Increased AXLhigh myeloid cells as pathognomonic marker in Langerhans cell histiocytosis and Langerin expression dependence of mTOR inhibition.

Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXLhigh cells in the CD11c+ subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.

Modeled and measured SARS-CoV-2 virus in septic tank systems for wastewater surveillance.

SARS-CoV-2 wastewater surveillance (WWS) at wastewater treatment plants (WWTPs) can reveal sewered community COVID-19 prevalence. For unsewered areas using septic tank systems (STSs) or holding tanks, how to conduct WWS remains unexplored. Here, two large STSs serving Zuma Beach (Malibu, CA) were studied. Supernatant and sludge SARS-CoV-2 concentrations from the directly-sampled STSs parameterized a dynamic solid-liquid separation, mass balance-based model for estimating the infection rate of users. Pumped septage before hauling and upon WWTP disposal was also sampled and assessed. Most (96%) STS sludge samples contained SARS-CoV-2 N1 and N2 genes, with concentrations exceeding the supernatant and increasing with depth while correlating with total suspended solids (TSS). The trucked septage contained N1 and N2 genes which decayed (coefficients: 0.09-0.29 h-1) but remained detectable. Over approximately 5 months starting in December 2020, modeled COVID-19 prevalence estimations among users ranged from 8 to 18%, mirroring a larger metropolitan area for the first 2 months. The approaches herein can inform public health intervention and augment conventional WWS in that: (1) user infection rates for communal holding tanks are estimable and (2) pumped and hauled septage can be assayed to infer where disease is spreading in unsewered areas.

Oxygen transfer comparison of jets and coarse bubble aeration in concentrated sludge.

The South Truckee Meadows Water Reclamation Facility (STMWRF) in Washoe County, Nevada, commissioned a biosolids facility with jet aerated aerobic digestion. The jet aerators were not performing as designed, so they were tested on-site in the new tanks in both clean and process water according to ASCE standards. The aerators failed by substantial margins. To make up for the aeration shortfall, Washoe County elected to replace the jet aerators with coarse bubble aerators and to add the additional blower capacity necessary to meet the oxygen requirements in this configuration. After partial replacement, with one basin containing coarse bubble diffusers and the other still containing jets, the efficiency of both systems was tested in process water. The jets and coarse bubble diffusers had similar results for OTE and αSOTE, whereas the coarse bubble diffusers had substantially higher aeration efficiency after accounting for the jet pump power draw. Overall, the project demonstrated the deleterious effects of highly concentrated non-Newtonian sludge on the coalescence of fine bubbles and ultimately jet aeration efficiency, confirming the incompatibility of fine bubbles and thick sludge. Our results can be extended to other bioreactors operating at MLSS concentration above 1%. PRACTITIONER POINTS: Fine bubble systems perform worse than coarse bubbles in thick sludge due to bubble coalescence. The alpha factor is a function of sludge thickness; hence, claims of constant alpha are unrealistic. Polymers and additives for sludge thickening should be carefully evaluated because they can affect adversely oxygen transfer. Independent verification of aeration system manufacturer claims prevents design issues and subsequent disputes.

Seasonal occurrence and fate of nanoparticles in two biological wastewater treatment plants in Southern California.

Nano-sized particles in wastewater are generally considered colloids, but their production and size distribution are not well understood. Organic nano-sized particles are more abundant than engineered nanomaterials in wastewater, where they may cause membrane fouling, harbor pathogens, and transport contaminants to the environment. To our knowledge, this study is the first to examine the seasonal behavior, removal, and the quantity and size of suspended particles (both unfiltered and filtered through a 450 nm filter) at multiple points within different processes along two water resource recovery facilities (WRRFs, formerly wastewater treatment plants). In Southern California where wastewater is often reused or reclaimed, a better understanding of nano-sized particles generation and removal may help reduce cost. We found that both types of the biological secondary treatments investigated (conventional activated sludge process and trickling filter) were more efficient in removing suspended particles larger than 450 nm than they were smaller ones. However, the results show that current treatment processes are not designed to remove nano-sized particles efficiently. We also investigated the factors that correlate with their occurrence and found that there was a significant and direct correlation between influent dissolved chemical oxygen demand (COD) and the abundance of suspended particles both larger and smaller than 450 nm, suggesting that the suspended particles increased with dissolved COD in the WRRFs and thus were biogenically generated during the wastewater treatment. Although no conclusive seasonal correlations were found, dissolved COD management may control nano-sized particle production. PRACTITIONER POINTS: Conventional secondary treatments (activated sludge and trickling filter) could efficiently remove particles but not as efficiently for nano-sized particles (40.1-52.7% removal). At one facility, particles of all sizes were found to correlate with dissolved carbon and EPS, meaning they were biogenic. Monitoring dissolved carbon or EPS precursors may help control membrane fouling post-secondary treatment, and this warrants more studies.

