Estudo longitudinal de famílias / Longitudinal study of families / Estudio longitudinal de familias

Introdução: O desenvolvimento da família é influenciado por diversos fatores de sua organização interna e de ordem ambiental, social, cultural, econômica e política. Em contexto de pobreza os riscos são maiores. Fatores de proteção, como boa organização familiar e rede social de apoio podem diminuir as consequências negativas da pobreza. São escassas as pesquisas longitudinais sobre vulnerabilidade e resiliência nas famílias. Objetivo: Este artigo descreve o desenvolvimento de três famílias ao longo de 15 anos, estudadas por meio de entrevistas em casa, parte de uma coorte populacional de um bairro de Porto Alegre (RS). Buscaram-se associações entre a qualidade das relações nessas famílias e sua saúde física e mental, especialmente a do filho, foco da pesquisa. Métodos: Selecionaram-se no arquivo da pesquisa as três primeiras famílias (do total de 148) das quais se tinham os resultados completos das cinco visitas realizadas aos quatro meses e aos dois, quatro, nove e 15 anos de um filho. Realizou-se análise qualitativa dos registros em busca de categorias para compreender a vida e as relações interpessoais nas famílias. O estudo foi realizado em conjunto por duas pesquisadoras, médicas especialistas em desenvolvimento humano. As categorias identificadas na análise e estudadas nas cinco etapas foram: configuração familiar, situação socioeconômica, situações traumáticas, saúde física, saúde relacional e mental, evolução cognitiva e escolar do filho. Resultados: As três famílias, todas de classe C, com filhos sem problemas de saúde física, tiveram evolução suficientemente boa, apesar de todas enfrentarem múltiplos problemas, inclusive separações e mortes precoces. A relação com o sistema de saúde e escola era boa e similar para as três. A jovem com menos problemas de saúde mental foi aquela que sofreu perdas mais importantes: morte dos pais. Tinha uma estrutura familiar multigeracional sólida desde a primeira infância, com relações interpessoais predominantemente colaborativas e amorosas. Conclusões: O artigo busca avançar na compreensão da resiliência nas famílias em situações de vulnerabilidade. Concluímos que essas três famílias, uma delas mais que as outras, foram suficientemente saudáveis na tarefa de educar seus filhos sem desenvolverem problemas mentais graves. Propomos que o bom desenvolvimento se associa com a adequação e amorosidade dos cuidados com a etapa do ciclo vital, mesmo enfrentando situações problemáticas. Essas qualidades precisam estar associadas à estabilidade socioeconômica básica e a bons serviços de saúde e escola.

Introduction: Family development is influenced by it's internal organization and environmental factors, socioeconomic, cultural and political. In poor contexts there are more risks to development. Protection factors like good family organization and social network may decrease the risks. Longitudinal research about vulnerability and resilience in families is scarse. Objective: This article describes the development of three families over 15 years through interviews at home. The families were part of a populational cohort of a neighborhood in Porto Alegre (RS). We looked for links between the quality of relationships and the physical and mental health of these families, especially of the child focus of the research. Methods: We selected in the research archives the first three families (of a total of 148) for which we had full results of the five interviews at four months and two, four, nine and fifteen years of a child. We did a qualitative analysis of the records looking for parameters to understand the life and interpersonal relationships of these families. This study was done by two researchers, both experts in Human Development. The categories identified in the analysis of the five phases were: family structure, socioeconomic situation, traumatic experiences, physical, mental and relational health and cognitive evolution of the child. Results: All three families belonged to economical class C. The children were in good physical health and had sufficiently good general development, having faced multiple problems, including parental separation and early parental death. The relationship with the health and school systems was good in all of them. The youth with less mental health problems was the one who suffered the heaviest loss: early death of both parents. Her family had strong multigenerational ties since her early days, with predominant collaborative and loving relationships. Conclusions: This article aims to contribute to the comprehension of resilience in families in the context of vulnerability. We can say that these three families were healthy enough in the task of bringing up children without any serious mental health problem. We suggest that healthy development is associated with loving interfamily relationships adequate to each phase of development, notwithstanding dramatic events. This needs to be supported by basic economic stability and adequate school and health systems.

