Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD). OBJECTIVE: We sought to understand the mechanisms of eczema in DOCK8 deficiency. METHODS: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus. RESULTS: Skin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients' skin was colonized by Saureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8-/- mice exhibited reduced numbers of cutaneous T regulatory (Treg) cells and a normal skin barrier. Dock8-/- and mice with an inducible Dock8 deletion in Treg cells exhibited increased allergic skin inflammation after epicutaneous sensitization with OVA. DOCK8 was shown to be important for Treg cell stability at sites of allergic inflammation and for the generation, survival, and suppressive activity of inducible Treg cells. Adoptive transfer of wild-type, but not DOCK8-deficient, OVA-specific, inducible Treg cells suppressed allergic inflammation in OVA-sensitized skin of Dock8-/- mice. These mice developed severe allergic skin inflammation and elevated serum IgE levels after topical exposure to Saureus. Both were attenuated after adoptive transfer of WT but not DOCK8-deficient Treg cells. CONCLUSION: Treg cell dysfunction increases susceptibility to allergic skin inflammation in DOCK8 deficiency and synergizes with cutaneous exposure to Saureus to drive eczema in DOCK8 deficiency.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.

BACKGROUND: Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus' spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19. METHOD: This cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760. RESULTS: This study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19. CONCLUSION: Our study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.

Early predictors of colchicine resistance in familial Mediterranean fever.

OBJECTIVE: To explore early features that can predict colchicine resistance in familial Mediterranean fever (FMF) patients. METHODS: It included FMF cases who fulfilled the Yalcinkaya-Ozen criterion and were on colchicine for at least 6 months. Data were collected from medical files and interpreted with respect to clinical parameters, incluing the auto-inflammatory diseases activity index (AIDAI) and FMF severity score. FMF50 score assessed the treatment response. Laboratory findings and genetic analysis of Mediterranean fever (MEFV) mutations were evaluated according to the standard technique. Patients were classified into two groups according to their response to colchicine. Both groups were compared, and significant variables were entered into a logistic regression model to detect independent predictors. The diagnostic accuracy of these predictors was assessed using the receiver operating characteristic curve. RESULTS: In all, 120 FMF children were included. After the exclusion of 16 non-compliant patients (13.3%), colchicine responders were 66 (63.4%) (group I) and colchicine-resistant cases (group II) were 38 (36.5%). The fever duration after colchicine, number of attacks before/after colchicine, skin rash/erysipelas-like erythema, myalgia/protracted febrile myalgia, AIDAI before/after treatment, FMF severity score, and the maximum colchicine dose were higher in group II. Furthermore, high C-reactive protein and neutropenia were frequent in group II. However, different MEFV mutations, including M694V were similar between the two groups. Eight variables were detected in the regression analysis model, and independent predictors were utilized to generate a scoring model. CONCLUSION: This study constructed a prediction model for colchicine nonresponse based on clinical and laboratory profiles. This model will be valuable for the treatment decisions of FMF children.

Digenic inheritance of IL-36RA and SEC61A1 mutations underlies generalized pustular psoriasis with hypogammaglobulinemia.

We report a female patient presenting with generalized pustular psoriasis and hypogammaglobulinemia due to digenic mutations in IL-36RA and SEC61A1. The patient presented with recurrent fevers, elevated inflammatory markers, hepatosplenomegaly, and recurrent sinopulmonary infections in the context of hypogammaglobulinemia which improved on immunoglobulin replacement. This report demonstrates how digenic inheritance leads to complex phenotypes, and illustrates the importance of following an unbiased approach to identifying variants, especially in patients with atypical clinical presentations.

Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry.

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD.

Thoracic Fluid Content in Neonates Presented with Respiratory Distress as a Predictive Tool for Transient Tachypnea of Newborn.

