The clinical and PET/CT imaging features of the two groups were analyzed. The predictive model and simplified scoring system for distinguishing between AMs and ABNs were built based on clinical and PET/CT risk factors using multivariable logistic regression in the training cohort. The performances of the predictive model and simplified scoring system in both the training and testing cohorts were evaluated by the areas under the receiver operating characteristic curves (AUCs) and calibration curves. The comparison of AUCs was evaluated by the DeLong test.A total of 303 patients who underwent P = 0.5733) and testing  datasets.The predictive model included four risk factors: sex, the ratio of the maximum standardized uptake value (SUVmax) of adrenal lesions to the mean liver standardized uptake value, the value on unenhanced CT (CTU), and the clinical stage of extra-adrenal malignancies. The model achieved an AUC of 0.936 with a specificity, sensitivity and accuracy of 0.918, 0.835, and 0.874 in the training dataset, respectively, while it yielded an AUC of 0.931 with a specificity, sensitivity, and accuracy of 1.00, 0.735, and 0.851 in the testing dataset, respectively. The simplified scoring system had comparable diagnostic value to the predictive model in both the training (AUC 0.938, sensitivity: 0.825, specificity 0.953, accuracy 0.885; Our study showed the potential ability of a machine learning model and a simplified scoring system based on clinical and 18F-FDG-PET/CT imaging features to predict AMs in patients with indeterminate adrenal nodules and extra-adrenal malignancies. The simplified scoring system is simple, convenient, and easy to popularize. The adrenal gland is the fourth most common metastatic site in patients with extra-adrenal cancer, primarily lung cancer 39%) and breast cancer (35%) , 2. Appr9% and brAccurate differential diagnosis of adrenal masses can mostly be performed in patients with extra-adrenal malignancy based on non-invasive imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT). Adrenal washout CT and the value on unenhanced CT images (CTU) have shown perfect ability to differentiate benign from malignant lesions –9. HowevRadiomics, as an advanced image analysis technology, has good differential diagnostic ability for adrenal lesions, especially malignant and benign tumors , 18. How18F-FDG-PET/CT is needed. Therefore, the purpose of the present study was to assess the accuracy of the predictive model and simplified scoring system based on 18F-FDG-PET/CT for differentiating AMs from ABNs in cancer patients with indeterminate adrenal nodules.Previous studies have demonstrated that 18F‐FDG‐PET/CT is extremely predictive and sensitive for differentiating adrenal tumours found in routine MRI or CT examinations in patients with or without a cancer history –22. In an = 15), if a new adrenal lesion had developed (n = 88) or if the size had increased or decreased after treatment in a short period of time (n = 62) [n = 59) or no change in size during at least 1 year of follow-up (n = 79). Because the patients in our study comprised a whole dataset, to test the predictive model, we randomly assigned the dataset to a training cohort  and a testing cohort  at a ratio of 6:4  patients with extra-adrenal malignancy confirmed by histopathology before performing 18F-FDG PET/CT examination; (2) complete PET/CT images and clinical information; and (3) indeterminate adrenal lesions: unilateral hyper-attenuating (CTU ≥ 10 HU) adrenal tumors (1 cm ≤ LD ≤ 3 cm). The reasons for the use of 1 cm as the cut-off for LD were as follows: (a) providing sufficient lesion volume for reliable quantitative measurement technology and (b) increasing confidence in the existence of true focal adrenal lesions. Finally, 165 patients met the eligibility criteria for diagnosing metastases if there is histologic confirmation ((n = 62) . A total18F-FDG (4.2 MBq/kg). Unenhanced CT images were first acquired with 120 kVp, 80 mAs, and a slice thickness of 5 mm from the top of the skull to the middle femur during tidal breathing, and then full-ring dedicated PET images were obtained from the middle thigh to the top of the head during shallow breathing. PET/CT images were reconstructed using the ordered-subset expectation maximization algorithms and CT scans for attenuation correction.The patients fasted for approximately 6 h and had a blood glucose level < 11 mmol/L before undergoing the examination. A Discovery Elite PET/CT scanner  was used to acquire images approximately 60 min after intravenous injection of A radiologist who had 6 years of PET/CT diagnostic experience and did not know the pathological and clinical information interpreted the CT and PET images. LD, short diameter (SD), left or right and CTU of the adrenal nodules were assessed on the image of the maximum axial area of the tumour. The region of interest (ROI) should contain two-thirds of the largest transverse section of the lesions, and adjacent fat should be avoided when manually measuring CTU. In addition, calcification, hemorrhagic components, and cystic degeneration or necrosis were excluded from the ROI measurements. The maximum standardized uptake value (SUVmax) for each adrenal nodule was recorded by manually drawing a circular oval ROI that included the tumour as much as possible on the axial PET image and while paying attention to avoid adjacent FDG-avid structures. Moreover, the average spleen and liver standardized uptake value (SUV) for each patient was recorded by manually drawing oval ROIs including the spleen or the right lobe of the liver as much as possible on the axial PET images. Then, the ratio of the adrenal lesion SUVmax to the average spleen SUV (SUV/spleen) and the ratio of adrenal lesion SUVmax to the average liver SUV (SUV/liver) were calculated Fig. .Fig. 2Thp values < 0.05 were considered statistically significant.R (version 4.1.2) was used to perform all statistical analyses. Differences in quantitative characteristics such as SD, LD, age, CTU, SUVmax, SUV/spleen, and SUV/liver were analyzed using the Wilcoxon rank-sum test. For qualitative characteristics such as sex, location, type and clinical stage of primary cancer, the chi-square test was used to analyze whether there was a significant difference between AMs and ABNs. The predictive model was developed based on the above significant factors by logistic regression, which was obtained using the function “lrm” (in the “rms” package). The area under the receiver operating characteristic (ROC) curves (AUCs) of risk factors and the predictive model and simplified scoring system were obtained using the function “reportROC” (in package “reportROC”). The function “nomogram” (in package “rms”) was used to draw the nomograms. The comparison between AUCs was evaluated by the DeLong test in MedCalc. Calibration curves were used to examine the performance characteristics of the nomogram and the simplified scoring system in detail , liver (5.45%), breast (4.24%), and kidney (4.24%) cancers and lymphoma (2.42%) malignancies. The extra-adrenal malignancies in the ABN group included malignancies in the lung (50.0%), gynaecological malignancies 10.87%) and breast cancers (10.14%), thyroid carcinoma (7.24%), and lymphoma (5.07%) (Table 0.87% andP > 0.05) between the training and testing datasets, showing the rationality of randomly grouping the total data. Patients with ABNs had a higher female percentage than patients with AMs in both the training  and testing  datasets. The AM group had a higher proportion of patients with clinical stage III/IV extra-adrenal cancers, while the ABN group had a lower proportion of those with clinical stage III/IV cancers in both the training (p < 0.001) and testing (p = 0.007) datasets. For the primary cancer types, the AM group had a higher primary lung cancer: other cancer ratio than the ABN group in both the training  and testing  datasets.The demographic details of the AM and ABN patients are presented in Table p < 0.001) and testing  datasets. The mean LDs of the ABN group were 1.5 cm and 1.5 cm in the training and testing datasets, respectively, which were significantly smaller than those of the AM group in both the training  and testing  datasets. The SUVmax, SUV/liver, and SUV/spleen of AMs were all significantly higher than those of ABNs in both the training and testing datasets   and testing dataset (P = 1.000), Fig. The simplified regression coefficients did not affect the accuracy of differential diagnosis of the score by ROC analyses , as a new dataset, were further analyzed. The simplified scores for the patients with histologic confirmation ranged from 3.63 to 21.53 points. When using the optimal cut-off value of 10.5, the specificity and sensitivity of the simplified scoring model were 96.6% and 86.7%, respectively, and accuracy was up to 94.6%, which indicates that compared with the original training and testing datasets, the simplified scoring system still has good diagnostic performance in the confirmed dataset . Since strong correlations were observed among SUVmax, SUV/liver, and SUV/spleen, we chose SUV/liver as a risk factor for reducing redundancy according to a previous study [In our study, the SUVmax, SUV/liver, and SUV/spleen were all higher for AMs than for ABNs in both the training and testing datasets (us study . The AUCus study . Boland us study . In addius study  and Launus study . The reaus study , 21. KunMost previous reports only focused on individual PET/CT imaging features to distinguish AMs and ABNs –22. Our We believe this may be a valuable predictive model for diagnosing AMs. Therefore, biopsy could be avoided in some cases.But there is a crucial point to note when using this model. In clinical practice, our proposed model may provide management recommendations for patients with indeterminate adrenal nodules and extra-adrenal malignancies. Generally, a higher score obtained from this simplified scoring system suggests an increased likelihood of the lesion being predicted as a metastasis. However, increasing the cut-off value reduces sensitivity, potentially leading to fail to detect metastases. This may result in inaccurate clinical staging of the primary cancer and impact the formulation of precise treatment plans. On the other hand, lowering the cut-off point reduces the rate of missed diagnoses but lowers specificity, which increases the risk of falsely detecting ABN as AM. This could result in unnecessary examinations and psychological pressure for patients. Therefore, we recommend engaging in careful communication with patients before establishing treatment protocols, as the choice of the cut-off value should depend on the level of risk both patients and doctors are willing to accept. Ultimately, the simplified scoring system serves as a convenient and valuable tool, providing evidence for doctors and patients.There were several limitations. Firstly, features such as CTU and SUVmax may be different among radiologists since they were manually extracted. Experienced radiologists may have more accurate measurement results than junior radiologists. Measuring such features through computer algorithms may improve the stability and reproducibility of models and features. Secondly, since only a small number of patients underwent pathological confirmation, the majority of adrenal nodules in our study were diagnosed based on follow-up imaging. However, this situation reflects current practices. Meanwhile, based on the confirmed dataset, we further validated the good diagnostic performance of our predictive model. Thirdly, in our study, thick-slice PET and CT images were utilized, and contrast-enhanced CT was not included as part of the PET/CT scanning procedure. It is important to note that previous studies have demonstrated a notable improvement in diagnostic accuracy when PET data is combined with contrast-enhanced CT data . TherefoIn summary, the predictive model and simplified scoring system based on traditional clinical and PET/CT imaging features showed good diagnostic performance for differentiating AMs from ABNs in cancer patients with indeterminate adrenal nodules and thus assisted clinicians in pre-treatment decision-making.


