Jonathan Z. Baskin

Implanted upper airway stimulation device for obstructive sleep apnea

Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success.

Three-Year Outcomes of Cranial Nerve Stimulation for Obstructive Sleep Apnea The STAR Trial

Objective To describe the 36-month clinical and polysomnography (PSG) outcomes in an obstructive sleep apnea (OSA) cohort treated with hypoglossal cranial nerve upper airway stimulation (UAS). Study Design A multicenter prospective cohort study. Setting Industry-supported multicenter academic and clinical setting. Subjects Participants (n = 116) at 36 months from a cohort of 126 implanted participants. Methods Participants were enrolled in a prospective phase III trial evaluating the efficacy of UAS for moderated to severe OSA. Prospective outcomes included apnea-hypopnea index, oxygen desaturation index, other PSG measures, self-reported measures of sleepiness, sleep-related quality of life, and snoring. Results Of 126 enrolled participants, 116 (92%) completed 36-month follow-up evaluation per protocol; 98 participants additionally agreed to a voluntary 36-month PSG. Self-report daily device usage was 81%. In the PSG group, 74% met the a priori definition of success with the primary outcomes of apnea-hypopnea index, reduced from the median value of 28.2 events per hour at baseline to 8.7 and 6.2 at 12 and 36 months, respectively. Similarly, self-reported outcomes improved from baseline to 12 months and were maintained at 36 months. Soft or no snoring reported by bed partner increased from 17% at baseline to 80% at 36 months. Serious device-related adverse events were rare, with 1 elective device explantation from 12 to 36 months. Conclusion Long-term 3-year improvements in objective respiratory and subjective quality-of-life outcome measures are maintained. Adverse events are uncommon. UAS is a successful and appropriate long-term treatment for individuals with moderate to severe OSA.

Randomized Controlled Withdrawal Study of Upper Airway Stimulation on OSA: Short- and Long-term Effect

Objective To assess the efficacy and durability of upper airway stimulation via the hypoglossal nerve on obstructive sleep apnea (OSA) severity including objective and subjective clinical outcome measures. Study Design A randomized controlled therapy withdrawal study. Setting Industry-supported multicenter academic and clinical setting. Subjects A consecutive cohort of 46 responders at 12 months from a prospective phase III trial of 126 implanted participants. Methods Participants were randomized to either therapy maintenance (“ON”) group or therapy withdrawal (“OFF”) group for a minimum of 1 week. Short-term withdrawal effect as well as durability at 18 months of primary (apnea hypopnea index and oxygen desaturation index) and secondary outcomes (arousal index, oxygen desaturation metrics, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, snoring, and blood pressure) were assessed. Results Both therapy withdrawal group and maintenance group demonstrated significant improvements in outcomes at 12 months compared to study baseline. In the randomized assessment, therapy withdrawal group returned to baseline, and therapy maintenance group demonstrated no change. At 18 months with therapy on in both groups, all objective respiratory and subjective outcome measures showed sustained improvement similar to those observed at 12 months. Conclusion Withdrawal of therapeutic upper airway stimulation results in worsening of both objective and subjective measures of sleep and breathing, which when resumed results in sustained effect at 18 months. Reduction of obstructive sleep apnea severity and improvement of quality of life were attributed directly to the effects of the electrical stimulation of the hypoglossal nerve.

