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For people with haemophilia (PwH) who live in developing countries, haemophilia continues to be a condition with serious medical and social consequences. In Morocco, the efforts of patient associations and medical teams have led to the creation of a national programme for haemophilia care since the end of 2012, and the country is no longer solely reliant on World Federation of Hemophilia (WFH) donations for access to factor products. There is growing recognition of the impact of the pain experienced by PwH. To continue to improve treatment for PwH in Morocco, it is important to ensure that they are also able to manage haemophilia-related pain.

The AguelmamAzegza lake is located in the Middle Atlas mountain range, this region consists of carbonate rocks of Lias. It is the best-watered and richest region in Morocco in terms of wetlands, especially natural lakes, rivers and fresh springs. The lake’s water supply is ensured by the inflows of water in the form of underwater sources fed by precipitation (rain and snow) following tectonics and the genesis of karstic formations by the dissolution of carbonate rocks. The declining trend in lake levels in recent years results from the decrease in precipitation which decreases during these years.

Investigating habitat selection and ecological factors trade-offs is a major avian ecology topic which is closely implicated for conservation purposes. Studies dealing with the impacts of ecological factors on wintering Spoonbills are overall scarce. Here, we used Principal Component Analyses (PCA) and Generalized Linear Mixed Models (GLMM) to test the relevance of geographical, environmental and anthropogenic factors in predicting the occupancy and abundance of the Eurasian spoonbills (Platalea leucorodia) during 2008-2011 within 28 Moroccan wetlands. The Eurasian Spoonbill mean annual occurrence was 59.2% (± 1.5% SE; 95%CI: 56.3%-62.1%). Among the occupied wetlands, 15 (83.3%) were regularly occupied. We found that the Eurasian spoonbill occurrence was negatively related to distance to coastline, altitude and human presence, whereas its abundance increased significantly with increasing mudflat areas. These findings highlight the significant effect of human presence in selecting wintering sites, but not in the prediction of abundance. Management strategies should therefore address specific attributes of coastal wetlands and should carefully consider the effects of habitat use especially those related to mudflats. We further suggest guidelines for future studies to understand the dynamic of Eurasian spoonbills wintering in the region.

Tourism merits on natural spaces are not exhausted, namely economic dynamics, development of the local population’s life conditions, species conservation and awareness of environmental protection. However, the damage caused by Coronavirus to natural and rural spaces has impacted such merits negatively, for example, suspension of tourism and recreation activities. Further, the rebirth of ecotourism will be slower and necessitates profound changes in travel design and service delivery. Hence, sustainability, sanitary and regulatory measures will probably help manage ecotourism systems. Nevertheless, these will be affected by the increase in exploring relations between nature and wildlife regarding zoonotic and vector-borne infections and the fragility of biodiversity. Because of his mobility, a tourist appears to be a potential pathogen transmission factor of infections to natural areas, local communities, ecotourism destinations, his country and the crossed ones. New procedures would reduce travel and control traveler’s behavior, and interactions between travelers and wild animals. The slowdown in demand may thus hinder the development of ecotourism. Sensitivity to epidemiological risk and vector-borne diseases will be greater and the need for health-friendly tourism will be further strengthened.

