A retrospective investigation of the relationship between neuroblastoma response to anti-GD2 monoclonal antibodies and exposure to opioids for pain management.

OBJECTIVE: Recent increased awareness and research studies reflect possible associations between opioid exposure and cancer outcomes. Children with neuroblastoma (NB) often require opioid treatment for pain. However, associations between tumor response to chemotherapy and opioid exposure have not been investigated in clinical settings. METHODS: This is a single-institution retrospective review of patients with NB treated between 2013 and 2016. We evaluated opioid consumption quantified in morphine equivalent doses (mg/kg) based on nurse- or patient-controlled analgesia during antibody infusions. We also analyzed their associations with change in primary tumor volume and total tumor burden. RESULTS: Of 42 patients given opioids for pain related to anti-disialoganglioside monoclonal antibodies (anti-GD2 mAb), data completion was achieved for 36, and details of statistical analyses were entered. Median total weight-based morphine equivalent (over 8 days) was 4.71 mg/kg (interquartile range 3.49-7.96). We found a statistically insignificant weak negative relationship between total weight-based morphine equivalents and tumor volume ratio (correlation coefficient -.0103, p-value .9525) and a statistically insignificant weak positive relationship between total weight-based morphine equivalent and Curie score ratio (correlation coefficient .1096, p-value .5247). CONCLUSION: Our study found no statistically significant correlation between opioid consumption and natural killer (NK) cell-mediated killing of NB cells as measured by effects on tumor volume/tumor load.

Palliative Sedation Therapy Practice Comparison - A Survey of Pediatric Palliative Care and Pain Management Specialists.

Context: Palliative sedation therapy (PST) can relieve suffering at end-of-life (EOL) in children with intolerable and refractory symptoms. However, updated and consistent guidance on PST practices are imperative. Objectives: We investigate current variations in clinical practice and PST implementation among pediatric palliative care (PPC) and pain management (PM) specialists. Methods: We distributed an IRB-exempt electronic anonymous survey via email through the Society of Pediatric Pain Medicine, and the American Academy of Hospice and Palliative Medicine. Survey responses were collated and descriptively reported. Results: Of 83 survey responses, the majority (75%) represented large academic children's hospitals. The distribution between PPC and pediatric pain management specialists' responses was 60% and 40%, respectively. Most respondents reported having designated pain management and/or palliative care teams (70% and 90%, respectively). Approximately half (48%) reported following an institutional PST protocol, most not requiring formal ethics consult (69%). Only 54% of respondents noted that the Do Not Resuscitate (DNR) order was required prior to PST initiation. PST was primarily utilized for children with oncologic diagnoses (76%). The primary and secondary medications of choice for PST implementation were reported to be opioids (39%) and benzodiazepines (36%) by pain management specialists, and benzodiazepines (52%) and barbiturates (28%) by palliative care specialists. Conclusions: Our study highlights the variability in the practice and implementation of PST. Further educational efforts are key for establishing PST practices and efficient protocol development.

Palliative Sedation Therapy in Pediatrics: An Algorithm and Clinical Practice Update.

Palliative sedation therapy (PST) is an important clinical intervention for pediatric patients with refractory symptoms and suffering during the end-of-life (EOL) period. Variations in PST implementation including medication selection, limited literature regarding feasibility in various clinical settings, particularly non-intensive care units, and lack of education on evolving definitions and ideal practices may all contribute to the current underutilization of this valuable resource. We therefore offer a clinical algorithm for identifying appropriate patients for PST, ensuring all other modalities for symptom management have been considered and/or optimized, and present a guideline for PST implementation that can be adapted and individualized based on institutional experience and resource availability. Furthermore, through case-based clinical scenarios, we demonstrate how to incorporate this algorithm into EOL practice.

Monsoonal variations of lead (Pb) in coastal waters around Singapore.