Microplastics separation using stainless steel mini-hydrocyclones fabricated with additive manufacturing.

Microplastics have been widely detected in natural and engineered water systems and removing microplastics from various water matrices has become a major challenge. Mini-hydrocyclones (MHCs) have been previously applied to separate mediums of different phases. Given MHCs' capability of separating fine particles from liquid phase, three MHCs were designed and fabricated in stainless steel with 3D printing. Microplastics of densities that were both lower (<1 g·cm-3) and higher (>1 g·cm-3) than water's density were used to test the separation efficiency in ultra-purified water. The separation test was performed on single-stage MHC as well as MHCs in series in a closed hydraulic circuit. A range of important operational parameters, including split ratio, feed pressure, feed flow rate, and solid concentration, were evaluated to optimize the separation efficiency. The single-stage MHC experiment revealed that >80 % microplastics >20 µm can be effectively removed at the concentration tested, and the separation efficiency peaked at the split ratio of 35 %. MHCs in series demonstrated their ability to further enhance the separation efficiency of the ones with the same density, as well as separate microplastics of different densities. Mini-hydrocyclones' were also used to separate microplastics in synthetic stormwater, and separation efficiency reached 84 % and 98.1 % for low-density polyethylene (LDPE) and polyamide (PA). The results indicated the MHCs' potential for large-scale application in microplastic separation for industrial and municipal wastewater.

Monitoring Circulating CD207+CD1a+ Cells in Langerhans Cell Histiocytosis and Clinical Implications.

Langerhans cell histiocytosis (LCH) is a disorder characterized by an abnormal accumulation of CD207+ and CD1a+ cells in almost any tissue. Currently, there is a lack of prognostic markers to follow up patients and track disease reactivation or treatment response. Putative myeloid precursors CD207+ and CD1a+ cells were previously identified circulating in the blood. Therefore, we aim to develop a sensitive tracing method to monitor circulating CD207+ and CD1a+ cells in a drop of blood sample of patients with LCH. A total of 202 blood samples from patients with LCH and 23 controls were tested using flow cytometry. A standardized cellular score was defined by quantifying CD207+ and CD1a+ expression in monocytes and dendritic cells, based on CD11b, CD14, CD11c, and CD1c subpopulations, resulting in a unique value for each sample. The scoring system was validated by a receiver operating characteristic curve showing a reliable discriminatory capacity (area under the curve of 0.849) with a threshold value of 14, defining the presence of circulating CD207+ and CD1a+ cells. Interestingly, a fraction of patients with no evident clinical manifestation at the time of sampling also showed presence of these cells (29.6%). We also found a differential expression of CD207 and CD1a depending on the organ involvement, and a positive correlation between the cellular score and plasma inflammatory markers such as soluble CD40L, soluble IL-2Ra, and CXCL12. In conclusion, the analysis of circulating CD207 and CD1a cells in a small blood sample will allow setting a cellular score with minimal invasiveness, helping with prognostic accuracy, detecting early reactivation, and follow-up.

The third route: A techno-economic evaluation of extreme water and wastewater decentralization.

Water systems need to become more locally robust and sustainable in view of increased population demands and supply uncertainties. Decentralized treatment is often assumed to have the potential to improve the technical, environmental, and economic performance of current technologies. The techno-economic feasibility of implementing independent building-scale decentralized systems combining rainwater harvesting, potable water production, and wastewater treatment and recycling was assessed for six main types of buildings ranging from single-family dwellings to high-rise buildings. Five different treatment layouts were evaluated under five different climatic conditions for each type of building. The layouts considered varying levels of source separation (i.e., black, grey, yellow, brown, and combined wastewater) using the corresponding toilet types (vacuum, urine-diverting, and conventional) and the appropriate pipes and pumping requirements. Our results indicate that the proposed layouts could satisfy 100% of the water demand for the three smallest buildings in all but the aridest climate conditions. For the three larger buildings, rainwater would offset annual water needs by approximately 74 to 100%. A comprehensive economic analysis considering CapEx and OpEx indicated that the cost of installing on-site water harvesting and recycling systems would increase the overall construction cost of multi-family buildings by around 6% and single-family dwellings by about 12%, with relatively low space requirements. For buildings or combined water systems with more than 300 people, the estimated total price of on-site water provision (including harvesting, treatment, recycling, and monitoring) ranged from $1.5/m3 to $2.7/m,3 which is considerably less than the typical tariffs collected by utilities in the United States and Western Europe. Where buildings can avoid the need to connect to centralized supplies for potable water and sewage disposal, water costs could be even lower. Urine-diversion has the potential to yield the least expensive solution but is the least well developed and had higher uncertainty in the cost analysis. More mature layouts (e.g., membrane bioreactors) exhibited less cost uncertainty and were economically competitive. Our analysis indicates that existing technologies can be used to create economically viable systems that greatly reduce demands on centralized utilities and, under some conditions, eliminate the need for centralized water supply or sewage collection.