Introducción: El desarrollo de la familia es influenciado por su organización interna y factores ambientales, sociales, culturales, económicos y políticos. En contextos pobres los riesgos son mayores. Factores de protección como buena organización familiar y red social de apoyo pueden disminuir las consecuencias negativas de la pobreza. Son pocas las investigaciones longitudinales de vulnerabilidad y resiliencia de las familias. Objetivo: Este artículo describe el estudio del desarrollo de tres familias a lo largo de 15 años, a través de entrevistas en domicilio, parte de una cohorte poblacional de un barrio de Porto Alegre (RS). Se buscaron correlaciones entre la calidad de las relaciones de esas familias y su salud física y mental, especialmente la del hijo foco de la investigación. Métodos: Fueron seleccionadas en el archivo de la investigación las tres primeras familias (de un total de 148) de las cuales se tenían los resultados completos de las cinco visitas realizadas, a los 4 meses, y a los 2, 4, 9, y 15 años de un hijo. Fue realizado un análisis cualitativo de los registros en busca de categorías para comprender la vida y las relaciones interpersonales en las familias. El estudio fue hecho en conjunto por dos investigadoras, médicas especialistas en desarrollo humano. Las categorías identificadas en el análisis y estudiadas en las cinco etapas fueron: configuración familiar, situación socioeconómica, situaciones traumáticas, salud física, salud relacional y mental, evolución cognitiva y escolar del hijo. Resultados: Las tres familias, todas de clase C, con hijos sin problemas de salud física, tuvieron evolución suficientemente buena, a pesar de que todas enfrentaron múltiples problemas, incluso separaciones y muertes precoces. La relación con el sistema de salud y escuela era buena y similar para las tres. La joven con menos problemas de salud mental fue aquella que sufrió las mayores pérdidas: muerte de los padres. Tenía una estructura familiar multigeneracional sólida desde la primera infancia, con relaciones interpersonales predominantemente colaborativas y amorosas. Conclusiones: El artículo pretende avanzar en la comprensión de la resiliencia en las familias en situaciones de vulnerabilidad. Concluimos que esas tres familias, una de ellas más que las otras, fueron suficientemente saludables en la tarea de educar a sus hijos sin que desarrollaran problemas mentales graves. Proponemos que el buen desarrollo se asocia con el amor y adecuación de los cuidados a la etapa del ciclo vital, aun enfrentando situaciones problemáticas. Esas calidades necesitan estar asociadas a la estabilidad socioeconómica básica y buenos servicios de salud y escuela.

Clinical Manifestations and Outcomes of Ocular Graft Versus Host Disease following Allogeneic Stem Cell Transplantation.

Purpose: To evaluate clinical presentation of chronic ocular graft-versus-host disease (GVHD), laterality of presentation, and longitudinal changes in patients undergoing allogeneic stem cell transplantation. Methods: This is a retrospective longitudinal analysis of 60 eyes from 30 patients who had undergone hematopoietic stem cell transplantation. Demographic characteristics, clinical history, comorbidities, and other organ involvements were taken into account for analysis. We also undertook complete evaluation of the eyes, including cornea and anterior segment, posterior segment, Schirmer test, tear break-up time, ocular surface disease index, and intraocular pressure. Results: The mean age of the patients was 34.3 ± 11 years. The mean time for the diagnosis of ocular GVHD was 232.8 days (95% CI: 153.6, 311.9). The common findings at the first visit were bilateral blepharitis (n = 5, 17%), meibomitis (n = 4, 13%), and conjunctival congestion (n = 3, 10%). While bilateral cataract was present in one (3%) patient at the first visit, at 18 months, five (17%) patients had bilateral cataract and one (3%) patient had unilateral cataract. Grade 1 (n = 17), grade 2 (n = 9), and grade 3 (n = 4) superficial punctate epithelial erosions (SPEEs) were also observed at the first visit. However, SPEEs were seen in only 11 eyes at 18 months; all of these cases were grade 1 SPEEs. Long-term findings included cataract, telangiectasia, blepharospasm, conjunctival congestion, grade 1 SPEEs, corneal filaments, and tear film debris. Conclusion: Although the initial presentations were SPEEs, meibomitis, blepharitis, and conjunctival congestion, these inflammatory conditions were reduced over time with proper management. However, there was an increase in the proportion of patients with cataract. It is important to regularly monitor these patients in order to identify and manage the initial as well as the late ocular manifestations of chronic GVHD.

Factors affecting Kaposi's sarcoma-associated herpesvirus transmission in rural Ugandan households, a longitudinal study.

