Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections.

Impact of COVID-19 on child tuberculosis hospitalization.

INTRODUCTION: Morocco has made remarkable progress in the fight against tuberculosis, but the Covid-19 pandemic has affected tuberculosis control worldwide, with notable fluctuations in tuberculosis epidemiology during and after the pandemic. AIM: To describe the impact of the Covid-19 pandemic on the rate of hospitalization for tuberculosis and its different localizations in children. METHODS: We conducted a retrospective study based on the analysis of medical records of TB patients hospitalized within the Children's Hospital in Casablanca, during the periods before (2018-2019), during (2020) and after (2021-2022) Covid-19 quarantine. RESULTS: Throughout the study period (2018-2022), the total number of patients hospitalized in our department was 7390, including 283 children were hospitalized for tuberculosis, with a mean age of 6 years. Before the Covid-19 pandemic, the average number of tuberculosis cases was 49 per year, of which the percentage of pulmonary tuberculosis was 32% and extra-pulmonary tuberculosis 68%. The number of cases was 23 per year during the quarantine period, with a percentage of pulmonary tuberculosis of 26% and extra-pulmonary tuberculosis of 74%. After the quarantine period, this number rose to 81 cases per year, of which 21% were pulmonary tuberculosis and 79% extrapulmonary tuberculosis (pleural tuberculosis was predominant in 44.1% of cases). CONCLUSION: These results are consistent with data published by the World Health Organization, and with the findings of another study we carried out on the impact of COVID-19 on hospital admissions for acute lower respiratory tract infections. It is very likely that the reduction in the number of tuberculosis cases during the quarantine period is due to social distancing, which leads to a reduction in the transmission of tuberculosis between people as well as to the disruption of the national tuberculosis control program in Morocco, when positive cases are identified.

Comparison of NEWS2 and PSI as mortality predictors in patients with community acquired pneumonia.

In the West, National Early Warning Score 2 (NEWS2) is commonly applied to predict the severity of illness using only bedside variables unlike the extensive Pneumonia Severity Index (PSI). The objective of this study was to compare these scores as mortality predictors in patients admitted with community acquired pneumonia (CAP). This cross-sectional study was conducted in Jinnah Postgraduate Medical Centre, Karachi, Pakistan, for six months in 2020 on 116 patients presenting with CAP. Cases of aspiration pneumonia, hospital acquired pneumonia, pulmonary tuberculosis, pulmonary embolism, and pulmonary oedema were excluded. In-hospital mortality was taken as the outcome of this study. The mean age of the participants was 46.9±20.5 years. The in-hospital mortalities were 45(38.8%). NEWS2 was 97.8% sensitive but only 15.5% specific in predicting the outcome, whereas PSI was less sensitive (68.9%) but more specific (50.7%), which showed that in comparison with PSI, NEWS2 is a more sensitive mortality predicting score among hospitalised CAP patients.

Impact of bioplastic contamination on the mechanical recycling of conventional plastics.

Quality assurance of a recycled product is currently one of the biggest issues that the plastic recycling industry faces. The purity of the input plastic waste stream has significant influence over the quality of the recycled product. This research evaluated the impact of polylactic acid (PLA) contamination within the input waste stream of high-density polyethylene (HDPE) recycling. The ultimate tensile strength was noted to reduce by 50% when PLA contamination was at 10%. An investigation into the effect that UVA radiation (simulating solar radiation) has on HDPE contaminated with PLA was also performed to determine the long-term effect of the bioplastic contamination. After UVA treatment, the ultimate tensile strength was reported to reduce by 51% when PLA contamination was only at 2.5%. A water contact angle analysis indicated the PLA contamination increased the hydrophilic nature of the HDPE sheets, potentially creating issues if the intended use of the recycled product was to store liquids. Microscopic analysis of the HDPE sheets contaminated with PLA showed deformations, ridges, cracks, and holes appear on the surface due to the immiscibility of the two polymers that was confirmed by FTIR analysis. Colour changes were visibly noted, with UVA exposure increasing the rate of colour change. Based on the findings in this study, PLA contamination of even 1% in a HDPE waste stream would significantly reduce the quality of the recycled product.

