Evidence for transient deleterious thermal acclimation in field recapture rates of an invasive tropical species, Bactrocera dorsalis (Diptera: Tephritidae).

Knowing how environmental conditions affect performance traits in pest insects is important to improve pest management strategies. It can be informative for monitoring, but also for control programs where insects are mass-reared, and field-released. Here, we investigated how adult thermal acclimation in sterile Bactrocera dorsalis affects dispersal and recapture rates in the field using a mark-release-recapture method. We also considered how current abiotic factors may affect recapture rates and interact with thermal history. We found that acclimation at 20 or 30 °C for 4 d prior to release reduced the number of recaptures in comparison with the 25 °C control group, but with no differences between groups in the willingness to disperse upon release. However, the deleterious effects of acclimation were only detectable in the first week following release, whereafter only the recent abiotic conditions explained recapture rates. In addition, we found that recent field conditions contributed more than thermal history to explain patterns of recaptures. The two most important variables affecting the number of recaptures were the maximum temperature and the average relative humidity experienced in the 24 h preceding trapping. Our results add to the handful of studies that have considered the effect of thermal acclimation on insect field performance, but notably lend support to the deleterious acclimation hypothesis among the various hypotheses that have been proposed. Finally, this study shows that there are specific abiotic conditions (cold/hot and dry) in which recaptures will be reduced, which may therefore bias estimates of wild population size.

Long-term outcomes among survivors of childhood osteosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

PURPOSE: Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes. METHODS: Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5 years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis. RESULTS: A total of 1257 survivors of osteosarcoma were followed on average for 24.4 years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status. CONCLUSION: Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations.

Effects of Physiological Status and Environmental Factors on the Lure Responses of Three Pest Fruit Fly Species (Diptera: Tephritidae).

Biotic and abiotic factors influence how insects respond to stimuli. This can make it challenging to interpret captures in traps used to monitor pest abundance in management programmes. To address this, the lure response of three pest fruit flies (Diptera: Tephritidae) was evaluated in a semi-field setting with respect to several physiological and environmental factors. Using standardised methods with known fly numbers in field cages, the response to Biolure (food-based lure) was evaluated for Ceratitis capitata, Ceratitis cosyra and Bactrocera dorsalis. Response to the male lures was tested: E.G.O PheroLure for C. capitata and C. cosyra, Trimedlure for C. capitata, and methyl eugenol for B. dorsalis. The physiological variables evaluated were fly age, sex, weight, and total body nutritional composition. The environmental effects of temperature, relative humidity and light intensity were also assessed. Protein-deprived adults responded more strongly to Biolure. The response to Biolure was not sex-specific. Fly age influenced the response of all species to all tested lures. However, this effect was species and lure specific. Temperature was the most influential environmental factor, with response generally increasing with temperature. Lower thresholds for lure response, despite the proximity of responsive flies, range from 12.21 to 22.95 °C depending on the species and lure tested. These results indicate that trapping systems and management activity thresholds must take physiological and environmental variation into account to increase their accuracy.

Surgical management of liver tumors.

Two percent of pediatric malignancies arise primarily in the liver; roughly 60% of these cancers are hepatoblastoma (HB). Despite the rarity of these cases, international collaborative efforts have led to the consistent histological classification and staging systems, which facilitate ongoing clinical trials. Other primary liver malignancies seen in children include hepatocellular carcinoma (HCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), undifferentiated embryonal sarcoma of the liver (UESL), and hepatocellular neoplasm not otherwise specified (HCN-NOS). This review describes principles of surgical management of malignant pediatric primary liver tumors, within the context of comprehensive multidisciplinary care.

Poverty, race, ethnicity, and survival in pediatric nonmetastatic osteosarcoma: a Children's Oncology Group report.