BACKGROUND: We report the impact of HIV infection within a household on oral Kaposi's sarcoma-associated herpesvirus (KSHV) shedding. METHODS: We enrolled 469 individuals from 90 households. Mouthwash rinse samples collected at three monthly visits were analyzed for KSHV DNA using quantitative polymerase chain reaction (qPCR). Generalized linear mixed effects logistic models were applied to analyze factors associated with KSHV ever shedding, and among shedders, always versus intermittent shedding. Linear mixed effects models were applied to models of KSHV viral loads. Intraclass correlation coefficients (ICCs) were calculated to assess the contribution of household-level factors to variations in shedding probabilities. Hotspot analyses of geospatial feature clusters were calculated using Getis-Ord Gi* statistic and visualized using inverse distance weighted interpolation. RESULTS: Analyses included 340 KSHV seropositive individuals, aged 3 + years, with qPCR results from 89 households. Forty households had 1 + persons living with HIV (PLWH), while 49 had none. Among participants, 149(44%) were KSHV ever shedders. Of 140 who shed KSHV at two or more visits, 34(24%) were always shedders. Increasing number of KSHV seropositive household members was significantly associated with ever shedding [Odds ratio(OR) (95% Confidence Interval(95%CI)):1.14(1.03,1.26);p = 0.013]. Among KSHV shedders, a statistically significant age-related trend was identified with 10-19 years being more likely to be always shedders (type III test p = 0.039) and to have higher viral loads (type III test p = 0.027). In addition, higher viral loads were significantly associated with increasing number of household members [coefficient(95%CI):0.06(0.01,0.12);p = 0.042], increasing number of KSHV seropositive members [coefficient(95%CI):0.08(0.01,0.15);p = 0.021], and living in households with 1 + PLWH [coefficient(95%CI):0.51(0.04,0.98);p = 0.033]. Always shedders exhibited higher viral loads than intermittent shedders [coefficient(95%CI):1.62(1.19,2.05);p < 0.001], and viral loads increased with the number of visits where KSHV DNA was detected in saliva (type III test p < 0.001). Household-level factors attributed for 19% of the variability in KSHV shedding (ICC:0.191;p = 0.010). Geospatial analysis indicated overlapping hotspots of households with more KSHV seropositive individuals and KSHV shedders, distinct from areas where PLWH were clustered. DISCUSSION: KSHV oral shedding is influenced by multiple factors at the individual, household, and regional levels. To mitigate ongoing KSHV transmission a comprehensive understanding of factors contributing to oral KSHV reactivation and transmission within households is needed.

Anterior cervical controllable Antedisplacement and Fusion (ACAF) versus Anterior Cervical Corpectomy and Fusion (ACCF) for ossification of the cervical posterior longitudinal ligament (OPLL) in Chinese population: a systematic review and meta-analysis.

This study aimed to systematically review and compare the efficacy and safety of anterior cervical controllable antedisplacement and fusion (ACAF) versus anterior cervical corpectomy and fusion (ACCF) in treating ossification of the cervical posterior longitudinal ligament (OPLL), focusing on surgery-related indicators and postoperative outcomes. This review was conducted and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards. The methodological quality of this systematic review was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) checklist. A detailed search strategy was implemented to retrieve literature from electronic databases, including PubMed, EMBASE, and the Cochrane Library, followed by quality assessment and data extraction for eligible studies. A total of 5 studies involving 366 participants were included. ACAF was associated with significantly fewer complications (OR = 0.25, 95% CI [0.12, 0.51], p = 0.000), including a lower incidence of cerebrospinal fluid (CSF) leakage (OR = 0.20, 95% CI [0.08, 0.52], p = 0.000). ACAF also showed better outcomes in postoperative neck disability index (NDI) scores (SMD = -0.48, 95% CI [-0.81, -0.15], p = 0.020), C2-C7 angle (SMD = 1.29, 95% CI [0.56, 2.03], p = 0.000), spinal canal area (SCA) (SMD = 0.93, 95% CI [0.56, 1.29], p = 0.000), and diameter of the spinal cord (DSC) (SMD = 0.38, 95% CI [0.11, 0.66], p = 0.010). Additionally, ACAF improved The Japanese Orthopedic Association (JOA) scores (SMD = 0.29, 95% CI [0.01, 0.57], p = 0.040) but required longer operation time (SMD = 1.08, 95% CI [0.01, 2.15], p = 0.049). No significant differences were found in blood loss (SMD = 0.23, 95% CI [-0.34, 0.79], p = 0.431), hospital stay (SMD = 0.65, 95% CI [-1.46, 2.76], p = 0.547), and improvement rate (IR) (SMD = 0.38, 95% CI [-0.10, 0.86], p = 0.118). The current meta-analysis indicated that ACAF surgery can effectively reduce the incidence of complications, significantly increase the spinal canal area and improve the spatial conditions of the spinal cord compared to those associated with ACCF surgery. This is more advantageous for the postoperative neurological recovery of patients. Nonetheless, it is crucial to approach these findings with a degree of caution.

Acute Paraplegia Following Spinal Anesthesia in a Patient With Unrecognized Thoracic Ossification of the Posterior Longitudinal Ligament and Spinal Stenosis: A Case Report.