Discrimination of Genetic Biomarkers of Disease through Machine-Learning-Based Hypothesis Testing of Direct SERS Spectra of DNA and RNA.

Cancer is globally a leading cause of death that would benefit from diagnostic approaches detecting it in its early stages. However, despite much research and investment, cancer early diagnosis is still underdeveloped. Owing to its high sensitivity, surface-enhanced Raman spectroscopy (SERS)-based detection of biomarkers has attracted growing interest in this area. Oligonucleotides are an important type of genetic biomarkers as their alterations can be linked to the disease prior to symptom onset. We propose a machine-learning (ML)-enabled framework to analyze complex direct SERS spectra of short, single-stranded DNA and RNA targets to identify relevant mutations occurring in genetic biomarkers, which are key disease indicators. First, by employing ad hoc-synthesized colloidal silver nanoparticles as SERS substrates, we analyze single-base mutations in ssDNA and RNA sequences using a direct SERS-sensing approach. Then, an ML-based hypothesis test is proposed to identify these changes and differentiate the mutated sequences from the corresponding native ones. Rooted in "functional data analysis," this ML approach fully leverages the rich information and dependencies within SERS spectral data for improved modeling and detection capability. Tested on a large set of DNA and RNA SERS data, including from miR-21 (a known cancer miRNA biomarker), our approach is shown to accurately differentiate SERS spectra obtained from different oligonucleotides, outperforming various data-driven methods across several performance metrics, including accuracy, sensitivity, specificity, and F1-scores. Hence, this work represents a step forward in the development of the combined use of SERS and ML as effective methods for disease diagnosis with real applicability in the clinic.

Influence of bioaugmented fungi on tolerance, growth and phytoremediation ability of Prosopis juliflora Sw. DC in heavy metal-polluted landfill soil.

The research aimed to determine the influence of endophytic fungi on tolerance, growth and phytoremediation ability of Prosopis juliflora in heavy metal-polluted landfill soil. A consortium of 13 fungal isolates as well as Prosopis juliflora Sw. DC was used to decontaminate heavy metal-polluted landfill soil. Enhanced plant growth (biomass and root and shoot lengths) and production of carotenoids, chlorophyll and amino acids L-phenylalanine and L-leucine that are known to enhance growth were found in the treated P. juliflora. Better accumulations of heavy metals were observed in fungi-treated P. juliflora over the untreated one. An upregulated activity of peroxidase, catalase and ascorbate peroxidase was recorded in fungi-treated P. juliflora. Additionally, other metabolites, such as glutathione, 3,5,7,2',5'-pentahydroxyflavone, 5,2'-dihydroxyflavone and 5,7,2',3'-tetrahydroxyflavone, and small peptides, which include Lys Gln Ile, Ser Arg Ala, Asp Arg Gly, Arg Ser Ser, His His Arg, Arg Thr Glu, Thr Arg Asp and Ser Pro Arg, were also detected. These provide defence supports to P. juliflora against toxic metals. Inoculating the plant with the fungi improved its growth, metal accumulation as well as tolerance against heavy metal toxicity. Such a combination can be used as an effective strategy for the bioremediation of metal-polluted soil.

An overview of a preliminary multicenter retrospective study on food and drug allergies in Moroccan pediatric population.

