Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features / 中华外科杂志

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

Plurihormonal PIT1-lineage pituitary neuroendocrine tumors: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

El papel de los parámetros metabólicos de la 18F-FDG PET/TC en el linfoma linfoblástico pediátrico / The role of 18F-FDG PET/CT metabolic parameters in pediatric lymphoblastic lymphoma

Objetivo: Este estudio retrospectivo tuvo como objetivo evaluar el papel de los parámetros metabólicos de la 18F-FDG PET/TC en el linfoma linfoblástico pediátrico (LBL).Métodos: Treinta pacientes con LBL se sometieron a 42 exploraciones. Los parámetros metabólicos, que incluyeron el valor máximo de captación estandarizado (SUVmax), el volumen tumoral metabólico total (TMTV) y la glucólisis de lesión total (TLG), se midieron en la PET/TC basal. Se realizaron análisis univariantes y multivariantes de la supervivencia para evaluar su valor pronóstico. Doce pacientes se sometieron a PET/TC después del régimen de reinducción, y se calcularon la sensibilidad, la especificidad, el valor predictivo positivo (VPP), el valor predictivo negativo (VPN) y la precisión de la PET/TC para predecir la recaída.Resultados: Los pacientes con estadio IV tuvieron una TMTV más alta que los que tenían un estadio III (p=0,031). Además, los pacientes con T-LBL o afectación mediastínica tenían una TMTV y TLG altos (p<0,05). No hubo diferencias significativas en los parámetros metabólicos de la PET/TC entre los pacientes con diferente evolución (p>0,05). Los niños con una TMTV baja (<242,91cm3) tuvieron una mejor EFS a los 3 años comparados con aquellos con una TMTV elevada (88.9% vs. 56,3%; p=0,036). El SUVmax y el TLG no fueron predictivos de la EFS (p=0,874; p=0,152). Sin embargo, ninguno de los parámetros metabólicos de la PET/TC basales fueron factores pronósticos independientes para los resultados del LBL pediátrico. La PET/TC realizada después del régimen de reinducción presentó una mayor sensibilidad (50% vs. 0%) y VPN (90% vs. 83,3%) para predecir la recaída que la TC sola.Conclusiones: Los parámetros metabólicos de la PET/TC de referencia no fueron predictivos de los resultados en los niños con LBL. La PET/TC realizada después del régimen de reinducción tuvo una mejor sensibilidad y VPN que la TC sola, y una exploración

Objective: This retrospective study aimed to evaluate the role of metabolic parameters of 18F-FDG PET/CT in pediatric lymphoblastic lymphoma (LBL).Methods: Thirty patients with LBL underwent 42 scans. Metabolic parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) were measured at baseline PET/CT. Univariate and multivariate analysis for survival were performed to assess their prognostic value. Twelve patients underwent PET/CT after reinduction regime, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for predicting relapse were calculated.Results: Patients with stage IV had a higher TMTV than those with stage III (P=0.031). Besides, patients with T-LBL or mediastinal involvement had a high TMTV and TLG (P<0.05). There was no significant difference in PET/CT metabolic parameters between patients with different outcomes (P>0.05). Children with a low TMTV (<242.91cm3) had a better 3-year EFS compared with those with a high TMTV (88.9% vs. 56.3%; P=0.036). SUVmax and TLG were not predictive of EFS (P=0.874; P=0.152). However, none of the metabolic parameters of baseline PET/CT were independent prognostic factors for outcomes of pediatric LBL. PET/CT underwent after reinduction regime present with higher sensitivity (50% vs. 0%) and NPV (90% vs. 83.3%) for predicting relapse than CT alone.Conclusions: Metabolic parameters of baseline PET/CT were not predictive of outcomes in children with LBL. PET/CT done after the reinduction regime had better sensitivity and NPV than CT alone, and a negative scan could be a reliable indicator for sustained remission (AU)

Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention. One Sentence SummarySingle-cell profiling demonstrates multifarious dysregulation of innate immune phenotype associated with COVID-19 severity.