Spinal coning is a rare complication in spinal anesthesia that results in acute neurological deterioration. It occurs when a pre-existing spinal stenosis alters the CSF flow, creating a high-pressure area beneath the stenosis. The introduction of a needle into this relatively high-pressure area would cause a decrease in CSF pressure, exacerbating the spinal cord compression. This article reports a 50-year-old female who presented with urinary frequency for six months and was diagnosed with urethra spasm. Following spinal anesthesia, a botulinum toxin injection over the urethra was performed by a urologist. The patient did not recover from the anesthesia, which subsequently resulted in acute paraplegia status with bowel and bladder dysfunction. An MRI of her thoracic spine revealed ossification of the posterior longitudinal ligament with severe spinal stenosis. She received decompressive surgery and recovered well. Surgeons and anesthesiologists should be aware of patients who may have pre-existing spinal stenosis to avoid the use of spinal anesthesia and thus prevent spinal coning. Rapid neurological deterioration and severe disability warrant early aggressive surgical treatment for better recovery.

Speckle-tracking echocardiography as screening tool for myocardial fibrosis and Iron overload in transfusion-dependent beta-thalassemia.

BACKGROUND: Transfusion-dependent beta thalassemia (TDT) is a genetic disorder characterized by low haemoglobin levels, often leading to myocardial iron overload (MIO) and myocardial fibrosis (MF). Cardiac Magnetic Resonance (CMR) represents the gold standard for MIO and MF assessment, although its limited availability and high costs pose challenges. Left Ventricular Global Longitudinal Strain (LV GLS) measured by Speckle Tracking Echocardiography (STE) could offer a valuable alternative. METHODS: A monocentric diagnostic accuracy study was conducted to compare the performance of LV GLS with CMR using T2* for evaluating MIO and late gadolinium enhancement (LGE) for detecting MF. Between January 2022 and January 2023, 44 consecutive patients with TDT were enrolled. For each participant was performed LV GLS with STE, including CMR with T2* technique and LGE sequences. RESULTS: CMR identified MIO in 8 patients (18 %) and MF in 5 (11 %). LV GLS STE was normal in patients without MIO (-20.6 ± 3.1 %) or MF (-20.6 ± 2.8 %), significantly differing from those with MIO (-18.2 ± 2.1 %, p = 0.043) and MF (-16.4 ± 1.7 %, p = 0.002). ROC analysis indicated an optimal LV GLS STE cutoff of -19.8 % for MIO (AUC = 0.76, 95 % CI: 0.59-0.93, p = 0.054) with an overall diagnostic accuracy of 64 % and an optimal cutoff of -18.3 % for MF (AUC = 0.93, 95 % CI: 0.85-1.00, p = 0.009) with an accuracy of 86 %. CONCLUSIONS: The findings of this pilot study indicate that LV GLS with STE, may be a cost-effective screening tool for the early detection of MIO and MF in TDT patients.

Application of the "Klotski Technique" in Cervical Ossification of the Posterior Longitudinal Ligament With En Bloc Type Dura Ossification.

OBJECTIVE: The anterior controllable antedisplacement and fusion (ACAF) technique is a new procedure for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) that requires management of the disc adjacent to the ossification. This study describes a novel technique to reduce the number of fixed segments, namely, the "Klotski technique." The efficacy of ACAF using the Klotski technique was compared with that of anterior cervical corpectomy and fusion (ACCF) in the treatment of OPLL with en bloc type dural ossification (DO). METHODS: The clinical data of 25 patients with severe OPLL and en bloc type DO who were treated by the ACAF Klotski technique or ACCF at our hospital from January 2020 to January 2022 were retrospectively analyzed. In the Klotski technique, the number of segments fused within the OPLL is limited. The antedisplacement space was designed according to the shape of the vertebrae-OPLL-DO complex (VODC). Then, the entire VODC was antedisplaced as in Klotski. Neurological function and image examination were assessed preoperatively and postoperatively. Complications associated with surgery were recorded. RESULTS: Patients were followed up for 24-36 months. There were 11 patients who were treated with ACAF and 14 patients who were treated with ACCF. At 2 weeks after surgery, the incidence of neurological deterioration was 21.4% (3 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The incidence of intraoperative cerebrospinal fluid leakage (CFL) was 35.7% (5 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The postoperative follow-up JOA scores of the patients in both groups were significantly better than their preoperative JOA scores (p<0.05). CONCLUSION: The Klotski technique for ACAF is a good option for the treatment of patients with en bloc type OPLL-DO, as it limits the number of fused segments, has a low incidence of CFL and neurologic deficits and is associated with good neurological recovery.

