A sustainable-circular citrus closed-loop supply chain configuration: Pareto-based algorithms.

Configuration of sustainable supply chains for agricultural products has been a well-known research field recently which is continuing to evolve and grow. It is a complex network design problem, and despite the abundant literature in the field, there are still few models offered to integrate social impacts and environmental effects to support network design decision-making to support the configuration of the citrus supply chain. In this work, the citrus supply chain design problem is investigated by integrating the production, distribution, inventory control, recycling and locational decisions in which the triple bottom lines of sustainability, as well as circularity strategy, are addressed. Accordingly, a novel multi-objective Mixed-Integer Linear Programming (MILP) model is proposed to formulate a multi-period multi-echelon problem to design the sustainable citrus Closed-Loop Supply Chain (CLSC) network. To solve the developed model, the ε-constraint approach is employed in small-sized problems. Furthermore, Strength Pareto Evolutionary Algorithm II (SPEA-II) and Pareto Envelope-based Selection Algorithm II (PESA-II) algorithms are used in medium- and large-sized problems. Taguchi design technique is then utilized to adjust the parameters of the algorithms efficiently. Three well-known assessment metrics and convergence analysis are regarded to test the efficiency of the suggested algorithms. The numerical results demonstrate that the SPEA-II algorithm has a superior efficiency over PESA-II. Moreover, to validate the applicability of the developed methodology, a real case study in Mazandaran/Iran is investigated with the help of a set of sensitivity analyses.

Designing a new sustainable Test Kit supply chain network utilizing Internet of Things.

The advent of COVID-19 put much economic pressure on countries worldwide, especially low-income countries. Providing test kits for Covid-19 posed a huge challenge at the beginning of the pandemic. Especially the low-income and less developed countries that did not have the technology to produce this kit and had to import it into the country, which itself cost a lot to buy and distribute these kits. This paper proposes a sustainable COVID-19 test kits supply chain network (STKSCN) for the first time to fill this gap. Distribution and transportation of test kits, location of distribution centers, and management of used test kits are considered in this network. A mixed integer linear programming Multi-Objective (MO), multi-period, multi-resource mathematical model is extended for the proposed supply chain. Another contribution is designing a platform based on the Internet of Things (IoT) to increase the speed, accuracy and security of the network. In this way, patients set their appointment online by registering their personal details and clinical symptoms. An augmented ɛ-constraint2 (AUGMECON2) is proposed for solving small and medium size of problem. Also, two meta-heuristic algorithms, namely NSGA-II and PESA-II are presented to solve the small, medium and large size of the problem. Taguchi method is utilized to control the parameters, and for comparison between meta-heuristic, five performance metrics are suggested. In addition, a case study in Iran is presented to validate the proposed model. Finally, the results show that PESA-II is more efficient and has better performance than the others based on assessment metrics and computational time.

A new vaccine supply chain network under COVID-19 conditions considering system dynamic: Artificial intelligence algorithms.

