Real-World Observations and Practical Considerations of Subcutaneous Daratumumab Administration in Multiple Myeloma

Background: Subcutaneous daratumumab (dara-SC) has several advantages over intravenous daratumumab (dara-IV). It has significantly shorter administration time, lower rates of systemic reactions, and smaller administration volume, while maintaining comparable efficacy and safety. Its fixed dosing allows for easier preparation. At our institution, standard approach is to monitor for 4h following the initial dara-SC dose for those at high risk for systemic reactions, defined as no prior dara use, treatment break ≥90d, or any prior history of reactions. We also administer montelukast and fexofenadine for the first 2 doses of dara-SC in addition to the usual standard pre-medications. Herein, we share our experience with dara-SC use in both dara-naïve and dara-exposed patients in order to gain practical insight, such as optimal monitoring duration, considerations for transitioning between dara-IV and dara-SC, and the place of therapy for dara-IV based on adverse events (AEs). Methods: Between June 2020 and June 2021, patients who received at least one dose of dara-SC were identified and their record was reviewed for any systemic reactions, hypersensitivity medication use, and patient reported AEs. Results: Since June 2020, our dara-SC drug use increased from 38% to 91% of all doses. There were 208 patients who received at least 1 dose of dara-SC. Of 208 patients, 99 (47.6%) were dara-naïve and 109 (52.4%) had prior dara exposure - either transitioning from dara-IV on schedule or had dara-IV as a past line of therapy. We identified 124 patients who met the criteria for 4h post dara-SC injection monitoring: dara-naïve (79.8%), treatment break ≥90d (18.5%), or prior history of reactions (1.6%). Only 5 experienced systemic reactions, representing 4% among those at high risk. All reactions were mild requiring minimal intervention and occurred following the first dara-SC dose. Onset of reactions and type of intervention during the 4h monitoring window were: hypotension (2h; fluid), nausea/vomiting (2.5h; hypersensitivity medications), and sinus tachycardia (4h), while 2 patients had transient chest pressure/tightness at home (1 within 24h, 1 between 1-6d following the dose). Eleven patients (5%) receiving dara-SC converted back to dara-IV, with AEs being the most common reason. Diarrhea, fatigue, and injection site reactions were among the most frequent patient-reported AEs. When transitioning back to dara-IV, a 90min rapid infusion rate was used if >4 prior dara doses were given. No infusion-related reactions were observed. Conclusion: The introduction of dara-SC has significantly improved patient experience. We observed a lower rate of systemic reactions compared to previous reports of 10% with first dose of dara-SC. This may be partly due to our strengthened pre-medication strategy. Opportunities exist to further improve and apply practical considerations when administering dara-SC. Based on our results, shortening on-site monitoring time may be feasible. Disclosures O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Branagan: Adaptive: Consultancy; Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Yee: GSK: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy.

Excision of intra-dural dorsal spine meningioma with intra-operative neuromonitoring in a patient with post-pneumonectomy status- an anaesthetic challenge

Post-pneumonectomy status is associated with various anatomical and physiological changes. Intra-operative neuromonitoring allows for safe neurosurgery with minimal neurological damage. Intra-operative neuromonitoring requires that the anaesthetic technique be modified taking into considerations the effects of various anaesthetic agents on evoked potentials to allow for optimal monitoring. We present a case of 65 year old female patient, with post-pneumonectomy status posted for excision of intra-dural D10 meningioma with intra-operative neuromonitoring. The case was successfully conducted with meticulous planning and preparation with complete excision of lesion and no neurological deficit post-operatively.

