Case-control Study Design Research Articles

Lack of Association between BDNF rs6265 and Multiple Sclerosis: A Case-Control Study.

Data on the association between BDNF rs6265 and multiple sclerosis (MS) are scarce and heterogeneous. We undertook a case-control study design. Newly diagnosed individuals with MS based on the 2017 revision of the McDonald criteria were recruited from the Neurology Department of the General University Hospital of Larissa. Healthy controls with a free medical and family history were also recruited. The relationship between BDNF rs6265 and MS was defined as the primary outcome. The association between rs6265 and age of MS onset, spinal lesions, and clinical manifestations at the time of MS onset were defined as the secondary outcomes. We genotyped a total of 200 patients with MS and 205 healthy controls, yielding a sample power of approximately 80%. BDNF rs6265 was in Hardy-Weinberg Equilibrium among healthy participants (p = 0.64). No significant relationship was revealed between rs6265 and MS [log-additive OR = 0.83 (0.57,1.21), over-dominant OR = 0.73 (0.48,1.14), recessive OR = 1.24 (0.37,4.12), dominant OR = 0.77 (0.50,1.17), co-dominant OR1 = 0.74 (0.48,1.14) and co-dominant OR2 = 1.13 (0.34,3.80)]. Additionally, rs6265 was unrelated to the age of MS onset according to both unadjusted and sex-adjusted cox-proportional models. Finally, rs6265 was not associated with the presence of spinal lesions (cervical or thoracic) at MS onset, according to both unadjusted and age and sex-adjusted logistic regression models. We failed to establish an association between BDNF rs6265 and the risk of MS, the age of onset, the presence of spinal lesions, and the clinical manifestations at the onset.

Analysis of influencing factors for postoperative brain injury in patients with cardiac surgery

Objective To identify risk factors in people with heart disease prior to undergoing cardiac surgery and to provide a prediction model. Methods 106 patients who underwent cardiac surgery were selected by convenience sampling method. Case-control study design was used to divide them into control and observation groups according to whether there was postoperative brain injury. General demographic data, perioperative surgery, postoperative recovery, past medical history and preoperative conditions, laboratory test indicators were collected. Univariate and multivariate Logistic regression analyses were performed to select influencing factors. A nomogram model for predicting postoperative brain injury was established. Results Univariate Logistic regression analysis showed that age, female, stroke, diabetes mellitus, perioperative administration of dexmedetomidine, intraoperative use of cardiopulmonary bypass were related factors for postoperative brain injury(p < 0.05). Multivariate Logistic regression analysis showed that females, history of stroke, and intraoperative use of cardiopulmonary bypass were risk factors, and perioperative administration of dexmedetomidine was protective factor(p < 0.05). Nomogram model was established with an AUC of 0.847 and accuracy of 84.7%. Conclusion Preoperative stroke history and females are risk factors for brain injury after coronary artery bypass grafting under cardiopulmonary bypass, and perioperative use of dexmedetomidine is protective factor.

Analysis of factors affecting pulmonary tuberculosis incidence

Introduction: Pulmonary Tuberculosis is an infectious disease caused by bacteria that can affect the lungs and other organs, specifically Mycobacterium tuberculosis. Mycobacterium belongs to a group of acid-fast bacteria commonly known as AFB (Acid-Fast Bacilli). To this day, pulmonary tuberculosis remains one of the most dangerous infectious diseases worldwide. This study aims to analyze the factors influencing the incidence of pulmonary tuberculosis. Research Methodology: This research employs an observational study with a case-control study design. The sample consists of 69 individuals diagnosed with pulmonary tuberculosis. The sampling technique used is purposive sampling. Data collection was conducted using questionnaires, and data analysis was performed using the chi-square test. Result: The results of this study indicate that occupation (p=0.000), income (p=0.000), housing conditions (p=0.000), and smoking (p=0.018) significantly influence the incidence of pulmonary tuberculosis. All variables examined in this study showed an impact on individuals affected by pulmonary tuberculosis. Conclusion: This study concludes that occupation, income, housing conditions, and smoking are significant factors influencing the incidence of pulmonary tuberculosis. Improving these factors may help reduce the prevalence of pulmonary tuberculosis in the community. Therefore, individuals are expected to adopt healthier lifestyles by maintaining cleanliness and a healthy home environment, making it a habit to cover their mouths when sneezing or coughing, and avoiding spitting indiscriminately. Additionally, they are encouraged to actively seek information about pulmonary tuberculosis and participate in educational sessions on the disease.