Introduction: this study aimed to investigate the prevalence and management of food allergies (FA) and drug allergies (DA) in Morocco. Sparse and conflicting epidemiological data exist on the exact prevalence of allergies in the country. The rise in allergies can be attributed to various factors. Methods: the study analyzed data from patients with suspected FA and DA who sought medical attention. Statistical tests were used to analyze the data, percentages were computed for qualitative variables, and for quantitative variables, medians or means accompanied by standard deviations (SD) were calculated. The Chi-square test was employed to assess categorical variables. A p-value < 0.05 was considered statistically significant. Results: Cow's milk was the most reported food allergen (58.2%), followed by egg and nuts (23.4% and 12.1%, respectively). The most affected age group was children under 5 years. Antibiotics were the leading cause of reported drug allergies (44.8%), particularly Beta-lactams. Immediate reactions were commonly associated with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Symptoms of FA included acute urticaria, vomiting, anaphylactic shock, and facial edema. Urticaria was the most frequent symptom of DA. Antihistamines and corticosteroids were the main treatments used for both FA and DA. Conclusion: the prevalence of FA and DA in Morocco remains uncertain due to limited data. There is a need for centralized data collection and awareness among clinicians and the general population regarding allergies. The study highlights the importance of proper diagnosis and management of allergies to ensure patient safety. The findings emphasize the necessity of establishing a mandatory center for allergy care in Morocco to improve the understanding and management of allergic conditions.

Autoimmune cytopenias in children: When to think of primary immunodeficiency?

Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.

An overview of risk factors in children with febrile seizures.

INTRODUCTION: Febrile seizures (FS) are the most common neurologic disorder seen in children. Caused mainly by fever without any damage to the central nervous system (CNS). The associations of several factors, which we can find in the inflammatory response and genetic predisposition, are involved in the occurrence of FS. AIM: This review provides insight into risk factors, particularly the involvement of the inflammatory response and genetic susceptibility in the occurrence of FS. METHODS: A PubMed search was performed using the keywords « febrile seizures ¼, « inflammatory response ¼, « Pro-inflammatory cytokines ¼, «And anti-inflammatory cytokines ¼. The search strategy included meta-analyses, prospective case-control studies, clinical trials, observational studies, and reviews. RESULTS: Febrile seizures with a peak incidence of 18 months usually occur between 6 months and 5 years. A variety of genetic, inflammatory, and environmental factors, including viruses and vaccines, trigger FS. A positive family history of febrile seizures increases the risk for FS occurrence with (20%) in siblings and (33%) in one parent. The involvement of inflammatory response genes, including the cytokine genes IL1B, IL1R, IL6, and IL4. According to these findings, FS is associated with the activation of a cascade of pro- and anti-inflammatory cytokines and the unbalance between these cytokines in the inflammation regulation plays a role in the development of FS. CONCLUSION: Current knowledge suggests that genetic susceptibility and inflammatory response dysregulation contribute to FS's genesis.

Advancing the initiatives of sustainable coastal and marine areas development in Pakistan through marine spatial planning.

Coastal states are currently transitioning their traditional socio-economic activities into a single platform to address the emerging issues of the coast and marine environment. For countries like Pakistan, managing multiple coastal and marine activities is a significant challenge. The lack of proper management policies and an inefficient decision-making process put various types of pressure on the ecological functions of Pakistan's coastal and marine areas. The Government of Pakistan has not yet prioritized coastal and marine affairs in its policy agenda, resulting in a halt to the process of sustainable development. Moreover, a lack of financial allocation for large-scale coastal and marine projects, a shortage of trained human resources, insufficient coordination among organizations, and unstable political decisions and governance impede the sustainable delivery of the projects. This paper discusses Pakistan's coastal and marine policy targets and highlights various issues through PESTLE analysis, which encompasses political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) factors that limit the advancement of sustainable coastal and marine development. This paper aims to determine the advantages of adopting marine spatial planning (MSP) in Pakistan and how its implementation can bring social, ecological, and economic prosperity. The study provides a baseline for the country's coastal and marine policymakers regarding the advancement of a blue economy through MSP.

Classification of common variable immunodeficiency through immunological and clinical phenotyping in Moroccan patients.