The risk factors determined by four machine learning methods for the change of difference of bone mineral density in post-menopausal women after three years follow-up.

The prevalence of osteoporosis has drastically increased recently. It is not only the most frequent but is also a major global public health problem due to its high morbidity. There are many risk factors associated with osteoporosis were identified. However, most studies have used the traditional multiple linear regression (MLR) to explore their relationships. Recently, machine learning (Mach-L) has become a new modality for data analysis because it enables machine to learn from past data or experiences without being explicitly programmed and could capture nonlinear relationships better. These methods have the potential to outperform conventional MLR in disease prediction. In the present study, we enrolled a Chinese post-menopause cohort followed up for 4 years. The difference of T-score (δ-T score) was the dependent variable. Information such as demographic, biochemistry and life styles were the independent variables. Our goals were: (1) Compare the prediction accuracy between Mach-L and traditional MLR for δ-T score. (2) Rank the importance of risk factors (independent variables) for prediction of δ T-score. Totally, there were 1698 postmenopausal women were enrolled from MJ Health Database. Four different Mach-L methods namely, Random forest (RF), eXtreme Gradient Boosting (XGBoost), Naïve Bayes (NB), and stochastic gradient boosting (SGB), to construct predictive models for predicting δ-BMD after four years follow-up. The dataset was then randomly divided into an 80% training dataset for model building and a 20% testing dataset for model testing. A 10-fold cross-validation technique for hyperparameter tuning was used. The model with the lowest root mean square error for the validation dataset was viewed as the best model for each ML method. The averaged metrics of the RF, SGB, NB, and XGBoost models were used to compare the model performance of the benchmark MLR model that used the same training and testing dataset as the Mach-L methods. We defined that the priority demonstrated in each model ranked 1 as the most critical risk factor and 22 as the last selected risk factor. For Pearson correlation, age, education, BMI, HDL-C, and TSH were positively and plasma calcium level, and baseline T-score were negatively correlated with δ-T score. All four Mach-L methods yielded lower prediction errors than the MLR method and were all convincing Mach-L models. From our results, it could be noted that education level is the most important factor for δ-T Score, followed by DBP, smoking, SBP, UA, age, and LDL-C. All four Mach-L outperformed traditional MLR. By using Mach-L, the most important six risk factors were selected which are, from the most important to the least: DBP, SBP, UA, education level, TG and sleeping hour. δ T score was positively related to SBP, education level, UA and TG and negatively related to DBP and sleeping hour in postmenopausal Chinese women.

Analysis of Longitudinal Trajectory and Influencing Factors of Supportive Care Needs in Colorectal Cancer Patients With Enterostomy.

AIMS: The aim of this study was to understand the dynamic changes in the needs of patients with enterostomy during the 3 months after discharge and its possible influencing factors. DESIGN: A prospective observational design. METHODS: This study investigated the supportive care needs of patients who underwent colorectal cancer surgery with colostomy in three Chinese hospitals from May 2023 to October 2023 during the 3 months following discharge from the hospital. The growth mix model was used to describe the needs trajectory and analyse the heterogeneity of the trajectory. Univariate analysis was used to find the factors that might affect the heterogeneity of needs trajectory of patients with enterostomy, and then logistic regression analysis was used to determine the influencing factors of the heterogeneity of needs trajectory of patients with enterostomy. The reporting of this study adhered to the STROBE checklist. RESULTS: A total of 232 patients with enterostomy completed follow-up. There was heterogeneity in the developmental trajectories of supportive care needs of enterostomy patients and the trajectories of the five dimensions of supportive care needs. The heterogeneity factors affecting the trajectory of supportive care needs included the enterostomy patient's psychosocial adjustment score, type of enterostomy, and educational background and the heterogeneity factors affecting the five dimensions trajectory of supportive care needs include psychosocial adjustment score, tumour staging, type of enterostomy, smoking, chemotherapy and enterostomy self-care knowledge score. CONCLUSIONS: The needs of patients with enterostomy within 3 months after discharge were dynamic. Identifying and meeting the unmet needs of patients with enterostomy was crucial to improving the health-related quality of life of patients with enterostomy. PATIENT OR PUBLIC CONTRIBUTION: None. RELEVANCE TO CLINICAL PRACTICE: The needs of patients with enterostomy were dynamic, with the needs of most patients with enterostomy decreasing within 3 months of discharge, but some patients with enterostomy continued to have high needs at 3 months after discharge, and clinical nurses were expected to pay special attention to these patients.

The Risk and Reversibility of Osimertinib-related Cardiotoxicity in a Real-World Population.