Dynamic alpha factors: Prediction in time and evolution along reactors.

The performance of aeration - one of the most costly processes at water resource recovery facilities - is heavily impacted by actual wastewater characteristics which are commonly taken into account using the alpha factor (α). This factor varies depending on hydraulic and organic loading; such variance includes both time and spatial fluctuations. In standard design practice, it is often considered as a fixed number, or at best, a predefined time series. The objective of this paper is to propose a new method of predicting plantwide trends in the α factor through the use of process modelling which can accommodate diurnal and seasonal variations. The authors' concept takes into account the dependence of α on sludge retention time in the form of degradation kinetics, the effects of organic loading (influent filtered COD), the presence or absence of anoxic zones, diffuser depth, and the impact of high MLSS found in certain, e.g., MBR, technologies. The developed model was calibrated using data from numerous facilities, relying on off-gas measurements and tests in clean and process water. Model validation was carried out against averaged α factor gradient data from one plant, and against diurnal air flow measurements from another. The Benchmark Simulation Model 1 configuration was used to demonstrate the applicability of the proposed model - in estimation of blower energy consumption and peak air flow requirements - comparing it with constant and scheduled α factor-based approaches.

A proof-of-concept experimental study for vacuum-driven anaerobic biosolids fermentation using the IntensiCarb technology.

This study demonstrates the potential of an innovative anaerobic treatment technology for municipal biosolids (IntensiCarb), which relies on vacuum evaporation to decouple solids and hydraulic retention times (SRT and HRT). We present proof-of-concept experiments using primary sludge and thickened waste activated sludge (50-50 v/v mixture) as feed for fermentation and carbon upgrading with the IntensiCarb unit. IntensiCarb fully decoupled the HRT and SRT in continuously stirred anaerobic reactors (CSAR) to achieve two intensification factors, that is, 1.3 and 2, while keeping the SRT constant at 3 days (including in the control fermenter). The intensified CSARs were compared to a conventional control system to determine the yields of particulate hydrolysis, VFA production, and nitrogen partitioning between fermentate and condensate. The intensified CSAR operating at an intensification factor 2 achieved a 65% improvement in particulate solubilization. Almost 50% of total ammonia was extracted without pH adjustment, while carbon was retained in the fermentate. Based on these results, the IntensiCarb technology allows water resource recovery facilities to achieve a high degree of plant-wide intensification while partitioning nutrients into different streams and thickening solids. PRACTITIONER POINTS: The IntensiCarb reactor can decouple hydraulic (HRT) and solids (SRT) retention times in anaerobic systems while also increasing particulate hydrolysis and overall plant capacity. Using vacuum as driving force of the IntensiCarb technology, the system could achieve thickening, digestion, and partial dewatering in the same unit-thus eliminating the complexity of multi-stage biosolids treatment lines. The ability to partition nutrients between particulate, fermentate, and condensate assigns to the IntensiCarb unit a key role in recovery strategies for value-added products such as nitrogen, phosphorus, and carbon, which can be recovered separately and independently.

How elevation dictates technology selection in biological wastewater treatment.

Most wastewater treatment facilities are built using procedures from previous designs which are predominantly from sites and regions not located at high elevation. Recognizing this limitation, we assessed the effects of elevation above sea level on the suitability of process configurations and technologies as well as their associated energy costs. Using the International Water Association (IWA) benchmark simulation model No. 2 (modified Ludzack-Ettinger process layout) as a reference, we simulated scenarios including different activated sludge process configurations, operating under different environmental and process conditions. In order to include a wide sample of environmental conditions, data on atmospheric pressure, wastewater temperature, air temperature, and relative humidity (for average, warmest, and coldest months) were collected from municipal wastewater treatment plants located at different latitudes and elevations. The results confirm that elevation is a driver against the selection of diffused aeration technologies. Aeration costs for aerobic wastewater treatment are highly influenced by local project conditions, particularly by elevation and wastewater temperature, which together influence the driving force for oxygen transfer into water. When the driving force is low, operating costs are high. Recommendations for designing treatment processes effectively, including diffused aeration systems operating at high elevations above sea level, are proposed.