Objective: Common variable immunodeficiency (CVID) is a complex inborn error of humoral immunity with complications of both infectious and non-infectious origins. Classifications of CVID patients provide a clearer understanding of the pathogenesis, prediction, and management of non-infectious complications. This study aims to classify Moroccan CVID patients based on the European classification (EUROclass). Materials and Methods: We recruited 20 CVID patients meeting standard diagnostic criteria (5-6). After collecting clinical and demographic data, we used flow cytometry to analyze B-cell subsets and group patients and assess the relation of each group with clinical manifestations. Results: 90% of the patients in our cohort study had a history of respiratory infections. The noninfectious manifestations included splenomegaly, autoimmunity, lymphadenopathy, and granulomatous diseases diagnosed in 50%, 45%, 40%, and 25% of patients, respectively. We observed significant co-occurrence of splenomegaly with autoimmunity and granulomatous diseases to a lesser extent. Patients had a significant reduction in total, switched memory, marginal zone-like, plasma blasts, and a substantial increase in the percentage of activated B cells, suggesting a defect in the late phases of B-cell differentiation. This condition was linked with an increased occurrence of splenomegaly and granulomatous affections. Besides, patients also had an expansion of CD21low B-cells, which was strongly associated with splenomegaly. Conclusion: The classification of the first Moroccan cohort of CVID patients showed agreement with previous results. It suggests the possibility of adopting this approach on a global scale for better diagnosis and follow-up of CVID patients.

Mendelian susceptibility to mycobacterial diseases: State of the puzzle.

The constant progress of genomics and the establishment of new functional tests have paved the way for identifying monogenic defects conferring a selective predisposition to infections by certain microbes as a new type of inborn errors of immunity (IEIs). Mendelian susceptibility to mycobacterial diseases (MSMD) is the most characterized of these IEIs, with 36 different disorders found in 20 distinct genes (IFNGR1, IFNGR2, IFNG, IL12RB1, IL12RB2, IL23R, IL12B, ISG15, USP18, ZNFX1, TBX21, STAT1, TYK2, IRF8, IRF1, CYBB, JAK1, RORC, NEMO, and SPPL2A) over the last 20 years. MSMD confers a selective susceptibility to infections with weakly virulent mycobacteria, including the M. bovis Bacille Calmette-Guerin (BCG) vaccines and various environmental mycobacteria in patients, primarily children, without classical immune defects. These patients may also present severe forms of tuberculosis, and about half of them might develop non-typhoidal salmonellosis. In some cases, patients also suffer from chronic mucocutaneous candidiasis (CMC), while in others, patients also present severe viral, parasitic, fungal, and/or bacterial diseases. Despite this clinical and genetic heterogeneity, almost all genetic etiologies of MSMD alter the interferon-gamma (IFN-γ)- mediated immunity by impairing or abolishing IFN-γ production or the response to this cytokine. It was proven that the human IFN-γ level is a quantitative trait that defines the outcome of mycobacterial infection. The study of these monogenic defects contributes to understanding the molecular mechanism of mycobacterial diseases in humans and to the development of new diagnostic and therapeutic approaches to improve care and prognosis. For example, MSMD patients with impaired production of IFN-γ may benefit from injections of human recombinant IFN-γ, while for patients with abolished response to this cytokine, hematopoietic stem cell transplantation (HSCT) and promising gene therapy are the only current therapeutic options. These discoveries also bridge the gap between simple Mendelian inheritance and complex human genetics.

Efficacy of Anakinra Treatment in two Moroccan Patients With Mevalonate Kinase Deficiency.

Mevalonate kinase deficiency (MKD) is a rare hereditary autoinflammatory disease, with a widely variable clinical spectrum. It is characterized by febrile recurrent episodes and systemic inflammation. Data on therapeutic options for MKD are still limited and remain unknown in our country. We report Moroccan cases with MKD referred in our unit and treated with Anakinra, an interleukin-1 receptor antagonist. Through this study, we evaluate the efficacy of this bioagent, in our 2 MKD patients, in whom Anakinra has shown a complete clinical remission, with a remaining mild inflammation for one case, and normalization of growth with rare episodes of cervical adenopathies for the second case. Our experience provides an additional argument supporting the efficacy of Anakinra treatment, demonstrated previously but still lacks of objective data.

Student's attitudes towards medical education in Arabic (Morocco 2020).

