LPS-responsive beige-like anchor gene mutation associated with possible bronchiolitis obliterans organizing pneumonia associated with hypogammaglobulinemia and normal IgM phenotype and low number of B

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs * 2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency. © 2016 Tehran University of Medical Sciences. All rights reserved

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Surgical intervention for treating an extensive internal resorption with unfavorable crown-to-root ratio

Internal resorption is a rare lesion in permanent teeth. Managing perforating internal resorption is a great challenge for dentists. This report presents a successful surgical treatment of a maxillary central incisor that had extensive root perforation due to internal resorption. After unsuccessful nonsurgical approach, during surgical intervention apical part of the resorption defect was removed and the coronal part was filled with mineral trioxide aggregate. Three years later the tooth was symptom free with normal mobility and pocket depth despite unfavorable crown-to-root ratio. This case report have shown that surgical intervention and using mineral trioxide aggregate as root canal filling material in a tooth with extensive internal resorption and unfavorable crown-to-root ratio can be considered as a treatment option

Effect of Occlusal Reduction on Postoperative Pain in Teeth with Irreversible Pulpitis and Mild Tenderness to Percussion

Introduction: Pain management after root canal treatment is a very important issue in clinical practice. The purpose of this study was to evaluate the effect of occlusal reduction on postoperative pain in teeth with irreversible pulpitis and tenderness to percussion. Methods: Fifty-four posterior vital teeth with sensitivity to percussion requiring endodontic treatment were included in this study. After administration of local anesthesia, the root canals were instrumented, and an intracanal calcium hydroxide dressing was 'placed. The patients were randomly divided into 2 groups of 27 each. In 1 group the occlusal surface was reduced (OR group), whereas in the other group the occlusal surface was not modified (no occlusal reduction, NOR group). Each patient was asked to record their postoperative pain on a visual analogue scale with 4 categories at 6 hours, 12 hours, 18 hours, 1 day, and then daily for 6 days after this treatment. Data were analyzed by ttest, Cochran Q, chi(2), and Mann-Whitney tests. Results: Forty-six patients returned the visual analogue scale forms. There was no significant difference in postoperative pain between the 2 groups (P>.05) after root canal preparation and calcium hydroxide dressing. Conclusions: Occlusal surface reduction did not provide any further reduction in postoperative pain for teeth with irreversible pulpitis and mild tenderness to percussion compared with no occlusal reduction. (1 Endod 2013;39:1-5

Wellbeing and burnout amongst interventional radiologists in the United Kingdom

Purpose: To assess the prevalence of burnout amongst Interventional Radiologists (IRs) in the United Kingdom and identify demographic and practice-related stressors that may adversely affect wellbeing. Materials and Methods: A survey of 36 questions were divided into two sections. Section A consisted of 14 questions that assessed demographics and work characteristics; Section B assessed burnout, utilising the 22-item Maslach burnout inventory. Four additional open-ended questions were included to allow participants to voice opinions on the biggest contributors to workplace burnout and plans that could be implemented to alleviate this. The questionnaire was distributed to the British Society of interventional (BSIR) members. The study was conducted between August and September 2022. Results: Moderate to severe scores in emotional exhaustion (EE) were recorded in 65% of participants (moderate 26%; severe 39%) of participants r. Moderate to severe depersonalization (DP) scores were recorded in 46% of participants(moderate 23%; severe 23%). Low-moderate levels of personal accomplishment (PA) scores were recorded in 77% of respondents (low 50%; moderate 27%). Weekly hours and out-of-hour IR cover were statistically significant in predicting emotional exhaustion. Age, sex (male), time available for teaching, and weekly hours were statistically significant in predicting the depersonalisation score. Age was a predictive factor for personal accomplishment. The most recurring themes in open response to major contributors of burnout were shortage of IR clinicians and supporting staff as well as the increasing IR workload. Conclusions: This survey has demonstrated high prevalence of Burnout amongst Interventional Radiologists in UK. Urgent measures are required to tackle the workforce shortage, recognition of IR workload and control IR resources

Genicular artery embolisation in patients with osteoarthritis of the knee (GENESIS) using permanent microspheres: long-term results

Purpose: To report the 2-year follow-up of patients with mild-to-moderate knee osteoarthritis (OA) treated with genicular artery embolisation (GAE) as part of the GENESIS study. Materials and methods: Forty-six patients, median age = 60 (45-83) underwent GAE using permanent microspheres (100-300 μm). Technical success was defined as embolisation of the targeted genicular arteries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) (0-100 mm) were recorded at baseline, 6 weeks, 3 months, 1, 2 years. Contrast-enhanced MRI knee scans were acquired at baseline and 1 year, and evaluated with the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Functional MRI brain imaging and psychometric assessments were undertaken to investigate correlation between neuropsychological phenotypes and clinical outcome. Adverse events were recorded prospectively. Results: Technical success was achieved in forty patients (87%). Mean VAS improved from 58.63 (SD = 20.57, 95% CI 52.7-65.5) at baselines to 37.7 at 2-years (SD = 26.3, 95% CI 27.0-47.5). Whole and subgroup KOOS were significantly improved at each timepoint with associated reductions in analgesia usage. WORMS analysis demonstrated significant reduction in synovitis (p < 0.05) with no cases of osteonecrosis. Self-limiting skin discolouration occurred in four patients. A self-limiting groin haematoma and single case of deep-vein thrombosis due to immobilisation were also recorded. Nine patients subsequently underwent knee arthroplasty with no additional operational complexities identified. Neuropsychometric assessment elucidated a correlation between baseline catastrophising and greater reduction in pain post GAE. Conclusion: GAE is a safe intervention for mild-moderate knee osteoarthritis, with sustained efficacy at 2 years. These results are promising and justify ongoing controlled trials

Phenotyping and follow up of forty-seven Iranian patients with common variable immunodeficiency

Background: Common variable immune deficiency (CVID) is a heterogeneous syndrome with a wide variety of signs and symptoms. This study describes the phenotyping and survival of the CVID patients in the allergy and clinical immunology department of Rasol-E-Akram Hospital of Iran University of Medical Sciences in Tehran. Method: We retrospectively reviewed hospital files of CVID patients in our department until January 2014. All patients were diagnosed with standard diagnostic criteria of CVID, treated and visited monthly, during the follow-up period. We divided the patients into four phenotypes; infection only, cytopenia, polyclonal lymphocytic infiltration and unexplained enteropathy. The immunologic, demographic and clinical findings in different phenotypes were analysed. Results: The study included 47 CVID patients with mean age at onset of symptoms and diagnosis of 11.2 and 20.2 years, respectively. Phenotyping of our patients was: only infection (62), cytopenia (26) and PLI (19) and 94 of cases had only one phenotype. We did not find a significant relation between the clinical phenotypes and immunologic or demographic data. Rate of parental consanguinity in our cases was 47. Parental consanguinity was related to lower age at onset, lower age at diagnosis and higher baseline IgG levels. Patients with malignancy and autoimmunity had significantly higher age at onset. Our patients were followed-up for 6.9 years and the mortality rate during this time was 6. Conclusions: Parental consanguinity and age at onset of CVID symptoms may have important roles in CVID manifestations. © 2015 SEICAP

LPS-responsive beige-like anchor gene mutation associated with possible bronchiolitis obliterans organizing pneumonia associated with hypogammaglobulinemia and normal IgM phenotype and low number of B

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs * 2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency. © 2016 Tehran University of Medical Sciences. All rights reserved