Predictive Factors Driving Positive Awake Test in Carotid Endarterectomy Using Machine Learning

Positive neurologic awake testing during the carotid cross-clamping may be present in around 8% of patients undergoing carotid endarterectomy (CEA). The present work aimed to assess the accuracy of an artificial intelligence (AI)-powered risk calculator in predicting intraoperative neurologic deficits (IND). Data was collected from carotid interventions performed between January 2012 and January 2023 under regional anesthesia. Patients with IND were selected along with consecutive controls without IND in a case-control study design. A predictive model for IND was developed using machine learning (ML), specifically Extreme Gradient Boosting (XGBoost) model, and its performance was assessed and compared to an existing predictive model. Shapley Additive exPlanations (SHAP) analysis was employed for the model interpretation. Among 216 patients, 108 experienced IND during CEA. The AI-based predictive model achieved a robust area under the curve (AUC) of 0.82, with an accuracy of 0.75, precision of 0.88, sensitivity of 0.59, and F1Score of 0.71. High body mass index (BMI) increased contralateral carotid stenosis, and a history of limb paresis or plegia were significant IND risk factors. Elevated preoperative platelet and haemoglobin levels were associated with reduced IND risk. This AI model provides precise IND prediction in CEA, enabling tailored interventions for high-risk patients and ultimately improving surgical outcomes. BMI, contralateral stenosis, and selected blood parameters emerged as pivotal predictors, bringing significant advancements to decision-making in CEA procedures. Further validation in larger cohorts is essential for broader clinical implementation.

Therapy for Non-Diabetic Foot Infections After Orthopedic Foot and Ankle Surgery: The Duration of Post-Debridement Antibiotic Treatment Does Not Alter Failure Risk.

Despite growing numbers of scientific publications on the optimal antibiotic treatment for diabetic foot infections, the data on the adult population with non-diabetic (postsurgical) foot infections is limited. Therefore, one of the largest single-center databases at the Balgrist University Hospital in Zurich, Switzerland, was established between January 2014 and August 2022. Using a case-control study design, we retrospectively investigated failures of combined surgical and antibiotic therapy for surgical site foot infections (SSIs). Overall, 17.4% of the episodes experienced therapeutic failures, particularly in patients with infected ankle prostheses. However, age, biological sex, pathogens, the duration of post-debridement antibiotic treatment, the number of surgical debridements, or the use of negative-pressure wound care altered the failure risk. In the multivariate logistic regression analyses, the duration of postsurgical antibiotic use was completely indifferent (as a continuous variable with an odds ratio of 1.0 and a 95% confidence interval ranging from 0.96 to 1.03) when stratified into inter-tertiary groups. Our findings suggest that shorter courses of systemic antibiotics may be appropriate in non-diabetic adults, supporting better antibiotic stewardship. Ongoing randomized controlled trials are under way to investigate which patients might safely receive shorter antibiotic treatments for surgical site infections following elective foot and ankle procedures.

Investigating psychiatric morbidity, hopelessness and suicide risk in patients with 22q11.2 deletion syndrome: a case-control study

Background The psychiatric phenotype of the 22q11.2 deletion syndrome (22q11DS) has been largely described. Objectives With a case-control study design, we now compared a sample of 22q11DS patients with a psychiatric diagnosis with a sample of psychiatric patients without 22q11DS to investigate possible differences between groups for depression severity, hopelessness, and suicide. Patients with 22q11DS were divided into two groups according to the levels of hopelessness to evaluate the relationship between hopelessness and the severity of the 22q11DS, the level of disability, functional impairment, physical frailty, and autonomy level. Results Results showed that suicide risk evaluated with the C-SSRS was similar in the two groups of patients and that a diagnosis of 22q11DS does not appear to be a risk factor for suicide; however, 22q11DS patients had more severe hopelessness. Patients with a more severe clinical presentation and worse overall functioning have higher levels of depressive symptoms and hopelessness. Conclusions The results suggest the need to assess and monitor psychiatric symptoms in patients with 22q11DS.