Muscle stem cells (MuSCs) enable muscle growth and regeneration after exercise or injury, but how metabolism controls their regenerative potential is poorly understood. We describe that primary metabolic changes can determine murine MuSC fate decisions. We found that glutamine anaplerosis into the tricarboxylic acid (TCA) cycle decreases during MuSC differentiation and coincides with decreased expression of the mitochondrial glutamate deaminase GLUD1. Deletion of Glud1 in proliferating MuSCs resulted in precocious differentiation and fusion, combined with loss of self-renewal in vitro and in vivo. Mechanistically, deleting Glud1 caused mitochondrial glutamate accumulation and inhibited the malate-aspartate shuttle (MAS). The resulting defect in transporting NADH-reducing equivalents into the mitochondria induced compartment-specific NAD + /NADH ratio shifts. MAS activity restoration or directly altering NAD + /NADH ratios normalized myogenesis. In conclusion, GLUD1 prevents deleterious mitochondrial glutamate accumulation and inactivation of the MAS in proliferating MuSCs. It thereby acts as a compartment-specific metabolic brake on MuSC differentiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Importance: Spontaneous coronary artery dissection is a rare cause of acute coronary syndromes not related to atherosclerosis. It involves the sudden tearing of the coronary artery wall, separating the inner intimal lining from the outer vessel wall, typically affecting a single coronary vessel. In 20% of cases, the cause of spontaneous coronary artery dissection is unknown. The other cases often occur in pregnant or postpartum women or in individuals with conditions such as connective tissue disorders or vasculitis., Case Presentation: Here, we describe a case of a 69-year-old African female presenting with non-ST-segment elevation myocardial infarction. Coronary angiography revealed an unusual triple-vessel spontaneous coronary artery dissection affecting peripheral segments, with further investigations suggesting polyarteritis nodosa., Conclusion: While triple-vessel spontaneous coronary artery dissection and polyarteritis nodosa (PAN) are individually rare, their coexistence is exceptionally uncommon and presents diagnostic and therapeutic challenges. Clinicians should be alert to vasculitic causes in patients with spontaneous coronary artery dissection, especially with atypical clinical features., (© 2024. The Author(s).)