With the discovery of the COVID-19 vaccine, what has always been worrying the decision-makers is related to the distribution management, the vaccination centers' location, and the inventory control of all types of vaccines. As the COVID-19 vaccine is highly demanded, planning for its fair distribution is a must. University is one of the most densely populated areas in a city, so it is critical to vaccinate university students so that the spread of this virus is curbed. As a result, in the present study, a new stochastic multi-objective, multi-period, and multi-commodity simulation-optimization model has been developed for the COVID-19 vaccine's production, distribution, location, allocation, and inventory control decisions. In this study, the proposed supply chain network includes four echelons of manufacturers, hospitals, vaccination centers, and volunteer vaccine students. Vaccine manufacturers send the vaccines to the vaccination centers and hospitals after production. The students with a history of special diseases such as heart disease, corticosteroids, blood clots, etc. are vaccinated in hospitals because of accessing more medical care, and the rest of the students are vaccinated in the vaccination centers. Then, a system dynamic structure of the prevalence of COVID -19 in universities is developed and the vaccine demand is estimated using simulation, in which the demand enters the mathematical model as a given stochastic parameter. Thus, the model pursues some goals, namely, to minimize supply chain costs, maximize student desirability for vaccination, and maximize justice in vaccine distribution. To solve the proposed model, Variable Neighborhood Search (VNS) and Whale Optimization Algorithm (WOA) algorithms are used. In terms of novelties, the most important novelties in the simulation model are considering the virtual education and exerted quarantine effect on estimating the number of the vaccines. In terms of the mathematical model, one of the remarkable contributions is paying attention to social distancing while receiving the injection and the possibility of the injection during working and non-working hours, and regarding the novelties in the solution methodology, a new heuristic method based on a meta-heuristic algorithm called Modified WOA with VNS (MVWOA) is developed. In terms of the performance metrics and the CPU time, the MOWOA is discovered with a superior performance than other given algorithms. Moreover, regarding the data, a case study related to the COVID-19 pandemic period in Tehran/Iran is provided to validate the proposed algorithm. The outcomes indicate that with the demand increase, the costs increase sharply while the vaccination desirability for students decreases with a slight slope.

Imaging of congenital genitourinary anomalies.

Congenital genitourinary anomalies are among the most frequent types of birth defects in neonates. Some anomalies can be a significant cause of morbidity in infancy, while others remain asymptomatic even until adulthood and can be at times the only manifestation of a complex systemic disease. The spectrum of these anomalies results from the developmental insults that can occur at various embryologic stages, and an understanding of the formation of the genitourinary system is helpful in the evaluation and treatment of a child with a congenital genitourinary anomaly. Imaging plays an essential role in the diagnosis of congenital genitourinary anomalies and treatment planning. In this article, we highlight the embryologic and characteristic imaging features of various congenital genitourinary anomalies, demonstrate the utility of different imaging modalities in management, and review specific imaging modalities and protocols for image optimization.

Investigating a Dual-Channel Network in a Sustainable Closed-Loop Supply Chain Considering Energy Sources and Consumption Tax.

This paper proposes a dual-channel network of a sustainable Closed-Loop Supply Chain (CLSC) for rice considering energy sources and consumption tax. A Mixed Integer Linear Programming (MILP) model is formulated for optimizing the total cost, the amount of pollutants, and the number of job opportunities created in the proposed supply chain network under the uncertainty of cost, supply, and demand. In addition, to deal with uncertainty, fuzzy logic is used. Moreover, four multi-objective metaheuristic algorithms are employed to solve the model, which include a novel multi-objective version of the recently proposed metaheuristic algorithm known as Multi-Objective Reptile Search Optimizer (MORSO), Multi-Objective Simulated Annealing (MOSA), Multi-Objective Particle Swarm Optimization (MOPSO), and Multi-Objective Grey Wolf (MOGWO). All the algorithms are evaluated using LP-metric in small sizes and their results and performance are compared based on criteria such as Max Spread (MS), Spread of Non-Dominance Solution (SNS), the number of Pareto solutions (NPS), Mean Ideal Distance (MID), and CPU time. In addition, to achieve better results, the parameters of all algorithms are tuned by the Taguchi method. The programmed model is implemented using a real case study in Iran to confirm its accuracy and efficiency. To further evaluate the current model, some key parameters are subject to sensitivity analysis. Empirical results indicate that MORSO performed very well and by constructing solar panel sites and producing energy out of rice waste up to 19% of electricity can be saved.

Designing a sustainable closed-loop supply chain network of face masks during the COVID-19 pandemic: Pareto-based algorithms.