Anthropogenic lead (Pb) has been the overwhelming Pb source to the global ocean, primarily contributed from Pb gasoline and industrial emissions. However, since Pb gasoline has been phased out globally, questions about whether there was a decrease in seawater Pb concentration, or if there are other sources taking over remains unclear in Southeast Asia. Here, combining Pb concentrations in seawater from Singapore Strait in 2010-2017; trap sediment in 2018-2019; and the previously published coral reconstruction covering 1975-2010; we found that the seawater Pb concentration in Singapore Strait over past decades followed the regional gasoline emissions, and no additional major source had contributed the Pb in the seawater since ~2010. The present-day Pb in Singapore Straits' water mainly follows the monsoonal current reversals, with variable degrees of scavenging that peak in inter-monsoon season. Minor Pb sources still contribute to some local-scale variabilities, despite a decadal-scale decreasing trend of Pb in seawater.

Low-dose ketamine infusions reduce opioid use in pediatric and young adult oncology patients.

BACKGROUND: Ketamine is an NMDA-receptor antagonist with analgesic and opioid-sparing properties. Although well studied in adults, more robust evidence supporting ketamine's use for pediatric pain management is needed. This retrospective study evaluates ketamine's opioid-sparing effectiveness in pediatric and young adult oncology and hematology patients. PROCEDURE: Continuous ketamine infusions administered for pain management between 2010-2020 were reviewed. Data including demographic characteristics, oncology/hematology and pain diagnoses, concurrent pain medications, and ketamine infusions' dose and duration were collected. Opioid consumption data based on delivery via patient-controlled analgesia were collected 1 day before (D1), all days during (cumulatively named D2), and 1 day after (D3) ketamine infusions and calculated as morphine-equivalent doses (mg/kg/day). Data were reported for the entire study group as well as for distinct oncology and end-of-life categories, and short-term acute pain circumstances which included vaso-occlusive crises in hematology patients. Side effects were reviewed. RESULTS: Significantly lower daily opioid consumption was noted in the oncology group, while decreases were not significant in the end-of-life group and in the overall study population. The acute pain group did not show an opioid reduction associated with the ketamine infusions. A largely tolerable side-effect profile was observed, with no differences among each group's incidence. CONCLUSIONS: Ketamine infusions were associated with significantly reduced opioid consumption for oncology patients. The opioid-sparing effects of ketamine may vary according to clinical diagnoses and circumstances of use. Overall, low-dose ketamine infusions present an acceptable safety profile in pediatric and young adult patients; nevertheless, individual risks and benefits should be considered.

Coral-associated nitrogen fixation rates and diazotrophic diversity on a nutrient-replete equatorial reef.

The role of diazotrophs in coral physiology and reef biogeochemistry remains poorly understood, in part because N2 fixation rates and diazotrophic community composition have only been jointly analyzed in the tissue of one tropical coral species. We performed field-based 15N2 tracer incubations during nutrient-replete conditions to measure diazotroph-derived nitrogen (DDN) assimilation into three species of scleractinian coral (Pocillopora acuta, Goniopora columna, Platygyra sinensis). Using multi-marker metabarcoding (16S rRNA, nifH, 18S rRNA), we analyzed DNA- and RNA-based communities in coral tissue and skeleton. Despite low N2 fixation rates, DDN assimilation supplied up to 6% of the holobiont's N demand. Active coral-associated diazotrophs were chiefly Cluster I (aerobes or facultative anaerobes), suggesting that oxygen may control coral-associated diazotrophy. Highest N2 fixation rates were observed in the endolithic community (0.20 µg N cm-2 per day). While the diazotrophic community was similar between the tissue and skeleton, RNA:DNA ratios indicate potential differences in relative diazotrophic activity between these compartments. In Pocillopora, DDN was found in endolithic, host, and symbiont compartments, while diazotrophic nifH sequences were only observed in the endolithic layer, suggesting a possible DDN exchange between the endolithic community and the overlying coral tissue. Our findings demonstrate that coral-associated diazotrophy is significant, even in nutrient-rich waters, and suggest that endolithic microbes are major contributors to coral nitrogen cycling on reefs.