The purpose of this study is to compare and analyze the clinicopathological characteristics and prognosis of patients with invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) and invasive ductal carcinoma (IDC) in triple-negative breast cancer (TNBC), and to explore the factors affecting the prognosis, so as to provide new ideas for clinical diagnosis and treatment of these patients.The patients with TNBC underwent surgery in the Department of Breast Surgery of Harbin Medical University Cancer Hospital from October 2012 to December 2018 were retrospectively analyzed and divided into IDC-DCIS group and IDC group. The clinicopathological characteristics and prognosis of the two groups were compared. P < 0.05 was considered statistically significant.A total of 358 patients were enrolled. There were significant differences in age (P = 0.002), family history (P = 0.016), menopausal status (P = 0.003), KI-67% (P < 0.001), lymphovascular invasion (P = 0.010), histologic grade of IDC (P < 0.001) and multifocal (P < 0.001) between the two groups. The disease-free survival (DFS) of the IDC-DCIS group was better than that of the IDC group , but the overall survival (OS) of the two groups was not statistically significant . In addition, the coexistence of DCIS (P = 0.030), lymph node pathologic stage (P = 0.001), tumor location (P = 0.011), and adjuvant chemotherapy (P < 0.001) were independent prognostic factors for DFS.In TNBC, the IDC-DCIS group had less invasive biological characteristics. The DFS of the IDC-DCIS group was better than that of the IDC group, but there was no statistical difference in OS between the two groups. In addition, the coexistence of DCIS, lymph node stage, tumor location and adjuvant chemotherapy may be independent prognostic factors for DFS. Breast cancer has a high incidence among female cancer patients in the world, and its related mortality has jumped to the second place ; non-primary breast cancer or combined with other malignancies; immunohistochemical type or Her-2 positive; histologic types except simple IDC and IDC-DCIS; pT4; distant metastasis before treatment; bilateral breast cancer; clinicopathological data and follow-up information was incomplete.The pathological sections were independently reviewed by experienced pathologists. The results of ER and PR showed that the proportion of positive cells ≥ 1% was positive, and the proportion of positive cells less than 1% was negative. Evaluation of the Her-2 result: According to the guidelines for Her-2 detection in breast cancer, it was negative 0; negative 1; uncertain 2; positive 3 + . For the areas with uncertain 2 + , the final results were positive or negative by FISH (in situ hybridization). The results of KI-67 showed that the positive rate of tumor nuclei cells ≥ 20% was high expression, and that of tumor nuclei cells < 20% was low expression. According to the Nottingham grading system, the histological grading system of IDC can be divided into low (G1 level), intermediate (G2 level) and high (G3 level). According to the criteria established by AJCC, the TNM pathological staging of breast cancer has been adopted. In addition, for cases of invasive ductal carcinoma with ductal carcinoma in situ, the pathological results are based on the invasive components.The data of this study were statistically analyzed using SPSS 26.0 software. T-test is used to compare the differences between the two groups for the measurement data that conform to the normal distribution; Mann‐Whitney U test is used to compare the differences between the two groups for the measurement data that do not conform to the normal distribution; Chi-square test is used to compare the count data of the two groups. The survival curve was plotted using GraphPadPrism9.0 software and analyzed using the Kaplan–Meier method, and the difference in survival between the two groups was analyzed using the log-rank test. The primary endpoint of this study was DFS, defined as the time from diagnosis of breast cancer to first breast cancer recurrence, distant metastasis, or no breast cancer recurrence to death. The secondary endpoint was OS, defined as the time from diagnosis of breast cancer to death from any cause. Univariate and multivariate Cox regression were used to determine the hazard ratio (HR), 95% confidence interval (CI), and risk factors associated with survival. P < 0.05 was considered statistically significant.From October 2012 to December 2018, a total of 358 patients met the inclusion criteria and had complete data. According to the postoperative pathological report, the patients were divided into IDC-DCIS group and IDC group. Among them, there were 169 cases in IDC-DCIS group and 189 cases in IDC group. The mean age of the IDC-DCIS group was 53 years old, and that of the IDC group was 49 years old (P = 0.002). There are 11 cases (6.5%) in the IDC-DCIS group had family history, 3 cases (1.6%) in the IDC group had family history (P = 0.016); In the IDC-DCIS group, 117 cases (69.2%) had a KI-67% of 20% or higher, while in the IDC group, 178 cases (94.2%) had a KI-67% of 20% or higher (P < 0.001). In the IDC-DCIS group, 18 cases (10.7%) showed lymphovascular invasion, while in the IDC group, 39 cases (20.6%) showed the same (P = 0.010); in the IDC-DCIS group, 4 cases (2.4%) were classified as histologic grade G1, 117 cases (69.2%) as histologic grade G2, and 48 cases (28.4%) as histologic grade G3. In comparison, in the IDC group, 33 cases (17.5%) were classified as histologic grade G2 and 156 cases (82.5%) were classified as histologic grade G3 (P < 0.001); in the IDC-DCIS group, 17 cases (10.1%) were identified as multifocal, whereas in the IDC group, only 2 cases (1.1%) were identified as multifocal (P < 0.001). , and 5 deaths were observed. In the IDC group, 17 recurrences, 22 metastases , and 9 deaths were observed. . The IDC-DCIS group was more likely to have a family history . The IDC-DCIS group was more likely to be postmenopausal . Similar results were also reported by Goh et al. KI-67% was more highly expressed in the IDC group . Wong et al. retrospectively analyzed the pathological data of 1355 cases of IDC-DCIS and IDC and obtained similar results , lymph node pathologic stage , lymphovascular invasion , tumor location , adjuvant chemotherapy , adjuvant radiotherapy  are all factors that influence DFS in univariate analysis. Inclusion of these factors in the multivariate analysis revealed that IDC , lymph node pathological stage N3 , tumor location in the upper inner quadrant or central area , not receiving adjuvant chemotherapy  are independent risk factors for DFS. Goh et al. also found that coexistence of DCIS and lymph node status were independent prognostic factors affecting DFS (Goh et al. This study is a retrospective study and it is a single center, which has limitations, and selection bias will inevitably occur. Secondly, due to the long follow-up period, which leads to a small increase in the loss to follow-up rate, and the small sample size may cause statistical differences, large-scale multicenter prospective randomized controlled trials are still needed for research.In TNBC patients, the IDC-DCIS group had less aggressive biological characteristics than the IDC group. The DFS of the IDC-DCIS group was better than that of the IDC group in TNBC, but there was no statistical difference in OS between the two groups. Independent prognostic factors affecting DFS included coexistence of DCIS, lymph node pathologic stage, tumor location, and adjuvant chemotherapy.


Interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A concentrations correlated with MLS . IL-5 concentrations correlated with more favorable GOS-E scores at 3, 6, and 12 months . Regulated on activation, normal T-cell expressed and secreted (RANTES) concentrations correlated with complete cSDH resolution . The decision tree model identified that higher concentrations of CXCL9 were predictive of MLS (risk ratio [RR] = 12.0), higher concentrations of IL-5 were predictive of cSDH thickness (RR = 4.5), and lower concentrations of RANTES were predictive of cSDH recurrence (RR = 2.2). CXCL9, IL-6, VEGF, IL-5, and RANTES are associated with recurrence after surgery and may be potential biomarkers for predicting cSDH recurrence and neurological outcomes.The elderly population are at high risk for developing chronic subdural hematoma (cSDH). Surgical evacuation of cSDH is one of the most common procedures performed in neurosurgery. The present study aims to identify potential inflammatory biomarkers associated with its development and recurrence. Patients (>65 years of age) who presented with symptomatic cSDH (≥1 cm thickness or ≥5 mm midline shift [MLS]), requiring surgical intervention, were prospectively enrolled. The collected cSDH fluid was analyzed for inflammatory markers. Computed tomography (CT) scan data included pre-operative cSDH thickness and MLS. Outcome data included Glasgow Outcome Scale-Extended (GOS-E) score at 3, 6, and 12 months post-surgery, as well as cSDH recurrence. A decision tree model was used to determine the predictive power of extracted analytes for MLS, cSDH thickness, and recurrence. This pilot study includes 20 enrolled patients . Rate of cSDH recurrence was 42%, with 21% requiring reoperation. Chemokine (C-X-C motif) ligand 9 (CXCL9) concentrations correlated with cSDH thickness ( This propagates a sustained inflammatory response with continuous blood and fluid collection.23 Ducruet and colleagues reported higher recurrence rates after twist-drill craniostomy (28.1%) compared to craniotomy (19.4%) and burr hole craniostomy (11.7%).24 Management of recurrent cSDH remains a challenge to the clinician because this pathology is associated with increased hospital stay, morbidity, and mortality in a high-risk population.11Mortality rate ranges from 2.7% to 4.6%, and an estimated 5–33% of patients have recurrent cSDH requiring repeated surgeries.14 However, the complete mechanistic pathway is yet to be elucidated. Pro- and anti-inflammatory biomarkers have the potential to aid clinical decision making regarding diagnosis, prognosis, and providing markers by which to target treatments. Predictive models that utilize concentrations of peripheral or local biomarkers have yet to be performed. By recruiting persons undergoing cSDH evacuation, the purpose of this pilot study is to provide proof of concept that serum, plasma, and/or intraoperative specimens can be useful for identifying prognostic biomarkers of post-surgical cSDH recurrence.An active field of research on cSDH is the exploration of peripheral or local biomarkers to guide the prediction of patient outcomes and risk of recurrence. Past research suggests that there is an inflammatory drive in its formation.Each participant was prospectively enrolled under an institutional review board–approved protocol. Patients who underwent cSDH evacuation at the University of Pittsburgh Medical Center from September 2019 to September 2020 were enrolled in the Brain Trauma Research Center (BTRC). Inclusion criteria included the following: 1) >65 years of age; 2) CT scan consistent with a diagnosis of cSDH with >/ = 10 mm thickness and/or >/ = 5 mm midline shift (MLS); 3) intent to undergo surgical intervention for cSDH with collection of subdural fluid; and 4) signed informed consent from a legal authorized representative. Patients with the following medical conditions were excluded: 1) active malignancy or medical condition which in the opinion of the investigator would compromise analysis; 2) neurodegenerative disease ; 3) debilitating neuropsychiatric disease ; or 4) past medical history of a chronic immunosuppressive state . Patients were excluded if their cSDH was iatrogenic  or if they were pregnant.Enrolled patients were taken to the operating room for surgical evacuation, and the specimens were collected under sterile conditions. Surgical techniques included a minicraniotomy or through burr hole craniostomy with subdural drain placement. Serum and plasma were collected perioperatively from an existing vascular access site or by venipuncture.