This study develops a novel mathematical model to design a sustainable mask Closed-Loop Supply Chain Network (CLSCN) during the COVID-19 outbreak for the first time. A multi-objective Mixed-Integer Linear Programming (MILP) model is proposed to address the locational, supply, production, distribution, collection, quarantine, recycling, reuse, and disposal decisions within a multi-period multi-echelon multi-product supply chain. Additionally, sustainable development is studied in terms of minimizing the total cost, total pollution and total human risk at the same time. Since the CLSCN design is an NP-hard problem, Multi-Objective Grey Wolf Optimization (MOGWO) algorithm and Non-Dominated Sorting Genetic Algorithm II (NSGA-II) are implemented to solve the proposed model and to find Pareto optimal solutions. Since Meta-heuristic algorithms are sensitive to their input parameters, the Taguchi design method is applied to tune and control the parameters. Then, a comparison is performed using four assessment metrics including Max-Spread, Spread of Non-Dominance Solution (SNS), Number of Pareto Solutions (NPS), and Mean Ideal Distance (MID). Additionally, a statistical test is employed to evaluate the quality of the obtained Pareto frontier by the presented algorithms. The obtained results reveal that the MOGWO algorithm is more reliable to tackle the problem such that it is about 25% superior to NSGA-II in terms of the dispersion of Pareto solutions and about 2% superior in terms of the solution quality. To validate the proposed mathematical model and testing its applicability, a real case study in Tehran/Iran is investigated as well as a set of sensitivity analyses on important parameters. Finally, the practical implications are discussed and useful managerial insights are given.

A possibilistic-robust-fuzzy programming model for designing a game theory based blood supply chain network.

This paper presents a bi-level blood supply chain network under uncertainty during the COVID-19 pandemic outbreak using a Stackelberg game theory technique. A new two-phase bi-level mixed-integer linear programming model is developed in which the total costs are minimized and the utility of donors is maximized. To cope with the uncertain nature of some of the input parameters, a novel mixed possibilistic-robust-fuzzy programming approach is developed. The data from a real case study is utilized to show the applicability and efficiency of the proposed model. Finally, some sensitivity analyses are performed on the important parameters and some managerial insights are suggested.

A new humanitarian relief logistic network for multi-objective optimization under stochastic programming.

Millions of affected people and thousands of victims are consequences of earthquakes, every year. Therefore, it is necessary to prepare a proper preparedness and response planning. The objectives of this paper are i) minimizing the expected value of the total costs of relief supply chain, ii) minimizing the maximum number of unsatisfied demands for relief staff and iii) minimizing the total probability of unsuccessful evacuation in routes. In this paper, a scenario based stochastic multi-objective location-allocation-routing model is proposed for a real humanitarian relief logistics problem which focused on both pre- and post-disaster situations in presence of uncertainty. To cope with demand uncertainty, a simulation approach is used. The proposed model integrates these two phases simultaneously. Then, both strategic and operational decisions (pre-disaster and post-disaster), fairness in the evacuation, and relief item distribution including commodities and relief workers, victim evacuation including injured people, corpses and homeless people are also considered simultaneously in this paper. The presented model is solved utilizing the Epsilon-constraint method for small- and medium-scale problems and using three metaheuristic algorithms for the large-scale problem (case study). Empirical results illustrate that the model can be used to locate the shelters and relief distribution centers, determine appropriate routes and allocate resources in uncertain and real-life disaster situations.

An integrated sustainable medical supply chain network during COVID-19.

Nowadays, in the pharmaceutical industry, a growing concern with sustainability has become a strict consideration during the COVID-19 pandemic. There is a lack of good mathematical models in the field. In this research, a production-distribution-inventory-allocation-location problem in the sustainable medical supply chain network is designed to fill this gap. Also, the distribution of medicines related to COVID-19 patients and the periods of production and delivery of medicine according to the perishability of some medicines are considered. In the model, a multi-objective, multi-level, multi-product, and multi-period problem for a sustainable medical supply chain network is designed. Three hybrid meta-heuristic algorithms, namely, ant colony optimization, fish swarm algorithm, and firefly algorithm are suggested, hybridized with variable neighborhood search to solve the sustainable medical supply chain network model. Response surface method is used to tune the parameters since meta-heuristic algorithms are sensitive to input parameters. Six assessment metrics were used to assess the quality of the obtained Pareto frontier by the meta-heuristic algorithms on the considered problems. A real case study is used and empirical results indicate the superiority of the hybrid fish swarm algorithm with variable neighborhood search.