Growth and carbonate production of crustose coralline algae on a degraded turbid reef system.

Crustose coralline algae (CCA) and other encrusting calcifiers drive carbonate production on coral reefs. However, little is known about the rates of growth and calcification of these organisms within degraded turbid reef systems. Here we deployed settlement cards (N = 764) across seven reefs in Singapore for two years to examine spatio-temporal variation in encrusting community composition and CCA carbonate production. Our results showed that CCA was the dominant encrusting taxa (63.7% ± 18.3SD) across reefs. CCA carbonate production rates (0.009-0.052 g cm-2 yr-1) were less than half of those reported for most Indo-Pacific reefs, but similar to other turbid reef systems. Highest CCA carbonate production rates were observed furthest from Singapore's main shipping port, due to a relative increase in CCA cover on the offshore reefs. Our results suggest that proximity to areas of high industrialisation and ship traffic may reduce the cover of encrusting calcifying organisms and CCA production rates which may have negative, long-term implications for the stabilisation of nearshore reefs in urbanised settings.

Liposomal Bupivacaine for Pediatric Celiac Plexus Block: A Case Report of Refractory Constipation Management.

Liposomal bupivacaine is a long-acting amide local anesthetic with a limited list of indications. At the time of publication, use is limited to field block and surgical wound infiltration and, more recently, interscalene nerve block. Although commonly used in adults, less is known about the safety and efficacy in pediatric patients. We present the use of liposomal bupivacaine for pediatric celiac plexus block in a 12-year-old boy suffering from gastrointestinal complications (eg, pain, constipation, and ileus) after bone marrow transplantation. Celiac plexus block utilizing liposomal bupivacaine was successfully used to palliate his pain and to normalize bowel function.

Focal limbic sources create the large slow oscillations of the EEG in human deep sleep.

BACKGROUND: Initial observations with the human electroencephalogram (EEG) have interpreted slow oscillations (SOs) of the EEG during deep sleep (N3) as reflecting widespread surface-negative traveling waves that originate in frontal regions and propagate across the neocortex. However, mapping SOs with a high-density array shows the simultaneous appearance of posterior positive voltage fields in the EEG at the time of the frontal-negative fields, with the typical inversion point (apparent source) around the temporal lobe. METHODS: Overnight 256-channel EEG recordings were gathered from 10 healthy young adults. Individual head conductivity models were created using each participant's own structural MRI. Source localization of SOs during N3 was then performed. RESULTS: Electrical source localization models confirmed that these large waves were created by focal discharges within the ventral limbic cortex, including medial temporal and caudal orbitofrontal cortex. CONCLUSIONS: Although the functional neurophysiology of deep sleep involves interactions between limbic and neocortical networks, the large EEG deflections of deep sleep are not created by distributed traveling waves in lateral neocortex but instead by relatively focal limbic discharges.

Physics-constrained, low-dimensional models for magnetohydrodynamics: First-principles and data-driven approaches.

Plasmas are highly nonlinear and multiscale, motivating a hierarchy of models to understand and describe their behavior. However, there is a scarcity of plasma models of lower fidelity than magnetohydrodynamics (MHD), although these reduced models hold promise for understanding key physical mechanisms, efficient computation, and real-time optimization and control. Galerkin models, obtained by projection of the MHD equations onto a truncated modal basis, and data-driven models, obtained by modern machine learning and system identification, can furnish this gap in the lower levels of the model hierarchy. This work develops a reduced-order modeling framework for compressible plasmas, leveraging decades of progress in projection-based and data-driven modeling of fluids. We begin by formalizing projection-based model reduction for nonlinear MHD systems. To avoid separate modal decompositions for the magnetic, velocity, and pressure fields, we introduce an energy inner product to synthesize all of the fields into a dimensionally consistent, reduced-order basis. Next, we obtain an analytic model by Galerkin projection of the Hall-MHD equations onto these modes. We illustrate how global conservation laws constrain the model parameters, revealing symmetries that can be enforced in data-driven models, directly connecting these models to the underlying physics. We demonstrate the effectiveness of this approach on data from high-fidelity numerical simulations of a three-dimensional spheromak experiment. This manuscript builds a bridge to the extensive Galerkin literature in fluid mechanics and facilitates future principled development of projection-based and data-driven models for plasmas.