Bone marrow aplasia is a rare and serious hematologic disorder. Although benign, it is a hematologic disorder whose prognosis can be poor and whose spontaneous development can be fatal. Treatment is long, difficult and costly. In developing countries, the mortality rate is high due to the difficulties of therapeutic management, both supportive and specific. We conducted a retrospective study of 92 cases of AM identified in the Pediatric Hematology and Oncology Department of the 20 Août University Hospital in Casablanca over a 10-year period (January 2010-January 2020). In this work, we present an overview of the situation and highlight the difficulties encountered in the management of AM in the Pediatric Hematology and Oncology Department of the University Hospital of Casablanca. In our study, the mean age was 19 years, ranging from 3 months to 29 years, with a peak in the 15-20 age group. The sex ratio (M/F) was 2.06, with a male predominance of 67%. In our series, only 35% of patients had complete bone marrow failure. An anemic syndrome was present in 92% of patients, and hemorrhagic and infectious syndromes were present in 70% and 41% of patients, respectively. The median time from diagnosis to treatment was 82 days. According to the Camitta score, 31% of our patients had mild AM, 41% had severe AM, and 28% had very severe AM. After etiologic evaluation, we concluded that 90% of the patients had idiopathic bone marrow aplasia, 2% had constitutional bone marrow aplasia, and 8% of the patients were suspected to have secondary bone marrow aplasia: post-hepatitis (3 cases), toxic (2 cases), drug-induced (1 case), and aplastic PNH (1 case). Mortality in the first three months after diagnosis was 21%. Sixty-nine percent of our patients received specific treatment: 28 were treated with cyclosporin (CIS) alone as first-line therapy, 20 received a combination of antilymphocyte serum (ALS) and cyclosporin, 2 received hematopoietic stem cell transplantation (HSCT), while 3 were treated with androgens alone. The overall response rate was 30% with CIS, 42% with ALS+CIS and 100% with HSCT. In our study, the overall death rate was 44%, while the one-year survival rate was 40%. It is important to note that septic shock was the leading cause of death (53% of deaths), followed by hemorrhagic shock (24%). This highlights the lack of hemodynamic resuscitation and symptomatic treatment. Our multivariate study defined the following risk factors as predictive of worse survival: age greater than 16 years (RR: 3.28; CI: 1.29-8.33; P=0.012), PNN less than 200 or very severe bone marrow aplasia (RR: 3.01; 1.1-8.08; P=0.028), and failure to receive any specific treatment (RR: 4.07; 1.77-9.35; P=0.0003). The high overall mortality in our series was due to several factors: inaccessibility to effective therapies, delayed diagnosis, failure to initiate specific treatment, inadequate symptomatic treatment, and geographical and financial inaccessibility., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Phase-shift contrast agents consist of a liquid perfluorocarbon core that can be vaporized by ultrasound to generate echogenic contrast with excellent spatiotemporal control. The purpose of the present work was to evaluate the in vitro and in vivo behavior of condensed lipid-shelled nanodroplets (NDs) using different analytical procedures., Methods: Perfluorobutane NDs were prepared by condensation of precursor fluorescently labeled lipid-shelled microbubbles (MBs) and were characterized in terms of size distribution, gas core content and in vitro stability in blood, as well as for their acoustic vaporization behavior using a custom-made setup. In particular, the in vivo behavior of the NDs was thoroughly investigated after intravenous bolus injection in rats. To this end, we report, for the first time, the efficient use of three complementary detection procedures to assess the in vivo persistence of NDs: (i) ultrasound contrast imaging of vaporized NDs, (ii) gas chromatography-mass spectrometry to determine the perfluorobutane core content and (iii) fluorescence intensity measurement in the collected blood samples., Results: The Coulter Counter Multisizer results confirmed the size distribution shift post-condensation. Furthermore, similar PFB concentrations from MB and ND suspensions were obtained, indicating an exceptionally low rate of MB breakage and spontaneous nanodroplet vaporization. As expected, these nanoscale droplets have longer circulation times compared with clinically approved MBs, and only slight variations in half-life were observed between the three monitoring procedures. Finally, echogenic signal observed in focal areas of the liver and spleen after vaporization was confirmed by accumulation of fluorescent nanodroplets in these organs., Conclusion: These results further contribute to our understanding of both the in vitro and in vivo behavior of sono-responsive nanodroplets, which is key to enabling efficient clinical translation., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Acute lymphoblastic leukemia is the most common childhood cancer, with an 80% frequency in children between 1 and 10 years old. The outcome and prognosis of acute lymphoblastic leukemia in children depends on various factors, such as age, clinical and biological features, and cytogenetic factors., Case Presentation: We report the case of a pediatric patient, a 4-year-old Moroccan female who was referred to the Hematology and Oncology Department of 20 August 1953 Hospital in Casablanca and diagnosed with B-cell acute lymphoblastic leukemia associated with a rare genetic chromosomal abnormality., Conclusion: Translocation (1;4)(p21;p15) is a relatively rare chromosomal abnormality found in human leukemia and was never described isolated in pediatric B-cell acute lymphoblastic leukemia patients. It showed a good evolution by complete remission and recovery of this patient after receiving all chemotherapy and after 8 years of follow-up., (© 2023. The Author(s).)

Purpose: Peripheral neuroblastic tumors are the most common extracranial cancers found in children, and they are characterized by a diverse spectrum of clinical manifestations and heterogeneous behaviors. This study aimed to investigate the epidemiological and clinical characteristics of children with peripheral neuroblastic tumors admitted to the Department of Pediatric Hematology and Oncology of the Hospital August 20 in Casablanca., Methods: The medical files of 48 children with peripheral neuroblastic tumors addressed to our department between February 2018 and February 2023 were reviewed. The clinical and demographic characteristics of patients were analyzed by the Statistical Package for the Social Sciences (SPSS), survival curves were obtained by Kaplan-Meier technique, and we assigned the tumor stage to patients based on the International Neuroblastoma Risk Group Staging System (INRGSS)., Results: The median age of diagnosis was 30 months (1-174), with a ratio F/M of 1.28. 93.75% of patients had neuroblastoma, and the rest had ganglioneuroma. About 64.6% of patients had at their initial presentations stage M of peripheral neuroblastic tumors. The adrenal region made up 71% of the primary tumor site. The bone was one of the most prevalent metastatic sites (54.2%). The five-year overall survival rate was 35.4%., Conclusion: Overall, this study revealed a high stage of peripheral neuroblastic tumors in the majority of the diagnosed patients in our Department of Pediatric Hematology and Oncology. Moreover, the heterogeneity of peripheral neuroblastic tumors makes clinical recognition difficult and, in general, too late., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks., Competing Interests: J.G.H. received speaker honoraria from Dalcor and District 3 Innovation Centre. C.D.R. received research support from Agilent Technologies and is a scientific consultant for Larimar Therapeutics. P.B. is consultant for ADDMEDICA, NOVARTIS, ROCHE, GBT, Bluebird, EMMAUS, HEMANEXT, AGIOS, VERTEX, received lecture fees for NOVARTIS, ADDMEDICA, AGIOS, JAZZPHARMA, VERTEX, is on steering committee for NOVARTIS and ADDMEDICA, receives research support from ADDMEDICA, foundation Fabre, NOVARTIS, Bluebird, EMMAUS, GBT, and is cofounder of INNOVHEM., (© 2023 The Authors.)