The dietary phytochemical index and its relation to polycystic ovary syndrome: a case–control study

BackgroundPolycystic ovary syndrome (PCOS), a hormonal disorder affecting women of reproductive age, can be significantly impacted by diet. This study explores the relationship between a diet rich in phytochemicals, measured by the Dietary Phytochemical Index (DPI), and PCOS, along with associated health markers.MethodsA case–control study design was implemented with 480 individuals diagnosed with PCOS based on the Rotterdam criteria, paired with 480 controls matched in terms of age and BMI. The evaluation encompassed dietary intake, anthropometric measurements, and hormonal/metabolic markers. Additionally, the DPI score was determined based on the consumption of phytochemical-rich foods. The study also examined PCOS-related complications like acne and irregular menstrual cycles, as well as mental health using the Beck Depression Inventory (BDI-II) scores.ResultsWomen with PCOS had significantly lower DPI scores (32.42 vs 43.87, p < 0.001) compared to the control group, indicating a less phytochemical-rich diet. The DPI scores coincided with higher levels of hormones typically associated with PCOS, including Luteinizing Hormone (LH), Dehydroepiandrosterone Sulfate (DHEA-S), and testosterone. Additionally, these scores were associated with markers of metabolic dysfunction such as C-reactive Protein (CRP), Fasting Blood Sugar (FBS), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while positively correlating with Sex Hormone-Binding Globulin (SHBG) (all p < 0.050).). Higher DPI scores were associated with a significantly reduced risk of PCOS (OR: 0.13, 95% CI: 0.08, 0.23, P for trend: 0.001) and its complications, including acne and irregular menstrual cycles. Interestingly, a positive association emerged, suggesting better mental health (lower BDI-II scores) with higher DPI scores.ConclusionsIn conclusion, this study indicates that lower DPI scores are associated with a higher incidence and severity of PCOS, suggesting that a phytochemical-rich diet could potentially benefit the management of PCOS by enhancing hormonal profiles, metabolic health, and mental well-being in women.

Interleukin 37 Role in Diabetic Iraqi Patients: A comparison between patients treated with and without Insulin

Background: Diabetes Mellitus (DM) is defined as a metabolic disorder that is characterized by some clinical features, such as chronic hyperglycemia accompanied by impairment of carbohydrates metabolism, proteins, and lipids. However, relative or absolute insulin deficiency is associated with the high blood glucose levels, which is attributed to the β-cells dysfunction, insulin resistance or could be both. The anti-inflammatory cytokine interleukin-37 (IL-37) negatively regulates inflammation, therefore, reduces inflammation and alters metabolic pathways. It acts by suppressing inflammatory cytokines and chemokines, activation of IL-37 inhibits inflammation and obstructs the infiltration of pro-inflammatory cells, primarily neutrophils and eosinophils. Aim of Study: The estimation of IL 37 and other biochemical parameters in patients with Diabetes mellitus and study its role in the pathogenicity of the disease. Materials and methods: A case-control study design was adopted to study the relationship between Interleukin 37 and insulin treatment in Nasiriyah in the Diabetes and Endocrinology Specialized Center between December 2023 and January 2024. It was conducted on patients with Diabetes Mellitus type 2 (60 patients) divided into two groups (30 patients treated with Insulin injection) and (30 patient treated with oral tab only). On the other hand, 30 people were taken as a control group without Diabetes Mellitus.Result: Patients with diabetes mellitus have been noticed to have higher levels of IL-37 in comparison to the healthy control groups. In general, patients with diabetes mellitus have higher levels of IL-37 compared to three groups, G1, G2, and healthy control groups. Conclusion We demonstrated that serum levels concentration of IL 1b and IL 37 significantly increased in our patients also FBS, HbA1c, Insulin Resistance, HOMO IR, TG, cholesterol, and decrease C- peptide as compared to healthy individuals.

Effectiveness of Bivalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection-Increasing Community Access to Testing Program, United States, January-September 2023.

On September 2, 2022, bivalent COVID-19 mRNA vaccines, were recommended to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance. Using national pharmacy-based SARS-CoV-2 testing program data from January 15 to September 11, 2023, this test-negative, case-control design study assessed bivalent COVID-19 vaccine effectiveness (VE) against symptomatic infection. VE against symptomatic infection of a bivalent dose between 2 weeks and 1 month after bivalent vaccination ranged from 46% (95% CI: 38%-52%) for those aged ≥ 65 years to 61% (95% CI 41%-75%) for those aged 12-17 years. Bivalent vaccines protected against symptomatic infection. However, effectiveness waned over time, emphasizing the need to stay up to date with COVID-19 vaccination.