In vivo non-invasive near-infrared spectroscopy distinguishes normal, post-stroke, and botulinum toxin treated human muscles

In post-stroke hemiparesis, neural impairment alters muscle control, causing abnormal movement and posture in the affected limbs. A decrease in voluntary use of the paretic arm and flexed posture during rest also induce secondary tissue transformation in the upper limb muscles. To obtain a specific, accurate, and reproducible marker of the current biological status of muscles, we collected visible (VIS) and short-wave Infrared (SWIR) reflectance spectra in vivo using a portable spectroradiometer (350–2500 nm), which provided the spectral fingerprints of the elbow flexors and extensors. We compared the spectra for the affected and unaffected sides in 23 patients with post-stroke hemiparesis (25–87 years, 8 women) and eight healthy controls (33–87 years, 5 women). In eight patients, spectra were collected before and after botulinum toxin injection. Spectra underwent off-line preprocessing, principal component analysis, and partial least-squares discriminant analysis. Spectral fingerprints discriminated the muscle (biceps vs. triceps), neurological condition (normal vs. affected vs. unaffected), and effect of botulinum toxin treatment (before vs. 30 to 40 days vs. 110 to 120 days after injection). VIS-SWIR spectroscopy proved valuable for non-invasive assessment of optical properties in muscles, enabled more comprehensive evaluation of hemiparetic muscles, and provided optimal monitoring of the effectiveness of medication.

Assessing the Use of Optical Satellite Images to Detect Volcanic Impacts on Glacier Surface Morphology

Globally, about 250 Holocene volcanoes are either glacier-clad or have glaciers in close proximity. Interactions between volcanoes and glaciers are therefore common, and some of the most deadly (e.g., Nevado del Ruiz, 1985) and most costly (e.g., Eyjafjallajökull, 2010) eruptions of recent years were associated with glaciovolcanism. An improved understanding of volcano-glacier interactions is therefore of both global scientific and societal importance. This study investigates the potential of using optical satellite images to detect volcanic impacts on glaciers, with a view to utilise detected changes in glacier surface morphology to improve glacier-clad volcano monitoring and eruption forecasting. Roughly 1400 optical satellite images are investigated from key, well-documented eruptions around the globe during the satellite remote sensing era (i.e., 1972 to present). The most common observable volcanic impact on glacier morphology (for both thick and thin ice-masses) is the formation of ice cauldrons and openings, often associated with concentric crevassing. Other observable volcanic impacts include ice bulging and fracturing due to subglacial dome growth; localized crevassing adjacent to supraglacial lava flows; widespread glacier crevassing, presumably, due to meltwater-triggered glacier acceleration and advance. The main limitation of using optical satellite images to investigate changes in glacier morphology is the availability of cloud- and eruption-plume-free scenes of sufficient spatial- and temporal resolution. Therefore, for optimal monitoring and eruption prediction at glacier-clad volcanoes, optical satellite images are best used in combination with other sources, including SAR satellite data, aerial images, ground-based observations and satellite-derived products (e.g., DEMs).

Investigation Into the Optical Emission of Features for Powder-bed Fusion Am Process Monitoring

Process monitoring and control is an essential approach to improve additive manufacturing (AM) built quality. For the development of powder bed fusion (PBF) AM monitoring system, sensing process optical emission is a popular approach, as it provides rich information on melt pool condition which directly determines final part quality. However, the optical emission information is convoluted. And the lack of full understanding of it limits the further development of an optimal monitoring system. Therefore, the aim of this study is to explore the correlations between the optical emission and the processing condition to help enhance PBF process monitoring. A high-speed camera was used to acquire the images of the optical emission in the waveband of 800 nm – 1,000 nm. Several typical features were extracted and analyzed with the increase of laser power. The K-means clustering method was used to identify the hidden patterns of these features. The SVM model was built for quality identification. Five process patterns have been identified and therefore the collected dataset was partitioned into five subsets. The extracted features in each subset was characterized. It is found that plume area and plume orientation are the two most crucial features for processing condition monitoring. Number of spatters and spatter dispersion index are sensitive to some minor process vibrations which have little effect on built quality. Additionally, the time sequence information of the features can help improve the quality identification performance.

