A Study on Semaphorin 3A Level in Juvenile-onset Systemic Lupus Erythematosus Patients.

BACKGROUND: Juvenile-onset systemic lupus erythematosus (jSLE) is an uncommon yet severe autoimmune/inflammatory condition affecting multiple bodily systems, typically manifest-ing before the age of 18. This disease exhibits significant complexity, displaying considerable variation among patients. Its effects can range in severity from minor to fatal, characterized by a pattern of recurring flare-ups and periods of remission, making its natural progression difficult to predict. AIM OF THE WORK: The aim of this work is to investigate the correlation between semaphorin 3A and systemic lupus erythematosus patients who follow up at Pediatric Rheumatology Unit Chil-dren's Hospital at Cairo University. PATIENTS & METHODS: This cross-sectional research was performed at the Pediatric Rheumatology Unit Cairo University Children's Hospital and included cases with jSLE under treatment and fol-low-up from the period of August 2021 to August 2022. RESULTS: Regarding demographic data of the studied subjects, highly significant variances were noted among the patient group & control group regarding age (years) & sex. However, there were non-significant variances among the patient group and control group concerning weight. In the current research, median (IQR) onset of disease was 2 (1 3) years, mean ± SD age at dis-ease diagnosis was 8.98 ± 2.13 years, median (IQR) disease duration 2 (1 3) years, family history was negative in 36 (90.0%) patients and consanguinity was negative in 28 (70.0%). The distribution of the manifestations within the patients group was as follow 7 (17.5%) with mu-cocutaneous, 7 (17.5%) with vasculitis, 4 (10.0%) with serositis, 11 (27.5%) with cardiac, 17 (42.5%) with renal, 11 (27.5%) with GIT, 5 (12.5%) with hematological, and 4 (10.0%) with neu-rological manifestations. In addition, there were 2 (5.0%) with arthritis, 31 (77.5%) with arthral-gia, and 2 (5.0%) with fever mean ± SD systolic BP was 115.95 ± 8.38 & mean ± SD diastolic BP was 75.60 ± 6.11. Regarding treatments in the patients' group, the median steroid dose was 15mg (5-25) with medi-an duration of 2 (1 3), 38 (95.0%) patients received hydroxychloroquine with mean ± SD hy-droxychloroquine dose of 205.26 mg ± 51.71. 23 (57.5%) patients received cyclophosphamide with mean ± SD number of cyclophosphamide doses 7.17 mg ± 2.42. Mycophenolate was re-ceived in 27 (67.5%) with mean ± SD dose of 614.07 mg ± 225.85. There were highly statistically significant differences between control group and patients' group concerning TLC, creatinine, & ESR. Highly statistically significant variance was noted among the control group and patients group concerning CRP. Regarding the patients' group, the mean ± SD serum C3 was 99.89 mg/dl ± 28.45, median (IQR) serum C4 was 14.5 mg/dl (8.8 25.5), and median (IQR) albumin creatinine ratio was 27 IU/ML (16 186). There was positive ANA with titre and pattern in 34 patients (85.0%), positive antids-DNA in 25 patients (62.5%), and positive anticardiolipin IgM and IgG in 5 patients (12.5%). Renal biopsy was found to be normal in 23 (57.5 percent), lupus nephritis class II, III in 3 (7.5 percent), lupus nephritis class III in 10 (25.0%), and lupus nephritis class IV in 4 (10.0%). Urine analysis results showed the following: normal in 28 (70.0%), albumin in 2 (5.0%), casts in 2 (5.0%), pus cell in 4 (10.0%), albumin + casts in 2 (5.0%) and albumin + pus cell in 2 (5.0%). Regarding semaphorin 3A level, a highly statistically significant variance was noted among the control & patients group concerning semaphorin 3A level found to be lower in cases than control with a p-value below 0.001. In patients' group, a negative correlation for semaphorin 3A with SBP, DBP, AST and ESR and also a positive correlation with steroid duration in the studied pa-tients. In addition, highly significant association between semaphorin 3A & positive CRP. How-ever, no significant relationship between semaphorin 3A & SLE manifestations except arthritis was found related to semaphorin 3A level. ROC curve shows that the semaphorin 3A cut-off point to predict SLE ≤ 3 with sensitivity = 47.50, specificity=92.50, PPV=86.4, and NPV=63.8. CONCLUSION: Reduced plasma Semaphorin 3A levels were found in this study; furthermore, their clinical relationship in SLE proposes their significant job in this illness. Furthermore, the ROC results demonstrated that Semaphorin 3A could be a new symptomatic biomarker in SLE with very high sensitivity for the determination of SLE, demonstrating that they might be helpful bi-omarkers for the evaluation of SLE. However, extra studies that focus on the potential role of Semaphorin 3A in SLE are needed.

Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.

INTRODUCTION/AIMS: Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1. METHODS: Two individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES). RESULTS: The two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon. DISCUSSION: Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.

[Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report].

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 |IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

Angiogenesis Inhibitor Drug-induced Benign Migratory Glossitis in a Patient of Juvenile-onset Recurrent Respiratory Papillomatosis under Maintenance Therapy.

Background: Benign migratory glossitis or geographic tongue is a chronic recurring inflammatory condition of the oral cavity. With its ephemeral characteristics, there has been reported literature showing its association with the administration of certain drugs including angiogenesis inhibitors. The antiangiogenic drugs act by selectively inhibiting the vascular endothelial growth factor (VEGF) signaling. It has been widely used as an adjunct and a maintenance agent for the treatment of various cancers. Aims: This study aims to report probable characteristic oral mucosal changes in a patient with juvenile-onset recurrent respiratory papillomatosis (JORRP) under maintenance therapy with an antiangiogenesis drug. Case description: The patient was presented with a burning sensation on having spicy food. This occurred after the completion of three cycles of bevacizumab infusion. It was associated with the appearance of migratory lesions over the tongue and evolved periods of remission and exacerbation. Clinical examination revealed lesions characteristic of the geographic tongue on the anterior two-thirds of the dorsal surface as well as the lateral surface of the tongue classified as type 2, according to Hume criteria. Oral examination revealed dental caries in relation to 52, 54, 62, 63, 74, and 85 teeth and grossly decayed 64. Topical lignocaine gel was instituted for symptomatic relief of the lesion. Full mouth rehabilitation with preventive and restorative therapeutic interventions was carried out. Clinical significance and conclusion: The documented literature along with this report put forth a probable association of geographic tongue with the use of bevacizumab drugs which requires further detailed studies. These lesions generally require symptomatic treatment with assurance only. The etiology is poorly understood. How to cite this article: Kalra N, Tyagi R, Khatri A, et al. Angiogenesis Inhibitor Drug-induced Benign Migratory Glossitis in a Patient of Juvenile-onset Recurrent Respiratory Papillomatosis under Maintenance Therapy. Int J Clin Pediatr Dent 2024;17(1):92-96.

Type I interferon associated epistasis may contribute to early disease-onset and high disease activity in juvenile-onset lupus.

Pathologic type I interferon (T1IFN) expression is a key feature in systemic lupus erythematosus (SLE) that associates with disease activity. When compared to adult-onset disease, juvenile-onset (j)SLE is characterized by increased disease activity and damage, which likely relates to increased genetic burden. To identify T1IFN-associated gene polymorphisms (TLR7, IRAK1, miR-3142/miR-146a, IRF5, IRF7, IFIH1, IRF8, TYK2, STAT4), identify long-range linkage disequilibrium and gene:gene interrelations, 319 jSLE patients were genotyped using panel sequencing. Coupling phenotypic quantitative trait loci (QTL) analysis identified 10 jSLE QTL that associated with young age at onset (<12 years; IRAK1 [rs1059702], TLR7 [rs3853839], IFIH1 [rs11891191, rs1990760, rs3747517], STAT4 [rs3021866], TYK2 [rs280501], IRF8 [rs1568391, rs6638]), global disease activity (SLEDAI-2 K >10; IFIH1 [rs1990760], STAT4 [rs3021866], IRF8 [rs903202, rs1568391, rs6638]), and mucocutaneous involvement (TLR7 [rs3853839], IFIH1 [rs11891191, rs1990760]). This study suggests T1IFN-associated polymorphisms and gene:gene interrelations in jSLE. Genotyping of jSLE patients may allow for individualized treatment and care.