Analysis of Risk Factors for the Occurrence of Diabetic Foot Ulcers in Patients with Type II Diabetes Mellitus

Background: Diabetes Mellitus (DM) has become a prevalent disease, imposing a significant burden on public health due to its widespread occurrence and association with numerous disabilities and fatalities. Uncontrolled DM can lead to severe metabolic complications and long-term vascular issues, including microangiopathy and macroangiopathy. Additionally, individuals with DM are highly susceptible to foot infections, which can escalate into gangrene if not properly managed. Purpose: This study aimed to determine the risk factors for diabetic foot ulcers in patients with Type II Diabetes Mellitus at the Hospital Infatil e Maternidade Jardim Amalia Methods: The research employed an analytical survey method with a case-control study design. Purposive sampling was utilized to select a total of 134 participants, comprising 67 individuals in the case group (those with diabetic foot ulcers) and 67 in the control group (those without diabetic foot ulcers). Data collection was conducted using a structured questionnaire, and the results were analyzed using the Odds Ratio (OR) test to identify significant risk factors. Findings: The findings of the study indicated that age is a risk factor for developing diabetic foot ulcers in patients with Type II DM, with an OR of 3.15 (95% CI: 0.43-17.216). The duration of diabetes also emerged as a significant risk factor, with an OR of 3.13 (95% CI: 0.62-14.12). Furthermore, foot care practices were identified as a crucial risk factor, with an OR of 4.13 (95% CI: 0.72-12.45). Conclusion: this study demonstrates that age, the length of time a patient has had diabetes, and their foot care routines are significant risk factors for the development of diabetic foot ulcers in patients with Type II Diabetes Mellitus at Hospital Infatil e Maternidade Jardim Amalia. These findings underscore the importance of early intervention and targeted patient education to mitigate these risks and improve patient outcome

Influenza vaccine effectiveness in Ireland during two influenza seasons, 2022/23 and 2023/24

Abstract Background Live Attenuated Influenza Vaccine (LAIV) is recommended in Ireland for all children aged 2-17 years. Quadrivalent influenza vaccine is recommended for all others eligible for vaccination, including those aged ≥18 years with underlying medical conditions and all aged ≥65 years. We aimed to estimate influenza vaccine effectiveness (IVE) against Acute Respiratory Infection (ARI) presentations to primary care due to influenza over two influenza seasons in Ireland, to inform vaccination recommendations and communication campaigns. Methods We undertook a test-negative design case control study within the national sentinel surveillance General Practice network, as part of the European Vaccine Effectiveness Burden and Impact Studies (VEBIS) network. We compared influenza vaccination status among influenza Polymerase Chain Reaction (PCR) positive cases with influenza PCR negative controls, amongst patients consulting with ARI. We verified vaccination status using the national influenza vaccination database. We estimated end of season IVE for 2022/23, and mid-season IVE (up to 7th April 2024) for 2023/24, using multivariable logistic regression and adjusting for age, onset time, medical condition, and sex. Results In 2022/23, there were 288 cases and 765 controls. In 2023/24 there were 515 cases and 1,482 controls. Overall vaccination coverage was 23% in both seasons. Coverage in 2-17 year-olds was 10% in 2022/23 and 12% in 2023/24. In 2022/23, overall IVE was 42% (95%CI 9-54) and 50% (95%CI -30-83) in 2-17 year-olds. Overall IVE in 2023/24 was 37% (95%CI 16-54) and was 67% (95%CI 28-87) in 2-17 year-olds. Conclusions Influenza vaccination reduced medical attendance to primary care with ARI due to influenza, demonstrating benefits of vaccination, particularly among children. Influenza vaccination should continue to be offered and promoted to recommended groups, including children. Key messages • This study suggests that influenza vaccination protected population health and the health service from medical attendance to primary care with acute respiratory infection due to influenza. • Higher influenza vaccine effectiveness was observed in children aged 2-17 years. These findings can inform influenza vaccination programmes with LAIV for children in Ireland and internationally.