INTRODUCTION: Respiratory conditions are the most common reason for admission of newborns to a neonatal care unit. The index of contractility (ICON) can be used to measure the thoracic fluid content (TFC) in neonates which is a significant parameter in cases presented with transient tachypnea of newborn (TTN). OBJECTIVE: The objective was to compare TFC between newborn infants with TTN compared with other causes of respiratory distress (RD). We tested the hypothesis that TFC would be higher in infants with TTN. STUDY DESIGN: In total, 105 newborns were enrolled at the delivery room and were categorized into three groups: TTN, other causes of RD, and control, according to physical examination and Chest X-Ray. TFC was measured within the first 6 hours for all infants and at 24 and 48 hours for the first two groups. RESULTS: Demographic data showed higher male participants and use of antenatal steroid therapy in RD groups. TFC within the first 6 hours was higher in RD groups. However, TFC at 24 hours of ≤24 mL/kg, and TFC drop rate at 24 hours of >12% are statistically significant discriminators of TTN from non-TTN, with sensitivity and specificity of 97.1 and 47.1%, and 60 and 82.4%, respectively (Fig 1 and 2). CONCLUSION: ICON can be used in conjunction with clinical parameters and CXR as a tool for differentiation between TTN and other causes of RD within the first 24 hours of life by using the cutoff value of TFC at 24 hours and TFC drop rate. This will allow earlier and optimum management of different causes of RD. KEY POINTS: · Thoracic fluid content. · Neonatal respiratory distress. · Newborn.

Cardiac implications of multisystem inflammatory syndrome associated with COVID-19 in children under the age of 5 years.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is responsible for significant lung disease in adults. Despite mild manifestations in most children, multisystem inflammatory syndrome (MIS-C) associated with COVID-19 is well described in older children with cardiac manifestations. However, MIS-C-related cardiac manifestations are not as well described in younger children. METHODS: The study is a retrospective analysis of MIS-C patients under the age of 5 years admitted between May and November 2020 to a single centre. Included cases fulfilled the case definition of MIS-C according to Royal College of Pediatrics and Child Health criteria with laboratory, electrocardiogram, or echocardiographic evidence of cardiac disease. Collected data included patients' demographics, laboratory results, echocardiographic findings, management, and outcomes. RESULTS: Out of 16 MIS-C cases under 5 years of age, 10 (62.5%) had cardiac manifestations with a median age of 12 months, 9 (90%) were previously healthy. Cardiac manifestations included coronary arterial aneurysms or ectasia in five (50%) cases, two (20%) with isolated myopericarditis, coronary ectasia with myocarditis in two (20%), and supraventricular tachycardia in one (10%). Intravenous immunoglobulins were given in all cases with coronary involvement or myocarditis. The median duration of hospitalisation was 7 (6-14) days; two (20%) cases with cardiac disease were mechanically ventilated and mortality in MIS-C cases below 5 years was 12.5%. Normalisation of systolic function occurred in half of the affected cases within 1 week and reached 100% by 30 days of follow-up. CONCLUSIONS: MIS-C associated with SARS-CoV-2 has a high possibility of serious associated cardiac manifestations in children under the age of 5 years with mortality and/or long-term morbidities such as coronary aneurysms even in previously healthy children.

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity.

BACKGROUND: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. METHODS: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. RESULTS: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). CONCLUSIONS: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.

Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency.

BACKGROUND: Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentially life-threatening complication, but studies focusing on large cohorts of patients transplanted for primary immunodeficiency are lacking. OBJECTIVES: This study sought to determine the incidence, risk factors, and outcomes of post-HCT AIC and B-lymphocyte function following rituximab. METHODS: We retrospectively studied 502 children with primary immunodeficiency who were transplanted at our center between 1987 and 2018. RESULTS: Thirty-six patients (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, anti-thymocyte antiglobulin, and acute and chronic graft versus host disease were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (subdistribution hazard ratio, 9.0; 95% CI, 1.50-54.0; P = .02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin achieved remission in 50% (n = 18), additional rituximab led to remission in 25% (n = 9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n = 5), bortezomib (n = 3), mycophenolate mofetil (n = 2), splenectomy (n = 2), and second HCT (n = 3). The mortality of post-HCT AIC reduced from 25% (4 of 16) prior to 2011 to 5% (1 of 20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, and 4 were in remission with ongoing sirolimus and low-dose steroids. Of the 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on intravenous immunoglobulin replacement, 2 had second HCT, and 3 died. CONCLUSIONS: The frequency of post HCT AIC in our cohort was 9%, and the most significant risk factors for its occurrence were the presence of graft versus host disease and the use of alemtuzumab.

Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2).

