Significant Predictive Value Research Articles

Tetraspanins predict the prognosis and characterize the tumor immune microenvironment of glioblastoma

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor. Conventional treatments have not achieved breakthroughs in improving survival. Therefore, novel molecular targets and biomarkers need to be identified. As signal transduction docks on the cell membrane, tetraspanins (TSPANs) are associated with various tumors; however, research on their role in GBM remains extremely scarce. Gene expression and clinicopathological characteristic data were obtained from GEPIA, CGGA, HPA, cBioPortal, and GSCA databases to analyze the mRNA and protein expression levels, prognostic value, clinical relevance, mutation status, and targeted drug sensitivity of TSPANs in GBM. Gene set enrichment analysis (GSEA), Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for biological process enrichment. Data from TCGA and TCIA were used to construct the tumor immune microenvironment landscape of TSPANs. Different R software algorithms were used to analyze the immune score, immune cell infiltration, and immune checkpoint correlation. Univariate and multivariate analyses were performed for TSPAN4, which had the most significant predictive prognostic value, and a nomogram model was constructed to predict individual outcomes. The expression and function of TSPAN4 were verified in vitro. TSPAN3/4/6/11/12/18/23/24/25/26/27/28/29/30/31expressions were significantly upregulated in GBM, and TSPAN3/4/6/11/18/24/25/26/29/30 were strongly correlated with prognosis. The expression of multiple TSPANs significantly correlated with 1p/19q co-deletion status, IDH mutation status, recurrence, age, and tumor grade. GSEA and GO analyses revealed the potential contribution of TSPANs in cell adhesion and migration. Immune correlation analysis revealed that TSPANs are related to the formation of the GBM tumor microenvironment (TME) and may influence immunotherapy outcomes. TSPAN4 is an independent prognostic factor and TSPAN4 knockdown has been demonstrated to strongly inhibit glioma cell proliferation, invasion, and migration in vitro. We comprehensively elaborated the prognostic value and potential role of differentially expressed TSPANs in GBM, including molecules that scientists have previously overlooked. This study provides a novel and comprehensive perspective on the pathological mechanisms of GBM and the future direction of individualized tumor immunotherapy, which may be a critical link between GBM malignant progression and TME remodeling.

Low serum progesterone on day of transfer adversely impacts ongoing pregnancy rates in hormonally prepared single blastocyst frozen embryo transfer cycles

ObjectiveTo evaluate if serum progesterone (P) levels on the day of transfer influence ongoing pregnancy rate (OPR) in hormonally prepared single blastocyst frozen embryo transfer (FET) cycles?Study Design.Single center prospective cohort study conducted between June 2021 and August 2022 analyzed 217 single good quality blastocyst FET cycles hormonally prepared with oral estradiol valerate and micronized vaginal progesterone 400 mg twice daily. ResultsMean serum P on the day of embryo transfer (ET) was 9.76 ± 5.19 ng/ml. Receiver operator curve (ROC) showed a significant predictive value of serum P levels on the day of ET for OPR, with an area under curve (AUC) (95 %CI) = 0.58 (0.49–0.66). Optimal serum P threshold for OPR was 7.7 ng/ml (Sensitivity 76.8%, Specificity 43.7%). 35.9% patients had serum P below this threshold. BMI was significantly higher (26.8 ± 3.7 vs 25.6 ± 4.3; p = 0.048) in patients with serum P < 7.7 ng/ml vs ≥ 7.7 ng/ml. OPR was significantly lower (24.4% vs 45.3%; p = 0.002) and clinical miscarriage rates significantly higher (37.9% vs 19.2%; p = 0.042) if serum P < 7.72 ng/ml vs ≥ 7.7 ng/ml. ConclusionThis study found that serum P level on the day of transfer in hormonally prepared FET cycles was a significant predictor of OPR.

Macrophage Profiling in Head and Neck Cancer to Improve Patient Prognosis and Assessment of Cancer Cell-Macrophage Interactions Using Three-Dimensional Coculture Models.