® Human Cytokine/Chemokine/Growth Factor Panel A, which was a broad array including 48 analytes (pg/mL) for inflammatory markers, with the capability to calculate concentrations for each biomarker in subdural fluid samples, as used previously in our laboratory.Collected samples were stored within the biorepository system at the BTRC. They were centrifuged and stored in 0.5-mm aliquots at −80°C for future batch analyses. Samples were analyzed by a central, independent laboratory at the Hillman Cancer Center using a Luminex assay, specifically, MILLIPLEXDemographic and clinical data were collected by research nurse coordinators, including patient age, sex, mechanism of injury, admission symptoms and neurological status , and use of antiplatelets and -coagulants. All study patients were followed post-operatively and were assessed by the primary neurological outcome Glasgow Outcome Scale–Extended (GOS-E) at 3, 6, and 12 months as well as secondary neurological outcomes, including mortality, cSDH recurrence, and other complications.Radiographical findings were collected and analyzed by a trained neurosurgeon. Patient CT scans were examined before surgery to ascertain pathology, MLS (mm), and thickness of the subdural hematoma (mm). Magnetic resonance imaging (MRI) T1-weighted image (T1WI) scans were also obtained before surgery in order to classify each cSDH as hyperdense, hypodense, isodense, or mixed-density collections. Along with post-operative clinical examinations, immediate post-evacuation CT imaging and at follow-up were analyzed. Determination of the complete resolution of cSDH after evacuation was based on a formal evaluation by a board-certified neuroradiologist.Descriptive statistics for continuous variables are reported as means and standard deviations (SDs) and, for categorical variables, are reported as percentages. Pearson correlations for continuous variables and Spearman correlations for ordinal variables were performed. Mean concentrations and SDs of each biomarker measured in the subdural fluid are reported in the supplementary material . A minimPost hoc relative risk ratios  and 95% confidence intervals (CIs) were conducted to identify the risk of the predictor at the algorithm-identified cut point for the outcome. Binary variables were created for each cut point, and univariate logistic regression models were built to obtain the percent variance (R2) of the most important predictor from each model to the outcome. Only subdural fluid biomarkers were included as potential predictors in the decision tree. Three decision tree models were built, predicting three different outcomes: 1) cSDH recurrence; 2) MLS; and 3) cSDH thickness. cSDH recurrence was the primary outcome, but midline shift and hematoma size were included because previous research has repeatedly demonstrated that they are strong predictors of recurrence.26 This analysis was performed using SPSS Modeler software (v 18.1).The decision tree is built such that the strongest predictor appears at the first “split” and continues iteratively down the tree until no further splits contribute to information gain. N = 13; 65%). All patients presented with a GCS score of 15, and the mechanism of injury in 17 patients (85%) was a fall, whereas 3 patients (15%) presented with no known mechanism. Primary admission symptoms included headache , gait disturbance , altered mental state , speech issues , hemiparesis , syncope , and seizure . Anticoagulant and -platelet usage upon admission included none , aspirin , clopidogrel , both aspirin and clopidogrel , and apixaban .Patient demographic, clinical, and radiographical characteristics are summarized below . BetweenN = 11; 55%) and left  sides of the brain, as well as bilaterally . CT findings yielded an average cSDH thickness of 20.0 (±5.9) mm and MLS of 6.4 (±4.1) mm. Pre-operative MRI characteristics included hyperdense , hypodense , not applicable , isodense , and mixed density . cSDH was evacuated using the minicraniotomy technique in 85% of patients (N = 17) and burr hole craniostomy in 15% of patients (N = 3), supplemented by subdural drain placement in 95% of patients (N = 19). Complete resolution of cSDH after evacuation was achieved in 15% of patients (N = 3).Radiographical and intraoperative data are summarized below . By lateN = 1), temporal venous stroke (N = 1), hypoxic respiratory failure (N = 1), post-operative recurrence (N = 1), seizures (N = 1), and meningitis (N = 1). The patient with hypoxic respiratory failure died before post-operative CT imaging was obtained. Of the remaining 19 patients, cSDH recurrence occurred in 8 patients (42%), with 4 patients (21%) requiring reoperation. Median GOS-E scores at 3, 6, and 12 months were 7 (N = 17), 7.5 (N = 14), and 6.5 (N = 10), respectively. Favorable outcome, as defined by a GOS-E score of 4–8, was recorded in 12 of 17 patients at the 3-month time point (70.6%), 9 of 14 recorded patients at 6 months (64.3%), and 5 of 10 patients at 12 months (50.0%).Outcome measures are summarized below . In-hospOf the 48 biomarkers measured by the Luminex assay, 17 met the minimum mean threshold of 1000 pg/mL for the present analysis. Their mean concentrations are reported below . Chemokir = 0.975, p = 0.040; r = 0.974, p = 0.005). Further, patients with higher VEGF-A levels had a moderately positive correlation with MLS . Higher RANTES values had a moderately positive correlation with the complete resolution of cSDH after evacuation .Higher CXCL9 levels had a very high positive correlation with cSDH thickness on the presenting CT scan (p < 0.001) compared to patients with a CXCL9 concentration below that value. When using the CXCL9 cutoff as a predictor in a univariate logistic regression model of MLS >10 mm, it accounted for 51% of the variance . An MLS >10 mm on the presenting CT scan has been found to be significantly related to cSDH recurrence.The C5.1 algorithm built a decision tree model with 90% accuracy and an area under the curve (AUC) of 0.83 . The onlp < 0.001) compared to patients with an IL-5 concentration below that value. When using the IL-5 cutoff as a predictor in a univariate logistic regression model of hematoma thickness >20 mm, it accounted for 85% of the variance . cSDH thickness >20 mm on the presenting CT scan has been found to be an independent predictor of cSDH recurrence.The C5.1 algorithm built a decision tree model with 90% accuracy and an AUC = 0.94 . The onlp = 0.01) compared to patients with a RANTES concentration above the cutoff. When using the RANTES cutoff as a predictor in a logistic regression model of recurrence, it accounted for 49% of the variance .The C5.1 algorithm built a decision tree model with 95% accuracy and an AUC = 1.0. The algorithm identified the RANTES concentration of 1649.24 as the strongest differentiator of cSDH recurrence , such thTwo other blood biomarkers were included in the decision tree model. Among patients with lower RANTES values, G-CSF concentrations ≤45,978.2 pg/mL had recurrence at a 73% rate compared to the patients with higher G-CSF values (0% recurrence rate). Among patients with lower RANTES and lower G-CSF values, patients with PDGF-AA concentrations ≤3401.45 pg/mL had recurrence at a 100% rate compared to patients above the PDGF-AA cutoff (40% recurrence rate).1–13 Further, cSDH can go unnoticed clinically, given that symptoms become more detectable over the course of weeks.28 Notably, the 20 patients included in the current study all presented with a GCS score of 15. Mild symptomology can lead to CT scans not being utilized. Advances in clinical management inclusive of predictive models are a necessity for improved diagnosis, treatment, and detection of recurrence. Increased feasibility of peripheral and local biomarkers as a supplement to clinical management stems from recent advancements in biomarker analysis technology, setting the stage for their usage in a predictive model.29–31 Inflammatory markers CXCL9, IL-6, VEGF-A, IL-5, and RANTES correlate with neurological outcome, cSDH thickness, MLS, and complete resolution of cSDH after evacuation. CXCL9 was predictive of MLS, IL-5 was predictive of cSDH thickness, and RANTES was predictive of cSDH recurrence. Our results mark these five biomarkers as potential candidates for a preliminary model that is not yet suitable for clinical use.As cSDH increases in prevalence in an aging population, concern of its socioeconomic burden on the elderly and the healthcare system grows.32 An animal model study found that CXCL9 promotes neural differentiation in neural precursor cells, which respond to central nervous system injury, as well as the maturation of oligodendrocytes.33 Stanisic and colleagues found that CXCL9 levels in cSDH fluid were significantly greater than levels in serum, suggesting a local mechanism confined to the hematoma area acting as an impetus to cSDH growth.34 This is consistent with the present study that higher CXCL9 levels are correlated with greater cSDH thickness and predictive of MLS, which may be attributable to its role in a local mechanism of angiogenesis inhibition and tissue extravasation. CXCL9 has already been proven as a viable biomarker in cardiac disease,36 bolstering the case for its use in a predictive cSDH model.CXCL9, also known as monokine induced by gamma interferon, participates in the inflammatory response through promotion of chemotaxis and differentiation of leukocytes, inhibition of angiogenesis, and tissue extravasation.38 Results from a mouse model study suggest that IL-5 plays a role in the interplay between immune cells and brain cells,39 whereas another rodent model of blast neurotrauma exhibited elevated levels of IL-5 in various parts of the brain, suggesting that IL-5 may be a key inflammatory mediator