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a syndrome with pleiotropic manifestations including vasculitis and hematologic compromise. A systematic definition of the relationship between adenosine deaminase 2 (ADA2) mutations and clinical phenotype remains unavailable. OBJECTIVE: We sought to test whether the impact of ADA2 mutations on enzyme function correlates with clinical presentation. METHODS: Patients with DADA2 with severe hematologic manifestations were compared with vasculitis-predominant patients. Enzymatic activity was assessed using expression constructs reflecting all 53 missense, nonsense, insertion, and deletion genotypes from 152 patients across the DADA2 spectrum. RESULTS: We identified patients with DADA2 presenting with pure red cell aplasia (n = 5) or bone marrow failure (BMF, n = 10) syndrome. Most patients did not exhibit features of vasculitis. Recurrent infection, hepatosplenomegaly, and gingivitis were common in patients with BMF, of whom half died from infection. Unlike patients with DADA2 with vasculitis, patients with pure red cell aplasia and BMF proved largely refractory to TNF inhibitors. ADA2 variants associated with vasculitis predominantly reflected missense mutations with at least 3% residual enzymatic activity. In contrast, pure red cell aplasia and BMF were associated with missense mutations with minimal residual enzyme activity, nonsense variants, and insertions/deletions resulting in complete loss of function. CONCLUSIONS: Functional interrogation of ADA2 mutations reveals an association of subtotal function loss with vasculitis, typically responsive to TNF blockade, whereas more extensive loss is observed in hematologic disease, which may be refractory to treatment. These findings establish a genotype-phenotype spectrum in DADA2.

Does Taper Design Affect Taper Fretting Corrosion in Ceramic-on-Polyethylene Total Hip Arthroplasty? A Retrieval Analysis.

BACKGROUND: Ceramic-on-polyethylene (CoP) implants have exhibited lower fretting and corrosion scores than metal-on-polyethylene implants. This study aims at investigating the effect of taper design on taper corrosion and fretting in modular CoP total hip arthroplasty (THA) systems. METHODS: Under an institutional review board--approved protocol, a query of an implant retrieval library from 2002 to 2017 identified 120 retrieved CoP THA systems with zirconia toughened alumina femoral heads. Femoral stem trunnions were visually evaluated and graded for fretting, corrosion, and damage at the taper interface. Medical records were reviewed for patient demographics and implant characteristics. Data were statistically analyzed using Spearman correlation and rank-sum tests with a Dunn's post hoc test, with a significance level of α = 0.05. RESULTS: Four different taper designs were evaluated: 11/13 (n = 18), 12/14 (n = 53), 16/18 (n = 21), and V40 (n = 28). There were no statistically significant demographic differences between taper groups for duration of implantation, laterality, patient age, and patient sex, but patients with 16/18 tapers had a higher body mass index than V40 tapers (P = .012). Duration of implantation had a weak positive correlation with both trunnion fretting (ρ = 0.224, P = .016) and corrosion (ρ = 0.253, P = .006). Summed fretting and corrosion scores were significantly greater on the V40 and 16/18 tapers compared with the 12/14 tapers (all P ≤ .001). CONCLUSION: Taper fretting and corrosion were observed in CoP THA implants and were greatest with V40 and 16/18 tapers and lowest with 12/14 tapers. Differences in taper design characteristics may lead to greater micromotion at the taper-head interface, leading to increased fretting and corrosion.

Multidrug-Resistant Organisms in the Setting of Periprosthetic Joint Infection-Diagnosis, Prevention, and Treatment.

BACKGROUND: Periprosthetic joint infection (PJI) is a rare yet challenging problem in total hip and knee arthroplasties. The management of PJI remains difficult primarily due to the evolution of resistance by the infecting organisms. METHODS: This review profiles acquired mechanisms of bacterial resistance and summarizes established and emerging techniques in PJI diagnosis, prevention, and treatment. RESULTS: New techniques in PJI diagnosis and prevention continue to be explored. Antibiotics combined with 1 or 2-stage revision are associated with the higher success rates and remain the mainstay of treatment. CONCLUSION: With higher prevalence of antibiotic-resistant organisms, novel antibiotic implant and wound care materials, improved methods for organism identification, and well-defined organism-specific treatment algorithms are needed to optimize outcomes of PJI.

Cost Analysis, Complications, and Discharge Disposition Associated With Simultaneous vs Staged Bilateral Total Knee Arthroplasty.