Integrating Virus Monitoring Strategies for Safe Non-potable Water Reuse.

Wastewater reclamation and reuse have the potential to supplement water supplies, offering resiliency in times of drought and helping meet increased water demands associated with population growth. Non-potable water reuse represents the largest potential reuse market. Yet economic constraints for new water reuse infrastructure and safety concerns due to microbial water quality, and especially viral pathogen exposure, limit widespread implementation of water reuse. Cost-effective, real-time methods to measure or indicate viral quality of recycled water would do much to instill greater confidence in the practice. This manuscript discusses advancements in monitoring and modeling of viral health risks in the context of water reuse. First, we describe the current wastewater reclamation processes and treatment technologies with an emphasis on virus removal. Second, we review technologies for the measurement of viruses, both culture- and molecular-based, along with their advantages and disadvantages. We introduce promising viral surrogates and specific pathogenic viruses that can serve as indicators of viral risk for water reuse. We suggest metagenomic analyses for viral screening and flow cytometry for quantification of virus-like particles as new approaches to complement more traditional methods. Third, we describe modeling to assess health risks through quantitative microbial risk assessments (QMRAs), the most common strategy to couple data on virus concentrations with human exposure scenarios. We then explore the potential of artificial neural networks (ANNs) to incorporate suites of data from wastewater treatment processes, water quality parameters, and viral surrogates. We recommend ANNs as a means to utilize existing water quality data, alongside new complementary measures of viral quality, to achieve cost-effective strategies to assess risks associated with infectious human viruses in recycled water. Given the review, we conclude that technologies are ready for identifying and implementing viral surrogates for health risk reduction in the next decade. Incorporating modeling with monitoring data would likely result in more robust assessment of water reuse risk.

Quantification of energy and cost reduction from decreasing dissolved oxygen levels in full-scale water resource recovery facilities.

Aeration systems often lack the efficiency to maintain a desired residual dissolved oxygen (DO) concentration in the tank in part because little consideration is given to the dynamic daily and seasonal loading conditions. Although advanced aeration controllers exist, the majority of plants have DO set points typically based on common practice and literature values rather than site-specific conditions, which can result in DO set points higher than those necessary to meet treatment objectives. DO set point reduction strategies have primarily been proposed through either static or dynamic simulations. In this study, the substantial improvements associated with DO set point reduction are demonstrated at full scale. A yearlong characterization of full-scale aeration dynamics captured the effect of diurnal and seasonal fluctuations on oxygen transfer and energy demand and so facilitated the estimation of the potential savings of DO reduction strategies. Full-scale validation provided direct evidence of DO reduction strategies inducing an overall enhancement of oxygen transfer efficiency along the different bioreactors, while confirming that energy savings as high as 20% were feasible. This study quantifies the influence of oxygen transfer efficiency on operating choices and site-specific conditions (control strategy, loading conditions, and influent flow variability). PRACTITIONER POINTS: We quantified the energy reduction and cost savings associated with a DO reduction in an aeration tank. For each 0.2 mg/L of DO decreased, the average power demand reduction per unit water treated exceeded 17%. Field measurements of dynamic alpha values eliminate the uncertainty in estimating aeration energy and cost savings from DO variations.

Soft Sensing for On-Line Fault Detection of Ammonium Sensors in Water Resource Recovery Facilities.

The increasing demand for online sensors applied to advanced control strategies in water resource recovery facilities has resulted in the increasing investigation of fault-detection methods to improve the reliability of sensors installed in harsh environments. The study herein focuses on the fault detection of ammonium sensors, especially for effluent monitoring, given their potential in ammonium-based aeration control applications. An artificial neural network model was built to predict the ammonium content in the effluent by employing the information from five other sensors installed in the activated sludge tank: NH4+, pH, ORP, DO, and TSS. The residual between the model prediction and the effluent ammonium sensor signal was utilized in a fault-detection mechanism based on principal component analysis and Shewhart monitoring charts. In contrast to previous studies, the present work utilizes typical faults collected from a 1 year historic dataset of an actual sensor setup. Treatment process anomalies, calibration bias faults, and fouling drifts were the most common issues identified from the historic dataset, and they were promptly identified by the proposed fault-detection methodology. Once a fault is detected, the model prediction can be actively used in place of the sensor for process control without affecting the treatment process by utilizing faulty datasets.

