 autogenous and 21 alloplastic reconstructions. There were 8 total complications: partial flap loss with implant exposure (n = 5), cranioplasty infection (n = 2), and wound dehiscence (n = 1). Alloplastic implants experienced more frequent complications than autologous reconstructions (33.3% versus 5.3%, P = 0.046). Titanium implants demonstrated the higher rates of complications than other groups (P = 0.014). Titanium implants also had more complications relative to poly-ether-ether-ketone implants (60.0% versus 9.1%, P = 0.024). Immediate alloplastic cranioplasty was associated with a significant increase in complications relative to autogenous reconstruction (54.5% versus 5.5%, P = 0.027), and no significant difference in the delayed group (10% versus 0%, P = 0.740). CONCLUSION: According to authors' knowledge, myofascial flaps yield the lowest complication rate and when possible, autologous cranioplasty is preferred. When defects are too large to accommodate autogenous bone, the authors prefer delayed prefabricated poly-ether-ether-ketone implant reconstruction.

Manifestations of Apprehension and Anxiety in a Sprague Dawley Cranial Defect Model.

BACKGROUND: Syndrome of the trephined is a neurologic condition that commonly arises in patients who undergo craniectomy and have a prolonged cranial defect. Symptoms of this condition include headache, difficulties concentrating, diminished fine motor/dexterity skills, mood changes, and anxiety/apprehension. The authors hypothesize that an animal model demonstrating anxiety/apprehension in rats who undergo craniectomy is feasible utilizing standardized animal behavioral testing. METHODS: Sprague Dawley rats were the stratified to 1 of 2 groups for comparison of neurobehavioral outcomes. Group #1 (closed cranial group) had their cranial trephination immediately closed with acrylic to restore normal cranial anatomy and Group #2 (open cranial group) had their cranial trephination enlarged to represent a decompressive hemicraniectomy immediately. Anxiety/apprehension was studied using a standardized rodent open field test. Statistical comparison of differences among the 2 groups was performed. RESULTS: Ten rats were studied with 5 rats in each group. Standard rodent open field testing of anxiety demonstrated no difference among the 2 groups at 1 week. Rats in the "Open cranial group" demonstrated progressively more anxiety over the following 3-month period. Rats in the "Open cranial group" demonstrated increasing anxiety levels as compared with rats in the "Closed cranial group." At week 16, the "Open cranial group" anxiety levels were significantly greater than week 4 (t = 2.24, P = 0.04) demonstrating a significant linear trend over time (R = 0.99; P = 0.002). The "Closed cranial group" did not show this trend (R = 07; P = 0.74). CONCLUSION: Our study demonstrates that anxiety and apprehension are more prevalent in rats with an open, prolonged cranial defect in comparison to those with a closed cranium. This correlates with similar finds in humans with syndrome of the trephined.

Timing and Modulation of Activity in the Lower Limb Muscles During Indoor Rowing: What Are the Key Muscles to Target in FES-Rowing Protocols?

The transcutaneous stimulation of lower limb muscles during indoor rowing (FES Rowing) has led to a new sport and recreation and significantly increased health benefits in paraplegia. Stimulation is often delivered to quadriceps and hamstrings; this muscle selection seems based on intuition and not biomechanics and is likely suboptimal. Here, we sample surface EMGs from 20 elite rowers to assess which, when, and how muscles are activated during indoor rowing. From EMG amplitude we specifically quantified the onset of activation and silencing, the duration of activity and how similarly soleus, gastrocnemius medialis, tibialis anterior, rectus femoris, vastus lateralis and medialis, semitendinosus, and biceps femoris muscles were activated between limbs. Current results revealed that the eight muscles tested were recruited during rowing, at different instants and for different durations. Rectus and biceps femoris were respectively active for the longest and briefest periods. Tibialis anterior was the only muscle recruited within the recovery phase. No side differences in the timing of muscle activity were observed. Regression analysis further revealed similar, bilateral modulation of activity. The relevance of these results in determining which muscles to target during FES Rowing is discussed. Here, we suggest a new strategy based on the stimulation of vasti and soleus during drive and of tibialis anterior during recovery.

Outcomes of Head and Neck Microvascular Reconstruction in Hypercoagulable Patients.