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies., (© 2023. Springer Nature Limited.)

Providing sufficient energy for autonomous systems at the nanoscale is one of the major challenges of the Internet of Nano Things (IoNT). Existing battery technologies and conventional integrated circuits cannot be used in such small dimensions. Even if they are small enough to be used at the nano level, they still cannot be used in medical applications due to biocompatibility issues. M13 is a very promising virus with piezoelectric properties, which has attracted much interest in the scientific community as a bioenergy harvester. However, M13 studies presented so far in the literature are designed only for macroscale systems. In this paper, we simulate two designs of a bio-inspired nanogenerator based on the properties of M13 for nanosystems. We derive the stiffness matrix of M13, its dielectric and piezoelectric matrices and its density. We verify our calculated values by comparing our simulations with the results of experimental studies presented in the literature. We also evaluate the system's performance in terms of frequency response and loading characteristics. The results presented in this study show that a single M13 is a very promising nano-generator that can be used for medical applications.

In this paper, we propose a bio-inspired receiver, which detects the electrons transmitted through a nanowire, then, it converts the detected information to blue light using bioluminescence. We simulate the construction of the nanowire, present its electrical characteristics and calculate its maximum capacity for a better design of the receiver. The designed receiver contains two parts; a part that detects the transmitted electrons, which we model by using an equivalent circuit, and a part that converts the detected electrons to blue light. We derive the analytical expressions of the components of the equivalent circuit and give an approximation of their values. We calculate the probability of photons emission for each electrical pulse detected. We also determine the optimal threshold for Integrate Sample and Dump (ISD) receiver. We calculate the error probability of bits detection and present analytical and simulation results to evaluate the performance of the designed receiver. The results of this study show that the designed receiver can accurately detect the electrons sent through a conductive nanowire. Thus providing, to the best of our knowledge, the first technical solution that leads towards integrated wired electrical and optical nanonetworks.

Primary renal marginal zone B lymphoma is extremely rare. The renal involvement by the lymphoma is most often a manifestation of a disseminated disease. We report the case of a 53-year-old patient who presented lower back pain and kidney failure. The renal biopsy showed a marginal zone B lymphoma type MALT and the PET scan showed bilateral renal involvement. A treatment based on rituximab combined with chemotherapy (cyclophosphamide, prednisone and oncovin) was started with good outcome.