A case of juvenile-onset ankylosing spondylitis effectively treated with tumour necrosis factor-alpha inhibitor agents.

A 15-year-old girl had experienced hip pain at 11 years of age. At 15 years of age, the patient complained of persistent generalised pain. Her rheumatoid factor and serum matrix metalloproteinase-3 levels were below standard values; there were no inflammatory responses, and the human leukocyte antigen test was negative for B27 and positive for B52 and B62. The bath ankylosing spondylitis disease activity index (BASDAI) value was 8.0 at the time of induction and 3.1 at 6 months after the introduction of adalimumab (at a dose of 40 mg). The BASDAI value improved with an increase in the dose of adalimumab to 80 mg at 8 months after the initial introduction of adalimumab (at 40 mg), although it remained at 4.8 at 16 months after the dose increase. The BASDAI value was 2.6 at 6 months, 2.7 at 1 year, and 1.8 at 1.5 years after the introduction of infliximab, indicating that the patient had progressed well without any adverse events. Based on this case, juvenile ankylosing spondylitis is a differential diagnosis for low back pain and generalised pain since childhood. Tumour necrosis factor (TNF) inhibitors were promptly introduced in this case, although it took 4 years from the initial presentation. TNF inhibitors were effective in treating juvenile ankylosing spondylitis in the present case without any adverse events. This case is notable because juvenile onset ankylosing spondylitis is one of the reasons for severe lumbago since childhood and because TNF inhibitors were administered promptly after diagnosis.

Factors associated with early-onset intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Recently, the importance of attribute-based medicine has been emphasized. The effects of early-onset intracranial aneurysms on patients can be significant and long-lasting. Herein, we compared the factors associated with intracranial aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) according to age categories (≥ 50 years, < 50 years). METHODS: We included 519 ADPKD patients, with a median age of 44 years, estimated glomerular filtration rate of 54.5 mL/min/1.73 m2, and total follow-up duration of 3104 patient-years. Logistic regression analyses were performed to determine factors associated with intracranial aneurysms. RESULTS: Regarding the presence of intracranial aneurysm, significant interactions were identified between the age category (age ≥ 50 years), female sex (P = 0.0027 for the interaction) and hypertension (P = 0.0074 for the interaction). Female sex and hypertension were associated with intracranial aneurysm risk factors only in patients aged ≥ 50 years. The presence of intracranial aneurysm was significantly associated with chronic kidney disease (CKD) stages 4-5 (odds ratio [OR] = 3.87, P = 0.0007) and family history of intracranial aneurysm or subarachnoid hemorrhage (OR = 2.30, P = 0.0217) in patients aged < 50 years. For patients aged ≥ 50 years, in addition to the abovementioned factors [OR = 2.38, P = 0.0355 for CKD stages 4-5; OR = 3.49, P = 0.0094 for family history of intracranial aneurysm or subarachnoid hemorrhage], female sex (OR = 4.51, P = 0.0005), and hypertension (OR = 5.89, P = 0.0012) were also associated with intracranial aneurysm. CONCLUSION: Kidney dysfunction and family history of intracranial aneurysm or subarachnoid hemorrhage are risk factors for early-onset intracranial aneurysm. Patients aged < 50 years with a family history of intracranial aneurysm or subarachnoid hemorrhage or with CKD stages 4-5 may be at an increased risk of early-onset intracranial aneurysm.

Laryngeal Suction tube: A Novel Technique for Tracheal Ventilation in an Obstructed Airway in a Child with Respiratory Papillomatosis.

Background: Airway obstruction in a child requires expedite management in addition to comprehensive discussion between the Otolaryngology and Anaesthesiology team to formulate a treatment plan to ensure safe airway. Juvenile-onset recurrent respiratory papillomatosis (JORRP) is an exophytic benign laryngeal lesion which poses a great challenge when presented with respiratory distress. Objective: This paper presents a novel, safe and cost-effective approach to temporary tracheal ventilation of the obstructed airway in a child with juvenile-onset recurrent respiratory papillomatosis using the laryngeal suction tube connected to general anaesthetic (GA) machine. Result and Conclusion: Rigid laryngeal suction tube is placed through the side-port of Lindholm laryngoscope and connected to breathing circuit of GA machine. Manual bagging ventilation with 100% FiO2 achieved good oxygenation throughout the debulking of the papilloma without hindering the surgical field. Our technique utilizes the readily available equipment whilst enabling safe anaesthesia and providing good surgical field during excision of obstructive papillomatous airway lesion.