Tumor-associated macrophages are key components of the tumor microenvironment and play important roles in the progression of head and neck cancer, leading to the development of effective strategies targeting immune cells in tumors. Our study demonstrated the prognostic potential of a new scoring system (Macroscore) based on the combination of the ratio and the sum of the high and low densities of M1 (CD80+) and M2 (CD163+) macrophages in a series of head and neck cancer patients, including a training population (n = 54) and a validation population (n = 19). Interestingly, the Macroscore outperformed TNM criteria and p16 status, showing a significant association with poor patient prognosis, and demonstrated significant predictive value for overall survival. Additionally, 3D coculture spheroids were established to analyze the crosstalk between cancer cells and monocytes/macrophages. Our data revealed that cancer cells can induce monocyte differentiation into protumoral M2 macrophages, creating an immunosuppressive microenvironment. This coculture also induced the production of immunosuppressive cytokines, such as IL10 and IL8, known to promote M2 polarization. Finally, we validated the ability of the macrophage subpopulations to induce apoptosis (M1) or support proliferation (M2) of cancer cells. Overall, our research highlights the potential of the Macroscore as a valuable prognostic biomarker to enhance the clinical management of patients and underscores the relevance of a spheroid model in gaining a better understanding of the mechanisms underlying cancer cell-macrophage interactions.

Postoperative clinical analyze of 450 eyelid tumors

BackgroundThe eyelids are a small anatomical structure, yet they contain several histological layers from which benign and malignant tumors can originate. Compared to other parts of the face, the eyelids are often the first place where neoplasms or disease changes are noticed. AimTo analyze localization and its predictive malignancy of eyelid tumors over a 10-year period. MethodA retrospective study of 436 (450 eyes) patients operated on over a 10-year period. Descriptive, dispersion and correlation analyzes were performed. ResultsThe results provide a clear assessment of the distribution and incidence of eyelid tumors according to the localization of the defect, involvement of the lash line, inflammatory response, etc. Tumor distribution is significantly skewed in favor of the medial canthus, 80% to 20% by all tumors. The involvement of the lid margin occurs in 83% of malignant tumors and has significant predictive value. ConclusionThe lower eyelid and the medial canthus are preferred locations for malignant tumors, and the upper eyelid for benign ones. Our study does not affect the types of surgical techniques; its purpose is to show the expected malignancy of the different combinations by location. The location of the tumor is a leading factor in the choice of the oculoplastic reconstructive procedure.

Clinical application of serum NLRP3 on the diagnosis and prognosis of sepsis patients complicated with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a common complication of sepsis, which significantly increases the mortality rate. This work explored the diagnostic value of serum NOD-like receptor family pyrin domain containing 3 (NLRP3) concentration in patients with sepsis for ARDS, and the predictive value of serum NLRP3 concentration at the time of diagnosis for death 28 days after treatment. A total of 150 sepsis patients were included in this study, including age-matched two groups of patients, 75 patients with ARDS and 75 patients without ARDS. In addition, 60 age-matched healthy patients with physical examination were recruited in this study. Serum NLRP3 concentration was determined by enzyme-linked immunosorbent assay (ELISA). The diagnostic values of serum NLRP3 concentration for ARDS in sepsis patients were evaluated by receiver operating characteristics (ROC) analysis. Correlation of serum NLRP3 with APACHE II score and SOFA were performed by Spearman correlation analysis. Pulmonary infection, APACHE II score and serum NLRP3 concentration were risk factors for patients with sepsis complicated with ARDS. ROC curve results showed that the specificity of serum NLRP3 concentration was 74.67%, the sensitivity was 76.00%, and the area under the curve (AUC) was 0.82 (p<0.001). APACHE II score and SOFA were significantly positively correlated with serum NLRP3 concentration. Baseline serum NLRP3 levels had significant predictive value for 28-day mortality in sepsis patients complicated with ARDS. Serum NLRP3 concentration has clinical value in the diagnosis of sepsis complicated with ARDS.