Assessment of Risk Factors of The Patients With Lateral Epicondylitis

Background: Lateral epicondylitis, is prevalent in the world of sports; however, this injury still causes confusion among healthcare professionals. Numerous studies have evaluated treatment options, but few have taken into consideration the extent to which tennis players, themselves, understand this ailment. Objectives: To identify the risk factors associated with lateral epicondylitis. Materials and methods: An observational case control study design was carried out among 120 patients attended at outdoor Department of Physical Medicine and Rehabilitation, BSMMU, Dhaka from April 2018 to march 2019. Sixty (60) patients with lateral epicondylitis as case group and another 60 patients without lateral epicondylitis as control group. Data was collected using a structured interviewer- administered questionnaire, enquiring about demographic data and details of risk factors. Result: The mean age was found 39.4:6.3 years in case group and 36.97.4 years in control group. Twenty- seven (45.0%) patients had more than 2 hours of use hand in case group and 12(20.0%) in control group. More than half (53.3%) patients had moderate VAS scale in case group and 9(15.0%) in control group, Nine (15.0%) patients were found past history of recurrent injury in case group and not found in control group. The difference was statistically significant (p&lt;0.05) between two groups. Patients having use hand more than 2 hours 3.273 (95% CI 1.453% to 7.36%) times more likely to developed lateral epicondylitis. Conclusion: Use of hand with repetitive wrist extension more than 2 hours was significantly associated with lateral epicondylitis. J Dhaka Med Coll. 2023; 32(1) : 77-84

Case–control study of fatal bicycle crashes in peri-urban areas of Delhi

ObjectivesThere is a lack of evidence on interventions to improve the safety of cycling use in low- and middle-income countries. We investigated the impact of road design and traffic characteristics...

Changes functional prediction of ear canal flora in chronic bacterial otitis externa.

To investigate ear canal microflora's structure, composition and function in patients with chronic bacterial otitis externa. A case-control study design method was used to collect the ear canal secretions from 14 patients with chronic bacterial external otitis (CB group) and 14 healthy controls (H group) treated in the Department of Otolaryngology and Head and Neck Surgery in the First Affiliated Hospital of Hainan Medical University. 16S rRNA high-throughput sequencing technology was used to sequence the ear canal microflora's V3 ~ V4 region gene amplification products in the participating population. The α diversity of ear canal microflora in 2 groups was analyzed. Based on the weighted Unifrac distance, principal coordinate analysis was performed to compare the β diversity of ear tract microflora between the two groups. The differences in ear microflora at phylum and genus levels were analyzed. PICRUSt2 function prediction and BugBase phenotype prediction were also performed. α diversity analysis showed that the diversity and richness of auricular microflora in the CB group were significantly lower than those in the H group. β diversity analysis showed that there were some differences between the two groups. At the phylum level, the relative abundance of Bdellovibrionota, Campylobacterota, and WPS-2 in the microbiota of patients in the CB group was significantly lower than that in the H group, and the differences were statistically significant. At the genus level, the relative abundance of Pseudomonas, Acinetobacter, Pelomonas, Sphingomonas, Bradyrhizobium, Brevundimonas, Enhydrobacter, Actinomyces, Paracoccus and Chryseobacterium in the ear canal of Group H is significantly higher than that of Group CB. Functional prediction of PICRUSt2 suggests that amino acid biosynthesis and bacterial microbiota may be related. In BugBase phenotypic prediction, the contribution of aerobic phenotype in group CB was significantly lower than that in group H. The diversity and abundance of the ear canal flora of patients with chronic bacterial otitis externa were significantly lower than those of the healthy population, and their bacterial colony structure was significantly altered. Dysbiosis of the ear canal flora may be an important cause of chronic bacterial otitis externa.

Goat seropositivity as an indicator of Rift Valley fever (RVF) infection in human populations: A case-control study of the 2018 Rift Valley fever outbreak in Wajir County, Kenya