Methylmalonic aciduria (MMA) is an inborn error of metabolism with multiple monogenic causes and a poorly understood pathogenesis, leading to the absence of effective causal treatments. Here we employ multi-layered omics profiling combined with biochemical and clinical features of individuals with MMA to reveal a molecular diagnosis for 177 out of 210 (84%) cases, the majority (148) of whom display pathogenic variants in methylmalonyl-CoA mutase (MMUT). Stratification of these data layers by disease severity shows dysregulation of the tricarboxylic acid cycle and its replenishment (anaplerosis) by glutamine. The relevance of these disturbances is evidenced by multi-organ metabolomics of a hemizygous Mmut mouse model as well as through identification of physical interactions between MMUT and glutamine anaplerotic enzymes. Using stable-isotope tracing, we find that treatment with dimethyl-oxoglutarate restores deficient tricarboxylic acid cycling. Our work highlights glutamine anaplerosis as a potential therapeutic intervention point in MMA., (© 2023. The Author(s).)

Cancer cells reprogram their metabolism to support growth and invasion. While previous work has highlighted how single altered reactions and pathways can drive tumorigenesis, it remains unclear how individual changes propagate at the network level and eventually determine global metabolic activity. To characterize the metabolic lifestyle of cancer cells across pathways and genotypes, we profiled the intracellular metabolome of 180 pan-cancer cell lines grown in identical conditions. For each cell line, we estimated activity for 49 pathways spanning the entirety of the metabolic network. Upon clustering, we discovered a convergence into only two major metabolic types. These were functionally confirmed by 13 C-flux analysis, lipidomics, and analysis of sensitivity to perturbations. They revealed that the major differences in cancers are associated with lipid, TCA cycle, and carbohydrate metabolism. Thorough integration of these types with multiomics highlighted little association with genetic alterations but a strong association with markers of epithelial-mesenchymal transition. Our analysis indicates that in absence of variations imposed by the microenvironment, cancer cells adopt distinct metabolic programs which serve as vulnerabilities for therapy., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: In 2018, the World Health Organization (WHO) launched the Global Initiative for Childhood Cancer (GICC). The goal is to achieve a global survival rate of at least 60% for all children with cancer by 2030. Morocco was designated as a pilot country for this initiative., Procedure: This retrospective study included a cohort of children aged 0-15 years, with one of the six indexed cancers (acute lymphoblastic leukemia [ALL], Burkitt lymphoma [BL], Hodgkin lymphoma, retinoblastoma [RB], Wilms tumor or nephroblastoma, low-grade glioma), diagnosed between January 1, 2017 and December 31, 2019 at the six Moroccan Pediatric Hematology and Oncology units. Patients were followed-up until August 31, 2020. The Kaplan-Meier method was used to estimate survival rates, the log-rank test for comparing survival curves, and the Cox model for identifying prognostic factors., Results: Data on 878 patients were included in the study. The most frequently reported cancer type was ALL (n = 383, 43.6%), followed by Wilms tumor (n = 139, 15.8%) and BL (n = 133, 15%). Most patients were less than 5 years of age (n = 446, 50.9%) and the male/female ratio was 1.46. The 1, 2, and 3-year overall survival rates were 80.1%, 73.6%, and 68.2%, respectively. In a multivariable Cox regression model, care center, cancer type, age group, and distance to the care center were statistically significantly associated to survival. Patients aged 10 years and older and patients living more than 100 km from the care center were more likely to die (respectively, HR = 1.39, p = .045 and HR = 1.44, p = .010)., Conclusion: The reported results represent the baseline for measuring the impact of GICC implementation in Morocco., (© 2022 Wiley Periodicals LLC.)

Breeding hybrids with maximum heterosis requires efficient cross-pollination and an improved male sterility system. Renewed efforts have been made to dissect the phenotypic variation and genetic basis of hybrid floral traits, although the potential of tailoring the appropriate flower design on seed setting is less known. To this end, elite wheat genotypes were crossed using a chemical hybridizing agent at different doses. A total of 23 hybrids were developed from a partial diallel design; and planted in an alpha lattice design with their parents at two locations in Morocco, for two years, to evaluate for yield components, heterosis and combining abilities. The 13.5 L ha -1 dose induced a maximum level of sterility (95%) and seed set showed large phenotypic variation and high heritability. In parallel, seed set showed tight correlation with pollen mass (0.97), visual anther extrusion (0.94) and pollen shedding (0.91) ( p < 0.001), allowing direct selection of the associated traits. Using the combined data, mid-parent heterosis ranges were -7.64-14.55% for biomass (BM), -8.34-12.51% for thousand kernel weight (TKW) and -5.29-26.65% for grain yield (YLD); while best-parent heterosis showed ranges of -11.18-7.20%, -11.35-11.26% and -8.27-24.04% for BM, TKW and YLD, respectively. The magnitude of general combining ability (GCA) variance was greater than the specific combining ability (SCA) variance suggesting a greater additive gene action for BM, TKW and YLD. The favorable GCA estimates showed a simple method to predict additive effects contributing to high heterosis and thus could be an effective approach for the selection of promising parents in early generations.