Positive Fecal Occult Blood Test and Colonoscopy With Histopathology Findings in Saudi Adults.

Background/aims Colorectal cancer cases are on the rise in developing countries, necessitating dependable detection tests. Moreover,medical procedures have become increasingly burdensome for both patients and healthcare professionals. This study aims to delve deeper into the fecal occult blood test (FOBT) as a potential solution. Settings and design The research took place atthe Gastroenterology Specialized Clinic (Human Clinic) in Riyadh, Saudi Arabia. The study gathered results fromcolonoscopy/sigmoidoscopy, histopathology, and FOBTscreening. Essential variables linked tocolorectal cancer, including gastrointestinal symptoms, chronic diseases, hemoglobin (Hgb), body mass index (BMI), and medication usage, were documented to evaluate their potential predictive significance for positive outcomes. Methods and materials In line with the study aims, inclusion criteria covered Saudi adults aged 18 and above, experiencing lower GI symptoms, with colonoscopy or sigmoidoscopy, FOBT, and histopathological results. The resultant sample size was 72 patients. Non-Saudi individuals, symptoms-free patients, and those below 18 years were excluded. This retrospective analysis spanned from September 2021 to September 2022. For statistical analysis, after the data rationality was checked, parametric or non-parametric tests were used. P ≤ 0.05 was set as the significant level. Results Among the 72 patients, ranging in age from 18 to 80(mean 42.94),males (57) outnumbered females (15). The average BMI was 27.56, withone-third of patients classified as overweight or obese. A majority of47 (65.2%) exhibited normal Hgb levelswhile only five (7%) had abnormal levels. Results from colonoscopy or sigmoidoscopy and FOBT displayed statistical similarity between positive and negative outcomes. Additionally, the notable prevalence of positive results compared to negative ones underscores the resemblance between FOBT andcolonoscopy/sigmoidoscopy findings. Conclusion Chronic illness, constitutional symptoms, BMI, and Hgb did not display a significant predictive value, However, the group with GI symptoms exhibited a strong prediction for favorable colonoscopy/sigmoidoscopy and histology outcomes. Additional research is necessary to validate these observed patterns.

Assessment of Fraction of Exhaled Nitric Oxide and Soluble Receptor for Advanced Glycation End Products Biomarkers for Jordanian Asthmatic Children.

Fraction of exhaled nitric oxide (FeNO) and soluble advanced glycation end-product receptor (sRAGE) are proposed as biomarkers of asthma, therefore we sought to assess their use in asthmatic children of Jordan. We conducted a case-control study at The University of Jordan Hospital. A total of 141 asthmatic children followed by respiratory pediatricians and 118 healthy children aged 4-18 years were recruited. FeNO was measured by NObreath device and serum sRAGE by ELISA that detect endogenously soluble isoform (esRAGE) and total soluble RAGE (sRAGE). sRAGE in asthmatic was half of the control (p <0.001). In addition, ratio of esRAGE/sRAGE was two-fold higher in asthmatic (p = <0.001). Neither FeNO nor esRAGE levels were significantly different between groups. FeNO and asthma control test (ACT) score were negatively correlated corrected for age and body mass index (BMI), (r = -0.180, p= 0.034). For the uncontrolled asthma group, esRAGE/sRAGE negatively correlated with ACT score (r = -.329, p = 0.038). Receiver operating curve (ROC) analysis revealed significant predictive value (PV) for sRAGE and esRAGE/sRAGE in asthma detection with area under the curve (AUC) of (0.751 ± 0.031) and (0.711±.033), consequently. However, no biomarker had a significant PV for lack of control. The current study supports utilizing sRAGE as a marker for asthma and present a potential therapeutic target. However, our results indicate that both FeNO and sRAGE have a limited role in the management of asthmatic children or assessment of asthma control.