BACKGROUND: Children living in poverty and those of marginalized race or ethnicity experience inferior disease outcomes across many cancers. Whether survival disparities exist in osteosarcoma is poorly defined. We investigated the association between race, ethnicity, and proxied poverty exposures and event-free and overall survival for children with nonmetastatic osteosarcoma receiving care on a cooperative group trial. METHODS: We conducted a retrospective cohort study of US patients with nonmetastatic, osteosarcoma aged 5-21 years enrolled on the Children's Oncology Group trial AOST0331. Race and ethnicity were categorized to reflect historically marginalized populations, as Hispanic, non-Hispanic Black, non-Hispanic Other, and non-Hispanic White. Poverty was proxied at the household and neighborhood levels. Overall survival and event-free survival functions of time from trial enrollment were estimated using the Kaplan-Meier method. Hypotheses of associations between risks for event-free survival, death, and postrelapse death with race and ethnicity were assessed using log-rank tests. RESULTS: Among 758 patients, 25.6% were household-poverty and 28.5% neighborhood-poverty exposed. Of the patients, 21% of children identified as Hispanic, 15.4% non-Hispanic Black, 5.3% non-Hispanic Other, and 54.0% non-Hispanic White. Neither household or neighborhood poverty nor race and ethnicity were statistically significantly associated with risks for event-free survival or death. Postrelapse risk for death differed statistically significantly across race and ethnicity with non-Hispanic Black patients at greatest risk (4-year postrelapse survival 35.7% Hispanic vs 13.0% non-Hispanic Black vs 43.8% non-Hispanic Other vs 38.9% non-Hispanic White; P = .0046). CONCLUSIONS: Neither proxied poverty exposures or race and ethnicity were associated with event-free survival or overall survival, suggesting equitable outcomes following frontline osteosarcoma trial-delivered therapy. Non-Hispanic Black children experienced statistically significant inferior postrelapse survival. Investigation of mechanisms underlying postrelapse disparities are paramount.

Shaping the Microbial Landscape: Parasitoid-Driven Modifications of Bactrocera dorsalis Microbiota.

Koinobiont endoparasitoids regulate the physiology of their hosts through altering host immuno-metabolic responses, processes which function in tandem to shape the composition of the microbiota of these hosts. Here, we employed 16S rRNA and ITS amplicon sequencing to investigate whether parasitization by the parasitoid wasps, Diachasmimorpha longicaudata (Ashmaed) (Hymenoptera: Braconidae) and Psyttalia cosyrae (Wilkinson) (Hymenoptera: Braconidae), induces gut dysbiosis and differentially alter the gut microbial (bacteria and fungi) communities of an important horticultural pest, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). We further investigated the composition of bacterial communities of adult D. longicaudata and P. cosyrae to ascertain whether the adult parasitoids and parasitized host larvae share microbial taxa through transmission. We demonstrated that parasitism by D. longicaudata induced significant gut perturbations, resulting in the colonization and increased relative abundance of pathogenic gut bacteria. Some pathogenic bacteria like Stenotrophomonas and Morganella were detected in both the guts of D. longicaudata-parasitized B. dorsalis larvae and adult D. longicaudata wasps, suggesting a horizontal transfer of microbes from the parasitoid to the host. The bacterial community of P. cosyrae adult wasps was dominated by Arsenophonus nasoniae, whereas that of D. longicaudata adults was dominated by Paucibater spp. and Pseudomonas spp. Parasitization by either parasitoid wasp was associated with an overall reduction in fungal diversity and evenness. These findings indicate that unlike P. cosyrae which is avirulent to B. dorsalis, parasitization by D. longicaudata induces shifts in the gut bacteriome of B. dorsalis larvae to a pathobiont-dominated community. This mechanism possibly enhances its virulence against the pest, further supporting its candidacy as an effective biocontrol agent of this frugivorous tephritid fruit fly pest.

Addition of Selected Plant-Derived Semiochemicals to Yellow Sticky Traps Does Not Improve Citrus Psyllid Captures.