BACKGROUND: Inherited coagulopathies and previous thrombotic events are often considered relative contraindications to microvascular reconstruction. We hypothesize that with planning, head and neck microvascular reconstruction can be successfully performed in hypercoagulable individuals. METHODS: A retrospective review was conducted of subjects with coagulopathies or previous thrombotic events who underwent microvascular head and neck reconstruction. Outcomes studied were "flap-related complications" (arterial/venous compromise or flap loss) and "patient-related complications" (hematoma, deep venous thrombosis, pulmonary embolism, infection, stroke, or death). RESULTS: One hundred thirty-four microvascular flaps were performed in 117 subjects. Twenty-four subjects (20.5%) had a preoperative hypercoagulable condition and underwent 28 microvascular reconstructions. Twenty-three of 24 subjects had a previous thrombotic event, with five subjects identified with an inherited or acquired coagulopathy. All microvascular reconstructions were successful; however, complications occurred in 12 of 28 reconstructions (42.9%). Complications were "flap related" in four reconstructions (14.3%), "patient related" in nine reconstructions (32.1%), and both in one reconstruction (3.6%). Flap-related complications included small partial flap loss (n = 2), arterial compromise (n = 1), and venous compromise (n = 1), with all undergoing successful salvage. Patient-related complications included hematoma (n = 3), pulmonary embolism (n = 2), infection (n = 2), deep venous thrombosis (n = 1), and death (n = 1). Statistical analysis demonstrated that complications were more common in subjects with inferior vena cava filters (p = 0.06) and hematomas were associated with the use of therapeutic heparin infusion (p = 0.04). CONCLUSION: Microvascular head and neck reconstruction can be successfully performed in hypercoagulable subjects. However, patient-related complications remain a concern in these subjects.

Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies.

BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. RESULTS: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. CONCLUSIONS: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Risk Assessment of Isolated Single-Wall Orbit Fractures and Eye Injury.

INTRODUCTION: Ideally, all patients with isolated orbit fracture would undergo ophthalmologic evaluation before surgical intervention to rule out concomitant globe injury and possible vision loss. Unfortunately, not all institutions are capable of providing the evaluation before surgery. The authors hypothesize that the anatomic location of a single-wall orbit isolated orbit fracture can help predict the likelihood of ocular injury and thus identify high-risk patients who mandate ophthalmologic evaluation before surgical repair. METHODS: A retrospective chart review was performed at a tertiary academic medical center using the institutional trauma registry for maxillofacial trauma. All subjects with an isolated single-wall orbit fracture were included in this study. Statistical analysis was performed using a Fisher exact test. RESULTS: Two hundred seventy-nine subjects with orbit fractures were identified for inclusion in this study. Forty-one of the 279 (14.7%) subjects had isolated single-wall orbit fractures. Isolated single-wall fractures included orbit floor = 19 of 41 (46.3%), medial wall = 15 of 41 (36.6%), lateral wall = 4 of 41 (9.8%), and orbit roof = 3 of 41 (7.3%). Concomitant ocular injury (13 of 41, 31.8%) was associated with isolated orbit wall fractures as follows: orbit floor = 4 of 19 (21.1%), medial wall = 6 of 15 (40%), lateral wall = 2 of 4 (50%), and orbit roof = 1 of 3 (33.3%). A Fisher exact test demonstrated that there was no statistically significant association between individual isolated wall fractures and ocular injury (P = 0.5000). CONCLUSIONS: Isolated orbit wall fractures are common in maxillofacial trauma and often require surgical repair. Concomitant ocular injury is common (31.8%) with this highest incidence occurring with lateral wall fractures (50%); however, statistical analysis did not demonstrate a significant relationship between the anatomic location of an isolated single-wall fracture and eye injuries.

Longitudinal Assessment of Developmental Outcomes in Infants Undergoing Late Craniosynostosis Repair.

Evaluation of infants with craniosynostosis for surgical intervention, as opposed to conservative management, remains a challenge within the field of craniofacial surgery. Studies have consistently demonstrated that surgical repair of craniosynostosis is ideally performed between 3 and 12 months of age. As such, there is limited data regarding neurocognitive development in infants who initially present with uncorrected craniosynostosis after 12 months of age. Moreover, the impact of cranial vault surgery on neurocognitive development at all ages remains under investigation. A prospective, nonrandomized study was performed. All children with nonsyndromic craniosynostosis who presented for initial evaluation after 12 months of age were enrolled. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) was utilized to assess pre- and postoperative cognitive development and comparisons were made to normative values. Developmental delay is defined as scoring < 85. Five infants, average age 26 months (13-43 months) at initial presentation, underwent cranial vault remodeling and developmental testing. Fused cranial sutures involved: metopic (n = 4), and right coronal (n = 1). Cognitive testing demonstrated that 4 of 5 infants (80%) were developmentally delayed at presentation (scores: 60, 70, 72, and 80), and 1 infant was within normal limits (score: 100). Postoperative testing was performed between 2 and 12 months postoperatively. Universal improvement was observed in infants who were delayed prior to surgery (80, 80, 75, and 90, respectively). The infant who was not delayed prior to surgery remained within normal limits after surgery. This study demonstrates an association between cranial vault surgery and cognitive improvement in infants presenting late with developmental delay.

Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction.