Involving citizens in urgent missing person cases. An application of the Theory of Planned Behaviour within District Criminal Investigations Teams

ABSTRACT This article examines the use of citizen participation by detectives in urgent missing person cases. Citizens can make a valuable contribution to finding a missing person, but this kind of assistance is often underutilised. We applied the Theory of Planned Behaviour to explore the extent to which attitudes, subjective norms, and perceived behavioural control influence detectives’ intentions to involve citizens and the detectives’ considerations underlying such intentions. To this end, a quantitative questionnaire was developed and administered to detectives from four regional police units. The best goodness-of-fit of the theoretical model was found for officers who deal with urgent missing persons cases regularly, but not often; for this group, the model explained 39 percent of the variance observed. The results show that intention is significantly related to detectives’ attitudes. Subjective norms had a significant predictive value, except for officers who encounter missing persons cases frequently. Perceived behavioural control had no significant effect. The study suggests that the choice to involve citizens is mainly attitude-driven, and is determined primarily by detectives’ personal affinity with citizen participation and their perception of its benefits. Perceived risks, such as damage to the investigation, have limited influence on decisions regarding citizen participation.

Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure.

Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Levels of MR-proADM (median: 2.07; (25th-75th percentiles: 1.40-3.02) vs. 1.11 (0.83-1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691-11,874) vs. 271 (89-931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13-7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42-30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05-9.91; p = 0.041). The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy.

S100B and brain ultrasound: Novel predictors for functional outcome in acute ischemic stroke patients

ObjectiveStroke is a leading cause of mortality and disability worldwide. This study aimed to assess the prognostic value of serum S100B protein, transcranial color-coded duplex sonography (TCCD), and optic nerve sheath diameter (ONSD) in predicting functional outcomes in critically ill patients with acute ischemic stroke (AIS). MethodsIn this prospective observational study, 80 adult AIS patients were evaluated. Serum S100B protein levels, ONSD, and middle cerebral artery pulsatility index (MCA PI) were measured on days 1 and 3. Functional outcomes at 90 days were assessed using the modified Rankin Scale (mRS) and categorized into favourable (mRS 0–2) or unfavourable (mRS 3–6) groups. The association of demographic, clinical, laboratory, and imaging parameters with mRS outcomes was analyzed. ResultsPoor mRS outcomes occurred in 82.5 % of patients. Factors significantly associated with poor outcomes were female sex, higher National Institutes of Health Stroke Scale (NIHSS) scores on days 1, 3, and 7, and larger stroke size. Receiver Operating Characteristic (ROC) curve analysis revealed that ONSD at days 1 and 3, serum S100B levels at day 1, and right MCA PI at day 1 had significant predictive value for poor mRS outcome. Multivariate analysis identified female sex, S100B on day 1, and NIHSS on days 1, 3, and 7 as independent predictors of poor mRS outcomes. ConclusionsThe combination of S100B, ONSD, and MCA PI improved the prediction of functional outcomes in critically ill AIS patients. Early S100B measurement and brain ultrasound evaluation may serve as valuable prognostic tools for guiding therapeutic decision-making. This study provides novel insights into the role of S100B and brain ultrasound in stroke outcome prediction, particularly in critically ill AIS patients.

Platelet-to-Monocyte Ratio as a Novel Promising Agent for the Prognosis of Hepatitis B Virus-Associated Decompensated Cirrhosis.

The present study aimed at investigating associations of the platelet-to-monocyte ratio (PMR), a novel hematological indicator of inflammatory responses with 30-day outcomes in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). We recruited 329 patients with HBV-DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30-day mortality. Receiver operating characteristic curve analysis was performed to compare the predictive values of prognostic markers. During the 30-day follow-up period, 21 (6.4%) patients died. The PMR was significantly different between nonsurvivors and survivors. Lower PMR was found to be associated with an increased risk of 30-day mortality, and PMR (odds ratio: 1.011; 95% CI: 1.003-1.019; P=0.005) was found to be an independent predictor of 30-day mortality in patients with HBV-DeCi with a significant predictive value (AUC = 0.826, 95% CI: 0.781-0.865). The combination of PMR and MELD score could improve prognostic accuracy in these patients (AUC = 0.911, 95% CI: 0.876-0.940). Our results demonstrate that low PMR may be an independent predictor of 30-day mortality in patients with HBV-DeCi, and combined with the MELD score, it may be useful to complement other conventional measures to enable effective management of these patients.

