Association of hypoglossal nerve stimulator response with machine learning identified negative effort dependence patterns.

BACKGROUND: Hypoglossal nerve stimulator (HGNS) is a therapeutic option for moderate to severe obstructive sleep apnea (OSA). Improved patient selection criteria are needed to target those most likely to benefit. We hypothesized that the pattern of negative effort dependence (NED) on inspiratory flow limited waveforms recorded during sleep, which has been correlated with the site of upper airway collapse, would contribute to the prediction of HGNS outcome. We developed a machine learning (ML) algorithm to identify NED patterns in pre-treatment sleep studies. We hypothesized that the predominant NED pattern would differ between HGNS responders and non-responders. METHODS: An ML algorithm to identify NED patterns on the inspiratory portion of the nasal pressure waveform was derived from 5 development set polysomnograms. The algorithm was applied to pre-treatment sleep studies of subjects who underwent HGNS implantation to determine the percentage of each NED pattern. HGNS response was defined by STAR trial criteria for success (apnea-hypopnea index (AHI) reduced by > 50% and < 20/h) as well as by a change in AHI and oxygenation metrics. The predominant NED pattern in HGNS responders and non-responders was determined. Other variables including demographics and oxygenation metrics were also assessed between responders and non-responders. RESULTS: Of 45 subjects, 4 were excluded due to technically inadequate polysomnograms. In the remaining 41 subjects, ML accurately distinguished three NED patterns (minimal, non-discontinuous, and discontinuous). The percentage of NED minimal breaths was significantly greater in responders compared with non-responders (p = 0.01) when the response was defined based on STAR trial criteria, change in AHI, and oxygenation metrics. CONCLUSION: ML can accurately identify NED patterns in pre-treatment sleep studies. There was a statistically significant difference in the predominant NED pattern between HGNS responders and non-responders with a greater NED minimal pattern in responders. Prospective studies incorporating NED patterns into predictive modeling of factors determining HGNS outcomes are needed.

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production.

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H2O2. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.

Optimization of Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea With Ultrasound Assessment of Tongue Movement.

BACKGROUND: Hypoglossal nerve stimulation (HGNS) is an Food and Drug Administration-approved therapy for obstructive sleep apnea. Initial programming of HGNS is based on the observation of anterior tongue movement, which may not reflect opening at the retroglossal airway. We developed an ultrasonographic technique to assess the base of tongue movement with HGNS to be used to optimize the initial voltage settings. STUDY QUESTION: This study aimed to investigate the use of ultrasound to assess tongue movement with HGNS and related this measure to the apnea hypopnea index (AHI) on subsequent home sleep apnea testing or in-laboratory polysomnography with therapy. STUDY DESIGN: Seventeen subjects (n = 17) implanted with HGNS were enrolled at least 1 month postimplantation. Ultrasonographic measures were then used to optimize HGNS voltage to produce observable base of tongue protrusion without producing discomfort. Responders were defined as a reduction in AHI > 50% and an AHI of <20 events/h. RESULTS: There were 17 subjects, 11 men and 6 women, with age = 64.6 ± 9.8 years, body mass index = 27.9 ± 2.7 kg/m2, and pretreatment AHI = 36.5 ± 14.4/h, T-90% = 10.7 ± 14.8%. The mean hyoid bone excursion (HBE) in responders = 1.0 ± 0.13 cm versus 0.82 ± 0.12 cm in nonresponders (P = 0.017). HBE was correlated with AHI during HGNS treatment (coef. -0.54, P = 0.03). Best subsets regression analysis using treatment-based AHI as the dependent variable and age, body mass index, baseline AHI, HBE, and HGNS voltage as independent variables showed that HBE (coef. -44.6, P = 0.044) was the only independent predictor of response. Receiver operator curve analysis showed that HBE > 0.85 cm had a sensitivity of 83.3% and specificity of 80.0% with a positive likelihood ratio of 4.17 to predict responder status. CONCLUSION: We demonstrated that ultrasound assessment of HBE during HGNS programming is a useful tool to optimize therapy.

Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead.

The mainstay of treatment for obstructive sleep apnea is positive airway pressure therapy, which may be difficult for some patients to tolerate leading to compromised adherence and requiring alternative therapies. Hypoglossal nerve stimulation has become an option for those who meet implantation criteria. Implantation of the device is an ambulatory surgical procedure and is generally well-tolerated, though rare adverse events have been reported. We report an unusual complication of hypoglossal nerve stimulation in a patient who had initial success with this therapy. After 3 years of treatment, the sensor lead penetrated into the pleural space. Components of the hypoglossal nerve stimulation were explanted, and a new sensor lead and generator were reimplanted. The new device was activated, and therapy was successfully resumed. This case demonstrates that there is a potential for a delayed complication of sensor lead penetration into the pleural space, which has only rarely been reported. CITATION: Lou B, Hahn S, Korotun M, Quintero L, Shikowitz M, Greenberg H. Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead. J Clin Sleep Med. 2021;17(11):2329-2332.