BACKGROUND: Simultaneous vs staged bilateral total knee arthroplasty (BTKA) has long been debated. The primary objective of this study was to compare actual hospital costs and complication rates in patients undergoing simultaneous BTKA (simBTKA) and staged BTKA (staBTKA) at a single institution. METHODS: A total joint arthroplasty database from a single hospital was used to identify all patients who underwent primary BTKA from 2013 to 2016 and divided into simultaneous and staged groups. StaBTKA patients were included if both procedures were performed within 1 year by the same surgeon. The combined total hospital cost of both procedures was used, and inpatient rehabilitation (IPR) costs were added for all patients discharged to IPR. RESULTS: There were 225 simBTKA and 337 staBTKA patients. SimBTKA patients were younger (61 ± 8 vs 66 ± 8 years, P < .001), had lower body mass index (31.3 ± 5.9 vs 34.0 ± 7.2, P < .001), were more predominately male (48% vs 38%, P = .029), and more likely to require IPR as compared with staBTKA patients. There was no difference in total hospital cost for simBTKA as compared with staBTKA ($24,596 ± $5652 vs $24,915 ± $5756, P = .586). Complications were more prevalent in the simBTKA group, including venous thromboembolism (5.4% vs 1.4%, P = .006) and blood transfusions (15.8% vs 6.2%, P < .001). CONCLUSION: There were higher complication rates with no significant cost savings in actual hospital costs associated with simBTKA, when accounting for the cost of IPR, as compared with staBTKA. The total cost analysis of simBTKA vs staBTKA, using actual cost data, merits further evaluation.

Four Weeks in a Single-Leg Weight-Bearing Hip Spica Cast is Sufficient Treatment for Isolated Femoral Shaft Fractures in Children Aged 1 to 3 Years.

BACKGROUND: Hip spica casting regimens for the treatment of femoral shaft fractures in a pediatric population aged 1 to 3 years vary. Patient charts were reviewed to determine if there are any clinical differences between 3 and 4 weeks in an ambulatory single-leg hip spica (SLHS) cast versus 6 to 8 weeks in a standard double-leg, non-weight-bearing hip spica cast. METHODS: The medical records of 109 patients with femoral shaft fractures treated with a hip spica casting from January 1, 2008 to December 31, 2011 were examined. After exclusions, 94 patients were eligible for inclusion in the study. Patient records were assessed, noting age, weight, type of cast, time in cast, and complications. All casts were applied by senior pediatric orthopaedic surgeons at a single institution. RESULTS: Two groups were evaluated: 59 patients in the SLHS group and 35 in the double-leg hip spica group. The 2 groups were demographically similar with an average age of 2 years, 70.2% of patients were male, 45.7% were black, and 35.1% were white. The average time to cast removal was 4.1 weeks for the single-leg group and 5.3 weeks for the double-leg group (P<0.001). Both groups had similar low rates of loss of reduction. The double-leg group had a significantly higher incidence of clinically significant limb-length discrepancy (7/35, 20%), compared with the single-leg group (1/59, 1.7%, P=0.004). In addition, the double-leg group also had more skin problems (11/35, 31.4%) compared with the single-leg group (6/59, 10.2%, P=0.013). Seventeen patients in the single-leg group were documented as walking in the cast as compared with no patients in the double-leg group (P<0.001). CONCLUSIONS: Patients treated with a single-leg spica cast for 4 weeks had fewer complications than patients treated in a traditional double-leg cast. Femoral shaft fractures in patients less than 4 years old can be treated in a weight-bearing SLHS casts for approximately 4 weeks with fewer alignment and skin complications. LEVEL OF EVIDENCE: Level III-clinical retrospective comparative study.

Long noncoding RNAs (CTC-471J1.2, NeST) as epigenetic risk factors of active juvenile lupus nephritis: a case-control study.

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.

Offset Acetabular Liners: Safer Than Previously Thought.