Effects of flow velocity and bubble size distribution on oxygen mass transfer in bubble column reactors-A critical evaluation of the computational fluid dynamics-population balance model.

Computational fluid dynamics (CFD) is used to simulate a bubble column reactor operating in the bubbly (homogenous) regime. The Euler-Euler two-fluid model, integrated with the population balance model (PBM), is adopted to compute the flow and bubble size distribution (BSD). The CFD-PBM model is validated against published experimental data for BSD, global gas holdup, and oxygen mass transfer coefficient. The sensitivity of the model with respect to the specification of boundary conditions and the bubble coalescence/breakup models is assessed. The coalescence model of Prince and Blanch (1990) provides the best results, whereas the output is shown to be insensitive to the breakup model. The CFD-PBM study demonstrates the importance of considering the BSD in order to correctly model mass transfer. Results show that the constant bubble size assumption results in a large error in the oxygen mass transfer coefficient, while giving acceptable results for gas holdup. PRACTITIONER POINTS: Constant bubble size (CBS) and population balance model (PBM) are compared for a bubble column reactor. Both PBM and CBS can predict gas holdup; however, PBM can correctly predict gas-liquid mass transfer whereas CBS cannot. Best practices for selecting coalescence, breakup, and drag models are determined.

Dynamic load shifting for the abatement of GHG emissions, power demand, energy use, and costs in metropolitan hybrid wastewater treatment systems.

The installation of satellite water resource recovery facilities (WRRFs) has strengthened the ability to provide cheap and reliable recycled water to meet the increasing water demand of expanding cities. As a result, recent studies have attempted to address the problem of how to optimally integrate satellite systems with other sectors of the urban sphere, such as the local economy, the power supply, and the regional carbon footprint. However, such studies are merely based on the spatial domain, thus neglecting potential time-dependent strategies that could further improve the sustainability of metropolitan water systems. Therefore, in this study a new conceptual framework is proposed for the dynamic management of hybrid systems comprised of both centralized and satellite WRRFs. Furthermore, a novel set of integrated real-time control (RTC) strategies are considered to analyze three different scenarios: 1) demand response, 2) flow equalization of the centralized WRRF and 3) reduction of greenhouse gas emissions. Data from a case study in California is used to develop an integrated dynamic model of a system of 8 facilities. Our results show that by dynamically shifting the dry-weather influent wastewater flows between hydraulically connected WRRFs, a reduction in power demand (up to 25%), energy use (4%), operating costs (8.5%) and indirect carbon emissions (4.5%) can be achieved. Therefore, this study suggests that a certain degree of hydraulic interconnection coupled with dynamic load-shifting strategies, can broaden the operational flexibility and overall sustainability of hybrid WRRF systems.

Comparison of methods for nitrous oxide emission estimation in full-scale activated sludge.

Nitrous oxide (N2O) gas transfer was studied in a full-scale process to correlate liquid phase N2O concentrations with gas phase N2O emissions and compare methods of determining the volumetric mass transfer coefficient, KLa. Off-gas and liquid phase monitoring were conducted at the Viikinmäki wastewater treatment plant (WWTP) over a two-week period using a novel method for simultaneous measurement of dissolved and off-gas N2O and O2 from the same location. KLa was calculated with three methods: empirically, based on aeration superficial velocity, from experimentally determined O2 KLa, and using a static value of best fit. The findings of this study indicated trends in local emitted N2O consistently matched trends in local dissolved N2O, but the magnitude of N2O emissions could not be accurately estimated without correction. After applying a static correction factor, the O2 method, using experimentally determined O2 KLa, provided the best N2O emission estimation over the data collection period. N2O emissions estimated using the O2 method had a root mean square error (RMSE) of 70.5 compared against measured concentrations ranging from 3 to 1,913 ppm and a maximum 28% error. The KLa value, and therefore the method of KLa determination, had a significant impact on estimated emissions.

Oxygen transfer and plant-wide energy assessment of primary screening in WRRFs.