Premature epiphyseal growth plate arrest after isotretinoin therapy for high-risk neuroblastoma: A case series and review of the literature.

BACKGROUND: Vitamin A-derived retinoids have been reported to cause skeletal abnormalities ranging from hypercalcemia to premature epiphyseal closure. Isotretinoin is a retinoid used as standard therapy for high-risk neuroblastoma and has been reported to cause premature epiphyseal growth plate arrest. PROCEDURE: We identified patients from the Children's Hospital Los Angeles (CHLA) database with high-risk neuroblastoma diagnosed from 1991 to 2018 who experienced premature epiphyseal growth plate arrest and compared their characteristics to other patients with high-risk neuroblastoma. We then performed a literature review of this complication. Data collection included diagnosis age of neuroblastoma, presentation age, agent of exposure, dose, exposure range, and skeletal deformity. RESULTS: Among 216 patients, high-risk neuroblastoma was diagnosed before age of five years (n = 165), between ages of 5 and 10 years (n = 41), and after 10 years of age (n = 13). Three out of 216 patients developed premature epiphyseal growth arrest after isotretinoin exposure (overall incidence = 1.38%). The incidence of bony abnormalities was significantly higher in patients diagnosed in 5- to 10-year age group than in other two groups (P = 0.014). Literature review identified eight additional patients with neuroblastoma who presented with retinoid associated skeletal abnormalities. The median range of isotretinoin exposure for these 11 patients was between 6.5 and 7.625 years (range, 2-14) with no cases of isotretinoin therapy completion before age 5 years. CONCLUSION: Bone toxicity associated with isotretinoin exposure is a concern. Growth plate arrest is a serious adverse effect that is attributable to isotretinoin therapy. Our findings suggest the prepubescent growth plate may be most at risk, and we recommend special attention to this population.

A bi-objective home healthcare routing and scheduling problem considering patients' satisfaction in a fuzzy environment.

Home care services are an alternative answer to hospitalization, and play an important role in reducing the healthcare costs for governments and healthcare practitioners. To find a valid plan for these services, an optimization problem called the home healthcare routing and scheduling problem is motivated to perform the logistics of the home care services. Although most studies mainly focus on minimizing the total cost of logistics activities, no study, as far as we know, has treated the patients' satisfaction as an objective function under uncertainty. To make this problem more practical, this study proposes a bi-objective optimization methodology to model a multi-period and multi-depot home healthcare routing and scheduling problem in a fuzzy environment. With regards to a group of uncertain parameters such as the time of travel and services as well as patients' satisfaction, a fuzzy approach named as the Jimenez's method, is also utilized. To address the proposed home healthcare problem, new and well-established metaheuristics are obtained. Although the social engineering optimizer (SEO) has been applied to several optimization problems, it has not yet been applied in the healthcare routing and scheduling area. Another innovation is to develop a new modified multi-objective version of SEO by using an adaptive memory strategy, so-called AMSEO. Finally, a comprehensive discussion is provided by comparing the algorithms based on multi-objective metrics and sensitivity analyses. The practicality and efficiency of the AMSEO in this context lends weight to the development and application of the approach more broadly.

Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.

PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. METHODS: A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.

The Utility of Cranial Ultrasound for Detection of Intracranial Hemorrhage in Infants.