after blast injury.40 Further, studies have found elevated IL-5 levels in cSDH compared to cerebrospinal fluid (CSF) and venous blood.42 Eosinophils play a conductive role in the development of cSDH inflammation and membranes,43 with data from one study displaying a statistically significant correlation between IL-5 and eosinophil-derived neurotoxin (EDN), and EDN with the percentage of eosinophils in cSDH fluid.41 This supports the present findings, that increased IL-5 can be predictive of hematoma thickness.Similarly, IL-5 is a proinflammatory cytokine that acts as a key mediator in the growth, migration, and activation of eosinophils.44 Further, IL-6 aids in the shift from acute to chronic inflammation.45 In the brain, IL-6 fosters the synthesis of nerve growth factor, as well as the survival and differentiation of neurons, with evidence suggesting its expression to be favorable post-injury.46–49 Whereas levels of IL-6 in CSF remain low under homeostatic conditions, they have been shown to spike post-TBI.51 In cSDH patients, Suzuki and colleagues found significantly greater concentrations of IL-6 in subdural fluid than in blood samples.52 Moreover, Frati and colleagues found significantly higher levels of IL-6 in subdural fluid in patients who presented with cSDH recurrence than patients without recurrence.53 These previous studies are consistent with our findings that higher IL-6 levels correlate with greater MLS, which may represent a dose-response relationship with cSDH severity, suggesting its potential role as a predictive biomarker.IL-6 is a proinflammatory cytokine that plays a key role in the host defense response to infection or tissue damage by catalyzing the acute immune response and hematopoiesis.54–56 In the brain, VEGF additionally acts to moderate neuroprotection and neural migration; however, excessive concentrations can lead to edema through increased leakage across intracellular barriers and has also been linked to neurological disorders such as ischemic stroke.57 Immunohistochemical findings exhibit substantial expression of VEGF in inflammatory cells permeating cSDH neomembranes.58 Similar to IL-6, studies reported VEGF to have greater concentrations in subdural fluid than in serum.58–60 Though VEGF is an important contributor of cSDH development, as previously described,61 findings from a recent study suggest that VEGF is not a reliable predictive biomarker for cSDH recurrence.62 Despite our findings indicating a correlation between VEGF concentration and greater MLS, further studies are required to determine its potential as a biomarker predictive of cSDH recurrence.VEGF-A, also simply called VEGF, is the chief moderator of blood vessel formation, playing a key role in the inflammatory process through angiogenesis, vasculogenesis, hematopoiesis, and by increasing vascular permeability.63 Although RANTES is associated with chronic inflammation and might be a factor in angiogenesis,64 studies indicate that RANTES has a neuroprotective role and increases neuronal survival.66 Further investigation is required to fully elucidate the role of RANTES in cSDH recurrence.The current study found a positive correlation between higher levels of RANTES with complete resolution of cSDH after evacuation, and our decision tree model found RANTES to be predictive of cSDH recurrence, with concentrations <1649.24 pg/mL associated with a greatly increased risk of recurrence. This is an interesting finding, given that a previous study reported a positive association between RANTES and cSDH recurrence requiring reoperation.Our findings are limited by the sample size, yet we intend to broaden the study population as our research continues. As such, the decision trees presented should not be considered suitable for clinical use at this time. Further, several analyte data values were absent from our current analysis because of being outside the Luminex assay's range of sensitivity. Future studies should incorporate least absolute shrinkage and selection operator regression in order to maximize usage of the collected analyte data. The scope of the current study focused on subdural fluid; however, analyzing analyte concentrations in plasma and serum are part of our future directives. We aimed our pilot investigation at the analytes that met a minimum mean threshold of 1000 pg/mL; however, future directives should contrarily examine analytes below a maximum mean threshold to determine whether any analytes are being suppressed in cSDH compared to baseline.This pilot study is the first analysis to date to compare analyte levels from operative cSDH fluid with neurological outcomes. This analysis identified five biomarkers  as possible biomarkers for predicting cSDH characteristics, recurrence, and neurological outcomes. These preliminary results suggest the need for a larger study for validation and comparative analyses in peripheral plasma and/or serum biospecimens. These analytes play specific roles in proinflammatory response and angiogenesis, elevated levels of which can be associated not only with larger initial cSDH and mass effect, but also higher risk of recurrence after surgical evacuation. Future analyses could allow for a predictive, peripheral surrogate marker for cSDH reoccurrence and radiological imaging.


Median survival duration was lower in the non-HIV group . The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group . Initial mRS score  and highly active antiretroviral therapy (HAART) in HIV patients  had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4,  PML is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions, such as human immunodeficiency virus (HIV) infection, lymphoproliferative disorders, post-organ transplantation immunosuppression, and autoimmune diseases2. Several studies in the United States and Europe reported that 44–49% of patients were diagnosed with HIV, 22–31% with hematologic malignancies, 9–20% with chronic inflammatory diseases, and 3–4% with solid organ transplants4. Recently, PML has been associated with immunomodulatory medications such as natalizumab, efalizumab, and rituximab7.Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of the John Cunningham virus (JCV), leading to oligodendrocyte destruction and subsequent demyelination8. Introduction of highly active antiretroviral therapy (HAART) increased the median survival of HIV patients from 0.4 to 1.8 years; however, the overall mortality rate remained at 74.5–78.0%9. Interestingly, in the non-HIV population, the median time to death after PML diagnosis was two months, and the case-fatality rate was 90%10.Despite advances in treatment options such as pembrolizumab or BK virus-specific T cell-based immunotherapy, PML is a severe and fatal infection with a reported 1-year mortality rate of 38.2%12 However, therapeutic agents like cytarabine, cidofovir, mefloquine, alpha-interferon, and serotonin antagonists have not shown potential in the prognosis of PML patients17. Therefore, it is necessary to study whether the recent development of HAART and changes in HAART initiation, regardless of CD4 cell count, will improve PML prognosis in HIV patients18. In addition, an increase in the number of patients receiving immunosuppressive treatments has led to PML occurrence in various immunosuppressive conditions2. Despite this, studies on PML are still lacking due to its low prevalence and incidence.Several potential therapeutic options have been used to improve this poor prognosis, but exhibited only a few clear benefits. Initiation of HAART in HIV patients has shown a clear survival benefitTherefore, this study aimed to investigate the long-term prognosis and prognostic factors for overall mortality of patients with PML through an extended observation period of over 21 years.19. The median age was 46 years , and 74.5% were male patients  diagnostic criteria were enrolled Fig. 19. The m2O , and median CSF white blood cell count was 1 cell/µL . The median time from symptom onset to PML diagnosis was 46 days .The most frequently observed symptoms in patients with PML were motor weakness (51.1%), gait instability (46.8%), speech abnormalities , and apraxia 42.6%) (Table .6% (Tablp = 0.020); however, most other symptoms were not significantly different. In HIV patients, the neutrophil count was low , whereas the lymphocyte ratio was high  and consequently, lower NLR ratios were observed . Furthermore, the detection rate of JCV  was higher in HIV patients . The 30-day, 90-day, and 1-year mortality rates were overall higher in the non-HIV group, with the 1-year mortality rate being statistically significant . The overall mortality rate was also significantly higher in the non-HIV group , which was further confirmed by the Kaplan–Meier curve and log-rank test (p = 0.007)  (Table 91 (Tablep = 0.020). Patients with moderately severe disability with 4 points or higher mRS, unable to walk without assistance, were 85.0% in the non-HIV group and 59.2% in the HIV group. All patients with improved mRS score during follow-up period were HIV PML patients . Significant differences in overall mortality according to the mRS cutoff point 4 were confirmed by the Kaplan–Meier curve and log-rank test (p = 0.013)  (Table –6 (Tablep = 0.038) was associated with increased overall mortality (Table p = 0.038) was related to increased overall mortality, and HAART  was associated with decreasing overall mortality  in the HIV group and 184 days (IQR 74–1566) in the non-HIV group. Additionally, the overall mortality rate of patients with PML during the long observational period was 40.7% in the HIV group and 80.0% in the non-HIV group. Although advances in treatment options have been considered for only a few patients, the prognosis of PML has improved compared to the previous decade8. As the introduction of HAART had a significant effect on the median survival of PML patients in HIV population, it is likely that changes in HAART initiation regardless of CD4 count will further improve the prognosis of PML.In previous studies, the median survival duration increased up to 66 months after the introduction of HAART in the HIV population; however, the overall mortality rate was 74.5–78.0%p = 0.010) and HAART  were associated with overall mortality of patients with PML2. In a similar report, a higher baseline CD4 + T cell count (HR 0.33) and CSF inflammatory profile (HR 0.12) were significantly related to the long-term survival of patients with PML21. Another report by Koralnik et al. showed an association between JCV-specific cytotoxic T-lymphocytes (CTLs) and HIV-positive PML survivors and HIV-negative PML patients with improving clinical status22. In a comparative study, Marzocchetti reported that JCV-specific CTLs were associated with a trend toward more prolonged survival in patients with PML23. Our study showed that higher initial mRS score was a significant risk factor for overall mortality in a long-term follow up period. In