INTRODUCTION: While osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, as the first-line therapy for metastatic non-small cell lung cancer (NSCLC) has shown significant survival benefits, concerns have arisen regarding its potential cardiotoxicity, particularly in real-world clinical settings. We aimed to investigate the incidence, risk factors, and reversibility of osimertinib-related cardiotoxicity. METHODS: We analyzed 1,126 NSCLC patients treated with osimertinib from May 2016 to April 2023 in two cancer centers. Osimertinib-related cardiotoxicity was defined as a composite of osimertinib-related cardiac dysfunction (ORCD), newly developed arrhythmia, and cardiac death. Total follow-up duration was 20.6 (10.8-35.2) months. RESULTS: The osimertinib was administered for a median of 12.4 months. The incidence of osimertinib-related cardiotoxicity was 4.7%. Advanced age (adjusted hazard ratio with 95% confidence interval; 1.07 [1.04-1.09], P < 0.001), a history of heart failure (HF; 3.35 [1.67-9.64], P = 0.025), atrial fibrillation (AF; 3.42 [1.27-9.22], P = 0.015), and baseline low left ventricle strain (0.87 [0.79-0.96], P = 0.005) were independently associated with development of cardiotoxicity. The recovery rate of ORCD was 82.4%, which did not differ between patients who discontinued medication and those who did not. CONCLUSION: In real-world practice, the incidence of osimertinib-related cardiotoxicity was 4.7%, including 3.4% for ORCD requiring cardiologic intervention, which is higher than previously reported. Given the long-term medication of osimertinib and increased mortality associated with cardiotoxicity, vigilant monitoring is crucial, especially in patients with advanced age, history of HF, AF, or decreased baseline LV strain.

Biomarker trajectory for earlier detection of lung cancer.

BACKGROUND: To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4 MP) for lung cancer risk assessment results in improved performance over a single time measurement. METHODS: We conducted data analysis of the 4 MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history at each time point, was compared to a single-threshold (ST) method. FINDINGS: Among ever-smoker participants, the PEB approach yielded an additional 4% improvement in the AUC compared to the ST approach (P-value: 0.009). When considering an ≥10 PY smoking history and at a fixing the specificity corresponding to 1% 6-year lung cancer risk, PEB resulted in significant improvement in the sensitivity (SenPEB:96.3% vs SenST:91.0%; P-value: 6.7e-3). The PEB algorithm identified 17 of the 35 cases that remained ST negative, at an average of 1.26 years before diagnosis. Ten case individuals who were positive based on ST at an average of 1.03 years prior to diagnosis were identified earlier by PEB, at an average of 2.70 years. INTERPRETATION: An algorithm based on repeated measurements of the 4 MP improves sensitivity and results in an earlier detection of lung cancer compared to a single-threshold method. FUNDING: This study was supported by NIH Grant Nos. U01CA271888, U01CA194733, U01CA213285, NCI EDRN U01 CA200468, P30CA016672, and U24CA086368; the Cancer Prevention & Research Institute of Texas RP180505 and RP160693; the SPORE P50CA140388; the CCTS TR000371; and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Lyda Hill Foundation.

Long-Term Functional and Radiological Results in Tonkin Type 3B Thumb Hypoplasia Treated With Nonvascularized Toe Phalanx Transfer as an Alternative to Pollicization.

PURPOSE: Parents of children with hypoplastic thumbs often reject the option of pollicization for various reasons and enquire about alternate choices. Our study aimed to assess the outcome in children who underwent nonvascularized toe phalanx transfer for Tonkin type 3B thumb hypoplasia and compare it with a similar cohort of children treated with pollicization. METHODS: At an average follow-up of 7 years for toe phalanx transfer and 6 years of pollicization, five children from each group were tested for thumb length, stability of the first carpometacarpal (CMC) joint, mobility, opposition, and donor-site morbidity. Parents were asked to report improvements in function and appearance. All cases were Tonkin type 3B thumb hypoplasia. RESULTS: The CMC joint was found to be stable in all children, and the Kapandji score was 6 in 3 children and 5 in 2 children with toe phalanx transfer compared to 9 in all children with pollicization. The average palmar abduction was 24°, and the average radial abduction was 36° in the toe phalanx transfer group compared to 40° and 45°, respectively, in children with pollicization. The average thumb length was 50.8% of the index finger's proximal phalanx in the toe phalanx group compared to 60 % in the pollicization group. The mean visual analog scale scores for the thumb's function and appearance were 6.8 and 6.4, respectively, compared to 9.2 and 8.8, respectively, in the pollicization group. No resorption was noted in the donor phalanx at a mean follow-up of 7 years with no donor-site morbidity other than mild shortening of the toes. CONCLUSIONS: We noted increased palmar abduction and radial abduction in the pollicization group. No resorption was noted in the donor toe phalanx at the longest follow-up of 9 years. Toe phalanx can be considered an alternative for those children in whom a five-finger hand is a priority. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial.