OBJECTIVE: The objective of this study was to evaluate the sensitivity and specificity of cranial ultrasound (CUS) for detection of intracranial hemorrhage (ICH) in infants with open fontanels. METHODS: This was a retrospective study of infants younger than 2 years who had a CUS performed for the evaluation of potential ICH. We excluded patient with CUSs that were done for reasons related to prematurity, transplant or oncologic evaluations, routine follow-up or preoperative screen, or congenital and known perinatal anomalies. Two clinicians independently classified each of the patients with ICH into significant or insignificant based on the radiology reports. RESULTS: Of 4948 CUS studies performed during the 5-year study period, 283 studies fit the inclusion criteria. Patient age ranged from 0 to 458 days, with a median of 33 days. There were 39 total cases of ICH detected, with 27 significant bleeds and 12 insignificant bleeds. Using computed tomography, magnetic resonance imaging, or clinical outcome as criterion standard, the overall ultrasound sensitivity and specificity for bleed were 67% (confidence interval [CI], 50%-81%) and 99% (CI, 97%-100%), respectively. For those with significant bleeds, the overall sensitivity was 81% (CI, 62%-94%), and for those with insignificant bleeds, it was 33% (CI, 1%-65%). CONCLUSIONS: The sensitivity of CUS is inadequate to justify its use as a screening tool for detection of ICH in young infants.

Testicular Adrenal Rest Tumors in Boys and Young Adults with Congenital Adrenal Hyperplasia.

PURPOSE: Testicular adrenal rest tumors are a well-known complication in males who have congenital adrenal hyperplasia with potential infertility in adulthood. We assessed the prevalence of testicular adrenal rest tumors in infants to young men presenting to a congenital adrenal hyperplasia Comprehensive Care Center. MATERIALS AND METHODS: A total of 35 males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency underwent scrotal ultrasonography, including 7 younger than 5 years, 9 who were 5 to 12 years old and 19 who were older than 12 years. Three and 35 patients had classic and nonclassic congenital adrenal hyperplasia, respectively. Bone age x-ray or advanced bone age x-ray history, glucocorticoid dose, fludrocortisone dose, and serum 17-hydroxyprogesterone, testosterone and androstenedione levels within 3 months of ultrasound were also recorded. RESULTS: Testicular adrenal rest tumors were detected in 5 of 35 patients (14%), including 1 of 9 (11%) who were 5 to 12 years old and 4 of 19 (21%) who were older than 12 years. The tumors were not detected in any patients younger than 5 years, including 1 infant with poor hormonal control. The youngest patient with positive findings was 6.6 years old. All patients with positive findings had bilateral disease and only 1 had suspicious physical findings. The glucocorticoid dose and 17-hydroxyprogesterone did not differ between patients with vs without a testicular adrenal rest tumor. Those with a tumor were more likely to have advanced bone age x-ray results (100% vs 42%, p = 0.04) and higher fludrocortisone dose (p <0.01). All males with nonclassic congenital adrenal hyperplasia had negative tumor findings. CONCLUSIONS: Testicular adrenal rest tumors were present in young males with classic congenital adrenal hyperplasia but not in infants or toddlers. These tumors were associated with higher fludrocortisone requirements and a history of advanced bone age x-ray results. However, the tumors did not develop in all poorly controlled males. Longitudinal studies are needed to understand the individual predisposition to testicular adrenal rest tumors and the age at which to begin screening patients with congenital adrenal hyperplasia.

A Phase I New Approaches to Neuroblastoma Therapy Study of Buthionine Sulfoximine and Melphalan With Autologous Stem Cells for Recurrent/Refractory High-Risk Neuroblastoma.