addition, the introduction of HAART was a predictor of long-term survival in HIV-positive PML patients.Various studies have attempted to elucidate predictors of prognosis and mortality in patients with PML. Khanna et al. showed that baseline CD4 + T cell count 2. In our study, patients with HIV with HAART had a 63% reduction in overall mortality in PML compared to non-HIV patients. Therefore, HAART  in HIV patients was associated with decreasing overall mortality or long-term survival of PML patients.HAART is the mainstream treatment for HIV-positive patients with PML. Various studies have reported a decrease in the incidence and mortality of PML in HIV-positive patients after the introduction of HAART. In the Eurosida cohort, the incidence of PML decreased from 0.7 to 0.07 per 100 cases per year (PY) after the introduction of HAART27. However, in this study, 29.6% (8 of 27) of HIV patients were diagnosed with PML during HAART. The 1-year mortality rate in the group receiving HAART was lower than that in the group newly starting HAART ; however, no statistical difference was observed (Supplementary Table p = 0.243). This suggests that the prognosis may be better in HIV patients receiving HAART (who recovered some immune response) than in naive HIV patients. However, the factors contributing to the disease course of PML in HIV patients receiving HAART are unknown. Genetic risk factors, such as mutations in VP1 or polymorphisms in the tumor suppressor protein p53, may affect the pathogenesis of PML29. In this regard, a prospective study is required to analyze and compare the immunological characteristics of the two groups.PML may rarely occur in HIV patients receiving continuous HAART24. PML pathophysiology involves oligodendrocyte destruction and subsequent demyelination of the CNS1. Currently, treatments that can reverse CNS destruction and subsequent demyelination are unavailable, so early recognition of possible PML and achieving immune reconstitution are crucial for improving prognosis.Our study also showed that the initial mRS score is an important prognosis factor, and in particular, the long-term prognosis is poor in the case of mRS score of 4 or higher through the Cox regression model. PML was dominated by motor weakness (51.1%), gait instability (46.8%), speech abnormalities (46.8%), and apraxia (42.6%), but various symptoms may appear depending on the site of involvement. Since PML can occur not only in the case of hematologic malignancy (14.9%) and HIV infection (57.4%) but also in various disease groups taking immune-modulating agents, its diagnosis is difficult and time-consuming. Early detection contributes to a better prognosis of PML with limited disease progression and rapid and effective immune reconstitution30. The fact that dimethyl fumarate-associated PML typically occurs in the context of severe lymphopenia, whereas abnormal production of IL-10, expression of PD-1, and reduced expression of CD49d by JCV-specific T cells are observed in natalizumab-induced PML, suggests that not only the number of lymphocytes but also their composition is important in the pathogenesis of PML32. In addition, chronic infection with persistent antigens can lead to immune exhaustion, eventually rendering T cells unable to respond effectively to persistent antigens33. CD8 + T cells are specialized for intracellular pathogen clearance, but a combination of decreased effector function, inhibitory receptor expression, and cytokine hyporesponsiveness can lead to CD8 + T cell exhaustion in chronic viral infections35. CD4 + T cells are essential for the immune response to chronic viral infection, but due to decreased production of IL-2, TNFα, and IFNγ and increased expression of the suppressive cytokine IL-10, CD4 + T cells exhibit altered function during chronic infection, which is considered a form of functional exhaustion37.In this study, the median lymphocyte count was 785 cells/microliter, which was not as severe as expected. This may be due to the fact that HIV-negative patients had a much lower baseline lymphocyte rate of 3.5% (3.3–5.7%), while HIV-positive patients had a baseline lymphocyte rate of 26.3% (15.4–29.9%) and 830 (580–1530). PML was also observed in patients with already recovered lymphocytes, with eight patients taking HAART and nine patients suffering from immune reconstitution inflammatory syndrome (IRIS). Lymphopenia is a risk factor for PML, but monitoring of absolute lymphocyte counts alone is not an accurate predictor of risk because it does not take into account the complexity and diversity of the immune system39. In addition, the long-term prognosis was evaluated by reflecting the overall PML occurring under various immunosuppressive conditions through increased use of immunosuppressive agents. For patients with hopeless discharge or loss of follow-up, accurate mortality data could be obtained from the Ministry of the Interior and Safety of South Korea. This allowed us to accurately assess mortality or long-term prognosis, the primary or secondary endpoint of our study.Our study had several strengths. The long-term prognosis was evaluated while fully reflecting the introduction of HAART and the recommendation of antiretroviral treatment regardless of CD4 cell count in randomized controlled trials such as Temprano ANRS 12,136 and STARTOur study has certain limitations. Due to the retrospective nature of this study, PML diagnosis or treatment may have physician-dependent selection bias. Furthermore, there were some cases where brain biopsy could not be performed depending on the patient's condition; the diagnosis was made based on clinical and radiographic findings. In addition, due to the low prevalence of PML, the sample size was small despite the long observation period. Therefore, to overcome this low prevalence and incidence, our team is planning a nationwide PML study through a multicenter study or anonymized data linkage.With the widespread adoption of HAART, the survival duration of HIV-positive patients with PML has extended. However, the mortality rate and the prognosis for PML in non-HIV patients remain frustrated. Initial mRS score is a significant risk factor for long-term overall mortality in patients with PML. Early detection of PML and early initiation of HAART in patients with HIV may improve prognosis.We screened approximately 1.51 million hospitalized patients with electronic medical records who were admitted to two tertiary hospitals with 2,400 and 1,000 beds from March 1999 to June 2021. Of these, we retrospectively reviewed patients with PML using International Classification of Diseases-9, 10 diagnostic codes 046.3 and A81.2. Eligibility criteria included age > 18 years and patients with PML diagnosed by the AAN criteria. Excluded patients were those with insufficient clinical data (n = 2) and who did not meet PML diagnostic criteria, such as diffuse large B-cell lymphoma (n = 2), glioma (n = 1), non-small cell lung cancer brain metastasis (n = 1), Bickerstaff encephalopathy (n = 1), adult-onset neuronal intra-nuclear inclusion disease (n = 1), progressive vascular leukoencephalopathy (n = 1), CNS demyelinating disorder (aquaporin-4) (n = 1), progressive myoclonic epilepsy (n = 1), multiple sclerosis (n = 2), Parkinson’s disease (n = 2), toxic encephalopathy (n = 1), toxoplasmosis (n = 1), and viral encephalitis (n = 1)  of Yonsei University College of Medicine (IRB no. 4-2021-1045). Informed consent was waived by the IRBs of Yonsei University College of Medicine due to the retrospective nature of the study. This study complied with the Declaration of Helsinki and Good Clinical Practice guidelines.19. Its diagnostic classification includes definite, probable, and possible PML19. Definite PML diagnosis is confirmed by neuropathologic demonstration of the typical histopathologic triad  coupled with the presence of JCV, or typical clinical and radiographic features with JCV detection19. Probable PML is based on either histopathologic triad with no JCV detection or JCV polymerase chain reaction (PCR) positivity in the cerebral spinal fluid (CSF) with the absence of clinical features or neuroimaging19. Possible PML diagnosis requires the presence of JCV without the typical histopathologic triad, or clinical and radiological features with negative CSF JCV PCR, or positive CSF JCV PCR without clinical and radiological features19. The degree of neurological disability was measured with the modified Rankin Scale (mRS) at each clinical follow-up40. IRIS is an inflammatory process that occurs through immune reconstitution during HAART in HIV patients that cannot be explained by new opportunistic infection or drug toxicity41.PML was defined according to the AAN diagnostic criteria with clinical features, neuroimaging, pathology, and laboratory dataImmunosuppressive agents include tacrolimus, corticosteroids, methotrexate, mycophenolate mofetil, and cyclosporine. Chemotherapeutic agents include adriamycin, bevacizumab, bortezomib, carboplatin, cisplatin, cyclophosphamide, cytarabine, etoposide, ifosfamide, irinotecan, melphalan, mitomycin, oxaliplatin, pazopanib, pomalidomide, rituximab, thiotepa, vincristine, 5-Fluorouracil, and tegafur/gimeracil/oteracil potassium. Other underlying medication treatments include ustekinumab, total body irradiation, and radiation therapy, used in combination with immunosuppressive or chemotherapeutic agents.The mortality data were obtained from the Ministry of the Interior and Safety of South Korea, which collects mortality data of all Korean citizens.The primary endpoint of this study was overall mortality during the observational period. Overall mortality was defined as death from any cause. The secondary endpoints were 30-day mortality, 90-day mortality, 1-year mortality, and mRS score of the last follow-up visit.p-value of < 0.05 was considered statistically significant. A Kaplan–Meier curve was drawn using patient survival data from the time of admission to either death or the last follow-up date. The log-rank test was used to determine the difference in survival distributions between the two groups. Hazard ratio (HR) and 95% confidence intervals (CIs) of variables for overall mortality were analyzed using a Cox proportional hazards model. Variables for multivariable analysis were selected based on the clinically significant risk factors in univariable analysis. Statistical analysis was performed using IBM SPSS Statistics for Windows version 26 .Comparison between groups was performed using the Chi-squared and Fisher’s exact tests for categorical variables and the Mann–Whitney U test for continuous variables. The This study was approved by the Institutional Review Boards (IRBs) of Yonsei University College of Medicine (IRB no. 4-2021-1045). Informed consent was waived due to the retrospective nature of the study. This study complied with the Declaration of Helsinki and Good Clinical Practice guidelines.Supplementary Table 1.


