Creutzfeldt-Jakob Disease: A Rare Case of Dementia.

Prion diseases are rare neurodegenerative diseases that have a rapid evolution. Creutzfeldt-Jakob disease (CJD) is the most common and its sporadic form the most frequent. Definitive diagnosis is only obtained through autopsy, and there are currently no available treatments. Here, we present a case of an 84-year-old woman presenting with resting tremor, abnormal gait, frequent falls, apraxia, visual hallucinations, and delirium. There were no signs of relevant metabolic, infectious, or nutritional alterations, and brain computed tomography (CT) scan and magnetic resonance imaging (MRI) had no significant findings. Two months later, the patient was completely immobile with mutism, seizures, and myoclonus. In the presence of a rapidly progressive dementia associated with myoclonus, it was hypothesized that the patient had CJD. The patient's clinical state deteriorated, she died, and autopsy confirmed sporadic CJD. The purpose of this case is to highlight a rare disease that can go undiagnosed because of low awareness and clinical suspicion and the importance of the differential diagnosis of dementia, a common disease at this age.

The impact of nintedanib and pirfenidone on lung function and survival in patients with idiopathic pulmonary fibrosis in real-life setting.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2-5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. METHODS: A real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020. Two groups (under nintedanib or pirfenidone) were analyzed at diagnosis through their clinical features and radiological patterns. Lung function was assessed at diagnosis (time 0) and after 6, 12 and 24 months of treatment. We also compared this antifibrotic cohort with an older naïve antifibrotic cohort, mainly treated with immunosuppressive drugs and/or N- acetylcysteine. Survival was analyzed and prognostic features were also studied. Statistical analysis was performed with IBM® SPSS®. RESULTS: A cohort of 108 patients under antifibrotics (nintedanib n = 54; pirfenidone n = 54) was assessed. Lung function analysis showed an overall stabilization in FVC and DLCO mean predicted percentages at 6, 12 and 24 months of treatment. The mean decline in FVC and DLCO, at 12 months, was -40.95 ± 438.26 mL and -0.626 ± 1.31 mL/min/mmHg, respectively. However, during this period, 34.2% of the patients died mostly due to acute exacerbation associated with a poorer lung function at diagnosis. Mean survival in the naïve antifibrotic cohort was significantly lower than in the antifibrotic cohort (39.9 months versus 58.2 months; p < 0.005). Regarding lung function evolution and survival, we found no differences between definitive or probable UIP radiological patterns, both on patients under nintedanib and pirfenidone (p = 0.656). CONCLUSIONS: In this real-life observational study, the positive impact of antifibrotic therapy on the IPF clinical course and on survival was corroborated. Regarding efficacy, there was no difference between patients taking nintedanib or pirfenidone. The need for an early treatment was also demonstrated, since a worse outcome is clearly associated with lower lung volumes and lower diffusing capacity at diagnosis.

Mortality risk prediction with ILD-GAP index in a fibrotic hypersensitivity pneumonitis cohort.

BACKGROUND: Fibrotic hypersensitivity pneumonitis (fHP) is associated with significant morbidity and mortality. Interstitial lung disease-gender-age-physiology (ILD-GAP) performance in fHP outside the initial cohort was never performed. AIM: To assess the ILD-GAP index's ability to predict mortality in a Portuguese cohort of patients with fHP and analyse whether other clinical variables add value. METHODS: Retrospective analysis of fHP cohort in two Portuguese ILD centres. The baseline ILD-GAP index was calculated. Survival was analysed in months; mortality was the primary outcome. Univariate and multivariate analyses to identify mortality risk factors were performed. RESULTS: A total of 141 patients were included. Fifty-three patients (37.6%) died during the follow-up. The usual interstitial pneumonia (UIP) pattern was found in 49.6%, and their survival was inferior to non-UIP [32 months (interquartile range, IQR = 19, 60) versus 52 months (IQR = 28, 98), p = 0.048]. Patients with an ILD-GAP index higher than three double their risk of mortality [hazard ratio (HR) = 6.48, 95% confidence interval (CI) = (3.03-13.96)] when compared with the patients with an index between 2 and 3 [HR = 3.04, 95% CI = (1.62-5.71)] adjusting for acute exacerbation history. Even though UIP patients had worse survival, it did not reach statistical significance when UIP pattern was added to this model. Acute exacerbation history was an independent risk factor for mortality; however, ILD-GAP still predicted mortality after adjusting for this factor. PaO2 and 6-minute walk test desaturation were not significant risk factors. CONCLUSION: ILD-GAP index is a good predictor for mortality in fHP, even after adjusting for other mortality risk factors.

Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case-control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Single- and multi-locus analyses were performed to investigate the predictive potential of specific variants in IPF susceptibility and survival. Multifactor dimensionality reduction (MDR) was employed to uncover predictive multi-locus interactions underlying IPF susceptibility. The MUC5B rs35705950 SNP was significantly associated with IPF: T allele carriers were significantly more frequent among IPF patients (75.0% vs 20.3%, P < 1.0 × 10-6). Genotypic and allelic distributions of TOLLIP, PLAU, and SERPINB1 SNPs did not differ significantly between groups. However, the MUC5B-TOLLIP T-C-T-C haplotype, defined by the rs35705950-rs111521887-rs5743894-rs5743854 block, emerged as an independent protective factor in IPF survival (HR = 0.37, 95% CI 0.17-0.78, P = 0.009, after adjustment for FVC). No significant multi-locus interactions correlating with disease susceptibility were detected. MUC5B rs35705950 was linked to an increased risk for IPF, as reported for other populations, but not to disease survival. A haplotype incorporating SNPs of the MUC5B-TOLLIP locus at 11p15.5 seems to predict better survival and could prove useful for prognostic purposes and IPF patient stratification. KEY MESSAGES : The MUC5B rs35705950 minor allele is associated with IPF risk in the Portuguese. No predictive multi-locus interactions of IPF susceptibility were identified by MDR. A haplotype defined by MUC5B and TOLLIP SNPs is a protective factor in IPF survival. The haplotype may be used as a prognostic tool for IPF patient stratification.

Detection of SARS-CoV-2 infection in thyroid follicular cells from a COVID-19 autopsy series.

Objective: To understand whether thyroid cells can be directly infected by the SARS-CoV-2 virus and to establish a putative correlation with the expression of the host entry machinery: ACE-2, TMPRSS2, and furin. Methods: We assessed the presence of SARS-CoV-2 virus at the gene level by RT-PCR, viral RNA transcripts localization by in situ hybridization, and by detecting viral proteins by immunohistochemistry for the nucleocapsid and the spike proteins. Furthermore, we also described the immunoexpression of key host factors for virus entry in the COVID-19 thyroid samples. Results: We performed RT-PCR for SARS-CoV-2 in all autopsy specimens and detected viral genome positivity in 13 of 15 thyroid tissues and in a lung specimen. In 9 of the 14 positive samples, we were also able to confirm SARS-CoV-2 signal by in situ hybridization. Immunohistochemistry for the viral nucleocapsid and spike protein was also positive for ten and nine of the RT-PCR-positive cases, respectively, but revealed a lower sensitivity. We also described, for the first time in a COVID-19 series, the immunohistochemical expression of ACE-2, TMPRSS2, and furin in the thyroid. Conclusions: Our results obtained in thyroid specimens from deceased COVID-19 patients indicate that thyrocytes can be directly infected by SARS-CoV-2 since we detected the presence of SARS-CoV-2 genome in follicular cells. Nevertheless, we did not find a clear correlation between the presence of viral genome and the expression of the host factors for virus entry, namely ACE-2, TMPRSS2, and furin.

A 30-Year-Old Man With Cough, Dyspnea, and Upper Lobe Opacities.

CASE PRESENTATION: A 30-year-old man presents with dry cough and dyspnea on exertion (modified Medical Research Council dyspnea scale of 3), with progressive worsening over several months. He denies other respiratory or cardiac symptoms such as wheezing, hemoptysis, thoracalgia, palpitations, or leg swelling. He also denies constitutional symptoms, namely fever, sweating, anorexia, or weight loss. The patient is a current smoker (five cigarettes per day), with no other significant exposures, diseases, or medications. He had no personal history of respiratory diseases or TB. Relevant family history included an aunt with nonspecified interstitial lung disease and lung transplant.