Upper Airway Stimulation for Obstructive Sleep Apnea : Patient-Reported Outcomes after 48 Months of Follow-up

Objective To assess patient-based outcomes of participants in a large cohort study—the STAR trial (Stimulation Therapy for Apnea Reduction)—48 months after implantation with an upper airway stimulation system for moderate to severe obstructive sleep apnea. Study Design A multicenter prospective cohort study. Setting Industry-supported multicenter academic and clinical setting. Subjects Participants (n = 91) at 48 months from a cohort of 126 implanted participants. Methods A total of 126 participants received an implanted upper airway stimulation system in a prospective phase III trial. Patient-reported outcomes at 48 months, including Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and snoring level, were compared with preimplantation baseline. Results A total of 91 subjects completed the 48-month visit. Daytime sleepiness as measured by ESS was significantly reduced (P = .01), and sleep-related quality of life as measured by FOSQ significantly improved (P = .01) when compared with baseline. Soft to no snoring was reported by 85% of bed partners. Two patients required additional surgery without complication for lead malfunction. Conclusion Upper airway stimulation maintained a sustained benefit on patient-reported outcomes (ESS, FOSQ, snoring) at 48 months in select patients with moderate to severe obstructive sleep apnea.

Threshold Model for Extremity Compartment Syndrome in Swine

BACKGROUND Extremity compartment syndrome occurs when swelling develops within a muscle compartment to such an extent that the microvasculature is compressed and tissue perfusion is compromised. Untreated, this condition can result in widespread tissue destruction and loss of the affected limb. METHODS Swine were subjected to diffuse muscle compression injury using a balloon catheter inserted between the anterior muscle compartment of the hind limb and the anterior face of the tibia. Balloons were inflated with saline to produce a sustained intramuscular pressure (IMP) of approximately 30 mmHg greater than mean arterial pressure. Following injury the IMP was monitored for up to 8 h. At the end of the monitoring period, the tibialis anterior muscle was collected and examined for injury. RESULTS One animal receiving 6 h injury dislodged the implanted pressure transducers and was dropped from the data analysis. In all other limbs (n = 8) receiving 6 h injury, significant spontaneous increases in IMP were observed following injury. The tibialis anterior in all of the 6 h injury limbs also showed extensive tissue damage. In the limbs injured for 5 h (n = 10), only three showed a significant increase in IMP. The magnitude and duration of this increase closely resembled that seen following 6 h injury. Tissue damage was reduced in comparison with 6 h injury. CONCLUSIONS The injury technique described here provides a potential useful threshold model for studying extremity compartment syndrome and the influence of related factors on the progression of this condition.

Extremity compartment syndrome in pigs during hypobaric simulation of aeromedical evacuation.

INTRODUCTION Extremity compartment syndrome (ECS) is diagnosed when the pressure within a muscle compartment increases to within 45 mmHg of mean arterial pressure. Increased pressure limits perfusion and eventually produces tissue necrosis. This can result in disability or loss of the affected limb. Hypobaric pressure during aeromedical evacuation (AE) has been hypothesized to increase the incidence of ECS. This was tested in a threshold model of ECS in swine. METHODS Injury was induced by placing an angioplasty balloon between the tibia and the anterior muscle compartment and inflating the balloon to produce an intracompartmental pressure (ICP) 30 mmHg greater than mean arterial pressure for either 5 h or 6 h. Afterwards, animals were maintained either at ground level pressure or at a pressure equivalent to a simulated altitude of 2135 m above sea level for 8 h. ICP was monitored for signs of ECS development. At the end of the period the muscle was collected and evaluated for pathological changes and expression of various molecules associated with inflammation and tissue injury. RESULTS Simulated altitude did not increase incidence of ECS, peak intracompartmental pressures, or time to onset of ECS. However, muscle degeneration and formation of microvascular thrombi were reduced by exposure to altitude. TNF, IL-1 b, IL-6, IGFBP5, and TGFB2 were increased (P < 0.05) by exposure to altitude, whereas FGF, IGF1, IGFBP4, BMP4, nitrotyrosine, and nitrate were unchanged (P > 0.05). DISCUSSION Simulated altitude did not increase incidence of ECS. Inflammatory protein expression was increased in muscle, but some aspects of pathology were less severe following altitude exposure.

Improving outcomes of locoregional flaps: an emphasis on anatomy and basic science.

