Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Polymer-lipid hybrid nanomedicines to deliver siRNA in and against glioblastoma cells.

Small interfering RNA (siRNA) holds great potential to treat many difficult-to-treat diseases, but its delivery remains the central challenge. This study aimed at investigating the suitability of polymer-lipid hybrid nanomedicines (HNMeds) as novel siRNA delivery platforms for locoregional therapy of glioblastoma. Two HNMed formulations were developed from poly(lactic-co-glycolic acid) polymer and a cationic lipid: 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol). After characterization of the HNMeds, a model siRNA was complexed onto their surface to form HNMed/siRNA complexes. The physicochemical properties and siRNA binding ability of complexes were assessed over a range of nitrogen-to-phosphate (N/P) ratios to optimize the formulations. At the optimal N/P ratio of 10, complexes effectively bound siRNA and improved its protection from enzymatic degradation. Using the NIH3T3 mouse fibroblast cell line, DOTAP-based HNMeds were shown to possess higher cytocompatibility in vitro over the DC-Chol-based ones. As proof-of-concept, uptake and bioefficacy of formulations were also assessed in vitro on U87MG human glioblastoma cell line expressing luciferase gene. Complexes were able to deliver anti-luciferase siRNA and induce a remarkable suppression of gene expression. Noteworthy, the effect of DOTAP-based formulation was not only about three-times higher than DC-Chol-based one, but also comparable to lipofectamine model transfection reagent. These findings set the basis to exploit this nanosystem for silencing relevant GB-related genes in further in vitro and in vivo studies.

Successful lung transplantation in genetic methionyl-tRNA synthetase-related alveolar proteinosis/lung fibrosis without recurrence under methionine supplementation: Medium-term outcome in 4 cases.

Pulmonary alveolar proteinosis (PAP) results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages, and can be associated with pulmonary fibrosis, with a need for lung transplantation (LTx). Causes of PAP are autoimmune (90%-95%), secondary (5%), or hereditary (<1%). Patients with hereditary PAP are generally not considered for isolated LTx, due to the high probability of recurrence after LTx, and only a challenging scenario with sequential LTx followed by hematopoietic stem cell transplantation (HSCT) was reported as successful. Recently, a new genetic cause of PAP linked to mutations in the methionyl-tRNA synthetase (MARS) gene has been reported, with a highly variable clinical presentation. Because clinical correction of the defective MARS activity with methionine supplementation has been reported in nontransplanted children, we reassessed the feasibility of LTx for candidates with MARS-related PAP/fibrosis. We report 3 cases of LTx performed for MARS-related pulmonary alveolar proteinosis-pulmonary fibrosis without recurrence under methionine supplementation, whereas another fourth case transplanted without supplementation had fatal PAP recurrence. These results suggest the effectiveness of methionine in correcting defective MARS activity and also looking for this very rare diagnosis in case of unclassified PAP/fibrosis. It argues for not excluding the feasibility of isolated LTx in patients with MARS mutation.

Inflammatory rebound and postinfectious inflammatory response in children with pleural infection: A single-center retrospective study.

INTRODUCTION: As pleural inflammation plays a central role in pleural infection (PI), corticosteroids are increasingly being considered as a potential therapy. However, the timing of treatment and the identification of patients who might benefit most remain unresolved. The aim of this study was therefore to investigate the inflammatory trajectories of children with PI. METHODS: This retrospective single-center study included children aged 3 months to 17 years and 11 months hospitalized for PI due to Streptococcus pyogenes, Streptococcus pneumonia, and Staphylococcus aureus over 10 years. An inflammatory rebound was defined biologically as a reincrease in C-reactive protein (CRP) of at least 50 mg/L after an initial decrease in CRP of at least 50 mg/L. RESULTS: We included 53 cases of PI, including 16 due to S. pyogenes, 27 due to S. pneumonia, and 10 due to S. aureus. An inflammatory rebound occurred in 20 patients (38%) after a median of 4.5 (3-6) days. This inflammatory rebound occurred in 9 (56%) children with S. pyogenes, 8 (30%) children with S. pneumonia, and 3 (30%) children with S. aureus. Children with an inflammatory rebound also had a higher rate of persistent fever after Day 7 and a longer length of stay (p = .01 for both). CONCLUSION: We postulate that the inflammatory rebound identified in nearly 40% of our patients corresponds to an early postinfectious inflammatory response, and thus that corticosteroids may be most beneficial for children with PI if administered early (between Days 2 and 5).

Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities.

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. STATEMENT OF SIGNIFICANCE: Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments.

Global Emergency Medicine: A Scoping Review of the Literature from 2022.

OBJECTIVE: The objective was to identify the highest quality global emergency medicine (GEM) research published in 2022. The top articles are compiled in a comprehensive list of all the year's GEM articles and narrative summaries are performed on those included. METHODS: A systematic PubMed search was conducted to identify all GEM articles published in 2022 and included a manual supplemental screen of 11 organizational websites for gray literature (GRAY). A team of trained reviewers and editors screened all identified titles and abstracts, based on three case definition categories: disaster and humanitarian response (DHR), emergency care in resource-limited settings (ECRLS), and emergency medicine development (EMD). Articles meeting these definitions were independently scored by two reviewers using rubrics for original research (OR), review (RE) articles, and GRAY. Articles that scored in the top 5% from each category as well as the overall top 5% of articles were included for narrative summary. RESULTS: The 2022 search identified 58,510 articles in the main review, of which 524 articles screened in for scoring, respectively, 30% and 18% increases from last year. After duplicates were removed, 36 articles were included for narrative summary. The GRAY search identified 7755 articles, of which 33 were scored and one was included for narrative summary. ECRLS remained the largest category (27; 73%), followed by DHR (7; 19%) and EMD (3; 8%). OR articles remained more common than RE articles (64% vs. 36%). CONCLUSIONS: The waning of the COVID-19 pandemic has not affected the continued growth in GEM literature. Articles related to prehospital care, mental health and resilience among patients and health care workers, streamlining pediatric infectious disease care, and disaster preparedness were featured in this year's review. The continued lack of EMD studies despite the global growth of GEM highlights a need for more scholarly dissemination of best practices.

NTPDase1/CD39 Ectonucleotidase Is Necessary for Normal Arterial Diameter Adaptation to Flow.

NTPDase1/CD39, the major vascular ectonucleotidase, exerts thrombo-immunoregulatory function by controlling endothelial P2 receptor activation. Despite the well-described release of ATP from endothelial cells, few data are available regarding the potential role of CD39 as a regulator of arterial diameter. We thus investigated the contribution of CD39 in short-term diameter adaptation and long-term arterial remodeling in response to flow using Entpd1-/- male mice. Compared to wild-type littermates, endothelial-dependent relaxation was modified in Entpd1-/- mice. Specifically, the vasorelaxation in response to ATP was potentiated in both conductance (aorta) and small resistance (mesenteric and coronary) arteries. By contrast, the relaxing responses to acetylcholine were supra-normalized in thoracic aortas while decreased in resistance arteries from Entpd1-/- mice. Acute flow-mediated dilation, measured via pressure myography, was dramatically diminished and outward remodeling induced by in vivo chronic increased shear stress was altered in the mesenteric resistance arteries isolated from Entpd1-/- mice compared to wild-types. Finally, changes in vascular reactivity in Entpd1-/- mice were also evidenced by a decrease in the coronary output measured in isolated perfused hearts compared to the wild-type mice. Our results highlight a key regulatory role for purinergic signaling and CD39 in endothelium-dependent short- and long-term arterial diameter adaptation to increased flow.

Children's views on artificial intelligence and digital twins for the daily management of their asthma: a mixed-method study.

New technologies enable the creation of digital twin systems (DTS) combining continuous data collection from children's home and artificial intelligence (AI)-based recommendations to adapt their care in real time. The objective was to assess whether children and adolescents with asthma would be ready to use such DTS. A mixed-method study was conducted with 104 asthma patients aged 8 to 17 years. The potential advantages and disadvantages associated with AI and the use of DTS were collected in semi-structured interviews. Children were then asked whether they would agree to use a DTS for the daily management of their asthma. The strength of their decision was assessed as well as the factors determining their choice. The main advantages of DTS identified by children were the possibility to be (i) supported in managing their asthma (ii) from home and (iii) in real time. Technical issues and the risk of loss of humanity were the main drawbacks reported. Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. Those with the best computer skills were more likely to choose the DTS, while those who placed a high value on the physician-patient relationship were less likely to do so.   Conclusions: The majority of children were ready to use a DTS for the management of their asthma, particularly if it was more effective than current care. The results of this study support the development of DTS for childhood asthma and the evaluation of their effectiveness in clinical trials. What is Known: • New technologies enable the creation of digital twin systems (DTS) for children with asthma. • Acceptance of these DTSs by children with asthma is unknown. What is New: • Half of the children (56%) were willing to use a DTS for the daily management of their asthma if it was as effective as current care, and up to 93% if it was more effective. •Children identified the ability to be supported from home and in real time as the main benefits of DTS.