Additional analyses exploring the hypothesized transdifferentiation of plasmablasts to developing neutrophils in severe COVID-19

We thank Alquicira-Hernandez et al. for their reanalysis of our single-cell transcriptomic dataset profiling peripheral immune responses to severe COVID-19. We agree that careful analysis of single-cell sequencing data is important for generating cogent hypotheses but find several aspects of their criticism of our analysis to be problematic. Here we respond briefly to misunderstandings and inaccuracies in their commentary that may have led to misinformed interpretation of our results.

A single-cell atlas of the peripheral immune response to severe COVID-19

There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.

Causality in objective world: Directed Acyclic Graphs-based structural parsing / 中华流行病学杂志

The overall details of causality frames in the objective world remain obscure, which poses difficulty for causality research. Based on the temporality of cause and effect, the objective world is divided into three time zones and two time points, in which the causal relationships of the variables are parsed by using Directed Acyclic Graphs (DAGs). Causal DAGs of the world (or causal web) is composed of two parts. One is basic or core to the whole DAGs, formed by the combination of any one variable originating from each time unit mentioned above. Cause effect is affected by the confounding only. The other is an internal DAGs within each time unit representing a parent-child or ancestor-descendant relationship, which exhibits a structure similar to the confounding. This paper summarizes the construction of causality frames for objective world research (causal DAGs), and clarify a structural basis for the control of the confounding in effect estimate.

Identification and drug susceptibility testing of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis / 中华流行病学杂志

Objective: To understand the etiological characteristics and drug susceptibility of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis and provide evidence for the prevention and control of infectious mastitis in cows. Methods: The milk sample was collected from a cow with mastitis, which was pretreated with 4% NaOH and inoculated with L-J medium for Mycobacterium isolation. The positive cultures were initially identified by acid-fast staining and multi-loci PCR, then Mycobacterium species was identified by the multiple loci sequence analysis (MLSA) with 16S rRNA, hsp65, ITS and SodA genes. The drug sensitivity of the isolates to 27 antibiotics was tested by alamar blue assay. Results: Two anti-acid stain positive strains were isolated from the milk of a cow with mastitis, which were identified as non-tuberculosis mycobacterium by multi-loci PCR, and multi-loci nucleic acid sequence analysis indicated that one strain was Mycobacterium thermoresistibile and another one was Mycobacterium elephantis. The results of the drug susceptibility test showed that the two strains were resistant to most antibiotics, including rifampicin and isoniazid, but they were sensitive to amikacin, moxifloxacin, levofloxacin, ethambutol, streptomycin, tobramycin, ciprofloxacin and linezolid. Conclusions:Mycobacterium thermoresistibile and Mycobacterium elephantis were isolated in a cow with mastitis and the drug susceptibility spectrum of the pathogens were unique. The results of the study can be used as reference for the prevention and control the infection in cows.

Exposure-preceding-outcome regarding time sequence among cohort studies in real world / 中华流行病学杂志

One of the commonly accepted merits of cohort studies (CSs) refers to the exposure precedes outcome superior to other observational designs. We use Directed Acyclic Graphs to construct a causal graph among research populations under CSs. We notice that the substitution of research population in place of a susceptible one can be used for effect estimation. Its correctness depends on the outcome-free status of the substituted population and the performance of both screening and diagnosis regarding the outcomes under study at baseline. The temporal precedence of exposure over outcome occurs theoretically, despite the opposite happens in realities. Correct effect estimate is affected by both the suitability of population substitution and the validities of outcome identification and exclusion.