MYASTHENIA GRAVIS IN PREGNANCY: A RARE ASSOCIATION WITH AN UNPREDICTABLE EVOLUTION – THREE CASES PRESENTATION

Myasthenia gravis is a neuro-immunological disease due to the blockage of motor plate post-synaptic receptors by antiacetylcholine receptors antibodies, causing excessive fatigability of skeletal striated muscles. Thus, vital prognosis is engaged by swallowing disorders and respiratory distress related to pharyngeal striated and intercostal muscles damage. Myasthenia evolves by flare-ups, with two peaks of prevalence: first one, between 20 and 30 years-old with femal predominance. Then after 40 years-old, sex ratio evens out. Therefore, association of myasthenia and pregnancy is not exceptional, hence the interest in knowing particularities of these pregnancies, to ensure optimal monitoring for both mother and child. Indeed, mother’s risk is myasthenia decompensation, while child’s risk is neonatal myasthenia gravis. We report three myasthenia and pregnancy cases, from prenatal period to pueripartum, then we discuss in literature light, myasthenia gravis bidirectional influence on pregnancy, as well as impact of anti-myasthenic treatments on pregnancy.

The Safety of Continuous Infusion Propofol in Mechanically Ventilated Adults With Coronavirus Disease 2019

Background: Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown. Objective: To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19. Methods: This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for <12 hours, were transferred from an outside hospital while on mechanical ventilation, or did not have a triglyceride concentration obtained during the infusion were excluded. Results: A total of 252 patients were included. Hypertriglyceridemia (serum triglyceride concentration ≥ 400 mg/dL) occurred in 38.9% of patients after a median cumulative dose of 4307 mg (interquartile range [IQR], 2448-9431 mg). The median time to triglyceride elevation was 3.8 days (IQR, 1.9-9.1 days). In the multivariable regression analysis, obese patients had a significantly greater odds of hypertriglyceridemia (odds ratio = 1.87; 95% CI = 1.10, 3.21). There was no occurrence of acute pancreatitis. The incidence of possible propofol-related infusion syndrome was 3.2%. Conclusion and Relevance: Hypertriglyceridemia occurred frequently in patients with COVID-19 who received propofol but did not lead to acute pancreatitis. Elevated triglyceride concentrations occurred more often and at lower cumulative doses than previously reported in patients without COVID-19. Application of these data may aid in optimal monitoring for serious adverse effects of propofol in patients with COVID-19.

Optimal monitoring of the ocean surface by observing the transport crossroads

&lt;p&gt;In the context of tracer transport in the ocean, we introduce a quantity, the crossroadness [1], which allows identifying the optimal disposition of a set of locations in order to monitor a given ocean surface region. The optimization is performed so that these sites observe the largest amount of water coming from the region and, at the same time, monitor waters coming from separate parts of the ocean. These are key criteria when deploying a marine observing network. Considering surface circulation, crossroadness measures at any location the extent of the ocean surface which transits in its neighborhood in a given time window. When the analysis is performed backward in time, this method allows us to identify the major sources which feed a target region. The method is first applied to a minimalistic model of a mesoscale eddy field, and then to realistic satellite-derived ocean currents in the Kerguelen area. In this region, we identify the optimal location of fixed stations capable of intercepting the trajectories of 43 surface drifters. We then illustrate the temporal persistence of the stations determined in this way. Finally, we identify possible hotspots of micro-nutrient enrichment for the recurrent spring phytoplanktonic bloom occurring there. Promising applications to other fields, such as larval connectivity or contaminant detection are discussed.&lt;/p&gt;&lt;p&gt;[1] A. Baudena, E. Ser-Giacomi, C. L&amp;#243;pez, E. Hern&amp;#225;ndez-Garc&amp;#237;a, F. d&amp;#8217;Ovidio, Crossroads of the mesoscale circulation, Journal of Marine Systems 192, 1-14 (2019).&lt;/p&gt;