Fast and effective monitoring and surveillance techniques are crucial for the swift implementation of control methods to prevent the spread of Huanglongbing, a devastating citrus disease, and its invasive psyllid vector, Asian citrus psyllid, Diaphorina citri, into South Africa, as well as to control the native vector, African citrus triozid, Trioza erytreae. Monitoring for citrus psyllid pests can be improved by using semiochemical odorants to augment already visually attractive yellow sticky traps. However, environmental variables such as temperature and humidity could influence odorant release rates. Five field cages were used to test the ability of a selection of odorants to improve yellow sticky trap efficacy in capturing citrus psyllids. Environmental effects on odorant loss from the dispensers were also investigated. The odorants that most improved yellow sticky trap captures in field cages were then tested under open field conditions alongside lower concentrations of those same lures. Gas chromatography-mass spectrometry was used to calculate odorant release rates as well as to determine if any contamination occurred under field conditions. None of the odorants under field cage or field conditions significantly improved psyllid capture on yellow sticky traps. Temperature influenced odorant loss, and release rate from polyethylene bulbs decreased over time. Based on these results, the use of unbaited yellow sticky traps seems to be the most effective method for monitoring of Huanglongbing vectors.

Pheromonal variation and mating between two mitotypes of fall armyworm (Spodoptera frugiperda) in Africa.

In the Americas, the fall armyworm (Spodoptera frugiperda) exists in two genetically distinct strains, the corn (C) and rice (R) strains. Despite their names, these strains are not associated with host plant preferences but have been shown to vary in pheromone composition and male responses. Recently, S. frugiperda was detected in Africa as an invasive species, but knowledge about variation in strain types, pheromone composition and inter-strain mating of populations of the pest in the continent has not been fully examined. Therefore, this study aimed to investigate variations, if any in the pheromone composition of female moths, male moth responses, and mating between C and R mitotypes of S. frugiperda populations in Kenya, as well as their geographic distribution. Strains (mitotypes) of S. frugiperda were identified using mitochondrial DNA (mtDNA) markers, and their pheromonal composition determined by coupled gas chromatography-mass spectrometric (GC-MS) analysis. Male moth responses to these compounds were evaluated using GC-electroantennographic detection (EAD), electroantennogram (EAG), and wind tunnel assays. Oviposition assays were used to determine whether R and C mitotype moths could mate and produce eggs. The results showed that both the R and C mitotypes were present, and there were no statistically significant differences in their distribution across all sampled locations. Five pheromone compounds including (Z)-7-dodecenyl acetate (Z7-12:OAc), (Z)-7-tetradecenyl acetate (Z7-14:OAc), (Z)-9-tetradecenyl acetate (Z9-14:OAc), (Z)-11-tetradecenyl acetate (Z11-14:OAc) and (Z)-11-hexadecenyl acetate (Z11-16:OAc), were detected in the pheromone glands of female moths of both mitotypes, with Z9-14:OAc being the most abundant. The relative percentage composition of Z9-14:OAc was similar in both mitotypes. However, the R mitotype had a 2.7 times higher relative percentage composition of Z7-12:OAc compared to the C mitotype moth, while the C mitotype moth had a 2.4 times higher relative percentage composition of Z11-16:OAc than the R mitotype moth. Male moths of both mitotypes exhibited similar responses to the pheromone compounds, showing the strongest responses to Z9-14:OAc and Z7-12:OAc in electrophysiological and behavioural assays. There was mating between R and C mitotypes with egg production comparable to mating within the same mitotype. Our results revealed that differences between the two S. frugiperda mitotypes are characterized by female moth pheromone composition rather than male moth responses to the pheromones, and that this does not prevent hybridisation between the mitotypes, which may have implications for their management.

Positron emission tomography in the diagnosis and management of primary pediatric lung tumors.

Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18F-fluorodeoxyglucose (FDG) PET and 68Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this pictorial essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies.

Critical elements of pediatric liver cancer surgery.

The appropriate management of pediatric liver malignancies, primarily hepatoblastoma and hepatocellular carcinoma, requires an in depth understanding of contemporary preoperative risk stratification, experience with advanced hepatobiliary surgery, and a good relationship with one's local or regional liver transplant center. While chemotherapy regimens have become more effective, operative indications more well-defined, and overall survival improved, the complexity of liver surgery in small children provides ample opportunity for protocol violation, inadequate resection, and iatrogenic morbidity. These guidelines represent the distillation of contemporary literature and expert opinion as a means to provide a framework for preoperative planning and intraoperative decision-making for the pediatric surgeon.