Purpose of reviewThere has been renewed interest by surgeons in locoregional flaps for facial renconstructive problems previously thought to be optimally managed by microvascular tissue transfer. Complication rates of locoregional flaps are similar to those of free flaps. Successful reconstruction using local flaps is largely based on an understanding of regional vascular anatomy. Recent findingsSternocleidomastoid and trapezius muscle flap studies have elucidated patterns of arterial and venous anatomy to allow for improved flap design. Perioral vascular studies in cadavers demonstrate consistent and reliable patterns of blood supply. The terminal vascular anatomy of the submental island flap has been recently studied. The reverse-flow submental artery flap has been used to reconstruct periorbital soft tissue defects. Preliminary studies show that a full-thickness forehead flap can be utilized to simultaneously reconstruct both the external and internal surfaces of the nose. Basic fibroblast growth factor has been found to have a protective effect on random skin flap viability. SummaryLocoregional flaps remain a useful tool for head and neck reconstruction, and often provide unique characteristics not available with free flap reconstruction. A sound understanding of vascular anatomy and recent basic science discoveries will significantly improve success of locoregional reconstruction.

A selected review of the recent advances in craniomaxillofacial bone tissue engineering.

Purpose of reviewCraniofacial surgeons must continually make decisions about how to best reconstruct the craniomaxillofacial skeleton (CFS). A high priority has been placed on the search for bone substitute materials (BSMs) that are both mechanically and biologically optimized for these reconstructions. This review is intended to present the complexity of this undertaking to physicians and scientists by reviewing the technological advances published in the last 2 years. Recent findingsAdvances in bone tissue engineering took place in the areas of scaffolds, bioactive factors (e.g. growth factors, cytokines, and pharmaceuticals), and cellular components. Recent literature highlighted the complex interplay between these elements. Researchers also made great strides in merging high-resolution imaging with computer-aided tissue engineering. SummaryDeveloping BSMs that fulfill the many needs in the CFS is difficult and there are multiple barriers to clinical translation. However, based on the progress in the last 2 years in the individual elements of BSM development as well as integration of those elements into implantable constructs, it appears that a product with specific CFS applications is on the horizon.

Nanophase bone substitute in vivo response to subcutaneous implantation

A collagen-apatite composite designed as a load-bearing bone substitute implant is used to characterize the relationship between implant morphology and in vivo behavior. This nanophase bone substitute (NBS) is studied morphologically using a nondestructive imaging technique and biologically using the rodent subcutaneous model. Porosity and pore interconnectivity are correlated with histological outcomes showing cellular invasion occurs with average pore sizes below 100 μm. Crosslinking with D-ribose is shown to affect cellular infiltration in a dose-response manner. These data suggest that collagen-apatite bone substitutes can support cellular infiltration with pore size significantly smaller than 100 μm, an encouraging result regarding development of the NBS into a platform of biomaterials with enhanced mechanical properties. The data also indicate that increasing crosslinking density decreases cellular infiltration of NBS. Thus, modulating mechanical properties of the material by altering crosslink density is likely to produce decreased biological response within the material.

Origins of and implementation concepts for upper airway stimulation therapy for obstructive sleep apnea

Upper airway stimulation, specifically hypoglossal (CN XII) nerve stimulation, is a new, alternative therapy for patients with obstructive sleep apnea hypopnea syndrome who cannot tolerate positive airway pressure, the first-line therapy for symptomatic patients. Stimulation therapy addresses the cause of inadequate upper airway muscle activation for nasopharyngeal and oropharyngeal airway collapse during sleep. The purpose of this report is to outline the development of this first-in-class therapy and its clinical implementation. Another practical theme is assessment of the features for considering a surgically implanted device and the insight as to how both clinical and endoscopic criteria increase the likelihood of safe and durable outcomes for an implant and how to more generally plan for management of CPAP-intolerant patients. A third theme is the team building required among sleep medicine and surgical specialties in the provision of individualized neurostimulation therapy.