Association between contrast sensitivity function and structural damage in primary open-angle glaucoma

AimsTo evaluate the association between contrast sensitivity function (CSF) and glaucomatous structural damage in primary open-angle glaucoma (POAG).MethodsA cross-sectional study was performed with 103 patients (103 eyes) aged 25–50 years...

Preoperatively assessed offset analgesia predicts acute postoperative pain following orthognathic surgery.

High intensity and longer duration of acute postoperative pain are generally associated with a higher risk of developing chronic postoperative pain. Therefore, it is important to identify the preoperative predictors for acute postoperative pain. Preoperative evaluation of offset analgesia (OA) and the Pain Catastrophising Scale (PCS) may be potential predictors for acute postoperative pain. This study aimed to investigate the relationship between preoperative OA, PCS, and acute postoperative pain following orthognathic surgery. Thirty patients (19 females) scheduled to undergo orthognathic surgery were included in this study. OA and PCS were evaluated preoperatively, and the patients reported their postoperative pain intensity using the visual analogue scale [0-100 mm] until it reached zero (number of days with pain). OA was induced on the dominant forearm via three consecutive painful heat pulses delivered for 5 s (T1=46 °C), 5 s (T2=47 °C), and 20 s (T3=46 °C). Subsequently, the associations between OA, PCS, and the number of days with pain were analysed. The median duration of postoperative pain was 10.3days. Multiple linear regression analysis showed a significant (p=0.0019) predictive value of OA (p=0.008) for the number of days with pain. The PCS-magnification component was positively correlated with the number of dayswith pain (R=0.369, p=0.045), with no predictive values of PCS-total and PCS-subscale scores observed. Preoperative evaluation of OA may be a new individualised, predictive tool for the number of days with acute postoperative pain following orthognathic surgery; hence, a possible biomarker for the patient's vulnerability to developing chronic postoperative pain. The study was approved by the Ethics Committee of Meikai University (A1624, A2113). This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) Clinical Trial (Unique ID: UMIN000026719, UMIN000046957).

Comparative study of preoperative functional imaging combined with tractography for prediction of iatrogenic motor deficits.

Robust preoperative imaging can improve the extent of resection in patients with brain tumors while minimizing postoperative neurological morbidity. Both structural and functional imaging techniques can provide helpful preoperative information. A recent study found that transcranial magnetic stimulation (TMS) tractography has significant predictive value for permanent deficits. The present study directly compares the predictive value of TMS tractography and task-based functional MRI (fMRI) tractography in the same cohort of glioma patients. Clinical outcome data were collected from charts of patients with motor eloquent glioma and preoperative fMRI and TMS studies. The primary outcome was a new or worsened motor deficit present at the 3-month postoperative follow-up, which was termed a "permanent deficit." Postoperative MR images were overlaid onto preoperative plans to determine which imaging features were resected. Multiple fractional anisotropic thresholds (FATs) were screened for both TMS and fMRI tractography. The predictive value of the various thresholds was modeled using receiver operating characteristic curve analysis. Forty patients were included in this study. Six patients (15%) sustained permanent postoperative motor deficits. A significantly greater predictive value was found for TMS tractography than for fMRI tractography regardless of the FAT. Despite 35% of patients showing clinically relevant neuroplasticity captured by TMS, only 2.5% of patients showed a blood oxygen level-dependent signal displaced from the precentral gyrus. Comparing the best-performing FAT for both modalities, TMS seeded tractography showed superior predictive value across all metrics: sensitivity, specificity, positive predictive value, and negative predictive value. The results from this study indicate that the prediction of permanent deficits with TMS tractography is superior to that with fMRI tractography, possibly because TMS tractography captures clinically relevant neuroplasticity. However, future large-scale prospective studies are needed to fully illuminate the proper role of each modality in comprehensive presurgical workups for patients with motor-eloquent tumors.