Rift Valley fever (RVF) is a viral zoonosis, which is considered as a threat to food security in the Horn of Africa. In Kenya, RVF is the 5th ranked priority zoonotic disease due to its high morbidity and mortality, frequent outbreak events, and associated socioeconomic impacts during outbreak events. In 2018, an RVF outbreak was confirmed in Kenya's Siaya, Wajir, and Marsabit counties. During this outbreak, 30 people were confirmed infected with RVF through laboratory tests; 21 in Wajir, 8 in Marsabit, and 1 in Siaya Counties.Seventy-five (75) households (15 cases and 60 controls) were selected and interviewed using a case-control study design in 2021 (?). A case was a household with a member who was diagnosed with RVF in 2018. In addition, a total of 1029 animals were purposively selected within these households and serologically tested for RVF. The study aimed to estimate the contribution of various risk factors to RVF human occurrence in Kenya with a special focus on Wajir County. Wajir County was chosen due to high number of confirmed human cases reported in the 2018 outbreak. A univariable regression model revealed that owner-reported RVF virus exposure in livestock significantly increased the odds of an RVF human case in the household by 32.7 times (95 % CI 4.0–267.4). The respondent being linked to a goat flock that was IgG-positive increased the odds of an RVF human case by 3.8 times (95 % CI 1.17–12.3). In the final multivariable analysis, the respondent being linked to their own animals affected by RVF increased odds of having an RVF human case in the household by 56.9 times (95 % CI 4.6–700.4), while the respondent being linked to a neighbor household member affected decreased odds of having a RVF human case by 0.1 times (95 % CI 0.08–0.75).In summary, these results have revealed a potential link for the spread of RVF infection from animals to humans in pastoralist households, hence it is critical to carry out targeted, community education, One Health surveillance, prevention, and control measures against the disease. This will be critical to protecting humans against potential spillovers of infections during outbreak events in livestock.

Achieved oxygen saturations and risk for bronchopulmonary dysplasia with pulmonary hypertension in preterm infants

ObjectiveCharacterisation of oxygen saturation (SpO2)-related predictors that correspond with both bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) development and survival status in infants with BPD-PH may improve patient outcomes. This investigation assessed...

Determinants of preterm delivery among mothers who gave birth in hospitals of Wolaita zone, southern Ethiopia, 2023: unmatched case-control study

BackgroundPreterm delivery refers to childbirth that occurs before 37 full weeks’ gestation. Globally, around 13.4 million babies are born preterm annually, a million died due to its complications. Identifying its determinants is mandatory to decrease preterm birth and thereby neonatal deaths. Therefore, this study aimed to identify the determinants of preterm delivery among mothers who gave birth in hospitals in the Wolaita zone, southern Ethiopia.MethodsA hospital-based unmatched case-control study design was conducted from March 29 to May 20, 2023, in the Wolaita zone, southern Ethiopia. Cases were women who gave birth after 28 weeks and before 37 completed weeks, and controls were women who gave birth at and after 37 and before 42 weeks of gestation from the first day of the last normal menstrual period. A consecutive sampling method was used. Data were collected by a structured interviewer-administered questionnaire. Data were coded and entered into Epi data 3.1 and analyzed by using SPSS version 25. Variables that had a P-value < 0.25 in the bivariate logistic regression analysis were entered into a multivariable logistic regression model. Finally, p-value < 0.05 was used to claim statistical significance.ResultFrom a total of 405 eligible participants, 399 respondents (133 cases and 266 controls) participated in this study with a response rate of 98.52%. The result of the multivariable analysis shows that mothers who resided in rural areas [AOR = 2.78:95% CI (1.51–5.12)], not receiving support from their partner [AOR = 2.37:95% CI (1.24–4.51)], less than four antenatal care visits [AOR = 4.52:95%CI (2.38–8.57)], developed pregnancy-induced hypertension [AOR = 5.25:95%CI (2.27–12.14)] and exposed for intimate partner violence [AOR = 2.95:95%CI (1.105–7.85)], had statistically significant association with experiencing preterm delivery.Conclusion and recommendationMost of the determinants for preterm delivery have been proven modifiable. Thus, designing new strategies, providing comprehensive mobile clinic services to address hard-to-reach areas and Health care providers should give due attention to mothers with pregnancy-induced hypertension and exposure to intimate partner violence and increase the awareness of antenatal care follow-up and benefit of support during pregnancy to reduce preterm delivery.