A protocol for evaluating the entomological impact of larval source reduction on mosquito vectors at hotel compounds in Zanzibar.

There is an increasing awareness of the association between tourism activity and risks of emerging mosquito-borne diseases (MBDs) worldwide. In previous studies we showed that hotels in Zanzibar may play an important role in maintaining residual foci of mosquito vectors populations of public health concern. These findings indicated larval sources removal (LSR) interventions may have a significant negative impact on vector communities. However, a thorough analysis of the response vector species to potential LSM strategies must be evaluated prior to implementation of a large-scale area-wide control campaign. Here we propose a protocol for evaluation of the impact of LSR against mosquito vectors at hotel settings in Zanzibar. This protocol is set to determine the efficacy of LSR in a randomized control partial cross-over experimental design with four hotel compounds representing the unit of randomization for allocation of interventions. However, the protocol can be applied to evaluate the impact of LRS in more than four sites. Proposed interventions are active removal of disposed containers, and installation of water dispenser to replace single use discarded plastic water bottles, which were identified as the most important source of mosquitoes studied hotels. The ideal time for allocating intervention to the intervention arms the dry season, when the mosquito abundance is predictably lower. The possible impact of interventions on mosquito occurrence and abundance risks is then evaluated throughout subsequent rainy and dry seasons. If an appreciable reduction in mosquito abundance and occurrence risks is observed during the trial period, intervention could be extended to the control arm to determine whether any potential reduction of mosquito density is reproducible. A rigorous evaluation of the proposed LRS interventions will inspire large scale trials and provide support for evidence-based mosquito management at hotel facilities in Zanzibar and similar settings.

Lymphatic Embolization for the Management of Post-operative Chyle Leaks Following Solid Tumor Resection in Pediatric Patients.

BACKGROUND: Chyle leaks are a common post-operative complication following solid-tumor resection in pediatric patients. Current treatments for persistent chyle leaks are limited, leading many patients to experience prolonged hospitalization, nutritional deficits and/or delays in cancer therapies. Lymphatic embolization is an emerging treatment option for chyle leaks, however, limited reports exist of its use in pediatric populations. METHODS: We conducted a retrospective review of pediatric patients (<18) who underwent lymphangiogram with intent for lymphatic embolization for the management of chyle leaks following solid-tumor resection between 2017 and 2022. RESULTS: Seven patients underwent a total of 11 attempted lymphatic embolization procedures after current standard of care treatments failed to resolve the leak. Lymphangiograms identified a chyle leak in 6 of 7 patients and embolization had a technical success rate of 73%. The complication rate was 9% and complications were limited to one episode of inadvertent gastric wall perforation that did not result in a gastric leak. Lymphatic embolization was ultimately associated with chyle leak resolution in 100% of patients within a median of 24 days, however, repeat embolization was required in 5 of 7 patients (83%). CONCLUSION: Lymphatic embolization appears to be a safe and effective treatment for persistent chyle leaks in pediatric patients, leads to a direction reduction in chyle output, and has high rates of technical and clinical success. Complete resolution of the chyle leak may require multiple embolization procedures. Further work is needed to determine whether earlier intervention may offer benefit for the management of pediatric chyle leaks. LEVEL OF EVIDENCE: IV.

Tethered-flight performance of thermally-acclimated pest fruit flies (Diptera: Tephritidae) suggests that heat waves may promote the spread of Bactrocera species.