High offset liners help to restore soft tissue tension after primary total hip arthroplasty (THA). However, prior research has reported increased rates of aseptic loosening when using offset components. The purpose of this study was to examine the postoperative complication and revision rates of neutral vs offset acetabular liners at our institution. Two hundred eight primary THAs in 206 patients performed between 2016 and 2018 using neutral or offset liners were reviewed. All patients had a minimum 2-year clinical follow-up (mean, 3.3 years; range, 2.0-5.7 years). Postoperative complications and revision surgeries were reviewed. All offset liners were 4 mm in thickness. Twelve (10.0%) complications occurred in the neutral liner group, and 13 (14.8%) complications occurred in the offset liner group. Two cases of aseptic loosening occurred in the neutral liner group, with no cases reported in the offset liner group. Nine cases (7.5%) in the neutral group required revision surgery, whereas 3 cases in the offset group required revision surgery. Chi-square analysis found no difference between the groups in the rate of postoperative complications, χ2 (1, N=208)=1.09 (P>.05), or the rate of revision, χ2 (1, N=208)=1.56 (P>.05). We found no significant differences between the neutral and offset groups regarding the rates of postoperative complications, aseptic loosening, or revision surgery. Our findings suggest that contemporary high offset liners, up to 4 mm, are safe and effective when attempting to restore native hip mechanics after THA. [Orthopedics. 2023;46(5):e298-e302.].

How multisystem inflammatory syndrome in children discriminated from Kawasaki disease: a differentiating score based on an inception cohort study.

BACKGROUND: About 25-50% of multisystem inflammatory syndrome in children (MIS-C) patients meet the criteria for diagnosis of Kawasaki disease (KD). The differentiation of both conditions is so challenging on clinical practice as the management of both is time dependant and precise diagnosis is fundamental. METHOD: Data were collected from children < 18 years old hospitalized with MIS-C or KD. Patient demographics, clinical, and laboratory data were compared, and a discrimination score was created to assist in clinical differentiation. RESULTS: 72 patients with MIS-C and 18 with KD were included in the study. Patients with MIS-C had a higher prevalence of abdominal pain (p = 0.02), vomiting (p = 0.03), and cervical lymphadenopathy (p = 0.02) compared with KD cases. MIS-C patients had higher liver enzymes (aspartate aminotransferase (AST) (p = 0.04), alanine aminotransferase (ALT) (p = 0.03), serum creatinine (p = 0.03), and lower platelet count nadir (p = 0.02) than KD. Four variables were detected in the regression analysis model, and the independent predictors were utilized to generate a scoring model that distinguished MIS-C from KD with an area under the curve of 0.70. CONCLUSION: This study constructed a prediction model for differentiation of MIS-C from KD based on clinical and laboratory profiles. This model will be valuable to guide clinicians in the treatment decisions. Key Points • Children with MIS-C are more likely to have gastrointestinal symptoms, cervical lymphadenopathy, and respiratory involvement than KD patients. • Elevated liver enzymes and lower platelet count are more pronounced laboratory findings in MIS-C than KD. • This study constructed a prediction model for differentiation of MIS-C from KD based on clinical and laboratory profiles. This model will be valuable to guide clinicians in the treatment decisions.

Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients.

Background Parasites are well-known immune-modulators. They inhibit some aspects of the immune system to ensure persistence inside the host for a long time; meanwhile, they stimulate other immune aspects to assure the survival of the host. Wide variations in the severity of coronavirus disease 2019 (COVID-19) among developed and developing countries were reported during the COVID-19 pandemic. Parasitic infections, including Toxoplasma gondii (T. gondii), were claimed to contribute to such variations. Methods To explore a possible relationship between latent toxoplasmosis and COVID-19 severity, our study included 44 blood samples from moderate/severe COVID-19 patients, who were admitted to Mansoura University Hospitals, Egypt, during the pandemic. Patients' sera were screened for Toxoplasma IgG antibodies using ELISA (Roche Diagnostics, Indianapolis, USA), and the gene expression of important immune markers (iNOS, arginase-1, IFN-γ, TNF-α, IL-6, IL-10, and TGF-ß) was checked using real-time quantitative PCR. Clinical and laboratory data were obtained from the patients' medical records. Results Toxoplasma IgG antibodies were detected in 33 (75%) of patients. None of the studied clinical or laboratory parameters showed any significant changes in relation to toxoplasmosis seroprevalence. Further classification of the patients according to COVID-19 severity and Toxoplasma seroprevalence did not reveal any changes related to toxoplasmosis as well. Conclusion Our study indicates that latent toxoplasmosis has no effect on the severity of COVID-19.