IDO1-mediated catabolism of tryptophan in gastric tumors: Its potential role in the axis of histopathology, differentiation and metastasis

BackgroundIndoleamine 2,3-Dioxygenase 1 (IDO1)-mediated tryptophan degradation, which is the rate-limiting enzyme of tryptophan/kynurenine pathway, may cause immune suppression in the tumor microenvironment, while potentiating proliferative and metastatic activity in the tumor focus, Phase studies of IDO1 inhibitors are ongoing, and our study aims to evaluate the potential contribution of IDO1 gene expression to the tryptophan/kynurenine pathway in tumor and tumor microenvironment foci in gastric cancer (GC) on a clinicopathological axis, MethodIn the case-control study design, the determination of tryptophan and its metabolites in the serum of 51 GC and 49 healthy controls was made using High Pressure Liquid Chromatography-Fluorescence Detector (HPLC-FD). IDO1 expression in a total of 102 tissues with tumor and tumor microenvironment was detected by quantitative PCR (q-PCR). ResultsIn gastric tumors, 3,25-fold decreased expression of IDO1 was detected according to the tumor microenvironment (p=0,05), IDO1 expression was found to be more than 2 times higher in signet ring cell carcinoma (SRCC) and poorly differentiated tumors without distant organ metastasis (p<0,05), In GC, tryptophan level was found to be 1,6 times lower than in control (AUC:0889; cut off≤21,57; p<0001), Low tryptophan level was found in advanced tumor stage compared to early stage and in the presence of perineural invasion compared to its absence (p<0,05) The level of kynurenine was found to be approximately 1,8 times lower in SRCC (p=0,04), ConclusionIncreased tryptophan accumulation in the gastric tumor and its microenvironment, when catabolized via IDO1, exhibits histological type, tumor differentiation, and metastasis-promoting effects more prominently in aggressive subtypes such as SRCC,

Design of a Location-Based Case-Control Study of Built Environment Risk Factors for Pedestrian Fatalities in the U.S.

The location-based case-control design is a useful approach for studies where the exposures of interest are aspects of the environment around the location of a health event such as a pedestrian fatality. In this design locations are the unit of analysis and an enumerated cohort of locations are followed through time for the health events of interest and a case-control study of locations is nested within the cohort. Locations where events occurred (case-locations) are compared to matched locations where these events did not occur (control-locations). We describe the application of this design to the issue of pedestrian fatalities using a cohort of 9,612,698 intersections, 17,737,728 road segments, and 222,318 entrance/exit ramp segments that existed in 2017 across all 384 U.S. Metropolitan Statistical Areas. This cohort of locations was followed up from Jan 1, 2017 to Dec 31, 2018 for pedestrian fatalities using the National Highway Traffic Safety Administration Fatality Analysis Reporting System. In total, 10,587 fatalities were identified as having occurred on cohort locations and 21,174 matched control locations were selected using incidence density sampling. Geographic information systems, spatially linked administrative data sets and virtual neighborhood audits via Google Street View are underway to characterize study locations.

Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia.

Although cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, ALL remains a leading cause of cancer death in children. Half of relapses arise in children initially classified with standard-risk (SR) disease. To identify genomic determinants of relapse in children with SR ALL, we performed genome and transcriptome sequencing of diagnostic and remission samples of children with SR (n = 1,381) or high-risk B-ALL with favorable cytogenetic features (n = 115) enrolled on Children's Oncology Group trials. We used a case-control study design analyzing 439 patients who relapsed and 1,057 who remained in complete remission for at least 5 years. Genomic subtype was associated with relapse, which occurred in approximately 50% of cases of PAX5-altered ALL (odds ratio [OR], 3.31 [95% CI, 2.17 to 5.03]; P = 3.18 × 10-8). Within high-hyperdiploid ALL, gain of chromosome 10 with disomy of chromosome 7 was associated with favorable outcome (OR, 0.27 [95% CI, 0.17 to 0.42]; P = 8.02 × 10-10; St Jude Children's Research Hospital validation cohort: OR, 0.22 [95% CI, 0.05 to 0.80]; P = .009), and disomy of chromosomes 10 and 17 with gain of chromosome 6 was associated with relapse (OR, 7.16 [95% CI, 2.63 to 21.51]; P = 2.19 × 10-5; validation cohort: OR, 21.32 [95% CI, 3.62 to 119.30]; P = .0004). Genomic alterations were associated with relapse in a subtype-dependent manner, including alterations of INO80 in ETV6::RUNX1 ALL, IKZF1, and CREBBP in high-hyperdiploid ALL and FHIT in BCR::ABL1-like ALL. Genomic alterations were also associated with the presence of minimal residual disease, including NRAS and CREBBP in high-hyperdiploid ALL. Genetic subtype, patterns of aneuploidy, and secondary genomic alterations determine risk of relapse in childhood ALL. Comprehensive genomic analysis is required for optimal risk stratification.