Early Gestational Diagnosis of Lethal Skeletal Dysplasias: A 15 Year Retrospective Cohort Reviewing Concordance between Ultrasonographic, Genetic and Morphological Features.

Aim: We evaluated the diagnostic accuracy of ultrasound, postmortem and genetic studies in classifying skeletal dysplasias in the first vs second trimester of pregnancy. Methods: We retrospectively gathered data from a 15 year period of all the prenatal ultrasounds, autopsies, and available genetic studies on fetuses with skeletal dysplasias from our institution. Results: Five (23%) and 17 (77%) fetuses were diagnosed during the first and second trimester of pregnancy respectively. Only partial characterization was possible with ultrasound in the first trimester. Complete characterization was established in five cases (30%) in the second trimester with ultrasound alone. Pathology provided an additional diagnostic yield of 40% and 47% and genetics an additional 40% and 11% in the first and second trimesters respectively. Conclusion: Ultrasound is an effective screening but not a diagnostic tool. Complete characterizations of dysplasia increased from 22% by ultrasound alone to 86% with pathology and genetics.

The Role of Ultrasonography in the Diagnosis and Decision Algorithm for the Management of Pneumothorax after Transbronchial Lung Cryobiopsy.

BACKGROUND: Pneumothorax is one of the main complications of transbronchial lung cryobiopsy (TBLC). Chest ultrasound (CUS) is a radiation-free alternative method for pneumothorax detection. OBJECTIVE: We tested CUS diagnostic accuracy for pneumothorax and assessed its role in the decision algorithm for pneumothorax management. Secondary objectives were to evaluate the post-procedure pneumothorax occurrence and risk factors. METHODS: Eligible patients underwent TBLC, followed by chest X-ray (CXR) evaluation 2 h after the procedure, as our standard protocol. Bedside CUS was performed within 30 min and 2 h after TBLC. Pneumothorax by CUS was defined by the absence of lung sliding and comet-tail artefacts and confirmed with the stratosphere sign on M-mode. Pneumothorax size was determined through lung point projection on CUS and interpleural distance on CXR and properly managed according to clinical status. RESULTS: Sixty-seven patients were included. Nineteen pneumothoraces were detected at 2 h after the procedure, of which 8 (42.1%) were already present at the first CUS evaluation. All CXR-detected pneumothoraces had a positive CUS detection. There were 3 discordant cases (κ = 0.88, 95% CI: 0.76-1.00, p < 0.001), which were detected by CUS but not by inspiration CXR. We calculated a specificity of 97.5% (95% CI: 86.8-99.9) and a sensitivity of 100% (95% CI: 87.2-100) for CUS. Pneumothorax rate was higher when biopsies were taken in 2 lobes and if histology had pleural representation. Final diagnosis was achieved in 79.1% of patients, with the most frequent diagnosis being hypersensitivity pneumonitis. Regarding patients with large-volume pneumothorax needing drainage, the rate of detection was similar between CUS and CRX. CONCLUSION: CUS can replace CXR in detecting the presence of pneumothorax after TBLC, and the lung point site can reliably indicate its size. This useful method optimizes time spent at the bronchology unit and allows immediate response in symptomatic patients, helping to choose optimal treatment strategies, while preventing ionizing radiation exposure.