Risk factors associated with attendance at postpartum blood pressure follow-up visit in discharged patients with hypertensive disorders of pregnancy

BackgroundThis study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum.MethodsThis study is a prospective cohort study of postpartum discharged HDP patients. Telephone follow-up was conducted at 6 weeks and 12 weeks postpartum, the maternal demographic characteristics, details of labor and delivery, laboratory test results of patients at admission, and adherence to BP follow-up visits postpartum were collected. While logistic regression analysis was used to analyze the factors associated with not returning to postpartum BP follow-up visit at 6 weeks and 12 weeks after delivery, the receiver operating characteristic (ROC) curve was drawn to evaluate the model’s predictive value for predicting not returning to postpartum BP visit at each follow-up time point.ResultsIn this study, 272 females met the inclusion criteria. 66 (24.26%) and 137 (50.37%) patients did not return for postpartum BP visit at 6 and 12 weeks after delivery. A multivariate logistic regression analysis identified education level of high school or below (OR = 3.71; 95% CI = 2.01–6.85; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.97; 95% CI = 0.94–0.99; p = 0.0230)and delivery gestational age (OR = 1.12; 95% CI = 1.005–1.244; p = 0.040)as independent risk factors in predicting not returning to postpartum BP follow-up visit at 6 weeks postpartum, and education level of high school or below (OR = 3.20; 95% CI = 1.805–5.67; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.95; 95% CI = 0.92–0.97; p = 0.000), delivery gestational age (OR = 1.13; 95% CI = 1.04–1.24; p = 0.006) and parity (OR = 1.63; 95% CI = 1.06–2.51; p = 0.026) as risk factors for not returning to postpartum BP follow-up visit at 12 weeks postpartum. The ROC curve analysis indicated that the logistic regression models had a significant predictive value for identify not returning to BP follow-up visit at 6 and 12 weeks postpartum with the area under the curve (AUC) 0.746 and 0.761, respectively.ConclusionAttendance at postpartum BP follow-up visit declined with time for postpartum HDP patients after discharge. Education at or below high school, maximum diastolic BP during pregnancy and gestational age at delivery were the common risk factors for not returning for BP follow-up visit at 6 and 12 weeks postpartum in postpartum HDP patients.

Searching for Situational Patterns in Cannabis Dealing, Possession and Use in a Scandinavian Context

Although cannabis is the most frequent illicit drug consumed in Sweden, little is known about the situations in which cannabis trade, possession and use occur. Following a recent strand of international research on the effect of recreational drugs on crime, this study uses a unique specially tailored database, Geographical Information Systems (GIS) and regression models, to investigate the situational conditions of cannabis offenses as they are detected in Stockholm, Sweden. Cannabis coincides with the location of drug markets initially delimited by the police but also extends over to locations far from the radar of the police, such as private residences (comfort places). Modeling results indicate that several land uses (convergent public places) have significant predictive value of the geography of cannabis offenses after controlling for other neighborhood characteristics. The article finishes by stating new research questions and making recommendations for practice.

O-184 Validation of a model capable of estimating the minimum number of mature oocytes needed to obtain at least one euploid blastocyst regarding female age