With the development and popularization of low-dose chest CT technology, the diagnosis and survival rates of patients with early lung cancer (LC) have significantly improved. The occurrence of colorectal cancer (CRC) as the second primary cancer (SPC) in primary lung cancer (PLC) survivors has become an essential factor affecting the prognosis of early LC. This study explored the potential association between PLC and CRC genetically, laying a foundation for developing SPC-CRC prevention strategies after primary early LC.Based on a two-sample bidirectional Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of PLC and CRC, applied inverse variance weighted (IVW) as the main method to assess the incidence association between the two cancers, and used a variety of other MR methods for supplementary analysis. Finally, the Genetic Risk Scores (GRS) method was used for secondary analysis to verify the results robustness further.From LC to CRC forward MR analysis, 20 genetic IVs of overall LC, 15 genetic IVs of squamous cell lung carcinoma (LUSC), and 10 genetic IVs of adenocarcinoma of the lung (LUAD) were screened. In the reverse MR analysis from CRC to LC, 47 genetic IVs for overall CRC, 37 for colon cancer, and 25 for rectal cancer were screened. The IVW method and a variety of MR methods all found that overall LC and CRC were significantly associated at the genetic level. Subgroup analysis also showed that LUSC was associated with CRC. And the results of the GRS method were consistent with those of the main analysis, confirming the robustness of the study.Our MR study found an association between LC and CRC, with an increased risk of SPC-CRC following PLC, especially LUSC. Our study provides an essential basis for the precise prevention of SPC-CRC after PLC, suggesting that we should pay more attention to the population with a history of PLC in clinical work, and pay close attention to the incidence of SPC-CRC, and carry out intervention and treatment as soon as possible.The online version contains supplementary material available at 10.1186/s12967-023-04612-7. Lung cancer (LC) is a highly prevalent malignancy and is the foremost cause of worldwide cancer-related mortality . Non-smavs 91.1% for lobectomy). Further analysis of the causes of death revealed that second primary cancer (SPC) is the second leading cause of mortality after LC itself. It is also one of the main factors contributing to better 5 year survival rates for patients undergoing segmental resection than lobectomy, with colorectal cancer (CRC) being the most common type among all SPCs [Currently, surgery is the recommended treatment for patients diagnosed with stage I-IIIA NSCLC . Lobectoall SPCs . In addiall SPCs . The stuMendelian randomization (MR) is a widely utilized method of etiological inference in genetic epidemiology . In receIn this study, we aim to utilize GWAS data of PLC and CRC to elucidate the correlation between these two cancers at the genetic level through a bidirectional two-sample MR analysis. Our study will provide a foundation for developing prevention strategies for CRC after early-stage PLC surgery in clinical practice.The overview of the study design of the MR is displayed in Fig. , which used 14,803 cases and 12,262 controls of European descent to genotype on the OncoArray and combined the results with the previously published results from aggregated GWAS analysis of LC on 29,266 patients and 56,450 controls [https://gwas.mrcieu.ac.uk/). We used only freely accessible summarized data in this study; therefore, this study did not require ethical approval.The genetic instrumental variables (IVs) for LC were derived from the largest sample size to date of the PLC GWAS published by James D. McKaycontrols . Regardi2 measure of linkage disequilibrium (LD) among IVs < 0.01 at a 500 kb window ; (b) P value less than the genome-wide significant level identified in the corresponding study ; (c) minor allele frequency (MAF) > 0.01 (mutations are present in more than 1% of the population); (d) nonpalindromic single-nucleotide polymorphisms ; (e) removal of IVs associated with confounding factors using the PhenoScanner  [The MR analysis evaluates the effect of a predictor on an outcome. There are three assumptions for a valid IVs—it must be: (a) associated with the exposure (the “relevance” assumption); (b) independent of the outcome given the exposure (the “exclusion restriction”); and (c) independent of all (both observed and unobserved) confounders (the “exchangeability” assumption) , 16. If ffected) .P < 0.05 is considered statistically significant. Weighted median and simple median method, which have the high tolerance for pleiotropic genetic variation that can obtain relatively stable effect values even when nearly half of the IVs are invalid. The key distinction between the two methods lies in their management of estimated medians, with the simple median method assigning equal weight to all values and the weighted median method incorporating weight for each value [The principal analyses were conducted using the inverse variance weighted (IVW) approach. The IVW method, the most commonly used and mainstream method for MR analysis, use meta-analysis approach to combine ratio estimates of SNPs in an inverse variance weighted way and obtain an estimate of the effect of risk factors on outcomes , 20. Ratch value , 23. MR-ch value . In concch value : (1) “MRch value . MR-Eggech value .α can be estimated by β values are estimated effects on the response variable or outcome with standard errors seβ [To validate the above MR results, we conducted a secondary analysis by applying the GRS method. We conducted the analyses utilizing R (version 3.5.3) with the “gtx” R package (version 0.0.8 for Windows), whose grs.summary module has the GRS function. The grs.summary module merely used single SNP association summarized data obtained from the results of the GWAS analysis, which is similar to a method which regresses an outcome onto an additive GRS , 28. ForP value of less than 0.05 with the exclusion of possible horizontal pleiotropy. If the P value of Cochran’s Q test was less than 0.05, the final results of MR referred to a multiplicative random-effects model of IVW. Leave-one-out sensitivity analysis was also performed to further assess each IV’s independent potency. We considered a P value of less than 0.05 to indicate a statistically significant genetic association between exposures and outcomes. The strength of the association between SNP and the exposures are evaluated using the F statistic [MR-Egger regression and the Cochran’s Q test were applied to estimate pleiotropy and heterogeneity, respectively. We eliminated the possibility that the MR-Egger intercept had a tatistic . No weakP < 0.05. R version 4.1.2 and the packages “MendelianRandomization”, “TwosampleMR”, “RAPS”, “PRESSO” and “gtx” were used for all analyses [A two-sided statistical analysis was conducted, and statistical significance was determined at analyses .P < 5 × 10–8). The overall LC, LUAD, and LUSC IVs datasets identified 3912, 1122, and 2755 IVs that were nonpalindromic sequences, respectively . Based on the LD status between genetic variant loci, 25, 13, and 15 independent IVs associated with overall LC, LUAD and LUSC were selected without LD correlation . Removal of IVs associated with confounders using the PhenoScanner database  [In LC to CRC MR analysis, 4002 overall LC, 1176 LUAD, and 2789 LUSC IVs in the GWAS study reached significant differences (1658797) , 32. UltP = 0.0029; Figs. P = 0.0012; weighted median: OR = 1.0040, 95% CI 1.0020–1.0060, P = 0.0001; MR-PRESSO: OR = 1.0026, 95% CI 1.0009–1.0043, P = 0.0080; MR-RAPS: OR = 1.0026, 95% CI 1.0013–1.0040, P = 0.0002; Fig. In forward-direction MR, in overall LC to overall CRC MR study, IVW analysis revealed a significant association between overall LC and overall CRC at the genetic level . A single palindromic sequence has been identified within the SNPs datasets . Based on the LD status between genetic variant loci, 50, 39, and 25 independent IVs associated with overall CRC, colon cancer and rectal cancer were selected without LD correlation . Removal of IVs associated with confounders using the PhenoScanner database . Ultimately, we identified 47 genetic IVs for overall CRC, 37 for colon cancer and 25 for rectal cancer  at the genetic level   at the genetic level   at the genetic level   at the genetic level   at the genetic level   at the genetic level    recommenThere are several advantages in our MR study. Firstly, to the best of our knowledge, this is the first study to evaluate the genetic association between LC and CRC based on a two sample MR analysis with large scale GWAS data. Compared to previous observational studies, MR analysis could effectively reduce potential bias including confounders and reverse causation, thus enhancing the causal inference. Secondly, GWAS datasets of LC and CRC applied were predominately based on populations of European ancestry, which was capable to minimize the impact of population stratification. Furthermore, we systematically screened confounding factors associated with PLC and CRC using the PhenoScanner database and eliminated IVs associated with confounding factors to avoid the potential horizontal pleiotropy of genetic IVs. Meanwhile, MR-Egger and MR-PRESSO (Outlier-corrected) outlier SNP evaluation methods were used to examine the influence of pleiotropy further and ensure the reliability of the results , 46. In In summary, this study has established a genetic association between PLC and CRC, which provides an essential basis for the precise prevention of SPC-CRC after PLC, suggesting that we should pay more attention to the incidence of SPC-CRC and carry out intervention and treatment as soon as possible.Additional file 1: Figure S1. MR leave-one-out sensitivity analysis for “exposure” on “outcome”.Additional file 2: Table S1. Results of heterogeneity test, horizontal pleiotropy test. LC: lung cancer; CRC: colorectal cancer; LUAD: adenocarcinoma of lung; LUSC: squamous cell lung carcinoma.Additional file 3: Table S2. Effect estimates for associations of genetic instruments with exposure.


Psycho-oncological screening is required to identify distressed patients and direct them to psycho-oncological care. In practice, screening procedure and related communication are still insufficient due to various barriers on the side of the medical team. The aim of this study is to evaluate the specifically developed training (OptiScreen training) on screening from nurses’ perspective.N = 72 nurses from visceral–oncological care at Hanover Medical School received the 6-h training, which consisted of three modules and targeted topics around screening, psycho-oncology and communication. The training was evaluated using a pre- and post-questionnaire assessing screening knowledge, uncertainties and further satisfaction outcomes.t(63) = − 13.32, p < .001, d = 1.67). General satisfaction with the training was achieved (62.0–98.6% satisfied with the training elements). Feasibility (69%) and general acceptance (94.3%) for the training were rated positively.Personal uncertainties were significantly reduced by the training (The nurses rated the training as useful to reduce personal uncertainties regarding the screening process. Acceptability, feasibility and satisfaction with the training from the nursing perspective were achieved. The training contributes to minimizing barriers to inform about psycho-oncology and to recommend appropriate support services to patients.The online version contains supplementary material available at 10.1007/s00432-023-04936-3. A cancer diagnosis is a high risk for experiencing a variety of psychosocial stressors. Approximately 50% of patients are significantly mentally distressed .Both before and after the training, the nurses completed an evaluation form. An anonymous return of these forms was given since nurses used their own personalized code. The mean time difference between the pre- and the post-evaluation was M = 9.77, SD = 5.00; range: 0–38). Due to shift changes and sick leave, a total of 2 persons did not complete module 1, but only module 2 and 3.72 nurses participated in OptiScreen-Training from January to March 2021 at Hanover Medical School. Inclusion criteria involved working in the visceral oncology centre as nurses or case managers . There were no exclusion criteria, as the entire team attended as mandatory training during working hours. Sixty-two were female, and most participants were between 20 and 64 years of age .The questionnaire was developed specifically for the evaluation of the OptiScreen-Training taking the hierarchical evaluation model into account  on the "uncertainties" scale items . For the total scale, differences of the pre-  and post-comparison  were significant (t(63) = − 13.322, p < 0.001), with an effect size of Cohen's d = 1.67.Table As an indication of the functional benefit of the training, 87.5% of participants reported that after the training, they knew where to find the screening questionnaire to hand out to patients.not at all useful" or "not very useful". The topics psychological disorders/distress in cancer patients were rated as "quite useful" or "very useful" by 90.6%, psycho-oncological care structures by 82.1%, psycho-oncological screening by 93.7%, communication with cancer patients by 92.2% and self-care by 82.8%.Regarding the usefulness of the respective training topics, none of the topics were rated as "I agree" and "I strongly agree" were scored as an indicator of satisfaction with each dimension  to recommend the training to colleagues, and 94.3% would like to receive regular training on psycho-oncology. 69.0% agreed or strongly agreed that the training was feasible. There is no difference between the fear of additional workload due to the training  and the evaluation of the current additional workload after the training  = 1.494, p = 0.140).Overall, 62 of 64 nurses (94.3%) would be likely Below is the link to the electronic supplementary material.


