Abstract: Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.

Abstract: A non-invasive electrical stimulation device shapes an elongated electric field of effect that can be oriented parallel to a long nerve, such as a vagus nerve in a patient's neck, producing a desired physiological response in the patient. The stimulator comprises a source of electrical power, at least one electrode and a continuous electrically conducting medium in which the electrode(s) are in contact. The stimulation device is configured to produce a peak pulse voltage that is sufficient to produce a physiologically effective electric field in the vicinity of a target nerve, but not to substantially stimulate other nerves and muscles that lie between the vicinity of the target nerve and patient's skin. Current is passed through the electrodes in bursts of preferably five sinusoidal pulses, wherein each pulse within a burst has a duration of preferably 200 microseconds, and bursts repeat at preferably at 15-50 bursts per second.

Abstract: Devices, systems and methods are disclosed for modulating cranial nerves, such as the sphenopalatine ganglion, to treat a medical condition of a patient, such as cluster headache. A stimulation device comprising a dipole antenna is advanced transnasally to a target site at or adjacent to the nasopharyngeal mucosa posterior to the middle turbinate. Electrical impulses are applied through one or more electrodes in the stimulation device to the target nerve sufficient to modulate the nerve and treat the medical condition.

Abstract: Transcutaneous electrical and magnetic nerve stimulation devices are disclosed, along with methods of treating lower urinary tract disorders using energy that is delivered noninvasively by the devices. The disorders comprise overactive bladder, urge incontinence, stress, incontinence, urge frequency, non-obstructive urinary retention and interstitial cystitis/painful bladder syndrome. In embodiments of the disclosed methods, a posterior tibial nerve of a patient is stimulated non-invasively. Methods are disclosed for selecting protocol parameters for a nerve stimulation session for treating each individual patient, wherein modules of the bladder of the patient are represented as coupled non-linear oscillators.

Abstract: Devices and methods are disclosed that treat a medical condition, such as migraine headache, by electrically stimulating a nerve noninvasively, which may be a vagus nerve situated within a patient's neck. Preferred embodiments allow a patient to self-treat his or her condition. Disclosed methods assure that the device is being positioned correctly on the neck and that the amplitude and other parameters of the stimulation actually stimulate the vagus nerve with a therapeutic waveform. Those methods comprise measuring properties of the patient's larynx, pupil diameters, blood flow within an eye, electrodermal activity and/or heart rate variability.

Abstract: Devices, systems and methods are disclosed that allow a patient to self-treat a medical condition, such as migraine headache, by electrical noninvasive stimulation of a vagus nerve. The system comprises a stimulator that is applied to the surface of the patient's neck, as well as a docking station that is used to charge a rechargeable battery within the stimulator. The docking station and stimulator housing transmit data to one another regarding the status of a stimulation session, as well as to a computer program in a patient interface device such as a mobile phone or computer. The interface device in turn communicates with medical record and billing databases contained within other computers, via the internet. The system is designed to address problems that arise particularly during self-treatment, when a medical professional is not present.

Abstract: The present invention provides systems and methods for treating and controlling obesity and/or type II diabetes. In one aspect of the invention, a device comprises a hollow sleeve sized and shaped for positioning within a duodenum of the patient, an anchor coupled to the proximal end of the sleeve and being sized and shaped to inhibit distal migration of the sleeve and a plurality of elastomeric objects coupled to the distal end of the sleeve and being sized and shaped to inhibit proximal migration of the sleeve through a pylorus of the patient. The bypass device can be placed and removed endoscopically through the patient's esophagus in a minimally invasive outpatient procedure and it is “self-anchoring” and does not require invasive tissue fixation within the patient's GI tract, thereby reducing collateral tissue damage and minimizing its impact on the digestive process.

Abstract: A non-invasive electrical stimulator shapes an elongated electric field of effect that can be oriented parallel to a long nerve, such as a vagus nerve in a patient's neck, producing a desired physiological response in the patient. The stimulator comprises a source of electrical power, at least one electrode and a continuous electrically conducting medium in contact with the electrodes. The conducting medium is also in contact with an interface element that may conform to the contour of a target body surface of the patient when the interface element is applied to that surface. When the interface element is made of insulating (dielectric) material, and disclosed stimulation waveforms are used, the power source need not supply high voltage, in order to capacitively stimulate the target nerve. The stimulator produces a peak pulse that is sufficient to produce a physiologically effective electric field in the vicinity of a target nerve.

Abstract: Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.

Abstract: Devices, systems and methods are disclosed for treating or preventing gastroparesis, functional dyspepsia, and other functional gastrointestinal disorders. The methods comprise transmitting impulses of energy non-invasively to selected nerve fibers, particularly those in a vagus nerve. The methods provide damaged interstitial cells of Cajal (ICC) with trophic factors via vagal afferent nerve fibers, thereby reversing ICC damage, and as a consequence improving gastric motility. The methods also increase levels of inhibitory neurotransmitters in the brain so as to decrease neural activity within the area postrema, or they deactivate a resting state neural network containing parts of the anterior insula and anterior cingulate cortex, which will thereby reduce abnormal interoception and visceral hypersensitivity.