Abstract Study question Which is the minimum number of mature oocytes needed to obtain at least one euploid blastocyst regarding female age in In Vitro Fertilization (IVF) treatments? Summary answer The validated model estimates with a 74% accuracy the probability of having one euploid blastocyst regarding the number of mature oocytes and female age. What is known already Female age is significantly and directly related to embryo aneuploidy rates, thus lowering the chances of success in IVF treatments. The current delay in motherhood has led to a large proportion of women of advanced maternal age seeking infertility treatment. The aim of the present study is to determine the number of metaphase II (MII) oocytes needed to obtain at least one euploid blastocyst regarding female age. This information will help to decide the best strategy for each patient, taking also into account other variables such as ovarian reserve, semen quality and oocyte quality. Study design, size, duration Retrospective analysis of IVF cycles with pre-implantational genetic testing for aneuploidies (PGT-A) performed over the last 5 years in an infertility clinic in Spain, from January 2017 to March 2022. Participants/materials, setting, methods Patients undergoing an IVF cycle in an infertility clinic with own or donated oocytes, regardless semen origin. Only trophoectoderm biopsies performed on day 5 or 6 of development and analyzed using Next Generation Sequencing (NGS) were included. PGT-A was used for reasons such as advanced maternal age, implantation failure and recurrent miscarriage. PGT-A cycles due to a known abnormal karyotype were excluded. Endpoints were analized using binary logistic regression models. Main results and the role of chance A total of 3840 IVF-PGT-A cycles meeting the inclusion criteria were performed in the study period. Of them, 939 cycles were discarded due to the absence of any biopsied/analyzed embryo (final sample size=2901). A model for the probability of having at least one euploid blastocyst (pEB) regarding female age and the number of MII oocytes retrieved was created with 80% of the sample (n = 2320) and validated in the remaining 20% (n = 581). The validation of this model showed that it was capable of estimate with an accuracy of 73.88%. The pEB was directly related to the number of MII oocytes retrieved (odds ratio (OR) 1.130, confidence interval (IC) 95% (1.110-1.150); p &amp;lt; 0.001), but indirectly related to female age (OR 0.751, IC95% (0.725-0.778); p &amp;lt; 0.001). The ROC curve showed a significant predictive value of the number of MII oocytes (area under the curve (AUC):0.8041 (0.7882-0.82)) for this model. A mathematical formula was created for the calculation of pEB using this model. The number of MII oocytes needed for a pEB of 75% regarding female age (female age:number MII) was 35:6, 36:9, 37:12, 38:15, 39:18, 40:21, 41:24, 42:27, 43:30, 44:32, 45:35, 46:38, 47:41, 48:44, 49:47, 50:50. Limitations, reasons for caution The main limitation of this study is its retrospective design. In addition, it’s important to keep in mind that many other variables should be taken into consideration along with maternal age in the assessment of the number of oocytes needed to obtain at least one euploid blastocyst in IVF treatments. Wider implications of the findings Results from this study may constitute a useful tool for both clinical and patient. The clinician may be able to better decide the best strategy for each patient, while the patient will understand more easily this information, helping her morally with the treatment. Trial registration number 2204-VLC-040-CR

P-222 Early blastulation on day 4 predicts ongoing pregnancy in fresh transfer cycles