INTRODUCTION: Several studies suggest that teaching medicine in the national language is essential for quality training and for communication with patients. AIM AND METHODS: To measure the students' level of understanding of their French language training and skills acquisition, as well as the difficulties they encounter in communicating with patients and their families, and the extent to which they accept medical studies in Arabic, we conducted a descriptive crosssectional study on a random sample of 450 students from the Faculty of Medicine and Pharmacy of Casablanca. RESULTS: 16% of the students had trouble assimilating their lessons in French, 48.9% of them had trouble communicating with the patient, and 22% were ready to study medicine in Arabic. Regarding the effect of teaching medicine in Arabic on different fields, 42.2% of the students mentioned a positive effect on the training, 85.2% on the communication with the patient during their training on field and 64.8% on the quality of care. CONCLUSION: Our study revealed the existence of multiple difficulties among students, particularly in the field of communication with the patient, which is a fundamental pillar for the quality of health care, hence the need to provide effective and rapid solutions to the problem of language in medical education.

Effectiveness of natural immune protection against COVID-19 reinfection: systematic review with meta-analysis.

INTRODUCTION: The future of the COVID-19 pandemic depends on the evolution of the virus and immune protection stimulated by vaccination or upon exposure to natural infection. While most research focuses on vaccine efficacy, data remain unclear on the efficacy and duration of natural immune protection against infection. AIM: In this article, we aim to determine the efficacy of natural immune protection against reinfection with COVID-19 or severe COVID-19. METHODS: We performed a systematic review of available studies in electronic databases followed by a meta-analysis to determine the efficacy of natural immune protection against COVID-19 reinfection and severe infection. RESULTS: Of the 414 studies identified for the full review, 8 studies met the inclusion criteria and were analyzed. The total number of individuals participating in the 8 studies included 19,837,147 people. Individuals with a history of SARS-CoV-2 infection (1,9% [0,6%-3,1%]) had a lower rate of infection than individuals without a history of infection (7,1% [3,9%-10,1%]). The mean efficacy of natural immune protection against reinfection was 84,7% [78,5%-90,9%], while the mean efficacy of natural immune protection against severe COVID-19 infection was 96,9% [94%-99,6%]. CONCLUSION: These results indicate that natural immune protection against reinfection is high, particularly against severe COVID-19. However, further research is needed to determine the duration of natural immune protection and the impact of different variants of SARS-CoV-2.

A DFT study on the probability of using the heteroatom decorated graphitic carbonitride (g-C3N4) species for delivering of three novel Multiple sclerosis drugs.

In this project, the possibility of drug delivery application of three anti-Multiple sclerosis (MS) agents (containing diroximel fumarate (DXF), dimethyl fumarate (DMF), and mono methyl fumarate (MMF)) by using some heteroatom decorated graphitic carbonitride (g-C3N4) (as nano-sized carriers) have been systematically investigated. The results of the study have indicated that As-g-C3N4 QD is not a suitable candidate for drug delivery (at least in the cases of DMF, and DXF drugs); while, it would be an accurate semiconductor sensor for selective detection of each mentioned agents. Also, the use of the P-doped as well as pristine g-C3N4 QD could lead to weak electronic signals with relatively same values (in electronvolts). It means that P-g-C3N4, and g-C3N4 QDs are not good sensors for detection of each of the three considered drugs. However, those two sorbents would be suitable carriers for delivering of all three mentioned pharmaceuticals.

Evaluating the generation of microplastics from an unlikely source: The unintentional consequence of the current plastic recycling process.