Presence of tubuloreticular inclusions in ultrastructural studies of renal biopsies in children with lupus nephropathy - one-center preliminary study.

Introduction: Juvenile systemic lupus erythematosus (jSLE) is an autoimmune disease that develops as a result of multi-level immune dysregulation, including the interferon pathway. Nephropathy develops at an early stage and eventually affects 90% of patients. A renal biopsy allows one to classify lupus nephritis and determine the proper treatment. Biopsy assessment should be done not only in a light microscope but also in a transmission electron microscope (TEM). Its usage may reveal the presence of intracellular tubuloreticular inclusions (TRIs), considered as a morphological marker of interferon hyperactivity. Material and methods: Renal biopsies of 10 children with jSLE and nephropathy were analyzed in TEM. The location, structure, and size of TRIs were assessed. Demographic data, nephropathy manifestation, non-renal symptoms, and serological activity of lupus were analyzed. Results: All the patients were female with an average onset at 12.7 years of age and met SLE criteria. Nephropathy manifested with proteinuria (n = 10) and hematuria (n = 6). Glomerular filtration rate (GFR) was normal in all patients. In three children with early disease onset, it manifested with hematological disorders. TRIs were revealed in 7 biopsies, with the highest expression in the youngest children, with peripheral cytopenia, membranous glomerulonephritis, and lupus nephritis. Conclusions: Demonstration of TRIs in renal biopsies of children with juvenile systemic lupus may confirm the diagnosis of lupus nephritis and is a sign of involvement of the interferon pathway at the early stage of the disease.

Gonioscopy-assisted transluminal trabeculotomy for open-angle glaucoma with failed incisional glaucoma surgery: two-year results.

BACKGROUND: To evaluate the safety and efficacy of gonioscopy-assisted transluminal trabeculotomy (GATT) in treating patients with open-angle glaucoma (OAG) who had failed prior incisional glaucoma surgery. METHODS: A consecutive case series of OAG patients aged ≥ 18 who underwent GATT with previous failed glaucoma incision surgery was retrospectively analyzed. Main outcome measures included intraocular pressure (IOP), the number of glaucoma medications, surgical success rate, and occurrence of complications. Success was defined as an IOP of ≤ 21 mmHg and a reduction of IOP by 20% or more from baseline with (qualified success) or without (complete success) glaucoma medications. For eyes with preoperative IOP of < 21 mmHg on 3 or 4 glaucoma medications, postoperative IOP of ≤ 18 mmHg without any glaucoma medications was also defined as complete success. RESULTS: Forty-four eyes of 35 patients (21 with juvenile-onset open-angle glaucoma and 14 with adult-onset primary open-angle glaucoma) with a median age of 38 years were included in this study. The proportion of eyes with 1 prior incisional glaucoma surgery was 79.5%, and the others had 2 prior surgeries. IOP decreased from 27.4 ± 8.8 mm Hg on 3.6 ± 0.7 medications preoperatively to 15.3 ± 2.7 mm Hg on 0.5 ± 0.9 medications at the 24-month visit (P < 0.001). The mean IOP and the number of glaucoma medications at each follow-up visit were lower than the baseline (all P < 0.001). At 24 months postoperatively, 82.1% of the eyes had IOP ≤ 18 mmHg (versus 15.9% preoperatively, P < 0.001), 56.4% reached IOP ≤ 15 mmHg (versus 4.6% preoperatively, P < 0.001), and 15.4% achieved IOP ≤ 12 mmHg (compared to none preoperatively, P = 0.009). While 95.5% of eyes took 3 or more medications preoperatively, 66.7% did not take glaucoma medication 24 months after GATT. Thirty-four (77.3%) eyes achieved IOP reduction greater than 20% on fewer medications. The complete and qualified success rates were 60.9% and 84.1%, respectively. No vision-threatening complications occurred. CONCLUSIONS: GATT was safe and effective in treating refractory OAG patients who failed prior incisional glaucoma surgery.