A structural classification of strategies for confounding control in research design / 中华流行病学杂志

Confounding affects the causal relation among the population. Depending on whether the confounders are known, measurable or measured, they can be divided into four categories. Based on Directed Acyclic Graphs, the strategies for confounding control can be classified as (1) the broken-confounding-path method, which can be further divided into single and dual broken paths, corresponding to exposure complete intervention, restriction and stratification, (2) and the reserved-confounding-path method, which can be further divided into incomplete exposure intervention (in instrumental variable design and non-perfect random control test), mediator method and matching method. Among them, random control test, instrumental variable design or Mendelian randomized design, mediator method can meet the requirements for controlling all four types of confounders, while the restriction, stratification and matching methods are only applicable to known, measurable and measured confounders. Identifying the mechanisms of confounding control is a prerequisite for obtaining correct causal effect estimates, which will be helpful in research design.

A cohort study on the association between dynamics of thyroid volume and the changes of physical growth as well as the comparison of different thyroid volume indexes in school-aged children / 中华流行病学杂志

Objectives: To investigate the association between the dynamics of thyroid volume and the changes of physical growth in school-aged children as well as to compare the applicability of different thyroid volume indexes, so as to explore more reliable methods for the assessment of thyroid volume. Methods: In October 2012, a multi-stage cluster sampling method was used to select a primary school in Minhang district of Shanghai, Haimen city of Jiangsu province and Yuhuan city of Zhejiang province, respectively. In these areas, a total number of 784 students aged 8-10 years were enrolled in the cohort. Demographic data was collected, while height and weight were measured, with BMI and body surface area (BSA) were calculated. Thyroid volume was examined by B-ultrasonography. Height volume index (HVI), weight and height volume index (WHVI), BMI volume index (BMIV) and BSA volume index (BSAV) were all applied to correct the thyroid volume. All students were followed up, one year later. Results: A total of 769 students with complete data on thyroid volume and physical growth were enrolled, including 378 boys (49.16%) and 391 girls (50.84%). Thyroid volume showed an increase with age, while growth of thyroid volume reduced with the increase of age (P<0.001). The thyroid volume showed a correlation with the changes of physical growth. The growth of height appeared as the dominant influencing factor for thyroid volume growth in those aged 8 and 10 years (P<0.05), while the growth of weight, BMI and BSA were all influencing factors for thyroid volume on students aged 9 years (P<0.05). Conclusions: Thyroid volume in school-aged children was a factor not only associated with age but also with physical growth which had not been considered in the currently used criteria. The inclusion of items as iodine intake, age, physical growth into the thyroid volume indexes seemed to be more reliable, in practice. For the assessment of goiter, HVI for students aged 8 and 10 years and BMIV for students aged 9 years might serve as better indicators.

Epidemiological features of adult chronic kidney diseases in a community-based population in Songjiang district, Shanghai / 中华流行病学杂志

Objective: To investigate the prevalence and associated factors of chronic kidney diseases (CKD) in adult residents living in a community of Songjiang district, Shanghai. Methods: A total of 9 257 residents aged 20-75 years old in Xinqiao township of Songjiang district were selected by random cluster sampling. All the participants were interviewed to complete a set of personal questionnaire and undergo physical examinations. Urine and blood tests including markers of kidney damage and related associated factors with CKD, were carried out. Results: Eligible data from 8 207 subjects were enrolled in the study. After adjustment for age and gender, the prevalence of CKD was 8.4% (95%CI: 7.8%-9.0%), with majority of the patients (76.5%) appeared in the early stage (Ⅰ and Ⅱ) of the disease. The prevalence of CKD increased with age and higher prevalence was seen in females than in males (P<0.001). Results from logistic regression analysis showed that factors as: being elderly or female, having hypertension, hyperuricemia, and hyperlipidemia were all independently associated with CKD. Conclusions: The prevalence of CKD appeared relatively high in adult residents of Xinqiao township, Songjiang district where CKD had become a public health problem. Factors as: being female or elderly, hypertension, hyperuricemia, and hyperlipidemia were found to be associated with CKD. Our findings suggested that early prevention and control on CKD to reduce the incidence of end-stage renal diseases and related complications had called for more urgent attention.