Lidocaine infusions and reduced opioid consumption-Retrospective experience in pediatric hematology and oncology patients with refractory pain.

BACKGROUND: Despite a more robust experience with lidocaine infusions for pain management in adults and general pediatric population, there is limited evidence of efficacy of lidocaine infusions for pain management in patients with pediatric hematology and oncology diagnoses. METHODS: Data pertaining to continuous intravenous lidocaine infusions prescribed between January 2009 and June 2019 were reviewed, including patients' demographic characteristics, hematology/oncology and pain diagnoses, concurrent pain medications, and lidocaine infusion dose regimens and duration. Pain scores and opioid consumption calculations based on morphine equivalent doses (mg/kg/day) of patient-controlled analgesia were collected 1 day before infusion (D1), during infusion (D2), and 1 day after infusion (D3). RESULTS: The mean opioid consumption on D3 was significantly lower than that on D2 (p = .01). The pain scores on D3 were significantly lower than those on D1 when measured as average pain scores per 24 hours (p < .001) or as single pain scores immediately before and after infusions (p < .001). No significant associations were found between cumulative doses of lidocaine (loading dose plus total infusion dose) and either a decrease in the opioid consumption or a decrease in pain scores. CONCLUSIONS: In this retrospective series of pediatric hematology and oncology cases, we report positive outcomes in reducing opioid consumption and pain scores after lidocaine infusions. Prospective investigations designed in a collaborative, multi-institutional fashion, including a variety of pediatric populations are needed to further investigate the efficacy of lidocaine infusions.

Does epidural analgesia really enhance recovery in pediatric surgery patients?

PURPOSE: We sought to determine the benefits of epidural anesthesia (EA) in pediatric surgical patients. METHODS: This study is a single-institution retrospective review of EA for pediatric patients undergoing thoracotomy or laparotomy from 2015 to 2020. Patients with recent or chronic opioid use were excluded. Urgent or emergent cases, patients with hemodynamic instability, or those with surgical complications that significantly impacted their post-operative course were also excluded. The primary objectives were comparison of pain scores and systemic opioid use between those patients with EA and those without EA. RESULTS: Epidural anesthesia was used in 151 (81.6%) laparotomies and 58 (77.3%) thoracotomies. EA use was associated with lower mean systemic opioid administration during the early post-operative period for laparotomy (POD#0-0.33 ± 0.3 oral morphine equivalents per kilogram (OME/Kg) with EA vs 0.93 ± 1.53, p < 0.001, POD#1-1.34 ± 1.79 OME/Kg with EA vs 2.61 ± 2.60, p < 0.001) and thoracotomy (POD#0-0.40 ± 0.37 OME/Kg with EA vs 0.68 ± 0.41, p = 0.008, POD#1-0.89 ± 0.86 OME/Kg with EA vs 2.02 ± 1.92, p < 0.001). There were no differences seen by POD#2. Average pain scores were significantly lower in patients with EA following laparotomy (POD#0-1.22 ± 0.99 with EA vs 1.75 ± 1.33, p = 0.008) and thoracotomy (POD#0-1.71 ± 1.13 with EA vs 2.40 ± 1.52, p = 0.04). CONCLUSIONS: The use of EA in pediatric surgery patients was associated with lower pain scores despite lower systemic opioid requirements in the early post-operative period.