Os sinais neurológicos motores discretos em indivíduos com e sem esquizofrenia / Motor neurological soft signs in individuals with and without schizophrenia / Signos neurológicos motores discretos en individuos con y sin esquizofrenia

Resumo Introdução: Os sinais neurológicos motores discretos (SNMD) correspondem à parte motora dos sistemas neurológicos discretos e abrangem os domínios da coordenação motora e sequencialização dos atos motores complexos, definidos como sintomas que se encontram associados a alterações motoras na esquizofrenia. Os SNMD parecem ser um dos indicadores precoces na diferenciação do diagnóstico de esquizofrenia, pelo que a sua identificação pode ajudar ao diagnóstico e monitorização do percurso da doença, bem como à escolha de métodos de tratamento mais adequados e eficazes, apesar da ainda escassez de evidências a nível nacional. Objetivo: Avaliar e comparar os SNMD de pessoas com e sem esquizofrenia. Métodos: Estudo transversal, descritivo e comparativo. Foi utilizada a Escala Motora Breve (EMoB) para avaliação do desempenho motor dos 60 participantes com (n=30) e sem (n=30) esquizofrenia, entre os 24 e os 93 anos de idade, 27 do género feminino e 33 do género masculino. Verificou-se a existência de diferenças significativas entre os dois grupos, visíveis em todos os itens e domínios psicomotores, especialmente ao nível da coordenação motora, da memória visual e de trabalho, da capacidade de atenção e raciocínio e ainda do planeamento e execução motora. Conclusões: Os indivíduos com esquizofrenia demonstraram um menor desempenho motor. Recomendações para a prática e investigação são apontadas.

Abstract Background: Motor neurological soft signs (SNMD) correspond to the motor part of discrete neurological systems and encompass the domains of motor coordination and sequencing of complex motor acts, defined as symptoms that are associated with motor changes in schizophrenia. SNMDs appear to be one of the early indicators in differentiating the diagnosis of schizophrenia, so their identification can help the diagnosis and monitoring of the course of the disease, as well as the choice of more adequate and effective treatment methods, despite the still scarce evidence a Nacional level. Aim: Evaluate and compare the SNMD of people with and without schizophrenia. Methods: The motor performance of the 60 participants with (n = 30) and without (n = 30) schizophrenia, between 24 and 93, 27 of the female gender and 33 of the male gender was evaluated by the Motor Brief Scale (EMoB). Results: There were significant differences between the two groups, visible in all items and psychomotor domains, especially at the level of motor coordination, visual and work memory, attention and reasoning ability, and motor planning and execution. Conclusions: Individuals with schizophrenia demonstrated a lower motor performance. Recommendations to practice and research are presented.

Resumen Introducción: Los signos neurológicos motores discretos (SNMD) corresponden a la parte motora de los sistemas neurológicos discretos y cubren los dominios de la coordinación motora y la secuenciación de actos motores complejos, definidos como síntomas que son cambios motores en la esquizofrenia. Las NMD parecen ser uno de los primeros indicadores para diferenciar el diagnóstico de la esquizofrenia, por lo que su identificación puede ayudar al diagnóstico y seguimiento del curso de la enfermedad, así como la elección de métodos de tratamiento más apropiados y eficaces, a pesar de la todavía escasez de pruebas a nivel nacional. Objetivo: Evaluar y comparar las NMD de las personas con y sin esquizofrenia. Metodología: El rendimiento motor de los 60 participantes con esquizofrenia (n-30) y sin (n-30), entre 24 y 93, 27 hembras de arena 33 macho fueron evaluados por la Brief Motor Scale (EMoB). Resultados: Hubo diferencias significativas entre los dos grupos, visibles en todos los elementos y dominios psicomotores, especialmente a nivel de coordinación motora, memoria visual y trabajo, habilidades de atención y razonamiento y también de la planificación y ejecución motora. Conclusiones: Las personas con esquizofrenia demostraron un menor rendimiento motor. Se señalan las recomendaciones para la práctica y la investigación.

Enlightening clinical and therapeutic heterogeneity in thoracic actinomycosis: A review in bronchiectasis and non-bronchiectasis patients.

Actinomycosis is a rare chronic infection triggered by species of Actinomyces. Although thoracic involvement represents about 15% of human actinomycosis, its true incidence may be underestimated, not only because of its challenging diagnosis, but also because it can be treated unintentionally with antibiotics for other diseases. In this sense, this work aims at providing an up-to-date literature review on thoracic actinomycoses, with particular emphasis on presentation, diagnostic and therapeutic approaches, also paving upcoming clinical interventions from findings obtained of a presentation of a case series. Data discussed here clearly denote the rarity, non-specificity and heterogeneity of clinical presentations of the disease, reinforcing the need for individualized therapeutic approaches.

Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic.

INTRODUCTION: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease's clonal monitoring. MATERIAL AND METHODS: An amplicon-based targeted gene NGS panel was used to analyse 101 plasma samples of advanced non-small cell lung cancer (NSCLC) patients with known oncogenic mutations, mostly EGFR mutations, serially collected at different clinically relevant time points of the disease. RESULTS: The variant allelic frequency (VAF) monitoring in consecutive plasma samples demonstrated different molecular response and progression patterns. The decrease in or the clearance of the mutant alleles was associated with response and the increase in or the emergence of novel alterations with progression. At the best response, the median VAF was 0% (0.0% to 3.62%), lower than that at baseline, with a median of 0.53% (0.0% to 9.9%) (p = 0.004). At progression, the VAF was significantly higher (median 4.67; range: 0.0-36.9%) than that observed at the best response (p = 0.001) and baseline (p = 0.006). These variations anticipated radiographic changes in most cases, with a median time of 0.86 months. Overall, the VAF evolution of different oncogenic mutations predicts clinical outcomes. CONCLUSION: The targeted NGS of circulating tumour DNA (ctDNA) has clinical utility to monitor treatment response in patients with advanced lung adenocarcinoma.

Clinical Application of Next-Generation Sequencing of Plasma Cell-Free DNA for Genotyping Untreated Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Analysis of circulating tumor DNA (ctDNA) has remarkable potential as a non-invasive lung cancer molecular diagnostic method. This prospective study addressed the clinical value of a targeted-gene amplicon-based plasma next-generation sequencing (NGS) assay to detect actionable mutations in ctDNA in patients with newly diagnosed advanced lung adenocarcinoma. METHODS: ctDNA test performance and concordance with tissue NGS were determined, and the correlation between ctDNA findings, clinical features, and clinical outcomes was evaluated in 115 patients with paired plasma and tissue samples. RESULTS: Targeted-gene NGS-based ctDNA and NGS-based tissue analysis detected 54 and 63 genomic alterations, respectively; 11 patients presented co-mutations, totalizing 66 hotspot mutations detected, 51 on both tissue and plasma, 12 exclusively on tissue, and 3 exclusively on plasma. NGS-based ctDNA revealed a diagnostic performance with 81.0% sensitivity, 95.3% specificity, 94.4% PPV, 83.6% NPV, test accuracy of 88.2%, and Cohen's Kappa 0.764. PFS and OS assessed by both assays did not significantly differ. Detection of ctDNA alterations was statistically associated with metastatic disease (p = 0.013), extra-thoracic metastasis (p = 0.004) and the number of organs involved (p = 0.010). CONCLUSIONS: This study highlights the potential use of ctDNA for mutation detection in newly diagnosed NSCLC patients due to its high accuracy and correlation with clinical outcomes.

Sporadic Creutzfeldt-Jakob disease presenting as epilepsia partialis continua and non-ictal nystagmus.

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is a rare form of rapidly progressive neurodegenerative disorder. Seizures are uncommon in the early stage of CJD, increasing diagnostic difficulty. METHODS: An autopsy-proven case of CJD presenting initially as an epilepsia partialis continua is reported, in which the initial workup was unremarkable. Retrospectively, the presence of nystagmus, which proved to be non-epileptic, pointed to a cerebellar lesion before a diagnosis of clinically probable CJD was made. RESULTS: A 70-year-old man presented with a 3-week history of intermittent rhythmic jerking tremors in his left limbs, interfering with his gait. Examination showed left body clonic movements. Electroencephalography revealed an ictal right centroparietal pattern of focal status epilepticus. Video-oculography revealed right-beating nystagmus (mean slow phase velocity [SPV] 3.4º/s) in the dark and left-beating nystagmus (SPV 2.6º/s) in the light, left-beating nystagmus after head shaking (SPV 4º/s) and during mastoid vibration (SPV 11º/s) and mildly hypoactive horizontal head impulses. Search for occult malignancy, serologies, cerebrospinal fluid analyses, anti-onconeural antigen, auto-immune panel and brain magnetic resonance imaging were unrevealing. Rapid neurological decline was observed. Three weeks later, cerebrospinal fluid was positive for 14.3.3 protein, electroencephalography showed generalized periodic sharp wave complexes and brain magnetic resonance imaging revealed diffusion restriction and T2/fluid-attenuated inversion recovery hyperintensities in the cerebellum, basal ganglia, thalamus and cortex. He died 1 month later. Neuropathological study confirmed the diagnosis of CJD. CONCLUSION: This case highlights that CJD should be considered in the differential diagnosis of new onset epilepsia partialis continua and that neuro-ophthalmological examination can be helpful in pointing to early asymmetric cerebellar involvement.