Did it move? Humans use spatio-temporal landmark permanency efficiently for navigation.

Visual landmarks provide crucial information for human navigation. But what characteristics define a landmark? To be uniquely recognized, a landmark should be distinctive and salient, while providing precise and accurate positional information. It should also be permanent. For example, to find back to your car, a nearby church seems a better landmark compared with a distinct truck or bicycle, because you learned that there is a chance that these objects might move. To this end, we investigated human learning of landmark permanency for navigation while treating spatiotemporal permanency as a probabilistic property. We hypothesized that humans will be able to learn the probabilistic nature of landmark permanency and assign higher weight to more permanent landmarks. To test this hypothesis, we designed a homing task where participants had to return to a position that was surrounded by three landmarks. In the learning phase we manipulated the spatiotemporal permanency of one landmark by secretly repositioning it before participants returned home. In the test phase, we investigated the weight allocated to the nonpermanent landmark by analyzing its influence on the navigational performance during homing. We conducted four experiments: In the first two experiments we altered the statistics of permanency and accordingly found an influence on participants' behavior, nonpermanent objects were used less for finding home. In the last two experiments we investigated the role of short-term learning of novel statistics versus long-term knowledge about such statistics. No carry-over effects in Experiment 3 and very little influence of object identity with different long-term permanency characteristics in Experiment 4 revealed a dominance of short-term learning over the use of long-term a priori knowledge about object permanency. This indicates that long-term prior beliefs are quickly updated by the current permanency statistics. Taken together, consistent with a Bayesian account for navigation these results indicate that humans quickly learn and update the statistics of landmark permanency and use it in an effective way, assigning gradually more weight to the more permanent landmark and making it more important for navigation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

High population prevalence of neonicotinoids in sharp-tailed grouse and greater prairie-chickens across an agricultural gradient during spring and fall.

Neonicotinoids have been detected in many species of wild birds; however, few studies have quantified population-level exposure. We examined population-level exposure to 7 neonicotinoids in 2 species that use agricultural areas, sharp-tailed grouse (Tympanuchus phasianellus) and greater prairie-chickens (T. cupido). We sampled fecal pellets at leks in spring and collected livers from hunter-harvested birds in fall along an agricultural gradient throughout their respective ranges in Minnesota, USA. Most sharp-tailed grouse (93 %) and prairie-chicken (80 %) fecal pellets and livers (90 % and 76 %, respectively) had detectable concentrations of ≥1 neonicotinoid, with imidacloprid (IMI) and clothianidin (CLO) most commonly detected. Spring detections of IMI in both species increased with the proportion of a 2-km buffer in cultivation surrounding sampling locations and varied by year. A similar relationship with cultivation was not supported for CLO, which may reflect differences in the availability of seed types treated with IMI and CLO on the soil surface after planting. However, we also detected IMI and CLO from birds sampled in areas of low cultivation. Sharp-tailed grouse and prairie-chickens may select crop fields preferentially to forage, and thus have a higher risk of exposure than would be expected based only on the amount of cultivation. Year was important in models of IMI and CLO in both species and seasons, which likely reflects differences in planting and in the availability of natural foods among years. In contrast, the proportion of surrounding area in cultivation was not supported in models of fall neonicotinoid detections. Fewer crops are planted in the fall in Minnesota and grouse may be exposed through routes other than treated seeds. High detections, even in areas with little cultivation and during seasons with little planting, likely reflect prairie grouse selection of cultivated fields for food, but may also indicate that exposure risk extends beyond sites of application.

The international humanitarian response to famine in Tigray, Ethiopia:lessons from the Nigerian Civil War, 1967-1970.