This study casts light on the potential of microplastic generation during plastic recycling - an unintended consequence of the process. To date, microplastics have been detected in the wastewater and sludge from plastic recycling facilities; however, generation pathways, factors and minimisation strategies are understudied. The purpose of this study is to identify the factors affecting microplastic generation, namely, plastic type and weathering conditions. The size reduction phase, which involved the mechanical shredding of the plastic waste material, was identified to be the predominate source of microplastic generation. Material type was found to significantly affect microplastic generation rates. Focussing on the microplastic particles in the size range of 0.212-1.18 mm, polycarbonate (PC), polyethylene terephthalate (PET), polypropylene (PP), and high-density polyethylene (HDPE) generated 28,600 ± 3961, 21,093 ± 2211, 18,987 ± 752 and 6807 ± 393 particles/kg of plastic material shredded, respectively. The significant variations between different plastic types were correlated (R2 = 0.88) to the hardness of the plastic. Environmental weathering was observed to significantly affect microplastic generation rates. Generation rates increased for PC, PET, PP, and HDPE by 185.05 %, 159.80 %, 123.70 % and 121.74 %, respectively, over a six-month environmental exposure period. The results in this study confirm production of large amounts of microplastics from the plastic recycling industry through its operational processes, which may be a significant source for microplastic pollution if measures to reduce their production and removal from wastewater and sludge are not considered.

Change in the chemical, mechanical and physical properties of plastics due to UVA degradation in different water matrices: A study on the recyclability of littered plastics.

To move towards a circular society, the recyclability potential of littered plastics should be explored to provide potential value for a product that is typically destined for landfill or incineration. This study aims to understand the changes in physical, mechanical, and chemical properties of four types of plastics (polyethylene terephthalate (PET), polypropylene (PP), polycarbonate (PC) and polylactic acid (PLA) after simulated environmental degradation. Plastic samples were subjected to different water matrices (in an attempt to simulate terrestrial, ocean, and river environments) to understand the role the environment plays on plastic degradation. Significant physical, mechanical, and chemical changes were observed for the PET, PP and PLA samples. Flakes and cracks were noted during the scanning electron microscopy (SEM) analysis of PET, PP and PLA illustrating the surface degradation that had occurred. Colour scanning of the samples provided complementary information about their suitability for upcycling or downcycling. Both PET and PP had visual colour changes, making them unsuitable for upcycling purposes. PLA had a significant decrease in its tensile strength in all environmental conditions, alongside significant chemical and surface change as revealed by Fourier-transform infrared (FTIR) and SEM analysis, respectively. PC had little to no changes in its chemical, mechanical, and physical properties due to high resistance to solar (UVA) degradation in presence of salt and natural organic matter in the form of humic acid. Therefore, out of the four types of plastics tested, PC was the only plastic determined to have good upcycling potential if collected from the environment. However, PET and PP could still be recycled into lower value products (i.e., construction materials).

Colorectal liver metastases that survive radioembolization display features of aggressive tumor behavior.

BACKGROUND: Radiation lobectomy is a therapeutic approach that involves targeted radiation delivery to induce future liver remnant hypertrophy and tumor control. In patients with colorectal liver metastases, only 30-40% have complete tumor regression. The importance of tumor biology in treatment response remains elusive. METHODS: Patients with colorectal liver metastases who received radiation lobectomy were selected from surgical pathology files. Using a machine learning scoring protocol, pathological response was correlated to tumor absorbed dose and expression of markers of radioresistance Ki-67 (proliferation), CAIX (hypoxia), Olfm4 (cancer stem cells) and CD45 (leukocytes). RESULTS: No linear association was found between tumor dose and response (ρ < 0.1, P = 0.73 (90Y), P = 0.92 (166Ho)). Response did correlate with proliferation (ρ = 0.56, P = 0.012), and non-responsive lesions had large pools (>15%) of Olfm4 positive cancer stem cells (Fisher's exact test, P = 0.0037). Responding lesions (regression grade ≤2) were highly hypoxic compared to moderate and non-responding lesions (P = 0.011). Non-responsive lesions had more tumor-infiltrating leukocytes (3240 cells/mm2 versus 650 cells/mm2), although this difference was not significant (P = 0.08). CONCLUSION: The aggressive phenotype of a subset of surviving cancer cells emphasizes the importance of prompt resection after radiation lobectomy.

Atypical Cutaneous Viral Infections Reveal an Inborn Error of Immunity in 8 Patients.

Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.