Massive sacrococcygeal teratoma in a preterm infant.

In extreme preterm infants, massive congenital sacrococcygeal teratomas with great hemodynamic commitment may be a situation for limitation of care.

Insights on chronic hypersensitivity pneumonitis' treatment: Factors associated with a favourable response to azathioprine.

BACKGROUND: The use of immunosuppressive and antifibrotic agents for the treatment of chronic hypersensitivity pneumonitis (CHP) appears promising, but there is still no evidence supporting the clinical decision regarding the implementation of each specific pharmacological strategy. METHODS: Patients diagnosed with CHP and treated with azathioprine (AZA) were retrospectively selected from a single centre for Interstitial Lung Diseases. Baseline clinical data, as well as functional, imaging, bronchoalveolar lavage (BAL) and histology features were assessed. Longitudinal data on functional parameters were collected and comparatively analysed with patients' characteristics. RESULTS: In this cohort of 80 patients, of those who reached 12 months of treatment, 78.3% presented a preserved forced vital capacity, with 59 being eligible to be classified as AZA responders (n = 36) or non-responders (n = 23). BAL lymphocytosis was associated with a favourable response to AZA treatment (OR 1.051; 95% CI 1.015-1.089), although it didn't identify all responders. CONCLUSIONS: AZA revealed to be effective in disease stabilisation in most patients, while ineffective for a subset. BAL lymphocytosis appears as a potentially valuable strategy to identify AZA responders, although with limited accuracy. Further studies are needed to clarify other response markers to immunosuppressive agents, in order to optimize the therapeutic options for this condition.

Mother-reported pain experience between ages 7 and 10: A prospective study in a population-based birth cohort.

BACKGROUND: Trajectory studies suggest considerable stability of persistent or recurrent pain in adolescence. This points to the first decade of life as an important aetiologic window for shaping future pain, where the potential for prevention may be optimised. OBJECTIVES: We aimed to quantify changes in mother-reported pain experience in children between ages 7 and 10 and describe clusters of different pain experiences defined by complementary pain features. METHODS: We conducted a prospective study using data from 4036 Generation XXI birth cohort participants recruited in 2005-06. Pain history was reported by mothers at ages 7 and 10 using the Luebeck pain screening questionnaire. We tracked changes in six pain features over time using relative risks (RRs) and their 95% confidence intervals (95% CIs). Clusters were obtained using the k-medoids algorithm. RESULTS: The risk of severe pain at age 10 increased with increasing severity at age 7, with RRs ranging from 2.18 (95% CI 1.90, 2.50) for multisite to 4.43 (95% CI 3.19, 6.15) for high frequency pain at age 7. A majority of children (59.4%) had transient or no pain but two clusters included children with stable recurrent pain (n = 404, 10.2% of the sample). One of those (n = 177) was characterised by higher probabilities of multisite pain (74.6% and 66.7% at ages 7 and 10, respectively), with psychosocial triggers/contexts (59.3% and 61.0%) and daily-living restrictions (72.2% and 84.6%). Most children in that cluster (58.3%) also self-reported recent pain at age 10 and had more frequent family history of chronic pain (60.5%). CONCLUSIONS: All pain features assessed tracked with a positive gradient between ages 7 and 10, arguing for the significance of the first decade of life in the escalation of the pain experience. Multisite pain and psychosocial attributions appeared to be early markers of more adverse pain experiences.