Inflammatory bowel disease (IBD) is a lifelong inflammatory disorder with relapsing-remission cycles, which is currently diagnosed by clinical symptoms and signs, along with laboratory and imaging findings. However, such clinical findings are not parallel to the disease activity of IBD and are difficult to use in treatment monitoring. Therefore, non-invasive quantitative imaging tools are required for the multiple follow-up exams of IBD patients in order to monitor the disease activity and determine treatment regimens. In this study, we evaluated a dual P- and E-selectin-targeted microbubble (MB Selectin ) in an interleukin-2 receptor α deficient (IL-2Rα -/- ) spontaneous chronic IBD mouse model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI). We used IL-2Rα -/- (male and female on a C57BL/6 genetic background; n = 39) and C57BL/6 wild-type (negative control; n = 6) mice for the study. USMI of the proximal, middle, and distal colon was performed with MB Selectin using a small animal scanner (Vevo 2100) up to six times in each IL-2Rα -/- mouse between 6-30 weeks of age. USMI signals were compared between IL-2Rα -/- vs. wild-type mice, and sexes in three colonic locations. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E-stained sections and for selectin expression by immunofluorescence staining. We successfully detected spontaneous chronic colitis in IL-2Rα -/- mice between 6-30 weeks (onset at 6-14 weeks) compared to wild-type mice. Both male and female IL-2Rα -/- mice were equally ( p = 0.996) affected with the disease, and there was no significant ( p > 0.05) difference in USMI signals of colitis between the proximal, middle, and distal colon. We observed the fluctuating USMI signals in IL-2Rα -/- mice between 6-30 weeks, which might suggest a resemblance of the remission-flare pattern of human IBD. The ex vivo H&E and immunostaining further confirmed the inflammatory changes, and the high expression of P- and E-selectin in the colon. The results of this study highlight the IL-2Rα -/- mice as a chronic colitis model and are suitable for the long-term assessment of treatment response using a dual P- and E-selectin-targeted USMI.

We characterized the size of the premarket safety population for 278 small-molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by the US Food and Drug Administration (FDA) between October 1, 2002, and December 31, 2014, evaluating the relationship of premarket safety population size to regulatory characteristics and postmarket safety outcomes. The median size of the safety population was 1,044, and was lower for NTBs than NMEs (median: 920 vs. 1,138, P = 0.04), orphan products than nonorphan products (393 vs. 1,606, P < 0.001), and for products with fast-track designation (617 vs. 1,455, P < 0.001), priority review (630 vs. 1,735, P < 0.001), and accelerated approval (475 vs. 1,164, P < 0.001), than products without that designation. The median number of postmarket safety label updates and issues added to the label were higher with larger premarket exposure among nonorphan products, but not among orphan products. Products with accelerated approval using a surrogate end point had a higher median number of safety issues added to the label than those with full approval, but this did not vary with the size of the safety population; fast-track and priority review were not associated with the number of safety issues added to the label. A smaller safety population size was associated with a longer time to first safety outcome for nonorphan products but not orphan products. For orphan and nonorphan products combined, smaller premarket safety population size is not associated with the number or timing of postmarket safety outcomes, regardless of expedited program participation., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)