BACKGROUND AND AIMS: The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF. METHODS: Strain sUrveillance during Chemotherapy for improving Cardiovascular Outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59±13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS and 3D echocardiography were tracked over 12 months. A total of 105 patients (age 59±13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) between cardioprotection with neurohormonal antagonists versus usual care were randomized. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI LVEF-defined CTRCD. RESULTS: During follow-up, 2 patients died and 2 developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (-2.5±5.4% vs -5.6±5.9%, p=0.009), follow-up LVEF was higher after cardioprotection (59±5% vs 55±6%, p<0.0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was -3.6% (-1.8% to -5.5%, p<0.001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (p=0.075). GLS improved at 3 months post-randomization in the cardioprotection group, with little change with usual care. CONCLUSIONS: In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care.

Flexible joint model for time-to-event and non-Gaussian longitudinal outcomes.

In medical studies, repeated measurements of biomarkers and time-to-event data are often collected during the follow-up period. To assess the association between these two outcomes, joint models are frequently considered. The most common approach uses a linear mixed model for the longitudinal part and a proportional hazard model for the survival part. The latter assumes a linear relationship between the survival covariates and the log hazard. In this work, we propose an extension allowing the inclusion of nonlinear covariate effects in the survival model using Bayesian penalized B-splines. Our model is valid for non-Gaussian longitudinal responses since we use a generalized linear mixed model for the longitudinal process. A simulation study shows that our method gives good statistical performance and highlights the importance of taking into account the possible nonlinear effects of certain survival covariates. Data from patients with a first progression of glioblastoma are analysed to illustrate the method.

Functional Status and Quality of Life in Light-Chain Amyloidosis: Advanced Imaging, Longitudinal Changes, and Outcomes.

BACKGROUND: In light-chain (AL) amyloidosis, whether functional status and heart failure-related quality of life (HF-QOL) correlate with cardiomyopathy severity, improve with therapy, and are associated with major adverse cardiac events (MACE) beyond validated scores is not well-known. OBJECTIVES: The authors aimed to: 1) correlate functional status and HF-QOL with cardiomyopathy severity; 2) analyze their longitudinal changes; and 3) assess their independent associations with MACE. METHODS: This study included 106 participants with AL amyloidosis, with 81% having AL cardiomyopathy. Functional status was evaluated using the NYHA functional class, the Karnofsky scale, and the 6-minute walk distance (6MWD), and HF-QOL using the MLWHFQ (Minnesota Living with Heart Failure Questionnaire). Cardiomyopathy severity was assessed by cardiac 18F-florbetapir positron emission tomography/computed tomography, cardiac magnetic resonance, echocardiography, and serum cardiac biomarkers. MACE were defined as all-cause death, heart failure hospitalization, or cardiac transplantation. RESULTS: NYHA functional class, Karnofsky scale, 6MWD, and MLWHFQ were impaired substantially in participants with recently diagnosed AL cardiomyopathy (P < 0.001), and correlated with all markers of cardiomyopathy severity (P ≤ 0.010). NYHA functional class, 6MWD, and MLWHFQ improved at 12 months in participants with cardiomyopathy (P ≤ 0.013). All measures of functional status and HF-QOL were associated with MACE (P ≤ 0.017), independent of Mayo stage for 6MWD and MLWHFQ (P ≤ 0.006). CONCLUSIONS: Functional status and HF-QOL were associated with AL cardiomyopathy severity, improved on therapy within 12 months, and were associated with MACE, independently of Mayo stage for 6MWD and MLWHFQ. They may be validated further in addition to prognostic scores and as surrogate outcomes for future studies.

A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use.

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.

Lifestyle, biological, and genetic factors related to brain iron accumulation across adulthood.

Iron is necessary for many neurobiological mechanisms, but its overaccumulation can be harmful. Factors triggering age-related brain iron accumulation remain largely unknown and longitudinal data are insufficient. We examined associations between brain iron load and accumulation and, blood markers of iron metabolism, cardiovascular health, lifestyle factors (smoking, alcohol use, physical activity, diet), and ApoE status using longitudinal data from the IronAge study (n = 208, age = 20-79, mean follow-up time = 2.75 years). Iron in cortex and basal ganglia was estimated with magnetic resonance imaging using quantitative susceptibility mapping (QSM). Our results showed that (1) higher peripheral iron levels (i.e., composite score of blood iron markers) were related to greater iron load in the basal ganglia; (2) healthier diet was related to higher iron levels in the cortex and basal ganglia, although for the latter the association was significant only in younger adults (age = 20-39); (3) worsening cardiovascular health was related to increased iron accumulation; (4) younger ApoE ε4 carriers accumulated more iron in basal ganglia than younger non-carriers. Our results demonstrate that modifiable factors, including lifestyle, cardiovascular, and physiological ones, are linked to age-related brain iron content and accumulation, contributing novel information on potential targets for interventions in preventing brain iron-overload.