Juvenile Huntington's disease in northern Brazil: a case series report / Doença de Huntington juvenil no norte do Brasil: relato de uma série de casos

Introduction: Huntington's disease (HD) is a neurodegenerative disorder caused by CAG expansion repeats in the HTT gene. Usually, the symptoms start to manifest in mid-adulthood. In about 5% of cases, however, the signs begin before the age of 20 years. These cases are known as juvenile HD (JHD). Objective: here we report a case series of JHD from Amazonas, a state where data are scarce due to the restricted access to specialized medical assistance for diagnosis and care. Case series: the patients were attended by neurologists specialized in movement disorders at Manaus. Two cases manifested the disease in childhood (6 and 7 years old) and two cases, in adolescence (12 and 16 years old). All cases showed dystonia and parkinsonism as predominant motor disorders. Moreover, signs of cognitive decline, depression, and psychosis were observed in all patients. Conversely, cerebellar signs, gait disturbances, seizures, and some psychiatric symptoms were variable among the cases. Expansion size varied from 66 to 84 to CAG repeats and the difference in age at onset between parent and child varied from 23 to 43 years. Conclusion: to our knowledge, these are the first clinical reports of JHD in northern Brazil. These cases illustrate the variability in clinical phenotypes and genetic features of JHD cases. Furthermore, they can contribute to the awareness of HD here, both by professionals and the public in general.

Introdução: a doença de Huntington (DH) é um distúrbio neurodegenerativo causado pela expansão de repetições CAG no gene HTT. Geralmente, os sintomas começam a se manifestar na vida adulta tardia. Em cerca de 5% dos casos, no entanto, os sinais começam antes da idade de 20 anos. Esses casos são conhecidos como DH juvenil (DHJ). Objetivo: neste estudo, nós reportamos uma série de casos de DHJ do Amazonas, um estado onde os dados ainda são escassos devido ao acesso restrito à assistência médica especializada para o diagnóstico e cuidado. Série de casos: os pacientes foram atendidos por neurologistas especializados em transtornos do movimento em Manaus. Dois casos manifestaram a doença na infância (6 e 7 anos) e dois casos, na adolescência (12 e 16 anos). Todos os casos apresentaram distonia e parkinsonismo como sintomas motores predominantes. Sinais de declínio cognitivo, depressão e psicose também foram observados em todos os pacientes. Por outro lado, sinais cerebelares, distúrbios da marcha, convulsões e alguns sintomas psiquiátricos foram variáveis entre os casos. O tamanho da expansão CAG variou de 66 a 84 repetições e a diferença na idade de início dos sintomas entre pais e filhos variou de 23 a 43 anos. Conclusão: ao nosso conhecimento, estes são os primeiros relatos clínicos da DHJ na região Norte. Esses casos ilustram a variabilidade nos fenótipos clínicos e nas características genéticas dos casos de DHJ. Além disso, eles podem contribuir para a conscientização da DH na região, tanto pelos profissionais quanto pelo público geral.

The duration of tracheostomy dependence in patients with juvenile-onset recurrent respiratory papillomatosis.

BACKGROUND: Tracheostomy is a vital therapy for juvenile-onset recurrent respiratory papillomatosis (JORRP) to maintain an adequate airway in an emergency, yet the relationship between cannulation duration and prognosis has not been extensively explored. OBJECTIVES: To investigate the predictive influence of the duration of tracheostomy dependence on JORRP remission. MATERIALS AND METHODS: A retrospective review of JORRP patients (n = 77) with tracheostomy treated in Beijing Tongren Hospital was performed. RESULTS: The rate of decannulation was 72.7%. After decannulation for one year, the percentage of distal spread fell from 42.9 to 30.4%. Twenty-six of 77 patients (33.8%) had remission of their disease, 40 (51.9%) continued to have active disease while 11 (14.3%) died during follow-up. The cannulation duration was positively correlated with the overall duration of this disease (r = 0.6). The cut-off point of 34.9 months for cannulation duration indicated the highest predictive value of remission. Duration of cannulation >34.9 months (OR = 0.33) and distal spread (OR = 0.29) decreased odds of remission. CONCLUSION: The study demonstrates that the time span before decannulation indicates the severity of disease and cannulation aggravates the distal spread. Patients with cannulation duration ≤ 34.9 months after tracheostomy are prone to possess a relatively pleasant prognosis.