Colour-related search tasks are common in many professional fields. The study investigated whether increasing chromatic saturation can enhance the visual performance of individuals with colour vision deficiency (CVD) in colour-related search tasks.10 normal trichromats  age: 23.1 (3.3) years) and 15 individuals with CVD [8 deutans and 7 protans identified by HRR plates]  years) participated in this study. Four naturalistic sceneries of everyday tasks/ birds, animals and flowers of 15 different colour combinations  were presented in ‘low’ saturation, ‘original’  and ‘high’ saturation condition using the Psychopy program on a colour-calibrated monitor. On each trial, the subject was asked to identify a specific-coloured target.-1) of the normal trichromats [Mean (SD):77.76% correct*s-1 (16.32)] was significantly higher than CVD [45.71% correct*s-1 (18.95)] in the “original” test images (p = 0.001), but in individuals with CVD, there was no significant difference between ‘original’ [45.71% correct*s-1 (18.95)] and ‘high’ saturation condition ([47.43% correct*s-1 (20.07)]; p > 0.05). However, colour-wise, increased saturation showed improvements (≥ 10%) in protans mainly for ‘red’ combinations with other colours such as white , purple, orange, grey, green, brown and black.Overall, the visual search performance index (expressed as product of accuracy and a reciprocal of reaction time (%correct*sThe study suggests that increasing the saturation of certain colour combinations can potentially aid in the visual search performance of individuals with CVD. This knowledge will help in better counselling and management of the patients. Colour-based visual search is a commonly encountered task in professions such as police , army, nIncreasing the chromatic saturation of the visual display may benefit individuals with CVD  becauseTwenty-five participants participated in the study. Out of which, 10 were normal trichromats  age:- 23.1 (3.3) years) and 15 individuals with colour vision deficiency [ years)]. The screening plates of Hardy Rand Rittler (HRR) pseudoisochromatic plates  distinguished normal trichromats from individuals with CVD, who were further tested using the Colour Assessment and Diagnosis (CAD) test  to identify the type and quantify the severity of colour vision defects. The test was performed according to the manufacturer’s instructions. The lighting for the HRR test was white light (standard office fluorescent lamp) with illumination of 300 lux. The individuals with CVD were subclassified as protans and deutans. All participants had a monocular visual acuity of at least 20/20 (logMAR– 0.0) with refractive correction in place. The participants were sourced primarily from patients who reported to the L V Prasad Eye Institute (LVPEI), Hyderabad campus. Individuals with CVD in staff and student cohorts were also recruited for the study. The study was conducted at the L V Prasad Eye Institute, Hyderabad. The participants were informed of the test duration and nature of the test. If the participants were interested, written informed consent was obtained prior to testing. This study adhered to the tenets of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of the L V Prasad Eye Institute, Hyderabad (Reference no: LEC-BHR-P-09020-509).https://www.flickr.com/explore) and 500px (https://500px.com/) websites that represented 15 colour combinations: brown/black, red/purple, red/green, red/white, red/brown, red/orange, red/grey, red/black, green/yellow, green/blue, green/white, green/brown, green/grey, orange/brown, and orange/yellow. The colour combinations were chosen based on the common colours confused by individuals with CVD ). Further post-hoc analysis using Bonferroni correction, with regard to saturation, revealed that the visual search performance index in both the ‘original’ and ‘high’ saturation conditions was significantly better than the ‘low’ saturation performance condition in individuals with CVD. However, there was no significant difference between the ‘original’ (45.17% correct*s-1(9.44)) and ‘high’ saturation condition (46.9% correct*s-1(10.52); p = 0.71) in individuals with CVD.The overall visual search performance index in normal trichromats (mean (SD): 77.8% correct*sp2 = 0.040), and protans performed better than deutans. There was also a significant interaction between saturation and defect type  = 4.7; p = 0.009, ηp2 = 0.02). Similar patterns were observed for other visual search parameters, such as accuracy and reaction time, except for the absence of a significant interaction between saturation and type of defect. Overall, compared to deutans, all outcome variables of protans were significantly better   on the visual search performance index was significant  = 26.8, p <0.0001, η) Tables .The minimum and the maximum difference in the visual search performance index of the individuals with CVD compared to the normal trichromats was noted in the ‘green/white’ and ‘red/grey’ combination respectively . In protThe normal trichromat performance in the ‘high’ saturation category was not significantly enhanced compared to the ‘original’ category. In protans, there were numerous colour combinations  which improved upon increasing chromatic saturation . HoweverThere are four key findings of this study. First, the visual search performance index in individuals with CVD was significantly poorer compared to normal trichromats . Second,The poor visual search performance index of individuals with CVD relative to normal trichromats is consistent with several other previous studies , 16, 19.Overall, the visual search performance of individuals with protan deficiency was better than that of individuals with deutan deficiency. The visual search task in this study was not a threshold-level task. It is possible that starting ‘chromatic saturation’ used in the ‘original’ image condition may itself be representative of a suprathreshold task, where protans perform better than deutans . BesidesChromatic displacement is a concept used in the CAD test as well, where the target and background are initially separated by a small chromatic displacement in the CIE colour space which is either increased or decreased based on the performance of the individual. Increasing the saturation should make the task easier. However, there is a caveat: this improvement is noticed only when the chosen colours are in different confusion lines. This may also explain why the effect of increasing chromatic saturation did not improve the visual search performance index for some colour combinations. There are few specific colour combinations where the visual search performance index worsens , it would be relatively easier to estimate the chromaticity of the targets in the realworld and ensure that modified coloured targets are of specified recommendations. However, the results of this study cannot be generalised to objects in the real world. Nevertheless, it provides a framework regarding which colour combinations can be potentially modified to enhance the visual search performance index in individuals with CVD.As CVD is not treatable  thereforThe present study has some limitations. The selection of individuals included almost an equal percentage of protan and deutan deficiencies which is inconsistent with the prevalence of CVD . HoweverThe study concluded that increased chromatic saturation produces a differential effect across various chromatic combinations, especially protans benefitting from higher saturations in most combinations containing red. Therefore, this study is the first step towards potentially modifying colour-specific environmental settings in an occupational environment based on increased chromatic saturation to aid individuals with CVD.S1 DataThe combinations highlighted in yellow are demonstrated in (XLSX)Click here for additional data file.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.


Abnormal birthweights are critical public health challenges accountable for most non-communicable diseases and perinatal mortalities. Regardless of the myriad of mixed evidence on maternal factors responsible for abnormal birthweight globally, most of these findings are attained from urban and rural settings. This study serves as one of the key pieces of evidence in view of the increasing prevalence of abnormal birthweight particularly in some parts of semi-rural Ghana. The study, therefore, aims to estimate the prevalence of abnormal birthweight and identify some possible maternal risk factors for abnormal birthweight in Northern Ghana.A retrospective cross-sectional study was conducted in Savelugu municipality from February–March 2022. A total of 356 mothers aged 16–46 years, having a neonate and attending postnatal care service, were recruited as study participants. Data were collected from maternal and child health record books and through structured interviews. To identify the maternal risk factors for abnormal birthweight, chi-square/Fischer’s exact test and multinomial logistic regression were employed as bivariate and multivariate analyses, respectively, at 95% confidence level.Prevalence rates of low birthweight and macrosomia were 22.2% and 8.7%, respectively. Maternal anaemia in first trimester  and third trimester  of gestation was strong predictors for low birthweight. Mothers belonging to minority ethnic groups ; mothers who had ≥ 8 antenatal care visits ; and mothers having neonates whose birth length > 47.5 cm  had reduced odds for low birthweight. Alternatively, mothers with gestational weeks ≥ 42  and mothers from the richest households (highest socioeconomic homes)  were more likely to birth to macrosomic infants.The prevalence rates of low birthweight and macrosomia were relatively high. Anaemia in the first and third trimesters was strong determinants of low birthweight. Being minority ethnic group, frequency of antenatal visits, and childbirth length reduced the risk of low-weight births. Advanced gestational age and socioeconomic status of mothers were also predictors of macrosomia. Hence, nutrition counselling, community health education, and promotion of lifestyle improvement coupled with strengthening of health service delivery are recommended interventions. Birthweight is the most measurable outcome of pregnancy categorized into normal, low, and high birthweights . GloballIt is estimated that yearly 15% to 20% of all births are less than 2500 g, representing more than 20 million births worldwide. In sub-Saharan Africa, the prevalence of low birthweight is around 13.0% which is more than double-folds in the developed countries . CorrespAccording to Ugwa et al., maternal anthropometry including weight, height, and body mass index (BMI) is a key indicator during antenatal care (ANC) and must not be underpinned in the healthcare system . EvidencDespite ongoing interventions which have been evidenced to have productive impact on pregnancy outcomes such as focused antenatal care; nutrition counselling and education; girls’ iron folic acid tablet supplementation; exclusive breastfeeding; micronutrient supplementation; and malaria prevention through the distribution of long-lasting insecticide nets, and intermittent preventive treatment in pregnancy , 24, abnMoreover, as evidenced in most developing countries, Ghana is also encountering nutrition transition where maternal under- and over-nutrition coexist reflecting the double-burden of malnutrition situation . The preA retrospective cross-sectional study was conducted in Savelugu municipality, Northern Region, Ghana, to estimate the prevalence of low birthweight and macrosomia among children of mothers attending postnatal care services and identify maternal factors responsible for these abnormal birthweights.Savelugu municipality is located in northern part of Northern Region of Ghana. Dagomba is the major ethnic group and agriculture accounts for the major source of income in the municipality. The municipality has five major public health facilities with 13 operational community-based health planning and services (CHPS) zones. The total number of reproductive-aged