Pain Characteristics of the Posterior Longitudinal Ligament in Percutaneous Endoscopic Lumbar Discectomy and its Significance: A Retrospective Study.

INTRODUCTION: In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported. METHODS: A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin-eosin (HE) staining and immunohistochemistry. RESULTS: Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (P < 0.05). The distribution of nociceptive nerve fibers in the dorsal side was uniform and scattered, while those in the ventral side were mainly distributed near the outer surface of the annulus fibrosus. The positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was higher in the ventral side of the PLL than in the dorsal side (P < 0.0001). CONCLUSIONS: Differences in pain distribution and intensity were observed when the PLL was incited at different spinal levels during PELD surgery.

Developmental trends in young children's device-measured physical activity and sedentary behaviour.

BACKGROUND: Knowledge of developmental trends in meeting age-specific 24-hour movement behaviour guidelines is lacking. This study describes developmental trends in device-measured physical activity and sedentary time over a three-year period among Western Australian children aged two to seven years, including differences between boys and girls. The proportion of children meeting age-specific physical activity guidelines before and after they transition to full-time school was also examined. METHODS: Data from waves 1 and 2 of the Play Spaces and Environments for Children's Physical Activity (PLAYCE) cohort study were used (analysis n = 1217). Physical activity and sedentary time were measured by accelerometry at ages two to five (preschool, wave 1) and ages five to seven (commenced full-time school, wave 2). Accelerometer data were processed using a validated machine-learning physical activity classification model. Daily time spent in sedentary behaviour, energetic play (moderate-to-vigorous physical activity (MVPA)), total physical activity, and meeting physical activity guidelines were analysed using linear and generalised linear mixed-effects models with age by sex interaction terms. RESULTS: All movement behaviours changed significantly with increasing age, and trends were similar in boys and girls. Total daily physical activity increased from age two to five then declined to age seven. Mean daily total physical activity exceeded 180 min/day from ages two to five. Daily energetic play increased significantly from age two to seven, however, was below 60 min/day at all ages except for seven-year-old boys. Daily sedentary time decreased to age five then increased to age seven but remained lower than at age two. All two-year-olds met their age-specific physical activity guideline, decreasing to 5% of girls and 6% of boys at age four. At age seven, 46% of boys and 35% of girls met their age-specific physical activity guideline. CONCLUSIONS: Young children's energetic play and total physical activity increased with age, but few children aged three to seven met the energetic play (MVPA) guideline. Interventions should focus on increasing children's energetic play in early childhood. Clearer guidance and strategies are needed to support young children as they change developmentally and as they transition from one age-specific movement guideline to the next.

Complex mechanism of brugada phenocopy: moderate hyponatremia and right ventricular compression by liver metastatic tumor - case report.

Brugada phenocopy (BrP) occurs in various clinical conditions and manifests as a Brugada-like ECG pattern with coved (type 1) or saddle-back (type 2) ST-segment elevation in the right precordial leads. Unlike Brugada syndrome (BrS), which is an inherited channelopathy, BrP is not associated with an increased risk of malignant arrhythmia. BrP has been reported in severe metabolic disturbances (significant hyponatremia, hypokalemia or hyperkalemia), mechanical heart compression, coronary artery disease, pulmonary embolism and myocarditis/pericarditis. The authors described a case of a 69-year-old female whose Brugada-like ECG was atypically associated with only moderate hyponatremia (127 mmol/l). She was admitted due to a skin and subcutaneous tissue infection of the left shank and coexistent urinary tract infection (without a fever). She had the history of advanced melanoma with multiple liver metastases. Her cardiac history was negative, especially the patient has never suffered from ventricular arrhythmias. ECG on admission showed saddle-back ST-segment elevation in the right precordial leads; however, the patient did not report any chest pain. Troponin I level and left ventricular function in echocardiography were normal while regional longitudinal strain in RV apex was decreased and showed post-systolic shortening. The substernal view revealed compression of the right ventricle (RV) by liver metastatic tumor. ECG changes disappeared quickly during natrium chloride supplementation and did not recur during hospitalization. This case illustrates that even moderate hyponatremia may be a reversible cause of BrP when other predisposing conditions (e.g. heart compression by tumor) coexist.