Abstract Study question Do embryos with early blastulation (EB) on D4 show higher implantation potential compared to top D5 blastocysts in fresh elective single embryo transfer (eSET) cycles? Summary answer Fresh EB transfer with time start to blastulation (tSB)&amp;lt;96.6h and time of expanded blastocyst (tEB)&amp;lt;100h post-insemination is predictive of ongoing pregnancy for patients &amp;lt;35. What is known already Expansion and hatching of blastocysts are correlated to implantation potential in fresh single transfers. Thanks to time-lapse morphokinetics, several time-points can be analyzed during embryonic growth. Embryos with faster growing speed are correlated to euploid status. The tSB of &amp;lt; 96.6h, day 4 post-insemination, is reported to have significant predictive value of euploid embryos, which are found to be associated not only with higher expansion scores, but also with shorter tSB, full expansion, and hatching. A study reported that significantly more embryos that reached the tSB by 100h implanted compared to those that did not. Study design, size, duration Prospective observational study in a single private hospital during 2022. In 160 cycles (n = 81 cIVF and n = 79 ICSI) an EB on D4 was observed. 48 patients (n = 28 ICSI and n = 20 cIVF) underwent a fresh eSET with an embryo showing EB on day 4. Participants/materials, setting, methods Patients with EB on D4 (tSB&amp;lt;96.6h, tEB&amp;lt;100h post-insemination) were enrolled regardless of indication, female age, attempt’s rank or technique. Those with a fresh eSET on D4 were included in this study. Gardner’s classification was used to rate the blastocysts in Embryoscope + (Vitrolife). The outcome data of transfer for D4 blastocysts (B3/B4 AA-AB-BA) were compared to eSET with top D5 (B4/B5 AA) of reference group (female age ≤35). The statistical analyses were performed by SPSS software. Main results and the role of chance In the study group, all the transferred embryos were graded according to Gardner’s classification as B3AA, or B3AB, or B3BA, or B4AA, or B4AB, or B4BA. In the reference group, we chose only the fresh transfer cycles with ultra-top grade D5 embryos classified as B4AA or B5AA. The results obtained in the overall population (n = 48) were compared to those obtained in the reference group (n = 92): age 34.0 ± 3.8 vs 31.8 ± 2.3, oocyte maturity (OM) 79.8% vs 80.3%, fertilization rate (FR) 80.0% vs 77.0%, overall blastulation rate (OBR) 78.1% vs 74.3%, top blastulation rate (TBR) 59.1% vs 54.4%, total pregnancy rate (PR) 75.5% vs 61.4%, implantation rate (IR) 58.3 vs 51.2% and ongoing pregnancy rate (OPR) 58.6% vs 47.1%, and showed a statistical difference only in PR (p&amp;lt;0.05). The results obtained in younger patients with age 32.1 ± 3.2 (n = 34) were also compared to reference group: OM 75.1% vs 80.3%, FR 85.0% vs 77.0%, OBR 78.1% vs 74.3%; TBR 58.7% vs 54.4% were comparable between the groups. A statistical difference was observed for PR (88.0% vs 61.4%, p&amp;lt;0.01) IR (70.6% vs. 51.2%, p&amp;lt;0.05) and OPR (70.6% vs 47.1%, p&amp;lt;0.05). Limitations, reasons for caution The small size of the sample needs to be expanded in order to confirm the encouraging findings in a larger population, especially in older patients yielding more aneuploid embryos. The study will continue during 2023 and will compel the live birth rate. Wider implications of the findings When a D4 embryo with EB is available, the best option is the fresh transfer on D4. The increased implantation with EB seems to correlate with embryo euploidy and the advanced endometrial receptivity in stimulated cycles. Higher IR and OPR are reported even in patients with lower rate of aneuploidy. Trial registration number not applicable

IGH rod-like tracer: An AlphaFold2 structural similarity extraction-based predictive biomarker for MRD monitoring in pre-B-ALL

Sequence variation resulting from the evolution of IGH clones and immunophenotypic drift makes it difficult to track abnormal B cells in children with precursor B cell acute lymphoblastic leukemia (pre-B-ALL) by flow cytometry, qPCR, or next-generation sequencing (NGS). The V-(D)-J regions of immunoglobulin and Tcell receptor of 47 pre-B-ALL samples were sequenced using the Illumina NovaSeq platform. The IGH rod-like tracer consensus sequence was extracted based on its rod-like alpha-helices structural similarity predicted by AlphaFold2. Additional data from published 203 pre-B-ALL samples were applied for validation. NGS-IGH (+) patients with pre-B-ALL had a poor prognosis. Consistent CDR3-coded protein structures in NGS-IGH (+) samples could be extracted as a potential follow-up marker for pre-B-ALL children during treatment. IGH rod-like tracer from quantitative immune repertoire sequencing may serve as a class of biomarker with significant predictive values for the dynamic monitoring of MRD in pre-B-ALL children.

Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2− and triple-negative breast cancer (TNBC). Among HR+HER2− breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2− or TNBC who may not benefit from NACT. HR+HER2− breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.