[Midterm follow-up outcomes of total hip arthroplasty in treatment for patients with juvenile-onset ankylosing spondylitis].

Objective: To assess the midterm follow-up outcomes of total hip arthroplasty (THA) for the treatment of patients with juvenile-onset ankylosing spondylitis (JAS). Methods: The clinical data of 81 patients (127 hips) with JAS (age≤16 years, JAS group) and 267 patients (391 hips) with adult onset ankylosing spondylitis (AAS) (age>16 years, AAS group) between January 2004 and March 2018 were retrospectively analysed. The baseline demographics, clinical, radiographic, and laboratory parameters were collected. Before operation and at last follow-up, the overall disease activity [Bath ankylosing spondylitis disease activity index (BASDAI)] and function status [Bath ankylosing spondylitis functional index (BASFI)], hip subjective score [Harris hip score (HHS)] and objective score [12-item short form health survey (SF-12), including physical component score (PCS) and mental component score (MCS)], and patient satisfaction for THA were reviewed. The major orthopedic complications, including periprosthetic infection, dislocation, periprosthetic fractures, and poor incision healing, were also recorded during the follow-up period. Results: The comparison of preoperative baseline parameters showed that the body mass, body mass index, age of onset, age of surgery, disease duration, and the proportion of combined smoking history in the JAS group were significantly lower than those in the AAS group ( P<0.05), the proportion of bilateral surgeries, proportion of uveitis, proportion of combined family history, C-reactive protein, albumin, and preoperative BASFI were significantly higher than those in the AAS group ( P<0.05). Both groups were followed up. The follow-up time in the JAS group was 29-199 months, with an average of 113 months; in the AAS group was 35-199 months, with an average of 98 months. Incisions in both groups healed by first intention. During the follow-up period, there were 1 case of periprosthetic fracture, 1 case of dislocation, and 1 case of ceramic fragmentation in the JAS group, 1 case of periprosthetic infection and 6 cases of periprosthetic fracture in the AAS group. There was no significant difference in the incidence of complications between the two groups ( P>0.05). At last follow-up, the BASDAI, BASFI, SF-12 MCS, SF-12 PCS, and HHS score of the two groups were significantly improved when compared with those before operation ( P<0.05); but there was no significan difference in the difference of the above parameters before and after operation and the patient satisfaction between the two groups ( P>0.05). Conclusion: The midterm follow-up outcomes of THA for the treatment of JAS patients were reliable. A low age at disease onset did not exert a significant negative effect on THA reconstruction for the treatment of ankylosing spondylitis.

High recurrence rate in patients with juvenile-onset respiratory papillomatosis and its risk factors.

PURPOSE: To identify the recurrence rate and risk factors for recurrence in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). METHODS: A retrospective review was performed for all JORRP patients who underwent surgery between 2002 and 2019 at our institution. The demographic characteristics and clinical parameters were recorded. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze the rate of recurrence and its risk factors. RESULTS: Our study included 721 patients. The cumulative recurrence rates at 1, 5, and 10 postoperative years following initial surgery were 74.2%, 90.0%, and 94.3%, respectively. Age at diagnosis younger than 4.5 years (HR = 2.380, 95% CI [1.169-4.846], P = 0.017), high Derkay anatomical score (HR = 1.136, 95% CI [1.043-1.236], P = 0.003) and HPV type 11 infection (HR = 2.947, 95% CI [1.326-6.551], P = 0.008) were independent risk factors for recurrence. Adjuvant therapy with interferon was less likely to recur (HR = 0.237, 95% CI [0.091-0.616], P = 0.003). Additionally, gender, tracheotomy, mode of delivery, parity, expression of Ki-67, HPV vaccination, and surgical treatment method were not independently associated with recurrence (P > 0.05). CONCLUSION: Age at diagnosis younger than 4.5 years, high Derkay anatomical score and HPV type 11 infection were associated with an increased risk for recurrence in patients with JORRP. Adjuvant therapy with interferon may reduce the risk of recurrence.