women in the municipality was 40,533 with an annual expected number of pregnancies of 6,700 in 2019 . AntenatThis study targeted nursing/lactating mothers having a neonate and living in the municipality. Mothers who possessed MCHRB and seeking first-day PNC services at the health facilities were recruited, while mothers with twin deliveries, home deliveries, and cardiovascular diseases were excluded from the study.n) was determined using Cochran’s (1977) formula; n =  p) of low birthweight and macrosomia in urban Northern Ghana were previously reported to be 29.6% and 10.5%, respectively [d) of 0.05, and standard z score The sample size  version 2021.2.4  of handheld tablet devices were administered from 1 February to 31 March 2022 through seven enumerators.Majority of data were collected from MCHRB which included: maternal anthropometry (pre-pregnancy BMI) determined from parameters measured in the first trimester of pregnancy; gestational weight gain (GWG) which was estimated as weight difference of mothers, measured within one week prior to delivery and the one recorded at the first ANC visit (first trimester) ; anthropRemaining data were collected through structured interviews with mothers in locally spoken language (Dagbani) consisting of: socio-demographic characteristics of each respondent including age, marital status, educational level, ethnic group, religion, sex of neonate, and household size , 19, 23;2), normal (≥ 18.5 to 24.9 kg/m2), and overweight/obese (≥ 25.0 kg/m2) using 2004 WHO standard criteria. Parity was classified into primiparity (0–1 delivery) and multiparity (≥ 2 deliveries), while gravidity was grouped into primigravida (0–1 pregnancy) and multigravida (≥ 2 pregnancies) [Statistical data analyses were performed by using STATA version 17.0  with all analyses determined at 95% confidence level. The data attained were transferred from ODK platform onto Microsoft excel version 16.6. Birthweight was grouped into low birthweight (< 2500 g), normal birthweight (≥ 2500 to 3999 g), and macrosomia (≥ 4000 g), whereas pre-pregnancy BMI was categorized into underweight (< 18.5 kg/mnancies) . GWG wasnancies) . Childbinancies) . ANC visnancies) . Categornancies) . Househonancies) . Maternanancies) .Bivariate analyses (chi-square/Fisher’s exact tests) were explored to estimate relationship between dependent variable (birthweight) and each independent (background) variable. The independent variables were made up of categorical variables, whereas the dependent variable was nominal .p < 0.05 in chi-square/Fisher’s exact test) were chosen as possible independent variables for logistic analyses. Multicollinearity was checked between the possible independent variables before employing them in the logistic analyses. Chi-square/Fisher’s exact test and variance inflation factor (VIF) were used to address multicollinearity between the variables. During chi-square testing, whenever there was significant association (p < 0.05) between the two categorical variables, the one possessing lesser p value with the dependent variable was chosen. Moreover, VIF was used to confirm multicollinearity between the variables. During the testing, the variable with VIF less than 10 was chosen for logistic analyses.In multivariate analyses, multinomial logistic regression was used to build the final model to identify factors for abnormal birthweight (low birthweight and macrosomia) by applying simultaneous variable entry. During the logistic analyses, birthweight was entered as low birthweight = 1, normal birthweight = 2, and macrosomia = 3 where normal birthweight was used as the base outcome (reference point). The independent variables with significant bivariate association with birthweight  were included for analysis due to non-refusal, and they all met the inclusion and exclusion criteria. The mean age ± sd of the mothers was 27.25 ± 5.44 years with most mothers (86.5%) found between 20 and 35 years of age. Greater proportion of the mothers were married (89.6%), practiced Islamic religion (87.6%), belonged to Dagomba/Mamprusi ethnic group (76.7%), and were self-employed (50.8%). Majority of neonates (70.2%) were older than one week of age, while male neonates (56.2%) were slightly more than females (43.8%). Surprisingly, majority of male neonates (63.6%) had abnormal birthweight. The prevalence rates of low birthweight and macrosomia were 22.2% (95% CI 17.9–26.9%) and 8.7% (95% CI 4.9–12.1%), respectively  gained at least six-kilogram body weight during pregnancy. About 53.7% of the mothers attended ANC clinics less than eight times. More than half of the mothers used insecticide-treated nets (61.2%) and ingested more than three doses of SP tablets (55.3%) during pregnancy (Table .6% gaineMajority of respondents were multiparous (72.7%) and multigravidae (75.3%). Preterm and post-term deliveries were 19.4% and 6.5%, respectively. Most mothers in the first (44.9%), second (56.2%) and third (44.4%) trimesters of pregnancy were anaemic. Nearly 50.0% of respondents had adequate knowledge on abnormal birthweight and its causes and effects. Few respondents had suffered from gestational diabetes (5.9%), hypertension (12.4%), hepatitis B (10.7%), and human immunodeficiency virus (1.7%) infections during pregnancy (Table p < 0.05) as shown in Tables Table p < 0.05) for independent factors including other (minor) ethnic groups, ANC visits ≥ 8, childbirth length > 47.5cm, and maternal anaemia in first and third trimesters of pregnancy for low birthweight (Table The model registered significant adjusted odds ratio (AOR) p < 0.0 for indep < 0.05)  as the significant risk factors for macrosomia p < 0.0 . There was also significant association between socioeconomic status  and minor ethnic groups (p = 0.047 in χ2/Fisher’s exact test). Thus, education and socioeconomic status of mothers from minor ethnic groups tend to have protection against malnutrition [In this study, the major ethnic group found was Dagomba/Mamprusi , while Frafra/Grusi  was the second largest group. Our study indicated that mothers belonging to other (minor) ethnic groups  were less likely to give birth to low-weight children, which is dissimilar to previous studies , 46. Thiutrition , 47, theWHO proposed the “2016 WHO ANC model” describing a new series of recommendations to improve the quality of ANC for progressive pregnancy outcomes . This mors = 0.175; p = 0.001). Therefore, mothers are slightly likely to possess greater height to genetically deliver tall children which serves as protection against low birthweight. However, length measurements of children at health facilities in the municipality may be over/underestimated due to possible errors and inaccuracies from the health workers. It usually becomes difficult for making children fully stretched during length measurement [The study revealed that mothers having children whose birth length was greater than 47.5cm were less likely to deliver low-weight children. This finding is in contrast to a study in Brazil . The lensurement .p = 0.048 in χ2/Fisher’s exact test). Additionally, 111 (69.4%) of these first-trimester anaemic mothers made less than eight ANC visits, while the rest made eight ANC visits or more (p = 0.001 in χ2/Fisher’s exact test). These earlier studies [Globally, anaemia during pregnancy is considered a public health concern, especially in developing countries . In our  studies , 50, 59 p = 0.001 in χ2/Fisher’s exact test). Larger segment  of these third-trimester anaemic mothers made less than eight ANC visits, while few made eight ANC visits or more (p = 0.001 in χ2/Fisher’s exact test). Lesser ANC visits and non-use of ITNs by mothers during pregnancy increased the risk of developing anaemia [Furthermore, mothers with anaemia in the third trimester of pregnancy had higher risk of giving birth to small-weight children. Not only were the results similar to a systematic review by Sukrat et al.  but also anaemia , 49, 50 Alternatively, the present study indicated that mothers with gestational age equal to or more than 42 weeks had higher risk of giving birth to macrosomic children. Giving birth at late gestational age is associated with maternal and perinatal deaths . Post-teMothers from the highest socioeconomic homes (richest households) were more likely to give birth to macrosomic children. This finding is in conformity with some community-based studies in India  and CanaOur study encountered some limitations. This study used existing anthropometric data  recorded in the MCHRB. Some of these data might not be correct due to mis-transcription, mis-recording, and mismeasurement by non-standardized methods. The study results could be under/overestimated due to the time/season of data collection. The data were collected from February to March 2022, the period of dry season in Savelugu municipality, Ghana. Since that period is a non-farming season, there is high cost of food due to scarcity of food commodities. This prevents most pregnant and nursing mothers from having access to diversified meals. Hence, this could lead to malnutrition among the mothers that could affect birth outcomes through foetal programming. Moreover, during this season, most pregnant and nursing mothers are prone to mild infections such as respiratory, malaria, diarrhoea, and other systemic infections which affect their nutritional status leading to abnormal birthweight. Meanwhile, data on maternal nutritional status and seasonal infections were not prospectively collected to determine possible correlations.Secondly, possible sampling bias could occur due to non-selection of mothers having lost or misplaced their MCHRB, absented from first-trimester ANC and PNC services, and with home deliveries. Finally, the study has limitations in generalizability due to the employment of cross section as the study design. Hence, it would need regional and/or national surveys to obtain generalizable findings and conclusions.The study demonstrated the prevalence of abnormal birthweight and the associated risk factors for abnormal birthweight among lactating mothers having a newborn in the past four weeks. The prevalence rates of low birthweight and macrosomia were relatively high. The present study identified that mothers from minority ethnic groups belonging to Bulsa, Dagaati, Ewe, Fulani, and Gonja; mothers who made eight ANC visits or more; and mothers having children born with length above 47.5 cm were less likely to deliver low birthweight children. Maternal anaemia in the first and third trimesters of pregnancy increased the risk of delivering low-weight children. Alternatively, mothers with advanced gestational age and those from richest households had higher risk of giving birth to macrosomic children.Our findings provide information for the Ghana Ministry of Health (MOH) particularly through Ghana Health Service (GHS) to be strongly committed to training and employing more public health nutritionists (PHNs) in its health service delivery system. Specifically, PHNs would educate and counsel semi-rural communities and pregnant women on appropriate diet practices in addressing most nutrition-related determinants of abnormal birthweight including anaemia. Moreover, enhancing the capacity of community health nurses and midwives should be considered to provide appropriate nutrition counselling to pregnant mothers in the health facilities. The MOH should enforce existing policies to strengthen obstetric protocols in the health system. Organizing regular community engagement on education and promotion of ANC visits in semi-rural communities should be collaborative efforts between GHS and local governments.It also becomes incumbent on the Ministry of Education (through Ghana Education Service) to introduce nutrition courses in the education curriculum at elementary, junior, and senior high schools. Children who are our future adults will be equipped with practical diet habits and nutrition knowledge on Developmental Origin of Health and Diseases (DOHaD) to improve the life course approach through the prevention of abnormal birthweight.