The Tigray crisis in Ethiopia is a grave humanitarian catastrophe with causes and consequences that resemble the Nigerian Civil War that ended with the defeat of secessionist Biafra five decades ago. As in the Biafra example, an ethnically distinct and embattled enclave is surrounded by hostile forces and cut off from commerce of any kind, producing starvation, forced migrant encampments, and pervasive dependence on externally provided food relief. Relief action strategies developed during the Nigerian Civil War were comprised of operational components that were often insufficiently integrated into a unified system for nutritional screening, referral, acute care, nutritional rehabilitation, and team deployment. This lack of strategic integration for post-conflict relief actions merits review for possible lessons that could avert its recurrence in Tigray. If evidence-based systems for relief organization had been comprehensively applied in Biafra, the pace of post-conflict nutritional recovery could have been accelerated. Although component strategies of the Biafra-Nigeria Relief Action are being replicated by various agencies that are providing humanitarian assistance in Tigray, their collective impact could be enhanced if these strategies were integrated into a unified, evidence-driven systems response to the emergency. The elements of such a systems approach for assisting Tigray are reviewed.

A role for ceruloplasmin in the control of human glioblastoma cell responses to radiation.

BACKGROUND: Glioblastoma (GB) is the most common and most aggressive malignant brain tumor. In understanding its resistance to conventional treatments, iron metabolism and related pathways may represent a novel avenue. As for many cancer cells, GB cell growth is dependent on iron, which is tightly involved in red-ox reactions related to radiotherapy effectiveness. From new observations indicating an impact of RX radiations on the expression of ceruloplasmin (CP), an important regulator of iron metabolism, the aim of the present work was to study the functional effects of constitutive expression of CP within GB lines in response to beam radiation depending on the oxygen status (21% O2 versus 3% O2). METHODS AND RESULTS: After analysis of radiation responses (Hoechst staining, LDH release, Caspase 3 activation) in U251-MG and U87-MG human GB cell lines, described as radiosensitive and radioresistant respectively, the expression of 9 iron partners (TFR1, DMT1, FTH1, FTL, MFRN1, MFRN2, FXN, FPN1, CP) were tested by RTqPCR and western blots at 3 and 8 days following 4 Gy irradiation. Among those, only CP was significantly downregulated, both at transcript and protein levels in the two lines, with however, a weaker effect in the U87-MG, observable at 3% O2. To investigate specific role of CP in GB radioresistance, U251-MG and U87-MG cells were modified genetically to obtain CP depleted and overexpressing cells, respectively. Manipulation of CP expression in GB lines demonstrated impact both on cell survival and on activation of DNA repair/damage machinery (γH2AX); specifically high levels of CP led to increased production of reactive oxygen species, as shown by elevated levels of superoxide anion, SOD1 synthesis and cellular Fe2 + . CONCLUSIONS: Taken together, these in vitro results indicate for the first time that CP plays a positive role in the efficiency of radiotherapy on GB cells.

Global emergency medicine: A scoping review of the literature from 2021.

OBJECTIVE: The objective was to identify the most important and impactful peer-reviewed global emergency medicine (GEM) articles published in 2021. The top articles are summarized in brief narratives and accompanied by a comprehensive list of all identified articles that address the topic during the year to serve as a reference for clinicians, researchers, and policy makers. METHODS: A systematic PubMed search was carried out to identify all GEM articles published in 2021. Title and abstract screening was performed by trained reviewers and editors to identify articles in one of three categories based on predefined criteria: disaster and humanitarian response (DHR), emergency care in resource-limited settings (ECRLS), and emergency medicine development (EMD). Included articles were each scored by two reviewers using established rubrics for original (OR) and review (RE) articles. The top 5% of articles overall and the top 5% of articles from each category (DHR, ECRLS, EMD, OR, and RE) were included for narrative summary. RESULTS: The 2021 search identified 44,839 articles, of which 444 articles screened in for scoring, 25% and 22% increases from 2020, respectively. After removal of duplicates, 23 articles were included for narrative summary. ECRLS constituted the largest category (n = 16, 70%), followed by EMD (n = 4, 17%) and DHR (n = 3, 13%). The majority of top articles were OR (n = 14, 61%) compared to RE (n = 9, 39%). CONCLUSIONS: The GEM peer-reviewed literature continued to grow at a fast rate in 2021, reflecting the continued expansion and maturation of this subspecialty of emergency medicine. Few high-quality articles focused on DHR and EMD, suggesting a need for further efforts in those fields. Future efforts should focus on improving the diversity of GEM research and equitable representation.