A case of juvenile-onset fibrillary glomerulonephritis diagnosed by mass spectrometry and immunohistochemistry of DNAJB9.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease. FGN is characterized by the deposition of randomly arranged, nonbranching microfibrils in the mesangium and glomerular basement membrane. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) in 2017 was a breakthrough, and DNAJB9 has been proven to be extremely useful for the definitive diagnosis of FGN. While FGN often occurs in middle-aged individuals, this case was diagnosed at a relatively young age of 17. We performed renal biopsy, and light microscopic study revealed mesangial proliferation with expansion and subepithelial deposits. Electron microscopic study showed glomerular deposition of randomly oriented nonbranching fibrils with a mean of 20 nm. However, direct first scarlet stain for amyloidosis was weakly positive. Therefore, we confirmed the diagnosis of FGN and eliminated the presence of amyloidosis with mass spectrometry. This is the first case in Japan in which the complication of amyloidosis was ruled out with mass spectrometry and FGN was diagnosed using immunostaining and mass spectrometry of DNAJB9. We began treatment with cyclosporine A. One and a half years after the start of the treatment, kidney function continues to be normal.

A case of juvenile-onset pheochromocytoma with KIF1B p.V1529M germline mutation.

In 2008, a familial noradrenergic pheochromocytoma (PCC) with a KIF1B germline mutation in exon 41 was reported in a 24-year-old female proband and her family. However, in 2020, the same research group reported that the cause of PCC in this family was a MAX germline mutation and was not due to the KIF1B mutation. In this study, we investigated the pathogenicity of a KIF1B germline mutation detected in a 26-year-old woman with juvenile-onset noradrenergic PCC. She was surgically treated and did not have a family history of PCC. We performed whole-exome sequencing, Sanger sequencing, and immunohistochemical and gene expression analyses of catecholamine-synthesizing enzymes. Three tumors with associated somatic mutations were used as the control group. Whole-exome sequencing revealed a p.V1529M KIF1B germline mutation in exon 41 in our patient, and no other associated germline and somatic mutations, including MAX, were detected. Sanger sequencing confirmed the presence of both mutant and wild-type alleles in the tumor. Among the catecholamine-synthesizing enzymes, the expression of phenylethanolamine-N-methyl transferase was suppressed. An in silico analysis of the p.V1529M mutation showed a score suggestive of pathogenicity. After evaluation with the international guideline for sequence variants, p.V1529M mutation was still classified as a variant with uncertain significance; however, our data, including the in silico analysis data, provided certain evidences that met the criteria supporting its pathogenicity. Therefore, this study can support future studies in proving the pathogenicity of the KIF1B p.V1529M mutation.

Tracheotomy as a predictor of remission and demise for juvenile-onset recurrent respiratory papillomatosis.

BACKGROUD: The pros and cons of tracheotomy, as a classic treatment of juvenile-onset recurrent respiratory papillomatosis (JORRP), have gradually been recognized, but the exact impact of tracheotomy on remission and demise is not clear. OBJECTIVES: To investigate the predicting influence of tracheotomy on prognosis for JORRP. MATERIAL AND METHODS: Three hundred forty two patients with JORRP treated in Beijing Tongren Hospital were retrospectively reviewed. The clinical characteristics and prognosis parameters were compared in the group of tracheotomy and non-tracheotomy. RESULTS: The rate of tracheotomy was 24.6% (84/342). Among these patients, 68 (81.0%) developed the tracheal papillomatosis. The onset age of RRP occurred earlier in tracheostomized group, and patients performed tracheotomy needed a greater number of surgeries and developed distal spread more easily (p < .05). The remission rate was significantly lower (35.1 vs. 53.7%) and the mortality higher (13.1 vs. 1.2%) in patients with tracheotomy than non-tracheotomy. Tracheotomy decreased odds of remission (OR = 0.48; 95%CI: 0.28-0.83) and increased odds of demise (OR = 11.98; 95%CI: 3.21-44.65). CONCLUSIONS: The age at diagnosis, the surgical frequency and the medical level of hospital are important factors affecting the occurrence of tracheotomy. Patients who had undergone tracheotomy are prone to possess the low remission rate and high mortality.

Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile-onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children.

BACKGROUND: Genetic variations of neutrophil cytosolic factor 2 (NCF2), a subunit of NADPH oxidase, are usually associated with chronic granulomatous disease, and their relationship with autoimmune disorders through the defective NADPH oxidase function during phagocytosis is suggested. Our study aimed to explore whether there is an association between the non-synonymous single nucleotide polymorphism in the NCF2 gene (rs17849502, NC_000001.11:g.183563445G>T) and the development of juvenile autoimmune rheumatic diseases. METHODS: In order to test this hypothesis, we conducted a pilot case-control study. In total, 709 children and adolescents, all Belarusians, were involved in the study including patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), Kawasaki disease (KD), and subjects without autoimmune and inflammatory diseases as the clinical control, as well as health newborns as the population control. Real-time polymerase chain reaction was used for genotyping. RESULTS: The minor T allele of NCF2 occurred most frequently in patients with JSLE (OR = 2.60, 95% CI = 1.18-5.73, p = 0.023 as compared to the clinical control). In groups with JIA and KD, its frequency did not differ from the control. The TT genotype was only observed in 5.7% of patients with JSLE (p = 0.007), but not in other groups. CONCLUSION: Therefore, our study suggested that NCF2 rs17849502 polymorphism is a potential genetic risk factor for JSLE, while it is probably not for such autoimmune rheumatic diseases as JIA or KD.

Juvenile-onset open-angle glaucoma - A clinical and genetic update.

Juvenile-onset open-angle glaucoma (JOAG) is a subset of primary open-angle glaucoma that is diagnosed before 40 years of age. The disease may be familial or non-familial, with proportions varying among different populations. Myocilin mutations are the most commonly associated. JOAG is characterized by high intraocular pressures (IOP), with many patients needing surgery. The mean age at diagnosis is in the 3rd decade, with a male preponderance. Myopia is a common association. The pathophysiology underlying the disease is immaturity of the conventional outflow pathways, which may or may not be observed on gonioscopy and anterior segment optical coherence tomography. The unique optic nerve head features include large discs with deep, steep cupping associated with high IOP-induced damage. Progression rates among JOAG patients are comparable to adult primary glaucomas, but as the disease affects younger patients, the projected disability from this disease is higher. Early diagnosis, prompt management, and life-long monitoring play an important role in preventing disease progression. Gene-based therapies currently under investigation offer future hope.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Scoping Review from 2009 to 2022.

BACKGROUND: Respiratory recurrent papillomatosis (RRP) is a fatal disease with no known cure. In severe RRP cases, systemic bevacizumab (SB) could be used as adjuvant therapy. OBJECTIVE: This study aims to determine the extent and type of evidence in relation to the clinical outcomes of RRP after SB treatment. METHODS: Participants with RRP of all genders are included in this scoping review. There were no exclusion criteria (country, language, or document type). The information sources included experimental, quasi-experimental, and analytical observational studies. Unpublished data will not be covered, but gray literature was covered. Screening, paper selection, and data extraction were all done by two independent reviewers. This procedure was performed blindly. RESULTS: Of the 175 unique records found, 15 were eligible for inclusion. Fourteen studies were included after applying inclusion and exclusion criteria. Thirty-four patients in these studies came from the United States, India, Germany, Colombia, Argentina, Chile, and Spain. In total, 17 and 34 patients were below 18 years old and were adults respectively. The most commonly reported dose was 10 mg/kg, which was received by 25 (73.5%) patients. According to reports, 58.8% of patients completed the questionnaire. Twelve (35%) patients did not require a repeat surgery. The time interval between surgical procedures has increased for patients who require them. CONCLUSION: SB may be a promissory treatment and control option for RRP. More research is needed to evaluate the efficiency and adverse effects in various populations.