Abstract: Devices and systems are disclosed for the non-invasive treatment of medical conditions through delivery of energy to target tissue, comprising a source of electrical power, a magnetically permeable toroidal core, and a coil that is wound around the core. The coil and core are embedded in a continuous electrically conducting medium, which is adapted to have a shape that conforms to the contour of an arbitrarily oriented target body surface of a patient. The conducting medium is applied to that surface by any of several disclosed methods, and the source of power supplies a pulse of electric charge to the coil, such that the coil induces an electric current and/or an electric field within the patient, thereby stimulating tissue and/or one or more nerve fibers within the patient. The invention shapes an elongated electric field of effect that can be oriented parallel to a long nerve. In one embodiment, the device comprises two toroidal cores that lie adjacent to one another.

Abstract: Non-invasive electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including sinus symptoms that resemble an immune-mediated response (“sinus” headaches), irrespective of whether those symptoms arise from an allergy that is co-morbid with the headache. The disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

Abstract: A method of inserting an intervertebral disc implant into a disc space includes accessing a spinal segment having a first vertebral body, a second vertebral body and a disc space between the first and second vertebral bodies. The method includes securing a first pin to the first vertebral body and a second pin to the second vertebral body, using the first and second pins for distracting the disc space, and providing an inserter holding the intervertebral disc implant. The method also desirably includes engaging the inserter with the first and second pins, and advancing the inserter toward the disc space for inserting the intervertebral disc implant into the disc space, whereby the first and second pins align and guide the inserter toward the disc space.

Abstract: Energy is transmitted noninvasively to a patient using electrode-based stimulation devices or magnetic stimulation devices that are designed to non-invasively stimulate nerves selectively. The devices produce impulses that are used to treat atrial fibrillation, by stimulating a vagus nerve of a patient. The devices are also used to forecast the imminent onset of atrial fibrillation and then avert it by stimulating a vagus nerve.

Abstract: Devices, systems, and methods for treating gastro-esophageal reflux disease (GERD) include anti-reflux valves and retainers for securing them within the lumen of the esophagus, stomach, or a hiatal hernia. The retainers contain inflatable balloons, some of which may be enveloped by a flexible shell that is used to secure the balloon to tissue. Methods are described for treating GERD patients who (1) have no hiatal hernia, (2) have a hiatal hernia that is fixed in place, or (3) have a hiatal hernia that slides above and below the diaphragm. Methods are also described for delivering GERD-treatment devices to their target locations within the patient's gastrointestinal tract.

Abstract: Devices, systems and methods for applying electrical impulse(s) to one or more selected nerves are described. An electrical stimulator is introduced through a to a target location within, adjacent to, or in close proximity with, the carotid sheath. The stimulator has an antenna that allows it to be powered solely by far-field or approximately plane wave electromagnetic radiation, having frequencies in the range of 0.3 to 10 GHz. Electrical impulses are applied through the stimulator to a vagus nerve to stimulate, block or otherwise modulate activity of the nerve and treat the patient's condition. The stimulator uses an adjustable number of fixed voltage (or fixed current) pulses with fixed duration to elicit desired changes in nerve response, the timing of which are controlled by an external power transmitter and controller.

Abstract: Devices, systems and methods are disclosed for modulating cranial nerves, such as the sphenopalatine ganglion, to treat a medical condition of a patient, such as cluster headache. A stimulation device is advanced transnasally to a target site at or adjacent to the nasopharyngeal mucosa posterior to the middle turbinate. Electrical impulses are applied through one or more electrodes in the stimulation device to the target nerve sufficient to modulate the nerve and treat the medical condition.

Abstract: Transcutaneous electrical and magnetic nerve stimulation devices and methods generate energy that is delivered noninvasively to selected nerve fibers within the patient to treat lower urinary tract disorders. The disorders comprise overactive bladder, urge incontinence, stress, incontinence, urge frequency, non-obstructive urinary retention and interstitial cystitis/painful bladder syndrome. In preferred embodiments, a posterior tibial nerve of a patient is stimulated non-invasively to treat bladder disorders.

Abstract: A non-invasive electrical stimulator shapes an elongated electric field of effect that can be oriented parallel to a long nerve, such as a vagus nerve in a patient's neck, producing a desired physiological response in the patient. The stimulator comprises a source of electrical power, at least one electrode and a continuous electrically conducting medium in contact with the electrodes. The conducting medium is also in contact with an interface element that may conform to the contour of a target body surface of the patient when the interface element is applied to that surface. When the interface element is made of insulating (dielectric) material, and disclosed stimulation waveforms are used, the power source need not supply high voltage, in order to capacitively stimulate the target nerve. The stimulator produces a peak pulse that is sufficient to produce a physiologically effective electric field in the vicinity of a target nerve.

Abstract: A method of inserting an intervertebral disc implant into a disc space includes accessing a spinal segment having a first vertebral body, a second vertebral body and a disc space between the first and second vertebral bodies. The method includes securing a first pin to the first vertebral body and a second pin to the second vertebral body, using the first and second pins for distracting the disc space, and providing an inserter holding the intervertebral disc implant. The method also desirably includes engaging the inserter with the first and second pins, and advancing the inserter toward the disc space for inserting the intervertebral disc implant into the disc space, whereby the first and second pins align and guide the inserter toward the disc space.