Anti-inflammatory, antinociceptive, and antipyretic effects of Lantana trifolia Linnaeus in experimental animals.

Lantana trifolia L. (Verbenaceae) is traditionally used as an anti-inflammatory medicinal plant in Venezuela. The methanol extract of the aerial parts of L. trifolia were assessed for the anti-inflammatory, anti-nociceptive and anti-pyretic properties. The extract produced an inhibition of carrageenan-induced edema in the rat paw over a dose range of 10-300 mg/kg i.p.; the dose-response curve was bell-shaped with a maximal effect at 100 mg/kg. The extract also produced a small but significant increase in the response latency of rats subjected to the hot plate, a thermal pain test that only detects analgesia by high-efficacy agents. The extract did not exhibit antipyretic activity. Thus, the L. trifolia extract could have therapeutically relevant anti-inflammatory and analgesic properties in humans.

Anti-inflammatory, antinociceptive, and antipyretic effects of Lantana trifolia linnaeus in experimental animals

Lantana trifolia Linnaeus (Verbenaceae) es tradicionalmente utilizada en Venezuela como una planta medicinal antiinflamatoria. Nosotros indagamos si el extracto metanólico de la parte aérea de L. trifolia posee propiedades antiinflamatoria, antinociceptiva y antipirética. El extracto produjo inhibición del edema inducido por carragenina en la pata trasera derecha de las ratas, en dosis de 10-300 mg/Kg de peso del animal., administradas vía i.p. La curva dosis-respuesta exhibe un máximo a la dosis de 100 mg/Kg. El extracto también produjo un leve pero significativo incremento en la respuesta de latencia de las ratas sometidas al plato caliente, una prueba que sólo detecta analgesia en agentes altamente eficaces. El extracto no exhibió actividad antipirética. El extracto de L. trifolia pudiera tener propiedades terapéuticas antiinflamatorias y analgésicas relevantes en humanos

Efecto de los implantes subcutáneos de melatonina y la suplementación alimentaria, sobre la inducción de la actividad ovárica en ovejas pelibuey durante la época de anestro / Effect of melatonin subcutaneous implants and feed supplementation on ovarian activity induction in Pelibuey ewes during the anestrous season

Se evaluó el efecto de implantes de melatonina sobre la inducción de la actividad ovárica en ovejas Pelibuey suplementadas o no durante la época de anestro. El estudio se realizó bajo condiciones de trópico húmedo (20º 4' latitud Norte). Se utilizaron 90 ovejas Pelibuey en anestro que parieron a finales del otoño (noviembre y diciembre). La mitad del rebaño se suplementó de febrero a junio con concentrado (14 por ciento PC y 3500 Kcal/kg). A mediados de marzo, los grupos suplementados y no suplementados fueron subdivididos para recibir o no un implante subcutáneo conteniendo 18 mg de melatonina, de esta manera se formaron los siguientes grupos: M + S (suplementado, con melatonina; n = 24), M + P (pastoreo con melatonina; n = 23); S (suplementado; n = 22) y testigo (en pastoreo; n = 21). La actividad ovárica en las ovejas fue seguida por determinación de niveles de progesterona plasmática y por detección diaria de estros. Sólo 54.4 por ciento del rebaño presentó estro. No se encontraron diferencias (P > 0.05) entre tratamientos en los porcentajes de ovejas que ovularon (M + S = 84.6 por ciento; M + P = 72.9 por ciento; S = 80.0 por ciento y testigo = 55.5 por ciento) y que mostraron estro (M + S = 70.8 por ciento; M + P = 47.8 por ciento; S = 45.4 por ciento y testigo = 52.3 por ciento), ni en el intervalo del inicio del tratamiento con melatonina a primera elevación de progesterona (11.6 ñ 2.9 días; 16.5 ñ 3.3 días; 12.2 ñ 1.3 días y 8.0 ñ 3.6 días para los grupos M + S, M + P, S y testigo, respectivamente). El intervalo inicio del tratamiento con melatonina-primer estro (M + S, 18.8 ñ 2.8 días; M + P, 14.0 ñ 1.9 días; S, 10.4 ñ 1.5 días; testigo, 11.5 ñ 1.9 días) también fue igual (P > 0.05) entre grupos. Se concluye que la rápida inducción de la actividad ovárica de las ovejas en anestro no fue debida a la melatonina exógena o a la suplementación con concentrado, sino a un posible "efecto macho".