BACKGROUND: Myeloablative therapy for high-risk neuroblastoma commonly includes melphalan. Increased cellular glutathione (GSH) can mediate melphalan resistance. Buthionine sulfoximine (BSO), a GSH synthesis inhibitor, enhances melphalan activity against neuroblastoma cell lines, providing the rationale for a Phase 1 trial of BSO-melphalan. PROCEDURES: Patients with recurrent/resistant high-risk neuroblastoma received BSO (3 gram/m(2) bolus, then 24 grams/m(2) /day infusion days -4 to -2), with escalating doses of intravenous melphalan (20-125 mg/m(2) ) days -3 and -2, and autologous stem cells day 0 using 3 + 3 dose escalation. RESULTS: Among 28 patients evaluable for dose escalation, one dose-limiting toxicity occurred at 20 mg/m(2) melphalan (grade 3 aspartate aminotransferase/alanine aminotransferase) and one at 80 mg/m(2) (streptococcal bacteremia, grade 4 hypotension/pulmonary/hypocalcemia) without sequelae. Among 25 patients evaluable for response, there was one partial response (PR) and two mixed responses (MRs) among eight patients with prior melphalan exposure; one PR and three MRs among 16 patients without prior melphalan; one stable disease with unknown melphalan history. Melphalan pharmacokinetics with BSO were similar to reports for melphalan alone. Melphalan Cmax for most patients was below the 10 µM concentration that showed neuroblastoma preclinical activity with BSO. CONCLUSIONS: BSO (75 gram/m(2) ) with melphalan (125 mg/m(2) ) is tolerable with stem cell support and active in recurrent/refractory neuroblastoma. Further dose escalation is feasible and may increase responses.

131I-metaiodobenzylguanidine with intensive chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma. A new approaches to neuroblastoma therapy (NANT) phase II study.

(131)I-Metaiodobenzylguanidine ((131)I-MIBG) has been used as a single agent or in combination with chemotherapy for the treatment of high-risk neuroblastoma. The activity and toxicity of (131)I-MIBG when combined with carboplatin, etoposide, and melphalan (CEM) and autologous stem cell transplantation (SCT) are now investigated in a phase II multicenter study. Fifty patients with MIBG-avid disease were enrolled into 2 cohorts, stratified by response to induction therapy. The primary study endpoint was response of patients with refractory (n = 27) or progressive disease (n = 15). A second cohort of patients (n = 8) with a partial response (PR) to induction therapy was included to obtain preliminary response data. (131)I-MIBG was administered on day -21 to all patients, with CEM given days -7 to -4, and SCT given on day 0. (131)I-MIBG dosing was determined by pre-therapy glomerular filtration rate (GFR), with 8 mCi/kg given if GFR was 60 to 99 mL/minute/1.73 m(2) (n = 13) and 12 mCi/kg if GFR ≥ 100 mL/minute/1.73 m(2) (n = 37). External beam radiotherapy was delivered to the primary and metastatic sites, beginning approximately 6 weeks after SCT. Responses (complete response + PR) were seen in 4 of 41 (10%) evaluable patients with primary refractory or progressive disease. At 3 years after SCT, the event-free survival (EFS) was 20% ± 7%, with overall survival (OS) 62% ± 8% for this cohort of patients. Responses were noted in 3 of 8 (38%) of patients with a PR to induction, with 3-year EFS 38% ± 17% and OS 75% ± 15%. No statistically significant difference was found comparing EFS or OS based upon pre-therapy GFR or disease cohort. Six of 50 patients had nonhematologic dose-limiting toxicity (DLT); 1 of 13 in the low GFR and 5 of 37 in the normal GFR cohorts. Hepatic sinusoidal obstructive syndrome (SOS) was seen in 6 patients (12%), with 5 events defined as dose-limiting SOS. The median times to neutrophil and platelet engraftment were 10 and 15 days, respectively. Patients received a median 163 cGy (61 to 846 cGy) with (131)I-MIBG administration, with 2 of 3 patients receiving >500 cGy experiencing DLT. The addition of (131)I-MIBG to a myeloablative CEM regimen is tolerable and active therapy for patients with high-risk neuroblastoma.

Pilot Feasibility Study of Comprehensive Pulmonary Evaluation Following Lung Radiation Therapy.