Primary screening is gaining interest as a method to achieve removal performances comparable to primary clarification while reducing the footprint and increasing operational elasticity. Aeration efficiency indicators in a pilot sequential batch reactor (SBR) and a full scale water resource recovery facility (WRRF) were investigated after the implementation of rotating belt filters/screens (RBF). To compare the impact between screened (350 µm) and nonscreened primary influent, two identical treatment lines were monitored using off-gas and respirometric measurements. The study provides the first result on improved oxygen transfer efficiency due to primary screening. Consistent aeration efficiency improvements of 27% and 20% between screened and nonscreened were obtained at pilot and full scale, respectively. Changes in aeration efficiency and carbon redirection were integrated into a set of models to investigate the primary screening impact on the WRRF energy balance. While the plant-wide assessment for different scenarios improved the energy balance up to 15%, a detailed comparative analysis between various treatment schemes gained insight into the advantages and limitations of the energetic sustainability of primary screening. PRACTITIONER POINTS: Aeration efficiency improved 27% at pilot scale Aeration efficiency improved 20% at full scale. Use of primary screening can improve the energy balance up to 15 Assessment of advantages and limitations of primary screening.

Dynamic impact of cellulose and readily biodegradable substrate on oxygen transfer efficiency in sequencing batch reactors.

Aeration is a major contributor to the high energy demand in municipal wastewater treatment plants. Thus, it is important to understand the dynamic impact of wastewater characteristics on oxygen transfer efficiency to develop suitable control strategies for minimizing energy consumption since aeration efficiency is influenced by the biodegradation of pollutants in the influent. The real-time impact of acetate as a readily biodegradable substrate and cellulose as a slowly biodegradable substrate were studied at different operational conditions. Cellulose in the influent wastewater can be removed efficiently using primary treatment technologies, such as the rotating belt filter (RBF). At an ambient DO of 2 mg l-1 and air flow of 1.02 m3h-1 (0.6 SCFM), the α-factor was more sensitive to readily biodegradable substrates than to cellulose. On average, α-factor decreased by 48% and 19% due to the addition of acetate and cellulose, respectively. At a DO of 4 mg l-1 and air flow of 1.7 m3h-1 (1 SCFM), α-factor remained constant irrespective of cellulose and acetate concentrations. Without active biomass, α-factor decreased by 47% and 43% at a DO of 2 mg l-1 (air flow of 1.02 m3h-1) and high DO of 5 mg l-1 (air flow of 1.7 m3h-1), respectively. An inverse correlation between α-factor and sCOD was defined and incorporated into a dynamic model to estimate the real-time airflow rates associated with the improvement of the oxygen transfer efficiency due to biodegradation. Finally, the RBF operated with a 158-µm mesh selectively removed cellulose, thus reducing air requirements, and energy by 25%.

Tumor pardo del paladar, presentación atípica de hiperparatiroidismo primario en adolescente: buena evolución y normalización de la masa ósea tras paratiroidectomía / Brown tumor of the palate, atypical presentation of primary hyperparathyroidism in an adolescent: good evolution and bone mass normalization after parathyroidectomy

El hiperparatiroidismo primario (HPTP) es poco frecuente en niños y adolescentes. Hay escasos datos para el manejo de estos pacientes en pediatría. Las glándulas paratiroideas son glándulas endocrinas que secretan hormona paratiroidea (PTH) y regulan el metabolismo del calcio y del fósforo. La sobreexpresión de PTH se llama hiperparatiroidismo, que se clasifica en primario, secundario y terciario. En los adolescentes, 80 a 92% de los hiperparatiroidismos primarios se deben a adenoma paratiroideo. Presentamos el caso clínico de una adolescente con una primera manifestación atípica de HPTP, la presencia de un tumor pardo del paladar, presentación rara de adenoma paratiroideo, acompañado de hipercalcemia, marcada elevación de PTH y varias lesiones óseas. (AU)

Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Guidelines for management in pediatric patients are limited. Parathyroid glands are endocrine glands that secrete parathyroid hormone (PTH) and regulate calciumphosphate metabolism. The overexpression of PTH is called hyperparathyroidism, and is classified as primary, secondary, and tertiary. In adolescents, 80 to 92% of PHPT cases are due to a parathyroid adenoma. We present here a case report of an adolescent with a brown tumor of the palate as the first manifestation of the disease, atypical and rare presentation of parathyroid adenoma in an adolescent. She had hypercalcemia, marked elevation of PTH and bone lesions. (AU)

Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study.

We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P = .035). For children with verified FHL (family history/genetically verified, n = 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n = 53) was significantly lower (52%; 95% CI, 38-65) (P = .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival. This trial was registered at www.clinicaltrials.gov as #NCT00426101.