BACKGROUND: Microvascular reconstruction of the anterior cranial fossa (ACF) creates difficult challenges. Reconstructive goals and flap selection vary based on the defect location within the ACF. This study evaluates the feasibility and reliability of free tissue transfer for salvage reconstruction of low, middle, and high ACF defects. METHODS: A retrospective review was performed. Reconstructions were anatomically classified as low (anterior skull base), middle (frontal bar/sinus), and high (frontal bone/soft tissue). Subjects were evaluated based on pathologic indication and goal, type of flap used, and complications observed. RESULTS: Eleven flaps in 10 subjects were identified and anatomic sites included: low (n = 5), middle (n = 3), and high (n = 3). Eight of 11 reconstructions utilized osteocutaneous flaps including the osteocutaneous radial forearm free flap (OCRFFF) (n = 7) and fibula (n = 1). Other reconstructions included a split calvarial graft wrapped within a temporoparietal fascia free flap (n = 1), latissimus myocutaneous flap (n = 1), and rectus abdominis myofascial flap (n = 1). All 11 flaps were successful without microvascular compromise. No complications were observed in the high and middle ACF defect groups. Two of five flaps in the low defect group using OCRFFF flaps failed to achieve surgical goals despite demonstrating healthy flaps upon re-exploration. Complications included persistent cerebrospinal fluid leak (n = 1) and pneumocephalus (n = 1), requiring flap repositioning in one subject and a second microvascular flap in the second subject to achieve surgical goals. CONCLUSION: In our experience, osteocutaneous flaps (especially the OCRFFF) are preferred for complete autologous reconstruction of high and middle ACF defects. Low skull base defects are more difficult to reconstruct, and consideration of free muscle flaps (no bone) should be weighed as an option in this anatomic area.

Development of Functional Electrical Stimulation Rowing: The Rowstim Series.

Potentially, functional electrical stimulation (FES)-assisted exercise may have an important therapeutic role in reducing comorbidities associated with spinal cord injury (SCI). Here, we present an overview of these secondary life-threatening conditions, discuss the rationale behind the development of a hybrid exercise called FES rowing, and describe our experience in developing FES rowing technology. FES rowing and sculling are unique forms of adaptive rowing for those with SCI. The paralyzed leg musculature is activated by multiple channels of electrical pulses delivered via self-adhesive electrodes attached to the skin. The stimulated muscle contractions are synchronized with voluntary rowing movements of the upper limbs. A range of steady-state FES rowing exercise intensities have been demonstrated from 15.2 ± 1.8 mL/kg/min in tetraplegia to 22.9 ±7.1 mL/kg/min in paraplegia. We expect that such high levels may help some to achieve significant reductions in the risks to their health, particularly where a dose-response relationship exists as is the case for cardiovascular disease and Type II diabetes. Furthermore, preliminary results suggest that cyclical forces more than 1.5 times body weight are imposed on the leg long bones which may help to reduce the risk of fragility fractures. We have demonstrated the feasibility of FES rowing on land and water using adapted rowing technology that includes; a fixed stretcher indoor ergometer (adapted Concept 2, Model E), a floating stretcher indoor ergometer (adapted Concept 2 Dynamic), a turbine powered water rowing tank, a custom hydraulic sculling simulator and a single scull (adapted Alden 16). This has involved volunteers with paraplegia and tetraplegia with SCI ranging from C4 to T12 AIS A using at least 4-channels of surface electrical stimulation. FES rowers, with SCI, have competed alongside non-SCI rowers over the Olympic distance of 2000 m at the British Indoor Rowing Championships in 2004, 2005, and 2006 and the World Indoor Rowing Championships in 2006 (CRASH-B's) in Boston, MA, USA. The best 2000 m FES rowing performance to date has been achieved by a 23-year-old male, Tom Aggar T12 AIS A, in 10 min 28 s. Moreover, two of our FES rowers with complete paraplegia have gone on to successfully compete in the Adaptive Rowing arms-only category (AM1x) at the World Rowing Championships and Paralympic Games.

Reducing Postoperative Bleeding After Craniosynostosis Repair Utilizing a Low-Dose Transexamic Acid Infusion Protocol.

BACKGROUND: Craniosynostosis surgery is associated with large volume blood loss and the need for blood transfusion. Recently, the use of tranexamic acid (TXA) has been demonstrated to be helpful in reducing perioperative blood loss in many pediatric procedures. This study used a low-dose pharmacokinetic TXA dosing protocol and assessed its ability to limit perioperative blood loss for craniosynostosis repairs. METHODS: A retrospective chart review was conducted of pediatric craniosynostosis surgeries performed at our institution between September 2011 and December 2014. Outcome measures included comparisons of perioperative blood loss and transfusion rates in patients who had surgery with or without TXA. RESULTS: Twenty-five patients met inclusion criteria. Nine patients had craniosynostosis surgery without TXA (no-TXA group) and 16 patients received TXA (TXA group). The TXA group had significantly higher postoperative hemoglobin levels than the no-TXA group (P = 0.009). This finding was supported by significantly higher postoperative estimated red cell volume in the TXA group (P = 0.017). Postoperative 24-hour drain output was significantly lower in the TXA group (P = 0.042). The volume of packed red blood cells transfused perioperatively was not significantly different between groups. CONCLUSIONS: Patients who received TXA during craniosynostosis surgery at our institution had higher postoperative hemoglobin levels and lower 24-hour drain output. However, TXA was not associated with lower perioperative blood transfusion rates.