BACKGROUND: Symptoms of pulmonary injury following lung irradiation may not manifest clinically in childhood. We performed comprehensive pulmonary evaluation of patients who had received lung irradiation for treatment of cancer. MATERIALS AND METHODS: Patients underwent a focused history and physical examination, computed tomography of the chest, pulmonary function test, and cardiopulmonary exercise stress test (CPET). Health-related Quality of Life was also measured. RESULTS: Fourteen patients were recruited with median age of 16 years (range, 6 to 21 y). Median time from pulmonary radiation to testing was 5 years (range, 2 to 11 y). Five patients reported pulmonary symptoms. Twelve patients (85.7%) had at least 1 pulmonary function test abnormality. Nine patients demonstrated CPET abnormalities; 7 patients had abnormal pulmonary limitation to exercise, and 5 patients had exercise-induced bronchospasm. The pulmonary limitations included abnormal ventilatory response to exercise in 5 patients, and gas exchange abnormalities in 4 patients. Chest computed tomography demonstrated grade 1-2 radiation-induced lung changes in 4 patients, and grade 3 abnormalities in 1 patient. CONCLUSIONS: Significant pulmonary dysfunction was observed in childhood cancer survivors who had received lung irradiation. CPET is feasible in childhood cancer survivors and can be valuable for assessment of pulmonary function and exercise capacity.

Pulmonary outcomes in patients with Hodgkin lymphoma treated with involved field radiation.

BACKGROUND: Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols. PROCEDURES: Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained. RESULTS: The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving >25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes. CONCLUSION: In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes.

An infant with an ectopic torsed testis in the abdominal wall.

We report a unique case of an infant with testicular torsion in the anterior abdominal wall. In the work-up of acute abdominal pain in a male infant with nonpalpable testes, a careful search for the testes using ultrasound can often identify undescended or ectopic testes. Testicular torsion should remain an important consideration as a potential cause of abdominal pain in this selected group of individuals.

Phase I trial of fenretinide delivered orally in a novel organized lipid complex in patients with relapsed/refractory neuroblastoma: a report from the New Approaches to Neuroblastoma Therapy (NANT) consortium.

BACKGROUND: A phase I study was conducted to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of fenretinide (4-HPR) delivered in an oral powderized lipid complex (LXS) in patients with relapsed/refractory neuroblastoma. PROCEDURE: 4-HPR/LXS powder (352-2,210 mg/m(2) /day) was administered on Days 0-6, in 21-day courses, by standard 3 + 3 design. RESULTS: Thirty-two patients (median age = 8 years, range 3-27 years) enrolled with 30 evaluable for dose escalation. Prior therapies included stem cell transplantation/support (n = 26), 13-cis-retinoic acid (n = 22), (125/131) I-MIBG (n = 13), and anti-GD2 antibody (n = 6). 170+ courses were delivered. Course 1 DLTs were a Grade 3 (n = 1) alkaline phosphatase at 352 mg/m(2) /day. Other major toxicities were Grade 4 (n = 1) alkaline phosphatases on Courses 5 and 6 at 774 mg/m(2) /day, and Grade 3 (n = 1) ALT/AST elevation on Course 2 at 1,700 mg/m(2) /day. Of 29 response-evaluable patients, six had stable disease (SD) (4-26 courses); four with marrow- or bone disease-only had complete responses (CR) (10-46 courses). 4-HPR plasma levels were several folds higher (P < 0.05) than previously reported using capsular fenretinide. The Day 6 mean peak 4-HPR plasma level at 1,700 mg/m(2) /day was 21 µM. An MTD was not reached. CONCLUSIONS: 4-HPR/LXS oral powder obtained higher plasma levels, with minimal toxicity and evidence of anti-tumor activity, than a previous capsule formulation. A recommended phase II schedule of 4-HPR/LXS powder is 1,500 mg/m(2) /day, TID, on Days 0-6, of a 21-day course.