Retrospective analysis of predisposing factors for difficult lumbar punctures requiring image guidance in pediatric oncology patients.

Success rates of lumbar punctures (LPs) in children are reportedly as low as 50%. In addition to procedural complications and failure, difficult LPs are a risk factor for traumatic LPs (TLPs), which can potentially affect diagnostic utility and alter treatment plans for pediatric oncology patients. To identify the intrinsic factors associated with technically difficult LPs in the pediatric oncology population, we performed a retrospective review of patients who required diagnostic imaging modalities for LP procedures at a single pediatric oncology institution between September 2008 and November 2018. We evaluated data from 64 LPs performed in 33 patients who were referred for image-guided LPs after undergoing technically difficult LPs that were unsuccessful using anatomic landmarks. In these cases, 96.9% of patients had at least one of the following intrinsic factors: body mass index (BMI) ≥ 25, anatomic spinal abnormalities, history of ≥ 5 previous LPs, age < 12 months, and history of back surgery. Elevated BMI was the most common factor associated with difficult LP (81.8%), followed by spinal abnormalities (51.5%), and history of ≥ 5 previous LPs (33.3%). Age < 12 months and history of back surgery were also associated with difficult LPs, but at a lower frequency. On the basis of these findings, we propose clinical recommendations for preprocedural identification of patients at risk of difficult LPs to reduce complications, including TLP, failure, and exposure to general anesthesia.

Transcranial Electrical Stimulation targeting limbic cortex increases the duration of human deep sleep.

BACKGROUND: Researchers have proposed that impaired sleep may be a causal link in the progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Several recent findings suggest that enhancing deep sleep (N3) may improve neurological health in persons with MCI, and buffer the risk for AD. Specifically, Transcranial Electrical Stimulation (TES) of frontal brain areas, the inferred source of the Slow Oscillations (SOs) of N3 sleep, can extend N3 sleep duration and improve declarative memory for recently learned information. Recent work in our laboratory using dense array Electroencephalography (dEEG) localized the sources of SOs to anterior limbic sites - suggesting that targeting these sites with TES may be more effective for enhancing N3. METHODS: For the present study, we recruited 13 healthy adults (M = 42 years) to participate in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic areas and a sham stimulation (placebo). We used a convolutional neural network, trained and tested on professionally scored EEG sleep staging, to predict sleep stages for each recording. RESULTS: When compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep. TES also significantly increased spectral power in the 0.5-1 Hz frequency band (relative to pre-TES epochs) in left temporoparietal and left occipital scalp regions compared to sham. CONCLUSION: These results suggest that even low-level TES, when specifically targeting anterior limbic sites, can increase deep (N3) sleep and thereby contribute to healthy sleep quality.

Epidural blood patch for post-dural puncture headaches in adult and paediatric patients with malignancies: a review.

Many anaesthetists are hesitant to perform epidural blood patch in patients with cancer because of the potential risk of seeding the CNS with malignant cells. Recent evidence suggests that anaesthetists may view malignancy as a relative contraindication to epidural blood patch rather than an absolute contraindication. This review article summarises the clinical dilemma, reviews the existing literature, and proposes a treatment algorithm that includes the utilisation of for the management of post-dural puncture headache in the oncology population.

Projections of coral cover and habitat change on turbid reefs under future sea-level rise.

Global sea-level rise (SLR) is projected to increase water depths above coral reefs. Although the impacts of climate disturbance events on coral cover and three-dimensional complexity are well documented, knowledge of how higher sea levels will influence future reef habitat extent and bioconstruction is limited. Here, we use 31 reef cores, coupled with detailed benthic ecological data, from turbid reefs on the central Great Barrier Reef, Australia, to model broad-scale changes in reef habitat following adjustments to reef geomorphology under different SLR scenarios. Model outputs show that modest increases in relative water depth above reefs (Representative Concentration Pathway (RCP) 4.5) over the next 100 years will increase the spatial extent of habitats with low coral cover and generic diversity. More severe SLR (RCP8.5) will completely submerge reef flats and move reef slope coral communities below the euphotic depth, despite the high vertical accretion rates that characterize these reefs. Our findings suggest adverse future trajectories associated with high emission climate scenarios which could threaten turbid reefs globally and their capacity to act as coral refugia from climate change.