BACKGROUND: Thermal history may induce phenotypic plasticity in traits that affect performance and fitness. One type of plastic response triggered by thermal history is acclimation. Because flight is linked to movement in the landscape, trapping and detection rates, and underpins the success of pest management tactics, it is particularly important to understand how thermal history may affect pest insect flight performance. We investigated the tethered-flight performance of Ceratitis capitata, Bactrocera dorsalis and Bactrocera zonata (Diptera: Tephritidae), acclimated for 48 h at 20, 25 or 30 °C and tested at 25 °C. We recorded the total distance, average speed, number of flight events and time spent flying during 2-h tests. We also characterized morphometric traits (body mass, wing shape and wing loading) that can affect flight performance. RESULTS: The main factor affecting most flight traits was body mass. The heaviest species, B. dorsalis, flew further, was faster and stopped less often in comparison with the two other species. Bactrocera species exhibited faster and longer flight when compared with C. capitata, which may be associated with the shape of their wings. Moreover, thermal acclimation had sex- and species-specific effects on flight performance. Flies acclimated at 20 °C stopped more often, spent less time flying and, ultimately, covered shorter distances. CONCLUSION: Flight performance of B. dorsalis is greater than that of B. zonata and C. capitata. The effects of thermal acclimation are species-specific. Warmer acclimation temperatures may allow pest fruit flies to disperse further and faster. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A single-institution pediatric and young adult interventional oncology collaborative: Novel therapeutic options for relapsed/refractory solid tumors.

BACKGROUND: Pediatric interventional oncology (PIO) is a growing field intended to provide additional or alternative treatment options for pediatric patients with benign or malignant tumors. Large series of patients treated uniformly and subjected to rigorous endpoints for efficacy are not available. METHODS: We designed a collaborative initiative to capture data from pediatric patients with benign and malignant tumors who underwent a therapeutic interventional radiology procedure. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized as a measure of radiologic response and data were collected regarding improvement in pain and functional endpoints. Cumulative incidence of progressive disease was calculated using both the treated site and the patient as the analytic unit. FINDINGS: Forty patients, 16 with malignant tumors and 24 with benign tumors, underwent a total of 88 procedures. Cryo- and radiofrequency ablation were the most frequently utilized techniques for both cohorts of patients. A complete or partial response, or prolonged disease stability, were achieved in approximately 40% of patients with malignant tumors and 60% of patients with benign tumors. No patients had progressive disease as their best response. Resolution of pain and improved mobility with return-to-baseline activity were demonstrated across patients from both cohorts. Only minor complications were experienced. INTERPRETATION: Interventional radiology-guided interventions can serve as an alternative or complementary approach to the treatment of benign and malignant tumors in pediatric patients. Prospective, multi-institutional trials are required to adequately study utility, treatment endpoints, and durability of response.

Cumulative burden of late, major surgical intervention in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS) cohort.

BACKGROUND: Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions. METHODS: We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in the USA, with a comparison group of nearest-age siblings of survivors selected by simple random sampling. The primary outcome was any self-reported late, major surgical intervention (defined as any anaesthesia-requiring operation) occurring 5 years or more after the primary cancer diagnosis. The cumulative burden was assessed with mean cumulative counts (MCC) of late, major surgical interventions. Piecewise exponential regression models with calculation of adjusted rate ratios (RRs) evaluated associations between treatment exposures and late, major surgical interventions. FINDINGS: Between Jan 1, 1970, and Dec 31, 1999, 25 656 survivors were diagnosed (13 721 male, 11 935 female; median follow-up 21·8 years [IQR 16·5-28·4]; median age at diagnosis 6·1 years [3·0-12·4]); 5045 nearest-age siblings were also included as a comparison group. Survivors underwent 28 202 late, major surgical interventions and siblings underwent 4110 late, major surgical interventions. The 35-year MCC of a late, major surgical intervention was 206·7 per 100 survivors (95% CI 202·7-210·8) and 128·9 per 100 siblings (123·0-134·7). The likelihood of a late, major surgical intervention was higher in survivors versus siblings (adjusted RR 1·8, 95% CI 1·7-1·9) and in female versus male survivors (1·4; 1·4-1·5). Survivors diagnosed in the 1990s (adjusted RR 1·4, 95% CI 1·3-1·5) had an increased likelihood of late surgery compared with those diagnosed in the 1970s. Survivors received late interventions more frequently than siblings in most anatomical regions or organ systems, including CNS (adjusted RR 16·9, 95% CI 9·4-30·4), endocrine (6·7, 5·2-8·7), cardiovascular (6·6, 5·2-8·3), respiratory (5·3, 3·4-8·2), spine (2·4, 1·8-3·2), breast (2·1, 1·7-2·6), renal or urinary (2·0, 1·5-2·6), musculoskeletal (1·5, 1·4-1·7), gastrointestinal (1·4, 1·3-1·6), and head and neck (1·2, 1·1-1·4) interventions. Survivors of Hodgkin lymphoma (35-year MCC 333·3 [95% CI 320·1-346·6] per 100 survivors), Ewing sarcoma (322·9 [294·5-351·3] per 100 survivors), and osteosarcoma (269·6 [250·1-289·2] per 100 survivors) had the highest cumulative burdens of late, major surgical interventions. Locoregional surgery or radiotherapy cancer treatment were associated with undergoing late surgical intervention in the same body region or organ system. INTERPRETATION: Childhood cancer survivors have a significant burden of late, major surgical interventions, a late effect that has previously been poorly quantified. Survivors would benefit from regular health-care evaluations aiming to anticipate impending surgical issues and to intervene early in the disease course when feasible. FUNDING: US National Institutes of Health, US National Cancer Institute, American Lebanese Syrian Associated Charities, and St Jude Children's Research Hospital.

Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee.

BACKGROUND: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. PROCEDURES: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. RESULTS: Thirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). CONCLUSION: VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

Perioperative hypertension and anesthetic management in patients undergoing resection of neuroblastoma.

INTRODUCTION: Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5-8% of all childhood cancers. Neuroblastomas arise from catecholamine-secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case reports exist documenting severe intraoperative hypertension. However, data on the incidence of intraoperative hypertension are lacking. METHODS: This report is a single-center retrospective review of patients with neuroblastoma who underwent surgical resection (n = 102) at Boston Children's Hospital from July 1, 2012 to February 28, 2021. Significant intraoperative hypertension was defined as maximum systolic blood pressure greater than 95th percentile +12 mmHg based on normative blood pressure data. Statistical analysis was performed using Fisher's exact test, Wilcoxon rank-sum test, and logistic regression. RESULTS: The overall incidence of intraoperative hypertension was 13% (n = 13/102). Higher American Society of Anesthesiologists (ASA) physical status was associated with intraoperative hypertension. Antihypertensive medications were administered intraoperatively in 9% of cases (n = 9), and the use was significantly associated with intraoperative hypertension. Of patients with preoperative urine catecholamine data (n = 82), all 10 patients who had intraoperative hypertension were noted to have elevated preoperative urine catecholamines. Intraoperative hypertension was not associated with postoperative hypertension, postoperative hypotension, or increased intensive care unit length of stay. DISCUSSION/CONCLUSION: Intraoperative hypertension in patients with neuroblastoma remains a relatively uncommon occurrence; however, it does occur at a frequency higher than previously described. While intraoperative hypertension is associated with an increased use of antihypertensive medications in the operating room, it is not associated with adverse perioperative outcomes.

An aptamer-based depot system for sustained release of small molecule therapeutics.

Delivery of hydrophilic small molecule therapeutics by traditional drug delivery systems is challenging. Herein, we have used the specific interaction between DNA aptamers and drugs to create simple and effective drug depot systems. The specific binding of a phosphorothioate-modified aptamer to drugs formed non-covalent aptamer/drug complexes, which created a sustained release system. We demonstrated the effectiveness of this system with small hydrophilic molecules, the site 1 sodium channel blockers tetrodotoxin and saxitoxin. The aptamer-based delivery system greatly prolonged the duration of local anesthesia and reduced systemic toxicity. The beneficial effects of the aptamers were restricted to the compounds they were specific to. These studies establish aptamers as a class of highly specific, modifiable drug delivery systems, and demonstrate potential usefulness in the management of postoperative pain.