Primary seminal vesicle epithelioid smooth muscle neoplasm of uncertain biologic potential.

We present the case of a 73-year-old male patient who presented with obstructive urinary symptoms, pelvic pressure, and hematuria. CT imaging revealed a heterogenous prostate enlargement, and MRI demonstrated the mass to be arising from the seminal vesicle. Prostate biopsies showed benign tissue. Surgical excision was completed and pathology revealed it to be an epithelioid smooth muscle neoplasm of uncertain biologic potential. This is only the second known case of such a seminal vesicle tumour. As soft tissue sarcomas of the seminal vesicle emerge in the literature, we may develop a better understanding of their biologic behaviour and prognostic potential.

Inoperable scalp cutaneous angiosarcoma: Complete response after definitive external beam radiation therapy - brachytherapy association.

Effective treatments are scarce in non-operable scalp cutaneous angiosarcoma patients. Curative-intent definitive sequential IMRT and plesiobrachytherapy allowed complete response with limited side effect in two elder patients. This could represent a non-invasive therapeutic option for patients with locally advanced presentation.

WEST NILE VIRUS EXPOSURE AND INFECTION AMONG HUNTER-HARVESTED RUFFED GROUSE (BONASA UMBELLUS) COHORTS IN A STABLE POPULATION.

West Nile virus (WNV) was introduced to North America two decades ago, but for many species, including Ruffed Grouse (Bonasa umbellus), the effects of WNV on individuals and populations remain poorly understood. Recent studies suggest the effect of WNV on Ruffed Grouse might vary among geographic regions, depending on habitat conditions. We studied WNV in Minnesota, US, during 2018-19, in a region known to have abundant Ruffed Grouse habitat and a population cycling around a stable long-term average. We worked with cooperating hunters to collect hearts, feathers, and blood on filter strips from birds harvested in the fall to examine exposure to the virus. We detected antibodies to WNV or a flavivirus (probably WNV) in 12.5% and 12.3% of birds in 2018 and 2019, respectively. However, we did not isolate the virus from any heart samples, indicating that exposed birds were not experiencing an active infection of WNV at the time of harvest. Our findings indicate that, although Minnesota Ruffed Grouse are exposed to WNV, some birds mount a successful immune response and survive. However, our sampling approach did not account for birds that might have become infected over the summer and died, so it is unknown how much WNV mortality occurred before the fall harvest. Birds lost to WNV over the summer could reduce the number of birds that hunters see in the fall, thus reducing the quality of their hunting experiences. Management options for mitigating WNV impacts and other stressors consist primarily of providing high-quality Ruffed Grouse habitat that produces birds in good condition that are more likely to recover from infection.

Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child.

We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3-dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.

Current Practices on Diagnosis, Prevention and Treatment of Post-Transplant Lymphoproliferative Disorder in Pediatric Patients after Solid Organ Transplantation: Results of ERN TransplantChild Healthcare Working Group Survey.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers' approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012-2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.

Assessing the indirect effects of COVID-19 on healthcare delivery, utilization and health outcomes: a scoping review.

BACKGROUND: The COVID-19 pandemic and global efforts to contain its spread, such as stay-at-home orders and transportation shutdowns, have created new barriers to accessing healthcare, resulting in changes in service delivery and utilization globally. The purpose of this study is to provide an overview of the literature published thus far on the indirect health effects of COVID-19 and to explore the data sources and methodologies being used to assess indirect health effects. METHODS: A scoping review of peer-reviewed literature using three search engines was performed. RESULTS: One hundred and seventy studies were included in the final analysis. Nearly half (46.5%) of included studies focused on cardiovascular health outcomes. The main methodologies used were observational analytic and surveys. Data were drawn from individual health facilities, multicentre networks, regional registries, and national health information systems. Most studies were conducted in high-income countries with only 35.4% of studies representing low- and middle-income countries (LMICs). CONCLUSION: Healthcare utilization for non-COVID-19 conditions has decreased almost universally, across both high- and lower-income countries. The pandemic's impact on non-COVID-19 health outcomes, particularly for chronic diseases, may take years to fully manifest and should be a topic of ongoing study. Future research should be tied to system improvement and the promotion of health equity, with researchers identifying potentially actionable findings for national, regional and local health leadership. Public health professionals must also seek to address the disparity in published data from LMICs as compared with high-income countries.