Bleaching-driven reef community shifts drive pulses of increased reef sediment generation.

The ecological impacts of coral bleaching on reef communities are well documented, but resultant impacts upon reef-derived sediment supply are poorly quantified. This is an important knowledge gap because these biogenic sediments underpin shoreline and reef island maintenance. Here, we explore the impacts of the 2016 bleaching event on sediment generation by two dominant sediment producers (parrotfish and Halimeda spp.) on southern Maldivian reefs. Our data identifies two pulses of increased sediment generation in the 3 years since bleaching. The first occurred within approximately six months after bleaching as parrotfish biomass and resultant erosion rates increased, probably in response to enhanced food availability. The second pulse occurred 1 to 3 years post-bleaching, after further increases in parrotfish biomass and a major (approx. fourfold) increase in Halimeda spp. abundance. Total estimated sediment generation from these two producers increased from approximately 0.5 kg CaCO3 m-2 yr-1 (pre-bleaching; 2016) to approximately 3.7 kg CaCO3 m-2 yr-1 (post-bleaching; 2019), highlighting the strong links between reef ecology and sediment generation. However, the relevance of this sediment for shoreline maintenance probably diverges with each producer group, with parrotfish-derived sediment a more appropriate size fraction to potentially contribute to local island shorelines.

Spatiotemporal Dynamics of Multiple Memory Systems During Category Learning.

The brain utilizes distinct neural mechanisms that ease the transition through different stages of learning. Furthermore, evidence from category learning has shown that dissociable memory systems are engaged, depending on the structure of a task. This can even hold true for tasks that are very similar to each other, which complicates the process of classifying brain activity as relating to changes that are associated with learning or reflecting the engagement of a memory system suited for the task. The primary goals of these studies were to characterize the mechanisms that are associated with category learning and understand the extent to which different memory systems are recruited within a single task. Two studies providing spatial and temporal distinctions between learning-related changes in the brain and category-dependent memory systems are presented. The results from these experiments support the notion that exemplar memorization, rule-based, and perceptual similarity-based categorization are flexibly recruited in order to optimize performance during a single task. We conclude that these three methods, along with the memory systems they rely on, aid in the development of expertise, but their engagement might depend on the level of familiarity with a category.

Effectiveness of Ultrasound-Guided Platelet-Rich Plasma Injections in Relieving Sacroiliac Joint Dysfunction.

OBJECTIVE: The aim of the study was to investigate the efficacy of ultrasound-guided platelet-rich plasma in reducing sacroiliac joint disability and pain. DESIGN: Prospective nonrandomized interventional study analyzing 50 patients with low back pain secondary to sacroiliac joint dysfunction. Platelet-rich plasma was injected into the sacroiliac joint under ultrasound guidance. Oswestry Disability Index and Numeric Rating Scale were measured at baseline, 2 wks, 4 wks, 3 mos, and 6 mos after injection. RESULTS: The mean reduction in Oswestry Disability Index and Numeric Rating Scale scores were significantly reduced at 6 mos after injection compared with baseline values (mean = -9.79%, 95% CI = -6.06 to -13.52) and (mean = -1.94, 95% CI = -1.14 to -2.78), respectively. All timeframes showed significant mean reduction compared with baseline, but overall improvement tapers off after 4 wks with no statistically significant reduction from 4 wks to 3 mos or 3 to 6 mos. CONCLUSIONS: Ultrasound-guided platelet-rich plasma injections in the sacroiliac joint are effective at reducing disability and pain with most improvement seen within 4 wks after injection and with sustained reduction at 6 mos.